Managing epidemics: key facts about major deadly diseases

Key facts about major deadly diseases Managing epidemics VERSION 1 Key facts about major deadly diseases Managing epidemics © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/ by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specifi c organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). 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Printed in Luxembourg Managing epidemics: key facts about major deadly diseases ISBN 978-92-4-156553-0 Contents The re-emergence of infectious diseases - The threat continues - The 21st century: already a long series of scourges - Faster and further with a greater impact - Ready and able to detect the next outbreak - One Health and emerging and re-emerging pathogens - Known epidemics: still a severe threat - Strengthening health systems: essential in epidemics Burden of epidemics: illustrations Challenges and risk factors for 21st century epidemics - New lifestyles spread diseases further - Revisiting traditional control measures - Equity and solidarity - Epidemics of rumours: a new risk to health Foreword About this handbook PART I : EPIDEMICS OF THE 21ST CENTURY 10 11 14 14 15 17 18 19 20 21 22 25 25 26 26 26 Key insights into infectious disease epidemics Response tips and checklists - Coordinating responders - Health Information - Communicating risk - Health Interventions Focus 1: Community engagement during epidemics - Defi ning a community - Why engage communities - Three elements of community engagement - Ten things to know - Ensuring effective community engagement Focus 2: Risk communication – a life-saving action in public health emergencies - The essence of risk communication - 21st century aspects change and complicate risk communication - Making it effective - Ten things to know and do - Other factors to remember Focus 3: Treating patients and protecting the health workforce - Advances in medicine: antibiotics, antivirals, vaccines and new treatments - Treating patients with supportive care - Protecting frontline responders - Confronting the human resources crisis 27 31 32 33 34 36 38 38 38 39 40 41 42 42 43 44 45 47 48 48 49 49 50 PART II: BE IN THE KNOW. 10 KEY FACTS ABOUT 15 DEADLY DISEASES 56 66 76 86 100 110 120 130 140 150 160 170 180 190 200 EBOLA VIRUS DISEASE LASSA FEVER CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF) YELLOW FEVER ZIKA CHIKUNGUNYA AVIAN AND OTHER ZOONOTIC INFLUENZA SEASONAL INFLUENZA PANDEMIC INFLUENZA MIDDLE EAST RESPIRATORY SYNDROME (MERS) CHOLERA MONKEYPOX PLAGUE LEPTOSPIROSIS MENINGOCOCCAL MENINGITIS PART III: TOOL BOXES Tool box 1: The role of WHO Tool box 2: The International Coordinating Group (ICG) on vaccine provision Tool box 3: Tables for laboratory diagnosis and shipment of infectious substances Tool box 4: Transport of infectious substances Tool box 5: Vector control during epidemics Acknowledgements 214 227 231 244 248 256 Foreword Can we create a pandemic-free world? There is no such thing as a guarantee, but with meticulous preparation and rapid response, we can prevent most outbreaks from getting out of control, and limit the impact of those that spread internationally. First, we must build and sustain resilient capacities at national, regional and global levels to prevent, detect and respond to outbreaks, in accordance with the International Health Regulations. And second, we must ensure that populations affected by emergencies have rapid access to essential life- saving health services, including medicines and vaccines. That’s why WHO works all around the world to strengthen health systems, built on the foundation of people-centred primary health care that focuses on health promotion and disease prevention, with a strong focus on surveillance systems. Delivering on these priorities will cost money of course, but only a fraction of what remaining unprepared will cost. In the end, prevention is not only better than cure; it’s cheaper. This year marks the 100th anniversary of Spanish fl u, the deadliest outbreak in recorded history. Up to 50 million people were killed, more than the death toll from the First World War. Thankfully, we have not seen a public health emergency on that scale since then. But we may at any time. Outbreaks are a fact of life, and the world remains vulnerable. We do not know where or when the next global pandemic will occur, but we do know that it will take a terrible toll, both on human life, and on the global economy. None of us will ever forget the West African Ebola outbreak in 2014. It taught us a valuable lesson: that global health security is only as strong as its weakest link. No-one is safe until everyone is safe. Keeping the world safe is one of WHO’s three top strategic priorities in our new General Programme of Work. We are setting ourselves a goal that over the next fi ve years, 1 billion more people will be better protected from epidemics and other health emergencies. This manual is a valuable tool to help countries make progress towards that goal. It offers expert guidance to help WHO’s country representatives and others to respond quickly in the earliest stages of an outbreak. But it’s not enough just to respond to outbreaks. We must do our best to prevent them by addressing the root cause of health insecurity: the lack of access of the most vulnerable people to essential health services. Ultimately, it’s the absence of universal health coverage that is the greatest threat to health security. Universal health coverage and health security are two sides of the same coin. 2018 is also a milestone year for WHO. It’s our 70th birthday – a reminder that the reasons we were created are as relevant now as they were at our beginning. WHO was founded on the principle that all people should be able to realize their right to the highest possible level of health. “Health for all” has always been our guiding vision. Dr Tedros Adhanom Ghebreyesus Director-General of the World Health Organization 10 About this handbook Handbook purpose Epidemics of infectious diseases are occurring more often, and spreading faster and further than ever, in many different regions of the world. The background factors of this threat are biological, environmental and lifestyle changes, among others. A potentially fatal combination of newly-discovered diseases, and the re-emergence of many long-established ones, demands urgent responses in all countries. Planning and preparation for epidemic prevention and control are essential. The purpose of this “Managing epidemics” manual is to provide expert guidance on those responses. Although this publication is open to a wide readership, it is primarily intended to help the World Health Organization (WHO) country representatives (WRs) to respond effectively and rapidly at the very start of an outbreak. The manual provides concise and basic up-to-date knowledge with which WRs can advise Ministries of Health in all countries. Specifi cally, it examines and explains in detail a total of 15 different infectious diseases and the necessary responses to each and every one of them. These diseases have been selected because they represent potential international threats for which immediate responses are critical. Nearly all of them are subject to WHO’s International Health Regulations (2005) monitoring, and are part of the Global Health Security Agenda. Perhaps the greatest threat outlined in the manual is an infl uenza pandemic, which is both unpredictable and inevitable. In the worst-case scenario, there will be no protective vaccine for six months or longer after the virus is identifi ed, and even there will be a global shortage of doses. On this and other threats, the manual focuses on practical and indispensable things to know about infectious diseases that are most important for national political and operational decision-makers; it also links readers to more exhaustive WHO guidance. It has been developed in parallel with the creation of the WHO MOOCs (Massive Open Online Courses) on openWHO (https://openwho.org). Handbook structure The manual is structured in three parts. • Part One “Epidemics of the 21st century” provides vital insights on the main features of the 21st century upsurge and the indispensable elements to manage them. • Part Two “Be in the know. 10 key facts about 15 deadly diseases” contains key information about 15 diseases (Ebola Virus Disease, Lassa Fever, Crimean-Congo haemorrhagic fever, Yellow Fever, Zika, Chikungunya, Avian and Other Zoonotic Infl uenza, Seasonal Infl uenza, Pandemic Infl uenza, Middle East Respiratory Syndrome, Cholera, Monkeypox, Plague, Leptospirosis and Meningococcal Meningitis). This section provides tips on the interventions required to respond to epidemics of all these diseases. • Part Three “Tool boxes” gives an overview and summarized guidance on some other important topics, including: the role of WHO, the International Coordinating Group, laboratory diagnosis and shipment of infectious diseases substances, and vector control. The handbook enables the three levels of WHO – its Headquarters, Regional Offi ces and Country Offi ces to work effi ciently together by building the foundations of a shared conceptual and thinking framework, which includes common terminology. This “Managing epidemics” manual will be regularly updated. The next versions will incorporate additional infectious diseases. 11 PART I Epidemics of the 21st century 13 The re-emergence of infectious diseases The threat continues We are continuously learning about the unpredictable powers of nature. This is nowhere more true than in the continuous evolution of new infectious threats to human health that emerge – often without warning – from the natural environment. Already in these fi rst two decades of the 21st century, the world has been sharply reminded time after time of the degree to which people in all countries and on all continents remain chronically vulnerable to infectious diseases, known and unknown. In the 1970s, and for years afterwards, this remarkable progress, including the development of new vaccines, antibiotics and other treatments and technologies, led to a proclamation of a victory of mankind over microbes. Many experts thought it was “the time to close the book on the problem of infectious diseases” (Jesse Steinfeld, MD, US Surgeon General, 1969). Here lay the roots of a dangerous complacency. The microbes didn’t go away. They just went out of sight. Instead, the focus turned to chronic, noncommunicable diseases, which came to receive much more attention. But nature was by no means in retreat. In fact, it seemed to return and took many health institutions and decision makers by surprise. Since 1970, more than 1,500 new pathogens were discovered, of which 70% proved to be of animal origin: a connection that deserves renewed scrutiny. Not all of them have had a public health impact but some of them have become famous. They included the Ebola virus, in 1976, and the human immunodefi ciency virus (HIV), in 1983. Pause for a moment and refl ect that HIV, a relatively new disease in human history, has infected about 70 million people in just 35 years, and killed an estimated 35 million people in the same period. Consider also that in the last 40 years, Ebola has surfaced in almost 25 separate and deadly outbreaks, often after long spells in which it has apparently lain dormant. And now ask the question: Will history repeat itself? The answer must be: Yes, it will. A new HIV, a new Ebola, a new plague, a new infl uenza pandemic are not mere probabilities. Whether transmitted by mosquitoes, other insects, contact with animals or person-to-person, the only major uncertainty is when they, or something equally lethal, will arrive. The obvious follow-up question is: So what are we doing about it? This purpose of this handbook is to provide as many answers as possible. In doing so it examines a range of challenges and real or potential solutions, ranging from the medical and technological to the social and political. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 14 The 21st century: already a long series of scourges In order to try to see the road ahead more clearly, we need frequently to look over our shoulders – all the more so, because these early years of the 21st century have already been deeply scarred by so many major epidemics. Take plague, one of the most ancient scourges. A thing of the past? By no means. A major outbreak in Madagascar in 2017 led to a total of at least 2,417 confi rmed, probable and suspected cases, including 209 deaths. Most cases were of the more fatal pneumonic type which is also transmissible from person to person, but there were also several hundred cases of bubonic plague. Nine countries and territories with trade and travel links to Madagascar were put on plague preparedness alert. The lesson here is that, over time, diseases very rarely disappear. And there always seems to be room for new ones. SARS – Severe acute respiratory syndrome - was unheard of before 2003. But it affected more than 8,000 people, killing about one in ten of them, causing fear and panic across the world, and infl icting enormous economic damage, especially in Asian countries. In 2009, a novel infl uenza virus, H1N1, started to spread, creating the fi rst infl uenza pandemic of the 21st century. But – and this is a reason for cautious hope - it was not as severe as expected thanks to recent preparedness efforts. The importance of these efforts is a core issue in this handbook. In 2012-2013, a new virus surfaced in the Middle East, causing an epidemic of what became MERS – Middle East respiratory syndrome – that spreads fatally into many countries beyond that region. The Ebola epidemic in West Africa (Guinea, Liberia, and Sierra Leone) in 2014 was unlike the previous 24 localized outbreaks observed since 1976. Instead of being restricted geographically, this one seriously affected three African countries and spread to six other countries in three continents, and sparked alarm worldwide. In 2015, the Zika virus, transmitted by the Aedes Aegypti mosquito, triggered a wave of microcephaly in Brazil. This disease causes dreadful damage in the brains of unborn babies. Almost 70 countries, one after another, then experienced their own Zika epidemic. There are probably many more to come, because most of the global intertropical zone has a high density of Aedes Aegypti that transports the disease. And so a clear pattern continues to take shape. Old diseases – Cholera, Plague, Yellow fever among them – often return, and new ones invariably arrive to join them. About 40 outbreaks of cholera alone are reported to WHO every year. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 15 Gavi, the Vaccine Alliance, is an international organisation that was created in 2000 to improve access to new and underused vaccines for children living in the world’s poorest countries. The International Health Regulations (2005) or IHR (2005) are an international law which helps countries work together to save lives and livelihoods caused by the international spread of diseases and other health risks. The IHR (2005) aim to prevent, protect against, control and respond to the international spread of disease while avoiding unnecessary interference with international traffic and trade. The Pandemic Influenza Preparedness (PIP) Framework brings together Member States, industry, other stakeholders and WHO to implement a global approach to pandemic influenza preparedness and response. Its key goals include: - to improve and strengthen the sharing of influenza viruses with human pandemic potential; and - to increase the access of developing countries to vaccines and other pandemic related supplies. The Global Outbreak Alert and Response Network (GOARN) is a technical collaboration of existing institutions and networks who pool human and technical resources for the rapid identification, confirmation and response to outbreaks of international importance. 2000 2015 2016 2017 201820142013201220112010200920082007200620052004200320022001M AJ O R EP ID EM IC T HR EA TS S IN CE 2 00 0 LEGEND IN TE RN AT IO N AL C O LL AB O RA TI O N E FF O RT S TO FI G HT E PI DE M IC T HR EA TS GAVI IHR (2005) PIP Framework PIP Review IHR Review GOARN Ebola (West Africa) Cholera (Haiti) MERS-CoV H1N1 H7N9 Zika Yellow fever (Central Africa, Brazil) H5N1 SARS Epidemic Pandemic Timeline Major infectious threats in the 21st Century & collaboration mechanisms to fight against them Cholera (Yemen) Plague (Madagascar) PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 16 Faster and further with a greater impact This pattern has another, deeply troubling aspect. The epidemics in the 21st century are spreading faster and further than ever. Outbreaks that were previously localized can now become global very rapidly – just as fast, in fact, as an intercontinental aircraft can fl y. Thus, an individual fl ying from one side of the world can introduce a new disease into the other, within hours, and before even showing symptoms. And in this way, far from its origins, the microbe fi nds a new home. For example, the infl uenza pandemic of 2009 reached all continents in less than nine weeks. In recent outbreaks, yellow fever made it all the way from Angola to China, but, fortunately, there were only imported cases with no sustainable circulation in the mosquito population. In 2015, it took just one traveler returning home to the Republic of Korea from spending time in the Middle East to bring MERS back with him. The consequences: a Korean outbreak, 186 cases, 36 deaths, and outbreak-related losses of approximately US$ 8 billion, all in the space of two months. Thus, 21st century epidemics can spread more widely and more quickly, potentially affecting ever-greater numbers of people. They also can have a ruinous impact on the economy of the affected country and spill over into to the global economy, disrupting travel, trade and livelihoods. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 17 Ready and able to detect the next outbreak Given the effects of globalization, the intense mobility of human populations, and the relentless urbanization, it is likely that the next emerging virus will also spread fast and far. It is impossible to predict the nature of this virus or its source, or where it will start spreading. But we can say, with a high degree of certainty, that when it comes, there will be (a) an initial delay in recognising it; (b) a serious impact on travel and trade; (c) a public reaction that includes anxiety, or even panic and confusion, and (d) this will be aided and abetted by media coverage. The concept of global health security, a central issue in this handbook, represents a new determination by, or on behalf of, human society to protect itself from the health impact and social disruption caused by outbreaks. It encompasses a spectrum of ways and means that offer worldwide protection against the threats of infectious diseases, backed by revised and more powerful International Health Regulations (2005). But to make the world safer, global health security depends crucially on much greater awareness, cooperation and collaboration between individual countries, agencies, organizations and communities. The continuing scientifi c uncertainty around disease emergence requires even more collaboration and global awareness than has previously existed, not least to improve early detection. Recent outbreaks, however, show how diffi cult this can be, even with good public health surveillance systems. Early recognition of emergence typically starts with clinicians who can detect unusual clusters of severe cases, take samples to allow laboratory diagnostics and alert surveillance units. Often, poorer communities around the world, especially those in remote areas, lack easy access to care. This has major implications when an infectious threat occurs. The Ebola outbreak in West Africa remained undiagnosed for more than two months. This time lag allowed the virus to spread unseen, and to reach capital cities where the outbreaks grew into large epidemics. In such circumstances, it is essential to raise clinicians’ awareness and provide them with the relevant knowledge and diagnostic tools to enable them to perform effectively as detectors and fi rst-line responders. As we have signaled earlier, another indispensable element of increasing health security is preparedness. This should be fl exible enough to adapt to any novel agent, but should be directed primarily at known pathogens because some of them are likely to behave differently than previously. The recent plague outbreak in Madagascar, described earlier, is a good example of known diseases with new patterns. In addition, the fear generated by the emergence of a previously-unknown infection may be greatly out of proportion to its real public health impact. Fear often generates inadequate decisions or inappropriate behaviours, including stigma of certain at-risk populations. The impact on travel and trade and on economies can be disproportionate, as it has been seen in the Republic of Korea during the MERS epidemic. To a certain extent, global health security also encompasses economic and human security. Thus, risk communication is critical to minimise the social, political and subsequently economic impact of an epidemic, and this is also a major focus of this publication. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 18 One Health and emerging and re-emerging pathogens Epidemics are sparked either by the re-emergence of pathogens that have been familiar for a long time, but now threaten new, immunologically vulnerable populations, or are newly-emerging ones. They come in a daunting array of species of bacteria, viruses, fungi and parasites. Some are borne in contaminated water or food; others are carried in the air we breathe and by human touch. As noted earlier, 70% of emerging human pathogens come from animals. This is a burgeoning threat, because animals are intensively farmed, transported for trade and kept in close contact with other species and humans in market places. Early detection often relies on close collaboration between the animal health and wildlife sectors (the “One Health” approach); otherwise early signals of emergence in animals or the environment are often missed. This collaborative approach, another pivotal element of global health security, can also contain outbreaks at an early stage by reducing animal-to-human transmission. Because these diseases are rare and outbreaks are generally contained quickly, these epidemics have not been a priority among the research community or manufacturers in the development of medical countermeasures. Nevertheless, more research is needed to identify precisely the modes of transmission and medical countermeasures. Today’s harsh reality is that there is as yet no vaccine or treatment for most emerging diseases. This is not as hopeless as it might seem at fi rst. WHO has developed a Research & Development (R&D) Blueprint for action to prevent epidemics: it is a global strategy and preparedness plan that allows the rapid activation of R&D activities during epidemics. Its aim is to fast-track the availability of effective tests, vaccines and medicines that can be used to save lives and avert large scale crisis. However, public health interventions have to rely primarily on social-distancing measures to reduce human transmission, and on controlling the source of infection (for instance by culling of infected animals/elimination of the reservoir). Thus, to prevent the spread of emerging diseases, it is vitally important to ensure early detection of a new pathogen and the start of human-to-human transmission. Enhanced international information and virus sharing among laboratories is being actively encouraged and pursued. This is necessary to enable research and development of countermeasures. The results of this sharing are potentially life-saving interventions (vaccines, diagnostics and therapeutics). But they also need to be underpinned by specifi c mechanisms to ensure they become widely available and accessible on an equitable basis. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 19 Known epidemics: still a severe threat Fortunately, control programmes are already long-established and widely-applied for some known epidemic diseases, such as cholera, HIV infection, infl uenza, meningitis, malaria, tuberculosis and yellow fever. However, even if medical countermeasures are available, these diseases remain a threat for many of the world’s populations, either because of their rapidly evolving nature (e.g. infl uenza) or because equitable access to effective public health measures is diffi cult. There are many reasons for limited access to vaccines: production capacity does not meet the demand (e.g. yellow fever, pandemic infl uenza), explosive outbreaks exhaust the available vaccines (e.g. meningitis), or the absence of markets prevents access to the intervention in case of emergencies (e.g. oral cholera vaccine). In addition, in many affected countries, the weakness of the existing health care system prevents effective access to medical interventions (diagnostics and treatment). Therefore, although it is reassuring that sound knowledge and a range of potential control interventions are available, expert guidance must be constantly updated to incorporate scientifi c and technological progress. Equally important, access to life-saving interventions must be improved in all settings worldwide. The current global strategy is to reach elimination or eradication of these diseases through vaccination or investment in and implementation of other countermeasures. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 20 Strengthening health systems: essential in epidemics In order to mitigate the impact of epidemics, protect the health workforce and ensure continuity of health services during and after them, stronger health systems are needed. Epidemics and pandemics put these systems under great pressure and stress. The sudden infl ux of large numbers of sick individuals to health facilities stretches the systems’ capacity and resources, even more so and more noticeably where resources are already scarce. When an epidemic emerges and spreads, it inevitably draws most of health responders’ attention and monopolizes most of the health system’s human and fi nancial resources, as well as medical products and technologies. People, efforts, and medical supplies all shift to respond to the emergency. This often leads to the neglect of basic and regular essential health services. People with health problems unrelated to the epidemic fi nd it harder to get access to health care services. Some may die as a result, if the disruption overwhelms the health system. Mortality rates of other diseases for which people could not get treatment may rise. Furthermore, health care settings, and especially emergency rooms, can become hubs of transmission. Many people get infected there, if prevention and control measures are not properly implemented. This is particularly true for unknown and emerging pathogens (for instance, MERS). A delay in the recognition of the disease will lead to delay in applying the right protection measures. Infected patients will be able to transmit the disease because health care workers, family members and other patients will not know how to protect themselves. Because health care settings and emergency rooms are usually crowded, the lack of appropriate infection prevention and control for example through triage, isolation, and other precautions can be very signifi cant. Health systems resilience after epidemics may be challenging for unprepared health systems. Indeed, if the health system is ill-prepared to cope with epidemics of infectious diseases, health care workers, at the frontline of the response, may themselves become infected and die. Tragic as such cases are, they have wider consequences. In countries where there are health staff shortages, the loss of several more health workers further weakens the health system. It takes years to train new medical staff and rebuild the health workforce. In the meantime, other constraints are burdening the health system that still has to provide the usual and regular services. Long-term substantial investments should therefore be made to strengthen health systems so they are able to provide safe, effective and qualitative health services before, during and after epidemics. Critical elements include an appropriate health fi nancing system and a fi t-for-purpose workforce that is trained, safe and provided with personal protective equipment. In addition, access to essential medical products and technologies and a business continuity plan are essential to ensure that health systems are strong enough to withstand the increased needs and to mitigate the impacts of very disruptive epidemics. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 21 14 8 9 30 36 10 2 4 2 6 4 9 9 13 7 9 9 34 36 9 13 7 9 5 8 6 7 8 7 13 15 17 7 10 7 10 10 6 5 13 26 9 22 16 12 8 5 7 14 6 1 13 4 4 57 4 7 4 7 9 11 1313 7 11 24 1 7 17 3 16 2 3 1 6 6 7 1 22 11 13 1 1 15 5 11 7 115 5 9 7 14 5 30 4 7 16 8 6 6 10 6 4 13 54 7 6 2 6 5 12 5 12 10 8 7 7 1 7 16 11 11 9 15 5 5 5 10 9 11 22 3 22 2 7 2 3 41 1 2 7 1 6 1 5 22 7 8 22 5 2 6 4 11 3 5 1 12 11 4 32 3 Burden of epidemics: illustrations Epidemic events* globally, 2011 – 2017**: A total of 1,307 epidemic events, in 172 countries * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Source: data reported to WHO and in media The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 22 Epidemic events* globally, 2011 – 2017**: A total of 1,307 epidemic events Number of epidemic events* by disease and year 2011 2012 2013 2014 2015 2016 2017** TOTAL Yellow fever Chikungunya Viral haemorrhagic fever Ebola virus disease Marburg virus disease Crimean-Congo haemorrhagic fever Rift Valley fever Cholera Typhoid fever Shigellosis Plague Lassa fever West Nile fever Zika virus disease Meningitis MERS-CoV Infl uenza A Monkeypox Nodding syndrome Nipah virus infection * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Source: data reported to WHO and in media PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 23 17 8 1 3 1 62 20 25 8 2 11 14 5 1 1 12 10 2 1 5 1 51 23 24 7 1 15 20 3 6 1 1 8 3 6 1 47 5 28 6 2 15 5 19 10 7 1 1 2 29 11 1 8 1 37 2 29 10 3 11 7 19 17 9 1 4 27 4 7 1 44 8 4 7 2 11 19 19 12 10 2 1 10 14 6 3 7 4 42 3 2 6 7 18 54 23 7 5 2 4 4 4 1 2 13 5 25 14 1 3 6 10 52 23 8 9 5 57 95 10 22 4 49 14 308 75 113 47 23 91 137 137 57 51 10 2 5 2011 179 183 164 197 182 213 189 220 200 180 160 140 120 100 80 60 40 20 0 2012 2013 2014 2015 2016 2017** * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Number of epidemic events* by year** Source: data reported to WHO and in media PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 24 The face of epidemics and pandemics has changed in the recent past and continues to do so. Many new factors contribute to an increase in the transmissibility and severity of infectious diseases. New lifestyles spread diseases further New and more intense factors amplify the transmission of diseases, either because they increase contacts between people, or between animals and people. In an era of rapid global change, many of these factors are almost inevitable. Among them are the fast and intense mobility of people, with increased transport and international travel, and greater inter-connectivity between megacities which are major transport hubs for aircraft, trains, road vehicles and ships. At the same time, globalization means increased trade among countries as well as greater movement of people within and between them. For decades, more and more people have been migrating from the countryside into cities, in search of better jobs and improved living standards. The unprecedented levels of urbanization and swelling populations of city dwellers inescapably pose greater risks of infectious disease transmission. These risks apply at least equally to densely populated areas on the periphery of cities, where rural areas overlap with them. Here, close and repeated contacts between people and livestock, domestic animals and wildlife raise the likelihood risk of new epidemics. To make matters worse, these peri-urban areas tend to be poorer, and local people have less access to health care facilities. The double jeopardy here is that their infections may go undetected and untreated, while the options for detection, prevention and control are reduced. The Ebola outbreak in 2014 has dramatically demonstrated this. Regrettably, the early years of the 21st century have seen many humanitarian emergencies, the massive displacement of populations fl eeing from civil unrest, political instability, confl icts wars and natural disasters. Millions of people have been uprooted from their homes and become either refugees, asylum- seekers or economic migrants, and fi nd themselves living in conditions, often overcrowded, that also increase infection risks. Challenges and risk factors for 21st century epidemics Potentially hazardous changes are also taking place in the use of land, agricultural practices and food production, such as live poultry and animal markets, and deforestation – which also leads to increased contact between people and wildlife. Some of these animals – monkeys, for example - are likely sources of new pathogens. Finally, ecological changes, such as climate change, also contribute to disease transmission. Other factors contribute to increase the virulence and mortality of epidemic diseases. Chief among them, as we have noted earlier, are limited access to health care, and poor health care systems that have inadequate infection prevention and control practices. The confl icts and wars referred to above not only cause civilian casualties and displacements: they destroy health care facilities exactly when and where they are most needed. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 25 Revisiting traditional control measures We have also seen that many traditional containment measures are no longer effi cient. They should therefore be re-examined in the light of people’s expectations of more freedom, including freedom of movement. Measures such as quarantine, for example, once regarded as a matter of fact, would be unacceptable to many populations today. The use of antibiotics to treat infections has been a turning point in the 20th century. Antimicrobial resistance is now on a rise. This is a major concern because a resistant infection may kill, can spread to others, and requires fi nding new ways to treat and limit the spread of the disease. Antimicrobial resistance occurs naturally, but is facilitated by the inappropriate use of medicines, for example using antibiotics for viral infections such as cold or fl u, or using antibiotics for animal growth in the animal sector. Among major infectious diseases, the treatment of tuberculosis is the most affected, and there are now strains of the microorganism that are multi-drug resistant. Equity and solidarity Epidemics are complex events: complex in their origins, their spread, their effects and their consequences – which can be at one and the same time medical, social, political and economic. The global impact of a single pathogen may vary signifi cantly between settings and there is no one-size-fi ts-all intervention strategy. Equity and solidarity issues are often part of the picture: access to medical countermeasures remains diffi cult, especially for low-income countries and countries facing humanitarian emergencies, and this diffi culty is worsened when vaccine or treatment production is limited. Market mechanisms do not ensure a fair distribution of resources based on public health demands. Global mechanisms are needed to ensure fair access to life-saving interventions during crises. A number of organizations are dedicated to this goal (among them are CEPI, the Coalition for Epidemic Preparedness Innovations; the International Coordinating Group; GAVI, the Vaccine Alliance; the Pandemic Infl uenza Preparedness Framework) but more efforts are required. Epidemics of rumours: a new risk to health A new word has entered the public health vocabulary: “infodemics”. These can be defi ned as the rapid spread of information of all kinds, including rumours, gossip and unreliable information. They are spread instantly and internationally through the growing popular use of mobile phones, social media, the internet and other communication technologies. A proliferation of web-based “experts” with diverse and often contradictory views can generate confusion, anxiety and even panic in times of serious infectious outbreaks. False or misleading information is dangerous. It can cause widespread public reluctance to adopt well- founded infection control measures promoted by health authorities – and thus delay essential interventions. This is why risk communication, a set of sophisticated skills, is increasingly employed by health authorities, agencies, physicians and professional health personnel. It is more important now than ever to learn and apply them. The latest and most accurate information must be conveyed frequently, and uncertainties related to an epidemic must be acknowledged in order to maintain credibility and public trust. Thus, we are recognizing that the complexity of 21st century epidemics and their prevention and control require not just new technologies techniques, but new skills and new attitudes all across the public health community. Risk communication is examined at greater length in a later section of this handbook. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 26 A whole-of-society approach is needed to tackle 21st century epidemics so that all the diverse disease drivers are taken into consideration: genetics and biological factors, ecology and the physical environment; human behaviour and demographics; social, political, and economic factors, and so on. This increasing convergence of many factors that drive and amplify outbreaks requires multi- disciplinary, multi-sectoral and multi-faceted approaches. Moreover, because epidemics are social problems as much as medical ones, we need to move beyond the traditional biomedical approaches to them. Social sciences should be an integral part of surge capacities adding anthropologists to the team of fi rst responders. Such a change enables issues of fear and trust to be addressed within the social context. Engaging communities and empowering them in advance as part of preparedness ensures that there is a better understanding of the human ecology. This will link community and biomedical perspectives for enhancing effective partnerships, ensuring that pre- existing relationships are built to respond to epidemics. Key insights into infectious disease epidemics PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 27 Because new infectious disease threats usually start locally, it is important to understand their dynamics in order to deny them the opportunity to spread further among people and overwhelm health systems. The dynamics of epidemic and pandemic diseases typically occur in four phases, although not all epidemic diseases necessarily go through each phase. The fi rst phase is the introduction or emergence in a community. The second phase is an outbreak with localized transmission, where sporadic infections with the pathogen occur. In the third phase, the outbreak amplifi es into an epidemic or pandemic - the pathogen is able to transmit from human to human and causes a sustained outbreak in the community, threatening to spread beyond it. The fourth phase is reduced transmission when human-to-human transmission of the pathogen decreases, owing to acquired population immunity or effective interventions to control the disease. These four phases are illustrated on this page. The dynamics of epidemics, as described above, defi ne the response and the sequence of interventions that then become necessary. Here, there are fi ve crucial stages. First is the anticipation of new and re-emerging diseases to facilitate faster detection and response; followed by their early detection of emergence in animal and human populations; the third stage is the containment of the disease at the early stages of transmission; followed by the control and mitigation of the epidemic during its amplifi cation; and fi fth, the elimination of the risk of outbreak or eradication of the infectious disease. These stages are elaborated in the illustration, and in the section that follows it. Epidemic phases INTRODUCT ION OR EMERGENCE LOCAL IZED TRANSMISS ION AMPL I F ICAT ION REDUCED TRANSMISS ION IMMUNITY PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 28 Anticipation: In this fi rst stage of response, emergence cannot be predicted, but it can certainly be anticipated, and the anticipation of risks enables a focus on the most likely threats. Anticipation encompasses forecasting the most likely diseases to emerge, and the quick identifi cation of the drivers that will worsen the impact or facilitate the spread. Preparedness plans, based on lessons learned from past experiences, should contain a variety of scenarios to allow for a reactive response to the unexpected. Early detection: Emerging and re-emerging diseases include new ones about which there is little scientifi c knowledge. These, therefore, often require investigation into their sources at the same time as the use of coordinated, rapid-containment measures. New diseases require new interventions. And because they appear irregularly or rarely, there is a need for constant vigilance, proactive risk assessment and the development of new management tools. Early detection allows the rapid implementation of containment measures, which are the key to reducing the risk of amplifi cation and potential international spread. Early detection begins at the health care setting, so health care workers must be trained to recognize potential epidemic disease, report quickly an unusual event (such as an unusual cluster of cases or deaths). Their role is also to reduce the risk of community transmission by isolating severely-ill patients; to prevent household transmission by protecting health care givers at home; and to reduce the mortality rate. Health care workers must also know how to protect themselves and employ infection prevention and control measures and how to avoid outbreaks amplifi ed in health care facilities. Epidemic phases and response interventions Anticipation Early detection Control and mitigation Elimination or eradicationContainment Introduction or emergence Localized transmission Amplification Reduced transmission Response interventions Epidemic phases PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 29 Once a new disease is recognized by the health system, early laboratory confi rmation is essential. When this cannot be done at country level, the affected countries must be confi dent they can count on the support of a network of more sophisticated regional or global laboratories. It is critically important for global health security that there is a system for safely taking samples and shipping specimens to relevant laboratories in full compliance with biosafety and biosecurity regulations. Containment: Effective and rapid containment of emerging diseases is just as vital as early detection in order to avoid a large scale epidemic. Rapid containment should start as soon as the fi rst case is detected regardless of the etiology, which is most likely to be unknown. It requires skilled professionals to safely implement the necessary countermeasures. Pre-training of these professionals is essential to guarantee the safety and effi ciency of the operations. Control and mitigation: Once the infectious disease threat reaches an epidemic or pandemic level, the goal of the response is to mitigate its impact and reduce its incidence, morbidity and mortality as well as disruptions to economic, political, and social systems. Elimination or eradication: Control of a disease may lead to its elimination, which means that is suffi ciently controlled to prevent an epidemic from occurring in a defi ned geographical area. Elimination means that the disease is no longer considered as a major public health issue. However, intervention measures (surveillance and control) should continue to prevent its re-emergence. Eradication of a disease – much more diffi cult and rarely achieved - involves the permanent elimination of its incidence worldwide. There is no longer a need for interventions measures. Three criteria need to be met in order to eradicate a disease: there must be an available intervention to interrupt its transmission; there must be available effi cient diagnostic tools to detect cases that could lead to transmission; and humans must be the only reservoir. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 30 Response tips and checklists A comprehensive outbreak response is always complex, comprising many elements that should be harmoniously coordinated. The following response tips are used to organize ideas and to make sure no important point is overlooked. In this handbook, specifi c tips are listed for each disease which will help keep focus on essential elements of each response. They are organized into four main blocks: • Coordinating responders (C) • Health Information (HI) • Communicating risk (C) • Health Interventions (HI) The checklists will help you assess what is important and necessary for the response. The outbreak response varies depending on the disease. For some diseases treatment is essential; for other diseases, vaccination is vital. C Coordinating responders C Communicating risk HI Health Information HI Health Interventions Note: Although Communicating risk (C) is part of Health Interventions (HI); it is seen here as a separate component in order to underscore the importance of risk communications. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 31 Coordinating responders An outbreak is by defi nition an exceptional event which often requires extra human and fi nancial resources and may also rely on additional partners, agencies and other sectors. Strong coordination is essential at all times to ensure that all those resources and partners are working effectively together to control the outbreak. WHO is often expected to lead the international response to support national health authorities. Effective coordination requires a dedicated physical space (usually an emergency operation centre); various tools to ensure optimal organization of meetings and fi ling of documentation (such as a list of contacts, and a meetings tracking system); a joint plan of action regularly updated as the situation evolves, to describe the interventions needed and the distribution of roles and responsibilities among stakeholders; and fi nally tools to ensure communication between the various stakeholders engaged in the response (phone numbers, a dashboard, maps, and a directory). Coordinating responders checklist ✔ What are the characteristics of the event that describe it as a crisis? ✔ Who are the people, groups and organizations who should work for the response? ✔ What should they do? (terms of reference, functions) ✔ Where can responders meet? (emergency operation centre) ✔ How do they share information? (share point, telephone numbers, generic email) For more information about coordinating responders: • Public Health Emergency Operations Centre Network (EOC-NET) http://www.who.int/ihr/eoc_net/en/ • WHO Emergency Response Framework (ERF) http://www.who.int/hac/about/erf/en/ MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 32 Health Information In every event, information is necessary to monitor it, measure the impact of interventions and to guide decision-making throughout the crisis. There are two particular types of information: surveillance of the disease, and information on the interventions (process and output indica- tors), which shows the coverage and impact of the interventions being performed. Surveillance provides information on the number of cases and deaths by period and place (people, time, and place). Information on the interventions enables knowing which ones are performed and what is their coverage and impact. Health Information checklist Surveillance ✔ Is there a case defi nition shared by all stakeholders? ✔ Which laboratories are involved in the testing /confi rmation of cases and deaths, and where are they situated? ✔ Is there an updated epidemiological curve and mapping of cases and deaths? ✔ Which are the risk groups, by gender and age? Interventions ✔ What is the target population? ✔ What material and human resources are needed and how much? ✔ What are the indicators of success? (e.g. vaccine coverage, house- holds targeted, number of people treated) PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 33 Communicating risk During the evolution of any major outbreak, cases and deaths will inevitably increase. An epidemic is the rapid spread of infectious disease to a large number of people in a given population within a short period of time. Similarly, there may well be another kind of epidemic – the rapid spread of information of all kinds, including rumours, gossip and unreliable information. We describe this phenomenon as an “infodemic”. Infodemics, like epidemics, can be managed. Field epidemiology is an important part of outbreak response. It encompasses three main areas: (1) monitoring and identifying health threats, (2) outbreaks investigation, and (3) actions for mitigation and control. Similarly, successful management of infodemics will be based on (1) monitoring and identifying them, (2) analysis of them, and (3) control and mitigation measures1. Risk communication is an essential intervention in any response to disease outbreaks, and is equally necessary to manage infodemics. Communicating risk in epidemics involves two-way communication that is dynamic and evolving as the outbreak develops. Outbreak risk communication involves three main strands that must work together. 1. Talk. Authorities, experts and response teams must quickly relay information on the nature of the event and the protective measures that people can take. We can use mass media including television, radio, newspapers and internet; social media and text-messaging; community radio; and leafl ets and posters. We can use social mobilizers and frontline responders; encourage community engagement; as well as face-to-face communication via trusted interlocutors such as community leaders, religious fi gures and community health workers. We must use translational communication approaches to develop messages that are appropriate for the target populations in terms of language, educational level and cultural contexts. 2. Listen. Responders, experts and authorities must quickly assess and understand the fears, concerns, perceptions and views of those affected; and tailor their interventions and messages to address such concerns. This requires the use of social science and community engagement expertise and methods. 3. Manage rumours. Disease outbreaks are often accompanied by the presence of false rumours and misinformation. Responders need to have ways to listen to such misinformation and correct examples of it in appropriate ways without delay. 1 This is called “infodemiology”. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 34 Communicating about the risks during outbreaks leads to specifi c outcomes. First, early, transparent and understandable communication on the event establishes lines of dialogue with affected populations and stakeholders, and builds trust in the response. This type of communication must have facts and information (that cater to the head); and include messages that acknowledge and respond to people’s concerns and fears (catering to the heart). Second, frequent but evolving communication will help create a trusted and dynamic relationship that can deliver advice on protective behaviors that populations and individuals can adopt. Third, communication must scope the risk in lay language, and also propose practical actions people can take. It must identify and help enable changes in people’s behaviours or practice (a temporary change) that can reduce exposure to and protection from the infectious hazard. Fourth, communication must display accountability by keeping people updated on the situation, on what is being done, and the impact of those actions in bringing the outbreak under control. Communicating risk checklist ✔ Has the situation been well analyzed in terms of audience, sources and specifi city of the context? ✔ Are tools in place in place to monitor an infodemic? Is monitoring reactive and adaptable enough? ✔ Has translational communication taken place (to transform scientifi c information into lay language and format)? ✔ Are the communication channels (and messengers) adequate, effective and acceptable to communities? (culturally, cost-effectively)? ✔ Is there a plan to communicate regularly with the various audiences? ✔ Have all personnel and volunteers in the risk communication response been trained in risk communication approaches, and consistent messaging? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 35 Health Interventions Each disease requires a different set of health interventions with the objectives of reducing (a) transmission, (b) severe morbidity and mortality (c) the impact on health systems and also on the political and other sectors. Health Interventions checklist ✔ What are the key interventions needed to control the outbreak at this stage of the event? ✔ Who should implement them? ✔ How is the impact measured on morbidity, mortality, transmission, and whole of society? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 36 Six critical functions of the Incident Management System (IMS) For more information about the management of events under the ERF: http://www.who.int/hac/about/erf/en/ The Emergency Response Framework (ERF) is an internal WHO tool that outlines a set of procedures to better respond to emergencies. Under this framework, for any emergency that requires a WHO operational response, the Organization activates the Incident Management System (IMS); recognized best practice for emergency management. WHO has adapted the IMS to consist of six critical functions. The four blocks and response tips are integrated into the Incident Management System. Although, all six functions of the IMS are critical for a successful response, the four blocks will highlight what is specifi c for each disease. Operations support & logistics Finance & administration Health operations & technical expertise HEALTH INFORMATION HEALTH INTERVENTIONS COMMUNICATING RISK Information & planning HEALTH INFORMATION Partner coordination COORDINATING RESPONDERS Leadership/ Incident management COORDINATING RESPONDERS PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 37 FOCUS 1 Community engagement during epidemics Defi ning a community “Community” is a broad term that can be applied to a variety of situations. It defi nes a distinct group of people who have a sense of belonging together. A community may be defi ned through the sharing of: • A common geographical location; • Common values or interests; • Common identity; • Etc. With new technologies, a community may be totally virtual, for instance a group of people sharing interests and points of view on social media. Why engage communities People live in unique social-cultural contexts, with relationship dynamics, and their own perception of risks, and trusted sources of advice. These all infl uence if they accept health advice or not. Experience has shown that merely telling people what to do, however scientifi c, does not always work. Engaging them is more effective. Even more fundamentally, people have a right to information that could protect their health and save lives, social fabric and economic well- being. Communities, when engaged are the frontline in detecting and managing epidemics. They are most affected and have the greatest infl uence in anticipation and preparedness as new diseases emerge or old ones re-emerge. They can detect outbreaks, and help in containment to prevent epidemic amplifi cation. They are able to implement mitigation measures (through change of individual and family practices change; implementing community measures and enabling changes at the systems level) to bring epidemics under control. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 38 Three elements of community engagement Disease outbreaks and epidemics are complex phenomena with three aspects that are intimately intertwined: medical, social and political. Community engagement is an approach to address the social (and to some degree the political) aspects of epidemics. Community engagement is essential for the effective control of infectious diseases, through acceptance of public health interventions. It is based on three elements: 1. Establishing a dialogue between responders and communities to understand the perceptions and beliefs on both sides, to identify the specifi c cultural and social patterns of transmission that exist at community level. 2. Building trust through this mutual understanding to fi nd joint solutions to reduce transmission. 3. Empowering communities, providing them with necessary medical and other supplies to implement the measures required to stop the disease, and progressively transferring knowledge for sustained and safe interventions within the community. A key community to empower during outbreaks are health care workers, and volunteers who are often the frontline responders. These frontline workers are “the face” or representatives of the whole outbreak response, to the community. Their attitude towards community members and their collaboration in implementing health advice can have signifi cant infl uence on how the advice is perceived and accepted, or rejected by community members. Key points of health action in epidemics that require intensive engagement of communities (affected populations as well as health care workers and frontline responders themselves) include: 1. Detecting an outbreak and detection of newly infected people (case detection, contact tracing); 2. Minimizing harmful practices (at individual and community levels) that can increase susceptibility and exposure; and adopting protective practices (medical and non- medical); 3. Seeking and providing health care as advised (in the household, community and health facility); 4. Re-integrating of survivors back into the community and to minimizing stigma; 5. Identifying and managing misinformation and rumours. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 39 Ten things to know 1. Disease outbreaks affect the social fabric of communities. A community is a social network, and infectious diseases outbreaks are deeply linked to the social life, the structure of society and people’s interactions. They spread through personal and social contacts and links at home or during professional and recreational activities. 2. Communities are the main actors in preventing, identifying, responding and recovering from the physical, psychological, social and economic impacts of epidemics. Communities are not passive subjects of interventions. 3. Epidemics are by nature rapidly evolving. The time pressure is particularly challenging for community engagement. The beginning of the outbreak is a crucial time to build the necessary trust with the population who can break the transmission cycle. Any outbreak response that builds on existing and trusted community engagement systems and work with trusted individuals and interlocutors are more likely to succeed. 4. Community understanding of diseases and their spread is complex, context-dependent and culturally mediated. Thus, a one-size- fi ts-all approach is neither desirable nor effective. 5. Communities are multi-layered, and power dynamics exist between individuals, groups and networks. Social scientists can help analyse these dynamics and work with specialists in health education, health promotion and local communities. There are simple tools that can assess relevant perceptions and beliefs for any outbreaks response. Together they can design the messages and interventions necessary to raise awareness, and adapt or change behaviours to meet the demands of a new infection. Embedding social scientists in response teams will also help to monitor how people adapt public health measures to different social contexts, and whether these are implemented in a way that respects social and cultural systems. 6. Community engagement helps to strengthen and ensure resilience to future outbreaks: when people have already learned how to implement their own solutions, they will be better able to deal with the next outbreak. 7. The approach and messaging directed towards each community has to evolve with the epidemic and incorporate new messages and communication methods as it unfolds. These messages must also proactively detect misinformation and rumours. Effective community engagement limits the opportunities for misunderstandings and the proliferation of rumours, and it mitigates the spread of fear and anxiety. 8. Identify people that the community trusts and build relationships with them. Involve them in decision-making to ensure interventions are collaborative, contextually appropriate and that communication is community-owned. 9. Two-way communication should be achieved through the most socially- acceptable and effective channels. Messages must be “translated” into local language, local context and to match the education levels and preferences (e.g. visual, written or oral cultures) of the target population. All communication with communities should be transparent, timely, easy-to-understand, acknowledge uncertainty, address affected populations, link to self-effi cacy, and be disseminated using multiple platforms, methods and channels. 10. Disease creates fear which often leads to practices that further amplify the epidemic. These can be both individual and collective. They can relate to the transmission of the disease, or the stigma, and extreme stress on the ties that bind communities. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 40 Ensuring effective community engagement To ensure effective community engagement: 3 elements are needed for communities and for fi eld responders. For communities: • Knowledge: communities must know what the disease is, how it is transmitted, and how to protect against it (social mobilisation messages); • Trust: it is the most important determinant to ensuring communities heed public health advice. Communities must be consulted, engaged, and whenever possible participate in identifying and implementing response measures that communities and responders want above all to treat patients and stop the epidemic; • Self-effi cacy: communities must be able to implement control measures (e.g. access to soap and water, to gloves, to waste management services, to transportation, to safe burial teams, etc.). For fi eld responders: • Understand: Field responders need to understand the local perceptions of the disease and of the response measures; • Listen: Field responders need to listen to communities’ fears and beliefs and adapt their own behaviours accordingly; • Support: Field responders need to support communities’ participation, ownership and resilience. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 41 FOCUS 2 Risk communication – a life-saving action in public health emergencies The essence of risk communication Risk communication is one of the key pillars of response to outbreaks. It refers to the real-time exchange of information, advice and opinions between health experts or offi cials and people who face a threat (hazard) to their survival, health or economic or social well-being. Its ultimate goal is that everyone at risk is able to take informed decisions to mitigate the effects a disease outbreak and take protective and preventive action. Effective risk communication not only saves lives and reduces illness (by informing people on how to protect their health), it also enables countries and communities to preserve their social, economic and political stability in the face of emergencies. For these reasons, risk communication is one of the core capacities that all countries have agreed to develop in order to prevent the international spread of disease and other dangers as required under the International Health Regulations (2005). PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 42 21st century aspects change and complicate risk communication There has been a paradigm shift from telling people what to do (message-based communication) to systematically listening to those affected, mainly due to new communication and media technologies and the way practices have evolved in the 21st century. The three big changes here are: 1. Experts and authorities are less trusted; 2. People now seek health advice mostly on public on-line sources, and their trusted social networks; 3. News media now function all day, every day. In addition, there is an increase of citizenship journalism and social media, as well as the rise of opinion versus well- sourced and referenced stories. In disease outbreaks and epidemics, life-saving decisions need to be made rapidly and actions must follow promptly, with the support of an informed public. Epidemics are unpredictable and alarming events that generate great anxiety in the general public, which can lead to extreme behaviours. Epidemics and the way they are managed have a high political profi le and capture the news media’s attention quickly leading to intense media interest (at national and international levels). Furthermore, emergency and outbreak communications now take place in a variety of contexts: • In a shifting complex, crowded environment: information is incomplete and many different actors are exchanging public health information and competing for authority. • Where communications are diverse: these include public communication, supporting national governments in risk communication, strategic communication, communication with affected communities and response personnel, media relations, knowledge transfer, message development, partner communication, internal communication and health promotion functions, etc. • Where risk communication is an under- resourced priority with a lack of investment in skills, resources and expertise at country level. • Where there is an increased public demand for participation in policy-making and for self-determination. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 43 Making it effective • Risk communication only works when there is communication based on trust between those who know (experts), those in charge (authorities or response teams) and those affected (communities). Without trust, people are unlikely to follow the advice given. Listening to and understanding peoples’ beliefs, concerns and perceptions is just as important as providing them with facts and advice. Explaining honestly what is known and admitting what is uncertain is essential. Effective risk communication thus depends on the credibility of those giving advice; their expressions of caring and empathy; and their ability to identify with people at risk. • Perception is key: - Experts and affected communities may not view the same infectious hazard – e.g. a disease outbreak – the same way. While experts depend on risk analysis based on biomedical and epidemiological data, affected communities use more sub- conscious pathways to defi ne risk; - People’s perception of risk can be affected by their beliefs, culture, education, political viewpoints, social norms and prior experience amongst others; - There are tried and trusted social science methods and approaches which can be used in epidemics to gauge perceptions. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 44 Ten things to know and do 1. Build trust • People must trust those responsible for managing the outbreak and for issuing information about it. Public confi dence that a government or agency is acting fi rst and foremost to safeguard their health will infl uence compliance with recommended control measures, and thus hasten outbreak containment. • Accountability is key: communicators must demonstrate that they and outbreak managers are accountable for what they say, promise, and do. • Evidence shows that to build trust, risk communication interventions should link to functioning and accessible services, be transparent, timely, easy-to-understand, acknowledge uncertainty, address affected populations, link to self-effi cacy and be disseminated using multiple platforms, methods and channels. • The building blocks of trust include: - Being perceived as experts with credibility by providing expert advice that is correct and accurate and being consistent with other trusted agencies and entities; - Being perceived as having a good character by telling the truth and not omitting important information, and acting on promises; - Identifying with the affected population as sharing the same concerns and fate; - Exhibiting good will through empathy and caring in messages and their delivery. 2. Communicate uncertainty proactively • Communication by authorities to the public should include explicit information about uncertainties associated with risks, events and interventions and indicate what is known and not known at a given time. • Announce the event as early as possible, even when the information is incomplete. This will establish you as the leader to communicate risk; it will build trust in you and the response; it will help enable changes in practice and behaviors to bring the outbreak under control; and it will minimize misinformation and rumours. • A good template to communicate uncertainty is as follows: - State what is known, what is unknown, and what you/your institution is doing about the issue; - Communicate early, be fi rst to announce the event if possible, communicate often, communicate regularly; - Provide information on the risk/danger; but supplement it with some advice on how people can protect themselves; - Speak as a human being, using empathy appropriately; - Do not over-reassure. 3. Engage communities • Identify people that the community trusts and build relationships with them and involve them in decision-making to ensure interventions are collaborative, contextually appropriate and that communication is community-owned. • Community engagement is one important start for communicating risk and facilitating changes in behaviours and practices (see Focus 1, page 38). 4. Message well • According to the latest evidence, risk should not be explained in technical terms as this is not helpful for promoting risk mitigation behaviours. Consistent messages should come from different information sources and emerge early in the outbreak. Messages should promote specifi c actions people can realistically take to protect their health. 5. Establish and use listening and feedback systems • Use multiple means (surveys, focus group discussions, community walk-throughs, key informants, feedback from front-line responders, partners’ and stakeholders’ PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 45 feedback, social media, etc.) to listen to the public and affected communities. • Use these to understand what concerns people regarding the outbreak or the measures we are asking them to adopt. • Use these systems to test messaging and materials developed to support risk communication. 6. Use social media as appropriate • Social media should be used to engage the public, facilitate peer-to- peer communication, create situational awareness, monitor and respond to rumours, public reactions and concerns during an emergency, and to facilitate local level responses. • Social media and traditional media should be part of an integrated strategy with other forms of communication to achieve convergence of verifi ed, accurate information. 7. Risk communication operations requires resources • Risk communication in epidemics is a massive operational undertaking and requires people, logistics, material and funds. • Different types of expertise in many areas are required: media communications, social media, spokespersons, social mobilization, health promotion, community engagement, behavioral change communication; stakeholder communication, communication related to travel and trade, social science methods, etc. 8. Treat Emergency risk communication as a strategic role, not an add-on • Emergency risk communication should be a designated strategic role in global and national emergency preparedness and response leadership teams. • The International Health Regulations (2005) require all Member States to build national capacity to communicate risk in two domains: - Systems capacities; - People capacities. • The Joint External Evaluation (JEE) process championed by the Global Health Security Agenda measures national risk communication capacity in six domains: - National strategies, policies and plan; - Coordination; - Stakeholder communication; - Public communication (using mass media approaches); - Communicating and engaging with communities; - Dynamic listening (to misinformation, fears, concerns) and rumour management. 9. Establish coordination and information systems • Develop and build on agency and organizational networks across geographic, disciplinary and, where appropriate, national boundaries. • Tailor information and communication systems to the needs of users and involve local stakeholders to guarantee the fl ow of information across sectors. 10. Build capacity for the next emergency • Preparation and training of personnel for emergency risk communication should be organized regularly and focus on coordination across agencies. • Emergency risk communication requires a defi ned and sustained budget which should be a part of core budgeting for emergency preparedness and response. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 46 Other factors to remember While there is an increasing body of evidence as to what constitutes effective risk communication, every outbreak is unique. Therefore risk communication must be adapted to: • The infectious hazard (its severity, lethality, modes of transmission, how it can be diagnosed, treated or managed); • The geography of the outbreak: contained or widely distributed; national or international spread; affecting certain vulnerable communities or the general population; in a remote forgotten village or major city; affecting to poor or affecting travel and trade; • The levels of trust that exit between the affected or at-risk populations and their authorities and experts; or the response teams; • People’s underlying beliefs, cultures, traditions, values and practices; • Education, levels of awareness, access to understandable information; and trusted channels of communication; • Self-effi cacy: do communities have the ability, resources and environment to follow health advice? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 47 FOCUS 3 Treating patients and protecting the health workforce Advances in medicine: antibiotics, antivirals, vaccines and new treatments With the remarkable progress in medicine and related technologies, briefl y mentioned at the beginning of this publication, many infectious diseases can now be prevented and treated. This is the result of a public health revolution that began in the 1940s with the discovery of antibiotics for bacterial diseases, and expanded with improvements in their safety, effi cacy and acceptability. Similarly, the development of vaccines, particularly for infants and young children, has given global protection against a number of childhood killers. For example, WHO estimates that there is now 86% global coverage of the combined diphtheria-tetanus-pertussis vaccine for babies1. In recent decades, hundreds of millions of children all over the world have grown up free of the risk of deadly and disabling diseases. Adults have benefi ted likewise, with protection against a wide range of infections that can explode into epidemics – cholera, infl uenza and yellow fever, for example. For many deadly diseases, there are vaccines that ideally should be administrated in routine, large-scale immunization to prevent the occurrence of the disease. Some vaccines can also be used during a reactive campaign when there is an epidemic in which the immunity of the population is not high enough. The public health revolution continued towards the end of the 20th century with the discovery of antivirals, such as that used against HIV. Meanwhile, there have also been great strides forward in the fi elds of diagnostics and treatments, such as monoclonal antibodies, that are also becoming more widely available but the price of some of them is still very high and they are not yet available for mass administration. Such advances – and the early problems that followed them – including a degree of public health complacency, and the emergence of antibiotic resistance - have completely changed the way infectious diseases are confronted today. 1 WHO data, 2016. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 48 Treating patients with supportive care But whether the focus is on antibiotics, antivirals, vaccines or the whole armoury of other treatments, the vital, universal fact is that they can only be benefi cial when they are administered by skilled, qualifi ed and dedicated health personnel, all across the spectrum of care. When, for example, no specifi c treatment is available for a given disease, adequate clinical management can still protect and save lives. This has been shown by a dramatic reduction in deaths from Ebola in West Africa in 2014 – from 75% to 33% mortality, achieved through the provision of better supportive care for patients. Protecting frontline responders The role of the health workforce should never be underestimated nor taken for granted. In general, much of their day-to-day work is mundane and routine, providing tried-and- tested care and treatment for familiar illnesses, disabilities and injuries. But when an epidemic strikes, they make a vital difference at all levels, whether as community health workers and volunteers, midwives, nurses, or doctors. With little or no warning, they are transformed into frontline responders, thrust into immediate contact with infected communities and individuals. Family members, too, take on the role of caring for their relatives at home, often linking up with health staff in clinics, hospitals and emergency centres. This transformation is double-edged and dangerous for frontline responders. First, their immediate priorities are to prevent the spread of an epidemic, protect those people who are most at risk, and to care by all possible means for those who are already infected. The related dangers are obvious: health workers are putting themselves at risk. They fi nd themselves in the most dangerous place at the most dangerous time. Yet, because their job is to care for the sick and injured, health care workers are often viewed as “immune” to injury or illness. Their patients come fi rst. However, human-to- human transmission is a major factor in many infectious diseases that cause epidemics. Patients are highly contagious and can spread the disease at home, at work, in public spaces, but also in hospitals. Thus, it is essential to protect them from infection – both for their own safety and for the wider protection of the affected community. It is here that emergency planning, preparation, training and coordination are so essential, as is the urgent provision of practical safeguards, especially the necessary personal protective equipment and the knowledge of how to use it properly. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 49 Confronting the human resources crisis These measures may seem obvious, but the role of frontline responders is frequently shackled by a major disadvantage: there are not nearly enough of them. This unpalatable truth applies to the health workforce in general. It is a global problem, but it is most acute in the poorest countries with weakest health systems, where epidemics are most likely to erupt. Protecting the occupational health of health workers is critical to have an adequate workforce of trained and healthy health personnel. This is nowhere more true than at the heart of an infectious disease epidemic. Around the world, health care facilities employ over 59 million workers2. Yet at the same time, there is a chronic shortage of them in more than 50 countries. This crisis in human resources for health has persisted for decades, despite numerous attempts to tackle it, but recent actions show notable progress. It is not just a matter of numbers. While there has long been an exclusive focus on how many there are, against how many are needed, there is growing public health agreement on according equal importance to accessibility, acceptability, quality and performance in addition to availability. These four factors are inter-related and inter- dependent. The absence or inadequacy of any one of them undermines all the others. Without suffi cient availability, accessibility to health workers cannot be guaranteed. If they are available and accessible, without acceptability, the health services may not be used. When the quality of the health workforce is inadequate, improvements in health outcomes will not be satisfactory. Elaboration of these complex issues at length goes beyond the scope of this handbook. But it is important that they are taken into account in the context of infectious disease prevention, treatment and control. Indeed, they lead to recognition that protecting health care workers has the added benefi t to contributing to quality patient care and health system strengthening. If it is accepted that health begins with health workers, their empowerment is necessary on a general basis. Their voice, rights and responsibilities must play a central role in developing and implementing solid policies and strategies towards universal health coverage. This applies to the context of epidemic disease control as much as it does to other health issues more widely. The engagement of communities during epidemics, including health workforce community, needs to be at the center of the epidemic response. For more information about protecting the health workforce: WHO global health workforce alliance website http://www.who.int/workforcealliance/en/ 2 WHO data: http://www.who.int/occupational_ health/topics/hcworkers/en/ PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 50 DISEASE SPECIFIC SUPPORTIVEMAJOR MODE OF TRANSMISSION Clinical management VACCINATION SAFE & DIGNIFIED BURIALS ENHANCED INFECTION PREVENTION & CONTROL VECTOR CONTROL WATER & SANITATION Chikungunya Cholera Dengue Ebola virus disease Hepatitis E Infl uenza Lassa fever Leptospirosis Malaria http://www.who.int/csr/disease/chikungunya/en/ http://www.who.int/cholera/en/ http://www.who.int/denguecontrol/en/ http://www.who.int/ebola/en/ http://www.who.int/mediacentre/factsheets/fs280/en/ http://www.who.int/infl uenza/en/ http://www.who.int/csr/disease/lassafever/en/ http://www.who.int/topics/leptospirosis/en/ http://www.who.int/malaria/en/ Vector Fecal oral / water Vector Animals / contact Fecal oral / water Respiratory Rodent / contact Rodent Vector Crimean-Congo haemorrhagic fever (CCHF) http://www.who.int/csr/disease/crimean_congoHF/en/ Animals (mainly ticks) / contact 1 Marburg virus disease http://www.who.int/csr/disease/marburg/en/ Animals / contact ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ 2 3 4 5 1 Ribavirin use currently under review by WHO; 2 Oral vaccines; 3 There is a vaccine (Dengvaxia®) currently under assessment; 4 Intramuscular and intranasal vaccines; 5 Safe and dignifi ed burials for highly pathogenic non-human infl uenza; Major modes of transmission and interventions per disease PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 51 Meningitis MERS/SARS Monkeypox Plague (pneumonic) Plague (bubonic) Polio Rickettsia Shigellosis Rift valley fever Smallpox Typhoid fever West Nile fever Yellow fever Zika http://www.who.int/csr/disease/meningococcal/en/ http://www.who.int/topics/coronavirus_infections/en/ http://www.who.int/mediacentre/factsheets/fs161/en/ http://www.who.int/csr/disease/plague/en/ http://www.who.int/csr/disease/plague/en/ http://www.who.int/topics/poliomyelitis/en/ http://www.who.int/csr/disease/riftvalleyfev/en/ http://www.who.int/csr/disease/smallpox/en/ http://www.who.int/immunization/diseases/typhoid/en/ http://www.who.int/mediacentre/factsheets/fs354/en/ http://www.who.int/csr/disease/yellowfev/en/ http://www.who.int/topics/zika/en/ Respiratory Respiratory Animals / contact Respiratory Rodent Fecal oral Vector Fecal oral / food Animals / vector Respiratory Food Vector Vector Vector Measles http://www.who.int/immunization/diseases/measles/en/ Respiratory DISEASE SPECIFIC SUPPORTIVEMAJOR MODE OF TRANSMISSION VACCINATION SAFE & DIGNIFIED BURIALS ENHANCED INFECTION PREVENTION & CONTROL VECTOR CONTROL WATER & SANITATION ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ 6 7 8 6 Oral and intramuscular/subcutaneous polio vaccines; 7 Intramuscular and scarifi cation vaccines; 8 Intramuscular/subcutaneous vaccines. Clinical management PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 52

PART II 10 KEY FACTS ABOUT 15 DEADLY DISEASES Be in the know EBOLA VIRUS DISEASE LASSA FEVER CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF) YELLOW FEVER ZIKA CHIKUNGUNYA AVIAN AND OTHER ZOONOTIC INFLUENZA SEASONAL INFLUENZA PANDEMIC INFLUENZA MIDDLE EAST RESPIRATORY SYNDROME (MERS) CHOLERA MONKEYPOX PLAGUE LEPTOSPIROSIS MENINGOCOCCAL MENINGITIS 10 THINGS YOU SHOULD KNOW Ebola virus disease 1. Ebola virus disease transmits from person to person through close contact 2. Health care workers, mourners and family members are the most at risk to get infected 3. At-risk persons should be informed about Infection Prevention and Control (IPC) measures and be provided with appropriate personal protective equipment 4. Community engagement, active case fi nding, contact tracing, laboratory support, and safe and dignifi ed burials are key to control outbreaks 5. Early supportive care improves survival 6. Ebola is diffi cult to distinguish from other diseases with haemorrhage presentation 7. The Ebola virus can persist in people recovering from the disease for several months 8. Ebola survivors may suffer from stigma and sequelae 9. There are ongoing researches for vaccines, diagnostics and treatments 10. Ebola is a viral haemorrhagic fever that occurs mostly in rural and remote areas of Africa EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 56 Ebola virus disease response tips Coordinating responders • Engage with partners involved in the response (community engagement, surveillance, laboratory, case management and IPC) • Engage with religious and community leaders Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate early and frequently • Key messages are: - Ebola is transmitted through contact with body fl uids of infected animals and humans - Dead bodies of patients are contagious - Apply IPC measures when in contact with sick or dead patients and animals - People are not infectious if they do not show symptoms - People with symptoms should seek medical advice as supportive treatment increases chances of survival Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive treatment - Protect health care workers • Surveillance, contact fi nding and contact tracing • Safe and dignifi ed burials • Vaccination under expanded access (rVSV-ZEBOV vaccine for Zaire Ebola virus) EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 57 Ebola virus disease transmits from person to person through close contact • Incubation period ranges from 2 to 21 days. • Humans are not infectious as long as they do not develop symptoms. During the course of the disease, they remain infectious as long as their blood contains the virus. • Ebola is fi rst introduced into the human population through close contact with the blood, secretions, organs or other body fl uids of infected animals such as fruit bats, chimpanzees, gorillas, monkeys, forest antelopes and porcupines found ill or dead, often in the rainforest. • Ebola then spreads through human- to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other body fl uids of infected people. - Infection can also occur if the broken skin or the mucous membranes of a healthy person comes into contact with items or environments contaminated with body fl uids from an infected person. These may include soiled clothing, bed linen, gloves, and protective equipment; - Medical waste, such as used syringes, should be disposed carefully, as they are a source of health care workers infection. • Ebola virus disease has not been reported to be transmitted by aerosols. It is not airborne. Health care workers, mourners and family members are the most at risk to get infected Population at high-risk of being infected include: • Health care workers if Infection Prevention and Control (IPC) measures are not in place or not well followed while caring for patients. • Mourners, as burial ceremonies involve direct contact with the body or body fl uids of the deceased (washing, touching…) because levels of Ebola virus remain high after death. • Family members or others in close contact with infected people and caring for them in contact with body fl uids or contaminated items. 1 2 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 58 At-risk persons should be informed about IPC measures and be provided with appropriate personal protective equipment • All health care providers working at all levels of the health system, and family members caring for the sick, should be fully informed about the disease and its mode of transmission and should follow recommended Infection Prevention and Control (IPC) measures strictly. • They should be provided with appropriate Personal Protective Equipment (PPE). • Standard precautions with all patients should be applied. They include: hand hygiene; use of gloves before contact with body fl uids, mucous membrane, non-intact skin and contaminated items; gown and eye protection before procedures and patient-care activities likely to involve contact with or projection of blood or body fl uids; injection safety practices; safe cleaning, disinfection and waste management; isolation of cases and appropriate fl ow of patients. 3 Community engagement, active case fi nding, contact tracing, laboratory support, and safe and dignifi ed burials are key to control outbreaks • The aim of Ebola response is to contain the outbreak at its source. Ebola virus transmission is stopped by : 1. Community engagement as communities are essential for responding to Ebola outbreaks. They have a role to play in the detection of new cases. Communities should be engaged in the response since the early stage and be provided by the necessary information so that they can adapt the public health measures to their socio-cultural beliefs and ensure compliance of the community members. 2. Active case fi nding, rapid isolation of patient and early laboratory confi rmation of suspected cases. Active 4 case fi nding refers to actively searching for new cases (for instance, going from house to house in the community, asking if people are sick or if people have died). New (suspected) cases should be rapidly and safely referred to treatment centres for isolation and treatment. 3. Laboratory testing in Ebola treatment units is crucial for classifi cation of cases, to streamline contact tracing, for patient triage and management and to support research and development (to develop and validate new point-of- care diagnostics, new therapeutics and new vaccines). 4. Contact tracing which refers to the follow-up of persons who may have come into contact with a person infected with the Ebola virus (or their body fl uids, exposed environment such as linens, a dead animal, etc.). Contacts should be followed-up over a period of 21 days after the last exposure, looking for symptoms such as fever, and referred to treatment centres if they become ill. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 59 5. Early supportive care (rehydration and pain relief) should be provided to patients as early as possible as it reduces mortality. 6. Safe and dignifi ed burials teams are necessary to facilitate mourning by affected families and communities and to stop transmission of Ebola virus from deceased patients. • Other key elements to put in place to control outbreaks are: - Surveillance and follow-up of survivors as the virus may persist in their body fl uids and they may be infectious; - Psychosocial support to patients and their families; - Public health emergency plans and standard operational procedures at designated points of entry, in accordance with the International Health Regulations (IHR) (2005). • After 42 days (two 21-day maximum incubation period for Ebola virus) with no new cases, the human-to- human transmission is controlled and the outbreak can be declared over. Early supportive care improves survival • Early supportive care, especially rehydration with oral or intravenous fl uids, and treatment of specifi c symptoms, improves survival. • Other treatments being used to help people survive Ebola virus disease include, where available and IPC measures strictly implemented, kidney dialysis, blood transfusions and plasma replacement therapy. • It is important that patients and families trust health workers to accept being care of in dedicated treatment facilities. • Care should be patient-centered and respect patients’ preferences. • There is, as yet, no commercially treatment available for Ebola. However, a range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. 5 • An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea. The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11841 people during 2015. Among the 5837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine. - The trial was led by WHO, together with Guinea’s Ministry of Health, Médecins sans Frontières and the Norwegian Institute of Public Health, in collaboration with other international partners. A ring vaccination protocol was chosen for the trial, where some of the rings are vaccinated shortly after a case is detected, and other rings are vaccinated after a delay of 3 weeks. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 60 Ebola is diffi cult to distinguish from other diseases with haemorrhage presentation • First symptoms are common to many other diseases, they are not specifi c: sudden onset of fever, fatigue, muscle pain, headache and sore throat. • These fi rst symptoms are usually followed by: vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding (e.g. oozing from the gums, blood in the stools). • Ebola virus infection can be confi rmed with laboratory diagnostics: - The diagnostic methods are the following: o Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; o Antibody-capture Enzyme-Linked Immunosorbent Assay (ELISA); o Antigen-capture detection test; o Serum neutralization test; o Electron microscopy; o Virus isolation by cell culture. - Current WHO recommended tests include: o Automated or semi-automated Nucleic Acid Tests (NAT) for routine diagnostic management; o Rapid antigen detection tests for use in remote settings where NAT are 6 not readily available. These tests are recommended for screening purposes as part of surveillance activities. However reactive tests should be confi rmed with NAT. - The preferred specimens for diagnosis include: o Whole blood collected from live patients exhibiting symptoms; o Oral fl uid specimen stored in universal transport medium collected from deceased patients or when blood collection is not possible (swab for dead bodies). • Recommended case defi nitions for Ebola or Marburg virus diseases can be found on: http://www.who.int/csr/resources/ publications/ebola/case-definition/en/. During an outbreak, case defi nitions are likely to be adapted to new clinical presentation(s) or different modes of transmission related to the local event. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 61 The Ebola virus can persist in people recovering from the disease for several months • People can survive from Ebola virus disease. • Ebola virus is known to persist in immune- privileged sites in some people who have recovered from Ebola virus disease. These sites include the testicles, the inside of the eye, and the central nervous system. In women who have been infected while pregnant, the virus may persist in the placenta, amniotic fl uid and fetus. In women who have been infected while breastfeeding, the virus may persist in breast milk. • Several cases of sexual transmission have been reported. All Ebola survivors and their sexual partners should receive counselling to ensure safe sexual practices, be provided with condoms when discharged from Ebola treatment unit and enrolled in national semen and body fl uid testing programmes. • Male Ebola survivors should be offered semen testing when discharged from Ebola treatment unit, and then, for those who test positive, every month thereafter until their semen tests negative for virus twice by RT-PCR, with a minimum interval of two weeks between tests. Relapse- symptomatic illness in someone who has recovered from EVD due to increased replication of the virus in a specifi c site is a rare event, but has been documented. Reasons for this phenomenon are not yet fully understood. 7 Ebola survivors may suffer from stigma and sequelae • Survivors may suffer from physical sequelae and should be followed- up. Most common physical sequelae are: musculoskeletal, ocular, auditory, abdominal, neurological, and sexual issues. • Survivors may suffer from stigma. They may be rejected from their community and should be followed-up and assisted, if needed, regarding employment, living conditions, family, social support from their community, etc. • They should receive education and counselling regarding the possible sequelae and psycho-social challenges they might face. • Specifi c follow-up considerations should be applied for children and pregnant women. 8 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 62 There are ongoing researches for vaccines, diagnostics and treatments • Research is ongoing to develop and evaluate vaccines, diagnostics tools and therapeutics. Currently, no vaccine, or new therapeutic has been licensed. • An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea. The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11 841 people during 2015. Results of effi cacy trial show to be 100% effective in those who received it as part of a ring vaccination trial. • There are 12 candidate vaccines and one (rVSV- ZEBOV, effi cient against Zaire Ebola virus) that could be used under expended access during outbreaks. • A range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. • Four Nucleic Acid Tests (NAT) and three Rapid Diagnostic Tests (RDT) were approved for emergency use during the Ebola crisis 2014-2016. These tests could be used during outbreak situation, in remote settings. 9 Ebola is a viral haemorrhagic fever that occurs mostly in rural and remote areas of Africa • Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe illness in humans. The average case fatality rate is around 50%. It has varied from 25% to 90% in past outbreaks. • Ebola virus disease is a zoonotic disease, transmittable from wild animals to humans. • Reservoir of the disease is fruit bats. The disease is also found in monkeys, apes, antelope and porcupines. Ebola virus disease should be suspected if any of these animals is found ill or dead in the rainforest. 10 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 63 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reservedSource: WHO/IHM, as of 15 February 2018 Geographic distribution of Ebola virus disease outbreaks (1976-2018) Country with serological evidence Country that reported Ebola virus disease imported cases Country that reported Ebola virus disease outbreaks EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 64 More information about Ebola virus disease: • Ebola WHO webpage: http://www.who.int/ebola/en/ • Ebola WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs103/en/ • Ebola and Marburg virus disease epidemics: preparedness, alert, control and evaluation http://www.who.int/csr/resources/publications/ebola/manual_EVD/en/ • Case defi nitions: http://www.who.int/csr/resources/publications/ebola/case-defi nition/en/ • Laboratory diagnosis: http://www.who.int/csr/resources/publications/ebola/laboratory- guidance/en/ • Clinical management: http://www.who.int/csr/resources/publications/clinical-management- patients/en/ • Clinical care for survivors of EVD: http://www.who.int/csr/resources/publications/ebola/guidance-survivors/en/ • Infection prevention and control guidance for care of patients if health care settings, with focus on Ebola: http://www.who.int/csr/resources/publications/ebola/fi lovirus_infection_ control/en/ • Safe and dignifi ed burials: http://www.who.int/csr/resources/publications/ebola/safe-burials/en/ • Ebola WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 65 1. The reservoir of Lassa fever is a rat 2. Humans are primarily infected through exposure to rats’ urine or faeces 3. Human-to-human transmission occurs then through direct contact with body fl uids of infected persons 4. Pregnant women and infants may experience severe disease 5. Lassa fever is hard to distinguish from other viral diseases 6. Hygiene and rodent control are the best prevention in communities 7. Strict implementation of infection prevention and control measures in health care settings is critical to prevent the spread of the disease 8. Early supportive treatment reduces mortality 9. Outbreak control relies on community engagement, active case fi nding, contact tracing and safe and dignifi ed burials 10. Lassa fever is a viral haemorrhagic fever that occurs in West Africa 10 THINGS YOU SHOULD KNOW Lassa fever LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 66 Lassa fever response tips Coordinating responders • Engage with partners involved in the response (surveillance, laboratory, case management, infection prevention and control (IPC) and community engagement) • Engage with religious and community leaders Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate about how to protect from becoming infected - Provide targeted communication to at-risk groups such as pregnant women • Key messages to general public: - Humans are primarily infected through exposure to rats’ urine or faeces - Avoid contact with body fl uids of sick people - Seek health advice rapidly if you show symptoms - Wash your hands regularly - Implement measures to reduce contact with rodents Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive treatment - Protect health care workers • Surveillance, contact fi nding and contact tracing • Safe and dignifi ed burials • Rodent control LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 67 The reservoir of Lassa fever is a rat • The animal reservoir of Lassa virus is a rodent : the Mastomys rat, commonly know as the “multimammate rat”. • Rat are infected at birth and are chronic asymptomatic carriers of Lassa virus. • The infected rats do not become ill but can shed the virus in their urine and faeces. • The virus is present in aerosolized excreta, particularly urine. Humans are primarily infected through exposure to rats’ urine or faeces • Humans usually become infected with Lassa virus from exposure to urine or faeces of infected rats. • Humans are infected through: - Direct contact by catching, handling and preparing Mastomys as a food source (more frequent); - Ingestion of food contaminated by infected rodent excreta; - Direct contact with objects and surfaces contaminated by rats’ urine and faeces; - Inhalation of aerosolized virus (rare). 1 2 • Transmission of Lassa fever virus from rats to humans is common, since these rodents scavenge on human food items and readily colonize areas where humans live. • People at high risk of being infected, through rat-to-human transmission, are: - Persons living in rural areas where Mastomys are usually found, especially in communities with poor sanitation or crowded living conditions; - Persons hunting and consuming rodent products. LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 68 Human-to-human transmission occurs then through direct contact with body fl uids of infected persons • Lassa virus may spread from human to human through direct contact with the blood, urine, faeces, or other body secretions of a person infected with Lassa fever. • Humans can also be infected through direct contact with contaminated bedding or clothing. • Human-to-human and laboratory transmission also occur, particularly in hospitals lacking adequate infection prevention and control measures (e.g. the virus may be spread by contaminated medical equipment, such as re-used needles). • People most at risk of being infected, through human-to-human transmission, are: - Health care workers or anyone caring for Lassa fever patients in the absence of proper infection prevention and control practices; - People handling dead bodies of infected patients (e.g. during funerals). • Sexual transmission of Lassa virus has also been reported. • There is no evidence supporting airborne spread between humans. 3 Pregnant women and infants may experience severe disease • Lassa fever occurs in all age groups and both sexes. • The disease is especially severe late in pregnancy: - Maternal mortality can be greater than 30% in third trimester and 50% in the last month; - Fetal loss is occurring in more than 80% of cases during the third trimester; - Pregnant women show increased level of viraemia (virus levels in the blood). • Infection in infants is also associated with a very high case fatality rate. • Infants (up to two years old) can present a “swollen baby syndrome” (edema, abdominal distension and bleeding, often leading to death). Older children experience similar symptoms as adults. 4 LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 69 Lassa fever is hard to distinguish from other viral diseases • Symptoms of Lassa fever are very varied and non-specifi c, which makes clinical diagnosis diffi cult, especially early in the course of the disease. Lassa fever can be diffi cult to distinguish from other viral haemorrhagic fevers (e.g. Ebola virus disease) as well as from other diseases that cause fever such as Malaria, Typhoid fever, Yellow fever, Infl uenza, Measles, Shigellosis, Cholera, Leptospirosis, Rickettsial infections, Relapsing fever, Meningitis, Bacterial sepsis, Hepatitis. • Symptoms of Lassa fever can occur from 2 to 21 days after coming into contact with the virus. The incubation period is usually from 7 to 10 days. • About 80% of infected people do not show symptoms (they are asymptomatic) or experience a mild disease. • The onset of the disease, when it is symptomatic, is usually gradual. Symptoms usually start with fever, general weakness, and malaise. • After a few days, headache, sore throat, muscle pain, chest pain, nausea, vomiting, diarrhoea, cough, and abdominal pain may follow. • In mild cases, the patient usually recovers rapidly. • In severe cases (20%) facial swelling, fl uid in the lung cavity, bleeding from the mouth, nose, vagina or gastrointestinal tract and low blood pressure may develop. Severe cases require hospitalization. 5 • Shock, seizures, tremor, disorientation, and coma may also be seen in the later stages. Death (1 to 2% of total infected symptomatic people: severe and mild cases) usually occurs within 14 days of onset in fatal cases. • Various degrees of deafness occur in 25% of severe cases who survive the disease. In half of these cases, hearing returns partially after 1–3 months. Transient hair loss and gait disturbance may occur during recovery. • Lassa fever should be considered in febrile patients returning from West Africa, especially if they have had exposures in rural areas or hospitals in countries where Lassa fever is known to be endemic. • Patient history is essential for diagnosis. Suspected case: Illness with gradual onset with one or more of the following: malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhoea, myalgia, chest pain hearing loss and a history of contact with rodents or with a case of Lassa fever. Probable case: A deceased suspected case (where it has not been able to collect specimen for laboratory confi rmation) that has an epidemiological link with a laboratory confi rmed case. Confi rmed case: A suspected case that is laboratory confi rmed (positive for IgM antibodies, positive for Lassa virus antigen, positive for Lassa RNA by RT- PCR or virus isolation). LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 70 • Lassa virus infections can only be diagnosed defi nitively in the laboratory using the following tests: - Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; - Antibody Enzyme-Linked Immunosorbent Assay (ELISA); - Antigen detection tests; - Virus isolation by cell culture. • Laboratory specimens may be hazardous and must be handled with extreme care. Handling specimens with live virus requires Biosafety level 4. • Diagnostic assays have also been made commercially available, but none have been evaluated by WHO prequalifi cation process. Hygiene and rodent control are the best prevention in communities • To prevent infection, people should follow basic hygiene practices: - Wash their hands regularly; - Cook food thoroughly. • Raising awareness is a fi rst step towards better rodent management. • At the community level, to reduce human- rodent contacts, people are advised to: - Store food in covered rodent-proof containers; - Keep homes clean and clear away any rubbish in or around the house; 6 - Keep a cat; - Implement measures to reduce rodent populations. This would require strong political commitment and sustained efforts. Techniques that could be used include: o Trapping and poisoning; o Using non-lethal, non-toxic alternatives to chemical rodenticides (research ongoing); o Reducing reproduction (fertility control); o Etc. Infectivity Days 0 1 2 3 4 5 6 8 97 • Fever • Extreme fatigue • General weakness • Face swelling • Low blood pressure • Nose bleeding • Headache • Severe sore throat • Diarrhoea LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 71 Strict implementation of infection prevention and control measures in health care settings is critical to prevent the spread of the disease • In health care settings, staff should always apply standard infection prevention and control precautions when caring for patients, regardless of their presumed diagnosis. These include: - Hand hygiene; - Respiratory hygiene; - Use of personal protective equipment (to block splashes or other contact with infected materials); - Safe injection practices; - Safe and dignifi ed burial practices. • Health care workers caring for patients with suspected or confi rmed Lassa fever should apply extra infection control measures to prevent contact with the patient’s blood and body fl uids and contaminated surfaces or materials such as clothing and bedding. When in close contact (within 1 metre) of patients with Lassa fever, health care workers should wear face protection (a face shield or a medical mask and goggles), a clean, non- sterile long-sleeved gown, and gloves (sterile gloves for some procedures). • Health care workers should remember that maternity wards are potential sites of amplifi cation as miscarriage and natural abortion with massive bleeding may conclude from women with Lassa fever. Early supportive treatment reduces mortality • Treatment is supportive: it consists in symptomatic treatment, rehydration, monitoring fl uid and electrolyte balance and renal function. • Antiviral drug ribavirin seems to be effective if given early in course of the disease. • There is no post-exposure prophylactic treatment. • There is currently no licensed or commercially available vaccine. New candidate vaccines are under development. • New candidate drugs are in development. 7 8 LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 72 Outbreak control relies on community engagement, active case fi nding, contact tracing and safe and dignifi ed burials The transmission of the disease can be stopped through: 1. Community engagement as communities are essential for controlling Lassa fever outbreaks. They have a role to play in the detection of new cases, and reduction of transmission through safe caring of the sick at home and safe and dignifi ed burial. Communities should be engaged in the response since the early stage and be provided with the necessary information and personal protective equipment so that they can adapt the public health measures to their socio- cultural beliefs and ensure compliance of the community members. 2. Active case fi nding, rapid isolation of patients and early laboratory confi rmation of suspected cases. Active case fi nding refers to actively searching for new cases (for instance, going from house to house in the community, asking if people are sick or if people have died). New (suspected) cases should be rapidly and safely referred to treatment centres for isolation and treatment. Lassa fever is a viral haemorrhagic fever that occurs in West Africa • Lassa fever is a viral haemorrhagic illness of 2-21 days duration that occurs in West Africa. • Lassa fever has been reported in Benin, Burkina Faso, Côte d’Ivoire, Ghana, Guinea, Liberia, Mali, Nigeria, Sierra Leone, and Togo, but should be considered endemic in other West African countries. • The overall case fatality rate is 1%. • Observed case fatality rate among patients hospitalized with severe presentation of Lassa fever is 15%. 9 10 3. Contact tracing which refers to the follow-up of persons who may have come into contact with a person infected with the Lassa virus (or their body fl uids, exposed environment such as linens, etc.). Contacts should be followed-up over a period of 21 days after the last exposure, looking for symptoms such as fever, and referred to treatment centres if they become ill. 4. Safe and dignifi ed burials. It is necessary to train people who will have close contact with dead bodies and provide them with the necessary personal protective equipment. People can be buried in a safe manner while respecting traditional beliefs. 5. Early supportive care (rehydration and pain relief) should be provided to patients as early as possible as it reduces mortality (see point 8). LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 73 Geographic distribution of Lassa fever in West African affected countries, 1969–2018 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 74 More information about Lassa fever: • Lassa fever WHO webpage http://www.who.int/csr/disease/lassafever/en/ • Lassa fever WHO fact sheet http://www.who.int/mediacentre/factsheets/fs179/en/ • Lassa fever WHO MOOC https://openwho.org/courses/pandemic-epidemic-diseases LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 75 1. The CCHF virus is transmitted by ticks and the disease is endemic where the tick vector is present 2. Humans are primarily infected through tick bite and secondary human-to-human transmission occurs through direct contact with the body fl uids of infected persons 3. Infected animals are not sick which makes it diffi cult to control the disease in animals and anticipate and prevent infection in humans 4. CCHF is a severe disease with high case fatality ratio 5. Early supportive care improves survival 6. Infection prevention and control measures are critical to control the infection when caring for patients or during burial ceremonies 7. Raising awareness on risk factors and preventive measures is key to reduce infection in people 8. Effi cient vector control measures are currently lacking 9. CCHF can be misdiagnosed with other viral haemorrhagic fevers and early laboratory confi rmation of suspected cases is critical to mount the response 10. CCHF is one of the priority disease for research and development in public health emergency contexts (R&D Blueprint) 10 THINGS YOU SHOULD KNOW Crimean-Congo haemorrhagic fever (CCHF) CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 76 Crimean-Congo haemorrhagic fever (CCHF) response tips Coordinating responders • Engage with partners involved in the response (community engagement, surveillance, laboratory, case management, IPC, and vector control) • Engage with the animal health and food production sectors Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate about how to protect from becoming infected • Key messages are: - CCHF is transmitted by ticks or through contact with body fl uids of infected animals and humans - Bodies of deceased patients are contagious - Apply IPC measures when in contact with sick or dead patients and animals - People with symptoms should seek medical advice as early treatment increases chances of survival Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive and antiviral treatment - Protect health care workers • Surveillance, and contact tracing • Safe and dignifi ed burials CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 77 The CCHF virus is transmitted by ticks and the disease is endemic where the tick vector is present • Ticks of the genus Hyalomma are the principal vector of the disease, although a number of tick are capable of becoming infected with CCHF virus. • Animals become infected by the bite of infected ticks and the virus remains in their bloodstream for about one week after infection, allowing the tick-animal- tick cycle to continue when another tick bites. • The hosts of the CCHF virus include a wide range of wild and domestic animals such as cattle, sheep and goats. Many birds are resistant to infection, but ostriches are susceptible and may show a high prevalence of infection in endemic areas. • CCHF is a viral haemorrhagic fever that is endemic where the tick vector is present: in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north – the geographical limit of the principal tick vector. Humans are primarily infected through tick bite and secondary human-to-human transmission occurs through direct contact with the body fl uids of infected persons • CCHF can cause severe outbreaks in humans. • Humans are infected either by ticks bite or through direct contact with blood or tissues of infected ticks or viraemic vertebrates including wild animals and livestock. • Most at-risk people for the animal- to-human transmission are people involved in the livestock industry, such as agricultural workers, slaughterhouse workers and veterinarians. • Secondary human-to-human transmission occurs through direct contact with the blood, secretions, organs or other body fl uids of infected persons. 1 2 • There is high human-to-human transmission risk when providing direct patient care or handling bodies of deceased individuals (funerals). • Hospital-acquired infections can also occur due to inappropriate infection prevention and control. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 78 Infected animals are not sick which makes it diffi cult to control the disease in animals and anticipate and prevent infection in humans • Infected animal are not sick and do not show any symptoms. This allows the virus to maintain itself in nature in unnoticed enzootic tick-vertebrate-ticks cycles and makes diffi cult to anticipate and prevent potential infection in humans. CCHF is a severe disease with high case fatality ratio • The mortality rate from CCHF is approximately 30% (it ranges from 10 to 50%), with death occurring in the second week of illness. In patients who recover, improvement generally begins on the ninth or tenth day after the onset of illness. • The length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, the incubation period is usually one to three days, with a maximum of nine days. The incubation period following contact with infected blood or tissues is usually fi ve to seven days, with a documented maximum of thirteen days. • Onset of symptoms is sudden, with fever, myalgia (muscle ache), dizziness, neck pain and stiffness, backache, headache, sore eyes and photophobia (sensitivity to light). There may be nausea, vomiting, diarrhoea, abdominal pain and sore 3 4 throat early on, followed by sharp mood swings and confusion. After two to four days, the agitation may be replaced by sleepiness, depression and lassitude, and the abdominal pain may localize to the upper right quadrant, with detectable hepatomegaly (liver enlargement). • Other clinical signs include tachycardia (fast heart rate), lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by bleeding into the skin) on internal mucosal surfaces, such as in the mouth and throat, and on the skin. The petechiae may give way to larger rashes called ecchymoses, and other haemorrhagic phenomena. There is usually evidence of hepatitis, and severely ill patients may experience rapid kidney and liver failure or pulmonary failure after the fi fth day of illness. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 79 Early supportive care improves survival • General supportive care with treatment of symptoms is the main approach to managing CCHF in people. • The antiviral drug ribavirin has been used to treat CCHF infection and may be benefi cial if used early in the course of the illness. Both oral and intravenous formulations exist and seem to be effective. Currently, WHO is reviewing evidence for ribavirin use for the treatment of CCHF. • There is currently no licensed or commercially available vaccine against CCHF for humans and the animal hosts. Infection prevention and control measures are critical to control the infection when caring for patients or during burial ceremonies • Infection prevention and control measures while providing care to patients with suspected or confi rmed Crimean-Congo haemorrhagic fever are the same as those for Ebola and Marburg haemorrhagic fever. 5 6 PRECAUTIONS TO BE TAKEN: When caring for patients Standards precautions regardless of the diagnosis • Hand hygiene • Respiratory hygiene • Use of personal protective equipment (to block splashes / other contact with infected material) • Safe injection practices During burial ceremonies • Only trained burial team should handle the bodies of people who may have died from CCHF • Burial teams should be trained & equipped to properly, safely and with dignity bury the dead Health care workers caring for patients with suspected or confirmed CCHF virus • Extra infection control measures to prevent contact with patient’s blood and body fluids and contaminated surface or material such as clothing or bedding • Face protection (a face shield or a medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures) should be worn when in close contact (within 1 metre) of patients with CCHF Caring of patients at home • Gloves and appropriate personal protective equipment should be worn • Regular hand washing CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 80 Raising awareness on risk factors and preventive measures is key to reduce infection in people • In the absence of a vaccine, the best way to reduce infection in people is by raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus. People should be informed about: • Measures to reduce the risk of tick-to- human transmission include: - Wearing protective clothing (long sleeves, long trousers); - Wearing light coloured clothing to allow easy detection of ticks on the clothes; - Using approved acaricides (chemicals intended to kill ticks) on clothing; - Using approved repellent on the skin and clothing; - Regularly examining clothing and skin for ticks; if found, removing them safely; - Seeking to eliminate or control tick infestations on animals or in stables and barns; - Avoiding areas where ticks are abundant and seasons when they are most active. • Measures to reduce the risk of animal-to- human transmission include: - Wearing gloves and other protective clothing while handling animals or their tissues in endemic areas, notably during slaughtering, butchering and culling procedures in slaughterhouses or at home; Effi cient vector control measures are currently lacking • Current vector control measures are not fully satisfactory: - Chemicals produce resistant ticks, food contamination, and environmental pollution. Furthermore, the tick vectors are numerous and widespread, so tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well- managed livestock production facilities; - Physical measures (heavy grazing, burning of grasslands) have an important negative impact on the environment; - Biological measures (e.g. use of hormones and growth regulators, use of predators, bacteria, nematodes and fungi) have not demonstrated full effi cacy. • An animal vaccine effective against Hyalomma ticks that prevent the tick- animal-tick cycle would decrease tick population, decrease CCHF prevalence in animals, and therefore decrease human exposure, being a cost effective CCHF prevention measure. 7 8 - Quarantining animals before they enter slaughterhouses or routinely treating animals with approved acaricides two weeks prior to slaughter. • Measures to reduce the risk of human- to-human transmission in the community include: - Avoiding close physical contact with CCHF-infected people; - Wearing gloves and protective equipment when taking care of ill people; - Washing hands regularly after caring for or visiting ill people. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 81 CCHF can be misdiagnosed with other viral haemorrhagic fevers and early laboratory confi rmation of suspected cases is critical to mount the response • Due to lack of standardized case defi nition and knowledge about CCHF, the disease can be misdiagnosed. This is why laboratory confi rmation is critical to guide response activities. 9 Proposed case defi nition: Suspected case: Illness with sudden onset of fever with one or more of the following: headache, myalgia, nausea, vomiting, diarrhoea, myalgia, abdominal pain and a history of tick bite or contact with wild animals or livestock or contact with a case of CCHF. Probable case: A deceased suspected case (where it has not been able to collect specimen for laboratory confi rmation) that has an epidemiological link with a laboratory confi rmed case. Confi rmed case: A suspected case that is laboratory confi rmed (positive for IgM antibodies, positive for CCHF virus antigen, positive for CCHF RNA by RT-PCR or virus isolation). • Samples taken from people with suspected CCHF should be handled by trained staff working in suitably equipped laboratories. • CCHF virus infection can be diagnosed by several different laboratory tests: - Enzyme-Linked Immunosorbent Assay (ELISA); - Antigen detection; - Serum neutralization; - Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; - Virus isolation by cell culture. • Patients with fatal disease, as well as in patients in the fi rst few days of illness, do not usually develop a measurable antibody response and so diagnosis in these individuals is achieved by virus or RNA detection in blood or tissue samples. • Tests on patient samples present an extreme biohazard risk and should only be conducted under maximum biological containment conditions (BSL4). However, if samples have been inactivated (e.g. with virucides, gamma rays, formaldehyde, heat, etc.), they can be manipulated in a basic biosafety environment. Days10d7d Incubation 3-6 days Prehaemorrhagic period 1-5 days Haemorrhagic period 2-5 days Convalescence 2-5 days Fever Virus / Antigen Neutralizing / IgG ELISA Antibodies IgM Antibodies Death (10-40%) Polymerase chain reaction: The first 9 days after onset Myalgia, fever, nausea, vomiting, diarrhea Bleeding from various sites (hematemesis, melena, etc.) somnolence IgM (7 days - 4 months) and IgG (7 days - 5 years) CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 82 CCHF is one of the priority disease for research and development in public health emergency contexts (R&D Blueprint) • Research and Development roadmaps and target product profi les are being developed in consultation with experts and stakeholders (as part of the R&D Blueprint). • Research is ongoing for therapeutics (rib- avirin, favipiravir, intravenous immuno- globulin, monoclonal antibodies), for rap- id diagnostics and for an animal anti-tick vaccine effective against Hyalomma ticks. • Given the epidemiology of CCHF, with a limited number of cases reported yearly, a human vaccine might not be the most cost-effective and viable control measure. 10 CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 83 50° North latitude: Limit for geographic distribution of genus Hyalomma ticks The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reservedSource: WHO/IHM as of July 2017 Geographic distribution of Crimean-Congo haemorrhagic fever Hyalomma ticks vector presence CCHF virological / serological evidence & vector presence 5–49 CCHF cases reported per year 50 and more CCHF cases reported per year CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 84 More information about Crimean-Congo haemorrhagic fever (CCHF): • CCHF WHO webpage http://www.who.int/csr/disease/crimean_congoHF/en/ • CCHF WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs208/en/ • R&D Blueprint: http://www.who.int/blueprint/en/ • Infection prevention and control guidance for care of patients in health care settings, with focus on Ebola: http://www.who.int/csr/resources/publications/ebola/fi lovirus_infection_ control/en/?ua=1 CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 85 1. Urban Yellow fever (YF), the most threatening form of YF epidemics, is transmitted through Aedes aegypti mosquito bites 2. Outbreaks of YF in urban areas can be devastating 3. Emergency mass vaccination and vector control are the two main pillars of YF outbreak response 4. YF vaccine is safe and provides lifelong immunity 5. Vaccine production is limited but there is a global emergency stockpile 6. Routine immunization in children is the key to preventing outbreaks 7. The risk of YF international spread exists but can be prevented by applying the International Health Regulations (IHR) recommendations 8. YF is hard to distinguish from some other diseases with similar symptoms 9. Early clinical management improves survival 10. African Ministers of Health (MOH) are committed to eliminating YF epidemics 10 THINGS YOU SHOULD KNOW Yellow fever YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 86 Yellow fever response tips Coordinating responders • Contact WHO/ICG for emergency vaccines • Engage partners and communities for vector control around cases • Organize emergency mass vaccination campaigns including cold chain and waste management Communicating risk • Encourage health authorities to: - Engage communities for vector control - Work with partners for social mobilization for vaccination campaigns - Ensure vector control in health facilities • Key messages are: - YF is transmitted by mosquitoes - Vaccine is safe and provides lifelong immunity - Seek medical care early as this increases chances of survival Health Information • Laboratory diagnosis may be diffi cult (serological tests cross-react with Dengue and other fl aviviruses) • Think of differential diagnosis of febrile jaundice • Distribute vaccination cards • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement • Emergency mass vaccination • Vector control • Control at borders (airports) • Patient supportive care, with bed nets (also during the day) YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 87 Urban Yellow fever (YF), the most threatening form of YF epidemics, is transmitted through Aedes aegypti mosquito bites • The yellow fever virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species (Aedes aegypti, which can transmit the disease from human to human in urban settings) – it is the same mosquito that spreads Zika, Chikungunya and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. Outbreaks of YF in urban areas can be devastating • YF outbreaks in urban settings can be very devastating as they have the potential to amplify rapidly and spread widely, especially to other countries, because of: - Increased human population densities that lead to rapid amplifi cation of the disease; - Increased density of the mosquito vector of urban YF epidemics that breeds in man-made containers of water, feeds predominantly on human blood and bites multiple individuals in a single blood meal, and lives in close association with human dwellings; - Ease and speed of population movements, as well as easy access to airports, facilitate spread of the disease and its exportation to other countries; 1 2 - Diffi culties in assessing target populations, and in mounting reactive interventions in informal urban settings. • There are three types of transmission cycles. However, with climate and demographic change in endemic settings, this classifi cation may be reviewed. - Sylvatic (or jungle) Yellow fever: In tropical rainforests, monkeys, which are the primary reservoir of yellow fever, are bitten by wild mosquitoes which pass the virus on to other monkeys. Occasionally, humans working or travelling in the forest are bitten by infected mosquitoes and develop yellow fever. This is the most common type of outbreak in the Americas; - Intermediate Yellow fever: In this type of transmission, semi-domestic mosquitoes (those that breed both in the wild and around households) infect both monkeys and people. Increased contact between people and infected mosquitoes leads to increased transmission and many separate villages in an area can develop outbreaks at the same time; - Urban Yellow fever: Large epidemics occur when infected people introduce the virus into heavily populated areas with high mosquito density and where most people have little or no immunity, due to lack of vaccination. In these conditions, infected Aedes Aegypti mosquitoes transmit the virus from person to person. This is the most serious outbreak because it amplifi es quickly. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 88 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 89 Emergency mass vaccination and vector control are the two main pillars of YF outbreak response Vector control: • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these interventions: - Elimination of breeding sites and eggs/larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up campaigns, etc.); - Targeted residual spraying of adult mosquitoes (in areas known to be resting sites for Aedes mosquitoes) and space spraying when there is an outbreak; - Mosquito control programmes targeting wild mosquitoes in forested areas are not practical and not recommended for preventing jungle (or sylvatic) yellow fever transmission. 3 • Additionally, personal preventive measures such as clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning are recommended to avoid mosquito bites. The use of insecticide-treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). Emergency mass vaccination: • Reactive mass vaccination campaigns, by increasing immunity in the population, reduce the possibility of transmission of the virus. Vaccine coverages greater than 80%, with a 60-80% security threshold, are necessary to interrupt autochthonous transmission (human- mosquito-human) of YF virus within a community and ensure that sporadic unvaccinated cases do not generate secondary cases. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 90 Vaccine production is limited but there is a global emergency stockpile • They are four prequalifi ed vaccine manufacturers and global supply production is limited. There is a global emergency stockpile of six million vaccine doses, which can be accessed by any country facing an outbreak, through a request to the International Coordinating Group (ICG). • For outbreak response, in case of shortage of vaccine, it is possible to use a fraction of the vaccine doses (1/5), in order to rapidly increase the population immunity and stop human-to-human transmission. - Children under two years of age should be offered a full dose, as they may have a weaker immune response to the vaccine than older people; - There is no evidence of increased serious adverse effects when using a fractional dose. 5YF vaccine is safe and provides lifelong immunity• There is a good vaccine against YF. It has been used for many decades and is safe and affordable, providing effective immunity against yellow fever within 10 days for more than 90% of people vaccinated and within 30 days for 99% of people vaccinated. A single dose provides lifelong protection. A booster dose of yellow fever vaccine is not needed. • Adverse effects of the Yellow fever vaccine are generally mild and may include headaches, muscle aches, and low-grade fevers. Serious adverse effects are rare. • In Yellow fever endemic countries, WHO strongly recommends routine vaccination for everyone older than 9 months. People over 60 years of age should be given the vaccine after a careful risk-benefi t assessment. Some people should not be routinely vaccinated, including: - Infants aged less than 9 months; - Pregnant women (unless during an outbreak if the risk of disease outweighs the potential adverse effect of the vaccine); - People with severe allergies to egg protein; and - People with severe immunodefi ciency. 4 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 91 Routine immunization in children is the key to preventing outbreaks • Vaccination is the single most important measure for preventing yellow fever. The prevention of outbreaks can only be achieved if the majority of the population is immunized. • YF routine immunization in the Expanded Programme on Immunization (EPI) can provide suffi cient population immunity. However, it takes about 30 years to build the population immunity to adequate levels to stop potentially large scale outbreaks. Mass preventive vaccination campaigns to other age groups accelerate the building of population immunity through what is called the YF “combined vaccination strategy”. 6 Population protected by routine immunization, preventive mass campaigns and combined vaccination strategy (A) Routine child immunization Number of years after the intervention (C) Combined vaccination strategy: Routine childhood immunization + one preventive mass vaccination campaign (B) Preventive mass vaccination campaign 100 90 80 70 60 50 40 30 20 10 0 1 10 2.3 22.8 45.6 68.4 91.2 20 30 Pro po rti on (% ) o f p op ula tio n p rot ect ed 40 100 90 80 70 60 50 40 30 20 10 0 1 10 80.0 55.1 26.6 0 0 20 30 40 1 10 82.3 77.9 72.2 91.2 68.4 20 30 40 100 90 80 70 60 50 40 30 20 10 0 Vaccine coverage security threshold YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 92 • It is recommended that major sectors recruiting international workers, with potential sylvatic exposure (extractive, mining, construction and forestry industries), take measures to ensure their staff and families are vaccinated. • To prevent international spread, it is essential that the International Health Regulations (2005) are applied and that travelers present yellow fever vaccination certifi cates. Under the IHR (2005), it is also essential to notify YF cases that have a serious public health impact and/or are unusual or unexpected, and/or could lead to international spread and/or present a signifi cant risk of travel or trade restrictions. • Vector control measures may be applied in various forms of transport, in accordance with the IHR (2005). The risk of YF international spread exists but can be prevent- ed by applying the International Health Regulations (IHR) recom- mendations • With the increasing occurrence of urban YF outbreaks comes an increased risk of international spread of diseases, because big cities are transport hubs with frequent transport connections. A particularly concerning scenario would be exportation of the disease to a country where the vector is present and population immunity levels are low, which could lead to local transmission. • For Yellow fever, exportation of cases to Asia is especially worrisome as all favorable conditions for local transmission (vector such as Aedes aegypti, non-immune populations) are present in this continent, as demonstrated by dengue activity. 7 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 93 YF is hard to distinguish from some other diseases with similar symptoms • Yellow fever is diffi cult to diagnose (especially during the early stages) because its symptoms are not specifi c and can be confused with other common diseases such as Malaria, Viral Hepatitis (when jaundice), Dengue, Leptospirosis (when jaundice), other arbovirus diseases, Ebola virus disease (when haemorrhagic) as well as with poisoning. - Once contracted, the Yellow fever virus incubates in the body for three to six days; - Most people (about 88% of those infected) do not experience symptoms; - Symptoms usually develop in two phases: o First to occur are common, unspecifi c symptoms, including fever, muscle pain with prominent backache, headache, loss of appetite, and nausea or vomiting. In most cases, symptoms disappear after three to four days. o A small percentage of patients (about 2-3% of infected people) will then enter a second, more toxic phase within 24 hours of recovering from initial symptoms. High fever returns and several body systems are affected, usually the liver and the kidney, hence the characteristic jaundice – which gives yellow fever its name - dark urine and abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes or stomach. Half of the patients who enter the toxic phase die within seven to ten days. The rest recover without signifi cant organ damage. 8 • Laboratory tests are necessary to confi rm yellow fever and access the global stockpile:- In the fi rst phase, blood is collected for RT- PCR – Reverse Transcription Polymerase Chain Reaction, to confi rm the presence of the virus (viremia); - In later stages of the disease, serology testing to identify antibodies is needed (ELISA, Enzyme-Linked Immunosorbent Assay and PRNT, Plaque Reduction Neutralization Test, for neutralizing antibodies). The detection of antibodies indicates that the person has either been infected or vaccinated, but it cannot distinguish between the two. The level of antibodies’ titres and their evolution over time, on a second sample, can provide indication of how acute the infection might be; - Whenever YF is suspected, there should also be systematic testing by serology and PCR for other arboviruses (such as Dengue, Zika, Chikungunya, West Nile, Rift Valley Fever) and viral haemorrhagic fever (VHF, such as Ebola, Lassa, Crimean- Congo haemorrhagic fever); - YF tests should be realized in laboratories with appropriate capacity to test for both YF and the differential diagnosis. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 94 African Ministers of Health (MOH) are committed to eliminating YF epidemics • Yellow fever is an acute viral haemorrhagic disease. The virus is endemic in tropical areas of Africa and the Americas. Susceptible non-human primates are the animal reservoir, they are necessary to maintain the endemicity. • Forty of the 47 YF-affected countries have been identifi ed as priority nations by the Eliminate Yellow Fever Epidemics (EYE) Strategy. The updated Strategy was developed by a coalition of countries and partners to respond to 10 the disease’s changing epidemiology, resurgence of mosquitoes, and the increased risk of urban outbreaks and international spread. • African Member States endorsed the (EYE) Strategy in 2017 and agreed on ten priority actions to guide countries to the elimination of YF epidemics by 2026. 9 Early clinical management improves survival • Good and early supportive treatment in hospitals improves survival rates. • There is currently no specifi c anti-viral drug for yellow fever but specifi c care to treat dehydration, liver and kidney failure, and fever improves outcomes. • Patients need to stay under mosquito nets during the day to limit the risk of spread to others through bites of mosquitoes. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 95 l, Cabo Verde Guinea-Bissau Gambia Senegal Sierra Leone Liberia Guinea – Côte d’Ivoire Ghana Burkina Faso Togo Benin Sao Tome and Principe Nigeria Gabon Congo Equatorial Guinea Camer oon – Angola Democratic Republic of the Congo South Africa Lesotho Swaziland Botswana Zimbabwe Namibia Zambia Malawi Mozambique Madagascar Comoros Rwanda Burundi United Republic of Tanzania Mauritius Seychelles Kenya Uganda Somalia – Ethiopia Djibouti South Sudan – Eritrea Sudan Chad Niger Central African Republic Egypt Libya Tunisia Algeria Mali Morocco Mauritania The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Yellow fever (YF) risk classifi cation, by country - Africa, 2016 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 96 Yellow fever (YF) risk classifi cation, by country – LAC* countries, 2016 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. This map illustrates a public-health-intervention oriented YF risk approach at country level. Its purpose is different from the YF risk area maps for travellers in the context of IHR. Argentina Uruguay Chile Peru Bolivia (Plurinational State of) Pa raguay Ecuador Colombia Panama Venezuela (Bolivarian Republic of) – Trinidad and Tobago Guyana Suriname French Guiana Brazil * LAC: Latin American and Caribbean High-risk Potential-risk No evidence available for YF or indicative arbovirus circulation YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 97 More information about Yellow fever • Yellow fever WHO webpage http://www.who.int/csr/disease/yellowfev/en/ • Yellow fever WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs100/en/ • EYE Strategy http://apps.who.int/iris/bitstream/10665/255040/1/WER9216.pdf?ua=1 • Yellow fever WHO MOOC https://openwho.org/courses/pandemic-epidemic-diseases • WHO standard case defi nitions http://www.who.int/csr/disease/yellowfev/case-defi nition/en/ YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 98

1. Zika virus is transmitted by Aedes mosquitoes, which primarily bite during the day 2. This virus infection is usually asymptomatic, but can lead to severe complications 3. Infection during pregnancy presents many serious hazards for mother and child (microcephaly in children) 4. Zika virus is a trigger of Guillain-Barré syndrome 5. The virus is also transmissible through sexual contact, blood transfusion, and organ transplantation 6. Vector control strategies are important for prevention and control 7. Individuals should protect themselves from mosquito bites 8. Access to laboratory testing is critical for pregnant women 9. There is no vaccine or specifi c treatment for Zika virus infection 10. Warnings have been issued for pregnant women and their male partners 10 THINGS YOU SHOULD KNOW Zika ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 100 Zika response tips Coordinating responders • Coordination of public health, maternal and child health, vector control and clinical services • Social services to support affected children and families Communicating risk • Encourage health authorities to: - Engage communities for eliminating mosquito breeding sites - Communicate with at-risk groups through their trusted sources of information • Key messages: - Zika is transmitted through mosquito bites during the day - The babies of pregnant women are at risk for adverse pregnancy outcomes - Zika can be sexually transmitted - Women of reproductive age should seek advice before getting pregnant during outbreaks and should seek medical advice if they fall pregnant Health Information • Early detection, reporting, and monitoring of cases • Laboratory capacity for diagnosis especially in pregnant women • Laboratory diagnosis may be diffi cult (serological tests cross-react with Dengue and other fl aviviruses) Health Interventions • Community engagement and health promotion • Early response • Prevention of infection by Aedes mosquitoes, particularly pregnant women • Reduce breeding sites of Aedes mosquitoes around dwellings • Clinical supportive care of patients with Guillain-Barré and severe symptoms • Support to babies born with microcephaly • Psychosocial counselling and support ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 101 Zika virus is transmitted by Aedes mosquitoes, which primarily bite during the day • The Zika virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species – it is the same mosquito that spreads Yellow fever, Chikungunya and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. • Local transmission of Zika virus by Aedes mosquitoes has been reported on the continents of Africa, the Americas, South- East Asia and the Western Pacifi c. • There are 2 types of Aedes mosquitoes known to be capable of transmitting Zika virus: - In most cases, Zika is spread through the Aedes aegypti mosquito in tropical and subtropical regions; - Aedes albopictus mosquitoes can also transmit Zika virus and can tolerate cooler temperatures; - Both species are found biting outdoors but Aedes aegypti will also feed indoors. This virus infection is usually asymptomatic, but can lead to severe complications • About 80% of infected people do not develop symptoms. • People with symptoms usually present with mild fever, rash, conjunctivitis (infl ammation of the eyes), muscle and joint pain, malaise, and headache. 1 2 • Symptoms normally last two to seven days. • The incubation period (the time from exposure to onset of symptoms) of Zika virus disease is unknown but is most likely less than one week if it is similar to that of other mosquito-borne fl aviviruses. • Zika virus infection can lead to severe neurological complications in a relatively small proportion of those infected: - Microcephaly and other congenital abnormalities; - Preterm birth and fetal death; - Guillain-Barré syndrome; - Investigations are ongoing on the links between Zika virus and other adverse outcomes. • Zika virus can be classifi ed into two main lineages: the Asian lineage and African lineage. To date, the Asian lineage Zika virus strain is responsible for the recent 2015/2016 epidemics. It is not known whether the African lineage Zika virus strains would produce neurological symptoms with similar or worse gravity than those observed in the 2015/2016 epidemics. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 102 Infection during pregnancy presents many serious hazards for mother and child (microcephaly in children) • Zika virus can be transmitted from mother to child during pregnancy, and can result in congenital abnormalities: - Microcephaly is a condition where the infant’s head is smaller than those of other babies of the same age and sex (more than three standard deviations below average for gestational age). Infants born with microcephaly are at risk for severe intellectual disability and may also develop convulsions and physical disabilities as they grow older. There is no specifi c treatment for microcephaly; o Diagnosis of microcephaly is often made at birth. All infants should have head circumference measured and recorded within 24 hours of birth. Early diagnosis of microcephaly can sometimes be made by fetal ultrasound. Prenatal diagnosis by ultrasound is more accurate in the second and third trimesters. - Other newborn complications associat- ed with in-utero Zika infection include brain calcifi cations, seizures, irritability, brainstem dysfunction such as swallowing Zika virus is a trigger of Guillain- Barré syndrome • Guillain-Barré syndrome (GBS) is a rare condition in which a person’s immune system attacks the peripheral nerves. • People of all ages can be affected, but it is more common in adults and in males. • Symptoms typically last a few weeks. If supported through the critical stages of disease, most individuals can recover without long-term complications. - The fi rst symptoms of Guillain-Barré syndrome include weakness or tingling, usually starting in the legs and can spread to the arms and face; - Some patients can develop paralysis of the legs, arms, or muscles in the face. In 20%–30 % of people, the chest muscles are affected, making it diffi cult to breathe; - The ability to speak and swallow may become affected in severe cases of Guil- lain-Barré syndrome; - Severe cases of Guillain-Barré syndrome are rare, but can result in near-total paralysis. • Guillain-Barré syndrome is therefore po- tentially life-threatening. People with Guil- lain-Barré syndrome should be treated and closely monitored; severe cases may require intensive care including ventilato- ry respiratory support. Treatment includes supportive care and some immunological therapies. • Even in the best of settings, 3%–5% of Guillain-Barré syndrome patients die from complications, which include paralysis of the muscles that control breathing, infection, sepsis, or cardiac arrest. 3 4 problems, limb contractures, develop- mental delay, hearing and sight abnor- malities, and other brain abnormalities; - Support services for affected infants and families are an important component of Zika programmes. • Other adverse pregnancy outcomes associated with Zika virus infection include preterm birth, miscarriage, and still birth. • Zika virus has been identifi ed in breast milk, but transmission by breastfeeding has not yet been reported. Current evidence suggests that the benefi ts of breastfeeding outweigh the theoretical risk of Zika virus infection transmission through breast milk. • More information is needed on the long term outcomes of infants infected during pregnancy, delivery, and in the early post- partum period. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 103 The virus is also transmissible through sexual contact, blood transfusion, and organ transplan- tation • Zika virus can be transmitted through sexual intercourse. This is of concern because of the association between Zika virus infection and adverse pregnancy outcomes. • In regions with active Zika virus transmission, health programmes should ensure that: - All people with Zika virus infection and their sexual partners (particularly pregnant women) receive information about the risks of sexual transmission of Zika virus; - Men and women receive counselling on safe sexual practices and are offered condoms; - Sexually active men and women should be counselled and offered a full range of contraceptive methods to make informed choices about whether and when to become pregnant, to prevent unintended pregnancies, and prevent possible adverse pregnancy outcomes; - Pregnant women should be advised not to travel to areas of ongoing Zika virus outbreaks. • Other modes of person-to-person Zika transmission include: blood transfusion, organ transplantation and laboratory or other blood-borne exposure. Vector control strategies are important for prevention and control • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these inter- ventions: - Elimination of breeding sites and eggs/ larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up cam- paigns, etc.); - Targeted residual spraying of adult mos- quitoes (in areas known to be resting sites for Aedes mosquitoes) and space spray- ing when there is an outbreak. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito popula- tions and prevention disease. Both larval and adult vector populations should be targeted for surveillance. 5 6 • Standard WHO recommendations regarding vector control at airports should be implemented in accordance with the IHR (2005). Countries should consider disinfection of aircraft. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 104 Access to laboratory testing is critical for pregnant women • Because of the association between Zika virus infection and adverse pregnancy and infant outcomes, it is important that women have access to laboratory testing. The woman (and her partner if she/he wishes) should be offered non-directive counselling so that she, in consultation with her health care provider, can make a fully informed choice about the next steps in the management of her pregnancy. • Laboratories should have the capacity to test for Zika: - Laboratory tests are done on blood or other body fl uids (e.g. urine, saliva, semen): o Polymerase Chain Reaction (PCR) during the acute phase of the disease; o Serological (IgM) testing and Nucleaic Acid Tests (NAT) testing with Plaque Re- duction Neutralization Test (PRNT). In- fection with Zika virus is diffi cult to con- fi rm retrospectively because serological tests cross react with other fl aviviruses, especially Dengue virus. 7 8 Individuals should protect them- selves from mosquito bites • The community, and particularly pregnant women and women of reproductive age, should be educated about the risk of transmission and how to minimize this risk by reducing contact with mosquitoes. • Personal preventive measures to avoid mosquito bites include clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning. The use of insecticide- treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 105 There is no vaccine or specifi c treatment for Zika virus infection • Currently, there are no antiviral drugs or specifi c treatment for people with Zika virus disease. Zika virus disease in individuals including non-pregnant women is usually mild and requires no specifi c treatment. Individuals with more severe symptoms should receive supportive care including rest, fl uids, and management of pain and fever. They should be offered psychosocial support. • Research is ongoing for potential therapies, for vaccines to prevent Zika virus infection or Congenital Zika Syndrome, and for diagnostic tests. Warnings have been issued for pregnant women and their male partners • There are no general restrictions on travel or trade with countries, areas and/or territories with Zika virus transmission. • However, WHO is advising pregnant women not to travel to the following Zika- affected areas: - Areas with new introduction of Zika virus since 2015 or where the virus has been re- introduced, with ongoing transmission; - Areas with evidence of Zika virus circulation before 2015 or with ongoing transmission (but not satisfying the category above). • Health authorities are responsible for advising travellers on risks and preventive measures. 9 10 ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 106 Countries and territories* with reported Zika virus transmission The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved * Note: This includes areas with new introduction or re-introduction with ongoing transmission; areas either with evidence of virus circulation before 2015 or area with ongoing transmission that is no longer in the new or re-introduction phase, but where there is no evidence of interruption; and areas with interrupted transmission and with potential for future transmission. Countries and territories* with reported Zika virus transmission Source: WHO/IHM; as of 15 January 2018 ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 107 More information about Zika • Zika WHO webpage: http://www.who.int/csr/disease/zika/en/ • Zika virus WHO fact sheet: http://www.who.int/mediacentre/factsheets/zika/en/ • Risk communications and community engagement http://www.who.int/csr/resources/publications/zika/community- engagement/en/ • Pregnancy management in the context of Zika virus infection: http://www.who.int/csr/resources/publications/zika/pregnancy- management/en/ • Care and support of people affected by complications associated with Zika virus: http://www.who.int/mental_health/neurology/zika_toolkit/en/ • Prevention of sexual transmission: http://www.who.int/csr/resources/publications/zika/sexual- transmission-prevention/en/ • Identifi cation and management of Guillain-Barré syndrome in the context of Zika virus: http://www.who.int/csr/resources/publications/zika/guillain-barre- syndrome/en/ ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 108

1. Chikungunya is transmitted by Aedes mosquitoes, which primarily bite during the day 2. Chikungunya outbreaks occur typically in urban settings 3. Chikungunya causes an acute febrile illness 4. Convalescence may be long and patients may present complications and sequelae 5. Treatment is directed primarily at relieving symptoms 6. Chikungunya is often misdiagnosed with Dengue and other diseases 7. Controlling the mosquito vector is key to outbreak prevention and control 8. Vector surveillance is critical to determine vector control strategies 9. Chikungunya virus infection seems to elicit long-lasting protective immunity 10. Chikungunya is emerging as a global disease 10 THINGS YOU SHOULD KNOW Chikungunya CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 110 Chikungunya response tips Coordinating responders • Coordination of public health, environmental, clinical services and vector control Communicating risk • Encourage health authorities to: - Communicate to the public about how to protect from the disease - Advise on seeking health care for high-risk groups - Eliminate mosquito breeding grounds • Key messages: - Chikungunya can cause acute and chronic illness - Chikungunya is transmitted by mosquitoes Health Information • Laboratory capacity for diagnosis and surveillance • Vector distribution surveillance • Early detection, reporting, response and monitoring Health Interventions • Community engagement and health promotion • Vector control: - Reduce breeding sites of Aedes mosquitoes around dwellings - Prevent mosquito bites during the day • Supportive care • Patient care with bed nets (also during the day) CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 111 Chikungunya is transmitted by Aedes mosquitoes, which primarily bite during the day • The Chikungunya virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species – it is the same mosquito that spreads Yellow fever, Zika and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. • There are 2 types of Aedes mosquitoes known to be capable of transmitting Chikungunya virus: - In most cases, Chikungunya is spread through the Aedes aegypti mosquito in tropical and subtropical regions; - Aedes albopictus mosquitoes can also transmit Chikugunya virus and can tolerate cooler temperatures; - Both species are found biting outdoors but Aedes aegypti will also feed indoors. • Transmission of the virus can also occur through blood transfusion and laboratory or other blood-borne exposure. Chikungunya outbreaks occur typically in urban settings • Human beings serve as the Chikungunya virus reservoir during epidemic periods. • Urban Chikungunya virus transmission follows those observed for Dengue virus. 1 2 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 112 Chikungunya causes an acute febrile illness • Chikungunya causes an acute febrile illness typically accompanied by arthralgia. • Other common symptoms and signs include muscle pain, headache, nausea, fatigue and rash. • The joint pain is often debilitating, usually lasting a few days, but may be prolonged to weeks. Hence, the virus can cause acute, subacute or chronic disease. • The disease shares some clinical signs with Dengue and can be misdiagnosed in areas where Dengue is common. • Children may experience other symptoms such as minor hemorrhagic manifesta- tions, arthralgia/arthritis, lymphadenop- athy, conjunctival injection, swelling of eyelids and pharyngitis. Rare clinical fea- tures include neurological manifestations including seizures, altered level of con- sciousness, and blindness due to retrob- ulbula neuritis and acute fl accid paralysis. • The disease is generally not fatal. Symptomatic treatment along with rest usually suffi ces. • After the bite of an infected mosquito, onset of illness occurs usually between four and eight days but can range from two to 12 days. • The acute phase of Chikungunya lasts for three to 10 days but convalescence can be prolonged up to one year and more. • There are asymptomatic patients but it is unknown how frequently it occurs. Convalescence may be long and patients may present complications and sequelae • Rare clinical manifestations of Chikungunya include neurological, hemorrhagic, and ocular and severe multiple organs system involvement. • In older people, the disease can contribute to earlier death that may be due to the frequency of concomitant underlying diseases or decreased immunologic response. • Some patients have reported disabling joint pain or arthritis, which may last for weeks or months. These patients may require long-term anti-infl ammatory therapy. • Patients with Chikungunya should be assisted from their communities and enabled to seek occupational and social rehabilitation. 3 4 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 113 Treatment is directed primarily at relieving symptoms • There is no specifi c antiviral drug treatment for Chikungunya. • Treatment is directed primarily at reliev- ing the symptoms using anti-pyretics (paracetamol is the drug of choice), op- timal analgesics and fl uids. Applying cold compresses have been reported to less- en the joint symptoms. • People with Chikungunya should rest and consume plenty of water. • Aspirin should be avoided due to its effect on platelets. Paracetamol or nonsteroidal anti-infl ammatory drugs may be used for symptom relief. • All suspected cases should be kept under mosquito nets during the febrile period. • Patients and their families should be provided with psychosocial support. • There is no Chikungunya vaccine although some candidate vaccines are being tested in human beings. Chikungunya is often misdiagnosed with Dengue and other diseases • Chikungunya patients may present nonspecifi c symptoms that could be confused with many other diseases such as Dengue, Leptospirosis, Malaria, Meningitis, and Rheumatic fever. Laboratory diagnosis is thus critical to establish the cause of diagnosis and initiate specifi c public health response. • Several methods can be used for diagnosis: - Molecular technique: Polymerase Chain Reaction (PCR); - Virus isolation: the virus may be isolated from the blood during the fi rst few days of infection. Various Reverse Transcription Polymerase Chain Reaction (RT–PCR) methods are available but are of variable sensitivity; - Serological tests such as Enzyme-Linked Immunosorbent Assays (ELISA), may confi rm the presence of IgM and IgG anti- chikungunya antibodies. IgM antibody levels are highest three to fi ve weeks after the onset of illness and persist for about two months. 5 6 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 114 Controlling the mosquito vector is key to outbreak prevention and control • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these interventions: - Elimination of breeding sites and eggs/larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up campaigns, etc.); - Targeted residual spraying of adult mosquitoes (in areas known to be resting sites for Aedes mosquitoes) and space spraying when there is an outbreak. • Additionally, personal preventive measures such as clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning are recommended to avoid mosquito bites. The use of insecticide-treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). • Standard WHO recom- mendations regarding vector control at airports should be implement- ed in keeping with the IHR (2005). Countries should consider disin- fection of aircraft. Vector surveillance is critical to determine vector control strategies • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. • These data will enable the selection and use of the most appropriate vector control tools, and can be used to monitor their effectiveness. 7 8 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 115 Chikungunya virus infection seems to elicit long-lasting protective immunity • There are still a lot of unknowns (including the clinical spectrum of the disease) and research is ongoing to fi ll scientifi c gaps in our understanding of the disease. • The reasons for the mysterious behavior of dramatic outbreaks interspersed by periods of prolonged absence, virus survival in nature and factors triggering outbreaks need to be further studied. • Research also focuses on diagnostics tests, treatments and vaccines. Chikungunya is emerging as a global disease • Urbanization, human travel, viral adaption, lack of effective control measures, and spread of new vectors likely have contributed to recent re-emergence of Chikungunya. • There is a risk of epidemics in subtropical and temperate regions of the world where Aedes albopictus is a potential vector. • The dramatic spread of the Dengue, Chikungunya, and Zika viruses in recent years highlights the urgent need to identify Aedes control options. 9 10 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 116 Predicted distribution of the Aedes Aegypti mosquito CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 117 Predicted distribution of the Aedes Albopictus mosquito CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 118 More information about Chikungunya: • Chikungunya WHO webpage: http://www.who.int/emergencies/diseases/chikungunya/en/ • Chikungunya WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs327/en/ • Prevention and control: http://www.wpro.who.int/mvp/topics/ntd/Chikungunya_WHO_ SEARO.pdf • WHO standard case defi nitions: http://www.who.int/wer/2015/wer9033.pdf?ua=1 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 119 1. Animal infl uenza viruses have occasionally infected humans (Avian, swine and other zoonotic infl uenza viruses) 2. Multisectoral coordination and communication are essential parts of any outbreak response 3. Protect all individuals with occupational or other risks of exposure 4. Eggs, poultry and poultry products can be safely consumed, provided these items are properly cooked and properly handled during food preparation 5. To minimize exposure of the public, encourage proper personal hygiene and instruct the public to seek medical help if illness develops 6. Increase surveillance for human cases of Avian infl uenza 7. Collecting appropriate samples, and rapid and precise characterization of virus isolates are essential for early detection and management of patients 8. Health care facilities need to be ready to manage patients with Avian infl uenza virus infections 9. The animal health sector is in charge of preventing and controlling outbreaks of disease in animals, including Avian infl uenza 10. Infl uenza A(H5N1) vaccines are not widely available and the decision to use them depends on the risk of infection 10 THINGS YOU SHOULD KNOW Avian and other zoonotic infl uenza AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 120 Avian and other zoonotic infl uenza response tips Coordinating responders • Multisectoral response: collaboration between animal health sector and public health sector is key in surveillance, response and prevention activities Communicating risk • Encourage health authorities to: - Have a way to compensate owners/farmers for the loss of sick animals to encourage early reporting - Have a multisector communications strategy in place • Key messages: - Avian infl uenza is transmitted primarily from infected animals to human through direct contact - There is usually no sustained human-to-human transmission - Promote good personal hygiene (i.e. handwashing) - Promote proper food safety guidance - Report sick animals to the authorities Health Information • Sharing information from the animal health sector with human health sector supports preventive action in the affected areas • Sharing information on human cases with the animal health sector is equally important so that they can target their response activities • Ensure sharing of viruses from human cases with WHO Collaborating Centres • Report cases to WHO, under the IHR (2005) Health Interventions • Investigate cases and enhance surveillance • Collect appropriate specimens • Antiviral and supportive treatment for cases • Monitoring of contacts • Vaccination of high-risk groups • Infection prevention and control measures: - Prevent nosocomial infections - Personal Protective Equipment AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 121 Animal infl uenza viruses have occasionally infected humans (Avian, swine and other zoonotic infl uenza viruses) • Wild aquatic birds are the reservoir for infl uenza A viruses. The emergence of a new and very different infl uenza A virus with the ability infect people and have sustained human-to-human transmission, can cause an infl uenza pandemic. • Humans can be infected with Avian, swine and other zoonotic infl uenza viruses. • Avian infl uenza is a disease of domestic and wild birds with severe consequences for the poultry sector when outbreaks of disease occur. Domesticated populations (poultry: chickens, ducks, turkeys) can become infected by contact with wild birds. Avian infl uenza viruses are categorized as either low pathogenic (LP) or highly pathogenic (HP) viruses, depending on the severity of the disease they cause in birds and poultry. These two terms do not refer to the disease in humans infected with these viruses. • Avian infl uenza A viruses are distinct from human infl uenza viruses and do not easily transmit between humans. Human infections are primarily acquired through direct contact with infected animals or contaminated environments, but do not result in effi cient transmission of these viruses between people. • Avian and other zoonotic infl uenza infections in humans may cause disease ranging from mild conjunctivitis to severe pneumonia and even death. Multisectoral coordination and communication are essential parts of any outbreak response • The fi rst occurrence of a poultry outbreak of highly pathogenic Avian infl uenza in a country often creates widespread concern and can disrupt social and economic life. Therefore, effective communication with all stakeholders is an essential part of any outbreak response. • Strong coordination between sectors (animals and human health) is needed for surveillance, risk communications and interventions monitoring. 1 2 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 122 Protect all individuals with occupational or other risks of exposure • Protect people involved in specifi c, high- risk tasks such as sampling sick birds, culling and disposing of infected birds and cleaning of contaminated premises. • Provide appropriate personal protective equipment and training on how to use it properly. • All persons involved in these tasks should be registered and monitored closely by local health authorities for seven days following the last day of contact with poultry or their environments. • Symptomatic persons should be treated according to WHO guidelines with infl uenza-specifi c antivirals. • If suffi cient antivirals are available, antiviral chemoprophylaxis can be considered (recommendations for regimen of antiviral prophylaxis can be found in the WHO guidelines). • Consideration should be given to the immunization of persons with high potential to be exposed to Avian infl uenza using the seasonal infl uenza vaccine. Eggs, poultry and poultry products can be safely consumed, provided these items are properly cooked and properly handled during food preparation • Inform the public about ways to promote safe food consumption. Promote thorough cooking of poultry and poultry products. Separate raw meat from cooked or ready-to-eat foods. Keep clean and wash your hands. Handle and store meat properly. • Live animal market hygiene and biosecurity should be assessed and improved where possible. • National food safety authorities and poultry producers should develop and implement quality assurance schemes in line with HACCP (Hazard Analysis Critical Control Point) principles and steps. • Carefully treat drinking water supplied from open surface water to minimize any potential risks. Be aware that properly treated waste water seems to pose only a small risk for humans. Be aware that in some cases, recreational water might be contaminated. And consider that faeces from infected animals can be infectious. 3 4 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 123 To minimize exposure of the public, encourage proper personal hygiene and instruct the public to seek medical help if illness develops • Minimize exposure of the public to potentially infected birds and other sources of contamination and encourage proper personal hygiene, especially frequent hand washing, and instruct people to seek medical help if illness develops. • When Avian infl uenza viruses circulate in an area, all the people who are exposed to infected birds are at risk, especially those who: keep live poultry in their backyards or homes, or purchase live poultry or birds at markets; slaughter, de- feather, or butcher poultry handle and prepare raw poultry for further cooking and consumption; transport or sell live poultry or carcasses; are involved in culling / depopulating / disposing of Increase surveillance for human cases of Avian infl uenza • Avian infl uenza is not easily transmitted from infected animals to humans and there has not been sustained human-to- human transmission. • However, it is important to ensure suspected human cases are investigated in order to give them the best possible treatment; to identify other potential human contacts in those cases and monitor them for occurrence of illness; and to identify if there is human-to- human transmission of the virus. • The most important goal for investigations of human cases of infections with Avian infl uenza viruses is to assess the extent of potential human-to-human transmission, especially in clusters of human cases and contacts of confi rmed cases. • Enhanced surveillance should consider the health care seeking behaviour of the population and can include a range of options such as active and passive approaches that are health care and/or community-based. • Persons with exposure to Avian infl uenza should monitor their health for the duration of the known exposure period plus an additional seven days. This will facilitate early detection of illness and timely commencement of antiviral treatment and isolation precautions. They should report any relevant health problems to a health care facility. 5 6 poultry work in the poultry industry, including farmers and veterinarians; have contact with poultry by-products (e.g. viscera, manure, feathers) or water contaminated with these by-products (e.g. waste water from a live bird market or a slaughtering facility); or consume raw poultry products. • The general public should minimize contact with chickens, ducks or other birds and avoid areas where poultry are housed, slaughtered or prepared. They also should: - Keep children away from birds and their waste, including feathers and manure. Children should neither collect eggs nor assist with slaughtering or food preparation; - Report sick or unexpectedly dead poultry to the authorities immediately; - Comply with all offi cial measures (e.g. animal movement restrictions) that are put in place; - Do not slaughter and/or consume birds that are showing signs of disease or that have unexpectedly died. AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 124 7 8 Collecting appropriate samples and rapid and precise characterization of virus isolates are essential for early detection and management of patients • Collection of appropriate specimens from suspected human cases for identifi cation by a qualifi ed laboratory, together with rapid and precise characterization of virus isolates at specialized reference laboratories, are essential for early detection of cases, proper management of patients, and understanding the epidemiology of the disease. • In addition, appropriate specimen collection is important for monitoring the development of resistance to antivirals, producing effective vaccines, and evaluating laboratory methods. • Ensure that specimen collection materials are available and collection of specimens is done safely, correctly and in a timely manner. • Promote virus/sample sharing with WHO- recognized laboratories. Health care facilities need to be ready to manage patients with Avian infl uenza virus infections • Implement early infection control precautions to prevent nosocomial (originating in a hospital) spread of the disease. • Manage cases properly to prevent severe illness and death. Administer neuraminidase inhibitors (oseltamivir, zanamivir) treatment as the primary choice of antiviral treatment, using the standard regimen for seasonal infl uenza virus infection, as soon as possible (ideally, within 48 hours following symptom onset) to maximize therapeutic benefi ts. Monitor patients and viruses for indications of antiviral resistance. • If there is an insuffi cient in-country supply of neuraminidase inhibitors, WHO can provide it from its strategic global stockpile. • Report laboratory-confi rmed cases to WHO, under the International Health Regulations (2005). AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 125 The animal health sector is in charge of preventing and controlling outbreaks of disease in animals, including Avian infl uenza • Controlling the disease in the animal source is critical to decrease risk to humans. • Reporting new and ongoing outbreaks in animals is important for focusing human health prevention action in the affected areas and raising awareness among professionals working with potentially infected animals, as well as with the public. The sharing of information on human cases with the animal health sector is equally important so that they can target their response activities. • The Food and Agriculture Organization (FAO) of the United Nations (UN) promotes food security and good nutrition by providing access to knowledge, policy advice and technical Infl uenza A(H5N1) vaccines are not widely available and the decision to use them depends on the risk of infection • WHO recommends the targeted administration of seasonal infl uenza vaccine to health care workers in all countries in order to protect their patients from seasonal infl uenza infections. In addition, WHO recommends vaccination against seasonal infl uenza infection to selected groups at increased risk of exposure to Avian infl uenza viruses, as one of several measures for reducing opportunities for the simultaneous infection of humans with Avian and human infl uenza viruses. • Vaccines for A(H5N1) virus for human use have been developed based on WHO- recommended candidate vaccine viruses and licensed in several countries. They are not widely available. Vaccination with A(H5N1) vaccines for human use are recommended for fi rst responders to human or animal A(H5N1) outbreaks, and for health care workers who evaluate or manage patients with suspected or confi rmed A(H5N1) virus infection in designated referral facilities. Be aware that WHO has no stockpile of A(H5N1) vaccines. 9 10 assistance to Member Countries. FAO publishes information and guidance on Avian infl uenza, provides direct technical assistance to countries and works closely with many stakeholders. • The World Organization for Animal Health (OIE) sets international standards for animal health and zoonoses, through the ‘OIE Code’ and ‘OIE Manual’ and is responsible for collecting and disseminating offi cial animal disease information from Member Countries. It collaborates with National Veterinary Services as well as with FAO at national, regional and global levels to provide technical assistance to countries (e.g. laboratory support). • National veterinary services, often located within the Ministry of Agriculture, are responsible for implementation of national Avian infl uenza measures to control and prevent the spread of the disease in poultry. AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 126 Nigeria Case: 1 Death: 1 Egypt Cases: 359 Deaths: 120 Turkey Cases: 12 Deaths: 4 Azerbaijan Cases: 8 Deaths: 5 Djibouti Cases: 1 Death: 0 Iraq Cases: 3 Deaths: 2 Pakistan Cases: 3 Death: 1 China Cases: 53 Deaths: 31 Bangladesh Cases: 8 Death: 1 Myanmar Case: 1 Death: 0 Thailand Cases: 25 Deaths: 17 Cambodia Cases: 56 Deaths: 37 Lao People's Democratic Republic Cases: 2 Deaths: 2 Indonesia Cases: 200 Deaths: 168 Member State Cases: cumulative number Deaths: cumulative number Areas with confirmed human cases for avian influenza Canada Case: 1 Death: 1 Viet Nam Cases: 127 Deaths: 64 Areas with confi rmed human cases for avian infl uenza A(H5N1) reported to WHO, 2003–2018* The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved * All dates refer to onset of illness Source: WHO/IHM, as of 16 February 2018 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 127 More information about Avian and other zoonotic infl uenza: • Avian and other zoonotic infl uenza WHO webpage: http://www.who.int/infl uenza/human_animal_interface/en/ • Avian and other zoonotic infl uenza WHO fact sheet: http://www.who.int/mediacentre/factsheets/avian_infl uenza/en/ • Avian and other zoonotic infl uenza WHO MOOC: https://openwho.org/courses/avian-and-other-zoonotic-infl uenza- introduction • WHO Summary Of Key Information Practical To Countries Experiencing Outbreaks Of A(H5N1) And Other Subtypes Of Avian Infl uenza, First Edition July 2016 http://apps.who.int/iris/bitstream/10665/246251/1/WHO-OHE-PED- GIP-EPI-2016.1-eng.pdf?ua=1 • Case defi nitions for the four diseases requiring notifi cation to WHO in all circumstances under the IHR (2005) http://www.who.int/ihr/survellance_response/case_defi nitions/en/ • Pandemic Infl uenza Preparedness Framework for sharing of infl uenza virus and access to vaccines and other benefi ts http://www.who.int/infl uenza/resources/pip_framework/en/ AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 128

1. Seasonal infl uenza is a respiratory disease transmitted through droplets 2. Infl uenza disease appears in seasonal epidemics and may be very disruptive 3. Infl uenza A and B viruses can cause epidemics 4. Infl uenza can be severe and fatal 5. Annual vaccination is the best way to prevent infection 6. Early treatment with antiviral drugs may reduce complications and deaths 7. Seasonal infl uenza is hard to differentiate clinically from other respiratory diseases 8. Non-pharmaceutical measures prevent and reduce transmission 9. Monitoring, regular surveillance and sharing of data and viruses are important 10. Border controls do not reduce international spread 10 THINGS YOU SHOULD KNOW Seasonal infl uenza SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 130 Seasonal infl uenza response tips Coordinating responders • WHO Global Infl uenza Surveillance and Response System (GISRS) monitors infl uenza activity globally and provides recommendations in areas including laboratory diagnostics, vaccines, antiviral susceptibility and risk assessment Communicating risk • Encourage health authorities to: - Educate on prevention measures - Communicate about vaccine effectiveness and safety, especially for high-risk groups • Promote hand and respiratory hygiene, and cough etiquette • Key messages: - Seasonal infl uenza is highly contagious - It spreads through droplets - Annual vaccination is the best prevention - High-risk groups such as the elderly, pregnant women, infants and people with underlying conditions are most at risk and should seek medical care Health Information • Regular sharing of epidemiological information and viruses helps to develop policy to reduce the infl uenza burden Health Interventions • Annual vaccination • Antiviral drugs • Non-pharmaceutical interventions: - Social distancing (e.g. school closure) - Hygiene: cough etiquette, hand hygiene SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 131 Seasonal infl uenza is a respiratory disease transmitted through droplets • Seasonal infl uenza (or “fl u”) is an acute respiratory disease. • It is highly contagious: it spreads easily from person to person through droplets when an infected individual coughs or sneezes. Sometimes, the transmission can be airborne, especially when aerosol- generating procedures are performed. • It can also be transmitted by touching contaminated surfaces or hands. • Therefore, rapid transmission can occur in crowded areas (e.g. schools or nursing homes). • Precautionary measures to limit transmis- sion include: hand hygiene, respiratory hygiene and cough etiquette, and drop- let precautions in hospital settings. Infl uenza disease appears in Seasonal epidemics and may be very disruptive • In temperate climates, seasonal epidemics occur mainly during winter. The epidemics generally last from eight to 10 weeks in temperate areas. • In tropical regions, the pattern of infl uenza epidemics is not always as regular. Some countries have two peaks and some do not have very regular epidemics. • Epidemics can be very disruptive. While the yearly burden is variable and the average burden is currently being evaluated, infl uenza does cause considerable disease in all countries. In addition to illness, epidemics can have a high economic impact because of work and school absenteeism, productivity losses and overwhelmed hospital capacity. 1 2 SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 132 Infl uenza A and B viruses can cause epidemics • There are four types of infl uenza viruses - types A, B, C and D - but only infl uenza A and B cause epidemics. Infl uenza A can infect many species (birds, humans, pigs, horses, etc.). Infl uenza B and C infect mainly humans. Infl uenza type C virus is less frequent and usually causes mild infections, thus presents less signifi cant public health implications. • The A type of infl uenza viruses are further classifi ed in subtypes based on their surface proteins. There are 18 different haemagglutinin (H) types and 11 different neuraminidase (N) types. Different combinations are possible. Currently, H3N2, H1N1pdm09 are circulating in humans as Seasonal infl uenza A viruses. Infl uenza can be severe and fatal • Infl uenza can cause severe illness or death in any person. • A wide range of complications can be caused by infl uenza virus infection of the upper respiratory tract (nasal passages, throat) and lower respiratory tract (lungs). Sinus and ear infections are examples of moderate complications from fl u, while pneumonia is a serious fl u complication, that people with chronic lung disease are at higher risk of developing. • Other possible serious complications triggered by fl u can include infl ammation of the heart (myocarditis), brain (encephalitis) or muscle (myositis, rhabdomyolysis) tissues, and multi-organ failure (for example, respiratory and kidney failure). Flu virus infection of the respiratory tract can trigger an extreme infl ammatory response in the body and can lead to sepsis. • People at higher risk of developing complications and severe Seasonal infl uenza are: a. Children younger than fi ve years; b. People older than 65 years; c. People with chronic medical conditions such as HIV/AIDS, asthma, heart and lung diseases and diabetes. • Flu also can make chronic medical problems worse. For example, people with asthma may experience asthma attacks while they have the fl u, and people with chronic heart disease may experience a worsening of this condition triggered by fl u. 3 4 • Infl uenza viruses are in constant mutation. This is called antigenic drift and results in changes to the viruses which make people susceptible to catch fl u every year, as they do not have immunity against the drifted viruses. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 133 Annual vaccination is the best way to prevent infection • The most effective way to prevent the disease is getting vaccinated every year. • Vaccination is especially important for pregnant women, people at high risk of exposure, people at higher risk of serious infl uenza complications, and for people who live with, or care for, high-risk individuals (health care workers). • Ideally, people should get vaccinated just before the infl uenza season begins for the most effective coverage, although getting vaccinated at any time during the infl uenza season can still help prevent infections. • Infl uenza viruses evolve constantly, and twice a year, WHO makes recommendations to update the vaccine compositions, based on the monitoring done through the Global Infl uenza Early treatment with antiviral drugs may reduce complications and deaths • Antiviral drugs may reduce severe complications and deaths. Ideally, they need to be administered early in the disease (within 48 hours of onset of symptoms). They are especially important for high-risk groups. • They are two types of drugs: neuraminidase inhibitors and adama- tanes. Currently, the majority of circulating infl uenza viruses are resistant to the adamantanes, limiting their effectiveness. Therefore, neuraminidase inhibitors (oseltamivir and zanamivir, peramivir and laninamivir) are the recommended fi rst-line treatment. • People with Seasonal infl uenza should always drink plenty of water, rest and not go to work, in order to reduce transmission. 5 6 Surveillance and Response System (GISRS). This maximises the effectiveness of the vaccines, as circulating viruses need to be well-matched with the viruses contained in the vaccines. • A number of inactivated infl uenza vaccines and recombinant infl uenza vaccines are available in injectable form. Live attenuated infl uenza vaccine is available as a nasal spray. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 134 7 Seasonal infl uenza is hard to differentiate clinically from other respiratory diseases• People with Seasonal infl uenza usually show non-specifi c symptoms. They include: sudden onset of fever, cough (usually dry), headache, muscle and joint pain, fatigue, and a runny nose. • The cough can be severe and can last two or more weeks. Most people recover within a week without requiring medical attention. • Incubation period is usually two days but may be from one to fi ve days. • An infected person may be infectious from one to two days before and until four to fi ve days after the onset of symptoms (children may be infectious for longer). • Laboratory diagnosis is critical to differentiate Seasonal infl uenza from other respiratory diseases: - The most appropriate specimens for the diagnosis of infl uenza are upper respiratory tract specimens. Samples should be taken from the deep nostrils (nasal swab), throat (oropharyngeal swab) and nasopharynx (nasopharyngeal swab). Nasopharyngeal aspirate and bronchial aspirate are also useful; - The Reverse Transcription Polymerase Chain Reaction (RT-PCR) is the preferred technique for diagnosis; - In addition to RT-PCR, other laboratory techniques are available for the detection, identifi cation and characterization of infl uenza virus including virus isolation in cell culture and the identifi cation of viral antigens (fl uorescent antibodies, FA, test or Enzyme-Linked Immunosorbent Assay, ELISA). Single serum is not ideal for diagnosis of an acute infection. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 135 Non-pharmaceutical measures prevent and reduce transmission • The implementation of non- pharmaceutical measures helps to prevent and slow transmission and control epidemics. • Before an epidemic, to reduce the potential disruptive effects of Seasonal infl uenza, it is critical that: - There is effective health planning in place so health education and immunization for at-risk patients, their close contacts and health care workers are implemented; - Increased demand for medical care and possible absenteeism of health care workers during the epidemic period are anticipated. • During an epidemic, to reduce transmission: - Health education should continue; - Hand hygiene, respiratory hygiene and cough hygiene (e.g. covering mouth and nose with a tissue when coughing and then throwing it out and washing hands) should be strictly observed by all; - Personal protective equipment in health care settings (masks) should be used when in contact with people with Seasonal infl uenza (the sick are wearing the mask); - Social distancing may help. It includes isolation of patients, staying at home when sick, and school closure. School closures have the greatest benefi t when applied early in the course of the outbreak. The benefi t has to be weighed against the cost of disruption; 8 - Risk communication and community engagement should be implemented so populations comply with recommended public health measures (especially needed to implement vaccination recommendations). SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 136 Border controls do not reduce international spread • Border control measures such as entry and exit screening and quarantining of travellers crossing international borders are generally not recommended, as they have not been shown to reduce the spread of infl uenza. • Screening for detecting people with fever might be ineffi cient as: - Infected people may travel during the incubation period, during which they will not show symptoms but will be able to transmit the disease; - People may be using anti-pyretics and not show fever. • Implementing borders control measures may also be very expensive and disruptive. 10 Monitoring, regular surveillance and sharing of data and viruses are important • Regular monitoring and surveillance are important to anticipate severe epidemics and plan health care services as well as to be prepared for a pandemic. • Since 1952, WHO has been coordinating a network which now has more than 150 laboratories and experts to analyse the spread of infl uenza and recommend the vaccine composition. • Sharing of viruses and data is also important to be able to update the vaccine and antiviral treatments. 9 SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 137 More information about Seasonal infl uenza: • Infl uenza WHO webpage: http://www.who.int/infl uenza/en/ • Seasonal infl uenza WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs211/en/ • Seasonal infl uenza WHO MOOC: https://openwho.org/courses/seasonal-infl uenza-introduction • Patient care: http://www.who.int/infl uenza/patient_care/en/ • Global Infl uenza Surveillance and Response System (GISRS): http://www.who.int/infl uenza/gisrs_laboratory/en/ SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 138

1. Another infl uenza pandemic is inevitable but unpredictable 2. Pandemics require global concerted actions 3. A pandemic happens when an infl uenza virus emerges to which most people have no immunity 4. Infl uenza pandemics may be mild or severe and can have a global impact 5. Vaccines will probably not be available in the fi rst months 6. Risk groups and symptoms will be unknown until the pandemic occurs 7. Early treatment with antivirals and other medical support can reduce complications and deaths 8. Non-pharmaceutical interventions may be the only effective initial measures in most countries 9. Communicating risk is critical 10. Pandemic response capacity can be built through Seasonal infl uenza 10 THINGS YOU SHOULD KNOW Pandemic infl uenza PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 140 Pandemic infl uenza response tips Coordinating responders • Multisectoral coordination • Whole-of-society approach Communicating risk • Encourage health authorities to: - Have a plan on the use of antivirals and vaccines - Have a multisectoral risk communication plan in place - Communicate early and frequently about how to protect from the disease • Engage communities and individuals to practice good hygiene • Key messages: - Pandemic infl uenza is caused by a new virus to which no one has immunity and protection - You can protect yourself by using proper cough hygiene, effective hand washing and by distancing yourself away from others if you fall sick - Stay at home, drink plenty of fl uids - Seek medical advice if you have severe symptoms or you already have other medical conditions that may put you at further risk of severe disease - Take the new vaccine when it became available if you are asked to do so Health Information • Notify a case of novel infl uenza to WHO, under the IHR (2005) • Share viruses and information with the WHO GISRS (Global Infl uenza Surveillance and Response System) • Consult WHO surveillance and severity assessment guidance Health Interventions • Vaccines • Antiviral treatment • Non-pharmaceutical interventions (at personal and community level): hygiene, social distancing etc. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 141 Another infl uenza pandemic is inevitable but unpredictable • It is not possible to predict when or where the next Pandemic infl uenza will occur, what subtype it will be, and what morbidity and mortality impact it will have, but it is certain that there will be one. • History has shown pandemics occur at 10- to 50-year intervals, with varying severity and impact. During the 20th century, there have been three infl uenza pandemics (in 1918, 1957 and 1968). Since 2000, there has been one infl uenza pandemic, in 2009. • Infl uenza viruses are very unstable and constantly mutating. They undergo small mutations (antigenic drift) and cause Seasonal infl uenza epidemics and out- of-season outbreaks. But a substantial change (antigenic shift) can occur at any time. It will result in a new virus (different subtype) which may lead to a pandemic. This antigenic shift can be the re-assortment of human infl uenza viruses with Avian or swine viruses, or signifi cant point mutations of Avian or swine viruses. Pandemics require global concerted actions • Infl uenza pandemics are very disruptive events that can cause severe social, economic, and political stress. Preparedness requires a whole-of-society approach to ensure that when the next pandemic strikes, the world will be able to respond rapidly and effectively to reduce morbidity and mortality. Not only the health sector but also all other sectors, individuals, families and communities, have a role to play in mitigating the effects of a pandemic. 1 2 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 142 A pandemic happens when an infl uenza virus emerges to which most people have no immunity • There are three necessary factors for the emergence of Pandemic infl uenza: - A new infl uenza virus emerges and causes illness in humans; - This virus has the ability to cause sustained human-to-human transmission; - Human population has little or no immunity to the virus. • Because it is a new virus to which people have not yet been exposed, the population has no or little immunity and the virus is able to spread quickly and cause illness in people. • A Pandemic infl uenza virus may arise when: - Genes from animal and human infl uenza viruses mix together to create a human- animal infl uenza re-assortant virus (genetic re-assortment); - Genes in an animal infl uenza virus change allowing the virus to infect humans and transmit easily among them (genetic mutation). • It is mandatory to notify a human infl uenza case caused by a new subtype to WHO, under the IHR (2005). 3 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 143 Vaccines will probably not be available in the fi rst months • Vaccines are one of the most effective ways to protect people during infl uenza epidemics and pandemics. • However, the availability of a pandemic vaccine will be delayed by several months because of the requirements for vaccine formulation and production lead-time. It is expected that it takes about 24 weeks (almost six months) for a vaccine to be available after the identifi cation of the pandemic virus. • It is probable that the worldwide production capacity will still be insuffi cient and restrict global access to the vaccine, at least during the fi rst phase of the pandemic. In the best case scenario, it has been estimated (2015) that annual production could reach about 6.2 billion 5 doses of vaccines , which is still insuffi cient to cover the world population because two doses of vaccines will probably be needed to fully protect against the virus. Furthermore, it is challenging to maintain this production capacity. • Vaccination should target the most at risk of exposure (health care workers, people living in crowded areas) and those most at risk of complications. • Antigen-sparing strategies can be used to increase vaccine availability. • Some countries are stockpiling pre- pandemic vaccines against some Avian infl uenza viruses. Infl uenza pandemics may be mild or severe and can have a global impact • Infl uenza pandemics have various levels of severity and impact. • It is hard to predict the characteristics, including level of severity, of the next pandemic. • During an infl uenza pandemic, severity assessments should be conducted regularly at local, national and global levels, to inform public health decisions (vaccine production and use, antivirals use, school closures, social distancing strategies, etc.). Key elements to take into consideration are: the transmissibility of the disease, its seriousness (complications, for which group of people, etc.), the impact on the health sector (whether it is overwhelmed or not). 4 Pandemic year of emergence and common name Area of origin Influenza A virus sub - type (type of animal genetic introduction/ recombination event) Estimated reproductive number Estimated case fatality Estimated attributable excess mortality worldwide Age group most affected 1918 “Spanish flu” Unclear H1N1 (unknown) 1.2–3.0 2–3% 20–50 million Young adults 1957–1958 “Asian flu” Southern China H2N2 (avian) 1.5 <0.2% 1–4 million All age groups 1968–1969 “Hong Kong flu” Southern China H3N2 (avian) 1.3–1.6 <0.2% 1–4 million All age groups 2009–2010 “influenza A(H1N1) 2009” North America H1N1 (swine) 1.1–1.8 0.02% 100 000–400 000 Children and young adults Characteristics of the past four infl uenza pandemics Source: Pandemics of the 20th–21st centuries. Stockholm, European Centre for Disease Prevention and Control. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 144 7 Early treatment with antivirals and other medical support can reduce complications and deaths • Antiviral drugs may reduce severe complications and deaths. Ideally, they need to be administered early in the disease (within 48 hours of onset of symptoms). They are especially important for high-risk groups. • During an infl uenza pandemic, antiviral drugs are an important tool to prevent the spread of the disease and severe outcome and complications, as vaccines will most likely not be available at an early stage. • Effectiveness of the drugs on the novel pandemic virus must be monitored, as some infl uenza viruses may be (or become) resistant to them. • Pharmaceutical interventions typically encompass the application of antivirals treatments and other drug treatment (e.g. antibiotics to target complications of infl uenza). Risk groups and symptoms will be unknown until the pandemic occurs • Although we start with the assumption that the risk groups for infection and severe outcome are the same as in Seasonal infl uenza, there might be differences. • Historical knowledge from the 1918 and 2009 pandemics indicates that healthy, young adults can be disproportionately and more severely affected. • Pandemic infl uenza might present differently from Seasonal infl uenza and symptoms may be more severe and complications more frequent. - People with infl uenza will usually develop the following symptoms: sudden onset of fever, cough (usually dry), headache, muscle and joint pain, fatigue, sore throat and a runny nose; - Complication can include pneumonia, sepsis, and infl ammation of the heart (myocarditis), brain (encephalitis) or muscle (myositis); - The incubation period is usually two days but may be from one to fi ve days. 6 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 145 Non-pharmaceutical interventions may be the only effective initial measures in most countries • Vaccination is the primary intervention to prevent infection and severe outcomes caused by infl uenza virus. However, at the beginning of a pandemic, Pandemic infl uenza vaccines, matching the new virus, will most likely not be available. • In addition to antiviral drugs administration (which might also be short in supply), non-pharmaceutical interventions (NPI) should be put in place, at the early stage of a pandemic, to slow transmission and reduce its impact. NPI include (but are not limited to): - Social distancing: staying at home when sick; - Hygiene such as cough etiquette (covering coughs and sneezes with a tissue), hand washing and cleaning of touched surfaces and objects; - During severe pandemics, more extreme measures can be implemented: using facemasks when sick, schools closures, decreasing the amount of contacts among people. • NPI will help to reduce the number of people who are exposed and then infected. 8 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 146 Pandemic response capacity can be built through Seasonal infl uenza • Pandemic infl uenza would require the implementation of the same control measures, on a larger scale: Infection Prevention and Control and Hygiene; Health Education; Vaccination; Early treatment; Social distancing; Risk communication and Community engagement. 10 Communicating risk is critical • Risk communication is particularly important in a rapidly evolving situation and when there is little known about an epidemic, which will be the case at the beginning of an infl uenza pandemic (novel virus). Without effective communication, the many unknowns give enough space for rumors to develop. • As the pandemic requires a whole- of-society approach, individuals and communities must be engaged, listened to and see that their concerns are addressed. People need to be informed on how to protect themselves and stop the spread of the disease. • Strong risk communication must be built before the emergency occurs. 9 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 147 Highlight: the PIP Framework • The Pandemic infl uenza Preparedness Framework or “PIP Framework” is an innovative public health instrument that seeks to better prepare the world to respond to Pandemic infl uenza. • It brings together Member States, industry, other stakeholders and WHO to implement a global approach to Pandemic infl uenza preparedness and response. • The PIP Framework has two objectives which are to be pursued on equal footing: - To improve the sharing of infl uenza viruses with the potential to cause a human pandemic; - To establish more predictable, effi cient, and equitable access to the benefi ts that result from the sharing of such viruses, notably vaccines and antiviral medicines. • The Framework, developed by Member States, came into effect on 24 May 2011, unanimously adopted by the World Health Assembly. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 148 More information about Pandemic infl uenza: • Infl uenza WHO webpage: http://www.who.int/infl uenza/en/ • Pandemic Infl uenza WHO MOOC: https://openwho.org/courses/pandemic-infl uenza-introduction • WHO Global Epidemiological Surveillance Standards for Infl uenza http://www.who.int/infl uenza/resources/documents/infl uenza_ surveillance_manual/en/ • WHO surveillance case defi nitions for infl uenza-like illness (ILI) and severe acute respiratory infections (SARI) http://www.who.int/infl uenza/surveillance_monitoring/ili_sari_ surveillance_case_defi nition/en/ • Pandemic Infl uenza Risk Management, WHO interim guidance, 2013 http://www.who.int/infl uenza/preparedness/pandemic/infl uenza_risk_ management/en/ • WHO Checklist for Pandemic Infl uenza Risk and Impact Management http://www.who.int/infl uenza/preparedness/pandemic/en/ • WHO Pandemic Infl uenza Severity Assessment (PISA) http://www.who.int/infl uenza/surveillance_monitoring/pisa/guidance/en/ • Pandemic Infl uenza Preparedness Framework: http://www.who.int/infl uenza/pip/en/ PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 149 1. MERS (Middle East respiratory syndrome) is a respiratory disease caused by a coronavirus whose reservoir is dromedary camels 2. Humans can be infected through direct or indirect contact with infected dromedary camels and potentially from camel products 3. The impact ranges from asymptomatic infection to severe pneumonia and death 4. People with weakened immune systems and chronic diseases are at high risk of severe disease 5. Early supportive clinical management reduces mortality 6. Infection prevention and control measures are critical to prevent the spread of human-to-human transmission 7. Laboratory diagnostics are available for MERS 8. Thorough case and outbreak investigation and other measures will help to prevent spread 9. Research is ongoing for treatment in humans and vaccines for camels and humans 10. MERS coronavirus (MERS-CoV) infection is a notifi able disease under the International Health Regulations (2005) 10 THINGS YOU SHOULD KNOW Middle East respiratory syndrome (MERS) MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 150 MERS response tips Coordinating responders • Coordination between animal and human health sectors is essential for: - Surveillance - Risk assessment - Investigation - Mitigation Communicating risk • Encourage health authorities to: - Identify and target at-risk populations with information on how to protect themselves and prevent further transmission - Have a multi-sectoral risk communication plan and to activate it • Key messages: - Precautions for people at high risk of developing severe disease include: practicing good personal hygiene, avoiding contact with camels; not drinking raw camel milk or camel urine; and not eating camel meat that has not been thoroughly cooked - Enhance infection prevention and control in health care facilities - Seek health care early on and follow medical advice Health Information • Report cases to WHO, under the IHR (2005) • WHO regularly conducts global risk assessments for MERS-CoV, these can be found here: http://www.who.int/csr/ disease/coronavirus_infections/archive_ updates/en/ • WHO has developed standard case reporting forms for data analysis and to guide actions Health Interventions • Active case fi nding and contact tracing • Supportive case management • Infection prevention and control measures to prevent health care workers infections MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 151 MERS (Middle East respiratory syndrome) is a respiratory disease caused by a coronavirus whose reservoir is dromedary camels • Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (Middle East respiratory syndrome coronavirus, or MERS-CoV) that was fi rst identifi ed in humans in the Kingdom of Saudi Arabia in 2012. • Coronaviruses are a large family of viruses that can cause diseases in humans, ranging from the common cold to Severe Acute Respiratory Syndrome (SARS). • Dromedary camels (one-humped camels) are the reservoir host for MERS-CoV. • Since 2012, MERS has been reported in 27 countries. Approximately 80% of human cases have been reported by the Kingdom of Saudi Arabia. Cases identifi ed outside the Middle East are people who were infected in the Middle East and then travelled elsewhere. On rare occasions, small outbreaks have occurred in areas outside the Middle East. 1 2 Humans can be infected through direct or indirect contact with infected dromedary camels and potentially from camel products • MERS-CoV is a zoonotic virus: it is transmitted between animal and people. • Dromedary camels are the main source of infection in humans: humans are infected through direct or indirect contact with infected dromedary camels. • At-risk groups of infection, because they are in contact with dromedary camels, include: camel farm workers; slaughterhouse workers; market workers; veterinarians; anyone handling dromedary camels or dromedary camels’ products (e.g. cooking). Health care workers caring for MERS patients without adequate personal protective equipment are also at high risk of infection. • It is recommended that these high-risk groups practice good personal hygiene, including frequent hand hygiene. Hands should be washed with soap and water and/or alcohol gel after every contact with an animal. Workers should wear facial protection where feasible; and protective clothing, which should be removed after work (followed by hand hygiene) and washed daily. • The consumption of raw or undercooked animal products, including milk and meat, carries a potential risk. Animal products that are processed appropriately through cooking or pasteurization are safe for consumption. Properly cooked products should also be handled with care to avoid cross contamination with uncooked foods. • As a general precaution, anyone visiting farms, markets, barns, or other places where dromedary camels and other animals are present should practice general hygiene measures, including regular hand washing before and after touching animals, and should avoid contact with sick animals. People should avoid unprotected direct contact with any animal that has been confi rmed positive for MERS-CoV infection. • There is no evidence of sustained human- to-human transmission: the virus does not pass easily from person to person unless there is close and unprotected contact. There has been limited human- to-human transmission among family members. However, human-to-human transmission has been repeatedly shown to be amplifi ed in health care settings, especially when infection prevention and control measures are inadequate. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 152 The impact ranges from asymptomatic infection to severe pneumonia and death • The clinical spectrum of MERS-CoV infection ranges from no symptoms (asymptomatic) or mild respiratory symptoms to severe acute respiratory disease and death. • MERS symptoms are non-specifi c and can include headache, tiredness, feverishness, mild cough, sore throat, and runny nose. Some patients may present with gastrointestinal symptoms such as 3 mild diarrhoea. Pneumonia is a common fi nding, but not always present. • Severe illness can cause respiratory failure that requires mechanical ventilation and support in an intensive care unit. • The average incubation period is estimated to be approximately fi ve days but may range from two to 14 days. • It is not always easy to detect cases early because symptoms are non-specifi c and this may lead to spread of the disease in health care settings. People with weakened immune systems and chronic diseases are at high risk of severe disease • The virus causes a more severe disease in older people, people with weakened immune systems, and those with chronic diseases such as renal disease, cancer, chronic lung disease, blood disease and diabetes. These people are also at increased risk of infection. • People at high risk of developing severe disease (people with underlying conditions) should avoid contact with camels. 4 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 153 Early supportive clinical management reduces mortality • Supportive therapies prevent complications and increase chances of survival. They include: oxygen, antimicrobials, specifi c treatment for underlying conditions such as diabetes, kidney failure, etc. • Treatment is based on a person’s clinical condition. • There is no specifi c treatment or vaccine available for MERS currently. 5 Infection prevention and control measures are critical to prevent the spread of human-to-human transmission • Standard precautions should be routinely applied to all patients. They include hand hygiene, respiratory hygiene, use of Personal Protective Equipment (PPE), safe waste management, cleaning and disinfection of equipment and cleaning of the environment. • Triage policies should be implemented to rapidly detect potential MERS-CoV cases and all cases with acute respiratory symptoms. • Triage, waiting areas and patient rooms should be adequately ventilated. • Health care workers involved in aerosol- generating procedures are at greater risk of infection. • Droplet precautions should be added to the standard precautions when providing care to any patient with symptoms of acute 6 respiratory infection (ARI). They include the use of a mask and eye-protection when working within 1-2 metres of the patient and patient isolation (organization of the space and processes to allow separation of at least 1-2 metres between patient with ARI and other individuals not wearing PPE). • When performing an aerosol-generating procedure in patient with ARI, airborne precautions should be applied. They include wearing an appropriate PPE, appropriate ventilation, avoiding unnecessary individuals in the room. • Health care workers should be educated and trained in infection prevention and control and should refresh these skills regularly. • Hospital cleaning staff should also be informed of and trained to take proper precautions when cleaning rooms of MERS patients. Infection prevention and control when caring for patients with MERS or suspected MERS All patients Patients with ARI When performing aerosol-generating procedures in patients with ARI Standard precautions, triage procedures Droplet precautions Airborne precautions MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 154 7 Laboratory diagnostics are available for MERS• Laboratory confi rmation of MERS-CoV infection requires good samples, high levels of biosafety and good laboratory capacities. Testing: • A case of MERS-CoV infection may be laboratory confi rmed by detection of viral nucleic acid or by using serology to demonstrate antibodies. • The presence of viral nucleic acid can be confi rmed by either: - A positive real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) on at least two specifi c genomic targets; o A case with a positive RT-PCR result for a single specifi c target without further testing but with a history of potential exposure and consistent clinical signs is considered a probable case. - Or a single positive target with sequencing. • If initial testing is negative in patient who is strongly suspected to have MERS- CoV infection, the patient should be resampled and include lower respiratory specimens. To confi rm clearance of the virus, respiratory samples should continue to be collected until there are two consecutive negative results at least 24 hours apart in clinically recovered persons. Samples: • It is strongly recommended that lower respiratory specimens such as sputum, endotracheal aspirate or broncho- alveolar lavage are collected for MERS- CoV when possible. • If not possible, upper respiratory tract specimens such as nasopharyngeal aspirate or combined nasopharyngeal and oropharyngeal swab should be collected. Biosafety: • Molecular testing for MERS-CoV should be conducted under Biosafety level 2 (BSL-2) conditions. Virus culture requires BSL-3 biosafety conditions. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 155 Thorough case and outbreak investigation and other measures will help to prevent spread • Each human case of MERS requires thorough investigation to understand the source of infection and the potential human-to-human spread amongst contacts. • Thorough case investigation includes the investigation of potential human, animal, and/or environmental sources of exposure(s) and risk factors for infection. Patients (confi rmed and suspected cases) and family members should be interviewed to collect: Essential basic information; Exposure information and travel history; and Clinical information. WHO has generated case report forms identifying the minimum amount of information that should be collected for each case of MERS. 8 • Once a case has been confi rmed, to prevent further spread of the disease, active case fi nding should be implemented in the community and in health care settings: - All close contacts should be identifi ed and monitored for the presence of symptoms for 14 days. A contact is any person who has cared for or lived with a confi rmed case, or had unprotected contact with that person’s respiratory secretions, body fl uids and/or excretions when that person was symptomatic; - Contacts should be placed under active surveillance for 14 days after last exposure to the confi rmed or probable case with monitoring for respiratory symptoms (a health care worker should visit or call them on a daily basis); - Any contacts who develop symptoms should be isolated in a health care facility and tested for MERS-CoV infection; - Health care workers with direct contact with a MERS patient should be closely monitored. • Health Education, including basic information about MERS, how to prevent against MERS-CoV infection for different groups (e.g. contacts of confi rmed patients, health care workers caring for MERS patients, occupational groups who work with dromedary camels, and populations at higher risk of severe disease) and what to do should an individual suspect they have MERS-CoV infection, should be provided by trained individuals. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 156 MERS-CoV infection is a notifi able disease under the International Health Regulations (2005) • Probable and confi rmed cases must be reported within 24 hours of classifi cation, with information about their exposure, testing and clinical course. MERS case defi nitions for reporting to WHO can be found here: http://www.who.int/csr/ disease/coronavirus_infections/case_ defi nition/en/ 10Research is ongoing for treatment in humans and vaccines for camels and humans• WHO has developed a MERS-CoV research agenda to address key unknowns for this virus focusing on fi ve major areas of research: i) virus origin and characteristics, ii) epidemiology and transmission, iii) clinical management and infection prevention and control measures, iv) product development and implementation, and v) impact of interventions and operational research. • WHO’s Research and Development Blueprint is working to accelerate the development of medical interventions for MERS. - Currently, there are no licensed treatments for MERS; - Currently, a dozen vaccine candidates for both humans and dromedary camels are in preclinical development. 9 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 157 Data as 12 December 2017 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Confi rmed global cases of MERS-CoV 2012 – 2017 Thailand Algeria Austria France Germany Greece The Islamic Republic of Iran Jordan Republic of KoreaKuwait Lebanon Oman Malaysia Netherlands Qatar Philippines United Arab Emirates Tunisia Turkey United Kingdom of Great Britain and Northern Ireland United States of America Saudi Arabia Yemen Egypt Italy China 2,119Total number of reported cases: Number of cases reported 1 - 5 6 - 20 21 - 150 151 - 500 501 - 1000 1000+ 2012 2013 20152014 Confirmed global cases or MERS-CoV by month reported Saudi Arabia Rest of the World Date reported to WHO 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 C as e C ou nt 240 220 200 180 160 140 120 100 80 60 40 20 0 Date reported to WHO 20172015201420132012 2016 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 158 More information about MERS: • MERS-CoV WHO website: http://www.who.int/emergencies/mers-cov/en/ • MERS WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Latest global risk assessment for MERS-CoV: http://www.who.int/csr/disease/coronavirus_infections/archive_updates/en/ • Guidance on laboratory testing: http://www.who.int/csr/disease/coronavirus_infections/mers-laboratory- testing/en/ • Surveillance guidance including recommendations on criteria for case investigation and testing: http://www.who.int/csr/disease/coronavirus_infections/surveillance- human-infection-mers/en/ • Guidance on the investigation of cases of MERS-CoV infection: http://www.who.int/csr/disease/coronavirus_infections/mers- investigation-cases/en/ • WHO case investigation form for MERS-CoV: http://www.who.int/csr/disease/coronavirus_infections/MERS_case_ investigation_questionnaire.pdf?ua=1 • MERS case defi nitions for reporting to WHO: http://www.who.int/csr/disease/coronavirus_infections/case_defi nition/en/ • Guidance on case management and Infection Prevention and Control: http://www.who.int/csr/disease/coronavirus_infections/technical- guidance-infection/en/ • Information about MERS-CoV Research and Development: http://www.who.int/blueprint/priority-diseases/key-action/mers-cov/en/ MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 159 1. Cholera is closely linked to inadequate access to clean water and sanitation 2. Cholera is transmitted by faecally-contaminated water and food 3. Cholera outbreaks can be explosive 4. Rapid detection of suspected cases and laboratory confi rmation are essential 5. People with Cholera experience acute watery diarrhoea with no fever 6. Severe forms of Cholera can kill within hours: early rehydration is the cornerstone of treatment 7. Oral Cholera Vaccines are safe and should be used with other prevention and control strategies 8. Populations at risk should be provided with safe water and basic sanitation 9. Mapping the origin of cases is critical to orient control activities 10. WHO can provide countries with Cholera kits 10 THINGS YOU SHOULD KNOW Cholera CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 160 Cholera response tips Coordinating responders • Intersectoral coordination at national and local level is critical to outbreak response • Epidemiological data on the origin of cases should drive the multisectoral response • Cholera kits are available for preparedness and immediate outbreak response • Contact WHO/ICG for emergency Oral Cholera Vaccines • Technical support is available through the Global Task Force on Cholera Control (GTFCC) Communicating risk • Encourage health authorities to: - Engage communities to enhance hygiene and food safety practices - Set up treatment facilities and let the public know how to access them - Make sure Oral Rehydration Salts are available • Key messages: - Cholera is transmitted through contaminated water or food - Cholera can rapidly lead to severe dehydration and death if left untreated: seek treatment quickly - Wash hands at critical moments - Mild cases can be treated at home with oral rehydration - Take the Cholera vaccine if advised, when there is a Cholera outbreak or its threat, in your area Health Information • Investigate the source of the outbreak • Once Vibrio Cholerae has been confi rmed by culture or PCR, the WHO clinical case defi nition is suffi cient to identify cases. Periodic sampling and testing on suspected cases should be carried out throughout the epidemic to monitor antimicrobial sensitivity Health Interventions • Provide populations with safe water and sanitation • Treat early (rehydration): - Oral rehydration points (ORPs) in the community facilitate early access to treatment - Cholera treatment centres (CTCs) provide 24-hour care for patients with more severe forms of Cholera • Infection prevention and control practices must be implemented in all health facilities receiving Cholera patients • Vaccination with Oral Cholera Vaccines in humanitarian emergencies and to prevent further spread of epidemics CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 161 Major Cholera Outbreaks in 2017 - 2018 Source: WHO, 2018 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved Mozambique (0.3%) Nigeria (1.3%) Sudan (2.2%) Angola (2%) Somalia (1.3%) Democratic Republic of the Congo (2.2%) Zambia (1.8%) Uganda (2.1%) Malawi (3.3%) Ethiopia (1.8%) Zimbabwe (5.1%) South Sudan (2.1%) Yemen (0.2%) Kenya (2%) United Republic of Tanzania (2%) 6,223 7,209 36,811 713 6,613 62,154 63,829 5,695 5,248 21,439 2,108 1,090,280 904 47,868 137 Map date: 01 May 2018 Not Applicable Ethiopia and Sudan: Reported as AWD Number of Cases Case Fatality Rate(CFR)* > 100,000 Haiti (1.2%) 818,000 < 1000 1000 to 5000 5000 to 20,000 20,000 to 100,000 0 100 200 km 0 750 1,500 km < 1% >1% to 2% >2% to 3% >3% to 4% >4% to 5.1% Period of Report *CFR Labelled for Each Country Angola: Dec 2017-March 2018 Democratic Republic of the Congo: Jan 2017 – April 2018 Ethiopia: Jan 2017 – April 2018 Haiti: Oct 2010 – Feb 2018 Kenya: Jan 2017-mid April 2018 Malawi: Nov 2017 – April 2018 Mozambique: Jan 2017 - 8 April 2018 Nigeria: Aug 2017 – April 2018 Somalia: March 2017 – March 2018 South Sudan: Aug 2016 – Dec 2017 Sudan: Aug 2016 – Feb 2018 United Republic of Tanzania: Jan 2017- mid April 2018 Uganda: Feb 2018 – April 2018 Yemen: April 2017 – April 2018 Zambia: Oct 2017 – April 2018 Zimbabwe: Jan – April 2018 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 162 1 2 Cholera is transmitted by faecally-contaminated water and food• A person can become infected by drinking water or eating food contaminated by the bacterium Vibrio Cholerae. • Bacteria present in the faeces of an infected person are the main source of contamination. • Food may be contaminated by soiled hands during preparation, or while eating or by some irrigation practices. • During funeral ceremonies, transmission may occur through consumption of food and beverages contaminated by someone who touched the corpse of the deceased and also prepared the food without adequately washing their hands, or by funeral attendees touching the corpse. • Beverages prepared with contaminated water and sold by street vendors are vehicles of Cholera transmission, as well as vegetables and fruits “freshened” with contaminated water and raw or undercooked seafood. • The bacterium can persist in water for long periods and multiply in moist left- over food. Cholera is closely linked to inadequate access to clean water and sanitation • The long-term solution for Cholera control lies in economic development and universal access to safe drinking water and adequate sanitation. These measures prevent both epidemic and endemic Cholera as well as other faeco- orally transmitted and water-borne diseases. They may require substantial long-term investments. • Cholera is closely linked to poor environmental conditions. The absence or shortage of safe water and of proper sanitation are the main contributors to the spread of the disease. Typical at- risk areas are peri-urban slums, with precarious basic infrastructure, as well as internally displaced or refugee camps. • Actions to reduce the transmission of Cholera include: - The implementation of adapted long- term sustainable WASH (Water Sanitation and Hygiene) solutions to ensure use of safe water, basic sanitation and good hygiene practices to populations most at risk of Cholera: o Interventions at the household level (water fi ltration, chemical or solar disinfection of water, safe water storage, the construction of systems for safe sewage disposal, including latrines); o Adoption of basic hygiene practices; o Access to safe water and sanitation in public areas such as health facilities and schools. - Rapid access to treatment; - Implementation of adapted infection control practices in treatment structures; - Vaccination. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 163 Cholera outbreaks can be explosive • The incubation period is very short. It ranges from two hours to fi ve days, usually two to three days. • This leads to explosive epidemics as the numbers of cases can rise extremely quickly. • Early detection and treatment of cases and rapid initiation of control activities are critical. • Asymptomatic carriers can transmit the infection. As long as stools are positive, infected people can transmit the disease. Even among asymptomatic carriers, the pathogens stay in their faeces for up to 14 days and are shed back into the environment, possibly infecting other individuals. 3 Rapid detection of suspected cases and laboratory confi rmation are essential • When an outbreak is suspected, a multidisciplinary team should be sent to the fi eld in order to confi rm the outbreak and to take the fi rst measures to control the spread of the disease. These teams should carry sampling materials, rapid diagnostic tests, the means to make clean water and ORS (Oral Rehydration Salts) at a minimum. More medical materials should be carried if a treatment facility is visited. • Rapid diagnostic tests (RDTs) should be used to reinforce suspicion of Cholera. This allows quick testing without the need for a laboratory and is frequently used to increase suspicion during outbreak investigations. The sensitivity and specifi city of Cholera RDTs are not suffi cient for them to be used as individual diagnostic tests. Send the RDT positive stool samples to the laboratory for confi rmation. • Cholera is confi rmed by identifying V. Cholerae in stool samples from affected patients using: - Culture for confi rmation and antibiotic sensitivity testing; - PCR (Polymerase Chain Reaction) for confi rmation. • Laboratory confi rmation is essential to confi rm that this is a Cholera outbreak. Once an outbreak is confi rmed, a clinical diagnosis using WHO standard case defi nition is suffi cient. 4 • Laboratory confi rmation should be carried out in each new area (district or region) reporting cases to confi rm extension of the outbreak. • Sporadic sampling and testing on suspected cases should be performed throughout an outbreak to monitor the outbreak, determine antibiotic sensitivity, and monitor the strain. • An outbreak is considered over when all samples from all suspected patients test negative by RDT, culture or PCR for a period of two weeks. • Do not wait for laboratory confi rmation before starting control activities. Access to clean water and basic sanitation, hygiene promotion and access to treatment are important public health interventions even if the outbreak is not confi rmed. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 164 People with Cholera experience acute watery diarrhoea with no fever • Most people infected with Cholera (approximately 80%) do not develop any symptoms although the bacteria are present in their faeces for up to 14 days after infection. • Among people developing symptoms, approximately 80% present with mild to moderate watery diarrhoea resulting in no or only minor signs of dehydration. The remaining 20% rapidly develop profuse watery diarrhoea that can lead to severe dehydration and to death if not treated. • Other signs and symptoms may include: - Profuse vomiting; - Abdominal or muscle cramps; - Hypoglycemia; - Hypokalaemia. • There is a high risk of fetal loss in pregnant woman with Cholera. • Fever is not a symptom of Cholera, but may be a result of co-morbidity in patients with Cholera. 5 Severe forms of Cholera can kill within hours: early rehydration is the cornerstone of treatment • The most important treatment is rehydration, which consists of prompt replacement of the fl uid and salts loss through severe diarrhoea and vomiting. Early rehydration can save the lives of nearly all Cholera patients. With early and proper treatment, the case fatality rate should remain below 1%. • Good assessment of the state of dehydration is key to appropriate treatment (see the assessment tool in the manual “First steps for managing an outbreak of acute diarrhoea”). • Patients with no signs or some signs of dehydration (approximately 80% of patients), both adults and children, can be rehydrated quickly and easily by following standard protocols for treatment with Oral Rehydration Solution (ORS). ORS should be given early at home, by volunteers and family members, to avert delays in rehydration and death. • Patients who become severely dehydrated need to receive fl uids intravenously (Ringer’s Lactate solution). • Continued breastfeeding of infants and young children is encouraged. • Zinc is also an important adjunctive therapy for children under fi ve years, which also reduces the duration of diarrhoea and may prevent future episodes of other causes on acute watery diarrhoea. 6 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 165 7 Oral Cholera Vaccines are safe and should be used with other prevention and control strategies• There are three Oral Cholera Vaccines (OCV): - Shanchol™ and Euvichol® are essentially the same vaccine. One dose can be used to contain epidemics (protection for at least six months). Two doses are required for longer protection (both vaccines provide sustained protection of >65% for at least three years after two doses). The two doses can be administered to all individuals over the age of one year with a minimum two-week interval between doses; - There is a third vaccine, Dukoral®, that is primarily used for travellers. It also confers signifi cant short-term protection against Enterotoxigenic Escherichia coli (ETEC). The vaccine is administered with a buffer solution. It can be given to all individuals over the age of two years with a minimum of a week between doses. • Oral Cholera Vaccines are considered safe for pregnant women. • OCV can be used for emergencies: - In humanitarian crises, OCV can be used to prevent Cholera, even before any suspected cases are reported; - For outbreak response, OCV is used to prevent further spread of Cholera. It should be used as early as possible to prevent the greatest number of cases; - All OCVs currently require cold chain (2- 8°C), but use out of cold chain is currently under review; - For emergency use of OCV, there is a global emergency stockpile of Oral Cholera Vaccine doses (Shanchol™ or Euvichol®) managed by the International Coordinating Group (ICG). • In endemic settings, Oral Cholera Vaccines are used as part of a longer-term Cholera control plan, including reinforcement of surveillance and laboratory diagnostic capacity and improving water, sanitation and hygiene conditions. OCV is used to provide mid-term protection to the population while longer term water, sanitation and hygiene solutions are being implemented. - OCV for endemic use is available via the Global Task Force on Cholera Control. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 166 Populations at risk should be provided with safe water and basic sanitation • During outbreaks: - People should be provided with safe water or means to prepare and store safe water at home; - Awareness campaigns should be organized, and information should be provided to the community about the potential risks and symptoms of Cholera, precautions to take to avoid Cholera, when and where to report cases, and to seek immediate treatment when symptoms appear. The location of appropriate treatment sites should also be shared. • Community engagement is critical, at any time, so that communities adopt preventive behaviors to avert contamination: 8 - Health education campaigns should promote the adoption of appropriate hygiene practices such as hand-washing with soap, safe preparation and storage of food and safe disposal of the faeces of children; - Handwashing should be promoted at key times; - Funeral practices for individuals who die from Cholera must be adapted to prevent infection among attendees; - Breastfeeding should be promoted; - Health campaigns should be adapted to local culture and beliefs. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 167 WHO can provide countries with Cholera kits • WHO can provide necessary materials for the investigation and confi rmation of Cholera outbreaks, as well as for the treatment of Cholera patients. Cholera kits are designed to help prepare for a potential Cholera outbreak and to support the fi rst month of the initial response. • There are six kits: - One kit provides the necessary materials for the investigation of Cholera outbreaks; - One provides the supplies for laboratory confi rmation of suspected Cholera cases. 10Mapping the origin of cases is critical to orient control activities• Mapping the origin of cases can help identify priority areas for water and sanitation activities and hygiene promotion. The more precise the mapping, the more effectively interventions can be targeted. • Access to treatment for people living in priority areas should also be ensured. • Oral rehydration points in key areas and transport services to Cholera treatment centres can save lives. • Active case fi nding should also be carried out in these areas. • In areas with community health programmes, the community health workers or volunteers can be trained to identify and report suspected Cholera, to safely make and give ORS, and to refer patients for treatment. 9 Note: triple packaging for sample transport is NOT included; - Three kits are designed for the treatment of Cholera patients within existing structures at the central, peripheral and community levels; - One kit provides the necessary material to set up a provisional structure for patient care when no existing structure is in place. • There is a tool that quickly estimates needs of Cholera kits (see link on next page). CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 168 More information about Cholera: • Cholera WHO webpage http://who.int/cholera/en/ • Cholera WHO factsheet http://who.int/mediacentre/factsheets/fs107/en/ • Ending Cholera: a global roadmap to 2030 http://www.who.int/cholera/publications/global-roadmap/en/ • Cholera kits http://who.int/cholera/kit/en/ • Cholera outbreak: assessing the outbreak response and improving preparedness http://who.int/cholera/publications/OutbreakAssessment/en/ • First steps for managing an outbreak of acute diarrhoea http://who.int/cholera/publications/fi rststeps/en/ • Interim guidance document for Cholera surveillance, Global Task Force on Cholera Control, Surveillance Working Group http://www.who.int/cholera/task_force/GTFCC-Guidance-cholera- surveillance.pdf?ua=1 • Interim technical notes on the Use of Cholera Rapid Diagnostic Tests, Global Task Force on Cholera Control, Surveillance and Laboratory Working Group http://www.who.int/cholera/task_force/Interim-guidance-cholera-RDT. pdf?ua=1 • Oral Cholera Vaccine and technical notes on the use of OCV in pregnant women and travellers http://www.who.int/cholera/vaccines/en/ • WHO Oral Cholera Vaccines position paper – 2017 http://apps.who.int/iris/bitstream/10665/258763/1/WER9234.pdf?ua=1 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 169 1. Monkeypox virus is in the same family of viruses as Smallpox virus (Orthopoxviruses) 2. Primary infection occurs through direct contact with body fl uids or lesions of infected animals 3. Secondary human-to-human transmission exists 4. Isolation of patients and standard infection prevention and control (IPC) measures are key to minimizing any possibility of human-to-human transmission 5. Avoid contact with animals that could harbour the virus, especially rodents and sick or dead animals 6. Active surveillance to ensure rapid identifi cation of new cases is critical for outbreak containment 7. There is no specifi c treatment or vaccine recommended for Monkeypox 8. Health education and raising population awareness are the best preventive measures in at-risk populations 9. Many animal species host the Monkeypox virus, primarily rodent species (rather than monkeys, after which the disease is named) 10. Monkeypox is a rare disease that occurs sporadically in remote tropical rainforest areas of Central and West Africa 10 THINGS YOU SHOULD KNOW Monkeypox MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 170 Monkeypox response tips Coordinating responders • Establish an Emergency Operations Centre if cases are above what is expected • Ensure the animal and wildlife sector is involved from the very beginning • Engage communities Communicating risk • Encourage health authorities to: - Engage communities to prevent exposure - Ensure training of clinicians for early detection, sampling and treatment • Key messages: - Avoid contact with dead animals (rats, squirrels and monkeys) - Human-to-human transmission occurs through respiratory droplets, contact with infected persons or contaminated materials - If you think you might have been exposed to Monkeypox and have any symptoms, go to the nearest health facility and avoid self- medication - Protect yourself when caring for patients with a rash Health Information • Develop a case defi nition and a case investigation form adapted to the context • Develop a consolidated laboratory/ surveillance database • Map cases residence • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and strong risk communication • Contact tracing • Isolation and supportive care for cases • Psychosocial support for all suspected cases and families • Safe and dignifi ed burials MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 171 1 2 Primary infection occurs through direct contact with body fl uids or lesions of infected animals • Primary infection occurs through direct contact with the blood, body fl uids, or cutaneous or mucosal lesions of infected animals. • Hunters in tropical forests of West and Central Africa and people who may be exposed to animals infected with Monkeypox are at higher risk of infection. • People living in or near the forested areas may have indirect or low-level exposure to infected animals, possibly leading to subclinical (asymptomatic) infection and concommitant acquisition of immunity, although this needs to be further explored. Monkeypox virus is in the same family of viruses as Smallpox virus (Orthopoxviruses) • Monkeypox is a rare viral zoonosis with symptoms similar to those seen in Smallpox patients, although less severe. Monkeypox and Smallpox are members of the Orthopoxvirus family. Smallpox was eradicated in 1980 and, along with it, the vaccination programme was discontinued. • The incubation period of Monkeypox is usually from six to 16 days but can range from fi ve to 21 days. • Monkeypox infection can be divided into two periods : - the invasion period (up to the fi rst fi ve days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle ache) and an intense asthenia (lack of energy); - the skin eruption period (within one to three days after appearance of fever) where the various stages of the rash appears, often beginning on the face and then spreading elsewhere on the body. The face (in 95% of cases), palms of the hands and soles of the feet (75%) are most affected. Evolution of the rash from maculopapules (lesions with a fl at bases) to vesicles (small fl uid-fi lled blisters), pustules, followed by crusts occurs in approximately 10 days. Three weeks might be necessary before the complete disappearance of the crusts. • The number of the lesions varies from a few to several thousand, affecting oral mucous membranes (in 70% of cases), genitalia (30%), and conjunctivae (eyelid) (20%), as well as the cornea (eyeball). • Monkeypox is usually a self-limited disease with the symptoms lasting from two to three weeks. • Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and severity of complications. • Case fatality rate in outbreaks has been between one percent and 10% depending on the clade of the virus. There are two distict clades, the Congo Basin which has a case fatality ratio (CFR) of up to 10% and the Western Africa clade with a CFR up to one percent. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 172 Secondary human-to-human transmission exists • It can result from close contact with infected respiratory tract secretions, skin lesions of an infected person or objects recently contaminated by patient fl uids or lesion materials. The virus does not transmit easily from human to human. • Persons become infectious to others once the rash appears. • As transmission occurs primarily via droplet respiratory particles and usually require prolonged face-to-face contact, household members of active cases and people caring for the sick are at greater risk of infection. • Transmission can also occur by parenteral means such as inoculation of the virus or via the placenta (congenital Monkeypox). • There is no evidence to date that person- to-person transmission alone can sustain Monkeypox infections in the human population. 3 Isolation of patients and standard infection prevention and control (IPC) measures are key to minimizing any possibility of human-to-human transmission • Patients should be isolated and treated symptomatically. Close physical contact with Monkeypox infected people should be avoided until the person has fully recovered. • Gloves and personnal protective equipment should be worn when taking care of ill people. • Regular hand washing should be carried out after caring for or visiting sick people. • Health care workers caring for patients with suspected or confi rmed Monkeypox virus infection, or handling specimens from them, should implement standard infection control precautions. 4 MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 173 Avoid contact with animals that could harbour the virus, especially rodents and sick or dead animals • In areas where Monkeypox occurs: - avoid contact with animals that could harbour the virus; - use appropriate infection prevention and control measures when handling animals. Gloves and other personal protective clothing should be worn while handling animals, their tissues, and during slaughtering procedures. • Eating thoroughly cooked animal products (blood, meat) is safe. However, preparation using animal products represents a signifi cant risk. • Not all animals show signs of illness but they can still be contagious, making risk communication diffi cult, especially in areas where communities rely on hunting. Risk communications need to take this into account. 5 Active surveillance to ensure rapid identifi cation of new cases is critical for outbreak containment• Laboratory confi rmation is important as Monkeypox is diffi cult to distinguish from other pox-like illnesses. The differential diagnoses to be considered include other rash illnesses, such as Chickenpox, Measles, bacterial skin infections, Scabies, Syphilis, Smallpox and medication- associated allergies. The development of severe lymphadenopathy before the appearance of the rash, in some patients, is a distinctive feature of Monkeypox compared to other similar diseases. • Monkeypox can be confi rmed in laboratory through several tests (Enzyme-Linked Immunosorbent Assay - ELISA, antigen detection, Polymerase Chain Reaction – PCR, or virus isolation in cell culture). The optimal diagnostic specimens are from lesions, either vesicular swabs of lesion exudate or crusts, stored in a dry, sterile tube (no viral transport media) and kept cold. Blood and serum do not give defi nitive results. 6 • Once a case of Monkeypox is detected, support enhanced surveillance measures to ensure additional Monkeypox cases are detected and that control measures are implemented. • At the beginning of an outbreak, develop a consolidated laboratory and surveillance database to keep track of the information collected in case report forms during outbreak investigation. • Contact tracing should be conducted for all suspected and confi rmed Monkeypox cases. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 174 Symptoms Monkeypox Smallpox Chickenpox Fever 1-3 days before the rash 2-4 days before the rash At the rash onset Rash appearance The rash evolves from maculopapules to vesicles, pustules, followed by crusts in approximatively 10 days Pocks at the same stage Pocks in several stages Rash distribution Typically starts on face and spreads to arms and legs, then hands and feet including palm and soles More dense on face and extremities; present on palms and soles More dense on the body; absent on palms and soles Other distinctive feature Patients present with lymphadenopathy (swollen lymph nodes) before the appearance of the rash No lymphadenopathy The rash itches Rash development Rapid Low Rapid Death 1-10% Around 30% Rare Clinical differential diagnosis between Monkeypox, Smallpox and Chickenpox Note: Smallpox has been eradicated and the information on disease comes from evidence gathered before 1980. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 175 Health education and raising population awareness are the best preventive measures in at-risk populations • In the absence of specifi c treatment or vaccine, the only way to limit infection in people is by raising awareness of the risk factors and educating people about the measures they can take to avoid exposure to the virus. • Health care workers should be trained to recognize the symptoms of the disease, ensure samples are collected for testing and manage patients. Most importantly, they should be trained on appropriate isolation and infection prevention and control procedures. 87 There is no specifi c treatment or vaccine recommended for Monkeypox• To date, there are no specifi c treatments or vaccines available for Monkeypox infection. • Given the genomic conservation among Orthopoxviruses, it is likely that Smallpox vaccine is protective against Monkeypox (estimated at 85% effectiveness) but the vaccine is no longer available to the general public, after Smallpox eradication in 1980. • Currently, studies are underway to better understand how effective newer Smallpox vaccines are at providing cross-protection against Monkeypox. • Prior Smallpox vaccination will likely result in a milder Monkeypox disease course. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 176 Monkeypox is a rare disease that occurs sporadically in remote tropical rainforest areas of Central and West Africa • Human Monkeypox is sporadically reported in Central and West Africa, particularly areas close to tropical rainforest where humans have frequent contact with animals. • Outbreaks have occured outside Africa (e.g. in the Midwest of the United States of America in 2003 due to imported animals) and outside Central and West Africa (e.g. in Sudan in 2005). 10Many animal species host the Monkeypox virus, primarily rodent species (rather than monkeys, after which the disease is named) • The name Monkeypox is misleading as the disease does not solely come from monkeys. In Africa, Monkeypox infection has been found in many animal species: rope squirrels, tree squirrels, Gambian rats, rodents, striped mice, dormice and monkeys. • Doubts persist on the natural history of the virus and further studies are needed to identify the major reservoir of the Monkeypox virus and how it is maintained in nature. 9 MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 177 Historical distribution of human monkeypox cases Country reporting monkeypox cases in 2017 and in previous years Countries reporting human monkeypox cases Country reporting monkeypox cases in previous years Liberia Sierra Leone Côte d’Ivoire Nigeria Cameroon Gabon Congo Central African Republic Democratic Republic of the Congo The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 178 More information about Monkeypox: • Monkeypox WHO factsheet http://www.who.int/mediacentre/factsheets/fs161/en/ MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 179 10 THINGS YOU SHOULD KNOW Plague 1. Pneumonic Plague can cause widespread epidemics and is diffi cult to control 2. The most common form of Plague – Bubonic Plague - is not transmittable from human to human 3. Early diagnosis and treatment are essential for survival 4. Health education, infection prevention and control and vector and rodent control are critical to prevent and manage epidemics 5. Safe and dignifi ed burials should be conducted to avoid further transmission 6. Initial symptoms of Plague are non-specifi c and diffi cult to distinguish from other acute febrile diseases 7. The potential Plague natural foci are distributed worldwide and are extending 8. Plague is a disease that usually affects disproportionately vulnerable populations 9. Septicaemic Plague is the third type of Plague, in addition to the Pneumonic and Bubonic forms, that occurs when the bacteria is circulating in the bloodstream 10. Plague is a zoonotic disease caused by bacteria usually found in small mammals (mostly rodents) PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 180 Plague response tips Coordinating responders • Engage with partners and communities for vector control in endemic areas Communicating risk • Encourage health authorities to: - Initiate health education and community engagement for vector control in endemic areas • Key messages: - Plague is treatable: people who have symptoms or have exposure to the disease should receive treatment - Transmission of Bubonic and Pneumonic Plague are different - Human-to-human transmission of Pneumonic Plague can occur through respiratory droplets - Patients with Bubonic Plague are not contagious - For Bubonic Plague, take precautions against fl ea bites and do not handle animal carcasses Health Information • There is a robust and sensitive rapid diagnostic test for Bubonic Plague • Find the source of infection for targeted control measures • Notify cases to WHO, under the IHR (2005) Health Interventions • Treat early with antibiotics • Ensure safe and dignifi ed burials • For Pneumonic Plague: - Closely follow close contacts and provide them with prophylaxis for seven days - Give chemoprophylaxis to health care workers - Infection prevention and control: Standard precautions and droplet precautions (Protective Personal Equipment- PPE) • For Bubonic Plague: - Vector and rodent control - Give chemoprophylaxis for people living in the same house as patients - Infection prevention and control (standard precautions) PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 181 Pneumonic Plague can cause widespread epidemics and is diffi cult to control • Pneumonic Plague can be transmitted from person to person via droplets in the air (coughing, respiratory secretions), so it has high epidemic potential and is the most diffi cult form of Plague to control. • It is the most virulent form of Plague: the incubation period can be as short as 24 hours, and untreated Pneumonic Plague is always fatal. • Pneumonic Plague occurs when it reaches the lungs, from the evolution of an advanced Bubonic Plague, through bloodstream, or directly from inhalation of infected respiratory droplets. • Patients with Pneumonic Plague should be isolated so they do not infect others via respiratory droplets and should be cared for by trained medical staff. Medical staff should wear Personal Protective Equipment and potentially receive chemoprophylaxis to prevent nosocomial transmission. • Close contacts must be kept under medical surveillance and must receive a prophylaxis with antibiotics for seven days. • Any suspect case should be treated. • In case of interhuman transmission, the incubation period is usually one to three days, followed by sudden onset of fever, headache, chills, pain, weakness, chest discomfort, shortness of breath, cough, and sometimes bloody or mucous secretions. The most common form of Plague – Bubonic Plague - is not transmittable from human to human • Bubonic Plague is the most common form of Plague. It cannot be transmitted from human to human unless there is contact with pus from suppurating buboes. • Around 10% of people with Bubonic Plague will develop Pneumonic Plague. • Bubonic Plague results from fl ea bites or direct contamination of an open skin lesion by Plague-infected materials or body fl uids (mostly nosocomial infections). Infection can occur when handling dead animals without the appropriate protective measures. The infection spreads via the lymphatic system to the nearest lymph node where 1 2 it replicates itself. The lymph node then becomes infl amed, tense and painful, and is called a “bubo”. At advanced stages of the infection, the infl amed lymph nodes can turn into suppurating open sores. • The incubation period is two to six days followed by sudden onset of illness: headaches, chills, fever, malaise and pain in the affected regional lymph nodes. Bubonic Plague forms buboes, infl ammation and swelling in the neck, groin, etc. • Measures to control an epidemic of Bubonic Plague include: chemopro- phylaxis for people living in the same house as patients, and vector and rodent control. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 182 Early diagnosis and treatment are essential for survival • Plague is treatable. • Treatment with common antibiotics and supportive care are very effi cient in curing human Plague but their effi cacy depends on early administration, which presumes early detection. This is especially important for the Pneumonic form, which is highly contagious, can kill in less than 24 hours, and is invariably fatal in the absence of treatment. If people are treated in time, both forms have good recovery rates. • Recommended antibiotics are: - For Bubonic Plague: tetracycline, doxycycline, chloramphenicol; - For Pneumonic or Septicaemic Plague: aminoglycosides, fl uoroquinolones; - For post-exposure presumptive treatment: tetracycline, doxycycline, sulfamethoxazole/ trimethoprim. • Early treatment requires early diagnosis. Confi rmation of Plague requires laboratory testing. The best practice is to identify the 3 bacteria Y Pestis in a sample of puss from a bubo, blood or sputum. It can be detected by different techniques: - Microscopy: Staining, Fluorescent Antibody test; - Isolation: Colony morphology, Biochemical reactions, Phage lysis; - Detection of antigen/antibody: ELISA (Enzyme-Linked Immunosorbent Assay), Fluorescent antibody test, PCR (Polymerase Chain Reaction). • There is an easy-to-use, robust, reliable and sensitive rapid diagnostic test for Bubonic Plague (dipstick test), that detects antigen and produces reliable results in 15 minutes, greatly facilitating containment efforts. It is recommended that this rapid diagnostic test is used in all endemic regions. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 183 5 Safe and dignifi ed burials should be conducted to avoid further transmission• The bacteria present in the body fl uids of deceased Plague patients can be a source of infection for people in contact with them during burials ceremonies. Safe burials, respecting local cultures and beliefs, must be implemented. Health education, infection prevention and control and vector and rodent control are critical to prevent and manage epidemics • In Plague endemic areas, it is critical to educate people on the disease, its symptoms and modes of transmission. People should be informed when zoonotic Plague is active in their environment and be advised to take precautions against fl ea bites and not to handle animal carcasses. • Avoiding touching dead animals and wearing insect repellent will help prevent Bubonic Plague in endemic areas. • Avoiding close contact (less than two metres) with suspected Pneumonic Plague patients who are coughing will help to prevent Pneumonic Plague. • Plague, “the Black Death”, can be a very scary disease as it has caused millions of deaths in the past, so health education is particularly essential to prevent panic during outbreaks. • Health care workers should specifi cally be informed and trained in infection prevention and control. They should be provided with the appropriate personal protective equipment and trained in how to use it. • In Plague endemic areas and during Bubonic Plague outbreaks, fl ea and reservoir (usually rodents) controls must be implemented. 4 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 184 The potential Plague natural foci are distributed worldwide and are extending • Although Plague is most common in Madagascar, the Democratic Republic of the Congo and Peru, the potential Plague natural foci (the bacteria, an animal reservoir and a vector) are distributed worldwide. • We are currently witnessing the reemergence of the disease in some places where it had disappeared and its emergence in other places where it had never occurred. • The natural foci are also expanding. This could be due to: 7Initial symptoms of Plague are non-specifi c and diffi cult to distinguish from other acute febrile diseases • People infected with Plague begin to develop non-specifi c symptoms after an incubation period of one to seven days. Typical symptoms are the sudden onset of fever, chills, head and body-aches and weakness, vomiting and nausea. These symptoms are diffi cult to differentiate from other common endemic pathogens. • Painful and infl amed lymph nodes secondarily appear during Bubonic Plague. • Symptoms of Pneumonic Plague appear quickly after infection (sometimes less than 24 hours). They include severe respiratory symptoms, such as shortness of breath and coughing, often with blood- tainted sputum. • The clinical picture is not very specifi c and misdiagnosis is common, thus the importance of Rapid Diagnostic Test, for rapid diagnosis and early treatment. 6 - Environmental modifi cations (e.g. deforestation); - Ongoing colonization of the black rat (one of the reservoirs); - Increased national and international exchanges; - Uncontrolled urbanization. • Furthermore, in endemic countries, entomological and zoological surveillance activities are expensive and complicated to maintain. They are very often neglected in the absence of any human cases and it is hard to obtain detailed knowledge about the status or development of natural foci. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 185 Septicaemic Plague is the third type of Plague, in addition to the Pneumonic and Bubonic forms, that occurs when the bacteria is circulating in the bloodstream • Septicaemic Plague is the third form of Plague which occurs when the infection spreads through the bloodstream. • Septicaemic Plague may result from fl ea bites and from direct contact with infective materials through cracks in the skin or follow a Bubonic Plague. It could result in Pneumonic Plague. 9Plague is a disease that usually affects disproportionately vulnerable populations • Plague is a disease that affects disproportionately vulnerable populations, because it thrives in overcrowded places with poor sanitary conditions and inadequate health services. • Outbreaks of Plague are often linked to civil disturbances and war, and when the health infrastructure and facilities have broken down. • Strengthening health systems thus reduces the risk of epidemics. 8 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 186 Plague is a zoonotic disease caused by bacteria usually found in small mammals (mostly rodents) • Plague is a zoonotic disease caused by the bacteria Yersinia pestis, usually found in small mammals (mostly rodents). It is transmitted between animals by their fl eas. • There is a risk of human Plague wherever the presence of Plague natural foci (the bacteria, an animal reservoir and a vector) and human populations co-exist. • There are three main forms of Plague infection, depending on the clinical presentation of infection: Bubonic, Septicaemic and Pneumonic. Humans can become infected by the bite of infected fl eas, by direct contact with infected materials, or by inhalation of infectious respiratory particles from another sick person with Pneumonic Plague. • There is a great risk of nosocomial (hospital) infection, especially for the Pneumonic form. • Human Plague is a severe disease, with a 30-100 % case fatality ratio, depending on the clinical form. 10 • However, when rapidly diagnosed and promptly treated, Plague may be successfully managed with antibiotics, reducing mortality to less than 15%. • Plague epidemics have occurred in Africa, Asia and South America. Since the 1990s, most human cases have occurred in Africa. The three most endemic countries are Madagascar, the Democratic Republic of Congo and Peru. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 187 Global distribution of natural Plague foci, as of March 2016 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Areas* with potential plague natural foci based on historical data and current information * First administrative level representation Source: WHO / IHM, as of March 2016 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 188 More information about Plague • WHO Fact sheet http://www.who.int/mediacentre/factsheets/fs267/en/ • Plague WHO webpage http://www.who.int/csr/disease/plague/en/ • Plague WHO MOOC https://openwho.org/courses/knowledge-resources-plague • Plague manual: epidemiology, distribution, surveillance and control http://who.int/csr/resources/publications/plague/WHO_CDS_CSR_ EDC_99_2_EN/en/ PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 189 1. Leptospirosis is a disease that usually follows natural disasters in tropical or subtropical climates 2. Rodents are the main reservoir of the Leptospira, causative bacteria of Leptospirosis but all kinds of mammals can play a role in human transmission 3. Humans are infected through direct or indirect exposure to infected animals’ urine 4. Risk of infection is increased in some activities and socioeconomic situations 5. Common antibiotics, if given early, are effective against Leptospirosis 6. Leptospirosis is under-recognized and often mistaken for others diseases 7. Laboratory diagnosis is challenging but critical to confi rm leptospirosis 8. Prevention and control measures should target the infection source, the route of transmission and the disease in humans 9. Climate change and urbanization will increase the frequency and intensity of outbreaks 10. A multi-sectorial and holistic approach is critical for prevention and control 10 THINGS YOU SHOULD KNOW Leptospirosis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 190 Leptospirosis response tips Coordinating responders • Engage with animal health sector Communicating risk • Encourage health authorities to: - Engage communities - Ensure training of clinicians for early detection and treatment - Prepare hospitals to receive severe cases requesting intensive care • Key messages: - Humans are infected through direct or indirect exposure to the urine of infected animals - Avoid contact with rodents - Exposure can occur through contaminated water - Immediately disinfect all skin injuries and avoid contact with untreated water - Seek treatment early if showing symptoms Health Information • Ensure laboratory confi rmation of suspected cases Health Interventions • Early detection of cases • Provide empirical treatment (antibiotics) for all probable cases • Provide population with treated water • Provide targeted chemoprophylaxis and protective equipment to very high- risk populations (rescue, sewage and sanitation workers) LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 191 Leptospirosis is a disease that usually follows natural disasters in tropical or subtropical climates • Leptospirosis is an infectious disease caused by bacteria belonging to the genus Leptospira. • Leptospirosis occurs worldwide, but is most prevalent in tropical and subtropical regions. • It often has a seasonal distribution, increasing with heavy rainfall or higher temperatures. • Outbreaks classically occur in association with natural disasters, especially fl ooding. Rodents are the main reservoir of the Leptospira, causative bacteria of Leptospirosis but all kinds of mammals can play a role in human transmission • Rodents are considered the primary source of infection to humans. • Virtually all wild and domestic mammals can harbour the bacteria that cause leptospirosis in their kidneys and genital tracts and act as source of infection to humans and to other animals. • Cattle, buffaloes, horses, sheep, goats, pigs and dogs are also considered common reservoirs of the bacteria that cause leptospirosis. • Natural history of the disease depends on the local ecological conditions. 1 2 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 192 Humans are infected through direct or indirect exposure to infected animals’ urine • Leptospirosis is a zoonosis, transmitted directly or indirectly from animals to humans. • Humans become infected through direct contact with the urine of infected animals or with a urine-contaminated environment. • The bacteria enter the body through cuts or abrasions on the skin, or through the mucous membranes of the mouth, nose and eyes. • Exposure through water contaminated by urine from infected animals is the most common route of infection. Leptospirosis can occasionally also be transmitted through the drinking of water or ingestion of food contaminated with urine of infected animals and when handling infected animal tissues. • Human-to-human transmission occurs only very rarely. 3 4 Risk of infection is increased in some activities and socioeconomic situations• The risk of infection depends on exposure. Some people have more contact with waters contaminated by rodents or other domestic animals. • People can be exposed through their occupation: Outdoor and agricultural workers (rice-paddy and sugarcane workers, for example); Abattoir workers; Veterinarians; Meat handlers; Pet-shop workers; Sewer workers. • People can also be exposed through recreational activities, through water sports such as swimming or canoeing. Survivors from natural disasters (e.g. fl ooding) are also at higher risk of infection. LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 193 Common antibiotics, if given early, are effective against Leptospirosis • Leptospirosis can be treated with antibiotics that should be given as early in the course of illness as possible, preferably before the fi fth day after the onset of illness. • Clinicians should never wait for the results of laboratory tests before starting treatment with antibiotics. • Treatment options include antibiotics such as amoxycillin, tretracycline, ampicillin and doxycycline, etc. • In severe cases, admission to a hospital is necessary. These severe cases should be treated with high doses of intravenous penicillin. Peritoneal or haemodialysis are indicated in case of renal failure. Mechanical ventilation is indicated for lung hemorrhagic manifestation. Severe forms, which require intensive care, make case management logistically complex to organize in an outbreak context. Leptospirosis is under-recognized and often mistaken for others diseases • Misdiagnosis is common because of Leptospirosis’ variable symptoms and non-specifi c presentations that can mimic many other infectious diseases. • The usual presentation is an acute illness with sudden onset of fever, headache, myalgia (particularly calf muscle) and prostration associated with any of the following symptoms/signs: conjunctival suffusion, anuria or oliguria, jaundice, cough, haemoptysis and breathlessness, haemorrhages (from the intestines, lung bleeding is notorious in some areas), meningeal irritation, cardiac arrhythmia or failure, and skin rash. Other common symptoms include nausea, vomiting, abdominal pain, diarrhoea and arthralgia. • The incubation period of Leptospirosis is usually fi ve to 14 days, with a range of two to 30 days. Although the disease is a self- limiting and often clinically unapparent illness in the majority of cases (there are 5 6 asymptomatic cases), 5-15% of untreated cases can progress to a more severe and potentially fatal stage. • There are four broad clinical categories of leptospirosis: - Mild infl uenza-like illness; - Weil’s syndrome (jaundice, renal failure, hemorrhage, myocarditis); - Meningitis; - Pulmonary hemorrhage and respiratory failure. • Suspicion of Leptospirosis is further increased for patients presenting the above symptoms if there is a history of occupational or recreational exposure to infected animals or to an environment potentially contaminated with animal urine. It is also important for clinicians to consider Leptospirosis in the differential diagnosis of febrile illnesses after fl ooding. • Misdiagnosis or delayed diagnosis have signifi cant clinical implications because early treatment of Leptospirosis is crucial to minimize morbidity and mortality and timely implement control measures. Mild forms Febrile hemorrhagic forms With severe pneumonia When icteric fever Leptospirosis presentations Diseases it could be confused with Malaria, Dengue, Influenza Viral haemorrhagic fevers Plague Yellow fever or Hepatitis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 194 2-10 d 4-7 d 1-3 d 0-10+ d Bacteria enter body through cuts or mucosal surfaces; bacterial flagellae aid tissue penetration Fever & other symptoms resolve temporarily prior to onset of Immune phase Recurring fever and CNS involvement (meningitis); primarily humoral response; antileptospiral antibodies lead to clearance of the organism from most tissues except kidney tubules; leptospires may continue to shed in the urine for long periods Abrupt onset of fever, headache, muscle pain, nausea; leptospires isolated from blood, CSF and most tissues; mostly anicteric, 5-10% have jaundice Incubation period Septicaemic phase Interphase Immune phase Typical course of Leptospirosis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 195 Laboratory diagnosis is challenging but critical to confi rm leptospirosis • Laboratory diagnostic is not easy because of the complexity of the pathogen: there are 300 species and 25 serogroups, divided into 250 serovars. • Laboratory support is needed: - To confi rm the diagnosis and distinguish it from other diseases; - To determine the serovar responsible for infection, which will help guide the control strategies. • Current recommendations for laboratory testing are: - Serology: Microscopic Agglutination Test (MAT) is the gold standard serologic test, due to its high specifi city; - Polymerase Chain Reaction – PCR. • IgM Enzyme-Linked Immunosorbent Assay (ELISA) test may be used but it requires a lag period after infection before antibodies become detectable. The results need to be interpreted carefully due to varying sensitivity and specifi city of the test method. Prevention and control measures should target the infection source, the route of transmission and the disease in humans • Control measures at the infection source (usually local reservoir species of animals) include: Reducing certain animal reservoir populations; Separating animal reservoirs from human habitations (by fences and screens); Immunizing dogs and livestock; Removing rubbish and keeping areas around human habitations clean; Disposing of excreta from domestic animals in such a way as to avoid contamination; Encouraging people not to leave food around, especially in recreational areas where rats may be present; Improving living conditions and sanitation systems, etc. • Measures to prevent transmission through avoiding contact with animal urine, infected animals or an infected environment, include: Wearing protective clothing; Covering skin lesions with waterproof dressings; Preventing access to, or giving adequate warning about water bodies known or suspected to be contaminated; Washing or showering after exposure to urine splashes or contaminated soil or water; Washing and cleaning wounds; Strictly maintaining hygienic measures during care or handling of all animals; Where feasible, disinfecting contaminated areas (scrubbing fl oors in stables, butcheries, abattoirs, etc.); Consuming clean drinking-water, etc. • Interventions at the level of the human host include: 7 8 - Raising awareness in both the general population and at-risk groups. People need to understand the disease and how to avoid risks, but also that timely medication helps. Doctors and veterinarians should consider leptospirosis as part of the differential diagnosis in appropriate cases; - Antibiotic prophylaxis should be used if exposure is known to have occurred (e.g. as a result of a laboratory accident or other high-risk exposure); - Immunization in humans is not recommended. Vaccines do not induce long-term protection against infection and do not provide cross-protective immunity against heterogenous leptospiral serovars (protective antibodies are produced only against the serovars present in the particular vaccine used). • In epidemic situations, strategic control measures include: - Detecting cases early; - Providing empirical treatment for all probable cases; - Providing the population with treated water; - Providing targeted chemoprophylaxis and protective equipment to very high- risk populations (rescue, sewage and sanitation workers); - Rodent control and animal immunization are useless at this stage. LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 196 Climate change and urbanization will increase the frequency and intensity of outbreaks • Leptospirosis infections are closely linked to the environment and climate change will lead to an escalation of the global burden of leptospirosis: - Climate change is expected to increase the occurrence of heavy rainfall and fl ooding and the intensity of tropical cyclones and storms, due to the rise of sea levels and the rise of sea and land surface temperatures; - Natural disasters also increase the risk of infectious disease by disrupting health services and infrastructures and damaging water and sanitation networks. • Urbanization also increases the incidence and intensity of leptospirosis. Fast urbanization usually goes with the development of urban slums, where overcrowding, poor sanitation, poor health care, poverty and abundance of rats and other animal reservoirs are risk factors of being infected. 9 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 197 A multi-sectorial and holistic approach is critical for prevention and control • Leptospirosis remains an unknown disease: transmission dynamics are poorly understood, symptoms are not specifi c, laboratory diagnosis is complex and laboratory confi rmation is often not available. • A One Health approach is critical to prevent and control this environmental disease that affects both humans and animal: - Relationships between animals, humans and ecosystems needs to be considered to better understand and manage the disease; - Research and control efforts require a truly integrated, multi-disciplinary and coordinated approach to improve prediction, detection, prevention and response to outbreaks of Leptospirosis. 10 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 198 More information about Leptospirosis: • Leptospirosis WHO webpage http://www.who.int/topics/leptospirosis/en/ • Leptospirosis WHO Western Pacifi c Region Offi ce factsheet: http://www.wpro.who.int/mediacentre/factsheets/fs_13082012_ leptospirosis/en/ • Leptospirosis WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Global Leptospirosis Environmental Action Network (GLEAN) website https://sites.google.com/site/gleanlepto/ • Human Leptospirosis: guidance for diagnosis, surveillance and control: http://apps.who.int/iris/bitstream/10665/42667/1/WHO_CDS_CSR_ EPH_2002.23.pdf LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 199 1. Meningococcal meningitis (MM) is an acute bacterial form of meningitis due to Neisseria meningitidis (N.m), a serious infection of the meninges (brain membranes) 2. MM occurs worldwide but its highest burden is in the African meningitis belt 3. Several types of N.m can cause epidemics 4. Humans are the only reservoir of MM, transmitted through direct contact and respiratory droplets 5. MM can have a fatality rate of up to 50% when untreated 6. Specifi c vaccines are used for prevention and outbreak response 7. Laboratory diagnosis is essential to ascertain whether N.m is the pathogen causing meningitis 8. Surveillance is critical to detect outbreaks and inform the epidemic response 9. Early antibiotic treatment is the most important factor to save life and reduce complications 10. Antibiotics reduce transmission risk for close contacts when given promptly 10 THINGS YOU SHOULD KNOW Meningococcal meningitis MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 200 Meningococcal meningitis response tips Coordinating responders • Make sure the epidemic preparedness and response committee is established before the epidemic season • Contact WHO/ICG for emergency vaccines and antibiotics Communicating risk • Ensure populations receive the vaccine to prevent this disease • Key messages are: - Human-to-human transmission occurs through droplets of respiratory or throat secretions - Asymptomatic carriers can transmit the disease - Practice hand hygiene and respiratory hygiene - Early antibiotic treatment reduces mortality and complications and therefore sick people should seek medical treatment early on Health Information • Identify the meningococcal serogroup through laboratory testing • Monitor thresholds that have been defi ned according to specifi c regional or country epidemiology Health Interventions • Early antibiotic treatment • Conduct vaccination campaigns promptly (according to local epidemiology) • Prophylaxis to close contacts (according to local epidemiology) MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 201 Meningococcal meningitis (MM) is an acute bacterial form of meningitis due to Neisseria meningitidis (N.m), a serious infection of the meninges (brain membranes) • MM is due to the bacteria Neisseria meningitidis. • A variety of other organisms including bacteria, fungi or viruses, can cause meningitis. • MM causes sporadic cases and also very large outbreaks. MM occurs worldwide but its highest burden is in the African meningitis belt • The highest burden is observed in the meningitis belt (26 countries) that stretches across Africa from Senegal to Ethiopia. • The meningitis belt is affected by seasonal endemicity and cyclical large scale epidemics, during the dry season (December to June). Several types of N.m can cause epidemics • Serogroups are named by a letter (A, B, C, etc.). 6 (out of 12) serogroups can cause large epidemics (A, B, C, W, X, Y). Geographic distribution differs according to serogroup. • In the meningitis belt, before 2010, serogroup A meningococcus accounted for an estimated 80–85% of all cases. Since the introduction of a new and very effi cient meningococcal A conjugate vaccine through mass preventive immunization campaigns, the proportion of N. meningitidis A has declined dramatically. • In Europe, the introduction of routine vaccination for N. meningitidis C led to the decline of serogroup C outbreaks. • Independently of the vaccination strategies, the epidemiology of serogroups fl uctuates over time and space for reasons that are not fully understood. 1 2 3 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 202 Humans are the only reservoir of MM, transmitted through direct contact and respiratory droplets • Neisseria meningitidis only infects humans. There is no animal reservoir. • The bacteria can be carried in the throat (asymptomatic carrier). By chance, it can overwhelm the body’s defenses allowing the bacteria to spread through the bloodstream to the brain. • The bacteria are transmitted from person-to-person through droplets of respiratory or throat secretions from carriers. Smoking, close and prolonged contact – such as kissing, sneezing or coughing on someone, or living in close quarters with an infected person (a carrier) – facilitate the spread of the disease. MM can have a fatality rate of up to 50% when untreated • The most common symptoms of the disease are high fever, headaches, stiff neck, vomiting, confusion, sensitivity to light and bulging of the fontanelle in infants. Sometimes, a haemorrhagic rash, ranging from a few petechiae to widespread ecchymoses, occurs as a result of septicaemia. • Even when the disease is diagnosed early and adequate treatment is started, 8–15% of patients die, often within 24 to 48 hours after the onset of symptoms. If untreated, MM is fatal in 50% of cases. • MM may result in brain damage, hearing loss or disability in 10% to 20% of survivors. 4 5 • Asymptomatic carriers can transmit the disease. It is believed that 1% to 10% of the population carries N. meningitidis in their throat in endemic situations. In epidemics, the carriage rate is higher (10% to 25%). • Infants and young adults are the most at risk of getting infected. • The incubation period is 2 to 10 days, usually 3 to 4 days. • Transmission of N. meningitidis is facilitated during mass gatherings (recent examples include the Haj pilgrimage, jamborees, etc.). MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 203 Specifi c vaccines are used for prevention and outbreak response • Vaccines are serogroup specifi c and confer varying degrees of duration of protection. • There are 3 types of vaccines available: - Polysaccharide vaccines are used for outbreak response mainly in Africa: o They are either bivalent (serogroups A and C), trivalent (A, C and W), or tetravalent (A, C, Y and W); o They are not effective before 2 years of age; o They offer a 3-year protection but do not induce herd immunity. - Conjugate vaccines are used in prevention (into routine immunization schedules) and outbreak response: o They confer longer-lasting immunity, prevent carriage and induce herd immunity; o They can be used as soon as one year of age; o Available vaccines include: 6 • Monovalent C and Tetravalent (serogroups A, C, Y, W). Both are currently expensive and mostly used in Canada, United States of America and Europe. • Monovalent A, used for mass preventive campaigns and routine infant immunization. - Protein-based vaccine against N. meningitidis B. It has been used in prevention (into the routine immunization schedule of one country, the UK) and outbreak response. • Reactive vaccination in affected and at- risk populations should be conducted promptly to prevent the spread of the disease. • In Africa, it is essential that a vaccination campaign is conducted within four weeks of crossing the epidemic threshold. • An international stockpile of vaccine has been constituted, that can be accessed by any country facing an outbreak, through a request to the International Coordinating Group on vaccine provision for Meningitis. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 204 Indicative decision tree for meningitis vaccine choice in a reactive vaccination campaign Source: WHO, Managing meningitis epidemics in Africa, Revised 2015 Alert threshold reached meningitis cases available Conduct investigation and obtain specimens no Main pathogen = Nm A Main pathogen = Nm C or W Main pathogen = Nm X Main pathogen = Spn / Hib ≥ 30% of Nm positive are Nm C or W Case management no vaccination yes no If epidemic threshold is crossed ACW containing vaccine Men A conjugate vaccine ACW containing vaccine yes REMEMBER If there are NmA cases in the population already vaccinated with MenA conjugate, conduct field investigation. * Confirmation includes a positive result from culture, polymerase chain reaction or rapid diagnostic test. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 205 Laboratory diagnosis is essential to ascertain whether N.m is the pathogen causing Meningitis • Confi rmation of the disease needs a laboratory test performed on Cerebrospinal Fluid (CSF) obtained through lumbar puncture: tests include culture (growing the bacteria), agglutination tests and Polymerase Chain Reaction (PCR). • At the fi eld level, to rapidly identify the N. meningitidis bacteria and the serogroups, rapid point-of-care diagnostic tests should be used. Rapid confi rmation of the pathogen is critical to determine appropriate treatment and epidemic response. Surveillance is critical to detect outbreaks and inform the epidemic response • Surveillance systems should be tailored to detect outbreaks, monitor disease trends and impact of vaccine. • Epidemiological and laboratory data should be linked. • The defi nition of a Meningococcal meningitis outbreak varies from country to country, based on local epidemiology and a comprehensive analysis of surveillance data. • In the African belt, standard case defi nitions are: - Suspected case (based on clinical presentation): any person with sudden onset of fever (>38.5 °C rectal or 38.0 °C axillary) and neck stiffness or another meningeal sign including bulging fontanelle in toddlers; - Probable case (based on non-specifi c laboratory test): any suspected case with macroscopic aspect of CSF turbid, cloudy or purulent; or with a CSF leukocyte count >10 cells/mm3; or with bacteria identifi ed by Gram stain in CSF; 7 8 o In infants: CSF leucocyte count >100 cells/mm3; or CSF leucocyte count 10– 100 cells/ mm3 AND either an elevated protein (>100 mg/dl) or decreased glucose (<40 mg/dl) level. - Confi rmed (based on laboratory test): any suspected or probable case that is laboratory confi rmed by culturing or identifying of Neisseria meningitidis in the CSF or blood. • In the African belt, incidence thresholds that will trigger prevention and control interventions are shown in the table on the following page. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 206 Incidence thresholds for detection and control of epidemic Meningococcal meningitis (2014) Source: WHO, Managing meningitis epidemics in Africa, Revised 2015 — Inform authorities — Strengthen surveillance — Investigate — laboratory) — Prepare for eventual response inhabitants / week (Minimum of 2 cases in one week) 2 suspected cases in one 100,000 week Or An increased incidence compared to previous non- epidemic years — Mass vaccination within four weeks of crossing the epidemic threshold — Distribute treatment to health centres — Treat according to epidemic protocol — Inform the public inhabitants / week 5 suspected cases in one week Or Doubling of the number of cases in a three-week period (e.g. Week 1: 1 case, Week 2: 2 cases, Week 3: 4 cases) If a neighbouring area to a population targeted for vaccination is considered to be at risk (e.g. cases early in the dry season, no recent relevant vaccination campaign, high population density), it should be included in a vaccination programme. In special situations such as mass gatherings, refugees, displaced prompt mass vaccination. POPULATION Intervention 30,000 – 100,000 Under 30,000 Alert threshold Epidemic threshold 100,000 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 207 Early antibiotic treatment is the most important factor to save life and reduce complications • Prompt treatment (within one hour of diagnosis) is crucial to prevent death and complications: - 5 days ceftriaxone (IV) - 7 days in infants (0-2 months old) - is recommended as a standard treatment during epidemics in the African belt. • Admission to a hospital or health centre is necessary, although isolation of the patient is not necessary. • If there is no improvement of patients’ condition within 48 hours of treatment of if exhibiting convulsions or comatose, they should be transferred to higher-level health facility. 9 Antibiotics reduce transmission risk for close contacts when given promptly• Outside the African meningitis belt, chemoprophylaxis is recommended for close contacts within the household. • In the meningitis belt, chemoprophylaxis for close contacts is recommended in non-epidemic situations. • Ciprofl oxacin antibiotic is the antibiotic of choice, and ceftriaxone an alternative. 10 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 208 C,W,X,A SEROGROUP SEROGROUP B,C,Y, W B,C,W B,C,W B,C,W,Y A,C B,C,W, A B,C,W B,W,Y The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved Source: WHO/IHM, as of 16 February 2018 Invasive Meningococcal Disease – Serogroup distribution, 2018 Most frequent Less frequent MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 209 More information about Meningococcal meningitis: • Meningococcal meningitis WHO webpage: http://www.who.int/csr/disease/meningococcal/en/ • Meningitis WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Meningococcal meningitis WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs141/en/ • Managing meningitis epidemics in Africa http://www.who.int/csr/resources/publications/HSE_GAR_ERI_2010_4/en/ • International Coordinating Group (ICG) on Vaccine Provision http://www.who.int/csr/disease/icg/en/ MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 210

PART III Tool boxes 213 TOOL BOX 1 The role of WHO Example • WHO is: - Working with countries to increase and sustain access to prevention, treatment and care; - Identifying priorities and setting strategies; - Leading and coordinating the health response during emergencies. • Through the International Health Regulations (2005), WHO helps the countries to strengthen their national core capacities for emergency risk management to prevent, prepare for, respond to and recover from health emergencies. WHO mandate – in light of infectious diseases WHO is directing and coordinating authority on international health within the United Nations’ system, by its six mains functions: 1. Providing leadership on matters critical to health and engaging in partnerships where joint action is needed; PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 214 2. Shaping the research agenda and stimulating the generation, translation and dissemination of valuable knowledge; Example • WHO Research & Development Blueprint is a global strategy and pre- paredness plan that allows the rapid activation of R&D activities during epidemics. Its aim is to fast-track the availability of effective tests, vaccines and medicines that can be used to save lives and avert large scale crisis. http://www.who.int/blueprint/en/ • The WHO public health research agenda for infl uenza provides a framework refl ecting public health research priorities for pandemic, zoonotic and seasonal epidemic infl uenza to reduce the risk of emergence of pandemic infl uenza, limit the spread of pandemic, zoonotic and seasonal epidemic infl uenza, minimize the impact of epidemics, optimize the treatment of patients and promote the development of modern public health tools. http://www.who.int/infl uenza/resources/research/en/ • The MERS-CoV research agenda has been developed by WHO to address key unknowns for this virus focusing on fi ve major areas of research: i) virus origin and characteristics, ii) epidemiology and transmission, iii) clinical management and infection prevention and control measures, iv) product development and implementation, and v) impact of interventions and operational research. http://www.who.int/emergencies/mers-cov/en/ TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 215 Articulating ethical and evidence-based policy options; Example • WHO publishes vaccine position papers, providing global vaccine and immunization recommendations that have an international public health impact. WHO position papers follow the recommendations of the WHO Strategic Advisory Group (SAGE) on immunization. The update of vaccine position paper depends on the availability of new scientifi c evidence and public health priorities. http://www.who.int/immunization/documents/positionpapers_intro/en/ 4. TOOL BOX 1 Setting norms and standards and promoting and monitoring their implementation; Example • WHO developed a pocketbook to provide guidance on best management practices for Viral Haemorrhagic Fevers across health care facilities. http://www.who.int/csr/resources/publications/clinical-management-patients/en/ • WHO developed a rapid advance guideline on recommendations for the use of Personal Protective Equipment for use in a fi lovirus disease outbreak http://www.who.int/csr/resources/publications/ebola/personal-protective- equipment/en/ 3. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 216 TOOL BOX 1 Monitoring the health situation and assessing health trends. Example • WHO conducts regular global risk assessments regarding infectious diseases and assesses the risk for any event which could have public health impact. • WHO publishes a summary of epidemiological situation and risk assessments of events that are being monitored through the disease outbreak news. http://who.int/csr/don/en/ • WHO also disseminates epidemiological information on outbreaks and on communicable diseases of public health importance through the Weekly Epidemiological Record. http://www.who.int/wer/en/ 6. Providing technical support, catalysing change, and building sustainable institutional capacity; Example • WHO has developed a web-based platform offering online courses to transfer knowledge on infectious diseases and improve preparedness and response to epidemics. Courses include global knowledge on managing epidemics and public heath interventions, as well as disease-specifi c knowledge. WHO Massive Open Online Courses: https://openwho.org/ 5. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 217 WHO and the International Health Regulations (IHR) creation: A need for global cooperation in public health The Cholera epidemics that overran Europe between 1830 and 1847 were catalysts for intensive infectious disease diplomacy and multilateral cooperation in public health. They showed that collaboration between countries was needed to control the spread of dangerous diseases across the world. This led to the fi rst International Sanitary Conference in Paris in 1851. In 1948, the WHO Constitution entered into force and in 1951, WHO Member States adopted the International Sanitary Regulations, which were replaced by and renamed the International Health Regulations in 1969. The 1969 Regulations were subject to minor modifi cations in 1973 and 1981. The IHR were primarily intended to monitor and control six serious infectious diseases: Cholera, Plague, Yellow fever, Smallpox, Relapsing fever and Typhus. Under the IHR (1969), only Cholera, Plague and Yellow fever remain notifi able, meaning that States are required to notify WHO if and when these diseases occur on their territory. Increase in cross-border travel and trade, the development of information and communication technologies, the resurgence of some well-known epidemic diseases, such as Cholera and Plague and the emergence of new infectious agents such as Ebola virus disease, as well as the limitations of IHR (1969) (narrow scope of three diseases and dependence on offi cial country notifi cations), led to their revision. The World Health Assembly adopted the IHR (2005) on 23 May 2005 and they entered into force on 15 June 2007. The International Health Regulations (2005) represent a binding international legal agreement involving 196 countries across the globe. They aim to prevent, protect against, control and respond to the international spread of disease while avoiding unnecessary interference with international traffi c and trade. Questions & Answers 1. What are the major changes between IHR (1969) and IHR (2005)? • The scope of the IHR (2005) is purposely broader and more inclusive in respect of the public health event to which they have application in order to maximize the probability that all such events that could have serious international consequences are identifi ed early and promptly reported by States Parties to WHO for assessment. • The IHR (2005) explicitly allow WHO to take into account information from sources other than offi cial notifi cations and consultations, and, after assessment, to seek verifi cation of specifi c events from the concerned States Parties. 2. What are the general obligations of States under the IHR 2005? Under the IHR (2005), States parties are required to: • Designate a National IHR Focal Point (it may be a team). Focal points are required to be available on a 24-hour basis, 7 days a week. • Assess events occurring in their territory and to notify WHO of all events that may constitute a public health emergency of international concern using the decision instrument. • Respond to requests for verifi cation of information regarding events that may constitute a public health emergency of international concern, to respond to public health risks which may spread internationally. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 218 • Develop, strengthen and maintain the capacity to detect, report and respond to public health events; to provide routine facilities, services, inspections and control activities at designated international airports, ports and ground crossings to prevent the international spread of disease. • Report to WHO evidence of a public health risk identifi ed outside their territory which may cause international disease spread, manifested by exported/imported human cases, vectors carrying infection or contamination, contaminated goods. • Respond appropriately to WHO- recommended measures. • Collaborate with other States Parties and with WHO on IHR (2005) implementation. OR Yes NoNo No Yes Yes Is the public health impact of the event serious? NoYes Is the event unusual or unexpected? Is the event unusual or unexpected? NoYes Is there a significant risk of international spread? Is there a significant risk of international spread? NoYes 1 As per WHO case definitions. 2 The disease list shall be used only for the purposes of these Regulations. OR EVENT SHALL BE NOTIFIED TO WHO UNDER THE INTERNATIONAL HEALTH REGULATIONS Not notified at this stage. Reassess when more information becomes available. • Is there a significant risk of inter- national travel or trade restrictions? Events detected by national surveillance system An event involving the following diseases shall always lead to utilization of the algorithm, because they have demonstrated the ability to cause serious public health impact and to spread rapidly internationally: • Cholera • Pneumonic plague • Yellow fever • Viral haemorrhagic fevers (Ebola,Lassa,Marburg) • West Nile fever • Other diseases that are of special national or regional concern, e.g. dengue fever, Rift Valley fever,and meningococcal disease. A case of the following diseases is unusual or unexpected and may have serious public health impact, and thus shall be notified 1, 2: • Smallpox • Poliomyelitis due to wild-type poliovirus • Human influenza caused by a new subtype • Severe acute respiratory syndrome (SARS). Any event of potential international public health concern, including those of unknown causes or sources and those involving other events or diseases than those listed in the box on the left and right shall lead to utilzation of the algorithm. OR Decision instrument for the assessment & notifi cation of events that may constitute a public health emergeny of international concern Source: Annex 2, International Health Regulations (2005) TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 219 3. What events should States Parties notify to WHO? Under the IHR, States Parties are required to notify WHO of all events that are assessed as possibly constituting a Public Health Event of International Concern (PHEIC), taking into account the context in which an event occurs. A decision instrument, provided in Annex 2 of the Regulations, identifi es four criteria that States Parties must follow in their assessment of events within their territories and their decision as to whether an event is notifi able to WHO: • Is the public health impact of the event serious? • Is the event unusual or unexpected? • Is there a signifi cant risk of international spread? • Is there a signifi cant risk of international restriction(s) to travel and trade? 4. What if States Parties have diffi culties to assess an event? State Parties have an option of initiating confi dential consultations with WHO and seeking advice on evaluation, assessment and appropriate health measures to be taken, in case they are unable to complete a defi nitive assessment. 5. How and when to report these events? • These notifi cations must occur within 24 hours of assessment by the country. • Notifi cations must be followed by ongoing communication of detailed public health information on the event, including, where possible, case defi nition, laboratory results, source and type of the risk, number of cases and deaths, conditions affecting the spread of the disease and the health measures employed. 6. What States Parties should do if they identify a public health risk outside their territory? States Parties must inform WHO through the National IHR Focal Point within 24 hours of receipt of evidence of a public health risk identifi ed outside their territory that may cause international disease spread, as manifested by imported or exported human cases, vectors which carry infection or contamination, or by contaminated goods. 7. Can WHO require more information to States Parties about events unoffi cially reported? States Parties are required under the IHR to respond to WHO Requests for Verifi cation. WHO has an express mandate to obtain verifi cation from States Parties concerning unoffi cial reports or communications, received from various sources, about events arising within their territories which may constitute a PHEIC. States Parties must acknowledge verifi cation requests by WHO within 24 hours and provide public health information on the status of the event, followed, in a timely manner. 8. What are the diseases that should be mandatorily notifi ed to WHO? Under the IHR (2005), all cases of four diseases must be automatically notifi ed to WHO: Smallpox, Poliomyelitis due to wild- type poliovirus, SARS and cases of human Infl uenza caused by a new subtype. 9. What are the core capacities? • Under the IHR (2005), each State Party is required to develop, strengthen and maintain core public health capacities for surveillance and response. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 220 • Public health capacity under the IHR (2005) is defi ned as the indispensable, fundamental actions that are the primary responsibility of each State Party for achieving the goal of national health security, i.e. to prevent the spread of diseases and to detect and investigate health risks in the community by effi cient multisectoral action (e.g. integrated disease surveillance systems, laboratory services and national, regional and global networks). • Core capacities at the local (community), intermediate and national levels, as well as key sanitary and health services needed at designated international airports, ports and ground crossings are described in Annex 1 of the IHR (2005). 10. What are the specifi c requirements for Yellow fever? • A proof of vaccination or prophylaxis against Yellow fever may be required for travellers as a condition of entry to a State. • States Parties must designate at least one Yellow fever vaccination centre. 11. Why developing the necessary public health capacities at points of entry will limit the spread of public health hazards? Today’s high traffi c at airports, ports and ground crossings – points of entry, can play a key role in the international spread of diseases through persons, conveyances and goods. This is why countries should be prepared to detect and respond to any health event that may be of international concern and contain risks at source, limiting unnecessary health-based restrictions on international traffi c and trade and protecting the health of travellers and populations. 12. What are the guiding principles for preparedness at points of entry? • Simplicity; • Proportionality and practicality: one size does not fi t all; • Minimal disruption; • Collaboration: multisectoral approach; • (Risk) Communication. For more information: • International Health Regulations (2005) http://www.who.int/ihr/ publications/9789241580496/en/ • More information about IHR http://www.who.int/ihr/about/en/ • More information about implementing IHR http://www.who.int/ihr/procedures/ implementation/en/ • More about public health at points of entry: http://www.who.int/ihr/ports_airports/ en/ • Joint External Evaluation Tool and Process Overview http://apps.who.int/iris/ bitstream/10665/252755/1/WHO-HSE- GCR-2016.18-eng.pdf?ua=1 TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 221 WHO management of events under the Emergency Response Framework (ERF) The ERF is an internal WHO tool that outlines a set of procedures to better respond to emergencies. The ERF provides WHO staff with essential guidance on how the Organization manages the assessment, grading and response to public health events and emergencies with health consequences, in support of Member States and affected communities. TOOL BOX 1 Ungraded Grade 1 Grade 2 A public health event or emergency that is being monitored by WHO but that does not require a WHO operational response. A single country emergency requiring a limited response by WHO, but that still exceeds the usual country-level cooperation that the WHO Country Office (WCO) has with the Member State. Most of the WHO response can be managed with in-country assets. Organizational and/or external support required by the WCO is limited. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office. A single country or multiple country emergency, requiring a moderate response by WHO. The level of response required by WHO always exceeds the capacity of the WCO. Organizational and/or external support required by the WCO is moderate. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office. An Emergency Officer is also appointed at headquarters to assist with the coordination of Organization-wide support. Grade 3 A single country or multiple country emergency, requiring a major/maximal WHO response. Organizational and/or external support required by the WCO is major and requires the mobilization of Organization-wide assets. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office(s). An Emergency Officer is also appointed at headquarters, to assist with the coordination of Organizationwide inputs. On occasion, the WHE Executive Director and the Regional Director may agree to have the Emergency Coordinator based in headquarters. For events or emergencies involving multiple regions, an Incident Management Support Team at headquarters will coordinate the response across the regions. Levels for graded emergencies Source: Emergency Response Framework, second edition, WHO PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 222 WHO internal grading of events • Once an event is detected or notifi ed to WHO, it will be verifi ed and analysed. Risk assessment would be conducted if the event is confi rmed. Risk assessment by WHO team may result in: - Monitoring, mitigation, preparedness and readiness if the risk is low or very low; - Grading the event and activating the Incident Management System and scaled response if the risk is high or very high. • Grading an event is a WHO internal process which purpose is to defi ne the level of operational response required by WHO. Grading takes into consideration 5 criteria: scale, complexity, urgency of the event, capacity to respond at local and national levels and reputational risk for WHO. • They are four levels for graded emergencies shown here at left. TOOL BOX 1 Linking risk assessment and situation analysis to WHO grading and operational response Source: Emergency Response Framework, second edition, WHO Discard Discard Close event WHO response required; Repurposing WCO WHO response required and/or high/very high risk Graded Emergency: G1 – G3 Ungraded / Pre-grading Ungraded / Pre-grading For acute events and emergencies, grading occurs within 24 hours of risk assessment/situation analysis Suspected public health event Monitoring, mitigation, prepardness & readiness Monitoring, mitigation, prepardness & readiness IMS activation & scaled response Risk assessment: low – very high Emergency Verification Grading Situation analysis Detection PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 223 WHO operational response through the ERF • Grading will trigger WHO emergency procedures and activities for the management of the response. It will activate the Incident Management System (IMS). The IMS is recognized best practice for emergency management. It is simple, fl exible and adaptable to any scenario: it may be applied in small, simple, or large, complex incidents. Scaling up or down the response can be quickly done to suit the changing needs. • The IMS is the combination of facilities, equipment, personnel, procedures and communications operating within a common organizational structure. It enables: - Common terminology and structure that enhance interoperability; - Clarifi cation of roles and responsibilities; - Flow of information and resources; - Rapid mobilization, deployment and tracking of resources. • The IMS implies: - Determining the overarching objectives (e.g. stop transmission of an infectious agent); - Establishing specifi c and measurable objectives for various functional activities; - Developing strategies and issuing plans, directions, procedures, and protocols; - Assigning tasks; - Establishing an evaluation process. • WHO has adapted the Incident Management System to consist of six critical functions: Leadership, Partner Coordination, Information and Planning, Health Operations and Technical Expertise, Operations Support and Logistics, and Finance and Administration. • WHO applies a no regret policy which affi rms that “it is better to err on the side of over-resourcing the critical functions rather than risk failure by under-resourcing”. In terms of fi nancial resources, the WHO representative and/or the Incident Manager has increased authority to approve expenditure. Immediate access to funds, for the fi rst three months of an acute emergency, is provided from either the Contingency Fund for Emergency (CFE) or the Regional Offi ce’s rapid response accounts. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 224 WHO’s Incident Management System organizational structure: critical functions and sub-functions Source: Emergency Response Framework, second edition, WHO IMS critical functions IMS sub-functions Leadership / Incident management Partner coordination Staff health, wellbeing & security Risk communication & community engagement External relations Liaison ProcurementField support Human resources & surge Health logistics EOC Management Health & intersectoral coordination Prevention & control measures Health service delivery Training of health staff Technical expertise, science & research Planning Finance, budget / grants management Supply chain managementInformation • Risk & needs assessment • Early warning & surveillance • Monitoring & evaluation • Information products • Strategic & operational planning • Project management Communications Information & planning Finance & administration Operations support & logistics Health operations & technical expertise PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 225 For more information: • Emergency Response Framework: http://www.who.int/hac/about/erf/en/ WHO monitoring of the response: a criteria for success • It is critical to evaluate the response to an event and learn the lessons from past responses, improving things that could have gone better and enforcing best practices. • During grade 2 and 3 emergencies, WHO performance standards and key performance indicators are monitored. - Performance standards should be monitored with the ERF Monitoring Tool. The responsibility for completing the ERF Monitoring Tool is with the Country Offi ce, with oversight from the Regional Offi ce. - Key performance indicators (not more 8) are agreed upon on a case-by-case basis for each response (e.g. case fatality ratio; vaccination coverage, etc.). TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 226 TOOL BOX 2 The International Coordinating Group (ICG) on vaccine provision What is the ICG? • The International Coordination Group (ICG) was established in 1997, following major outbreaks of Meningitis in Africa, as a mechanism to manage and coordinate the provision of emergency vaccine supplies and antibiotics to countries during major outbreaks. • The ICG monitors its vaccine security global stock levels for Cholera, Meningitis and Yellow fever to ensure availability of suffi cient supply to respond to disease outbreaks when they occur. • The ICG brings partners together to improve cooperation and coordinating of epidemic preparedness and response. • The ICG also works on forecasting vaccine stocks, negotiating vaccine prices through its networks or partners, evaluating interventions and standard protocols for managing diseases. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 227 Why is such mechanism needed? Though outbreaks of Meningitis, Yellow fever and Cholera are unpredictable events, they can each be controlled by the timely use of vaccine. Vaccine-preventable diseases typically affect people in vulnerable settings who have limited access to vaccines. But vaccines can take months to manufacture, and they are not always readily available in the amounts needed during emergencies. The resulting shortages have raised diffi cult issues about how limited supplies should be allocated during periods of high demand. That is why, after public health organizations found themselves unprepared to respond in a timely manner to a large-scale outbreak of Meningitis in Nigeria, the ICG mechanism was created in 1997. What is the ICG mandate? • The core mandate of the ICG is to make available and ensure equitable access to vaccines for Cholera, Meningitis, and Yellow fever during outbreaks. • The ICG mechanism seeks to ensure timely and targeted deployment so that vaccines can be used as effective outbreak responses where they are most needed. • The ICG also manages the global emergency vaccine stockpiles and, working with manufacturers, determines their size and composition with the goal of ensuring that adequate stocks of emergency supplies are accessible for emergency response. What are the guiding principles of the mechanism? Three principles guide the mechanism: • Equity: distribution of vaccine based on public health priorities; • Rapid and timely access: delivery of vaccine within a defi ned timeframe to control outbreaks; • Independence: decisions made independent of any political or economic infl uences with the sole goal of improving public health. TOOL BOX 2 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 228 Who are the ICG’s partners? The ICG is made up of four member agencies: • International Federation of the Red Cross and Red Crescent Societies (IFRC) - Has strong country presence for community health promotion, local social and resource mobilization and provides support to states during disasters and epidemics. • Médecins sans Frontières (MSF) - An independent, fi eld-based NGO that provides health care to vulnerable populations in emergency settings. • United Nations Children’s Fund (UNICEF) - Conducts wide scale vaccine procurement and shipment, and provides technical support on campaign planning and implementation in country focusing specially on social mobilization and cold chain. • World Health Organization (WHO) - Provides global public health advice and technical support to countries. During outbreaks, WHO focuses on vaccine stockpile management, surveillance, preparedness and response to disease outbreaks. Additional expertise and technical advice is provided on a case-by-case basis from partners including: Agence de Médecine Preventive, Epicentre, GAVI the Vaccine Alliance, WHO Collaborating Centres, the US Centers for Disease Control (CDC) and the European Community Humanitarian Offi ce (ECHO). Vaccine manufacturers, vaccine equipment providers and fi nancial donor institutions are also engaged in the ICG operations. Which vaccine stockpiles are available through the ICG? ICGs have been established to provide access to vaccines for Cholera, Meningitis and Yellow fever. TOOL BOX 2 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 229 For more information: • General information on the ICG: http://www.who.int/csr/disease/icg/en/ • Application forms and guidelines for Cholera: http://www.who.int/csr/disease/icg/ cholera/en/ • Application forms and guidelines for Meningitis: http://www.who.int/csr/disease/ meningococcal/icg/en/ • Application forms and guidelines for Yellow fever: http://www.who.int/csr/disease/icg/ yellow-fever/en/ Lead time for request reception to vaccine delivery How a country can access emergency vaccine stockpiles? • Vaccine security stocks can be accessed by ANY country facing an epidemic ANYWHERE in the world, as long as the country’s request fulfi lls ICG’s criteria for release of vaccine stocks. • As a fi rst step, a country must complete and submit a request to the ICG Secretariat using the standard application form. • The ICG Secretariat at WHO then circulates this request to the partners for review and assessment. Additional requests for information are sent back to the country, if needed. Following a rapid consultation and evaluation process, the decision to release vaccines and other supplies is communicated to the requesting country within 48 hours, once all necessary information has been provided. • If approved, UNICEF procures vaccines and injection materials and organizes delivery of vaccines to the country, ideally within 7 days. • Requests are evaluated taking into account the epidemiological situation, vaccination strategy, pre-existing stocks in the country and operational aspects of the epidemic response. TOOL BOX 2 1 day ICG Sec. ICG core members Procurement agency, ICG Secretariat Request Circulation Decision Delivery 2 working days 7 days PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 230 TABLE 1: Specimen collection and storage TOOL BOX 3 Tables for laboratory diagnosis & shipment of infectious substances Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Diarrhoeal Syndrome Cholera • Liquid stool specimen; • Rectal swab; • Culture isolates. • Container for stool specimen; • Cary-Blair transport medium for the swab; • Filter paper if Cary-Blair is not available, liquid stool sample may be blotted on fi lter paper. • Room temperature up to 4hrs, refrigerated if longer; • Sample in Cary-Blair can be stored at room temperature; • Sample on dry fi lter paper can be stored at room temperature; • Sample on moistened fi lter paper can be stored at room temperature; • Isolated strains from culture: • solid non selective culture medium in test tubes stored at room temperature for a few days; • In Stock Culture Agar at room temperature. Acute Haemorrhagic Fever Crimean-Congo haemorrhagic fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissue. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 231 TABLE 1: Specimen collection and storage, (continued) TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Haemorrhagic Fever Dengue • Whole blood (serum/plasma – 1ml). • Serum separator tubes; • Citrate and heparin plasma can be tested by RT-PCR; • EDTA may cause interference of PCR reagents and testing. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Ebola virus disease • Whole blood (1ml) collected on EDTA (alternative serum); • Oral fl uid collected from deceased patients; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Heparin can cause interference with PCR reagents and tests; • Dacron/polyester swab with fl ocked tip stored in universal transport medium. • < 24 hours: room temperature ; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Lassa fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissues For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 232 TABLE 1: Specimen collection and storage, (continued) TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Haemorrhagic Fever Marburg virus disease • Whole blood (2.5ml) collected on EDTA (alternative serum); • Oral fl uid collected from deceased patients; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Rift Valley fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Yellow fever • Whole blood (serum – 1ml); • Other: urine (10ml) has been recommended but is not a validated specimen type. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Acute Jaundice Syndrome Leptospirosis • Whole blood (250 uL); • Serum (250 uL); • Cerebrospinal fl uid (CSF - 250 uL); • Urine (10ml); • Isolate and media inoculated with clinical specimens (blood, tissue and urine). • Blood specimens should be collected in EDTA or Sodium Citrate tubes; • Blood specimens collected in heparin are not acceptable. • Cultures should be stored at room temperature; • Clinical specimens to be kept frozen at -20°C; • Serum to be stored at 4°C. * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 233 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Neurological Syndrome Meningococcal meningitis • Blood (Adult: 5-10ml / Child: 1-3ml); • Cerebrospinal fl uid (CSF – 3ml); • Aspirate or biopsy of any normally sterile site (e.g. cardiac fl uid) and/ or purpuric skin lesion. • CSF: - 1 dry tube and 1 Cryotube (for PCR); - If dry tube cannot be processed in <2 hours, inoculate into trans- isolate (T-I) medium; • Blood: Collected blood should be diluted in blood culture broth in order to obtain blood cultures. Specimens should be immediately inoculated (within one minute) into a blood culture bottle. • CSF in dry tube: room temperature; • CSF in Cryotube: stored at refrigerator temperature and transported in cold chain; • CSF isolates: stored frozen at -20°C to allow further testing; • Trans-isolate (TI) media vials should never be frozen. Before inoculation TI vials should be kept in the refrigerator. Once inoculated, TI vials should be kept at room temperature. Inoculated TI vials must be ventilated if not transported the same day; • Inoculated blood culture media should be protected from temperature extremes (<18°C or >37°C) with a transport carrier and thermal insulator (such as extruded polystyrene foam); • Inoculated blood culture bottles should not be placed in the refrigerator. Acute Respiratory Syndrome Anthrax • Whole blood; • Skin lesion exudates; • Pleural fl uid; • Cerebrospinal fl uid (CSF); • Rectal swab; • Ascites fl uid; • Tissues from biopsy or autopsy. • Blood specimens should be collected in EDTA or Sodium Citrate tubes (not heparin); • Tissues for Immunohistochemistry (IHC) should be formalin-fi xed. • Most samples can be sent 2-8°C; • Fresh tissue should be sent frozen and fi xed tissue can be sent at room temperature. TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 234 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Respiratory Syndrome Infl uenza • Virus isolates; • Respiratory clinical specimens (i.e. nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasal washes, lower respiratory tract specimens, broncho lavage); • Nucleic acid. (1ml) For suspected avian infl uenza samples: collect lower respiratory tract specimens in addition to upper respiratory tract specimens • Dacron or polyester fl ocked swabs with universal transport medium • Dacron orSpecimens received cold should be stored refrigerated (2°–8°C) for up to 72hrs before processing. • Dacron orStore any residual specimens at ≤ -70°C. • Dacron orAlthough optimal performance is met when testing fresh specimens within 72hrs of collection, performance has been demonstrated with frozen specimens: - If testing of a fresh specimen is not possible within 72 hours storage at 2–8°C, the specimen may be frozen at ≤ -70°C and tested at a later time; - Specimens received frozen should be stored at ≤ -70°C until processing; - Store any residual specimens at ≤ -70°C; - Ship extracted RNA and frozen specimen on dry ice. Plague • Bubonic plague: bubo aspirate plus, swabs in bacterial transport media (e.g. Cary-Blair); • Pneumonic plague: sputum plus swabs in bacterial transport media (e.g. Cary-Blair); • Blood for serology. Specimens should be collected during the acute phase of illness and ideally before commencement of antibiotic treatment • Fresh or frozen: swab, biopsy, touch prep slides, formalin-fi xed, paraffi n block; • Swabs should be made of nylon, polyester, or Dacron material. • Storage at 2-8°C TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 235 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Respiratory Syndrome MERS • Lower respiratory tract: - Sputum; - Aspirate; - Lavage; • Upper respiratory tract: • Naso-pharyngeal and Oro- pharyngeal swabs; • Naso-pharyngeal • wash / naso-pharyngeal aspirate; • Serum. (1ml) Collection of both upper and lower respiratory tract specimens is recommended • Dacron, polyester swabs with universal transport medium; • Blood: EDTA. • < 24 hrs: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Acute Dermatological Syndrome Cutaneous anthrax • Skin lesion exudates; • Tissues from biopsy or autopsy; • Other: - Whole blood; - Pleural fl uid; - Cerebrospinal fl uid (CSF); - Rectal swab; - Ascites fl uid. • Blood specimens should be collected in EDTA or Sodium Citrate tubes (not heparin); • Tissues for immunohistochemistry (IHC) should be formalin-fi xed. • Most samples can be sent 2-8°C; • Fresh tissue should be shipped frozen; • Fixed tissue should be shipped at room temperature. Monkeypox • Lesion fl uid and/or material: - Vesicle/pustule skin or fl uid; - Scab, crust; • Optional but not preferred: blood. (0.5ml for fl uids) • Swabs without individual holders may be stored in a sterile container; • Dry swabs are preferred but a minimal amount of viral transport media may be added. • Storage at 4°C, shipments within 72hrs TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 236 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Dermatological Syndrome Smallpox • Cutaneous lesion scabs; • Pustule fl uid. (0.5ml for fl uids) • Swabs without individual holders may be stored in a sterile container; • Dry swabs are preferred but a minimal amount of viral transport media may be added. • Storage at 4°C, shipments within 72hrs Acute Fever and Rash Chikungunya • Whole blood, serum (4-5ml venous blood); • Other: urine has been recommended but is not a validated specimen type; • CSF in meningoencephalitis cases: - Synovial fl uid in arthritis with effusion; - Autopsy material – serum or available tissues. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • Storage at 0 to 4ÐC Zika • Whole blood, serum, plasma (4- 5ml venous blood); • Urine; • Cerebrospinal fl uid (CSF – 0.25ml); • Other: semen. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • Storage at 4ÐC; • >48hrs, serum should be separated. TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 237 TABLE 2: Laboratory diagnosis and shipment of infectious substances TOOL BOX 3 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Diarrhoeal Syndrome Cholera • RDT for fi eld use (needs additional confi rmation); • PCR, MLVA, sequencing; • Culture; • Antibiotic susceptibility testing. • PCR: 24-48hrs; • Culture and susceptibility testing: up to 8 weeks. • Amoebic Dysentery • Cryptosporidiosis • Giardiasis • Shigellosis • E.coli (enterotoxigenic and enterohaemorrhagic) • Viral gastroenteritis (Norwalk-like and rotavirus) • Salmonellosis • Campylobacter • UN3373 - Biological Substance • Packing Instruction 650 Acute Haemorrhagic Fever Syndrome Crimean-Congo haemorrhagic fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Antigen detection; • Serum neutralization; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Dengue • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Antigen detection: IgM, IgG, RDTs; • Serology; IgM, RDTs; • Virus isolation. • PCR: 24hr;s • ELISA: 72hrs. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 238 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Haemorrhagic Fever Syndrome Ebola virus disease • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Antigen detection (RDT); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Lassa fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Marburg virus disease • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 239 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Haemorrhagic Fever Syndrome Rift Valley fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR:24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Yellow fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Neutralization assays; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 10 days; • PRNT: up to 2 weeks. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Acute Jaundice Syndrome Leptospirosis • Serology: MAT-micro agglutination; • Molecular: Polymerase Chain Reaction (PCR); • Microscopy. • 2 weeks; • Primary isolation from clinical specimens takes up to 6 months. • Hepatitis A-E • CMV • EBV • Other fl aviviruses • UN3373 - Biological Substance • Packing Instruction 650 Yellow fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Neutralization assays; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 10 days; • PRNT: up to 2 weeks. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 240 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Neurological Syndrome Meningococcal meningitis • Culture; • PCR. • PCR: 48hrs; • Culture: 4-5days. • H.infl uenzae • Strep. Pneumoniae • Enteroviral meningitis • Malaria • Poliomyelitis • Rabies and other lyssaviruses • African trypanosomiasis • Meningoencephalitis • Tick-borne encephalitis viruses • Japanese encephalitis • UN3373 - Biological Substance • Packing Instruction 650 Acute Respiratory Syndrome Anthrax • Culture; • PCR; • Immunohistochemistry (IHC); • Toxin detection. • PCR: 24hrs; • Culture, toxin detection: 2 weeks. • Diphtheria • Hantavirus Pulmonary Syndrome • Mycoplasma • Legionellosis • Respiratory syncytial virus • Pertussis • Other respiratory viruses • Cultures: - UN2814- Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Infl uenza • PCR; • Virus isolation; • HAI (Hemagglutination Inhibition Test). • PCR: 24hrs; • HAI: 72hrs; • Culture: 1-2 weeks. • Cultures of avian infl uenza and suspected avian/ pandemic infl uenza: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimen: - UN3373 - Biological Substance - Packing Instruction 650 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 241 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Respiratory Syndrome Plague • Rapid dipstick test; • PCR; • ELISA IgM; • culture; • DFA. • PCR: 24hrs; • Culture: 1 week. • Diphtheria • Hantavirus Pulmonary Syndrome • Mycoplasma • Legionellosis • Respiratory syncytial virus • Pertussis • Other respiratory viruses • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 MERS • Molecular: PCR positive on at least two gene targets: Screening assay (e.g. up E or N gene NAAT) and Confi rmatory assay (e.g. ORF 1a, ORF 1b or N gene NAAT); • Serology: immunofl uorescence assays, serum neutralization assays, protein microarray technology, recombinant nucleocapsid (N) and spike (S) protein-based indirect enzyme-linked immunosorbent (ELISA), and a neutralization test based on retroviral pseudoparticles. • PCR: 24hrs; • IFA: 24hrs; • ELISA and microneutralization: 1-3 days. • UN3373 - Biological Substance • Packing Instruction 650 TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 242 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Dermatological Syndrome Cutaneous anthrax • Culture; • PCR; • Immunohistochemistry (IHC); • Toxin detection. • 2 weeks • Chickenpox • Herpes • Enterovirus • Measles • Medication-associated allergies • Bacterial skin infections • Cultures: - UN2814- Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Monkeypox • PCR • 24hrs • UN2814- Infectious Substance affecting humans • Packing Instruction 620 Smallpox • PCR • 24hrs • UN2814- Infectious Substance affecting humans • Packing Instruction 620 Acute Fever and Rash Chikungunya • PCR; • Serology; • Viral culture. • PCR: 24hrs; • ELISA: 2-5 days; • Virus isolation ≤ 8 days. • Leptospirosis, • Alphavirus infections • Dengue • Malaria • Meningitis • Post-infectious arthritis (incl. rheumatic fever) • Invasive Meningococcal Disease • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Zika • PCR; • Serology; • Neutralization tests. • PCR: 24hrs; • ELISA: 2-5 days. • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 243 TOOL BOX 4 Transport of infectious substances Infectious substances: defi nition For the purposes of transport, infectious substances are defi ned as substances which are known or are reasonably expected to contain pathogens. Pathogens are defi ned as microorganisms (including bacteria, viruses, rickettsiae, parasites, fungi) and other agents such as prions, which can cause disease in humans or animals. This tool box highlights some important features of the Guidance on regulations for the Transport of Infectious Substance 2017-2018 1, World Health Organization, 2017. 1 The full guidance can be found on: http://www.who.int/ihr/publications/WHO-WHE-CPI-2017.8/en/ Laboratory diagnosis Patient Specimen collection National laboratory International laboratory The defi nition is applied to all specimens except those explicitly exempted: • Cultures; • Patient specimens; • Biological products; • Genetically modifi ed microorganisms (GMMOs) and organisms (GMOs); • Medical or clinical wastes. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 244 Classifi cation Infectious substances are classifi ed in Division 6.2 of the Dangerous Goods Regulations and assigned to proper shipping names according to their hazard classifi cation and their composition (UN 2814, UN 2900, UN 3291 or UN 3373). Infectious substances are divided into the following categories: • Category A - An infectious substance which is transported in a form that, when exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal disease in otherwise healthy humans or animals. • Category B - An infectious substance which does not meet the criteria for inclusion in Category A. • Exemptions. General preparation of shipments for transport Because of the differences in the hazards posed by Category A infectious substances (UN 2814 and UN 2900) and Category B infectious substances (UN 3373), there are variations in the packaging, labelling and documentation requirements for the two categories. Note 1: Hand carriage of Category A and Category B infectious substances and transport of these materials in diplomatic pouches are strictly prohibited by international air carriers. Note 2: Inner packaging containing infectious substances shall not be consolidated with inner packaging containing unrelated types of goods. Shippers of infectious substances shall ensure that packages are prepared in such a manner that they arrive at their destination in good condition and present no hazard to persons or animals during transport. Basic triple packaging system This system of packaging shall be used for all infectious substances. It consists of three layers as follows: • Primary receptacle. A primary watertight, leak-proof receptacle containing the specimen. The receptacle is packaged with enough absorbent material to absorb all fl uid in case of breakage or leakage. • Secondary packaging. A second durable, watertight, leak-proof packaging to enclose and protect the primary receptacle(s). Several cushioned primary receptacles may be placed in one secondary packaging, but suffi cient additional absorbent material shall be used to absorb all fl uid in case of breakage or leakage. • Outer packaging. Secondary packagings are placed in outer shipping packagings with suitable cushioning material. Outer packagings protect their contents from outside infl uences, such as physical damage, while in transit. The smallest overall external dimension shall be 10 x 10 cm. Each completed package is normally required to be correctly marked, labelled and accompanied with appropriate shipping documents (as applicable). There are specifi c packaging, labelling and documentation requirements for infectious substances in Category A and with lesser constrains for substances in Category B. Overpacks • For both categories it is possible to use overpacks. • “Overpack” is the term used when several packages are combined to form one unit and sent to the same destination by a single shipper. When refrigerants are used to protect contents, the overpacks may comprise insulated vessels or fl asks. Whenever an overpack is used, the required marks and labels shown on the outer packaging must be repeated on the outermost layer of the overpack. This requirement applies to infectious substances in Categories A and B. Overpacks are also required to be marked with the word “overpack”. • It is very important not to reproduce UN specifi cations mark on the overpack. TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 245 Reusing packaging materials Shipping packages can be reused. If the shipper plans on reusing a package, it must be appropriately disinfected. Before reusing a package, the shipper must make sure all marks and labels refl ect the substances actually being shipped. If the shipper plans on shipping an empty package, all non-applicable marks and labels must be removed or covered. Before an empty package is returned to the shipper, or sent elsewhere, it must be appropriately disinfected or sterilized to nullify any hazard. Any label or mark indicating that it had contained an infectious substance shall be removed or covered. Refrigerants • Refrigerants may be used to stabilize infectious substances in Categories A and B during transit. • Packed infectious substances requiring cooling meet the appropriate requirements as described in the guidance on regulations for the Transport of Infectious Substances 2017-2018. Trainings • The Dangerous Goods Regulations require all personnel involved in transport to undergo appropriate training. • For the transport of Category A infectious substances, personnel must undergo training in accordance with the modal requirements. This can involve attendance at approved courses and passing examinations. • For the transport of Category B infectious substances, there is a requirement that clear instructions on the use of the packaging are supplied to the user; this is regarded as suffi cient “training” for the shipping of these substances. However, if such specimens are consigned with other dangerous goods (e.g. fl ammable liquids, radioactive materials, liquefi ed gases, etc.), then personnel must be trained in the proper procedures for their transport. TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 246 Transport • It is the responsibility of the shipper to ensure the correct classifi cation, packaging, labelling, and documentation of all infectious substances destined for transport. • The effi cient transport and transfer of infectious substances requires good coordination between the sender, the carrier and the receiver to ensure that the material is transported safely and arrives on time and in good condition. Such coordination depends upon well-established communications and a good working relationship between the three parties. Main actors in the infectious substance transport chain are: • The shipper; • The carrier; • The receiver. Descriptions of their respective responsibilities and duties can be found in the guidance on regulations for the Transport of Infectious Substances 2017-2018. For more information on the transport of infectious substances: • Guidance on regulations for the transport of infectious substances 2017–2018, World Health Organization, 2017: http://www.who.int/ihr/publications/WHO-WHE- CPI-2017.8/en/ TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 247 TOOL BOX 5 Vector control Prevention of Vector-Borne Diseases and control measures against vectors during epidemic situations Some epidemic diseases are transmitted by arthropods vectors, such as ticks and insects. To prevent the transmission of these infectious diseases called Vector-Borne Diseases (VBDs), actions can be taken to protect human beings from the vectors and/or to eliminate or reduce vectors population. These actions include community engagement, personal protection and vector control operations. Recommendations and deployment of the available tools are modulated according to the level of the transmission of the disease, which can range from sporadic to endemic levels and fi nally to epidemic level. Coordination of the deployment of the different tools at different levels is aided by having a preparedness plan and trained staff. Countries are recommended to have national preparedness plans for the prevention and control of VBDs, as well as a training program for staff engaged in vector control activities. Regional coordination is also necessary as most of the VBDs cross borders. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 248 TOOL BOX 5 Below is a list of epidemic-prone VBDs that are included in the handbook. These are transmitted by different vectors but share the common transmission mode, via the bite (in other VBDs such as Chagas disease and Typhus, other transmission modes are found): These different vectors have different ecologies, behaviors, biting times and transmission cycles. The bionomics of the vectors affects the type of actions taken to prevent and control these diseases. In all situations, there are four key actions: a. Personal protection tools: Table 1 summarizes the biting behavior of the different vectors and the type of personal protection available. b. Vector control operations implemented by public and/or private agencies and deployed at the community level. Table 2 summarizes vector control tools available for each vector type. c. Community engagement, essential for outbreak response. d. Communication of the different actions, as an essential component for success. Public Health recommendations must take into account social and cultural factors. • The Crimean-Congo haemorrhagic fever virus (CCHFV) is transmitted by ticks of the family Ixodidae, mainly by Hyalomma genus. In the Mediterranean and Middle Asia regions, the most prominent vector is Hyalomma marginatum. • The Yellow fever (YFV), Zika (ZIKV) and Chikungunya (CHIKV) viruses are transmitted by mosquitoes, through different cycles from sylvatic (wild), rural, peri-urban and urban, with different vector species according to the cycle. Zoonoses can occur in sylvatic transmission involving various vector species, whereas epidemics are found to occur in rural and urban environments, with the main vector being Aedes aegypti, and an emerging secondary vector being Aedes albopictus. • The Plague is a bacterial disease transmitted by fl eas into wild cycles in which rodents’ fl eas are playing a major role. For epidemics in domiciliary environments, the rodent’s fl eas, such as the most known Xenopsylla cheopis, are the major vectors. However, the association between the disease caused by Yersinia pestis and the fl eas species is not very specifi c, thus many fl eas species can act as plague vectors. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 249 TABLE 1: Personal protection tools according to the type of vectors Type of vector (VBDs) Vectors bionomics Personal Protection tools Natural environment Biting time Need animal cycle Bednet Repulsive Window screen Insecticide Sprays Electric devices Elimination of domestic breeding sites Forest, wild Day Yes - ++ + + - - Ticks (CCHFV) Aedes mosquitoes (YFV, CHIKV, ZIKAV) Fleas (PLAGUE) Domestic, rural & urban Day No + +++ +++ +++ ++ +++ Domestic, wild All day Yes / No - ++ - ++ - +++ The vector control activities are deployed at the community level to eliminate the vectors and larvae as much as possible, in order to prevent or control the transmission of VBDs. The operationalization of vector control varies according to the type of vector and transmission intensity. • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. • Among the control measures, insecticide applications are the most frequently used, either on the animal bearing the vectors, such as the ticks and the fl eas, or in the breeding places to kill vectors’ larvae, and fi nally, as adulticide- spraying to eliminate adult female mosquitoes. • Other vector control activities include: - Environmental measures through sanitation, habitat management and livestock management; - Mechanical measures with trapping of vectors; - Biological tools using natural enemies and biological larvicides for mosquitoes; - Other chemicals such as the use of mimics of natural hormones to stop the insect development; - A new generation of vector control products is also arriving with genetically modifi ed organisms (e.g. bacteria Wolbachia). TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 250 TABLE 2: Vector control tools according to the type of vectors Type of vector (VBDs) Endemic situation Epidemic situation Insecticide against larvae Insecticide against adults Animal sprayed Physical elimination of all breeding sites (public and domestic) Mechanical trapping Environmental measures Insecticide against larvae Insecticide against adults Animal sprayed Physical elimination of all breeding sites (public and domestic) Mechanical trapping Environmental measures + + Yes + + + +++ +++ Yes + + + Ticks (CCHFV) Aedes mosquitoes (YFV, CHIKV, ZIKAV) Fleas (PLAGUE) +++ + No +++ + ++ +++ +++ No +++ +++ +++ +++ +++ Yes +++ ++ +++ +++ +++ Yes +++ +++ +++ • Vector control tools can be used alone or in combination, through an Integrated Vector Management (IVM) approach (WHO, 2012) 1. The deployment, effi ciency and results of the vector control activities require Monitoring and Evaluation (M&E), but the methods to perform this M&E, both at the level of the vector population, and in terms of disease transmission, are often lacking. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. Epidemiological and entomological surveillance/indicators should be collected and analyzed in close collaboration. This surveillance will include: - Mosquitoes densities and geographical distribution; - Contacts with human hosts; - Effectiveness of control tools (e.g. susceptibility of resistance to insecticides). TOOL BOX 5 1 WHO, Handbook for integrated vector Management, 2012 http://apps.who.int/iris/ bitstream/10665/44768/1/9789241502801_eng.pdf PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 251 Disease-specifi c approaches based on the vectors’ ecology and control options The Crimean-Congo haemorrhagic fever virus (CCHFV) is transmitted by Hyalomma marginatum ticks. • These ticks blood feed at all stages from the 6-legged larval stage to the adult stage to complete their development and mature their eggs. In addition to being transmission vectors, ticks fulfi l the role of reservoir of CCHFV. • The larval stages usually feed on small animals, and the adult stages feed on larger animals such as deer, sheep and cattle. The ticks do not have feeding preference for the host and humans are considered as accidental hosts. The CCHFV circulates into animal populations without causing diseases (except in ostriches) and humans are considered as dead-end hosts. • In the regions with transmission risks, where animals are infected by the CCHFV, the main objective is to inform the public and the local communities how to promote practices that decrease transmission of the disease. - Such practices would include preventing contacts with the blood of virus-infected animals (e.g. slaughtering activities), preventing tick bites, and preventing the transmission during care at home or during funerals. TOOL BOX 5 Key behavioral interventions Animal settings Home settings Health care settings • Reduce ticks in the environment and decrease tick infestations on animals or in stables/barns. The tick vectors are numerous and widespread and tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well-managed livestock production facilities. • Implement quarantine for animals before they enter slaughterhouses or routine treatment of ruminants with pesticides 2 weeks prior to slaughter. This activity will decrease the risk for animal to be viraemic during its slaughtering. • Wear personal protective equipment (masks, gloves and gowns) when slaughtering and butchering animals in slaughterhouses or at home. This will prevent skin contact with infected animal tissue or blood. • Wear protective clothing (long leaves, long pants, etc.) and light colored clothing (to allow easy detection of ticks on the clothes). • Avoid of areas where tick vectors are abundant, when they are active (spring to fall). • Regular examination of clothing and skin for ticks. • Use of repellents on the skin (e.g. DEET) and clothing (e.g. permethrin). • Remove ticks safely from the skin. • Seek early treatment for fever after a history of tick bites or contacts with CCHF patients. • Avoid any direct unprotected contact with blood or body fl uids when managing patients. • Wash hands with soap and clean water regularly. • Organise safe and dignifi ed funerals. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 252 • Current vector control measures are not fully satisfactory: - Chemical methods produce resistant ticks, food contamination, and environmental pollution. Furthermore, chemical tick control is only realistic for well-managed and suffi ciently resourced livestock production facilities that are rare in most affected countries; - Physical methods (e.g. heavy grazing, burning of grasslands) have an important environment negative impact; - Biological methods (e.g. use of hormones and growth regulators, use of predators, bacteria, nematodes, and fungi) have not demonstrated full effi cacy. • Vaccination is considered a promising alternative to control tick infestations. An animal vaccine effective against Hyalomma ticks that prevent the tick-animal-tick cycle would decrease tick population, decrease CCHF prevalence in animals, and therefore decrease human exposure, being a cost effective CCHF prevention measure. • The virus cannot be amplifi ed into humans and thus directly transmitted into a human cycle. It needs amplifying hosts (domestic and wild animals) to provide blood meals to support tick populations. The Yellow fever (YFV), Zika (ZIKV) and Chikungunya (CHIKV) viruses are transmitted at an epidemic level by mosquitoes belonging to the species Aedes aegypti and Aedes albopictus. The Aedes mosquitoes also transmit the Dengue virus (DENV). • Although these viruses can be transmitted by other mosquito vectors species in sylvatic environments and potentially cause zoonoses, only the Aedes species are responsible for epidemics as they have adapted to urban settings and can lay eggs in any kind of recipient containing water in and around houses and other human dwellings in urban and scattered rural areas. • The development of the larvae can be very short, less than a week, and thus the increase of the mosquito population can be exponential if the conditions are favorable (temperatures and water) in the absence of any vector or larvae control. • It is thus strongly recommended to maintain regular control of these mosquito populations through the physical elimination of all breeding sites, in private and public spaces, and through the use of larvicides in breeding places that cannot be eliminated. The biological larvicide with Bacillus thuringiensis var. israelensis toxins are recommended because of the lack of resistance and no environmental drawback. TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 253 • During an epidemic situation, all tools to protect humans from mosquito bites (Table 1), as well as all available tools to eliminate adult mosquitoes are recommended, with reinforcement of the elimination of breeding sites, use of larvicide and use of adulticide 2. - The effi cacy of the products needs to be monitored in advance with tests on resistance and, if necessary, an integrated resistance management plan must be developed. - The spraying of adulticides must be done on a daily basis until the mosquito populations are cut down under the necessary Breteau Index (BI) (that is the number of positive containers in 100 houses) which should be less than 1 3. - Community engagement is also a very important component for controlling Ae. aegypti and Ae. albopictus populations. Through participative actions, such as recommendations for personal protection in the working places and schools, elimination of breeding sites, installation of window screens, and overall surveillance of the environment to make it less favorable for mosquitoes, are some of the major actions that can be taken by communities. • Vector control against Ae. aegypti and Ae. albopictus, the main vectors of urban arboviruses have not been reported as effi cient as it is required due to many factors (including unplanned urbanization and lack of resources). However, these tools are the only ones available in many situations and will result in controlling the transmission if well applied. Plague circulates into mammals, especially rodents, in almost all regions of the world. • The humans are affected by Plague epidemics according to two main transmission modes. At the beginning of an epidemic, rodents are affected by the disease with fl eas as vectors, then the fl eas leave the dying rodents and move on to humans. At this stage, the Plague is called bubonic because bubonic abscesses are the main clinical symptoms. With the spread of the bacterial into the lungs, humans can directly transmit the Plague bacteria to other human beings, and the Plague is called pneumonic. • The fl eas are host-specifi c and animal fl eas bit human rather by accident. • Sanitation and rat control are the best practices to prevent human Plague. When Plague cases are reported, control measures must fi rst target fl eas and secondarily rodents, because the use of raticide may result in the adverse effect, with fl eas leaving the dead rats and moving onto humans. • Depending on environmental context, large deployment of insecticide baited traps for rats can be recommended. • Environmental measures to repel rat population as well as strong disinsectisation of places where rats are installed can also be applied. • The community engagement is also very important for coordinated rat control activities, management of wastes and domestic environment. 2 WHO, Pesticide and their application for the control of vectors and pests of public health importance, 2006. http://apps.who.int/iris/bitstream/10665/69223/1/WHO_CDS_NTD_WHOPES_GCDPP_2006.1_eng.pdf 3 Bowman LR,Runge-Ranzinger S and McCall PJ. Assessing the Relationship between Vector Indices and Dengue Transmission: A Systematic Review of the Evidence. PLoS Negl Trop Dis. 2014 May; 8(5): e2848. doi: 10.1371/ journal. pntd.0002848 TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 254

Acknowledgements The Managing epidemics handbook is a WHO collective endeavour with the involvement of the WHO Health Emergencies Programme (WHE) departments and, in particular, many Infectious Hazard Management (IHM) experts at HQ, Regional and Country levels. It has also been developed in collaboration with other departments within the WHO: The Special Programme for Research and Training in Tropical Diseases (TDR), Health Emergency Information & Risk Assessment (HIM), Emergency Operations (EMO), Country Health Emergency Preparedness & IHR (CPI), Information Evidence and Research (IER), Polio Eradication (POL), and Control of Neglected Tropical Diseases (NTD) departments. 256 Authors & contributors WHO acknowledges the contributions given by the following individuals who have provided inputs and/or contributed to the drafting, review and/or production of the handbook: Aysheshim Ademe, Hernando Agudelo, Kate Alberti, Sylvain Aldighieri, Yahaya Ali Ahmed, Sophie Allain Ioos, Yokouide Allarangar, Inacio Alvarenga, Javier Aramburu, Richelot Ayangma Mouko, Jean-Christophe Aze, Freddy Banza Mutoka, Cecile Barbou des Courieres, Mady Ba, Maurizio Barbeschi, Philippe Barboza, Jennifer Barragan, Ahmadou Barry, Rodrigue Barry, Bienvenu Baruani Ngoy, Marie Roseline Darnycka Belizaire, Luisa Belloni, Simeon Bennett, Justus Benzler, Isabelle Bergeri, Eric Bertherat, Terry Besselaar, Aphaluck Bhatiasevi, Viviane Bianco, Bonkoungou Boukaré, Anna Bowman, Rick Brennan, Sylvie Briand, Caroline Brown, Gisèle Bwende Kasungi, Jorge Castilla, Andersen Chimusoro, Stella Chungong, Laurence Cibrelus, Ian Clarke, Peter Clement, Rudi Coninx, Alejandro Costa, Ana Paula Coutinho Rehse, Fernando Da Silveira, Arsene Daizo, Farah Dakhlallah, Lucia Dell Amura, Ghyllain Demba Lubambo, Janet Diaz, Heidi Divecha, Devika Dixit, Mamoudou Harouna Djingarey, Sabelo Dlamini, Emmanuel Douba, Patrick Drury, Kara Durski, Amgad Abdalla Elkholy, Nedret Emiroglu, Rocío Escobar, Anthony Eshofonie, Socé Fall, Ana Fernandes, Katya Fernandez, Johanna Fihman, Julia Fitzner, Pierre Formenty, Florence Fouque, Mara Frigo, Florence Fuchs, Caroline Fuhrer, Christian Fuster, Gaya Gamhewage, Erika Garcia, Sandra Garnier, Semere Gebregiorgis, Yohannes Ghebrat, Carolina Gomes, Philip Gould, Peter Graaff, Michael Griffi n, Mary-Anne Groepe, Aspen Hammond, Alexandra Hill, Siddhivinayak Hirve, Daniel Hougendobler, Khelifi Houria, Stéphane Hugonnet, Poonam Huria, Anne Huvos, Benido Impouma, Christian Itama Mayikuli, Yurie Izawa, Alpha Jallow, Sandrine Joucla, Hilary Kagume Njenge, Arnaud Kahn, Lingawako Kalinde Mangachi, Ebba Kalondo, Masaya Kato, Erin Kenney, Joyce Kerubo Onsongo, Asheena Khalakdina, Moakofhi Kentse, James Kojo Teprey, Davi Kokou Mawulé, Innocent Komackech, Alexandra Kontic, Thomas d’Aquin Koyazegbe, Eve Lackritz, Andersson Latt, Sharmila Lareef-Jah, Anaïs Legand, Dominique Legros, Ellen Leroy, Ailan Li, Francois Libama, Maja Lievre, Clement Lingani, Jennifer Linkins, Daniel Lucey, André Lukusa, Nuha Mahmoud, Kevin Makadzange, Mamunur Malik, Awandha Mamahit, Koria Mankampa, Stephen Maphosa, Rima Marrouch, Christian Massidi, Humphreys Masuku, Margaux Mathis, Petrus Mhata, Ruhana Mirindi Bisimwa, Ann Moen, Vital Mondonge Makuma, Oliver Morgan, Sylvie Mortier, Amadou Mouctar Diallo, Mireille Flore Mouele, Ahamada Msa Mliva, Kelias Msymbaoza, Martin Muita, Marjorie Mupandare, Robert Musoke, Abrahams Mwanamwenge, Dhamari Naidoo, Michel N’da Konan Yao, Miriam Nanyunga, Jérôme Ndaruhutse, Charlotte Faty Ndiaye, Jean-Bosco Ndihokubwayo, Landry Ndriko Mayigane, Bla François Nguessan, Tim Nguyen, Dorit Nitzan, Lionel Nizigama, Ian Norton, Deo Nshimirimana, Alex Ntale Gasasira, Innocent Nzeyimana, Roderico Ofrin, Sally-Ann Ohene, Ifeanyi Okudo, Babatunde Olowokure, David Olson, Catherine Oswald, Heather Papowitz, Cyr Passi-Louamba, Scott Pendergast, William Augusto Perea Caro, Anne Perrocheau, Arturo Pesigan, Lorenzo Pezzoli, Marcia Poole, Jukka Tapani Pukkila, Arthur Rakotonjanabelo Lamina, Otim Patrick Cossy Ramadan, Bardan Jung Rana, João Rangel De Almeida, Peter Rehse, Bertrand Renaud, Tatiana Resnikoff, Amelie Rioux, Guenael Rodier, Jose Rovira Vilaplana, Olivier Ronveaux, André Rusanganwa, Florence Rusciano, Michael Ryan, Massambou Sacko, Grace Saguti, Niang Saidou Doro, Mohamed Sainda, Peter Salama, Rosine Sama Kanembe, Gina Samaan, Magdi Samaan, Ravi Santhana Gopala Krishnan, Nikki Shindo, Véronique Sicilia, Raphael Slattery, Catherine Smallwood, Vincent Sodjinou, Peter Songolo, Mary Stephen, Oliver Gerd Stucke, Ute Ströher, Aka Tano Bian, Israel Tareke, Joanna Tempowski, Michel Thieren, Desta Tiruneh, Ciro Ugarte Casafranca, Heini Utunen, Maria Van Kerkhove, Katelijn Vandemaele, Reinhilde Van De Weerdt, Raman Velayudhan, Sirenda Vong, Christèle Wantz, Sergio Yactayo, Sanyang Yaya, Daniel Yota, Zebulon Yoti, Wenqing Zhang, Ursula Zhao, Weigong Zhou. The development of the handbook was led by Sylvie Briand, Director of the Department of Infectious Hazard Management, and Margaux Mathis in collaboration with the experts mentioned above. Edited by: Thomson Prentice Design & layout by: Vivian Lee Illustrations by: Sam Bradd (Drawing Change) 257

Key facts about major deadly diseases Managing epidemics World Health Organization 20 Avenue Appia CH-1211 Geneva 27 Switzerland ISBN 978-92-4-156553-0

Key facts about major deadly diseases Managing epidemics VERSION 1 Key facts about major deadly diseases Managing epidemics © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/ by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specifi c organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). 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Printed in Luxembourg Managing epidemics: key facts about major deadly diseases ISBN 978-92-4-156553-0 Contents The re-emergence of infectious diseases - The threat continues - The 21st century: already a long series of scourges - Faster and further with a greater impact - Ready and able to detect the next outbreak - One Health and emerging and re-emerging pathogens - Known epidemics: still a severe threat - Strengthening health systems: essential in epidemics Burden of epidemics: illustrations Challenges and risk factors for 21st century epidemics - New lifestyles spread diseases further - Revisiting traditional control measures - Equity and solidarity - Epidemics of rumours: a new risk to health Foreword About this handbook PART I : EPIDEMICS OF THE 21ST CENTURY 10 11 14 14 15 17 18 19 20 21 22 25 25 26 26 26 Key insights into infectious disease epidemics Response tips and checklists - Coordinating responders - Health Information - Communicating risk - Health Interventions Focus 1: Community engagement during epidemics - Defi ning a community - Why engage communities - Three elements of community engagement - Ten things to know - Ensuring effective community engagement Focus 2: Risk communication – a life-saving action in public health emergencies - The essence of risk communication - 21st century aspects change and complicate risk communication - Making it effective - Ten things to know and do - Other factors to remember Focus 3: Treating patients and protecting the health workforce - Advances in medicine: antibiotics, antivirals, vaccines and new treatments - Treating patients with supportive care - Protecting frontline responders - Confronting the human resources crisis 27 31 32 33 34 36 38 38 38 39 40 41 42 42 43 44 45 47 48 48 49 49 50 PART II: BE IN THE KNOW. 10 KEY FACTS ABOUT 15 DEADLY DISEASES 56 66 76 86 100 110 120 130 140 150 160 170 180 190 200 EBOLA VIRUS DISEASE LASSA FEVER CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF) YELLOW FEVER ZIKA CHIKUNGUNYA AVIAN AND OTHER ZOONOTIC INFLUENZA SEASONAL INFLUENZA PANDEMIC INFLUENZA MIDDLE EAST RESPIRATORY SYNDROME (MERS) CHOLERA MONKEYPOX PLAGUE LEPTOSPIROSIS MENINGOCOCCAL MENINGITIS PART III: TOOL BOXES Tool box 1: The role of WHO Tool box 2: The International Coordinating Group (ICG) on vaccine provision Tool box 3: Tables for laboratory diagnosis and shipment of infectious substances Tool box 4: Transport of infectious substances Tool box 5: Vector control during epidemics Acknowledgements 214 227 231 244 248 256 Foreword Can we create a pandemic-free world? There is no such thing as a guarantee, but with meticulous preparation and rapid response, we can prevent most outbreaks from getting out of control, and limit the impact of those that spread internationally. First, we must build and sustain resilient capacities at national, regional and global levels to prevent, detect and respond to outbreaks, in accordance with the International Health Regulations. And second, we must ensure that populations affected by emergencies have rapid access to essential life- saving health services, including medicines and vaccines. That’s why WHO works all around the world to strengthen health systems, built on the foundation of people-centred primary health care that focuses on health promotion and disease prevention, with a strong focus on surveillance systems. Delivering on these priorities will cost money of course, but only a fraction of what remaining unprepared will cost. In the end, prevention is not only better than cure; it’s cheaper. This year marks the 100th anniversary of Spanish fl u, the deadliest outbreak in recorded history. Up to 50 million people were killed, more than the death toll from the First World War. Thankfully, we have not seen a public health emergency on that scale since then. But we may at any time. Outbreaks are a fact of life, and the world remains vulnerable. We do not know where or when the next global pandemic will occur, but we do know that it will take a terrible toll, both on human life, and on the global economy. None of us will ever forget the West African Ebola outbreak in 2014. It taught us a valuable lesson: that global health security is only as strong as its weakest link. No-one is safe until everyone is safe. Keeping the world safe is one of WHO’s three top strategic priorities in our new General Programme of Work. We are setting ourselves a goal that over the next fi ve years, 1 billion more people will be better protected from epidemics and other health emergencies. This manual is a valuable tool to help countries make progress towards that goal. It offers expert guidance to help WHO’s country representatives and others to respond quickly in the earliest stages of an outbreak. But it’s not enough just to respond to outbreaks. We must do our best to prevent them by addressing the root cause of health insecurity: the lack of access of the most vulnerable people to essential health services. Ultimately, it’s the absence of universal health coverage that is the greatest threat to health security. Universal health coverage and health security are two sides of the same coin. 2018 is also a milestone year for WHO. It’s our 70th birthday – a reminder that the reasons we were created are as relevant now as they were at our beginning. WHO was founded on the principle that all people should be able to realize their right to the highest possible level of health. “Health for all” has always been our guiding vision. Dr Tedros Adhanom Ghebreyesus Director-General of the World Health Organization 10 About this handbook Handbook purpose Epidemics of infectious diseases are occurring more often, and spreading faster and further than ever, in many different regions of the world. The background factors of this threat are biological, environmental and lifestyle changes, among others. A potentially fatal combination of newly-discovered diseases, and the re-emergence of many long-established ones, demands urgent responses in all countries. Planning and preparation for epidemic prevention and control are essential. The purpose of this “Managing epidemics” manual is to provide expert guidance on those responses. Although this publication is open to a wide readership, it is primarily intended to help the World Health Organization (WHO) country representatives (WRs) to respond effectively and rapidly at the very start of an outbreak. The manual provides concise and basic up-to-date knowledge with which WRs can advise Ministries of Health in all countries. Specifi cally, it examines and explains in detail a total of 15 different infectious diseases and the necessary responses to each and every one of them. These diseases have been selected because they represent potential international threats for which immediate responses are critical. Nearly all of them are subject to WHO’s International Health Regulations (2005) monitoring, and are part of the Global Health Security Agenda. Perhaps the greatest threat outlined in the manual is an infl uenza pandemic, which is both unpredictable and inevitable. In the worst-case scenario, there will be no protective vaccine for six months or longer after the virus is identifi ed, and even there will be a global shortage of doses. On this and other threats, the manual focuses on practical and indispensable things to know about infectious diseases that are most important for national political and operational decision-makers; it also links readers to more exhaustive WHO guidance. It has been developed in parallel with the creation of the WHO MOOCs (Massive Open Online Courses) on openWHO (https://openwho.org). Handbook structure The manual is structured in three parts. • Part One “Epidemics of the 21st century” provides vital insights on the main features of the 21st century upsurge and the indispensable elements to manage them. • Part Two “Be in the know. 10 key facts about 15 deadly diseases” contains key information about 15 diseases (Ebola Virus Disease, Lassa Fever, Crimean-Congo haemorrhagic fever, Yellow Fever, Zika, Chikungunya, Avian and Other Zoonotic Infl uenza, Seasonal Infl uenza, Pandemic Infl uenza, Middle East Respiratory Syndrome, Cholera, Monkeypox, Plague, Leptospirosis and Meningococcal Meningitis). This section provides tips on the interventions required to respond to epidemics of all these diseases. • Part Three “Tool boxes” gives an overview and summarized guidance on some other important topics, including: the role of WHO, the International Coordinating Group, laboratory diagnosis and shipment of infectious diseases substances, and vector control. The handbook enables the three levels of WHO – its Headquarters, Regional Offi ces and Country Offi ces to work effi ciently together by building the foundations of a shared conceptual and thinking framework, which includes common terminology. This “Managing epidemics” manual will be regularly updated. The next versions will incorporate additional infectious diseases. 11 PART I Epidemics of the 21st century 13 The re-emergence of infectious diseases The threat continues We are continuously learning about the unpredictable powers of nature. This is nowhere more true than in the continuous evolution of new infectious threats to human health that emerge – often without warning – from the natural environment. Already in these fi rst two decades of the 21st century, the world has been sharply reminded time after time of the degree to which people in all countries and on all continents remain chronically vulnerable to infectious diseases, known and unknown. In the 1970s, and for years afterwards, this remarkable progress, including the development of new vaccines, antibiotics and other treatments and technologies, led to a proclamation of a victory of mankind over microbes. Many experts thought it was “the time to close the book on the problem of infectious diseases” (Jesse Steinfeld, MD, US Surgeon General, 1969). Here lay the roots of a dangerous complacency. The microbes didn’t go away. They just went out of sight. Instead, the focus turned to chronic, noncommunicable diseases, which came to receive much more attention. But nature was by no means in retreat. In fact, it seemed to return and took many health institutions and decision makers by surprise. Since 1970, more than 1,500 new pathogens were discovered, of which 70% proved to be of animal origin: a connection that deserves renewed scrutiny. Not all of them have had a public health impact but some of them have become famous. They included the Ebola virus, in 1976, and the human immunodefi ciency virus (HIV), in 1983. Pause for a moment and refl ect that HIV, a relatively new disease in human history, has infected about 70 million people in just 35 years, and killed an estimated 35 million people in the same period. Consider also that in the last 40 years, Ebola has surfaced in almost 25 separate and deadly outbreaks, often after long spells in which it has apparently lain dormant. And now ask the question: Will history repeat itself? The answer must be: Yes, it will. A new HIV, a new Ebola, a new plague, a new infl uenza pandemic are not mere probabilities. Whether transmitted by mosquitoes, other insects, contact with animals or person-to-person, the only major uncertainty is when they, or something equally lethal, will arrive. The obvious follow-up question is: So what are we doing about it? This purpose of this handbook is to provide as many answers as possible. In doing so it examines a range of challenges and real or potential solutions, ranging from the medical and technological to the social and political. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 14 The 21st century: already a long series of scourges In order to try to see the road ahead more clearly, we need frequently to look over our shoulders – all the more so, because these early years of the 21st century have already been deeply scarred by so many major epidemics. Take plague, one of the most ancient scourges. A thing of the past? By no means. A major outbreak in Madagascar in 2017 led to a total of at least 2,417 confi rmed, probable and suspected cases, including 209 deaths. Most cases were of the more fatal pneumonic type which is also transmissible from person to person, but there were also several hundred cases of bubonic plague. Nine countries and territories with trade and travel links to Madagascar were put on plague preparedness alert. The lesson here is that, over time, diseases very rarely disappear. And there always seems to be room for new ones. SARS – Severe acute respiratory syndrome - was unheard of before 2003. But it affected more than 8,000 people, killing about one in ten of them, causing fear and panic across the world, and infl icting enormous economic damage, especially in Asian countries. In 2009, a novel infl uenza virus, H1N1, started to spread, creating the fi rst infl uenza pandemic of the 21st century. But – and this is a reason for cautious hope - it was not as severe as expected thanks to recent preparedness efforts. The importance of these efforts is a core issue in this handbook. In 2012-2013, a new virus surfaced in the Middle East, causing an epidemic of what became MERS – Middle East respiratory syndrome – that spreads fatally into many countries beyond that region. The Ebola epidemic in West Africa (Guinea, Liberia, and Sierra Leone) in 2014 was unlike the previous 24 localized outbreaks observed since 1976. Instead of being restricted geographically, this one seriously affected three African countries and spread to six other countries in three continents, and sparked alarm worldwide. In 2015, the Zika virus, transmitted by the Aedes Aegypti mosquito, triggered a wave of microcephaly in Brazil. This disease causes dreadful damage in the brains of unborn babies. Almost 70 countries, one after another, then experienced their own Zika epidemic. There are probably many more to come, because most of the global intertropical zone has a high density of Aedes Aegypti that transports the disease. And so a clear pattern continues to take shape. Old diseases – Cholera, Plague, Yellow fever among them – often return, and new ones invariably arrive to join them. About 40 outbreaks of cholera alone are reported to WHO every year. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 15 Gavi, the Vaccine Alliance, is an international organisation that was created in 2000 to improve access to new and underused vaccines for children living in the world’s poorest countries. The International Health Regulations (2005) or IHR (2005) are an international law which helps countries work together to save lives and livelihoods caused by the international spread of diseases and other health risks. The IHR (2005) aim to prevent, protect against, control and respond to the international spread of disease while avoiding unnecessary interference with international traffic and trade. The Pandemic Influenza Preparedness (PIP) Framework brings together Member States, industry, other stakeholders and WHO to implement a global approach to pandemic influenza preparedness and response. Its key goals include: - to improve and strengthen the sharing of influenza viruses with human pandemic potential; and - to increase the access of developing countries to vaccines and other pandemic related supplies. The Global Outbreak Alert and Response Network (GOARN) is a technical collaboration of existing institutions and networks who pool human and technical resources for the rapid identification, confirmation and response to outbreaks of international importance. 2000 2015 2016 2017 201820142013201220112010200920082007200620052004200320022001M AJ O R EP ID EM IC T HR EA TS S IN CE 2 00 0 LEGEND IN TE RN AT IO N AL C O LL AB O RA TI O N E FF O RT S TO FI G HT E PI DE M IC T HR EA TS GAVI IHR (2005) PIP Framework PIP Review IHR Review GOARN Ebola (West Africa) Cholera (Haiti) MERS-CoV H1N1 H7N9 Zika Yellow fever (Central Africa, Brazil) H5N1 SARS Epidemic Pandemic Timeline Major infectious threats in the 21st Century & collaboration mechanisms to fight against them Cholera (Yemen) Plague (Madagascar) PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 16 Faster and further with a greater impact This pattern has another, deeply troubling aspect. The epidemics in the 21st century are spreading faster and further than ever. Outbreaks that were previously localized can now become global very rapidly – just as fast, in fact, as an intercontinental aircraft can fl y. Thus, an individual fl ying from one side of the world can introduce a new disease into the other, within hours, and before even showing symptoms. And in this way, far from its origins, the microbe fi nds a new home. For example, the infl uenza pandemic of 2009 reached all continents in less than nine weeks. In recent outbreaks, yellow fever made it all the way from Angola to China, but, fortunately, there were only imported cases with no sustainable circulation in the mosquito population. In 2015, it took just one traveler returning home to the Republic of Korea from spending time in the Middle East to bring MERS back with him. The consequences: a Korean outbreak, 186 cases, 36 deaths, and outbreak-related losses of approximately US$ 8 billion, all in the space of two months. Thus, 21st century epidemics can spread more widely and more quickly, potentially affecting ever-greater numbers of people. They also can have a ruinous impact on the economy of the affected country and spill over into to the global economy, disrupting travel, trade and livelihoods. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 17 Ready and able to detect the next outbreak Given the effects of globalization, the intense mobility of human populations, and the relentless urbanization, it is likely that the next emerging virus will also spread fast and far. It is impossible to predict the nature of this virus or its source, or where it will start spreading. But we can say, with a high degree of certainty, that when it comes, there will be (a) an initial delay in recognising it; (b) a serious impact on travel and trade; (c) a public reaction that includes anxiety, or even panic and confusion, and (d) this will be aided and abetted by media coverage. The concept of global health security, a central issue in this handbook, represents a new determination by, or on behalf of, human society to protect itself from the health impact and social disruption caused by outbreaks. It encompasses a spectrum of ways and means that offer worldwide protection against the threats of infectious diseases, backed by revised and more powerful International Health Regulations (2005). But to make the world safer, global health security depends crucially on much greater awareness, cooperation and collaboration between individual countries, agencies, organizations and communities. The continuing scientifi c uncertainty around disease emergence requires even more collaboration and global awareness than has previously existed, not least to improve early detection. Recent outbreaks, however, show how diffi cult this can be, even with good public health surveillance systems. Early recognition of emergence typically starts with clinicians who can detect unusual clusters of severe cases, take samples to allow laboratory diagnostics and alert surveillance units. Often, poorer communities around the world, especially those in remote areas, lack easy access to care. This has major implications when an infectious threat occurs. The Ebola outbreak in West Africa remained undiagnosed for more than two months. This time lag allowed the virus to spread unseen, and to reach capital cities where the outbreaks grew into large epidemics. In such circumstances, it is essential to raise clinicians’ awareness and provide them with the relevant knowledge and diagnostic tools to enable them to perform effectively as detectors and fi rst-line responders. As we have signaled earlier, another indispensable element of increasing health security is preparedness. This should be fl exible enough to adapt to any novel agent, but should be directed primarily at known pathogens because some of them are likely to behave differently than previously. The recent plague outbreak in Madagascar, described earlier, is a good example of known diseases with new patterns. In addition, the fear generated by the emergence of a previously-unknown infection may be greatly out of proportion to its real public health impact. Fear often generates inadequate decisions or inappropriate behaviours, including stigma of certain at-risk populations. The impact on travel and trade and on economies can be disproportionate, as it has been seen in the Republic of Korea during the MERS epidemic. To a certain extent, global health security also encompasses economic and human security. Thus, risk communication is critical to minimise the social, political and subsequently economic impact of an epidemic, and this is also a major focus of this publication. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 18 One Health and emerging and re-emerging pathogens Epidemics are sparked either by the re-emergence of pathogens that have been familiar for a long time, but now threaten new, immunologically vulnerable populations, or are newly-emerging ones. They come in a daunting array of species of bacteria, viruses, fungi and parasites. Some are borne in contaminated water or food; others are carried in the air we breathe and by human touch. As noted earlier, 70% of emerging human pathogens come from animals. This is a burgeoning threat, because animals are intensively farmed, transported for trade and kept in close contact with other species and humans in market places. Early detection often relies on close collaboration between the animal health and wildlife sectors (the “One Health” approach); otherwise early signals of emergence in animals or the environment are often missed. This collaborative approach, another pivotal element of global health security, can also contain outbreaks at an early stage by reducing animal-to-human transmission. Because these diseases are rare and outbreaks are generally contained quickly, these epidemics have not been a priority among the research community or manufacturers in the development of medical countermeasures. Nevertheless, more research is needed to identify precisely the modes of transmission and medical countermeasures. Today’s harsh reality is that there is as yet no vaccine or treatment for most emerging diseases. This is not as hopeless as it might seem at fi rst. WHO has developed a Research & Development (R&D) Blueprint for action to prevent epidemics: it is a global strategy and preparedness plan that allows the rapid activation of R&D activities during epidemics. Its aim is to fast-track the availability of effective tests, vaccines and medicines that can be used to save lives and avert large scale crisis. However, public health interventions have to rely primarily on social-distancing measures to reduce human transmission, and on controlling the source of infection (for instance by culling of infected animals/elimination of the reservoir). Thus, to prevent the spread of emerging diseases, it is vitally important to ensure early detection of a new pathogen and the start of human-to-human transmission. Enhanced international information and virus sharing among laboratories is being actively encouraged and pursued. This is necessary to enable research and development of countermeasures. The results of this sharing are potentially life-saving interventions (vaccines, diagnostics and therapeutics). But they also need to be underpinned by specifi c mechanisms to ensure they become widely available and accessible on an equitable basis. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 19 Known epidemics: still a severe threat Fortunately, control programmes are already long-established and widely-applied for some known epidemic diseases, such as cholera, HIV infection, infl uenza, meningitis, malaria, tuberculosis and yellow fever. However, even if medical countermeasures are available, these diseases remain a threat for many of the world’s populations, either because of their rapidly evolving nature (e.g. infl uenza) or because equitable access to effective public health measures is diffi cult. There are many reasons for limited access to vaccines: production capacity does not meet the demand (e.g. yellow fever, pandemic infl uenza), explosive outbreaks exhaust the available vaccines (e.g. meningitis), or the absence of markets prevents access to the intervention in case of emergencies (e.g. oral cholera vaccine). In addition, in many affected countries, the weakness of the existing health care system prevents effective access to medical interventions (diagnostics and treatment). Therefore, although it is reassuring that sound knowledge and a range of potential control interventions are available, expert guidance must be constantly updated to incorporate scientifi c and technological progress. Equally important, access to life-saving interventions must be improved in all settings worldwide. The current global strategy is to reach elimination or eradication of these diseases through vaccination or investment in and implementation of other countermeasures. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 20 Strengthening health systems: essential in epidemics In order to mitigate the impact of epidemics, protect the health workforce and ensure continuity of health services during and after them, stronger health systems are needed. Epidemics and pandemics put these systems under great pressure and stress. The sudden infl ux of large numbers of sick individuals to health facilities stretches the systems’ capacity and resources, even more so and more noticeably where resources are already scarce. When an epidemic emerges and spreads, it inevitably draws most of health responders’ attention and monopolizes most of the health system’s human and fi nancial resources, as well as medical products and technologies. People, efforts, and medical supplies all shift to respond to the emergency. This often leads to the neglect of basic and regular essential health services. People with health problems unrelated to the epidemic fi nd it harder to get access to health care services. Some may die as a result, if the disruption overwhelms the health system. Mortality rates of other diseases for which people could not get treatment may rise. Furthermore, health care settings, and especially emergency rooms, can become hubs of transmission. Many people get infected there, if prevention and control measures are not properly implemented. This is particularly true for unknown and emerging pathogens (for instance, MERS). A delay in the recognition of the disease will lead to delay in applying the right protection measures. Infected patients will be able to transmit the disease because health care workers, family members and other patients will not know how to protect themselves. Because health care settings and emergency rooms are usually crowded, the lack of appropriate infection prevention and control for example through triage, isolation, and other precautions can be very signifi cant. Health systems resilience after epidemics may be challenging for unprepared health systems. Indeed, if the health system is ill-prepared to cope with epidemics of infectious diseases, health care workers, at the frontline of the response, may themselves become infected and die. Tragic as such cases are, they have wider consequences. In countries where there are health staff shortages, the loss of several more health workers further weakens the health system. It takes years to train new medical staff and rebuild the health workforce. In the meantime, other constraints are burdening the health system that still has to provide the usual and regular services. Long-term substantial investments should therefore be made to strengthen health systems so they are able to provide safe, effective and qualitative health services before, during and after epidemics. Critical elements include an appropriate health fi nancing system and a fi t-for-purpose workforce that is trained, safe and provided with personal protective equipment. In addition, access to essential medical products and technologies and a business continuity plan are essential to ensure that health systems are strong enough to withstand the increased needs and to mitigate the impacts of very disruptive epidemics. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 21 14 8 9 30 36 10 2 4 2 6 4 9 9 13 7 9 9 34 36 9 13 7 9 5 8 6 7 8 7 13 15 17 7 10 7 10 10 6 5 13 26 9 22 16 12 8 5 7 14 6 1 13 4 4 57 4 7 4 7 9 11 1313 7 11 24 1 7 17 3 16 2 3 1 6 6 7 1 22 11 13 1 1 15 5 11 7 115 5 9 7 14 5 30 4 7 16 8 6 6 10 6 4 13 54 7 6 2 6 5 12 5 12 10 8 7 7 1 7 16 11 11 9 15 5 5 5 10 9 11 22 3 22 2 7 2 3 41 1 2 7 1 6 1 5 22 7 8 22 5 2 6 4 11 3 5 1 12 11 4 32 3 Burden of epidemics: illustrations Epidemic events* globally, 2011 – 2017**: A total of 1,307 epidemic events, in 172 countries * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Source: data reported to WHO and in media The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 22 Epidemic events* globally, 2011 – 2017**: A total of 1,307 epidemic events Number of epidemic events* by disease and year 2011 2012 2013 2014 2015 2016 2017** TOTAL Yellow fever Chikungunya Viral haemorrhagic fever Ebola virus disease Marburg virus disease Crimean-Congo haemorrhagic fever Rift Valley fever Cholera Typhoid fever Shigellosis Plague Lassa fever West Nile fever Zika virus disease Meningitis MERS-CoV Infl uenza A Monkeypox Nodding syndrome Nipah virus infection * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Source: data reported to WHO and in media PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 23 17 8 1 3 1 62 20 25 8 2 11 14 5 1 1 12 10 2 1 5 1 51 23 24 7 1 15 20 3 6 1 1 8 3 6 1 47 5 28 6 2 15 5 19 10 7 1 1 2 29 11 1 8 1 37 2 29 10 3 11 7 19 17 9 1 4 27 4 7 1 44 8 4 7 2 11 19 19 12 10 2 1 10 14 6 3 7 4 42 3 2 6 7 18 54 23 7 5 2 4 4 4 1 2 13 5 25 14 1 3 6 10 52 23 8 9 5 57 95 10 22 4 49 14 308 75 113 47 23 91 137 137 57 51 10 2 5 2011 179 183 164 197 182 213 189 220 200 180 160 140 120 100 80 60 40 20 0 2012 2013 2014 2015 2016 2017** * Analysis excluded Poliomyelitis. The following epidemic and pandemic diseases were analysed: Avian Infl uenza A(H5N1), A(H7N9), A(H7N6) A(H10N8), A(H3N2), A(H5N6), A(H9N2), Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV, Monkeypox, Nodding syndrome, Nipah virus infection, Plague, Rift Valley fever, Shigellosis, Typhoid fever, Viral haemorrhagic fever, West Nile fever, Yellow fever, Zika virus disease. If a disease caused more than 1 epidemic event by year in a country, it was only counted once for the year it occurred in that country. Includes cases imported or locally transmitted. ** WHO/IHM data as of 12 January 2018 (note: 2017 data is not complete) Number of epidemic events* by year** Source: data reported to WHO and in media PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 24 The face of epidemics and pandemics has changed in the recent past and continues to do so. Many new factors contribute to an increase in the transmissibility and severity of infectious diseases. New lifestyles spread diseases further New and more intense factors amplify the transmission of diseases, either because they increase contacts between people, or between animals and people. In an era of rapid global change, many of these factors are almost inevitable. Among them are the fast and intense mobility of people, with increased transport and international travel, and greater inter-connectivity between megacities which are major transport hubs for aircraft, trains, road vehicles and ships. At the same time, globalization means increased trade among countries as well as greater movement of people within and between them. For decades, more and more people have been migrating from the countryside into cities, in search of better jobs and improved living standards. The unprecedented levels of urbanization and swelling populations of city dwellers inescapably pose greater risks of infectious disease transmission. These risks apply at least equally to densely populated areas on the periphery of cities, where rural areas overlap with them. Here, close and repeated contacts between people and livestock, domestic animals and wildlife raise the likelihood risk of new epidemics. To make matters worse, these peri-urban areas tend to be poorer, and local people have less access to health care facilities. The double jeopardy here is that their infections may go undetected and untreated, while the options for detection, prevention and control are reduced. The Ebola outbreak in 2014 has dramatically demonstrated this. Regrettably, the early years of the 21st century have seen many humanitarian emergencies, the massive displacement of populations fl eeing from civil unrest, political instability, confl icts wars and natural disasters. Millions of people have been uprooted from their homes and become either refugees, asylum- seekers or economic migrants, and fi nd themselves living in conditions, often overcrowded, that also increase infection risks. Challenges and risk factors for 21st century epidemics Potentially hazardous changes are also taking place in the use of land, agricultural practices and food production, such as live poultry and animal markets, and deforestation – which also leads to increased contact between people and wildlife. Some of these animals – monkeys, for example - are likely sources of new pathogens. Finally, ecological changes, such as climate change, also contribute to disease transmission. Other factors contribute to increase the virulence and mortality of epidemic diseases. Chief among them, as we have noted earlier, are limited access to health care, and poor health care systems that have inadequate infection prevention and control practices. The confl icts and wars referred to above not only cause civilian casualties and displacements: they destroy health care facilities exactly when and where they are most needed. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 25 Revisiting traditional control measures We have also seen that many traditional containment measures are no longer effi cient. They should therefore be re-examined in the light of people’s expectations of more freedom, including freedom of movement. Measures such as quarantine, for example, once regarded as a matter of fact, would be unacceptable to many populations today. The use of antibiotics to treat infections has been a turning point in the 20th century. Antimicrobial resistance is now on a rise. This is a major concern because a resistant infection may kill, can spread to others, and requires fi nding new ways to treat and limit the spread of the disease. Antimicrobial resistance occurs naturally, but is facilitated by the inappropriate use of medicines, for example using antibiotics for viral infections such as cold or fl u, or using antibiotics for animal growth in the animal sector. Among major infectious diseases, the treatment of tuberculosis is the most affected, and there are now strains of the microorganism that are multi-drug resistant. Equity and solidarity Epidemics are complex events: complex in their origins, their spread, their effects and their consequences – which can be at one and the same time medical, social, political and economic. The global impact of a single pathogen may vary signifi cantly between settings and there is no one-size-fi ts-all intervention strategy. Equity and solidarity issues are often part of the picture: access to medical countermeasures remains diffi cult, especially for low-income countries and countries facing humanitarian emergencies, and this diffi culty is worsened when vaccine or treatment production is limited. Market mechanisms do not ensure a fair distribution of resources based on public health demands. Global mechanisms are needed to ensure fair access to life-saving interventions during crises. A number of organizations are dedicated to this goal (among them are CEPI, the Coalition for Epidemic Preparedness Innovations; the International Coordinating Group; GAVI, the Vaccine Alliance; the Pandemic Infl uenza Preparedness Framework) but more efforts are required. Epidemics of rumours: a new risk to health A new word has entered the public health vocabulary: “infodemics”. These can be defi ned as the rapid spread of information of all kinds, including rumours, gossip and unreliable information. They are spread instantly and internationally through the growing popular use of mobile phones, social media, the internet and other communication technologies. A proliferation of web-based “experts” with diverse and often contradictory views can generate confusion, anxiety and even panic in times of serious infectious outbreaks. False or misleading information is dangerous. It can cause widespread public reluctance to adopt well- founded infection control measures promoted by health authorities – and thus delay essential interventions. This is why risk communication, a set of sophisticated skills, is increasingly employed by health authorities, agencies, physicians and professional health personnel. It is more important now than ever to learn and apply them. The latest and most accurate information must be conveyed frequently, and uncertainties related to an epidemic must be acknowledged in order to maintain credibility and public trust. Thus, we are recognizing that the complexity of 21st century epidemics and their prevention and control require not just new technologies techniques, but new skills and new attitudes all across the public health community. Risk communication is examined at greater length in a later section of this handbook. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 26 A whole-of-society approach is needed to tackle 21st century epidemics so that all the diverse disease drivers are taken into consideration: genetics and biological factors, ecology and the physical environment; human behaviour and demographics; social, political, and economic factors, and so on. This increasing convergence of many factors that drive and amplify outbreaks requires multi- disciplinary, multi-sectoral and multi-faceted approaches. Moreover, because epidemics are social problems as much as medical ones, we need to move beyond the traditional biomedical approaches to them. Social sciences should be an integral part of surge capacities adding anthropologists to the team of fi rst responders. Such a change enables issues of fear and trust to be addressed within the social context. Engaging communities and empowering them in advance as part of preparedness ensures that there is a better understanding of the human ecology. This will link community and biomedical perspectives for enhancing effective partnerships, ensuring that pre- existing relationships are built to respond to epidemics. Key insights into infectious disease epidemics PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 27 Because new infectious disease threats usually start locally, it is important to understand their dynamics in order to deny them the opportunity to spread further among people and overwhelm health systems. The dynamics of epidemic and pandemic diseases typically occur in four phases, although not all epidemic diseases necessarily go through each phase. The fi rst phase is the introduction or emergence in a community. The second phase is an outbreak with localized transmission, where sporadic infections with the pathogen occur. In the third phase, the outbreak amplifi es into an epidemic or pandemic - the pathogen is able to transmit from human to human and causes a sustained outbreak in the community, threatening to spread beyond it. The fourth phase is reduced transmission when human-to-human transmission of the pathogen decreases, owing to acquired population immunity or effective interventions to control the disease. These four phases are illustrated on this page. The dynamics of epidemics, as described above, defi ne the response and the sequence of interventions that then become necessary. Here, there are fi ve crucial stages. First is the anticipation of new and re-emerging diseases to facilitate faster detection and response; followed by their early detection of emergence in animal and human populations; the third stage is the containment of the disease at the early stages of transmission; followed by the control and mitigation of the epidemic during its amplifi cation; and fi fth, the elimination of the risk of outbreak or eradication of the infectious disease. These stages are elaborated in the illustration, and in the section that follows it. Epidemic phases INTRODUCT ION OR EMERGENCE LOCAL IZED TRANSMISS ION AMPL I F ICAT ION REDUCED TRANSMISS ION IMMUNITY PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 28 Anticipation: In this fi rst stage of response, emergence cannot be predicted, but it can certainly be anticipated, and the anticipation of risks enables a focus on the most likely threats. Anticipation encompasses forecasting the most likely diseases to emerge, and the quick identifi cation of the drivers that will worsen the impact or facilitate the spread. Preparedness plans, based on lessons learned from past experiences, should contain a variety of scenarios to allow for a reactive response to the unexpected. Early detection: Emerging and re-emerging diseases include new ones about which there is little scientifi c knowledge. These, therefore, often require investigation into their sources at the same time as the use of coordinated, rapid-containment measures. New diseases require new interventions. And because they appear irregularly or rarely, there is a need for constant vigilance, proactive risk assessment and the development of new management tools. Early detection allows the rapid implementation of containment measures, which are the key to reducing the risk of amplifi cation and potential international spread. Early detection begins at the health care setting, so health care workers must be trained to recognize potential epidemic disease, report quickly an unusual event (such as an unusual cluster of cases or deaths). Their role is also to reduce the risk of community transmission by isolating severely-ill patients; to prevent household transmission by protecting health care givers at home; and to reduce the mortality rate. Health care workers must also know how to protect themselves and employ infection prevention and control measures and how to avoid outbreaks amplifi ed in health care facilities. Epidemic phases and response interventions Anticipation Early detection Control and mitigation Elimination or eradicationContainment Introduction or emergence Localized transmission Amplification Reduced transmission Response interventions Epidemic phases PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 29 Once a new disease is recognized by the health system, early laboratory confi rmation is essential. When this cannot be done at country level, the affected countries must be confi dent they can count on the support of a network of more sophisticated regional or global laboratories. It is critically important for global health security that there is a system for safely taking samples and shipping specimens to relevant laboratories in full compliance with biosafety and biosecurity regulations. Containment: Effective and rapid containment of emerging diseases is just as vital as early detection in order to avoid a large scale epidemic. Rapid containment should start as soon as the fi rst case is detected regardless of the etiology, which is most likely to be unknown. It requires skilled professionals to safely implement the necessary countermeasures. Pre-training of these professionals is essential to guarantee the safety and effi ciency of the operations. Control and mitigation: Once the infectious disease threat reaches an epidemic or pandemic level, the goal of the response is to mitigate its impact and reduce its incidence, morbidity and mortality as well as disruptions to economic, political, and social systems. Elimination or eradication: Control of a disease may lead to its elimination, which means that is suffi ciently controlled to prevent an epidemic from occurring in a defi ned geographical area. Elimination means that the disease is no longer considered as a major public health issue. However, intervention measures (surveillance and control) should continue to prevent its re-emergence. Eradication of a disease – much more diffi cult and rarely achieved - involves the permanent elimination of its incidence worldwide. There is no longer a need for interventions measures. Three criteria need to be met in order to eradicate a disease: there must be an available intervention to interrupt its transmission; there must be available effi cient diagnostic tools to detect cases that could lead to transmission; and humans must be the only reservoir. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 30 Response tips and checklists A comprehensive outbreak response is always complex, comprising many elements that should be harmoniously coordinated. The following response tips are used to organize ideas and to make sure no important point is overlooked. In this handbook, specifi c tips are listed for each disease which will help keep focus on essential elements of each response. They are organized into four main blocks: • Coordinating responders (C) • Health Information (HI) • Communicating risk (C) • Health Interventions (HI) The checklists will help you assess what is important and necessary for the response. The outbreak response varies depending on the disease. For some diseases treatment is essential; for other diseases, vaccination is vital. C Coordinating responders C Communicating risk HI Health Information HI Health Interventions Note: Although Communicating risk (C) is part of Health Interventions (HI); it is seen here as a separate component in order to underscore the importance of risk communications. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 31 Coordinating responders An outbreak is by defi nition an exceptional event which often requires extra human and fi nancial resources and may also rely on additional partners, agencies and other sectors. Strong coordination is essential at all times to ensure that all those resources and partners are working effectively together to control the outbreak. WHO is often expected to lead the international response to support national health authorities. Effective coordination requires a dedicated physical space (usually an emergency operation centre); various tools to ensure optimal organization of meetings and fi ling of documentation (such as a list of contacts, and a meetings tracking system); a joint plan of action regularly updated as the situation evolves, to describe the interventions needed and the distribution of roles and responsibilities among stakeholders; and fi nally tools to ensure communication between the various stakeholders engaged in the response (phone numbers, a dashboard, maps, and a directory). Coordinating responders checklist ✔ What are the characteristics of the event that describe it as a crisis? ✔ Who are the people, groups and organizations who should work for the response? ✔ What should they do? (terms of reference, functions) ✔ Where can responders meet? (emergency operation centre) ✔ How do they share information? (share point, telephone numbers, generic email) For more information about coordinating responders: • Public Health Emergency Operations Centre Network (EOC-NET) http://www.who.int/ihr/eoc_net/en/ • WHO Emergency Response Framework (ERF) http://www.who.int/hac/about/erf/en/ MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 32 Health Information In every event, information is necessary to monitor it, measure the impact of interventions and to guide decision-making throughout the crisis. There are two particular types of information: surveillance of the disease, and information on the interventions (process and output indica- tors), which shows the coverage and impact of the interventions being performed. Surveillance provides information on the number of cases and deaths by period and place (people, time, and place). Information on the interventions enables knowing which ones are performed and what is their coverage and impact. Health Information checklist Surveillance ✔ Is there a case defi nition shared by all stakeholders? ✔ Which laboratories are involved in the testing /confi rmation of cases and deaths, and where are they situated? ✔ Is there an updated epidemiological curve and mapping of cases and deaths? ✔ Which are the risk groups, by gender and age? Interventions ✔ What is the target population? ✔ What material and human resources are needed and how much? ✔ What are the indicators of success? (e.g. vaccine coverage, house- holds targeted, number of people treated) PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 33 Communicating risk During the evolution of any major outbreak, cases and deaths will inevitably increase. An epidemic is the rapid spread of infectious disease to a large number of people in a given population within a short period of time. Similarly, there may well be another kind of epidemic – the rapid spread of information of all kinds, including rumours, gossip and unreliable information. We describe this phenomenon as an “infodemic”. Infodemics, like epidemics, can be managed. Field epidemiology is an important part of outbreak response. It encompasses three main areas: (1) monitoring and identifying health threats, (2) outbreaks investigation, and (3) actions for mitigation and control. Similarly, successful management of infodemics will be based on (1) monitoring and identifying them, (2) analysis of them, and (3) control and mitigation measures1. Risk communication is an essential intervention in any response to disease outbreaks, and is equally necessary to manage infodemics. Communicating risk in epidemics involves two-way communication that is dynamic and evolving as the outbreak develops. Outbreak risk communication involves three main strands that must work together. 1. Talk. Authorities, experts and response teams must quickly relay information on the nature of the event and the protective measures that people can take. We can use mass media including television, radio, newspapers and internet; social media and text-messaging; community radio; and leafl ets and posters. We can use social mobilizers and frontline responders; encourage community engagement; as well as face-to-face communication via trusted interlocutors such as community leaders, religious fi gures and community health workers. We must use translational communication approaches to develop messages that are appropriate for the target populations in terms of language, educational level and cultural contexts. 2. Listen. Responders, experts and authorities must quickly assess and understand the fears, concerns, perceptions and views of those affected; and tailor their interventions and messages to address such concerns. This requires the use of social science and community engagement expertise and methods. 3. Manage rumours. Disease outbreaks are often accompanied by the presence of false rumours and misinformation. Responders need to have ways to listen to such misinformation and correct examples of it in appropriate ways without delay. 1 This is called “infodemiology”. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 34 Communicating about the risks during outbreaks leads to specifi c outcomes. First, early, transparent and understandable communication on the event establishes lines of dialogue with affected populations and stakeholders, and builds trust in the response. This type of communication must have facts and information (that cater to the head); and include messages that acknowledge and respond to people’s concerns and fears (catering to the heart). Second, frequent but evolving communication will help create a trusted and dynamic relationship that can deliver advice on protective behaviors that populations and individuals can adopt. Third, communication must scope the risk in lay language, and also propose practical actions people can take. It must identify and help enable changes in people’s behaviours or practice (a temporary change) that can reduce exposure to and protection from the infectious hazard. Fourth, communication must display accountability by keeping people updated on the situation, on what is being done, and the impact of those actions in bringing the outbreak under control. Communicating risk checklist ✔ Has the situation been well analyzed in terms of audience, sources and specifi city of the context? ✔ Are tools in place in place to monitor an infodemic? Is monitoring reactive and adaptable enough? ✔ Has translational communication taken place (to transform scientifi c information into lay language and format)? ✔ Are the communication channels (and messengers) adequate, effective and acceptable to communities? (culturally, cost-effectively)? ✔ Is there a plan to communicate regularly with the various audiences? ✔ Have all personnel and volunteers in the risk communication response been trained in risk communication approaches, and consistent messaging? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 35 Health Interventions Each disease requires a different set of health interventions with the objectives of reducing (a) transmission, (b) severe morbidity and mortality (c) the impact on health systems and also on the political and other sectors. Health Interventions checklist ✔ What are the key interventions needed to control the outbreak at this stage of the event? ✔ Who should implement them? ✔ How is the impact measured on morbidity, mortality, transmission, and whole of society? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 36 Six critical functions of the Incident Management System (IMS) For more information about the management of events under the ERF: http://www.who.int/hac/about/erf/en/ The Emergency Response Framework (ERF) is an internal WHO tool that outlines a set of procedures to better respond to emergencies. Under this framework, for any emergency that requires a WHO operational response, the Organization activates the Incident Management System (IMS); recognized best practice for emergency management. WHO has adapted the IMS to consist of six critical functions. The four blocks and response tips are integrated into the Incident Management System. Although, all six functions of the IMS are critical for a successful response, the four blocks will highlight what is specifi c for each disease. Operations support & logistics Finance & administration Health operations & technical expertise HEALTH INFORMATION HEALTH INTERVENTIONS COMMUNICATING RISK Information & planning HEALTH INFORMATION Partner coordination COORDINATING RESPONDERS Leadership/ Incident management COORDINATING RESPONDERS PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 37 FOCUS 1 Community engagement during epidemics Defi ning a community “Community” is a broad term that can be applied to a variety of situations. It defi nes a distinct group of people who have a sense of belonging together. A community may be defi ned through the sharing of: • A common geographical location; • Common values or interests; • Common identity; • Etc. With new technologies, a community may be totally virtual, for instance a group of people sharing interests and points of view on social media. Why engage communities People live in unique social-cultural contexts, with relationship dynamics, and their own perception of risks, and trusted sources of advice. These all infl uence if they accept health advice or not. Experience has shown that merely telling people what to do, however scientifi c, does not always work. Engaging them is more effective. Even more fundamentally, people have a right to information that could protect their health and save lives, social fabric and economic well- being. Communities, when engaged are the frontline in detecting and managing epidemics. They are most affected and have the greatest infl uence in anticipation and preparedness as new diseases emerge or old ones re-emerge. They can detect outbreaks, and help in containment to prevent epidemic amplifi cation. They are able to implement mitigation measures (through change of individual and family practices change; implementing community measures and enabling changes at the systems level) to bring epidemics under control. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 38 Three elements of community engagement Disease outbreaks and epidemics are complex phenomena with three aspects that are intimately intertwined: medical, social and political. Community engagement is an approach to address the social (and to some degree the political) aspects of epidemics. Community engagement is essential for the effective control of infectious diseases, through acceptance of public health interventions. It is based on three elements: 1. Establishing a dialogue between responders and communities to understand the perceptions and beliefs on both sides, to identify the specifi c cultural and social patterns of transmission that exist at community level. 2. Building trust through this mutual understanding to fi nd joint solutions to reduce transmission. 3. Empowering communities, providing them with necessary medical and other supplies to implement the measures required to stop the disease, and progressively transferring knowledge for sustained and safe interventions within the community. A key community to empower during outbreaks are health care workers, and volunteers who are often the frontline responders. These frontline workers are “the face” or representatives of the whole outbreak response, to the community. Their attitude towards community members and their collaboration in implementing health advice can have signifi cant infl uence on how the advice is perceived and accepted, or rejected by community members. Key points of health action in epidemics that require intensive engagement of communities (affected populations as well as health care workers and frontline responders themselves) include: 1. Detecting an outbreak and detection of newly infected people (case detection, contact tracing); 2. Minimizing harmful practices (at individual and community levels) that can increase susceptibility and exposure; and adopting protective practices (medical and non- medical); 3. Seeking and providing health care as advised (in the household, community and health facility); 4. Re-integrating of survivors back into the community and to minimizing stigma; 5. Identifying and managing misinformation and rumours. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 39 Ten things to know 1. Disease outbreaks affect the social fabric of communities. A community is a social network, and infectious diseases outbreaks are deeply linked to the social life, the structure of society and people’s interactions. They spread through personal and social contacts and links at home or during professional and recreational activities. 2. Communities are the main actors in preventing, identifying, responding and recovering from the physical, psychological, social and economic impacts of epidemics. Communities are not passive subjects of interventions. 3. Epidemics are by nature rapidly evolving. The time pressure is particularly challenging for community engagement. The beginning of the outbreak is a crucial time to build the necessary trust with the population who can break the transmission cycle. Any outbreak response that builds on existing and trusted community engagement systems and work with trusted individuals and interlocutors are more likely to succeed. 4. Community understanding of diseases and their spread is complex, context-dependent and culturally mediated. Thus, a one-size- fi ts-all approach is neither desirable nor effective. 5. Communities are multi-layered, and power dynamics exist between individuals, groups and networks. Social scientists can help analyse these dynamics and work with specialists in health education, health promotion and local communities. There are simple tools that can assess relevant perceptions and beliefs for any outbreaks response. Together they can design the messages and interventions necessary to raise awareness, and adapt or change behaviours to meet the demands of a new infection. Embedding social scientists in response teams will also help to monitor how people adapt public health measures to different social contexts, and whether these are implemented in a way that respects social and cultural systems. 6. Community engagement helps to strengthen and ensure resilience to future outbreaks: when people have already learned how to implement their own solutions, they will be better able to deal with the next outbreak. 7. The approach and messaging directed towards each community has to evolve with the epidemic and incorporate new messages and communication methods as it unfolds. These messages must also proactively detect misinformation and rumours. Effective community engagement limits the opportunities for misunderstandings and the proliferation of rumours, and it mitigates the spread of fear and anxiety. 8. Identify people that the community trusts and build relationships with them. Involve them in decision-making to ensure interventions are collaborative, contextually appropriate and that communication is community-owned. 9. Two-way communication should be achieved through the most socially- acceptable and effective channels. Messages must be “translated” into local language, local context and to match the education levels and preferences (e.g. visual, written or oral cultures) of the target population. All communication with communities should be transparent, timely, easy-to-understand, acknowledge uncertainty, address affected populations, link to self-effi cacy, and be disseminated using multiple platforms, methods and channels. 10. Disease creates fear which often leads to practices that further amplify the epidemic. These can be both individual and collective. They can relate to the transmission of the disease, or the stigma, and extreme stress on the ties that bind communities. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 40 Ensuring effective community engagement To ensure effective community engagement: 3 elements are needed for communities and for fi eld responders. For communities: • Knowledge: communities must know what the disease is, how it is transmitted, and how to protect against it (social mobilisation messages); • Trust: it is the most important determinant to ensuring communities heed public health advice. Communities must be consulted, engaged, and whenever possible participate in identifying and implementing response measures that communities and responders want above all to treat patients and stop the epidemic; • Self-effi cacy: communities must be able to implement control measures (e.g. access to soap and water, to gloves, to waste management services, to transportation, to safe burial teams, etc.). For fi eld responders: • Understand: Field responders need to understand the local perceptions of the disease and of the response measures; • Listen: Field responders need to listen to communities’ fears and beliefs and adapt their own behaviours accordingly; • Support: Field responders need to support communities’ participation, ownership and resilience. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 41 FOCUS 2 Risk communication – a life-saving action in public health emergencies The essence of risk communication Risk communication is one of the key pillars of response to outbreaks. It refers to the real-time exchange of information, advice and opinions between health experts or offi cials and people who face a threat (hazard) to their survival, health or economic or social well-being. Its ultimate goal is that everyone at risk is able to take informed decisions to mitigate the effects a disease outbreak and take protective and preventive action. Effective risk communication not only saves lives and reduces illness (by informing people on how to protect their health), it also enables countries and communities to preserve their social, economic and political stability in the face of emergencies. For these reasons, risk communication is one of the core capacities that all countries have agreed to develop in order to prevent the international spread of disease and other dangers as required under the International Health Regulations (2005). PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 42 21st century aspects change and complicate risk communication There has been a paradigm shift from telling people what to do (message-based communication) to systematically listening to those affected, mainly due to new communication and media technologies and the way practices have evolved in the 21st century. The three big changes here are: 1. Experts and authorities are less trusted; 2. People now seek health advice mostly on public on-line sources, and their trusted social networks; 3. News media now function all day, every day. In addition, there is an increase of citizenship journalism and social media, as well as the rise of opinion versus well- sourced and referenced stories. In disease outbreaks and epidemics, life-saving decisions need to be made rapidly and actions must follow promptly, with the support of an informed public. Epidemics are unpredictable and alarming events that generate great anxiety in the general public, which can lead to extreme behaviours. Epidemics and the way they are managed have a high political profi le and capture the news media’s attention quickly leading to intense media interest (at national and international levels). Furthermore, emergency and outbreak communications now take place in a variety of contexts: • In a shifting complex, crowded environment: information is incomplete and many different actors are exchanging public health information and competing for authority. • Where communications are diverse: these include public communication, supporting national governments in risk communication, strategic communication, communication with affected communities and response personnel, media relations, knowledge transfer, message development, partner communication, internal communication and health promotion functions, etc. • Where risk communication is an under- resourced priority with a lack of investment in skills, resources and expertise at country level. • Where there is an increased public demand for participation in policy-making and for self-determination. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 43 Making it effective • Risk communication only works when there is communication based on trust between those who know (experts), those in charge (authorities or response teams) and those affected (communities). Without trust, people are unlikely to follow the advice given. Listening to and understanding peoples’ beliefs, concerns and perceptions is just as important as providing them with facts and advice. Explaining honestly what is known and admitting what is uncertain is essential. Effective risk communication thus depends on the credibility of those giving advice; their expressions of caring and empathy; and their ability to identify with people at risk. • Perception is key: - Experts and affected communities may not view the same infectious hazard – e.g. a disease outbreak – the same way. While experts depend on risk analysis based on biomedical and epidemiological data, affected communities use more sub- conscious pathways to defi ne risk; - People’s perception of risk can be affected by their beliefs, culture, education, political viewpoints, social norms and prior experience amongst others; - There are tried and trusted social science methods and approaches which can be used in epidemics to gauge perceptions. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 44 Ten things to know and do 1. Build trust • People must trust those responsible for managing the outbreak and for issuing information about it. Public confi dence that a government or agency is acting fi rst and foremost to safeguard their health will infl uence compliance with recommended control measures, and thus hasten outbreak containment. • Accountability is key: communicators must demonstrate that they and outbreak managers are accountable for what they say, promise, and do. • Evidence shows that to build trust, risk communication interventions should link to functioning and accessible services, be transparent, timely, easy-to-understand, acknowledge uncertainty, address affected populations, link to self-effi cacy and be disseminated using multiple platforms, methods and channels. • The building blocks of trust include: - Being perceived as experts with credibility by providing expert advice that is correct and accurate and being consistent with other trusted agencies and entities; - Being perceived as having a good character by telling the truth and not omitting important information, and acting on promises; - Identifying with the affected population as sharing the same concerns and fate; - Exhibiting good will through empathy and caring in messages and their delivery. 2. Communicate uncertainty proactively • Communication by authorities to the public should include explicit information about uncertainties associated with risks, events and interventions and indicate what is known and not known at a given time. • Announce the event as early as possible, even when the information is incomplete. This will establish you as the leader to communicate risk; it will build trust in you and the response; it will help enable changes in practice and behaviors to bring the outbreak under control; and it will minimize misinformation and rumours. • A good template to communicate uncertainty is as follows: - State what is known, what is unknown, and what you/your institution is doing about the issue; - Communicate early, be fi rst to announce the event if possible, communicate often, communicate regularly; - Provide information on the risk/danger; but supplement it with some advice on how people can protect themselves; - Speak as a human being, using empathy appropriately; - Do not over-reassure. 3. Engage communities • Identify people that the community trusts and build relationships with them and involve them in decision-making to ensure interventions are collaborative, contextually appropriate and that communication is community-owned. • Community engagement is one important start for communicating risk and facilitating changes in behaviours and practices (see Focus 1, page 38). 4. Message well • According to the latest evidence, risk should not be explained in technical terms as this is not helpful for promoting risk mitigation behaviours. Consistent messages should come from different information sources and emerge early in the outbreak. Messages should promote specifi c actions people can realistically take to protect their health. 5. Establish and use listening and feedback systems • Use multiple means (surveys, focus group discussions, community walk-throughs, key informants, feedback from front-line responders, partners’ and stakeholders’ PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 45 feedback, social media, etc.) to listen to the public and affected communities. • Use these to understand what concerns people regarding the outbreak or the measures we are asking them to adopt. • Use these systems to test messaging and materials developed to support risk communication. 6. Use social media as appropriate • Social media should be used to engage the public, facilitate peer-to- peer communication, create situational awareness, monitor and respond to rumours, public reactions and concerns during an emergency, and to facilitate local level responses. • Social media and traditional media should be part of an integrated strategy with other forms of communication to achieve convergence of verifi ed, accurate information. 7. Risk communication operations requires resources • Risk communication in epidemics is a massive operational undertaking and requires people, logistics, material and funds. • Different types of expertise in many areas are required: media communications, social media, spokespersons, social mobilization, health promotion, community engagement, behavioral change communication; stakeholder communication, communication related to travel and trade, social science methods, etc. 8. Treat Emergency risk communication as a strategic role, not an add-on • Emergency risk communication should be a designated strategic role in global and national emergency preparedness and response leadership teams. • The International Health Regulations (2005) require all Member States to build national capacity to communicate risk in two domains: - Systems capacities; - People capacities. • The Joint External Evaluation (JEE) process championed by the Global Health Security Agenda measures national risk communication capacity in six domains: - National strategies, policies and plan; - Coordination; - Stakeholder communication; - Public communication (using mass media approaches); - Communicating and engaging with communities; - Dynamic listening (to misinformation, fears, concerns) and rumour management. 9. Establish coordination and information systems • Develop and build on agency and organizational networks across geographic, disciplinary and, where appropriate, national boundaries. • Tailor information and communication systems to the needs of users and involve local stakeholders to guarantee the fl ow of information across sectors. 10. Build capacity for the next emergency • Preparation and training of personnel for emergency risk communication should be organized regularly and focus on coordination across agencies. • Emergency risk communication requires a defi ned and sustained budget which should be a part of core budgeting for emergency preparedness and response. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 46 Other factors to remember While there is an increasing body of evidence as to what constitutes effective risk communication, every outbreak is unique. Therefore risk communication must be adapted to: • The infectious hazard (its severity, lethality, modes of transmission, how it can be diagnosed, treated or managed); • The geography of the outbreak: contained or widely distributed; national or international spread; affecting certain vulnerable communities or the general population; in a remote forgotten village or major city; affecting to poor or affecting travel and trade; • The levels of trust that exit between the affected or at-risk populations and their authorities and experts; or the response teams; • People’s underlying beliefs, cultures, traditions, values and practices; • Education, levels of awareness, access to understandable information; and trusted channels of communication; • Self-effi cacy: do communities have the ability, resources and environment to follow health advice? PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 47 FOCUS 3 Treating patients and protecting the health workforce Advances in medicine: antibiotics, antivirals, vaccines and new treatments With the remarkable progress in medicine and related technologies, briefl y mentioned at the beginning of this publication, many infectious diseases can now be prevented and treated. This is the result of a public health revolution that began in the 1940s with the discovery of antibiotics for bacterial diseases, and expanded with improvements in their safety, effi cacy and acceptability. Similarly, the development of vaccines, particularly for infants and young children, has given global protection against a number of childhood killers. For example, WHO estimates that there is now 86% global coverage of the combined diphtheria-tetanus-pertussis vaccine for babies1. In recent decades, hundreds of millions of children all over the world have grown up free of the risk of deadly and disabling diseases. Adults have benefi ted likewise, with protection against a wide range of infections that can explode into epidemics – cholera, infl uenza and yellow fever, for example. For many deadly diseases, there are vaccines that ideally should be administrated in routine, large-scale immunization to prevent the occurrence of the disease. Some vaccines can also be used during a reactive campaign when there is an epidemic in which the immunity of the population is not high enough. The public health revolution continued towards the end of the 20th century with the discovery of antivirals, such as that used against HIV. Meanwhile, there have also been great strides forward in the fi elds of diagnostics and treatments, such as monoclonal antibodies, that are also becoming more widely available but the price of some of them is still very high and they are not yet available for mass administration. Such advances – and the early problems that followed them – including a degree of public health complacency, and the emergence of antibiotic resistance - have completely changed the way infectious diseases are confronted today. 1 WHO data, 2016. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 48 Treating patients with supportive care But whether the focus is on antibiotics, antivirals, vaccines or the whole armoury of other treatments, the vital, universal fact is that they can only be benefi cial when they are administered by skilled, qualifi ed and dedicated health personnel, all across the spectrum of care. When, for example, no specifi c treatment is available for a given disease, adequate clinical management can still protect and save lives. This has been shown by a dramatic reduction in deaths from Ebola in West Africa in 2014 – from 75% to 33% mortality, achieved through the provision of better supportive care for patients. Protecting frontline responders The role of the health workforce should never be underestimated nor taken for granted. In general, much of their day-to-day work is mundane and routine, providing tried-and- tested care and treatment for familiar illnesses, disabilities and injuries. But when an epidemic strikes, they make a vital difference at all levels, whether as community health workers and volunteers, midwives, nurses, or doctors. With little or no warning, they are transformed into frontline responders, thrust into immediate contact with infected communities and individuals. Family members, too, take on the role of caring for their relatives at home, often linking up with health staff in clinics, hospitals and emergency centres. This transformation is double-edged and dangerous for frontline responders. First, their immediate priorities are to prevent the spread of an epidemic, protect those people who are most at risk, and to care by all possible means for those who are already infected. The related dangers are obvious: health workers are putting themselves at risk. They fi nd themselves in the most dangerous place at the most dangerous time. Yet, because their job is to care for the sick and injured, health care workers are often viewed as “immune” to injury or illness. Their patients come fi rst. However, human-to- human transmission is a major factor in many infectious diseases that cause epidemics. Patients are highly contagious and can spread the disease at home, at work, in public spaces, but also in hospitals. Thus, it is essential to protect them from infection – both for their own safety and for the wider protection of the affected community. It is here that emergency planning, preparation, training and coordination are so essential, as is the urgent provision of practical safeguards, especially the necessary personal protective equipment and the knowledge of how to use it properly. PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 49 Confronting the human resources crisis These measures may seem obvious, but the role of frontline responders is frequently shackled by a major disadvantage: there are not nearly enough of them. This unpalatable truth applies to the health workforce in general. It is a global problem, but it is most acute in the poorest countries with weakest health systems, where epidemics are most likely to erupt. Protecting the occupational health of health workers is critical to have an adequate workforce of trained and healthy health personnel. This is nowhere more true than at the heart of an infectious disease epidemic. Around the world, health care facilities employ over 59 million workers2. Yet at the same time, there is a chronic shortage of them in more than 50 countries. This crisis in human resources for health has persisted for decades, despite numerous attempts to tackle it, but recent actions show notable progress. It is not just a matter of numbers. While there has long been an exclusive focus on how many there are, against how many are needed, there is growing public health agreement on according equal importance to accessibility, acceptability, quality and performance in addition to availability. These four factors are inter-related and inter- dependent. The absence or inadequacy of any one of them undermines all the others. Without suffi cient availability, accessibility to health workers cannot be guaranteed. If they are available and accessible, without acceptability, the health services may not be used. When the quality of the health workforce is inadequate, improvements in health outcomes will not be satisfactory. Elaboration of these complex issues at length goes beyond the scope of this handbook. But it is important that they are taken into account in the context of infectious disease prevention, treatment and control. Indeed, they lead to recognition that protecting health care workers has the added benefi t to contributing to quality patient care and health system strengthening. If it is accepted that health begins with health workers, their empowerment is necessary on a general basis. Their voice, rights and responsibilities must play a central role in developing and implementing solid policies and strategies towards universal health coverage. This applies to the context of epidemic disease control as much as it does to other health issues more widely. The engagement of communities during epidemics, including health workforce community, needs to be at the center of the epidemic response. For more information about protecting the health workforce: WHO global health workforce alliance website http://www.who.int/workforcealliance/en/ 2 WHO data: http://www.who.int/occupational_ health/topics/hcworkers/en/ PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 50 DISEASE SPECIFIC SUPPORTIVEMAJOR MODE OF TRANSMISSION Clinical management VACCINATION SAFE & DIGNIFIED BURIALS ENHANCED INFECTION PREVENTION & CONTROL VECTOR CONTROL WATER & SANITATION Chikungunya Cholera Dengue Ebola virus disease Hepatitis E Infl uenza Lassa fever Leptospirosis Malaria http://www.who.int/csr/disease/chikungunya/en/ http://www.who.int/cholera/en/ http://www.who.int/denguecontrol/en/ http://www.who.int/ebola/en/ http://www.who.int/mediacentre/factsheets/fs280/en/ http://www.who.int/infl uenza/en/ http://www.who.int/csr/disease/lassafever/en/ http://www.who.int/topics/leptospirosis/en/ http://www.who.int/malaria/en/ Vector Fecal oral / water Vector Animals / contact Fecal oral / water Respiratory Rodent / contact Rodent Vector Crimean-Congo haemorrhagic fever (CCHF) http://www.who.int/csr/disease/crimean_congoHF/en/ Animals (mainly ticks) / contact 1 Marburg virus disease http://www.who.int/csr/disease/marburg/en/ Animals / contact ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ 2 3 4 5 1 Ribavirin use currently under review by WHO; 2 Oral vaccines; 3 There is a vaccine (Dengvaxia®) currently under assessment; 4 Intramuscular and intranasal vaccines; 5 Safe and dignifi ed burials for highly pathogenic non-human infl uenza; Major modes of transmission and interventions per disease PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 51 Meningitis MERS/SARS Monkeypox Plague (pneumonic) Plague (bubonic) Polio Rickettsia Shigellosis Rift valley fever Smallpox Typhoid fever West Nile fever Yellow fever Zika http://www.who.int/csr/disease/meningococcal/en/ http://www.who.int/topics/coronavirus_infections/en/ http://www.who.int/mediacentre/factsheets/fs161/en/ http://www.who.int/csr/disease/plague/en/ http://www.who.int/csr/disease/plague/en/ http://www.who.int/topics/poliomyelitis/en/ http://www.who.int/csr/disease/riftvalleyfev/en/ http://www.who.int/csr/disease/smallpox/en/ http://www.who.int/immunization/diseases/typhoid/en/ http://www.who.int/mediacentre/factsheets/fs354/en/ http://www.who.int/csr/disease/yellowfev/en/ http://www.who.int/topics/zika/en/ Respiratory Respiratory Animals / contact Respiratory Rodent Fecal oral Vector Fecal oral / food Animals / vector Respiratory Food Vector Vector Vector Measles http://www.who.int/immunization/diseases/measles/en/ Respiratory DISEASE SPECIFIC SUPPORTIVEMAJOR MODE OF TRANSMISSION VACCINATION SAFE & DIGNIFIED BURIALS ENHANCED INFECTION PREVENTION & CONTROL VECTOR CONTROL WATER & SANITATION ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ 6 7 8 6 Oral and intramuscular/subcutaneous polio vaccines; 7 Intramuscular and scarifi cation vaccines; 8 Intramuscular/subcutaneous vaccines. Clinical management PART IMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 52

PART II 10 KEY FACTS ABOUT 15 DEADLY DISEASES Be in the know EBOLA VIRUS DISEASE LASSA FEVER CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF) YELLOW FEVER ZIKA CHIKUNGUNYA AVIAN AND OTHER ZOONOTIC INFLUENZA SEASONAL INFLUENZA PANDEMIC INFLUENZA MIDDLE EAST RESPIRATORY SYNDROME (MERS) CHOLERA MONKEYPOX PLAGUE LEPTOSPIROSIS MENINGOCOCCAL MENINGITIS 10 THINGS YOU SHOULD KNOW Ebola virus disease 1. Ebola virus disease transmits from person to person through close contact 2. Health care workers, mourners and family members are the most at risk to get infected 3. At-risk persons should be informed about Infection Prevention and Control (IPC) measures and be provided with appropriate personal protective equipment 4. Community engagement, active case fi nding, contact tracing, laboratory support, and safe and dignifi ed burials are key to control outbreaks 5. Early supportive care improves survival 6. Ebola is diffi cult to distinguish from other diseases with haemorrhage presentation 7. The Ebola virus can persist in people recovering from the disease for several months 8. Ebola survivors may suffer from stigma and sequelae 9. There are ongoing researches for vaccines, diagnostics and treatments 10. Ebola is a viral haemorrhagic fever that occurs mostly in rural and remote areas of Africa EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 56 Ebola virus disease response tips Coordinating responders • Engage with partners involved in the response (community engagement, surveillance, laboratory, case management and IPC) • Engage with religious and community leaders Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate early and frequently • Key messages are: - Ebola is transmitted through contact with body fl uids of infected animals and humans - Dead bodies of patients are contagious - Apply IPC measures when in contact with sick or dead patients and animals - People are not infectious if they do not show symptoms - People with symptoms should seek medical advice as supportive treatment increases chances of survival Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive treatment - Protect health care workers • Surveillance, contact fi nding and contact tracing • Safe and dignifi ed burials • Vaccination under expanded access (rVSV-ZEBOV vaccine for Zaire Ebola virus) EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 57 Ebola virus disease transmits from person to person through close contact • Incubation period ranges from 2 to 21 days. • Humans are not infectious as long as they do not develop symptoms. During the course of the disease, they remain infectious as long as their blood contains the virus. • Ebola is fi rst introduced into the human population through close contact with the blood, secretions, organs or other body fl uids of infected animals such as fruit bats, chimpanzees, gorillas, monkeys, forest antelopes and porcupines found ill or dead, often in the rainforest. • Ebola then spreads through human- to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other body fl uids of infected people. - Infection can also occur if the broken skin or the mucous membranes of a healthy person comes into contact with items or environments contaminated with body fl uids from an infected person. These may include soiled clothing, bed linen, gloves, and protective equipment; - Medical waste, such as used syringes, should be disposed carefully, as they are a source of health care workers infection. • Ebola virus disease has not been reported to be transmitted by aerosols. It is not airborne. Health care workers, mourners and family members are the most at risk to get infected Population at high-risk of being infected include: • Health care workers if Infection Prevention and Control (IPC) measures are not in place or not well followed while caring for patients. • Mourners, as burial ceremonies involve direct contact with the body or body fl uids of the deceased (washing, touching…) because levels of Ebola virus remain high after death. • Family members or others in close contact with infected people and caring for them in contact with body fl uids or contaminated items. 1 2 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 58 At-risk persons should be informed about IPC measures and be provided with appropriate personal protective equipment • All health care providers working at all levels of the health system, and family members caring for the sick, should be fully informed about the disease and its mode of transmission and should follow recommended Infection Prevention and Control (IPC) measures strictly. • They should be provided with appropriate Personal Protective Equipment (PPE). • Standard precautions with all patients should be applied. They include: hand hygiene; use of gloves before contact with body fl uids, mucous membrane, non-intact skin and contaminated items; gown and eye protection before procedures and patient-care activities likely to involve contact with or projection of blood or body fl uids; injection safety practices; safe cleaning, disinfection and waste management; isolation of cases and appropriate fl ow of patients. 3 Community engagement, active case fi nding, contact tracing, laboratory support, and safe and dignifi ed burials are key to control outbreaks • The aim of Ebola response is to contain the outbreak at its source. Ebola virus transmission is stopped by : 1. Community engagement as communities are essential for responding to Ebola outbreaks. They have a role to play in the detection of new cases. Communities should be engaged in the response since the early stage and be provided by the necessary information so that they can adapt the public health measures to their socio-cultural beliefs and ensure compliance of the community members. 2. Active case fi nding, rapid isolation of patient and early laboratory confi rmation of suspected cases. Active 4 case fi nding refers to actively searching for new cases (for instance, going from house to house in the community, asking if people are sick or if people have died). New (suspected) cases should be rapidly and safely referred to treatment centres for isolation and treatment. 3. Laboratory testing in Ebola treatment units is crucial for classifi cation of cases, to streamline contact tracing, for patient triage and management and to support research and development (to develop and validate new point-of- care diagnostics, new therapeutics and new vaccines). 4. Contact tracing which refers to the follow-up of persons who may have come into contact with a person infected with the Ebola virus (or their body fl uids, exposed environment such as linens, a dead animal, etc.). Contacts should be followed-up over a period of 21 days after the last exposure, looking for symptoms such as fever, and referred to treatment centres if they become ill. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 59 5. Early supportive care (rehydration and pain relief) should be provided to patients as early as possible as it reduces mortality. 6. Safe and dignifi ed burials teams are necessary to facilitate mourning by affected families and communities and to stop transmission of Ebola virus from deceased patients. • Other key elements to put in place to control outbreaks are: - Surveillance and follow-up of survivors as the virus may persist in their body fl uids and they may be infectious; - Psychosocial support to patients and their families; - Public health emergency plans and standard operational procedures at designated points of entry, in accordance with the International Health Regulations (IHR) (2005). • After 42 days (two 21-day maximum incubation period for Ebola virus) with no new cases, the human-to- human transmission is controlled and the outbreak can be declared over. Early supportive care improves survival • Early supportive care, especially rehydration with oral or intravenous fl uids, and treatment of specifi c symptoms, improves survival. • Other treatments being used to help people survive Ebola virus disease include, where available and IPC measures strictly implemented, kidney dialysis, blood transfusions and plasma replacement therapy. • It is important that patients and families trust health workers to accept being care of in dedicated treatment facilities. • Care should be patient-centered and respect patients’ preferences. • There is, as yet, no commercially treatment available for Ebola. However, a range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. 5 • An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea. The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11841 people during 2015. Among the 5837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine. - The trial was led by WHO, together with Guinea’s Ministry of Health, Médecins sans Frontières and the Norwegian Institute of Public Health, in collaboration with other international partners. A ring vaccination protocol was chosen for the trial, where some of the rings are vaccinated shortly after a case is detected, and other rings are vaccinated after a delay of 3 weeks. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 60 Ebola is diffi cult to distinguish from other diseases with haemorrhage presentation • First symptoms are common to many other diseases, they are not specifi c: sudden onset of fever, fatigue, muscle pain, headache and sore throat. • These fi rst symptoms are usually followed by: vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding (e.g. oozing from the gums, blood in the stools). • Ebola virus infection can be confi rmed with laboratory diagnostics: - The diagnostic methods are the following: o Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; o Antibody-capture Enzyme-Linked Immunosorbent Assay (ELISA); o Antigen-capture detection test; o Serum neutralization test; o Electron microscopy; o Virus isolation by cell culture. - Current WHO recommended tests include: o Automated or semi-automated Nucleic Acid Tests (NAT) for routine diagnostic management; o Rapid antigen detection tests for use in remote settings where NAT are 6 not readily available. These tests are recommended for screening purposes as part of surveillance activities. However reactive tests should be confi rmed with NAT. - The preferred specimens for diagnosis include: o Whole blood collected from live patients exhibiting symptoms; o Oral fl uid specimen stored in universal transport medium collected from deceased patients or when blood collection is not possible (swab for dead bodies). • Recommended case defi nitions for Ebola or Marburg virus diseases can be found on: http://www.who.int/csr/resources/ publications/ebola/case-definition/en/. During an outbreak, case defi nitions are likely to be adapted to new clinical presentation(s) or different modes of transmission related to the local event. EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 61 The Ebola virus can persist in people recovering from the disease for several months • People can survive from Ebola virus disease. • Ebola virus is known to persist in immune- privileged sites in some people who have recovered from Ebola virus disease. These sites include the testicles, the inside of the eye, and the central nervous system. In women who have been infected while pregnant, the virus may persist in the placenta, amniotic fl uid and fetus. In women who have been infected while breastfeeding, the virus may persist in breast milk. • Several cases of sexual transmission have been reported. All Ebola survivors and their sexual partners should receive counselling to ensure safe sexual practices, be provided with condoms when discharged from Ebola treatment unit and enrolled in national semen and body fl uid testing programmes. • Male Ebola survivors should be offered semen testing when discharged from Ebola treatment unit, and then, for those who test positive, every month thereafter until their semen tests negative for virus twice by RT-PCR, with a minimum interval of two weeks between tests. Relapse- symptomatic illness in someone who has recovered from EVD due to increased replication of the virus in a specifi c site is a rare event, but has been documented. Reasons for this phenomenon are not yet fully understood. 7 Ebola survivors may suffer from stigma and sequelae • Survivors may suffer from physical sequelae and should be followed- up. Most common physical sequelae are: musculoskeletal, ocular, auditory, abdominal, neurological, and sexual issues. • Survivors may suffer from stigma. They may be rejected from their community and should be followed-up and assisted, if needed, regarding employment, living conditions, family, social support from their community, etc. • They should receive education and counselling regarding the possible sequelae and psycho-social challenges they might face. • Specifi c follow-up considerations should be applied for children and pregnant women. 8 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 62 There are ongoing researches for vaccines, diagnostics and treatments • Research is ongoing to develop and evaluate vaccines, diagnostics tools and therapeutics. Currently, no vaccine, or new therapeutic has been licensed. • An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea. The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11 841 people during 2015. Results of effi cacy trial show to be 100% effective in those who received it as part of a ring vaccination trial. • There are 12 candidate vaccines and one (rVSV- ZEBOV, effi cient against Zaire Ebola virus) that could be used under expended access during outbreaks. • A range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. • Four Nucleic Acid Tests (NAT) and three Rapid Diagnostic Tests (RDT) were approved for emergency use during the Ebola crisis 2014-2016. These tests could be used during outbreak situation, in remote settings. 9 Ebola is a viral haemorrhagic fever that occurs mostly in rural and remote areas of Africa • Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe illness in humans. The average case fatality rate is around 50%. It has varied from 25% to 90% in past outbreaks. • Ebola virus disease is a zoonotic disease, transmittable from wild animals to humans. • Reservoir of the disease is fruit bats. The disease is also found in monkeys, apes, antelope and porcupines. Ebola virus disease should be suspected if any of these animals is found ill or dead in the rainforest. 10 EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 63 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reservedSource: WHO/IHM, as of 15 February 2018 Geographic distribution of Ebola virus disease outbreaks (1976-2018) Country with serological evidence Country that reported Ebola virus disease imported cases Country that reported Ebola virus disease outbreaks EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 64 More information about Ebola virus disease: • Ebola WHO webpage: http://www.who.int/ebola/en/ • Ebola WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs103/en/ • Ebola and Marburg virus disease epidemics: preparedness, alert, control and evaluation http://www.who.int/csr/resources/publications/ebola/manual_EVD/en/ • Case defi nitions: http://www.who.int/csr/resources/publications/ebola/case-defi nition/en/ • Laboratory diagnosis: http://www.who.int/csr/resources/publications/ebola/laboratory- guidance/en/ • Clinical management: http://www.who.int/csr/resources/publications/clinical-management- patients/en/ • Clinical care for survivors of EVD: http://www.who.int/csr/resources/publications/ebola/guidance-survivors/en/ • Infection prevention and control guidance for care of patients if health care settings, with focus on Ebola: http://www.who.int/csr/resources/publications/ebola/fi lovirus_infection_ control/en/ • Safe and dignifi ed burials: http://www.who.int/csr/resources/publications/ebola/safe-burials/en/ • Ebola WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases EBOLA VIRUS DISEASEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 65 1. The reservoir of Lassa fever is a rat 2. Humans are primarily infected through exposure to rats’ urine or faeces 3. Human-to-human transmission occurs then through direct contact with body fl uids of infected persons 4. Pregnant women and infants may experience severe disease 5. Lassa fever is hard to distinguish from other viral diseases 6. Hygiene and rodent control are the best prevention in communities 7. Strict implementation of infection prevention and control measures in health care settings is critical to prevent the spread of the disease 8. Early supportive treatment reduces mortality 9. Outbreak control relies on community engagement, active case fi nding, contact tracing and safe and dignifi ed burials 10. Lassa fever is a viral haemorrhagic fever that occurs in West Africa 10 THINGS YOU SHOULD KNOW Lassa fever LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 66 Lassa fever response tips Coordinating responders • Engage with partners involved in the response (surveillance, laboratory, case management, infection prevention and control (IPC) and community engagement) • Engage with religious and community leaders Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate about how to protect from becoming infected - Provide targeted communication to at-risk groups such as pregnant women • Key messages to general public: - Humans are primarily infected through exposure to rats’ urine or faeces - Avoid contact with body fl uids of sick people - Seek health advice rapidly if you show symptoms - Wash your hands regularly - Implement measures to reduce contact with rodents Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive treatment - Protect health care workers • Surveillance, contact fi nding and contact tracing • Safe and dignifi ed burials • Rodent control LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 67 The reservoir of Lassa fever is a rat • The animal reservoir of Lassa virus is a rodent : the Mastomys rat, commonly know as the “multimammate rat”. • Rat are infected at birth and are chronic asymptomatic carriers of Lassa virus. • The infected rats do not become ill but can shed the virus in their urine and faeces. • The virus is present in aerosolized excreta, particularly urine. Humans are primarily infected through exposure to rats’ urine or faeces • Humans usually become infected with Lassa virus from exposure to urine or faeces of infected rats. • Humans are infected through: - Direct contact by catching, handling and preparing Mastomys as a food source (more frequent); - Ingestion of food contaminated by infected rodent excreta; - Direct contact with objects and surfaces contaminated by rats’ urine and faeces; - Inhalation of aerosolized virus (rare). 1 2 • Transmission of Lassa fever virus from rats to humans is common, since these rodents scavenge on human food items and readily colonize areas where humans live. • People at high risk of being infected, through rat-to-human transmission, are: - Persons living in rural areas where Mastomys are usually found, especially in communities with poor sanitation or crowded living conditions; - Persons hunting and consuming rodent products. LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 68 Human-to-human transmission occurs then through direct contact with body fl uids of infected persons • Lassa virus may spread from human to human through direct contact with the blood, urine, faeces, or other body secretions of a person infected with Lassa fever. • Humans can also be infected through direct contact with contaminated bedding or clothing. • Human-to-human and laboratory transmission also occur, particularly in hospitals lacking adequate infection prevention and control measures (e.g. the virus may be spread by contaminated medical equipment, such as re-used needles). • People most at risk of being infected, through human-to-human transmission, are: - Health care workers or anyone caring for Lassa fever patients in the absence of proper infection prevention and control practices; - People handling dead bodies of infected patients (e.g. during funerals). • Sexual transmission of Lassa virus has also been reported. • There is no evidence supporting airborne spread between humans. 3 Pregnant women and infants may experience severe disease • Lassa fever occurs in all age groups and both sexes. • The disease is especially severe late in pregnancy: - Maternal mortality can be greater than 30% in third trimester and 50% in the last month; - Fetal loss is occurring in more than 80% of cases during the third trimester; - Pregnant women show increased level of viraemia (virus levels in the blood). • Infection in infants is also associated with a very high case fatality rate. • Infants (up to two years old) can present a “swollen baby syndrome” (edema, abdominal distension and bleeding, often leading to death). Older children experience similar symptoms as adults. 4 LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 69 Lassa fever is hard to distinguish from other viral diseases • Symptoms of Lassa fever are very varied and non-specifi c, which makes clinical diagnosis diffi cult, especially early in the course of the disease. Lassa fever can be diffi cult to distinguish from other viral haemorrhagic fevers (e.g. Ebola virus disease) as well as from other diseases that cause fever such as Malaria, Typhoid fever, Yellow fever, Infl uenza, Measles, Shigellosis, Cholera, Leptospirosis, Rickettsial infections, Relapsing fever, Meningitis, Bacterial sepsis, Hepatitis. • Symptoms of Lassa fever can occur from 2 to 21 days after coming into contact with the virus. The incubation period is usually from 7 to 10 days. • About 80% of infected people do not show symptoms (they are asymptomatic) or experience a mild disease. • The onset of the disease, when it is symptomatic, is usually gradual. Symptoms usually start with fever, general weakness, and malaise. • After a few days, headache, sore throat, muscle pain, chest pain, nausea, vomiting, diarrhoea, cough, and abdominal pain may follow. • In mild cases, the patient usually recovers rapidly. • In severe cases (20%) facial swelling, fl uid in the lung cavity, bleeding from the mouth, nose, vagina or gastrointestinal tract and low blood pressure may develop. Severe cases require hospitalization. 5 • Shock, seizures, tremor, disorientation, and coma may also be seen in the later stages. Death (1 to 2% of total infected symptomatic people: severe and mild cases) usually occurs within 14 days of onset in fatal cases. • Various degrees of deafness occur in 25% of severe cases who survive the disease. In half of these cases, hearing returns partially after 1–3 months. Transient hair loss and gait disturbance may occur during recovery. • Lassa fever should be considered in febrile patients returning from West Africa, especially if they have had exposures in rural areas or hospitals in countries where Lassa fever is known to be endemic. • Patient history is essential for diagnosis. Suspected case: Illness with gradual onset with one or more of the following: malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhoea, myalgia, chest pain hearing loss and a history of contact with rodents or with a case of Lassa fever. Probable case: A deceased suspected case (where it has not been able to collect specimen for laboratory confi rmation) that has an epidemiological link with a laboratory confi rmed case. Confi rmed case: A suspected case that is laboratory confi rmed (positive for IgM antibodies, positive for Lassa virus antigen, positive for Lassa RNA by RT- PCR or virus isolation). LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 70 • Lassa virus infections can only be diagnosed defi nitively in the laboratory using the following tests: - Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; - Antibody Enzyme-Linked Immunosorbent Assay (ELISA); - Antigen detection tests; - Virus isolation by cell culture. • Laboratory specimens may be hazardous and must be handled with extreme care. Handling specimens with live virus requires Biosafety level 4. • Diagnostic assays have also been made commercially available, but none have been evaluated by WHO prequalifi cation process. Hygiene and rodent control are the best prevention in communities • To prevent infection, people should follow basic hygiene practices: - Wash their hands regularly; - Cook food thoroughly. • Raising awareness is a fi rst step towards better rodent management. • At the community level, to reduce human- rodent contacts, people are advised to: - Store food in covered rodent-proof containers; - Keep homes clean and clear away any rubbish in or around the house; 6 - Keep a cat; - Implement measures to reduce rodent populations. This would require strong political commitment and sustained efforts. Techniques that could be used include: o Trapping and poisoning; o Using non-lethal, non-toxic alternatives to chemical rodenticides (research ongoing); o Reducing reproduction (fertility control); o Etc. Infectivity Days 0 1 2 3 4 5 6 8 97 • Fever • Extreme fatigue • General weakness • Face swelling • Low blood pressure • Nose bleeding • Headache • Severe sore throat • Diarrhoea LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 71 Strict implementation of infection prevention and control measures in health care settings is critical to prevent the spread of the disease • In health care settings, staff should always apply standard infection prevention and control precautions when caring for patients, regardless of their presumed diagnosis. These include: - Hand hygiene; - Respiratory hygiene; - Use of personal protective equipment (to block splashes or other contact with infected materials); - Safe injection practices; - Safe and dignifi ed burial practices. • Health care workers caring for patients with suspected or confi rmed Lassa fever should apply extra infection control measures to prevent contact with the patient’s blood and body fl uids and contaminated surfaces or materials such as clothing and bedding. When in close contact (within 1 metre) of patients with Lassa fever, health care workers should wear face protection (a face shield or a medical mask and goggles), a clean, non- sterile long-sleeved gown, and gloves (sterile gloves for some procedures). • Health care workers should remember that maternity wards are potential sites of amplifi cation as miscarriage and natural abortion with massive bleeding may conclude from women with Lassa fever. Early supportive treatment reduces mortality • Treatment is supportive: it consists in symptomatic treatment, rehydration, monitoring fl uid and electrolyte balance and renal function. • Antiviral drug ribavirin seems to be effective if given early in course of the disease. • There is no post-exposure prophylactic treatment. • There is currently no licensed or commercially available vaccine. New candidate vaccines are under development. • New candidate drugs are in development. 7 8 LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 72 Outbreak control relies on community engagement, active case fi nding, contact tracing and safe and dignifi ed burials The transmission of the disease can be stopped through: 1. Community engagement as communities are essential for controlling Lassa fever outbreaks. They have a role to play in the detection of new cases, and reduction of transmission through safe caring of the sick at home and safe and dignifi ed burial. Communities should be engaged in the response since the early stage and be provided with the necessary information and personal protective equipment so that they can adapt the public health measures to their socio- cultural beliefs and ensure compliance of the community members. 2. Active case fi nding, rapid isolation of patients and early laboratory confi rmation of suspected cases. Active case fi nding refers to actively searching for new cases (for instance, going from house to house in the community, asking if people are sick or if people have died). New (suspected) cases should be rapidly and safely referred to treatment centres for isolation and treatment. Lassa fever is a viral haemorrhagic fever that occurs in West Africa • Lassa fever is a viral haemorrhagic illness of 2-21 days duration that occurs in West Africa. • Lassa fever has been reported in Benin, Burkina Faso, Côte d’Ivoire, Ghana, Guinea, Liberia, Mali, Nigeria, Sierra Leone, and Togo, but should be considered endemic in other West African countries. • The overall case fatality rate is 1%. • Observed case fatality rate among patients hospitalized with severe presentation of Lassa fever is 15%. 9 10 3. Contact tracing which refers to the follow-up of persons who may have come into contact with a person infected with the Lassa virus (or their body fl uids, exposed environment such as linens, etc.). Contacts should be followed-up over a period of 21 days after the last exposure, looking for symptoms such as fever, and referred to treatment centres if they become ill. 4. Safe and dignifi ed burials. It is necessary to train people who will have close contact with dead bodies and provide them with the necessary personal protective equipment. People can be buried in a safe manner while respecting traditional beliefs. 5. Early supportive care (rehydration and pain relief) should be provided to patients as early as possible as it reduces mortality (see point 8). LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 73 Geographic distribution of Lassa fever in West African affected countries, 1969–2018 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 74 More information about Lassa fever: • Lassa fever WHO webpage http://www.who.int/csr/disease/lassafever/en/ • Lassa fever WHO fact sheet http://www.who.int/mediacentre/factsheets/fs179/en/ • Lassa fever WHO MOOC https://openwho.org/courses/pandemic-epidemic-diseases LASSA FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 75 1. The CCHF virus is transmitted by ticks and the disease is endemic where the tick vector is present 2. Humans are primarily infected through tick bite and secondary human-to-human transmission occurs through direct contact with the body fl uids of infected persons 3. Infected animals are not sick which makes it diffi cult to control the disease in animals and anticipate and prevent infection in humans 4. CCHF is a severe disease with high case fatality ratio 5. Early supportive care improves survival 6. Infection prevention and control measures are critical to control the infection when caring for patients or during burial ceremonies 7. Raising awareness on risk factors and preventive measures is key to reduce infection in people 8. Effi cient vector control measures are currently lacking 9. CCHF can be misdiagnosed with other viral haemorrhagic fevers and early laboratory confi rmation of suspected cases is critical to mount the response 10. CCHF is one of the priority disease for research and development in public health emergency contexts (R&D Blueprint) 10 THINGS YOU SHOULD KNOW Crimean-Congo haemorrhagic fever (CCHF) CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 76 Crimean-Congo haemorrhagic fever (CCHF) response tips Coordinating responders • Engage with partners involved in the response (community engagement, surveillance, laboratory, case management, IPC, and vector control) • Engage with the animal health and food production sectors Communicating risk • Encourage health authorities to: - Implement active case fi nding and contact tracing - Ensure protection of health care workers through IPC measures - Communicate about how to protect from becoming infected • Key messages are: - CCHF is transmitted by ticks or through contact with body fl uids of infected animals and humans - Bodies of deceased patients are contagious - Apply IPC measures when in contact with sick or dead patients and animals - People with symptoms should seek medical advice as early treatment increases chances of survival Health Information • Ensure early laboratory confi rmation of suspected cases • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and health promotion • Case management and IPC: - Isolation of cases - Early supportive and antiviral treatment - Protect health care workers • Surveillance, and contact tracing • Safe and dignifi ed burials CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 77 The CCHF virus is transmitted by ticks and the disease is endemic where the tick vector is present • Ticks of the genus Hyalomma are the principal vector of the disease, although a number of tick are capable of becoming infected with CCHF virus. • Animals become infected by the bite of infected ticks and the virus remains in their bloodstream for about one week after infection, allowing the tick-animal- tick cycle to continue when another tick bites. • The hosts of the CCHF virus include a wide range of wild and domestic animals such as cattle, sheep and goats. Many birds are resistant to infection, but ostriches are susceptible and may show a high prevalence of infection in endemic areas. • CCHF is a viral haemorrhagic fever that is endemic where the tick vector is present: in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north – the geographical limit of the principal tick vector. Humans are primarily infected through tick bite and secondary human-to-human transmission occurs through direct contact with the body fl uids of infected persons • CCHF can cause severe outbreaks in humans. • Humans are infected either by ticks bite or through direct contact with blood or tissues of infected ticks or viraemic vertebrates including wild animals and livestock. • Most at-risk people for the animal- to-human transmission are people involved in the livestock industry, such as agricultural workers, slaughterhouse workers and veterinarians. • Secondary human-to-human transmission occurs through direct contact with the blood, secretions, organs or other body fl uids of infected persons. 1 2 • There is high human-to-human transmission risk when providing direct patient care or handling bodies of deceased individuals (funerals). • Hospital-acquired infections can also occur due to inappropriate infection prevention and control. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 78 Infected animals are not sick which makes it diffi cult to control the disease in animals and anticipate and prevent infection in humans • Infected animal are not sick and do not show any symptoms. This allows the virus to maintain itself in nature in unnoticed enzootic tick-vertebrate-ticks cycles and makes diffi cult to anticipate and prevent potential infection in humans. CCHF is a severe disease with high case fatality ratio • The mortality rate from CCHF is approximately 30% (it ranges from 10 to 50%), with death occurring in the second week of illness. In patients who recover, improvement generally begins on the ninth or tenth day after the onset of illness. • The length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, the incubation period is usually one to three days, with a maximum of nine days. The incubation period following contact with infected blood or tissues is usually fi ve to seven days, with a documented maximum of thirteen days. • Onset of symptoms is sudden, with fever, myalgia (muscle ache), dizziness, neck pain and stiffness, backache, headache, sore eyes and photophobia (sensitivity to light). There may be nausea, vomiting, diarrhoea, abdominal pain and sore 3 4 throat early on, followed by sharp mood swings and confusion. After two to four days, the agitation may be replaced by sleepiness, depression and lassitude, and the abdominal pain may localize to the upper right quadrant, with detectable hepatomegaly (liver enlargement). • Other clinical signs include tachycardia (fast heart rate), lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by bleeding into the skin) on internal mucosal surfaces, such as in the mouth and throat, and on the skin. The petechiae may give way to larger rashes called ecchymoses, and other haemorrhagic phenomena. There is usually evidence of hepatitis, and severely ill patients may experience rapid kidney and liver failure or pulmonary failure after the fi fth day of illness. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 79 Early supportive care improves survival • General supportive care with treatment of symptoms is the main approach to managing CCHF in people. • The antiviral drug ribavirin has been used to treat CCHF infection and may be benefi cial if used early in the course of the illness. Both oral and intravenous formulations exist and seem to be effective. Currently, WHO is reviewing evidence for ribavirin use for the treatment of CCHF. • There is currently no licensed or commercially available vaccine against CCHF for humans and the animal hosts. Infection prevention and control measures are critical to control the infection when caring for patients or during burial ceremonies • Infection prevention and control measures while providing care to patients with suspected or confi rmed Crimean-Congo haemorrhagic fever are the same as those for Ebola and Marburg haemorrhagic fever. 5 6 PRECAUTIONS TO BE TAKEN: When caring for patients Standards precautions regardless of the diagnosis • Hand hygiene • Respiratory hygiene • Use of personal protective equipment (to block splashes / other contact with infected material) • Safe injection practices During burial ceremonies • Only trained burial team should handle the bodies of people who may have died from CCHF • Burial teams should be trained & equipped to properly, safely and with dignity bury the dead Health care workers caring for patients with suspected or confirmed CCHF virus • Extra infection control measures to prevent contact with patient’s blood and body fluids and contaminated surface or material such as clothing or bedding • Face protection (a face shield or a medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures) should be worn when in close contact (within 1 metre) of patients with CCHF Caring of patients at home • Gloves and appropriate personal protective equipment should be worn • Regular hand washing CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 80 Raising awareness on risk factors and preventive measures is key to reduce infection in people • In the absence of a vaccine, the best way to reduce infection in people is by raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus. People should be informed about: • Measures to reduce the risk of tick-to- human transmission include: - Wearing protective clothing (long sleeves, long trousers); - Wearing light coloured clothing to allow easy detection of ticks on the clothes; - Using approved acaricides (chemicals intended to kill ticks) on clothing; - Using approved repellent on the skin and clothing; - Regularly examining clothing and skin for ticks; if found, removing them safely; - Seeking to eliminate or control tick infestations on animals or in stables and barns; - Avoiding areas where ticks are abundant and seasons when they are most active. • Measures to reduce the risk of animal-to- human transmission include: - Wearing gloves and other protective clothing while handling animals or their tissues in endemic areas, notably during slaughtering, butchering and culling procedures in slaughterhouses or at home; Effi cient vector control measures are currently lacking • Current vector control measures are not fully satisfactory: - Chemicals produce resistant ticks, food contamination, and environmental pollution. Furthermore, the tick vectors are numerous and widespread, so tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well- managed livestock production facilities; - Physical measures (heavy grazing, burning of grasslands) have an important negative impact on the environment; - Biological measures (e.g. use of hormones and growth regulators, use of predators, bacteria, nematodes and fungi) have not demonstrated full effi cacy. • An animal vaccine effective against Hyalomma ticks that prevent the tick- animal-tick cycle would decrease tick population, decrease CCHF prevalence in animals, and therefore decrease human exposure, being a cost effective CCHF prevention measure. 7 8 - Quarantining animals before they enter slaughterhouses or routinely treating animals with approved acaricides two weeks prior to slaughter. • Measures to reduce the risk of human- to-human transmission in the community include: - Avoiding close physical contact with CCHF-infected people; - Wearing gloves and protective equipment when taking care of ill people; - Washing hands regularly after caring for or visiting ill people. CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 81 CCHF can be misdiagnosed with other viral haemorrhagic fevers and early laboratory confi rmation of suspected cases is critical to mount the response • Due to lack of standardized case defi nition and knowledge about CCHF, the disease can be misdiagnosed. This is why laboratory confi rmation is critical to guide response activities. 9 Proposed case defi nition: Suspected case: Illness with sudden onset of fever with one or more of the following: headache, myalgia, nausea, vomiting, diarrhoea, myalgia, abdominal pain and a history of tick bite or contact with wild animals or livestock or contact with a case of CCHF. Probable case: A deceased suspected case (where it has not been able to collect specimen for laboratory confi rmation) that has an epidemiological link with a laboratory confi rmed case. Confi rmed case: A suspected case that is laboratory confi rmed (positive for IgM antibodies, positive for CCHF virus antigen, positive for CCHF RNA by RT-PCR or virus isolation). • Samples taken from people with suspected CCHF should be handled by trained staff working in suitably equipped laboratories. • CCHF virus infection can be diagnosed by several different laboratory tests: - Enzyme-Linked Immunosorbent Assay (ELISA); - Antigen detection; - Serum neutralization; - Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay; - Virus isolation by cell culture. • Patients with fatal disease, as well as in patients in the fi rst few days of illness, do not usually develop a measurable antibody response and so diagnosis in these individuals is achieved by virus or RNA detection in blood or tissue samples. • Tests on patient samples present an extreme biohazard risk and should only be conducted under maximum biological containment conditions (BSL4). However, if samples have been inactivated (e.g. with virucides, gamma rays, formaldehyde, heat, etc.), they can be manipulated in a basic biosafety environment. Days10d7d Incubation 3-6 days Prehaemorrhagic period 1-5 days Haemorrhagic period 2-5 days Convalescence 2-5 days Fever Virus / Antigen Neutralizing / IgG ELISA Antibodies IgM Antibodies Death (10-40%) Polymerase chain reaction: The first 9 days after onset Myalgia, fever, nausea, vomiting, diarrhea Bleeding from various sites (hematemesis, melena, etc.) somnolence IgM (7 days - 4 months) and IgG (7 days - 5 years) CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 82 CCHF is one of the priority disease for research and development in public health emergency contexts (R&D Blueprint) • Research and Development roadmaps and target product profi les are being developed in consultation with experts and stakeholders (as part of the R&D Blueprint). • Research is ongoing for therapeutics (rib- avirin, favipiravir, intravenous immuno- globulin, monoclonal antibodies), for rap- id diagnostics and for an animal anti-tick vaccine effective against Hyalomma ticks. • Given the epidemiology of CCHF, with a limited number of cases reported yearly, a human vaccine might not be the most cost-effective and viable control measure. 10 CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 83 50° North latitude: Limit for geographic distribution of genus Hyalomma ticks The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reservedSource: WHO/IHM as of July 2017 Geographic distribution of Crimean-Congo haemorrhagic fever Hyalomma ticks vector presence CCHF virological / serological evidence & vector presence 5–49 CCHF cases reported per year 50 and more CCHF cases reported per year CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 84 More information about Crimean-Congo haemorrhagic fever (CCHF): • CCHF WHO webpage http://www.who.int/csr/disease/crimean_congoHF/en/ • CCHF WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs208/en/ • R&D Blueprint: http://www.who.int/blueprint/en/ • Infection prevention and control guidance for care of patients in health care settings, with focus on Ebola: http://www.who.int/csr/resources/publications/ebola/fi lovirus_infection_ control/en/?ua=1 CRIMEAN-CONGO HAEMORRHAGIC FEVER (CCHF)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 85 1. Urban Yellow fever (YF), the most threatening form of YF epidemics, is transmitted through Aedes aegypti mosquito bites 2. Outbreaks of YF in urban areas can be devastating 3. Emergency mass vaccination and vector control are the two main pillars of YF outbreak response 4. YF vaccine is safe and provides lifelong immunity 5. Vaccine production is limited but there is a global emergency stockpile 6. Routine immunization in children is the key to preventing outbreaks 7. The risk of YF international spread exists but can be prevented by applying the International Health Regulations (IHR) recommendations 8. YF is hard to distinguish from some other diseases with similar symptoms 9. Early clinical management improves survival 10. African Ministers of Health (MOH) are committed to eliminating YF epidemics 10 THINGS YOU SHOULD KNOW Yellow fever YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 86 Yellow fever response tips Coordinating responders • Contact WHO/ICG for emergency vaccines • Engage partners and communities for vector control around cases • Organize emergency mass vaccination campaigns including cold chain and waste management Communicating risk • Encourage health authorities to: - Engage communities for vector control - Work with partners for social mobilization for vaccination campaigns - Ensure vector control in health facilities • Key messages are: - YF is transmitted by mosquitoes - Vaccine is safe and provides lifelong immunity - Seek medical care early as this increases chances of survival Health Information • Laboratory diagnosis may be diffi cult (serological tests cross-react with Dengue and other fl aviviruses) • Think of differential diagnosis of febrile jaundice • Distribute vaccination cards • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement • Emergency mass vaccination • Vector control • Control at borders (airports) • Patient supportive care, with bed nets (also during the day) YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 87 Urban Yellow fever (YF), the most threatening form of YF epidemics, is transmitted through Aedes aegypti mosquito bites • The yellow fever virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species (Aedes aegypti, which can transmit the disease from human to human in urban settings) – it is the same mosquito that spreads Zika, Chikungunya and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. Outbreaks of YF in urban areas can be devastating • YF outbreaks in urban settings can be very devastating as they have the potential to amplify rapidly and spread widely, especially to other countries, because of: - Increased human population densities that lead to rapid amplifi cation of the disease; - Increased density of the mosquito vector of urban YF epidemics that breeds in man-made containers of water, feeds predominantly on human blood and bites multiple individuals in a single blood meal, and lives in close association with human dwellings; - Ease and speed of population movements, as well as easy access to airports, facilitate spread of the disease and its exportation to other countries; 1 2 - Diffi culties in assessing target populations, and in mounting reactive interventions in informal urban settings. • There are three types of transmission cycles. However, with climate and demographic change in endemic settings, this classifi cation may be reviewed. - Sylvatic (or jungle) Yellow fever: In tropical rainforests, monkeys, which are the primary reservoir of yellow fever, are bitten by wild mosquitoes which pass the virus on to other monkeys. Occasionally, humans working or travelling in the forest are bitten by infected mosquitoes and develop yellow fever. This is the most common type of outbreak in the Americas; - Intermediate Yellow fever: In this type of transmission, semi-domestic mosquitoes (those that breed both in the wild and around households) infect both monkeys and people. Increased contact between people and infected mosquitoes leads to increased transmission and many separate villages in an area can develop outbreaks at the same time; - Urban Yellow fever: Large epidemics occur when infected people introduce the virus into heavily populated areas with high mosquito density and where most people have little or no immunity, due to lack of vaccination. In these conditions, infected Aedes Aegypti mosquitoes transmit the virus from person to person. This is the most serious outbreak because it amplifi es quickly. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 88 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 89 Emergency mass vaccination and vector control are the two main pillars of YF outbreak response Vector control: • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these interventions: - Elimination of breeding sites and eggs/larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up campaigns, etc.); - Targeted residual spraying of adult mosquitoes (in areas known to be resting sites for Aedes mosquitoes) and space spraying when there is an outbreak; - Mosquito control programmes targeting wild mosquitoes in forested areas are not practical and not recommended for preventing jungle (or sylvatic) yellow fever transmission. 3 • Additionally, personal preventive measures such as clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning are recommended to avoid mosquito bites. The use of insecticide-treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). Emergency mass vaccination: • Reactive mass vaccination campaigns, by increasing immunity in the population, reduce the possibility of transmission of the virus. Vaccine coverages greater than 80%, with a 60-80% security threshold, are necessary to interrupt autochthonous transmission (human- mosquito-human) of YF virus within a community and ensure that sporadic unvaccinated cases do not generate secondary cases. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 90 Vaccine production is limited but there is a global emergency stockpile • They are four prequalifi ed vaccine manufacturers and global supply production is limited. There is a global emergency stockpile of six million vaccine doses, which can be accessed by any country facing an outbreak, through a request to the International Coordinating Group (ICG). • For outbreak response, in case of shortage of vaccine, it is possible to use a fraction of the vaccine doses (1/5), in order to rapidly increase the population immunity and stop human-to-human transmission. - Children under two years of age should be offered a full dose, as they may have a weaker immune response to the vaccine than older people; - There is no evidence of increased serious adverse effects when using a fractional dose. 5YF vaccine is safe and provides lifelong immunity• There is a good vaccine against YF. It has been used for many decades and is safe and affordable, providing effective immunity against yellow fever within 10 days for more than 90% of people vaccinated and within 30 days for 99% of people vaccinated. A single dose provides lifelong protection. A booster dose of yellow fever vaccine is not needed. • Adverse effects of the Yellow fever vaccine are generally mild and may include headaches, muscle aches, and low-grade fevers. Serious adverse effects are rare. • In Yellow fever endemic countries, WHO strongly recommends routine vaccination for everyone older than 9 months. People over 60 years of age should be given the vaccine after a careful risk-benefi t assessment. Some people should not be routinely vaccinated, including: - Infants aged less than 9 months; - Pregnant women (unless during an outbreak if the risk of disease outweighs the potential adverse effect of the vaccine); - People with severe allergies to egg protein; and - People with severe immunodefi ciency. 4 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 91 Routine immunization in children is the key to preventing outbreaks • Vaccination is the single most important measure for preventing yellow fever. The prevention of outbreaks can only be achieved if the majority of the population is immunized. • YF routine immunization in the Expanded Programme on Immunization (EPI) can provide suffi cient population immunity. However, it takes about 30 years to build the population immunity to adequate levels to stop potentially large scale outbreaks. Mass preventive vaccination campaigns to other age groups accelerate the building of population immunity through what is called the YF “combined vaccination strategy”. 6 Population protected by routine immunization, preventive mass campaigns and combined vaccination strategy (A) Routine child immunization Number of years after the intervention (C) Combined vaccination strategy: Routine childhood immunization + one preventive mass vaccination campaign (B) Preventive mass vaccination campaign 100 90 80 70 60 50 40 30 20 10 0 1 10 2.3 22.8 45.6 68.4 91.2 20 30 Pro po rti on (% ) o f p op ula tio n p rot ect ed 40 100 90 80 70 60 50 40 30 20 10 0 1 10 80.0 55.1 26.6 0 0 20 30 40 1 10 82.3 77.9 72.2 91.2 68.4 20 30 40 100 90 80 70 60 50 40 30 20 10 0 Vaccine coverage security threshold YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 92 • It is recommended that major sectors recruiting international workers, with potential sylvatic exposure (extractive, mining, construction and forestry industries), take measures to ensure their staff and families are vaccinated. • To prevent international spread, it is essential that the International Health Regulations (2005) are applied and that travelers present yellow fever vaccination certifi cates. Under the IHR (2005), it is also essential to notify YF cases that have a serious public health impact and/or are unusual or unexpected, and/or could lead to international spread and/or present a signifi cant risk of travel or trade restrictions. • Vector control measures may be applied in various forms of transport, in accordance with the IHR (2005). The risk of YF international spread exists but can be prevent- ed by applying the International Health Regulations (IHR) recom- mendations • With the increasing occurrence of urban YF outbreaks comes an increased risk of international spread of diseases, because big cities are transport hubs with frequent transport connections. A particularly concerning scenario would be exportation of the disease to a country where the vector is present and population immunity levels are low, which could lead to local transmission. • For Yellow fever, exportation of cases to Asia is especially worrisome as all favorable conditions for local transmission (vector such as Aedes aegypti, non-immune populations) are present in this continent, as demonstrated by dengue activity. 7 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 93 YF is hard to distinguish from some other diseases with similar symptoms • Yellow fever is diffi cult to diagnose (especially during the early stages) because its symptoms are not specifi c and can be confused with other common diseases such as Malaria, Viral Hepatitis (when jaundice), Dengue, Leptospirosis (when jaundice), other arbovirus diseases, Ebola virus disease (when haemorrhagic) as well as with poisoning. - Once contracted, the Yellow fever virus incubates in the body for three to six days; - Most people (about 88% of those infected) do not experience symptoms; - Symptoms usually develop in two phases: o First to occur are common, unspecifi c symptoms, including fever, muscle pain with prominent backache, headache, loss of appetite, and nausea or vomiting. In most cases, symptoms disappear after three to four days. o A small percentage of patients (about 2-3% of infected people) will then enter a second, more toxic phase within 24 hours of recovering from initial symptoms. High fever returns and several body systems are affected, usually the liver and the kidney, hence the characteristic jaundice – which gives yellow fever its name - dark urine and abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes or stomach. Half of the patients who enter the toxic phase die within seven to ten days. The rest recover without signifi cant organ damage. 8 • Laboratory tests are necessary to confi rm yellow fever and access the global stockpile:- In the fi rst phase, blood is collected for RT- PCR – Reverse Transcription Polymerase Chain Reaction, to confi rm the presence of the virus (viremia); - In later stages of the disease, serology testing to identify antibodies is needed (ELISA, Enzyme-Linked Immunosorbent Assay and PRNT, Plaque Reduction Neutralization Test, for neutralizing antibodies). The detection of antibodies indicates that the person has either been infected or vaccinated, but it cannot distinguish between the two. The level of antibodies’ titres and their evolution over time, on a second sample, can provide indication of how acute the infection might be; - Whenever YF is suspected, there should also be systematic testing by serology and PCR for other arboviruses (such as Dengue, Zika, Chikungunya, West Nile, Rift Valley Fever) and viral haemorrhagic fever (VHF, such as Ebola, Lassa, Crimean- Congo haemorrhagic fever); - YF tests should be realized in laboratories with appropriate capacity to test for both YF and the differential diagnosis. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 94 African Ministers of Health (MOH) are committed to eliminating YF epidemics • Yellow fever is an acute viral haemorrhagic disease. The virus is endemic in tropical areas of Africa and the Americas. Susceptible non-human primates are the animal reservoir, they are necessary to maintain the endemicity. • Forty of the 47 YF-affected countries have been identifi ed as priority nations by the Eliminate Yellow Fever Epidemics (EYE) Strategy. The updated Strategy was developed by a coalition of countries and partners to respond to 10 the disease’s changing epidemiology, resurgence of mosquitoes, and the increased risk of urban outbreaks and international spread. • African Member States endorsed the (EYE) Strategy in 2017 and agreed on ten priority actions to guide countries to the elimination of YF epidemics by 2026. 9 Early clinical management improves survival • Good and early supportive treatment in hospitals improves survival rates. • There is currently no specifi c anti-viral drug for yellow fever but specifi c care to treat dehydration, liver and kidney failure, and fever improves outcomes. • Patients need to stay under mosquito nets during the day to limit the risk of spread to others through bites of mosquitoes. YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 95 l, Cabo Verde Guinea-Bissau Gambia Senegal Sierra Leone Liberia Guinea – Côte d’Ivoire Ghana Burkina Faso Togo Benin Sao Tome and Principe Nigeria Gabon Congo Equatorial Guinea Camer oon – Angola Democratic Republic of the Congo South Africa Lesotho Swaziland Botswana Zimbabwe Namibia Zambia Malawi Mozambique Madagascar Comoros Rwanda Burundi United Republic of Tanzania Mauritius Seychelles Kenya Uganda Somalia – Ethiopia Djibouti South Sudan – Eritrea Sudan Chad Niger Central African Republic Egypt Libya Tunisia Algeria Mali Morocco Mauritania The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Yellow fever (YF) risk classifi cation, by country - Africa, 2016 YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 96 Yellow fever (YF) risk classifi cation, by country – LAC* countries, 2016 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. This map illustrates a public-health-intervention oriented YF risk approach at country level. Its purpose is different from the YF risk area maps for travellers in the context of IHR. Argentina Uruguay Chile Peru Bolivia (Plurinational State of) Pa raguay Ecuador Colombia Panama Venezuela (Bolivarian Republic of) – Trinidad and Tobago Guyana Suriname French Guiana Brazil * LAC: Latin American and Caribbean High-risk Potential-risk No evidence available for YF or indicative arbovirus circulation YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 97 More information about Yellow fever • Yellow fever WHO webpage http://www.who.int/csr/disease/yellowfev/en/ • Yellow fever WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs100/en/ • EYE Strategy http://apps.who.int/iris/bitstream/10665/255040/1/WER9216.pdf?ua=1 • Yellow fever WHO MOOC https://openwho.org/courses/pandemic-epidemic-diseases • WHO standard case defi nitions http://www.who.int/csr/disease/yellowfev/case-defi nition/en/ YELLOW FEVERMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 98

1. Zika virus is transmitted by Aedes mosquitoes, which primarily bite during the day 2. This virus infection is usually asymptomatic, but can lead to severe complications 3. Infection during pregnancy presents many serious hazards for mother and child (microcephaly in children) 4. Zika virus is a trigger of Guillain-Barré syndrome 5. The virus is also transmissible through sexual contact, blood transfusion, and organ transplantation 6. Vector control strategies are important for prevention and control 7. Individuals should protect themselves from mosquito bites 8. Access to laboratory testing is critical for pregnant women 9. There is no vaccine or specifi c treatment for Zika virus infection 10. Warnings have been issued for pregnant women and their male partners 10 THINGS YOU SHOULD KNOW Zika ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 100 Zika response tips Coordinating responders • Coordination of public health, maternal and child health, vector control and clinical services • Social services to support affected children and families Communicating risk • Encourage health authorities to: - Engage communities for eliminating mosquito breeding sites - Communicate with at-risk groups through their trusted sources of information • Key messages: - Zika is transmitted through mosquito bites during the day - The babies of pregnant women are at risk for adverse pregnancy outcomes - Zika can be sexually transmitted - Women of reproductive age should seek advice before getting pregnant during outbreaks and should seek medical advice if they fall pregnant Health Information • Early detection, reporting, and monitoring of cases • Laboratory capacity for diagnosis especially in pregnant women • Laboratory diagnosis may be diffi cult (serological tests cross-react with Dengue and other fl aviviruses) Health Interventions • Community engagement and health promotion • Early response • Prevention of infection by Aedes mosquitoes, particularly pregnant women • Reduce breeding sites of Aedes mosquitoes around dwellings • Clinical supportive care of patients with Guillain-Barré and severe symptoms • Support to babies born with microcephaly • Psychosocial counselling and support ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 101 Zika virus is transmitted by Aedes mosquitoes, which primarily bite during the day • The Zika virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species – it is the same mosquito that spreads Yellow fever, Chikungunya and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. • Local transmission of Zika virus by Aedes mosquitoes has been reported on the continents of Africa, the Americas, South- East Asia and the Western Pacifi c. • There are 2 types of Aedes mosquitoes known to be capable of transmitting Zika virus: - In most cases, Zika is spread through the Aedes aegypti mosquito in tropical and subtropical regions; - Aedes albopictus mosquitoes can also transmit Zika virus and can tolerate cooler temperatures; - Both species are found biting outdoors but Aedes aegypti will also feed indoors. This virus infection is usually asymptomatic, but can lead to severe complications • About 80% of infected people do not develop symptoms. • People with symptoms usually present with mild fever, rash, conjunctivitis (infl ammation of the eyes), muscle and joint pain, malaise, and headache. 1 2 • Symptoms normally last two to seven days. • The incubation period (the time from exposure to onset of symptoms) of Zika virus disease is unknown but is most likely less than one week if it is similar to that of other mosquito-borne fl aviviruses. • Zika virus infection can lead to severe neurological complications in a relatively small proportion of those infected: - Microcephaly and other congenital abnormalities; - Preterm birth and fetal death; - Guillain-Barré syndrome; - Investigations are ongoing on the links between Zika virus and other adverse outcomes. • Zika virus can be classifi ed into two main lineages: the Asian lineage and African lineage. To date, the Asian lineage Zika virus strain is responsible for the recent 2015/2016 epidemics. It is not known whether the African lineage Zika virus strains would produce neurological symptoms with similar or worse gravity than those observed in the 2015/2016 epidemics. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 102 Infection during pregnancy presents many serious hazards for mother and child (microcephaly in children) • Zika virus can be transmitted from mother to child during pregnancy, and can result in congenital abnormalities: - Microcephaly is a condition where the infant’s head is smaller than those of other babies of the same age and sex (more than three standard deviations below average for gestational age). Infants born with microcephaly are at risk for severe intellectual disability and may also develop convulsions and physical disabilities as they grow older. There is no specifi c treatment for microcephaly; o Diagnosis of microcephaly is often made at birth. All infants should have head circumference measured and recorded within 24 hours of birth. Early diagnosis of microcephaly can sometimes be made by fetal ultrasound. Prenatal diagnosis by ultrasound is more accurate in the second and third trimesters. - Other newborn complications associat- ed with in-utero Zika infection include brain calcifi cations, seizures, irritability, brainstem dysfunction such as swallowing Zika virus is a trigger of Guillain- Barré syndrome • Guillain-Barré syndrome (GBS) is a rare condition in which a person’s immune system attacks the peripheral nerves. • People of all ages can be affected, but it is more common in adults and in males. • Symptoms typically last a few weeks. If supported through the critical stages of disease, most individuals can recover without long-term complications. - The fi rst symptoms of Guillain-Barré syndrome include weakness or tingling, usually starting in the legs and can spread to the arms and face; - Some patients can develop paralysis of the legs, arms, or muscles in the face. In 20%–30 % of people, the chest muscles are affected, making it diffi cult to breathe; - The ability to speak and swallow may become affected in severe cases of Guil- lain-Barré syndrome; - Severe cases of Guillain-Barré syndrome are rare, but can result in near-total paralysis. • Guillain-Barré syndrome is therefore po- tentially life-threatening. People with Guil- lain-Barré syndrome should be treated and closely monitored; severe cases may require intensive care including ventilato- ry respiratory support. Treatment includes supportive care and some immunological therapies. • Even in the best of settings, 3%–5% of Guillain-Barré syndrome patients die from complications, which include paralysis of the muscles that control breathing, infection, sepsis, or cardiac arrest. 3 4 problems, limb contractures, develop- mental delay, hearing and sight abnor- malities, and other brain abnormalities; - Support services for affected infants and families are an important component of Zika programmes. • Other adverse pregnancy outcomes associated with Zika virus infection include preterm birth, miscarriage, and still birth. • Zika virus has been identifi ed in breast milk, but transmission by breastfeeding has not yet been reported. Current evidence suggests that the benefi ts of breastfeeding outweigh the theoretical risk of Zika virus infection transmission through breast milk. • More information is needed on the long term outcomes of infants infected during pregnancy, delivery, and in the early post- partum period. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 103 The virus is also transmissible through sexual contact, blood transfusion, and organ transplan- tation • Zika virus can be transmitted through sexual intercourse. This is of concern because of the association between Zika virus infection and adverse pregnancy outcomes. • In regions with active Zika virus transmission, health programmes should ensure that: - All people with Zika virus infection and their sexual partners (particularly pregnant women) receive information about the risks of sexual transmission of Zika virus; - Men and women receive counselling on safe sexual practices and are offered condoms; - Sexually active men and women should be counselled and offered a full range of contraceptive methods to make informed choices about whether and when to become pregnant, to prevent unintended pregnancies, and prevent possible adverse pregnancy outcomes; - Pregnant women should be advised not to travel to areas of ongoing Zika virus outbreaks. • Other modes of person-to-person Zika transmission include: blood transfusion, organ transplantation and laboratory or other blood-borne exposure. Vector control strategies are important for prevention and control • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these inter- ventions: - Elimination of breeding sites and eggs/ larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up cam- paigns, etc.); - Targeted residual spraying of adult mos- quitoes (in areas known to be resting sites for Aedes mosquitoes) and space spray- ing when there is an outbreak. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito popula- tions and prevention disease. Both larval and adult vector populations should be targeted for surveillance. 5 6 • Standard WHO recommendations regarding vector control at airports should be implemented in accordance with the IHR (2005). Countries should consider disinfection of aircraft. ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 104 Access to laboratory testing is critical for pregnant women • Because of the association between Zika virus infection and adverse pregnancy and infant outcomes, it is important that women have access to laboratory testing. The woman (and her partner if she/he wishes) should be offered non-directive counselling so that she, in consultation with her health care provider, can make a fully informed choice about the next steps in the management of her pregnancy. • Laboratories should have the capacity to test for Zika: - Laboratory tests are done on blood or other body fl uids (e.g. urine, saliva, semen): o Polymerase Chain Reaction (PCR) during the acute phase of the disease; o Serological (IgM) testing and Nucleaic Acid Tests (NAT) testing with Plaque Re- duction Neutralization Test (PRNT). In- fection with Zika virus is diffi cult to con- fi rm retrospectively because serological tests cross react with other fl aviviruses, especially Dengue virus. 7 8 Individuals should protect them- selves from mosquito bites • The community, and particularly pregnant women and women of reproductive age, should be educated about the risk of transmission and how to minimize this risk by reducing contact with mosquitoes. • Personal preventive measures to avoid mosquito bites include clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning. The use of insecticide- treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 105 There is no vaccine or specifi c treatment for Zika virus infection • Currently, there are no antiviral drugs or specifi c treatment for people with Zika virus disease. Zika virus disease in individuals including non-pregnant women is usually mild and requires no specifi c treatment. Individuals with more severe symptoms should receive supportive care including rest, fl uids, and management of pain and fever. They should be offered psychosocial support. • Research is ongoing for potential therapies, for vaccines to prevent Zika virus infection or Congenital Zika Syndrome, and for diagnostic tests. Warnings have been issued for pregnant women and their male partners • There are no general restrictions on travel or trade with countries, areas and/or territories with Zika virus transmission. • However, WHO is advising pregnant women not to travel to the following Zika- affected areas: - Areas with new introduction of Zika virus since 2015 or where the virus has been re- introduced, with ongoing transmission; - Areas with evidence of Zika virus circulation before 2015 or with ongoing transmission (but not satisfying the category above). • Health authorities are responsible for advising travellers on risks and preventive measures. 9 10 ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 106 Countries and territories* with reported Zika virus transmission The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved * Note: This includes areas with new introduction or re-introduction with ongoing transmission; areas either with evidence of virus circulation before 2015 or area with ongoing transmission that is no longer in the new or re-introduction phase, but where there is no evidence of interruption; and areas with interrupted transmission and with potential for future transmission. Countries and territories* with reported Zika virus transmission Source: WHO/IHM; as of 15 January 2018 ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 107 More information about Zika • Zika WHO webpage: http://www.who.int/csr/disease/zika/en/ • Zika virus WHO fact sheet: http://www.who.int/mediacentre/factsheets/zika/en/ • Risk communications and community engagement http://www.who.int/csr/resources/publications/zika/community- engagement/en/ • Pregnancy management in the context of Zika virus infection: http://www.who.int/csr/resources/publications/zika/pregnancy- management/en/ • Care and support of people affected by complications associated with Zika virus: http://www.who.int/mental_health/neurology/zika_toolkit/en/ • Prevention of sexual transmission: http://www.who.int/csr/resources/publications/zika/sexual- transmission-prevention/en/ • Identifi cation and management of Guillain-Barré syndrome in the context of Zika virus: http://www.who.int/csr/resources/publications/zika/guillain-barre- syndrome/en/ ZIKAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 108

1. Chikungunya is transmitted by Aedes mosquitoes, which primarily bite during the day 2. Chikungunya outbreaks occur typically in urban settings 3. Chikungunya causes an acute febrile illness 4. Convalescence may be long and patients may present complications and sequelae 5. Treatment is directed primarily at relieving symptoms 6. Chikungunya is often misdiagnosed with Dengue and other diseases 7. Controlling the mosquito vector is key to outbreak prevention and control 8. Vector surveillance is critical to determine vector control strategies 9. Chikungunya virus infection seems to elicit long-lasting protective immunity 10. Chikungunya is emerging as a global disease 10 THINGS YOU SHOULD KNOW Chikungunya CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 110 Chikungunya response tips Coordinating responders • Coordination of public health, environmental, clinical services and vector control Communicating risk • Encourage health authorities to: - Communicate to the public about how to protect from the disease - Advise on seeking health care for high-risk groups - Eliminate mosquito breeding grounds • Key messages: - Chikungunya can cause acute and chronic illness - Chikungunya is transmitted by mosquitoes Health Information • Laboratory capacity for diagnosis and surveillance • Vector distribution surveillance • Early detection, reporting, response and monitoring Health Interventions • Community engagement and health promotion • Vector control: - Reduce breeding sites of Aedes mosquitoes around dwellings - Prevent mosquito bites during the day • Supportive care • Patient care with bed nets (also during the day) CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 111 Chikungunya is transmitted by Aedes mosquitoes, which primarily bite during the day • The Chikungunya virus is transmitted to humans by infected mosquitoes, most commonly from the Aedes species – it is the same mosquito that spreads Yellow fever, Zika and Dengue viruses. • Outbreaks usually occur in areas where mosquitoes breed. • The current distribution of Aedes aegypti is the widest ever recorded and Aedes mosquitoes are present in all continents. Urbanization with resulting increased population densities, further enhanced by man-made larval habitats, amplifi es mosquito-transmitted diseases. • Aedes mosquitoes usually bite during the day, peaking during early morning and late afternoon/evening. • There are 2 types of Aedes mosquitoes known to be capable of transmitting Chikungunya virus: - In most cases, Chikungunya is spread through the Aedes aegypti mosquito in tropical and subtropical regions; - Aedes albopictus mosquitoes can also transmit Chikugunya virus and can tolerate cooler temperatures; - Both species are found biting outdoors but Aedes aegypti will also feed indoors. • Transmission of the virus can also occur through blood transfusion and laboratory or other blood-borne exposure. Chikungunya outbreaks occur typically in urban settings • Human beings serve as the Chikungunya virus reservoir during epidemic periods. • Urban Chikungunya virus transmission follows those observed for Dengue virus. 1 2 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 112 Chikungunya causes an acute febrile illness • Chikungunya causes an acute febrile illness typically accompanied by arthralgia. • Other common symptoms and signs include muscle pain, headache, nausea, fatigue and rash. • The joint pain is often debilitating, usually lasting a few days, but may be prolonged to weeks. Hence, the virus can cause acute, subacute or chronic disease. • The disease shares some clinical signs with Dengue and can be misdiagnosed in areas where Dengue is common. • Children may experience other symptoms such as minor hemorrhagic manifesta- tions, arthralgia/arthritis, lymphadenop- athy, conjunctival injection, swelling of eyelids and pharyngitis. Rare clinical fea- tures include neurological manifestations including seizures, altered level of con- sciousness, and blindness due to retrob- ulbula neuritis and acute fl accid paralysis. • The disease is generally not fatal. Symptomatic treatment along with rest usually suffi ces. • After the bite of an infected mosquito, onset of illness occurs usually between four and eight days but can range from two to 12 days. • The acute phase of Chikungunya lasts for three to 10 days but convalescence can be prolonged up to one year and more. • There are asymptomatic patients but it is unknown how frequently it occurs. Convalescence may be long and patients may present complications and sequelae • Rare clinical manifestations of Chikungunya include neurological, hemorrhagic, and ocular and severe multiple organs system involvement. • In older people, the disease can contribute to earlier death that may be due to the frequency of concomitant underlying diseases or decreased immunologic response. • Some patients have reported disabling joint pain or arthritis, which may last for weeks or months. These patients may require long-term anti-infl ammatory therapy. • Patients with Chikungunya should be assisted from their communities and enabled to seek occupational and social rehabilitation. 3 4 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 113 Treatment is directed primarily at relieving symptoms • There is no specifi c antiviral drug treatment for Chikungunya. • Treatment is directed primarily at reliev- ing the symptoms using anti-pyretics (paracetamol is the drug of choice), op- timal analgesics and fl uids. Applying cold compresses have been reported to less- en the joint symptoms. • People with Chikungunya should rest and consume plenty of water. • Aspirin should be avoided due to its effect on platelets. Paracetamol or nonsteroidal anti-infl ammatory drugs may be used for symptom relief. • All suspected cases should be kept under mosquito nets during the febrile period. • Patients and their families should be provided with psychosocial support. • There is no Chikungunya vaccine although some candidate vaccines are being tested in human beings. Chikungunya is often misdiagnosed with Dengue and other diseases • Chikungunya patients may present nonspecifi c symptoms that could be confused with many other diseases such as Dengue, Leptospirosis, Malaria, Meningitis, and Rheumatic fever. Laboratory diagnosis is thus critical to establish the cause of diagnosis and initiate specifi c public health response. • Several methods can be used for diagnosis: - Molecular technique: Polymerase Chain Reaction (PCR); - Virus isolation: the virus may be isolated from the blood during the fi rst few days of infection. Various Reverse Transcription Polymerase Chain Reaction (RT–PCR) methods are available but are of variable sensitivity; - Serological tests such as Enzyme-Linked Immunosorbent Assays (ELISA), may confi rm the presence of IgM and IgG anti- chikungunya antibodies. IgM antibody levels are highest three to fi ve weeks after the onset of illness and persist for about two months. 5 6 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 114 Controlling the mosquito vector is key to outbreak prevention and control • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. Community engagement is essential for these interventions: - Elimination of breeding sites and eggs/larvae/pupae in standing water (e.g. cleaning roof gutters, clean-up campaigns, etc.); - Targeted residual spraying of adult mosquitoes (in areas known to be resting sites for Aedes mosquitoes) and space spraying when there is an outbreak. • Additionally, personal preventive measures such as clothing minimizing skin exposure, use of repellents, as well as windows screens and air conditioning are recommended to avoid mosquito bites. The use of insecticide-treated bed nets is limited by the fact that Aedes mosquitos bite during daytime. • Eventually, economic development will reduce mosquito-borne diseases by improving standards of living (e.g. people living in houses with solid fl oors and roofs, window screens, and air conditioning). • Standard WHO recom- mendations regarding vector control at airports should be implement- ed in keeping with the IHR (2005). Countries should consider disin- fection of aircraft. Vector surveillance is critical to determine vector control strategies • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. • These data will enable the selection and use of the most appropriate vector control tools, and can be used to monitor their effectiveness. 7 8 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 115 Chikungunya virus infection seems to elicit long-lasting protective immunity • There are still a lot of unknowns (including the clinical spectrum of the disease) and research is ongoing to fi ll scientifi c gaps in our understanding of the disease. • The reasons for the mysterious behavior of dramatic outbreaks interspersed by periods of prolonged absence, virus survival in nature and factors triggering outbreaks need to be further studied. • Research also focuses on diagnostics tests, treatments and vaccines. Chikungunya is emerging as a global disease • Urbanization, human travel, viral adaption, lack of effective control measures, and spread of new vectors likely have contributed to recent re-emergence of Chikungunya. • There is a risk of epidemics in subtropical and temperate regions of the world where Aedes albopictus is a potential vector. • The dramatic spread of the Dengue, Chikungunya, and Zika viruses in recent years highlights the urgent need to identify Aedes control options. 9 10 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 116 Predicted distribution of the Aedes Aegypti mosquito CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 117 Predicted distribution of the Aedes Albopictus mosquito CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 118 More information about Chikungunya: • Chikungunya WHO webpage: http://www.who.int/emergencies/diseases/chikungunya/en/ • Chikungunya WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs327/en/ • Prevention and control: http://www.wpro.who.int/mvp/topics/ntd/Chikungunya_WHO_ SEARO.pdf • WHO standard case defi nitions: http://www.who.int/wer/2015/wer9033.pdf?ua=1 CHIKUNGUNYAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 119 1. Animal infl uenza viruses have occasionally infected humans (Avian, swine and other zoonotic infl uenza viruses) 2. Multisectoral coordination and communication are essential parts of any outbreak response 3. Protect all individuals with occupational or other risks of exposure 4. Eggs, poultry and poultry products can be safely consumed, provided these items are properly cooked and properly handled during food preparation 5. To minimize exposure of the public, encourage proper personal hygiene and instruct the public to seek medical help if illness develops 6. Increase surveillance for human cases of Avian infl uenza 7. Collecting appropriate samples, and rapid and precise characterization of virus isolates are essential for early detection and management of patients 8. Health care facilities need to be ready to manage patients with Avian infl uenza virus infections 9. The animal health sector is in charge of preventing and controlling outbreaks of disease in animals, including Avian infl uenza 10. Infl uenza A(H5N1) vaccines are not widely available and the decision to use them depends on the risk of infection 10 THINGS YOU SHOULD KNOW Avian and other zoonotic infl uenza AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 120 Avian and other zoonotic infl uenza response tips Coordinating responders • Multisectoral response: collaboration between animal health sector and public health sector is key in surveillance, response and prevention activities Communicating risk • Encourage health authorities to: - Have a way to compensate owners/farmers for the loss of sick animals to encourage early reporting - Have a multisector communications strategy in place • Key messages: - Avian infl uenza is transmitted primarily from infected animals to human through direct contact - There is usually no sustained human-to-human transmission - Promote good personal hygiene (i.e. handwashing) - Promote proper food safety guidance - Report sick animals to the authorities Health Information • Sharing information from the animal health sector with human health sector supports preventive action in the affected areas • Sharing information on human cases with the animal health sector is equally important so that they can target their response activities • Ensure sharing of viruses from human cases with WHO Collaborating Centres • Report cases to WHO, under the IHR (2005) Health Interventions • Investigate cases and enhance surveillance • Collect appropriate specimens • Antiviral and supportive treatment for cases • Monitoring of contacts • Vaccination of high-risk groups • Infection prevention and control measures: - Prevent nosocomial infections - Personal Protective Equipment AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 121 Animal infl uenza viruses have occasionally infected humans (Avian, swine and other zoonotic infl uenza viruses) • Wild aquatic birds are the reservoir for infl uenza A viruses. The emergence of a new and very different infl uenza A virus with the ability infect people and have sustained human-to-human transmission, can cause an infl uenza pandemic. • Humans can be infected with Avian, swine and other zoonotic infl uenza viruses. • Avian infl uenza is a disease of domestic and wild birds with severe consequences for the poultry sector when outbreaks of disease occur. Domesticated populations (poultry: chickens, ducks, turkeys) can become infected by contact with wild birds. Avian infl uenza viruses are categorized as either low pathogenic (LP) or highly pathogenic (HP) viruses, depending on the severity of the disease they cause in birds and poultry. These two terms do not refer to the disease in humans infected with these viruses. • Avian infl uenza A viruses are distinct from human infl uenza viruses and do not easily transmit between humans. Human infections are primarily acquired through direct contact with infected animals or contaminated environments, but do not result in effi cient transmission of these viruses between people. • Avian and other zoonotic infl uenza infections in humans may cause disease ranging from mild conjunctivitis to severe pneumonia and even death. Multisectoral coordination and communication are essential parts of any outbreak response • The fi rst occurrence of a poultry outbreak of highly pathogenic Avian infl uenza in a country often creates widespread concern and can disrupt social and economic life. Therefore, effective communication with all stakeholders is an essential part of any outbreak response. • Strong coordination between sectors (animals and human health) is needed for surveillance, risk communications and interventions monitoring. 1 2 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 122 Protect all individuals with occupational or other risks of exposure • Protect people involved in specifi c, high- risk tasks such as sampling sick birds, culling and disposing of infected birds and cleaning of contaminated premises. • Provide appropriate personal protective equipment and training on how to use it properly. • All persons involved in these tasks should be registered and monitored closely by local health authorities for seven days following the last day of contact with poultry or their environments. • Symptomatic persons should be treated according to WHO guidelines with infl uenza-specifi c antivirals. • If suffi cient antivirals are available, antiviral chemoprophylaxis can be considered (recommendations for regimen of antiviral prophylaxis can be found in the WHO guidelines). • Consideration should be given to the immunization of persons with high potential to be exposed to Avian infl uenza using the seasonal infl uenza vaccine. Eggs, poultry and poultry products can be safely consumed, provided these items are properly cooked and properly handled during food preparation • Inform the public about ways to promote safe food consumption. Promote thorough cooking of poultry and poultry products. Separate raw meat from cooked or ready-to-eat foods. Keep clean and wash your hands. Handle and store meat properly. • Live animal market hygiene and biosecurity should be assessed and improved where possible. • National food safety authorities and poultry producers should develop and implement quality assurance schemes in line with HACCP (Hazard Analysis Critical Control Point) principles and steps. • Carefully treat drinking water supplied from open surface water to minimize any potential risks. Be aware that properly treated waste water seems to pose only a small risk for humans. Be aware that in some cases, recreational water might be contaminated. And consider that faeces from infected animals can be infectious. 3 4 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 123 To minimize exposure of the public, encourage proper personal hygiene and instruct the public to seek medical help if illness develops • Minimize exposure of the public to potentially infected birds and other sources of contamination and encourage proper personal hygiene, especially frequent hand washing, and instruct people to seek medical help if illness develops. • When Avian infl uenza viruses circulate in an area, all the people who are exposed to infected birds are at risk, especially those who: keep live poultry in their backyards or homes, or purchase live poultry or birds at markets; slaughter, de- feather, or butcher poultry handle and prepare raw poultry for further cooking and consumption; transport or sell live poultry or carcasses; are involved in culling / depopulating / disposing of Increase surveillance for human cases of Avian infl uenza • Avian infl uenza is not easily transmitted from infected animals to humans and there has not been sustained human-to- human transmission. • However, it is important to ensure suspected human cases are investigated in order to give them the best possible treatment; to identify other potential human contacts in those cases and monitor them for occurrence of illness; and to identify if there is human-to- human transmission of the virus. • The most important goal for investigations of human cases of infections with Avian infl uenza viruses is to assess the extent of potential human-to-human transmission, especially in clusters of human cases and contacts of confi rmed cases. • Enhanced surveillance should consider the health care seeking behaviour of the population and can include a range of options such as active and passive approaches that are health care and/or community-based. • Persons with exposure to Avian infl uenza should monitor their health for the duration of the known exposure period plus an additional seven days. This will facilitate early detection of illness and timely commencement of antiviral treatment and isolation precautions. They should report any relevant health problems to a health care facility. 5 6 poultry work in the poultry industry, including farmers and veterinarians; have contact with poultry by-products (e.g. viscera, manure, feathers) or water contaminated with these by-products (e.g. waste water from a live bird market or a slaughtering facility); or consume raw poultry products. • The general public should minimize contact with chickens, ducks or other birds and avoid areas where poultry are housed, slaughtered or prepared. They also should: - Keep children away from birds and their waste, including feathers and manure. Children should neither collect eggs nor assist with slaughtering or food preparation; - Report sick or unexpectedly dead poultry to the authorities immediately; - Comply with all offi cial measures (e.g. animal movement restrictions) that are put in place; - Do not slaughter and/or consume birds that are showing signs of disease or that have unexpectedly died. AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 124 7 8 Collecting appropriate samples and rapid and precise characterization of virus isolates are essential for early detection and management of patients • Collection of appropriate specimens from suspected human cases for identifi cation by a qualifi ed laboratory, together with rapid and precise characterization of virus isolates at specialized reference laboratories, are essential for early detection of cases, proper management of patients, and understanding the epidemiology of the disease. • In addition, appropriate specimen collection is important for monitoring the development of resistance to antivirals, producing effective vaccines, and evaluating laboratory methods. • Ensure that specimen collection materials are available and collection of specimens is done safely, correctly and in a timely manner. • Promote virus/sample sharing with WHO- recognized laboratories. Health care facilities need to be ready to manage patients with Avian infl uenza virus infections • Implement early infection control precautions to prevent nosocomial (originating in a hospital) spread of the disease. • Manage cases properly to prevent severe illness and death. Administer neuraminidase inhibitors (oseltamivir, zanamivir) treatment as the primary choice of antiviral treatment, using the standard regimen for seasonal infl uenza virus infection, as soon as possible (ideally, within 48 hours following symptom onset) to maximize therapeutic benefi ts. Monitor patients and viruses for indications of antiviral resistance. • If there is an insuffi cient in-country supply of neuraminidase inhibitors, WHO can provide it from its strategic global stockpile. • Report laboratory-confi rmed cases to WHO, under the International Health Regulations (2005). AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 125 The animal health sector is in charge of preventing and controlling outbreaks of disease in animals, including Avian infl uenza • Controlling the disease in the animal source is critical to decrease risk to humans. • Reporting new and ongoing outbreaks in animals is important for focusing human health prevention action in the affected areas and raising awareness among professionals working with potentially infected animals, as well as with the public. The sharing of information on human cases with the animal health sector is equally important so that they can target their response activities. • The Food and Agriculture Organization (FAO) of the United Nations (UN) promotes food security and good nutrition by providing access to knowledge, policy advice and technical Infl uenza A(H5N1) vaccines are not widely available and the decision to use them depends on the risk of infection • WHO recommends the targeted administration of seasonal infl uenza vaccine to health care workers in all countries in order to protect their patients from seasonal infl uenza infections. In addition, WHO recommends vaccination against seasonal infl uenza infection to selected groups at increased risk of exposure to Avian infl uenza viruses, as one of several measures for reducing opportunities for the simultaneous infection of humans with Avian and human infl uenza viruses. • Vaccines for A(H5N1) virus for human use have been developed based on WHO- recommended candidate vaccine viruses and licensed in several countries. They are not widely available. Vaccination with A(H5N1) vaccines for human use are recommended for fi rst responders to human or animal A(H5N1) outbreaks, and for health care workers who evaluate or manage patients with suspected or confi rmed A(H5N1) virus infection in designated referral facilities. Be aware that WHO has no stockpile of A(H5N1) vaccines. 9 10 assistance to Member Countries. FAO publishes information and guidance on Avian infl uenza, provides direct technical assistance to countries and works closely with many stakeholders. • The World Organization for Animal Health (OIE) sets international standards for animal health and zoonoses, through the ‘OIE Code’ and ‘OIE Manual’ and is responsible for collecting and disseminating offi cial animal disease information from Member Countries. It collaborates with National Veterinary Services as well as with FAO at national, regional and global levels to provide technical assistance to countries (e.g. laboratory support). • National veterinary services, often located within the Ministry of Agriculture, are responsible for implementation of national Avian infl uenza measures to control and prevent the spread of the disease in poultry. AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 126 Nigeria Case: 1 Death: 1 Egypt Cases: 359 Deaths: 120 Turkey Cases: 12 Deaths: 4 Azerbaijan Cases: 8 Deaths: 5 Djibouti Cases: 1 Death: 0 Iraq Cases: 3 Deaths: 2 Pakistan Cases: 3 Death: 1 China Cases: 53 Deaths: 31 Bangladesh Cases: 8 Death: 1 Myanmar Case: 1 Death: 0 Thailand Cases: 25 Deaths: 17 Cambodia Cases: 56 Deaths: 37 Lao People's Democratic Republic Cases: 2 Deaths: 2 Indonesia Cases: 200 Deaths: 168 Member State Cases: cumulative number Deaths: cumulative number Areas with confirmed human cases for avian influenza Canada Case: 1 Death: 1 Viet Nam Cases: 127 Deaths: 64 Areas with confi rmed human cases for avian infl uenza A(H5N1) reported to WHO, 2003–2018* The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved * All dates refer to onset of illness Source: WHO/IHM, as of 16 February 2018 AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 127 More information about Avian and other zoonotic infl uenza: • Avian and other zoonotic infl uenza WHO webpage: http://www.who.int/infl uenza/human_animal_interface/en/ • Avian and other zoonotic infl uenza WHO fact sheet: http://www.who.int/mediacentre/factsheets/avian_infl uenza/en/ • Avian and other zoonotic infl uenza WHO MOOC: https://openwho.org/courses/avian-and-other-zoonotic-infl uenza- introduction • WHO Summary Of Key Information Practical To Countries Experiencing Outbreaks Of A(H5N1) And Other Subtypes Of Avian Infl uenza, First Edition July 2016 http://apps.who.int/iris/bitstream/10665/246251/1/WHO-OHE-PED- GIP-EPI-2016.1-eng.pdf?ua=1 • Case defi nitions for the four diseases requiring notifi cation to WHO in all circumstances under the IHR (2005) http://www.who.int/ihr/survellance_response/case_defi nitions/en/ • Pandemic Infl uenza Preparedness Framework for sharing of infl uenza virus and access to vaccines and other benefi ts http://www.who.int/infl uenza/resources/pip_framework/en/ AVIAN AND OTHER ZOONOTIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 128

1. Seasonal infl uenza is a respiratory disease transmitted through droplets 2. Infl uenza disease appears in seasonal epidemics and may be very disruptive 3. Infl uenza A and B viruses can cause epidemics 4. Infl uenza can be severe and fatal 5. Annual vaccination is the best way to prevent infection 6. Early treatment with antiviral drugs may reduce complications and deaths 7. Seasonal infl uenza is hard to differentiate clinically from other respiratory diseases 8. Non-pharmaceutical measures prevent and reduce transmission 9. Monitoring, regular surveillance and sharing of data and viruses are important 10. Border controls do not reduce international spread 10 THINGS YOU SHOULD KNOW Seasonal infl uenza SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 130 Seasonal infl uenza response tips Coordinating responders • WHO Global Infl uenza Surveillance and Response System (GISRS) monitors infl uenza activity globally and provides recommendations in areas including laboratory diagnostics, vaccines, antiviral susceptibility and risk assessment Communicating risk • Encourage health authorities to: - Educate on prevention measures - Communicate about vaccine effectiveness and safety, especially for high-risk groups • Promote hand and respiratory hygiene, and cough etiquette • Key messages: - Seasonal infl uenza is highly contagious - It spreads through droplets - Annual vaccination is the best prevention - High-risk groups such as the elderly, pregnant women, infants and people with underlying conditions are most at risk and should seek medical care Health Information • Regular sharing of epidemiological information and viruses helps to develop policy to reduce the infl uenza burden Health Interventions • Annual vaccination • Antiviral drugs • Non-pharmaceutical interventions: - Social distancing (e.g. school closure) - Hygiene: cough etiquette, hand hygiene SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 131 Seasonal infl uenza is a respiratory disease transmitted through droplets • Seasonal infl uenza (or “fl u”) is an acute respiratory disease. • It is highly contagious: it spreads easily from person to person through droplets when an infected individual coughs or sneezes. Sometimes, the transmission can be airborne, especially when aerosol- generating procedures are performed. • It can also be transmitted by touching contaminated surfaces or hands. • Therefore, rapid transmission can occur in crowded areas (e.g. schools or nursing homes). • Precautionary measures to limit transmis- sion include: hand hygiene, respiratory hygiene and cough etiquette, and drop- let precautions in hospital settings. Infl uenza disease appears in Seasonal epidemics and may be very disruptive • In temperate climates, seasonal epidemics occur mainly during winter. The epidemics generally last from eight to 10 weeks in temperate areas. • In tropical regions, the pattern of infl uenza epidemics is not always as regular. Some countries have two peaks and some do not have very regular epidemics. • Epidemics can be very disruptive. While the yearly burden is variable and the average burden is currently being evaluated, infl uenza does cause considerable disease in all countries. In addition to illness, epidemics can have a high economic impact because of work and school absenteeism, productivity losses and overwhelmed hospital capacity. 1 2 SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 132 Infl uenza A and B viruses can cause epidemics • There are four types of infl uenza viruses - types A, B, C and D - but only infl uenza A and B cause epidemics. Infl uenza A can infect many species (birds, humans, pigs, horses, etc.). Infl uenza B and C infect mainly humans. Infl uenza type C virus is less frequent and usually causes mild infections, thus presents less signifi cant public health implications. • The A type of infl uenza viruses are further classifi ed in subtypes based on their surface proteins. There are 18 different haemagglutinin (H) types and 11 different neuraminidase (N) types. Different combinations are possible. Currently, H3N2, H1N1pdm09 are circulating in humans as Seasonal infl uenza A viruses. Infl uenza can be severe and fatal • Infl uenza can cause severe illness or death in any person. • A wide range of complications can be caused by infl uenza virus infection of the upper respiratory tract (nasal passages, throat) and lower respiratory tract (lungs). Sinus and ear infections are examples of moderate complications from fl u, while pneumonia is a serious fl u complication, that people with chronic lung disease are at higher risk of developing. • Other possible serious complications triggered by fl u can include infl ammation of the heart (myocarditis), brain (encephalitis) or muscle (myositis, rhabdomyolysis) tissues, and multi-organ failure (for example, respiratory and kidney failure). Flu virus infection of the respiratory tract can trigger an extreme infl ammatory response in the body and can lead to sepsis. • People at higher risk of developing complications and severe Seasonal infl uenza are: a. Children younger than fi ve years; b. People older than 65 years; c. People with chronic medical conditions such as HIV/AIDS, asthma, heart and lung diseases and diabetes. • Flu also can make chronic medical problems worse. For example, people with asthma may experience asthma attacks while they have the fl u, and people with chronic heart disease may experience a worsening of this condition triggered by fl u. 3 4 • Infl uenza viruses are in constant mutation. This is called antigenic drift and results in changes to the viruses which make people susceptible to catch fl u every year, as they do not have immunity against the drifted viruses. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 133 Annual vaccination is the best way to prevent infection • The most effective way to prevent the disease is getting vaccinated every year. • Vaccination is especially important for pregnant women, people at high risk of exposure, people at higher risk of serious infl uenza complications, and for people who live with, or care for, high-risk individuals (health care workers). • Ideally, people should get vaccinated just before the infl uenza season begins for the most effective coverage, although getting vaccinated at any time during the infl uenza season can still help prevent infections. • Infl uenza viruses evolve constantly, and twice a year, WHO makes recommendations to update the vaccine compositions, based on the monitoring done through the Global Infl uenza Early treatment with antiviral drugs may reduce complications and deaths • Antiviral drugs may reduce severe complications and deaths. Ideally, they need to be administered early in the disease (within 48 hours of onset of symptoms). They are especially important for high-risk groups. • They are two types of drugs: neuraminidase inhibitors and adama- tanes. Currently, the majority of circulating infl uenza viruses are resistant to the adamantanes, limiting their effectiveness. Therefore, neuraminidase inhibitors (oseltamivir and zanamivir, peramivir and laninamivir) are the recommended fi rst-line treatment. • People with Seasonal infl uenza should always drink plenty of water, rest and not go to work, in order to reduce transmission. 5 6 Surveillance and Response System (GISRS). This maximises the effectiveness of the vaccines, as circulating viruses need to be well-matched with the viruses contained in the vaccines. • A number of inactivated infl uenza vaccines and recombinant infl uenza vaccines are available in injectable form. Live attenuated infl uenza vaccine is available as a nasal spray. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 134 7 Seasonal infl uenza is hard to differentiate clinically from other respiratory diseases• People with Seasonal infl uenza usually show non-specifi c symptoms. They include: sudden onset of fever, cough (usually dry), headache, muscle and joint pain, fatigue, and a runny nose. • The cough can be severe and can last two or more weeks. Most people recover within a week without requiring medical attention. • Incubation period is usually two days but may be from one to fi ve days. • An infected person may be infectious from one to two days before and until four to fi ve days after the onset of symptoms (children may be infectious for longer). • Laboratory diagnosis is critical to differentiate Seasonal infl uenza from other respiratory diseases: - The most appropriate specimens for the diagnosis of infl uenza are upper respiratory tract specimens. Samples should be taken from the deep nostrils (nasal swab), throat (oropharyngeal swab) and nasopharynx (nasopharyngeal swab). Nasopharyngeal aspirate and bronchial aspirate are also useful; - The Reverse Transcription Polymerase Chain Reaction (RT-PCR) is the preferred technique for diagnosis; - In addition to RT-PCR, other laboratory techniques are available for the detection, identifi cation and characterization of infl uenza virus including virus isolation in cell culture and the identifi cation of viral antigens (fl uorescent antibodies, FA, test or Enzyme-Linked Immunosorbent Assay, ELISA). Single serum is not ideal for diagnosis of an acute infection. SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 135 Non-pharmaceutical measures prevent and reduce transmission • The implementation of non- pharmaceutical measures helps to prevent and slow transmission and control epidemics. • Before an epidemic, to reduce the potential disruptive effects of Seasonal infl uenza, it is critical that: - There is effective health planning in place so health education and immunization for at-risk patients, their close contacts and health care workers are implemented; - Increased demand for medical care and possible absenteeism of health care workers during the epidemic period are anticipated. • During an epidemic, to reduce transmission: - Health education should continue; - Hand hygiene, respiratory hygiene and cough hygiene (e.g. covering mouth and nose with a tissue when coughing and then throwing it out and washing hands) should be strictly observed by all; - Personal protective equipment in health care settings (masks) should be used when in contact with people with Seasonal infl uenza (the sick are wearing the mask); - Social distancing may help. It includes isolation of patients, staying at home when sick, and school closure. School closures have the greatest benefi t when applied early in the course of the outbreak. The benefi t has to be weighed against the cost of disruption; 8 - Risk communication and community engagement should be implemented so populations comply with recommended public health measures (especially needed to implement vaccination recommendations). SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 136 Border controls do not reduce international spread • Border control measures such as entry and exit screening and quarantining of travellers crossing international borders are generally not recommended, as they have not been shown to reduce the spread of infl uenza. • Screening for detecting people with fever might be ineffi cient as: - Infected people may travel during the incubation period, during which they will not show symptoms but will be able to transmit the disease; - People may be using anti-pyretics and not show fever. • Implementing borders control measures may also be very expensive and disruptive. 10 Monitoring, regular surveillance and sharing of data and viruses are important • Regular monitoring and surveillance are important to anticipate severe epidemics and plan health care services as well as to be prepared for a pandemic. • Since 1952, WHO has been coordinating a network which now has more than 150 laboratories and experts to analyse the spread of infl uenza and recommend the vaccine composition. • Sharing of viruses and data is also important to be able to update the vaccine and antiviral treatments. 9 SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 137 More information about Seasonal infl uenza: • Infl uenza WHO webpage: http://www.who.int/infl uenza/en/ • Seasonal infl uenza WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs211/en/ • Seasonal infl uenza WHO MOOC: https://openwho.org/courses/seasonal-infl uenza-introduction • Patient care: http://www.who.int/infl uenza/patient_care/en/ • Global Infl uenza Surveillance and Response System (GISRS): http://www.who.int/infl uenza/gisrs_laboratory/en/ SEASONAL INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 138

1. Another infl uenza pandemic is inevitable but unpredictable 2. Pandemics require global concerted actions 3. A pandemic happens when an infl uenza virus emerges to which most people have no immunity 4. Infl uenza pandemics may be mild or severe and can have a global impact 5. Vaccines will probably not be available in the fi rst months 6. Risk groups and symptoms will be unknown until the pandemic occurs 7. Early treatment with antivirals and other medical support can reduce complications and deaths 8. Non-pharmaceutical interventions may be the only effective initial measures in most countries 9. Communicating risk is critical 10. Pandemic response capacity can be built through Seasonal infl uenza 10 THINGS YOU SHOULD KNOW Pandemic infl uenza PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 140 Pandemic infl uenza response tips Coordinating responders • Multisectoral coordination • Whole-of-society approach Communicating risk • Encourage health authorities to: - Have a plan on the use of antivirals and vaccines - Have a multisectoral risk communication plan in place - Communicate early and frequently about how to protect from the disease • Engage communities and individuals to practice good hygiene • Key messages: - Pandemic infl uenza is caused by a new virus to which no one has immunity and protection - You can protect yourself by using proper cough hygiene, effective hand washing and by distancing yourself away from others if you fall sick - Stay at home, drink plenty of fl uids - Seek medical advice if you have severe symptoms or you already have other medical conditions that may put you at further risk of severe disease - Take the new vaccine when it became available if you are asked to do so Health Information • Notify a case of novel infl uenza to WHO, under the IHR (2005) • Share viruses and information with the WHO GISRS (Global Infl uenza Surveillance and Response System) • Consult WHO surveillance and severity assessment guidance Health Interventions • Vaccines • Antiviral treatment • Non-pharmaceutical interventions (at personal and community level): hygiene, social distancing etc. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 141 Another infl uenza pandemic is inevitable but unpredictable • It is not possible to predict when or where the next Pandemic infl uenza will occur, what subtype it will be, and what morbidity and mortality impact it will have, but it is certain that there will be one. • History has shown pandemics occur at 10- to 50-year intervals, with varying severity and impact. During the 20th century, there have been three infl uenza pandemics (in 1918, 1957 and 1968). Since 2000, there has been one infl uenza pandemic, in 2009. • Infl uenza viruses are very unstable and constantly mutating. They undergo small mutations (antigenic drift) and cause Seasonal infl uenza epidemics and out- of-season outbreaks. But a substantial change (antigenic shift) can occur at any time. It will result in a new virus (different subtype) which may lead to a pandemic. This antigenic shift can be the re-assortment of human infl uenza viruses with Avian or swine viruses, or signifi cant point mutations of Avian or swine viruses. Pandemics require global concerted actions • Infl uenza pandemics are very disruptive events that can cause severe social, economic, and political stress. Preparedness requires a whole-of-society approach to ensure that when the next pandemic strikes, the world will be able to respond rapidly and effectively to reduce morbidity and mortality. Not only the health sector but also all other sectors, individuals, families and communities, have a role to play in mitigating the effects of a pandemic. 1 2 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 142 A pandemic happens when an infl uenza virus emerges to which most people have no immunity • There are three necessary factors for the emergence of Pandemic infl uenza: - A new infl uenza virus emerges and causes illness in humans; - This virus has the ability to cause sustained human-to-human transmission; - Human population has little or no immunity to the virus. • Because it is a new virus to which people have not yet been exposed, the population has no or little immunity and the virus is able to spread quickly and cause illness in people. • A Pandemic infl uenza virus may arise when: - Genes from animal and human infl uenza viruses mix together to create a human- animal infl uenza re-assortant virus (genetic re-assortment); - Genes in an animal infl uenza virus change allowing the virus to infect humans and transmit easily among them (genetic mutation). • It is mandatory to notify a human infl uenza case caused by a new subtype to WHO, under the IHR (2005). 3 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 143 Vaccines will probably not be available in the fi rst months • Vaccines are one of the most effective ways to protect people during infl uenza epidemics and pandemics. • However, the availability of a pandemic vaccine will be delayed by several months because of the requirements for vaccine formulation and production lead-time. It is expected that it takes about 24 weeks (almost six months) for a vaccine to be available after the identifi cation of the pandemic virus. • It is probable that the worldwide production capacity will still be insuffi cient and restrict global access to the vaccine, at least during the fi rst phase of the pandemic. In the best case scenario, it has been estimated (2015) that annual production could reach about 6.2 billion 5 doses of vaccines , which is still insuffi cient to cover the world population because two doses of vaccines will probably be needed to fully protect against the virus. Furthermore, it is challenging to maintain this production capacity. • Vaccination should target the most at risk of exposure (health care workers, people living in crowded areas) and those most at risk of complications. • Antigen-sparing strategies can be used to increase vaccine availability. • Some countries are stockpiling pre- pandemic vaccines against some Avian infl uenza viruses. Infl uenza pandemics may be mild or severe and can have a global impact • Infl uenza pandemics have various levels of severity and impact. • It is hard to predict the characteristics, including level of severity, of the next pandemic. • During an infl uenza pandemic, severity assessments should be conducted regularly at local, national and global levels, to inform public health decisions (vaccine production and use, antivirals use, school closures, social distancing strategies, etc.). Key elements to take into consideration are: the transmissibility of the disease, its seriousness (complications, for which group of people, etc.), the impact on the health sector (whether it is overwhelmed or not). 4 Pandemic year of emergence and common name Area of origin Influenza A virus sub - type (type of animal genetic introduction/ recombination event) Estimated reproductive number Estimated case fatality Estimated attributable excess mortality worldwide Age group most affected 1918 “Spanish flu” Unclear H1N1 (unknown) 1.2–3.0 2–3% 20–50 million Young adults 1957–1958 “Asian flu” Southern China H2N2 (avian) 1.5 <0.2% 1–4 million All age groups 1968–1969 “Hong Kong flu” Southern China H3N2 (avian) 1.3–1.6 <0.2% 1–4 million All age groups 2009–2010 “influenza A(H1N1) 2009” North America H1N1 (swine) 1.1–1.8 0.02% 100 000–400 000 Children and young adults Characteristics of the past four infl uenza pandemics Source: Pandemics of the 20th–21st centuries. Stockholm, European Centre for Disease Prevention and Control. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 144 7 Early treatment with antivirals and other medical support can reduce complications and deaths • Antiviral drugs may reduce severe complications and deaths. Ideally, they need to be administered early in the disease (within 48 hours of onset of symptoms). They are especially important for high-risk groups. • During an infl uenza pandemic, antiviral drugs are an important tool to prevent the spread of the disease and severe outcome and complications, as vaccines will most likely not be available at an early stage. • Effectiveness of the drugs on the novel pandemic virus must be monitored, as some infl uenza viruses may be (or become) resistant to them. • Pharmaceutical interventions typically encompass the application of antivirals treatments and other drug treatment (e.g. antibiotics to target complications of infl uenza). Risk groups and symptoms will be unknown until the pandemic occurs • Although we start with the assumption that the risk groups for infection and severe outcome are the same as in Seasonal infl uenza, there might be differences. • Historical knowledge from the 1918 and 2009 pandemics indicates that healthy, young adults can be disproportionately and more severely affected. • Pandemic infl uenza might present differently from Seasonal infl uenza and symptoms may be more severe and complications more frequent. - People with infl uenza will usually develop the following symptoms: sudden onset of fever, cough (usually dry), headache, muscle and joint pain, fatigue, sore throat and a runny nose; - Complication can include pneumonia, sepsis, and infl ammation of the heart (myocarditis), brain (encephalitis) or muscle (myositis); - The incubation period is usually two days but may be from one to fi ve days. 6 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 145 Non-pharmaceutical interventions may be the only effective initial measures in most countries • Vaccination is the primary intervention to prevent infection and severe outcomes caused by infl uenza virus. However, at the beginning of a pandemic, Pandemic infl uenza vaccines, matching the new virus, will most likely not be available. • In addition to antiviral drugs administration (which might also be short in supply), non-pharmaceutical interventions (NPI) should be put in place, at the early stage of a pandemic, to slow transmission and reduce its impact. NPI include (but are not limited to): - Social distancing: staying at home when sick; - Hygiene such as cough etiquette (covering coughs and sneezes with a tissue), hand washing and cleaning of touched surfaces and objects; - During severe pandemics, more extreme measures can be implemented: using facemasks when sick, schools closures, decreasing the amount of contacts among people. • NPI will help to reduce the number of people who are exposed and then infected. 8 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 146 Pandemic response capacity can be built through Seasonal infl uenza • Pandemic infl uenza would require the implementation of the same control measures, on a larger scale: Infection Prevention and Control and Hygiene; Health Education; Vaccination; Early treatment; Social distancing; Risk communication and Community engagement. 10 Communicating risk is critical • Risk communication is particularly important in a rapidly evolving situation and when there is little known about an epidemic, which will be the case at the beginning of an infl uenza pandemic (novel virus). Without effective communication, the many unknowns give enough space for rumors to develop. • As the pandemic requires a whole- of-society approach, individuals and communities must be engaged, listened to and see that their concerns are addressed. People need to be informed on how to protect themselves and stop the spread of the disease. • Strong risk communication must be built before the emergency occurs. 9 PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 147 Highlight: the PIP Framework • The Pandemic infl uenza Preparedness Framework or “PIP Framework” is an innovative public health instrument that seeks to better prepare the world to respond to Pandemic infl uenza. • It brings together Member States, industry, other stakeholders and WHO to implement a global approach to Pandemic infl uenza preparedness and response. • The PIP Framework has two objectives which are to be pursued on equal footing: - To improve the sharing of infl uenza viruses with the potential to cause a human pandemic; - To establish more predictable, effi cient, and equitable access to the benefi ts that result from the sharing of such viruses, notably vaccines and antiviral medicines. • The Framework, developed by Member States, came into effect on 24 May 2011, unanimously adopted by the World Health Assembly. PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 148 More information about Pandemic infl uenza: • Infl uenza WHO webpage: http://www.who.int/infl uenza/en/ • Pandemic Infl uenza WHO MOOC: https://openwho.org/courses/pandemic-infl uenza-introduction • WHO Global Epidemiological Surveillance Standards for Infl uenza http://www.who.int/infl uenza/resources/documents/infl uenza_ surveillance_manual/en/ • WHO surveillance case defi nitions for infl uenza-like illness (ILI) and severe acute respiratory infections (SARI) http://www.who.int/infl uenza/surveillance_monitoring/ili_sari_ surveillance_case_defi nition/en/ • Pandemic Infl uenza Risk Management, WHO interim guidance, 2013 http://www.who.int/infl uenza/preparedness/pandemic/infl uenza_risk_ management/en/ • WHO Checklist for Pandemic Infl uenza Risk and Impact Management http://www.who.int/infl uenza/preparedness/pandemic/en/ • WHO Pandemic Infl uenza Severity Assessment (PISA) http://www.who.int/infl uenza/surveillance_monitoring/pisa/guidance/en/ • Pandemic Infl uenza Preparedness Framework: http://www.who.int/infl uenza/pip/en/ PANDEMIC INFLUENZAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 149 1. MERS (Middle East respiratory syndrome) is a respiratory disease caused by a coronavirus whose reservoir is dromedary camels 2. Humans can be infected through direct or indirect contact with infected dromedary camels and potentially from camel products 3. The impact ranges from asymptomatic infection to severe pneumonia and death 4. People with weakened immune systems and chronic diseases are at high risk of severe disease 5. Early supportive clinical management reduces mortality 6. Infection prevention and control measures are critical to prevent the spread of human-to-human transmission 7. Laboratory diagnostics are available for MERS 8. Thorough case and outbreak investigation and other measures will help to prevent spread 9. Research is ongoing for treatment in humans and vaccines for camels and humans 10. MERS coronavirus (MERS-CoV) infection is a notifi able disease under the International Health Regulations (2005) 10 THINGS YOU SHOULD KNOW Middle East respiratory syndrome (MERS) MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 150 MERS response tips Coordinating responders • Coordination between animal and human health sectors is essential for: - Surveillance - Risk assessment - Investigation - Mitigation Communicating risk • Encourage health authorities to: - Identify and target at-risk populations with information on how to protect themselves and prevent further transmission - Have a multi-sectoral risk communication plan and to activate it • Key messages: - Precautions for people at high risk of developing severe disease include: practicing good personal hygiene, avoiding contact with camels; not drinking raw camel milk or camel urine; and not eating camel meat that has not been thoroughly cooked - Enhance infection prevention and control in health care facilities - Seek health care early on and follow medical advice Health Information • Report cases to WHO, under the IHR (2005) • WHO regularly conducts global risk assessments for MERS-CoV, these can be found here: http://www.who.int/csr/ disease/coronavirus_infections/archive_ updates/en/ • WHO has developed standard case reporting forms for data analysis and to guide actions Health Interventions • Active case fi nding and contact tracing • Supportive case management • Infection prevention and control measures to prevent health care workers infections MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 151 MERS (Middle East respiratory syndrome) is a respiratory disease caused by a coronavirus whose reservoir is dromedary camels • Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (Middle East respiratory syndrome coronavirus, or MERS-CoV) that was fi rst identifi ed in humans in the Kingdom of Saudi Arabia in 2012. • Coronaviruses are a large family of viruses that can cause diseases in humans, ranging from the common cold to Severe Acute Respiratory Syndrome (SARS). • Dromedary camels (one-humped camels) are the reservoir host for MERS-CoV. • Since 2012, MERS has been reported in 27 countries. Approximately 80% of human cases have been reported by the Kingdom of Saudi Arabia. Cases identifi ed outside the Middle East are people who were infected in the Middle East and then travelled elsewhere. On rare occasions, small outbreaks have occurred in areas outside the Middle East. 1 2 Humans can be infected through direct or indirect contact with infected dromedary camels and potentially from camel products • MERS-CoV is a zoonotic virus: it is transmitted between animal and people. • Dromedary camels are the main source of infection in humans: humans are infected through direct or indirect contact with infected dromedary camels. • At-risk groups of infection, because they are in contact with dromedary camels, include: camel farm workers; slaughterhouse workers; market workers; veterinarians; anyone handling dromedary camels or dromedary camels’ products (e.g. cooking). Health care workers caring for MERS patients without adequate personal protective equipment are also at high risk of infection. • It is recommended that these high-risk groups practice good personal hygiene, including frequent hand hygiene. Hands should be washed with soap and water and/or alcohol gel after every contact with an animal. Workers should wear facial protection where feasible; and protective clothing, which should be removed after work (followed by hand hygiene) and washed daily. • The consumption of raw or undercooked animal products, including milk and meat, carries a potential risk. Animal products that are processed appropriately through cooking or pasteurization are safe for consumption. Properly cooked products should also be handled with care to avoid cross contamination with uncooked foods. • As a general precaution, anyone visiting farms, markets, barns, or other places where dromedary camels and other animals are present should practice general hygiene measures, including regular hand washing before and after touching animals, and should avoid contact with sick animals. People should avoid unprotected direct contact with any animal that has been confi rmed positive for MERS-CoV infection. • There is no evidence of sustained human- to-human transmission: the virus does not pass easily from person to person unless there is close and unprotected contact. There has been limited human- to-human transmission among family members. However, human-to-human transmission has been repeatedly shown to be amplifi ed in health care settings, especially when infection prevention and control measures are inadequate. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 152 The impact ranges from asymptomatic infection to severe pneumonia and death • The clinical spectrum of MERS-CoV infection ranges from no symptoms (asymptomatic) or mild respiratory symptoms to severe acute respiratory disease and death. • MERS symptoms are non-specifi c and can include headache, tiredness, feverishness, mild cough, sore throat, and runny nose. Some patients may present with gastrointestinal symptoms such as 3 mild diarrhoea. Pneumonia is a common fi nding, but not always present. • Severe illness can cause respiratory failure that requires mechanical ventilation and support in an intensive care unit. • The average incubation period is estimated to be approximately fi ve days but may range from two to 14 days. • It is not always easy to detect cases early because symptoms are non-specifi c and this may lead to spread of the disease in health care settings. People with weakened immune systems and chronic diseases are at high risk of severe disease • The virus causes a more severe disease in older people, people with weakened immune systems, and those with chronic diseases such as renal disease, cancer, chronic lung disease, blood disease and diabetes. These people are also at increased risk of infection. • People at high risk of developing severe disease (people with underlying conditions) should avoid contact with camels. 4 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 153 Early supportive clinical management reduces mortality • Supportive therapies prevent complications and increase chances of survival. They include: oxygen, antimicrobials, specifi c treatment for underlying conditions such as diabetes, kidney failure, etc. • Treatment is based on a person’s clinical condition. • There is no specifi c treatment or vaccine available for MERS currently. 5 Infection prevention and control measures are critical to prevent the spread of human-to-human transmission • Standard precautions should be routinely applied to all patients. They include hand hygiene, respiratory hygiene, use of Personal Protective Equipment (PPE), safe waste management, cleaning and disinfection of equipment and cleaning of the environment. • Triage policies should be implemented to rapidly detect potential MERS-CoV cases and all cases with acute respiratory symptoms. • Triage, waiting areas and patient rooms should be adequately ventilated. • Health care workers involved in aerosol- generating procedures are at greater risk of infection. • Droplet precautions should be added to the standard precautions when providing care to any patient with symptoms of acute 6 respiratory infection (ARI). They include the use of a mask and eye-protection when working within 1-2 metres of the patient and patient isolation (organization of the space and processes to allow separation of at least 1-2 metres between patient with ARI and other individuals not wearing PPE). • When performing an aerosol-generating procedure in patient with ARI, airborne precautions should be applied. They include wearing an appropriate PPE, appropriate ventilation, avoiding unnecessary individuals in the room. • Health care workers should be educated and trained in infection prevention and control and should refresh these skills regularly. • Hospital cleaning staff should also be informed of and trained to take proper precautions when cleaning rooms of MERS patients. Infection prevention and control when caring for patients with MERS or suspected MERS All patients Patients with ARI When performing aerosol-generating procedures in patients with ARI Standard precautions, triage procedures Droplet precautions Airborne precautions MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 154 7 Laboratory diagnostics are available for MERS• Laboratory confi rmation of MERS-CoV infection requires good samples, high levels of biosafety and good laboratory capacities. Testing: • A case of MERS-CoV infection may be laboratory confi rmed by detection of viral nucleic acid or by using serology to demonstrate antibodies. • The presence of viral nucleic acid can be confi rmed by either: - A positive real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) on at least two specifi c genomic targets; o A case with a positive RT-PCR result for a single specifi c target without further testing but with a history of potential exposure and consistent clinical signs is considered a probable case. - Or a single positive target with sequencing. • If initial testing is negative in patient who is strongly suspected to have MERS- CoV infection, the patient should be resampled and include lower respiratory specimens. To confi rm clearance of the virus, respiratory samples should continue to be collected until there are two consecutive negative results at least 24 hours apart in clinically recovered persons. Samples: • It is strongly recommended that lower respiratory specimens such as sputum, endotracheal aspirate or broncho- alveolar lavage are collected for MERS- CoV when possible. • If not possible, upper respiratory tract specimens such as nasopharyngeal aspirate or combined nasopharyngeal and oropharyngeal swab should be collected. Biosafety: • Molecular testing for MERS-CoV should be conducted under Biosafety level 2 (BSL-2) conditions. Virus culture requires BSL-3 biosafety conditions. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 155 Thorough case and outbreak investigation and other measures will help to prevent spread • Each human case of MERS requires thorough investigation to understand the source of infection and the potential human-to-human spread amongst contacts. • Thorough case investigation includes the investigation of potential human, animal, and/or environmental sources of exposure(s) and risk factors for infection. Patients (confi rmed and suspected cases) and family members should be interviewed to collect: Essential basic information; Exposure information and travel history; and Clinical information. WHO has generated case report forms identifying the minimum amount of information that should be collected for each case of MERS. 8 • Once a case has been confi rmed, to prevent further spread of the disease, active case fi nding should be implemented in the community and in health care settings: - All close contacts should be identifi ed and monitored for the presence of symptoms for 14 days. A contact is any person who has cared for or lived with a confi rmed case, or had unprotected contact with that person’s respiratory secretions, body fl uids and/or excretions when that person was symptomatic; - Contacts should be placed under active surveillance for 14 days after last exposure to the confi rmed or probable case with monitoring for respiratory symptoms (a health care worker should visit or call them on a daily basis); - Any contacts who develop symptoms should be isolated in a health care facility and tested for MERS-CoV infection; - Health care workers with direct contact with a MERS patient should be closely monitored. • Health Education, including basic information about MERS, how to prevent against MERS-CoV infection for different groups (e.g. contacts of confi rmed patients, health care workers caring for MERS patients, occupational groups who work with dromedary camels, and populations at higher risk of severe disease) and what to do should an individual suspect they have MERS-CoV infection, should be provided by trained individuals. MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 156 MERS-CoV infection is a notifi able disease under the International Health Regulations (2005) • Probable and confi rmed cases must be reported within 24 hours of classifi cation, with information about their exposure, testing and clinical course. MERS case defi nitions for reporting to WHO can be found here: http://www.who.int/csr/ disease/coronavirus_infections/case_ defi nition/en/ 10Research is ongoing for treatment in humans and vaccines for camels and humans• WHO has developed a MERS-CoV research agenda to address key unknowns for this virus focusing on fi ve major areas of research: i) virus origin and characteristics, ii) epidemiology and transmission, iii) clinical management and infection prevention and control measures, iv) product development and implementation, and v) impact of interventions and operational research. • WHO’s Research and Development Blueprint is working to accelerate the development of medical interventions for MERS. - Currently, there are no licensed treatments for MERS; - Currently, a dozen vaccine candidates for both humans and dromedary camels are in preclinical development. 9 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 157 Data as 12 December 2017 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Confi rmed global cases of MERS-CoV 2012 – 2017 Thailand Algeria Austria France Germany Greece The Islamic Republic of Iran Jordan Republic of KoreaKuwait Lebanon Oman Malaysia Netherlands Qatar Philippines United Arab Emirates Tunisia Turkey United Kingdom of Great Britain and Northern Ireland United States of America Saudi Arabia Yemen Egypt Italy China 2,119Total number of reported cases: Number of cases reported 1 - 5 6 - 20 21 - 150 151 - 500 501 - 1000 1000+ 2012 2013 20152014 Confirmed global cases or MERS-CoV by month reported Saudi Arabia Rest of the World Date reported to WHO 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 01 03 05 07 09 11 C as e C ou nt 240 220 200 180 160 140 120 100 80 60 40 20 0 Date reported to WHO 20172015201420132012 2016 MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 158 More information about MERS: • MERS-CoV WHO website: http://www.who.int/emergencies/mers-cov/en/ • MERS WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Latest global risk assessment for MERS-CoV: http://www.who.int/csr/disease/coronavirus_infections/archive_updates/en/ • Guidance on laboratory testing: http://www.who.int/csr/disease/coronavirus_infections/mers-laboratory- testing/en/ • Surveillance guidance including recommendations on criteria for case investigation and testing: http://www.who.int/csr/disease/coronavirus_infections/surveillance- human-infection-mers/en/ • Guidance on the investigation of cases of MERS-CoV infection: http://www.who.int/csr/disease/coronavirus_infections/mers- investigation-cases/en/ • WHO case investigation form for MERS-CoV: http://www.who.int/csr/disease/coronavirus_infections/MERS_case_ investigation_questionnaire.pdf?ua=1 • MERS case defi nitions for reporting to WHO: http://www.who.int/csr/disease/coronavirus_infections/case_defi nition/en/ • Guidance on case management and Infection Prevention and Control: http://www.who.int/csr/disease/coronavirus_infections/technical- guidance-infection/en/ • Information about MERS-CoV Research and Development: http://www.who.int/blueprint/priority-diseases/key-action/mers-cov/en/ MIDDLE EAST RESPIRATORY SYNDROME (MERS)MANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 159 1. Cholera is closely linked to inadequate access to clean water and sanitation 2. Cholera is transmitted by faecally-contaminated water and food 3. Cholera outbreaks can be explosive 4. Rapid detection of suspected cases and laboratory confi rmation are essential 5. People with Cholera experience acute watery diarrhoea with no fever 6. Severe forms of Cholera can kill within hours: early rehydration is the cornerstone of treatment 7. Oral Cholera Vaccines are safe and should be used with other prevention and control strategies 8. Populations at risk should be provided with safe water and basic sanitation 9. Mapping the origin of cases is critical to orient control activities 10. WHO can provide countries with Cholera kits 10 THINGS YOU SHOULD KNOW Cholera CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 160 Cholera response tips Coordinating responders • Intersectoral coordination at national and local level is critical to outbreak response • Epidemiological data on the origin of cases should drive the multisectoral response • Cholera kits are available for preparedness and immediate outbreak response • Contact WHO/ICG for emergency Oral Cholera Vaccines • Technical support is available through the Global Task Force on Cholera Control (GTFCC) Communicating risk • Encourage health authorities to: - Engage communities to enhance hygiene and food safety practices - Set up treatment facilities and let the public know how to access them - Make sure Oral Rehydration Salts are available • Key messages: - Cholera is transmitted through contaminated water or food - Cholera can rapidly lead to severe dehydration and death if left untreated: seek treatment quickly - Wash hands at critical moments - Mild cases can be treated at home with oral rehydration - Take the Cholera vaccine if advised, when there is a Cholera outbreak or its threat, in your area Health Information • Investigate the source of the outbreak • Once Vibrio Cholerae has been confi rmed by culture or PCR, the WHO clinical case defi nition is suffi cient to identify cases. Periodic sampling and testing on suspected cases should be carried out throughout the epidemic to monitor antimicrobial sensitivity Health Interventions • Provide populations with safe water and sanitation • Treat early (rehydration): - Oral rehydration points (ORPs) in the community facilitate early access to treatment - Cholera treatment centres (CTCs) provide 24-hour care for patients with more severe forms of Cholera • Infection prevention and control practices must be implemented in all health facilities receiving Cholera patients • Vaccination with Oral Cholera Vaccines in humanitarian emergencies and to prevent further spread of epidemics CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 161 Major Cholera Outbreaks in 2017 - 2018 Source: WHO, 2018 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved Mozambique (0.3%) Nigeria (1.3%) Sudan (2.2%) Angola (2%) Somalia (1.3%) Democratic Republic of the Congo (2.2%) Zambia (1.8%) Uganda (2.1%) Malawi (3.3%) Ethiopia (1.8%) Zimbabwe (5.1%) South Sudan (2.1%) Yemen (0.2%) Kenya (2%) United Republic of Tanzania (2%) 6,223 7,209 36,811 713 6,613 62,154 63,829 5,695 5,248 21,439 2,108 1,090,280 904 47,868 137 Map date: 01 May 2018 Not Applicable Ethiopia and Sudan: Reported as AWD Number of Cases Case Fatality Rate(CFR)* > 100,000 Haiti (1.2%) 818,000 < 1000 1000 to 5000 5000 to 20,000 20,000 to 100,000 0 100 200 km 0 750 1,500 km < 1% >1% to 2% >2% to 3% >3% to 4% >4% to 5.1% Period of Report *CFR Labelled for Each Country Angola: Dec 2017-March 2018 Democratic Republic of the Congo: Jan 2017 – April 2018 Ethiopia: Jan 2017 – April 2018 Haiti: Oct 2010 – Feb 2018 Kenya: Jan 2017-mid April 2018 Malawi: Nov 2017 – April 2018 Mozambique: Jan 2017 - 8 April 2018 Nigeria: Aug 2017 – April 2018 Somalia: March 2017 – March 2018 South Sudan: Aug 2016 – Dec 2017 Sudan: Aug 2016 – Feb 2018 United Republic of Tanzania: Jan 2017- mid April 2018 Uganda: Feb 2018 – April 2018 Yemen: April 2017 – April 2018 Zambia: Oct 2017 – April 2018 Zimbabwe: Jan – April 2018 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 162 1 2 Cholera is transmitted by faecally-contaminated water and food• A person can become infected by drinking water or eating food contaminated by the bacterium Vibrio Cholerae. • Bacteria present in the faeces of an infected person are the main source of contamination. • Food may be contaminated by soiled hands during preparation, or while eating or by some irrigation practices. • During funeral ceremonies, transmission may occur through consumption of food and beverages contaminated by someone who touched the corpse of the deceased and also prepared the food without adequately washing their hands, or by funeral attendees touching the corpse. • Beverages prepared with contaminated water and sold by street vendors are vehicles of Cholera transmission, as well as vegetables and fruits “freshened” with contaminated water and raw or undercooked seafood. • The bacterium can persist in water for long periods and multiply in moist left- over food. Cholera is closely linked to inadequate access to clean water and sanitation • The long-term solution for Cholera control lies in economic development and universal access to safe drinking water and adequate sanitation. These measures prevent both epidemic and endemic Cholera as well as other faeco- orally transmitted and water-borne diseases. They may require substantial long-term investments. • Cholera is closely linked to poor environmental conditions. The absence or shortage of safe water and of proper sanitation are the main contributors to the spread of the disease. Typical at- risk areas are peri-urban slums, with precarious basic infrastructure, as well as internally displaced or refugee camps. • Actions to reduce the transmission of Cholera include: - The implementation of adapted long- term sustainable WASH (Water Sanitation and Hygiene) solutions to ensure use of safe water, basic sanitation and good hygiene practices to populations most at risk of Cholera: o Interventions at the household level (water fi ltration, chemical or solar disinfection of water, safe water storage, the construction of systems for safe sewage disposal, including latrines); o Adoption of basic hygiene practices; o Access to safe water and sanitation in public areas such as health facilities and schools. - Rapid access to treatment; - Implementation of adapted infection control practices in treatment structures; - Vaccination. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 163 Cholera outbreaks can be explosive • The incubation period is very short. It ranges from two hours to fi ve days, usually two to three days. • This leads to explosive epidemics as the numbers of cases can rise extremely quickly. • Early detection and treatment of cases and rapid initiation of control activities are critical. • Asymptomatic carriers can transmit the infection. As long as stools are positive, infected people can transmit the disease. Even among asymptomatic carriers, the pathogens stay in their faeces for up to 14 days and are shed back into the environment, possibly infecting other individuals. 3 Rapid detection of suspected cases and laboratory confi rmation are essential • When an outbreak is suspected, a multidisciplinary team should be sent to the fi eld in order to confi rm the outbreak and to take the fi rst measures to control the spread of the disease. These teams should carry sampling materials, rapid diagnostic tests, the means to make clean water and ORS (Oral Rehydration Salts) at a minimum. More medical materials should be carried if a treatment facility is visited. • Rapid diagnostic tests (RDTs) should be used to reinforce suspicion of Cholera. This allows quick testing without the need for a laboratory and is frequently used to increase suspicion during outbreak investigations. The sensitivity and specifi city of Cholera RDTs are not suffi cient for them to be used as individual diagnostic tests. Send the RDT positive stool samples to the laboratory for confi rmation. • Cholera is confi rmed by identifying V. Cholerae in stool samples from affected patients using: - Culture for confi rmation and antibiotic sensitivity testing; - PCR (Polymerase Chain Reaction) for confi rmation. • Laboratory confi rmation is essential to confi rm that this is a Cholera outbreak. Once an outbreak is confi rmed, a clinical diagnosis using WHO standard case defi nition is suffi cient. 4 • Laboratory confi rmation should be carried out in each new area (district or region) reporting cases to confi rm extension of the outbreak. • Sporadic sampling and testing on suspected cases should be performed throughout an outbreak to monitor the outbreak, determine antibiotic sensitivity, and monitor the strain. • An outbreak is considered over when all samples from all suspected patients test negative by RDT, culture or PCR for a period of two weeks. • Do not wait for laboratory confi rmation before starting control activities. Access to clean water and basic sanitation, hygiene promotion and access to treatment are important public health interventions even if the outbreak is not confi rmed. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 164 People with Cholera experience acute watery diarrhoea with no fever • Most people infected with Cholera (approximately 80%) do not develop any symptoms although the bacteria are present in their faeces for up to 14 days after infection. • Among people developing symptoms, approximately 80% present with mild to moderate watery diarrhoea resulting in no or only minor signs of dehydration. The remaining 20% rapidly develop profuse watery diarrhoea that can lead to severe dehydration and to death if not treated. • Other signs and symptoms may include: - Profuse vomiting; - Abdominal or muscle cramps; - Hypoglycemia; - Hypokalaemia. • There is a high risk of fetal loss in pregnant woman with Cholera. • Fever is not a symptom of Cholera, but may be a result of co-morbidity in patients with Cholera. 5 Severe forms of Cholera can kill within hours: early rehydration is the cornerstone of treatment • The most important treatment is rehydration, which consists of prompt replacement of the fl uid and salts loss through severe diarrhoea and vomiting. Early rehydration can save the lives of nearly all Cholera patients. With early and proper treatment, the case fatality rate should remain below 1%. • Good assessment of the state of dehydration is key to appropriate treatment (see the assessment tool in the manual “First steps for managing an outbreak of acute diarrhoea”). • Patients with no signs or some signs of dehydration (approximately 80% of patients), both adults and children, can be rehydrated quickly and easily by following standard protocols for treatment with Oral Rehydration Solution (ORS). ORS should be given early at home, by volunteers and family members, to avert delays in rehydration and death. • Patients who become severely dehydrated need to receive fl uids intravenously (Ringer’s Lactate solution). • Continued breastfeeding of infants and young children is encouraged. • Zinc is also an important adjunctive therapy for children under fi ve years, which also reduces the duration of diarrhoea and may prevent future episodes of other causes on acute watery diarrhoea. 6 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 165 7 Oral Cholera Vaccines are safe and should be used with other prevention and control strategies• There are three Oral Cholera Vaccines (OCV): - Shanchol™ and Euvichol® are essentially the same vaccine. One dose can be used to contain epidemics (protection for at least six months). Two doses are required for longer protection (both vaccines provide sustained protection of >65% for at least three years after two doses). The two doses can be administered to all individuals over the age of one year with a minimum two-week interval between doses; - There is a third vaccine, Dukoral®, that is primarily used for travellers. It also confers signifi cant short-term protection against Enterotoxigenic Escherichia coli (ETEC). The vaccine is administered with a buffer solution. It can be given to all individuals over the age of two years with a minimum of a week between doses. • Oral Cholera Vaccines are considered safe for pregnant women. • OCV can be used for emergencies: - In humanitarian crises, OCV can be used to prevent Cholera, even before any suspected cases are reported; - For outbreak response, OCV is used to prevent further spread of Cholera. It should be used as early as possible to prevent the greatest number of cases; - All OCVs currently require cold chain (2- 8°C), but use out of cold chain is currently under review; - For emergency use of OCV, there is a global emergency stockpile of Oral Cholera Vaccine doses (Shanchol™ or Euvichol®) managed by the International Coordinating Group (ICG). • In endemic settings, Oral Cholera Vaccines are used as part of a longer-term Cholera control plan, including reinforcement of surveillance and laboratory diagnostic capacity and improving water, sanitation and hygiene conditions. OCV is used to provide mid-term protection to the population while longer term water, sanitation and hygiene solutions are being implemented. - OCV for endemic use is available via the Global Task Force on Cholera Control. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 166 Populations at risk should be provided with safe water and basic sanitation • During outbreaks: - People should be provided with safe water or means to prepare and store safe water at home; - Awareness campaigns should be organized, and information should be provided to the community about the potential risks and symptoms of Cholera, precautions to take to avoid Cholera, when and where to report cases, and to seek immediate treatment when symptoms appear. The location of appropriate treatment sites should also be shared. • Community engagement is critical, at any time, so that communities adopt preventive behaviors to avert contamination: 8 - Health education campaigns should promote the adoption of appropriate hygiene practices such as hand-washing with soap, safe preparation and storage of food and safe disposal of the faeces of children; - Handwashing should be promoted at key times; - Funeral practices for individuals who die from Cholera must be adapted to prevent infection among attendees; - Breastfeeding should be promoted; - Health campaigns should be adapted to local culture and beliefs. CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 167 WHO can provide countries with Cholera kits • WHO can provide necessary materials for the investigation and confi rmation of Cholera outbreaks, as well as for the treatment of Cholera patients. Cholera kits are designed to help prepare for a potential Cholera outbreak and to support the fi rst month of the initial response. • There are six kits: - One kit provides the necessary materials for the investigation of Cholera outbreaks; - One provides the supplies for laboratory confi rmation of suspected Cholera cases. 10Mapping the origin of cases is critical to orient control activities• Mapping the origin of cases can help identify priority areas for water and sanitation activities and hygiene promotion. The more precise the mapping, the more effectively interventions can be targeted. • Access to treatment for people living in priority areas should also be ensured. • Oral rehydration points in key areas and transport services to Cholera treatment centres can save lives. • Active case fi nding should also be carried out in these areas. • In areas with community health programmes, the community health workers or volunteers can be trained to identify and report suspected Cholera, to safely make and give ORS, and to refer patients for treatment. 9 Note: triple packaging for sample transport is NOT included; - Three kits are designed for the treatment of Cholera patients within existing structures at the central, peripheral and community levels; - One kit provides the necessary material to set up a provisional structure for patient care when no existing structure is in place. • There is a tool that quickly estimates needs of Cholera kits (see link on next page). CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 168 More information about Cholera: • Cholera WHO webpage http://who.int/cholera/en/ • Cholera WHO factsheet http://who.int/mediacentre/factsheets/fs107/en/ • Ending Cholera: a global roadmap to 2030 http://www.who.int/cholera/publications/global-roadmap/en/ • Cholera kits http://who.int/cholera/kit/en/ • Cholera outbreak: assessing the outbreak response and improving preparedness http://who.int/cholera/publications/OutbreakAssessment/en/ • First steps for managing an outbreak of acute diarrhoea http://who.int/cholera/publications/fi rststeps/en/ • Interim guidance document for Cholera surveillance, Global Task Force on Cholera Control, Surveillance Working Group http://www.who.int/cholera/task_force/GTFCC-Guidance-cholera- surveillance.pdf?ua=1 • Interim technical notes on the Use of Cholera Rapid Diagnostic Tests, Global Task Force on Cholera Control, Surveillance and Laboratory Working Group http://www.who.int/cholera/task_force/Interim-guidance-cholera-RDT. pdf?ua=1 • Oral Cholera Vaccine and technical notes on the use of OCV in pregnant women and travellers http://www.who.int/cholera/vaccines/en/ • WHO Oral Cholera Vaccines position paper – 2017 http://apps.who.int/iris/bitstream/10665/258763/1/WER9234.pdf?ua=1 CHOLERAMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 169 1. Monkeypox virus is in the same family of viruses as Smallpox virus (Orthopoxviruses) 2. Primary infection occurs through direct contact with body fl uids or lesions of infected animals 3. Secondary human-to-human transmission exists 4. Isolation of patients and standard infection prevention and control (IPC) measures are key to minimizing any possibility of human-to-human transmission 5. Avoid contact with animals that could harbour the virus, especially rodents and sick or dead animals 6. Active surveillance to ensure rapid identifi cation of new cases is critical for outbreak containment 7. There is no specifi c treatment or vaccine recommended for Monkeypox 8. Health education and raising population awareness are the best preventive measures in at-risk populations 9. Many animal species host the Monkeypox virus, primarily rodent species (rather than monkeys, after which the disease is named) 10. Monkeypox is a rare disease that occurs sporadically in remote tropical rainforest areas of Central and West Africa 10 THINGS YOU SHOULD KNOW Monkeypox MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 170 Monkeypox response tips Coordinating responders • Establish an Emergency Operations Centre if cases are above what is expected • Ensure the animal and wildlife sector is involved from the very beginning • Engage communities Communicating risk • Encourage health authorities to: - Engage communities to prevent exposure - Ensure training of clinicians for early detection, sampling and treatment • Key messages: - Avoid contact with dead animals (rats, squirrels and monkeys) - Human-to-human transmission occurs through respiratory droplets, contact with infected persons or contaminated materials - If you think you might have been exposed to Monkeypox and have any symptoms, go to the nearest health facility and avoid self- medication - Protect yourself when caring for patients with a rash Health Information • Develop a case defi nition and a case investigation form adapted to the context • Develop a consolidated laboratory/ surveillance database • Map cases residence • Notify cases to WHO, under the IHR (2005) Health Interventions • Community engagement and strong risk communication • Contact tracing • Isolation and supportive care for cases • Psychosocial support for all suspected cases and families • Safe and dignifi ed burials MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 171 1 2 Primary infection occurs through direct contact with body fl uids or lesions of infected animals • Primary infection occurs through direct contact with the blood, body fl uids, or cutaneous or mucosal lesions of infected animals. • Hunters in tropical forests of West and Central Africa and people who may be exposed to animals infected with Monkeypox are at higher risk of infection. • People living in or near the forested areas may have indirect or low-level exposure to infected animals, possibly leading to subclinical (asymptomatic) infection and concommitant acquisition of immunity, although this needs to be further explored. Monkeypox virus is in the same family of viruses as Smallpox virus (Orthopoxviruses) • Monkeypox is a rare viral zoonosis with symptoms similar to those seen in Smallpox patients, although less severe. Monkeypox and Smallpox are members of the Orthopoxvirus family. Smallpox was eradicated in 1980 and, along with it, the vaccination programme was discontinued. • The incubation period of Monkeypox is usually from six to 16 days but can range from fi ve to 21 days. • Monkeypox infection can be divided into two periods : - the invasion period (up to the fi rst fi ve days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle ache) and an intense asthenia (lack of energy); - the skin eruption period (within one to three days after appearance of fever) where the various stages of the rash appears, often beginning on the face and then spreading elsewhere on the body. The face (in 95% of cases), palms of the hands and soles of the feet (75%) are most affected. Evolution of the rash from maculopapules (lesions with a fl at bases) to vesicles (small fl uid-fi lled blisters), pustules, followed by crusts occurs in approximately 10 days. Three weeks might be necessary before the complete disappearance of the crusts. • The number of the lesions varies from a few to several thousand, affecting oral mucous membranes (in 70% of cases), genitalia (30%), and conjunctivae (eyelid) (20%), as well as the cornea (eyeball). • Monkeypox is usually a self-limited disease with the symptoms lasting from two to three weeks. • Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and severity of complications. • Case fatality rate in outbreaks has been between one percent and 10% depending on the clade of the virus. There are two distict clades, the Congo Basin which has a case fatality ratio (CFR) of up to 10% and the Western Africa clade with a CFR up to one percent. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 172 Secondary human-to-human transmission exists • It can result from close contact with infected respiratory tract secretions, skin lesions of an infected person or objects recently contaminated by patient fl uids or lesion materials. The virus does not transmit easily from human to human. • Persons become infectious to others once the rash appears. • As transmission occurs primarily via droplet respiratory particles and usually require prolonged face-to-face contact, household members of active cases and people caring for the sick are at greater risk of infection. • Transmission can also occur by parenteral means such as inoculation of the virus or via the placenta (congenital Monkeypox). • There is no evidence to date that person- to-person transmission alone can sustain Monkeypox infections in the human population. 3 Isolation of patients and standard infection prevention and control (IPC) measures are key to minimizing any possibility of human-to-human transmission • Patients should be isolated and treated symptomatically. Close physical contact with Monkeypox infected people should be avoided until the person has fully recovered. • Gloves and personnal protective equipment should be worn when taking care of ill people. • Regular hand washing should be carried out after caring for or visiting sick people. • Health care workers caring for patients with suspected or confi rmed Monkeypox virus infection, or handling specimens from them, should implement standard infection control precautions. 4 MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 173 Avoid contact with animals that could harbour the virus, especially rodents and sick or dead animals • In areas where Monkeypox occurs: - avoid contact with animals that could harbour the virus; - use appropriate infection prevention and control measures when handling animals. Gloves and other personal protective clothing should be worn while handling animals, their tissues, and during slaughtering procedures. • Eating thoroughly cooked animal products (blood, meat) is safe. However, preparation using animal products represents a signifi cant risk. • Not all animals show signs of illness but they can still be contagious, making risk communication diffi cult, especially in areas where communities rely on hunting. Risk communications need to take this into account. 5 Active surveillance to ensure rapid identifi cation of new cases is critical for outbreak containment• Laboratory confi rmation is important as Monkeypox is diffi cult to distinguish from other pox-like illnesses. The differential diagnoses to be considered include other rash illnesses, such as Chickenpox, Measles, bacterial skin infections, Scabies, Syphilis, Smallpox and medication- associated allergies. The development of severe lymphadenopathy before the appearance of the rash, in some patients, is a distinctive feature of Monkeypox compared to other similar diseases. • Monkeypox can be confi rmed in laboratory through several tests (Enzyme-Linked Immunosorbent Assay - ELISA, antigen detection, Polymerase Chain Reaction – PCR, or virus isolation in cell culture). The optimal diagnostic specimens are from lesions, either vesicular swabs of lesion exudate or crusts, stored in a dry, sterile tube (no viral transport media) and kept cold. Blood and serum do not give defi nitive results. 6 • Once a case of Monkeypox is detected, support enhanced surveillance measures to ensure additional Monkeypox cases are detected and that control measures are implemented. • At the beginning of an outbreak, develop a consolidated laboratory and surveillance database to keep track of the information collected in case report forms during outbreak investigation. • Contact tracing should be conducted for all suspected and confi rmed Monkeypox cases. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 174 Symptoms Monkeypox Smallpox Chickenpox Fever 1-3 days before the rash 2-4 days before the rash At the rash onset Rash appearance The rash evolves from maculopapules to vesicles, pustules, followed by crusts in approximatively 10 days Pocks at the same stage Pocks in several stages Rash distribution Typically starts on face and spreads to arms and legs, then hands and feet including palm and soles More dense on face and extremities; present on palms and soles More dense on the body; absent on palms and soles Other distinctive feature Patients present with lymphadenopathy (swollen lymph nodes) before the appearance of the rash No lymphadenopathy The rash itches Rash development Rapid Low Rapid Death 1-10% Around 30% Rare Clinical differential diagnosis between Monkeypox, Smallpox and Chickenpox Note: Smallpox has been eradicated and the information on disease comes from evidence gathered before 1980. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 175 Health education and raising population awareness are the best preventive measures in at-risk populations • In the absence of specifi c treatment or vaccine, the only way to limit infection in people is by raising awareness of the risk factors and educating people about the measures they can take to avoid exposure to the virus. • Health care workers should be trained to recognize the symptoms of the disease, ensure samples are collected for testing and manage patients. Most importantly, they should be trained on appropriate isolation and infection prevention and control procedures. 87 There is no specifi c treatment or vaccine recommended for Monkeypox• To date, there are no specifi c treatments or vaccines available for Monkeypox infection. • Given the genomic conservation among Orthopoxviruses, it is likely that Smallpox vaccine is protective against Monkeypox (estimated at 85% effectiveness) but the vaccine is no longer available to the general public, after Smallpox eradication in 1980. • Currently, studies are underway to better understand how effective newer Smallpox vaccines are at providing cross-protection against Monkeypox. • Prior Smallpox vaccination will likely result in a milder Monkeypox disease course. MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 176 Monkeypox is a rare disease that occurs sporadically in remote tropical rainforest areas of Central and West Africa • Human Monkeypox is sporadically reported in Central and West Africa, particularly areas close to tropical rainforest where humans have frequent contact with animals. • Outbreaks have occured outside Africa (e.g. in the Midwest of the United States of America in 2003 due to imported animals) and outside Central and West Africa (e.g. in Sudan in 2005). 10Many animal species host the Monkeypox virus, primarily rodent species (rather than monkeys, after which the disease is named) • The name Monkeypox is misleading as the disease does not solely come from monkeys. In Africa, Monkeypox infection has been found in many animal species: rope squirrels, tree squirrels, Gambian rats, rodents, striped mice, dormice and monkeys. • Doubts persist on the natural history of the virus and further studies are needed to identify the major reservoir of the Monkeypox virus and how it is maintained in nature. 9 MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 177 Historical distribution of human monkeypox cases Country reporting monkeypox cases in 2017 and in previous years Countries reporting human monkeypox cases Country reporting monkeypox cases in previous years Liberia Sierra Leone Côte d’Ivoire Nigeria Cameroon Gabon Congo Central African Republic Democratic Republic of the Congo The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 178 More information about Monkeypox: • Monkeypox WHO factsheet http://www.who.int/mediacentre/factsheets/fs161/en/ MONKEYPOXMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 179 10 THINGS YOU SHOULD KNOW Plague 1. Pneumonic Plague can cause widespread epidemics and is diffi cult to control 2. The most common form of Plague – Bubonic Plague - is not transmittable from human to human 3. Early diagnosis and treatment are essential for survival 4. Health education, infection prevention and control and vector and rodent control are critical to prevent and manage epidemics 5. Safe and dignifi ed burials should be conducted to avoid further transmission 6. Initial symptoms of Plague are non-specifi c and diffi cult to distinguish from other acute febrile diseases 7. The potential Plague natural foci are distributed worldwide and are extending 8. Plague is a disease that usually affects disproportionately vulnerable populations 9. Septicaemic Plague is the third type of Plague, in addition to the Pneumonic and Bubonic forms, that occurs when the bacteria is circulating in the bloodstream 10. Plague is a zoonotic disease caused by bacteria usually found in small mammals (mostly rodents) PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 180 Plague response tips Coordinating responders • Engage with partners and communities for vector control in endemic areas Communicating risk • Encourage health authorities to: - Initiate health education and community engagement for vector control in endemic areas • Key messages: - Plague is treatable: people who have symptoms or have exposure to the disease should receive treatment - Transmission of Bubonic and Pneumonic Plague are different - Human-to-human transmission of Pneumonic Plague can occur through respiratory droplets - Patients with Bubonic Plague are not contagious - For Bubonic Plague, take precautions against fl ea bites and do not handle animal carcasses Health Information • There is a robust and sensitive rapid diagnostic test for Bubonic Plague • Find the source of infection for targeted control measures • Notify cases to WHO, under the IHR (2005) Health Interventions • Treat early with antibiotics • Ensure safe and dignifi ed burials • For Pneumonic Plague: - Closely follow close contacts and provide them with prophylaxis for seven days - Give chemoprophylaxis to health care workers - Infection prevention and control: Standard precautions and droplet precautions (Protective Personal Equipment- PPE) • For Bubonic Plague: - Vector and rodent control - Give chemoprophylaxis for people living in the same house as patients - Infection prevention and control (standard precautions) PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 181 Pneumonic Plague can cause widespread epidemics and is diffi cult to control • Pneumonic Plague can be transmitted from person to person via droplets in the air (coughing, respiratory secretions), so it has high epidemic potential and is the most diffi cult form of Plague to control. • It is the most virulent form of Plague: the incubation period can be as short as 24 hours, and untreated Pneumonic Plague is always fatal. • Pneumonic Plague occurs when it reaches the lungs, from the evolution of an advanced Bubonic Plague, through bloodstream, or directly from inhalation of infected respiratory droplets. • Patients with Pneumonic Plague should be isolated so they do not infect others via respiratory droplets and should be cared for by trained medical staff. Medical staff should wear Personal Protective Equipment and potentially receive chemoprophylaxis to prevent nosocomial transmission. • Close contacts must be kept under medical surveillance and must receive a prophylaxis with antibiotics for seven days. • Any suspect case should be treated. • In case of interhuman transmission, the incubation period is usually one to three days, followed by sudden onset of fever, headache, chills, pain, weakness, chest discomfort, shortness of breath, cough, and sometimes bloody or mucous secretions. The most common form of Plague – Bubonic Plague - is not transmittable from human to human • Bubonic Plague is the most common form of Plague. It cannot be transmitted from human to human unless there is contact with pus from suppurating buboes. • Around 10% of people with Bubonic Plague will develop Pneumonic Plague. • Bubonic Plague results from fl ea bites or direct contamination of an open skin lesion by Plague-infected materials or body fl uids (mostly nosocomial infections). Infection can occur when handling dead animals without the appropriate protective measures. The infection spreads via the lymphatic system to the nearest lymph node where 1 2 it replicates itself. The lymph node then becomes infl amed, tense and painful, and is called a “bubo”. At advanced stages of the infection, the infl amed lymph nodes can turn into suppurating open sores. • The incubation period is two to six days followed by sudden onset of illness: headaches, chills, fever, malaise and pain in the affected regional lymph nodes. Bubonic Plague forms buboes, infl ammation and swelling in the neck, groin, etc. • Measures to control an epidemic of Bubonic Plague include: chemopro- phylaxis for people living in the same house as patients, and vector and rodent control. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 182 Early diagnosis and treatment are essential for survival • Plague is treatable. • Treatment with common antibiotics and supportive care are very effi cient in curing human Plague but their effi cacy depends on early administration, which presumes early detection. This is especially important for the Pneumonic form, which is highly contagious, can kill in less than 24 hours, and is invariably fatal in the absence of treatment. If people are treated in time, both forms have good recovery rates. • Recommended antibiotics are: - For Bubonic Plague: tetracycline, doxycycline, chloramphenicol; - For Pneumonic or Septicaemic Plague: aminoglycosides, fl uoroquinolones; - For post-exposure presumptive treatment: tetracycline, doxycycline, sulfamethoxazole/ trimethoprim. • Early treatment requires early diagnosis. Confi rmation of Plague requires laboratory testing. The best practice is to identify the 3 bacteria Y Pestis in a sample of puss from a bubo, blood or sputum. It can be detected by different techniques: - Microscopy: Staining, Fluorescent Antibody test; - Isolation: Colony morphology, Biochemical reactions, Phage lysis; - Detection of antigen/antibody: ELISA (Enzyme-Linked Immunosorbent Assay), Fluorescent antibody test, PCR (Polymerase Chain Reaction). • There is an easy-to-use, robust, reliable and sensitive rapid diagnostic test for Bubonic Plague (dipstick test), that detects antigen and produces reliable results in 15 minutes, greatly facilitating containment efforts. It is recommended that this rapid diagnostic test is used in all endemic regions. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 183 5 Safe and dignifi ed burials should be conducted to avoid further transmission• The bacteria present in the body fl uids of deceased Plague patients can be a source of infection for people in contact with them during burials ceremonies. Safe burials, respecting local cultures and beliefs, must be implemented. Health education, infection prevention and control and vector and rodent control are critical to prevent and manage epidemics • In Plague endemic areas, it is critical to educate people on the disease, its symptoms and modes of transmission. People should be informed when zoonotic Plague is active in their environment and be advised to take precautions against fl ea bites and not to handle animal carcasses. • Avoiding touching dead animals and wearing insect repellent will help prevent Bubonic Plague in endemic areas. • Avoiding close contact (less than two metres) with suspected Pneumonic Plague patients who are coughing will help to prevent Pneumonic Plague. • Plague, “the Black Death”, can be a very scary disease as it has caused millions of deaths in the past, so health education is particularly essential to prevent panic during outbreaks. • Health care workers should specifi cally be informed and trained in infection prevention and control. They should be provided with the appropriate personal protective equipment and trained in how to use it. • In Plague endemic areas and during Bubonic Plague outbreaks, fl ea and reservoir (usually rodents) controls must be implemented. 4 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 184 The potential Plague natural foci are distributed worldwide and are extending • Although Plague is most common in Madagascar, the Democratic Republic of the Congo and Peru, the potential Plague natural foci (the bacteria, an animal reservoir and a vector) are distributed worldwide. • We are currently witnessing the reemergence of the disease in some places where it had disappeared and its emergence in other places where it had never occurred. • The natural foci are also expanding. This could be due to: 7Initial symptoms of Plague are non-specifi c and diffi cult to distinguish from other acute febrile diseases • People infected with Plague begin to develop non-specifi c symptoms after an incubation period of one to seven days. Typical symptoms are the sudden onset of fever, chills, head and body-aches and weakness, vomiting and nausea. These symptoms are diffi cult to differentiate from other common endemic pathogens. • Painful and infl amed lymph nodes secondarily appear during Bubonic Plague. • Symptoms of Pneumonic Plague appear quickly after infection (sometimes less than 24 hours). They include severe respiratory symptoms, such as shortness of breath and coughing, often with blood- tainted sputum. • The clinical picture is not very specifi c and misdiagnosis is common, thus the importance of Rapid Diagnostic Test, for rapid diagnosis and early treatment. 6 - Environmental modifi cations (e.g. deforestation); - Ongoing colonization of the black rat (one of the reservoirs); - Increased national and international exchanges; - Uncontrolled urbanization. • Furthermore, in endemic countries, entomological and zoological surveillance activities are expensive and complicated to maintain. They are very often neglected in the absence of any human cases and it is hard to obtain detailed knowledge about the status or development of natural foci. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 185 Septicaemic Plague is the third type of Plague, in addition to the Pneumonic and Bubonic forms, that occurs when the bacteria is circulating in the bloodstream • Septicaemic Plague is the third form of Plague which occurs when the infection spreads through the bloodstream. • Septicaemic Plague may result from fl ea bites and from direct contact with infective materials through cracks in the skin or follow a Bubonic Plague. It could result in Pneumonic Plague. 9Plague is a disease that usually affects disproportionately vulnerable populations • Plague is a disease that affects disproportionately vulnerable populations, because it thrives in overcrowded places with poor sanitary conditions and inadequate health services. • Outbreaks of Plague are often linked to civil disturbances and war, and when the health infrastructure and facilities have broken down. • Strengthening health systems thus reduces the risk of epidemics. 8 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 186 Plague is a zoonotic disease caused by bacteria usually found in small mammals (mostly rodents) • Plague is a zoonotic disease caused by the bacteria Yersinia pestis, usually found in small mammals (mostly rodents). It is transmitted between animals by their fl eas. • There is a risk of human Plague wherever the presence of Plague natural foci (the bacteria, an animal reservoir and a vector) and human populations co-exist. • There are three main forms of Plague infection, depending on the clinical presentation of infection: Bubonic, Septicaemic and Pneumonic. Humans can become infected by the bite of infected fl eas, by direct contact with infected materials, or by inhalation of infectious respiratory particles from another sick person with Pneumonic Plague. • There is a great risk of nosocomial (hospital) infection, especially for the Pneumonic form. • Human Plague is a severe disease, with a 30-100 % case fatality ratio, depending on the clinical form. 10 • However, when rapidly diagnosed and promptly treated, Plague may be successfully managed with antibiotics, reducing mortality to less than 15%. • Plague epidemics have occurred in Africa, Asia and South America. Since the 1990s, most human cases have occurred in Africa. The three most endemic countries are Madagascar, the Democratic Republic of Congo and Peru. PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 187 Global distribution of natural Plague foci, as of March 2016 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. Areas* with potential plague natural foci based on historical data and current information * First administrative level representation Source: WHO / IHM, as of March 2016 PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 188 More information about Plague • WHO Fact sheet http://www.who.int/mediacentre/factsheets/fs267/en/ • Plague WHO webpage http://www.who.int/csr/disease/plague/en/ • Plague WHO MOOC https://openwho.org/courses/knowledge-resources-plague • Plague manual: epidemiology, distribution, surveillance and control http://who.int/csr/resources/publications/plague/WHO_CDS_CSR_ EDC_99_2_EN/en/ PLAGUEMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 189 1. Leptospirosis is a disease that usually follows natural disasters in tropical or subtropical climates 2. Rodents are the main reservoir of the Leptospira, causative bacteria of Leptospirosis but all kinds of mammals can play a role in human transmission 3. Humans are infected through direct or indirect exposure to infected animals’ urine 4. Risk of infection is increased in some activities and socioeconomic situations 5. Common antibiotics, if given early, are effective against Leptospirosis 6. Leptospirosis is under-recognized and often mistaken for others diseases 7. Laboratory diagnosis is challenging but critical to confi rm leptospirosis 8. Prevention and control measures should target the infection source, the route of transmission and the disease in humans 9. Climate change and urbanization will increase the frequency and intensity of outbreaks 10. A multi-sectorial and holistic approach is critical for prevention and control 10 THINGS YOU SHOULD KNOW Leptospirosis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 190 Leptospirosis response tips Coordinating responders • Engage with animal health sector Communicating risk • Encourage health authorities to: - Engage communities - Ensure training of clinicians for early detection and treatment - Prepare hospitals to receive severe cases requesting intensive care • Key messages: - Humans are infected through direct or indirect exposure to the urine of infected animals - Avoid contact with rodents - Exposure can occur through contaminated water - Immediately disinfect all skin injuries and avoid contact with untreated water - Seek treatment early if showing symptoms Health Information • Ensure laboratory confi rmation of suspected cases Health Interventions • Early detection of cases • Provide empirical treatment (antibiotics) for all probable cases • Provide population with treated water • Provide targeted chemoprophylaxis and protective equipment to very high- risk populations (rescue, sewage and sanitation workers) LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 191 Leptospirosis is a disease that usually follows natural disasters in tropical or subtropical climates • Leptospirosis is an infectious disease caused by bacteria belonging to the genus Leptospira. • Leptospirosis occurs worldwide, but is most prevalent in tropical and subtropical regions. • It often has a seasonal distribution, increasing with heavy rainfall or higher temperatures. • Outbreaks classically occur in association with natural disasters, especially fl ooding. Rodents are the main reservoir of the Leptospira, causative bacteria of Leptospirosis but all kinds of mammals can play a role in human transmission • Rodents are considered the primary source of infection to humans. • Virtually all wild and domestic mammals can harbour the bacteria that cause leptospirosis in their kidneys and genital tracts and act as source of infection to humans and to other animals. • Cattle, buffaloes, horses, sheep, goats, pigs and dogs are also considered common reservoirs of the bacteria that cause leptospirosis. • Natural history of the disease depends on the local ecological conditions. 1 2 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 192 Humans are infected through direct or indirect exposure to infected animals’ urine • Leptospirosis is a zoonosis, transmitted directly or indirectly from animals to humans. • Humans become infected through direct contact with the urine of infected animals or with a urine-contaminated environment. • The bacteria enter the body through cuts or abrasions on the skin, or through the mucous membranes of the mouth, nose and eyes. • Exposure through water contaminated by urine from infected animals is the most common route of infection. Leptospirosis can occasionally also be transmitted through the drinking of water or ingestion of food contaminated with urine of infected animals and when handling infected animal tissues. • Human-to-human transmission occurs only very rarely. 3 4 Risk of infection is increased in some activities and socioeconomic situations• The risk of infection depends on exposure. Some people have more contact with waters contaminated by rodents or other domestic animals. • People can be exposed through their occupation: Outdoor and agricultural workers (rice-paddy and sugarcane workers, for example); Abattoir workers; Veterinarians; Meat handlers; Pet-shop workers; Sewer workers. • People can also be exposed through recreational activities, through water sports such as swimming or canoeing. Survivors from natural disasters (e.g. fl ooding) are also at higher risk of infection. LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 193 Common antibiotics, if given early, are effective against Leptospirosis • Leptospirosis can be treated with antibiotics that should be given as early in the course of illness as possible, preferably before the fi fth day after the onset of illness. • Clinicians should never wait for the results of laboratory tests before starting treatment with antibiotics. • Treatment options include antibiotics such as amoxycillin, tretracycline, ampicillin and doxycycline, etc. • In severe cases, admission to a hospital is necessary. These severe cases should be treated with high doses of intravenous penicillin. Peritoneal or haemodialysis are indicated in case of renal failure. Mechanical ventilation is indicated for lung hemorrhagic manifestation. Severe forms, which require intensive care, make case management logistically complex to organize in an outbreak context. Leptospirosis is under-recognized and often mistaken for others diseases • Misdiagnosis is common because of Leptospirosis’ variable symptoms and non-specifi c presentations that can mimic many other infectious diseases. • The usual presentation is an acute illness with sudden onset of fever, headache, myalgia (particularly calf muscle) and prostration associated with any of the following symptoms/signs: conjunctival suffusion, anuria or oliguria, jaundice, cough, haemoptysis and breathlessness, haemorrhages (from the intestines, lung bleeding is notorious in some areas), meningeal irritation, cardiac arrhythmia or failure, and skin rash. Other common symptoms include nausea, vomiting, abdominal pain, diarrhoea and arthralgia. • The incubation period of Leptospirosis is usually fi ve to 14 days, with a range of two to 30 days. Although the disease is a self- limiting and often clinically unapparent illness in the majority of cases (there are 5 6 asymptomatic cases), 5-15% of untreated cases can progress to a more severe and potentially fatal stage. • There are four broad clinical categories of leptospirosis: - Mild infl uenza-like illness; - Weil’s syndrome (jaundice, renal failure, hemorrhage, myocarditis); - Meningitis; - Pulmonary hemorrhage and respiratory failure. • Suspicion of Leptospirosis is further increased for patients presenting the above symptoms if there is a history of occupational or recreational exposure to infected animals or to an environment potentially contaminated with animal urine. It is also important for clinicians to consider Leptospirosis in the differential diagnosis of febrile illnesses after fl ooding. • Misdiagnosis or delayed diagnosis have signifi cant clinical implications because early treatment of Leptospirosis is crucial to minimize morbidity and mortality and timely implement control measures. Mild forms Febrile hemorrhagic forms With severe pneumonia When icteric fever Leptospirosis presentations Diseases it could be confused with Malaria, Dengue, Influenza Viral haemorrhagic fevers Plague Yellow fever or Hepatitis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 194 2-10 d 4-7 d 1-3 d 0-10+ d Bacteria enter body through cuts or mucosal surfaces; bacterial flagellae aid tissue penetration Fever & other symptoms resolve temporarily prior to onset of Immune phase Recurring fever and CNS involvement (meningitis); primarily humoral response; antileptospiral antibodies lead to clearance of the organism from most tissues except kidney tubules; leptospires may continue to shed in the urine for long periods Abrupt onset of fever, headache, muscle pain, nausea; leptospires isolated from blood, CSF and most tissues; mostly anicteric, 5-10% have jaundice Incubation period Septicaemic phase Interphase Immune phase Typical course of Leptospirosis LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 195 Laboratory diagnosis is challenging but critical to confi rm leptospirosis • Laboratory diagnostic is not easy because of the complexity of the pathogen: there are 300 species and 25 serogroups, divided into 250 serovars. • Laboratory support is needed: - To confi rm the diagnosis and distinguish it from other diseases; - To determine the serovar responsible for infection, which will help guide the control strategies. • Current recommendations for laboratory testing are: - Serology: Microscopic Agglutination Test (MAT) is the gold standard serologic test, due to its high specifi city; - Polymerase Chain Reaction – PCR. • IgM Enzyme-Linked Immunosorbent Assay (ELISA) test may be used but it requires a lag period after infection before antibodies become detectable. The results need to be interpreted carefully due to varying sensitivity and specifi city of the test method. Prevention and control measures should target the infection source, the route of transmission and the disease in humans • Control measures at the infection source (usually local reservoir species of animals) include: Reducing certain animal reservoir populations; Separating animal reservoirs from human habitations (by fences and screens); Immunizing dogs and livestock; Removing rubbish and keeping areas around human habitations clean; Disposing of excreta from domestic animals in such a way as to avoid contamination; Encouraging people not to leave food around, especially in recreational areas where rats may be present; Improving living conditions and sanitation systems, etc. • Measures to prevent transmission through avoiding contact with animal urine, infected animals or an infected environment, include: Wearing protective clothing; Covering skin lesions with waterproof dressings; Preventing access to, or giving adequate warning about water bodies known or suspected to be contaminated; Washing or showering after exposure to urine splashes or contaminated soil or water; Washing and cleaning wounds; Strictly maintaining hygienic measures during care or handling of all animals; Where feasible, disinfecting contaminated areas (scrubbing fl oors in stables, butcheries, abattoirs, etc.); Consuming clean drinking-water, etc. • Interventions at the level of the human host include: 7 8 - Raising awareness in both the general population and at-risk groups. People need to understand the disease and how to avoid risks, but also that timely medication helps. Doctors and veterinarians should consider leptospirosis as part of the differential diagnosis in appropriate cases; - Antibiotic prophylaxis should be used if exposure is known to have occurred (e.g. as a result of a laboratory accident or other high-risk exposure); - Immunization in humans is not recommended. Vaccines do not induce long-term protection against infection and do not provide cross-protective immunity against heterogenous leptospiral serovars (protective antibodies are produced only against the serovars present in the particular vaccine used). • In epidemic situations, strategic control measures include: - Detecting cases early; - Providing empirical treatment for all probable cases; - Providing the population with treated water; - Providing targeted chemoprophylaxis and protective equipment to very high- risk populations (rescue, sewage and sanitation workers); - Rodent control and animal immunization are useless at this stage. LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 196 Climate change and urbanization will increase the frequency and intensity of outbreaks • Leptospirosis infections are closely linked to the environment and climate change will lead to an escalation of the global burden of leptospirosis: - Climate change is expected to increase the occurrence of heavy rainfall and fl ooding and the intensity of tropical cyclones and storms, due to the rise of sea levels and the rise of sea and land surface temperatures; - Natural disasters also increase the risk of infectious disease by disrupting health services and infrastructures and damaging water and sanitation networks. • Urbanization also increases the incidence and intensity of leptospirosis. Fast urbanization usually goes with the development of urban slums, where overcrowding, poor sanitation, poor health care, poverty and abundance of rats and other animal reservoirs are risk factors of being infected. 9 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 197 A multi-sectorial and holistic approach is critical for prevention and control • Leptospirosis remains an unknown disease: transmission dynamics are poorly understood, symptoms are not specifi c, laboratory diagnosis is complex and laboratory confi rmation is often not available. • A One Health approach is critical to prevent and control this environmental disease that affects both humans and animal: - Relationships between animals, humans and ecosystems needs to be considered to better understand and manage the disease; - Research and control efforts require a truly integrated, multi-disciplinary and coordinated approach to improve prediction, detection, prevention and response to outbreaks of Leptospirosis. 10 LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 198 More information about Leptospirosis: • Leptospirosis WHO webpage http://www.who.int/topics/leptospirosis/en/ • Leptospirosis WHO Western Pacifi c Region Offi ce factsheet: http://www.wpro.who.int/mediacentre/factsheets/fs_13082012_ leptospirosis/en/ • Leptospirosis WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Global Leptospirosis Environmental Action Network (GLEAN) website https://sites.google.com/site/gleanlepto/ • Human Leptospirosis: guidance for diagnosis, surveillance and control: http://apps.who.int/iris/bitstream/10665/42667/1/WHO_CDS_CSR_ EPH_2002.23.pdf LEPTOSPIROSISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 199 1. Meningococcal meningitis (MM) is an acute bacterial form of meningitis due to Neisseria meningitidis (N.m), a serious infection of the meninges (brain membranes) 2. MM occurs worldwide but its highest burden is in the African meningitis belt 3. Several types of N.m can cause epidemics 4. Humans are the only reservoir of MM, transmitted through direct contact and respiratory droplets 5. MM can have a fatality rate of up to 50% when untreated 6. Specifi c vaccines are used for prevention and outbreak response 7. Laboratory diagnosis is essential to ascertain whether N.m is the pathogen causing meningitis 8. Surveillance is critical to detect outbreaks and inform the epidemic response 9. Early antibiotic treatment is the most important factor to save life and reduce complications 10. Antibiotics reduce transmission risk for close contacts when given promptly 10 THINGS YOU SHOULD KNOW Meningococcal meningitis MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 200 Meningococcal meningitis response tips Coordinating responders • Make sure the epidemic preparedness and response committee is established before the epidemic season • Contact WHO/ICG for emergency vaccines and antibiotics Communicating risk • Ensure populations receive the vaccine to prevent this disease • Key messages are: - Human-to-human transmission occurs through droplets of respiratory or throat secretions - Asymptomatic carriers can transmit the disease - Practice hand hygiene and respiratory hygiene - Early antibiotic treatment reduces mortality and complications and therefore sick people should seek medical treatment early on Health Information • Identify the meningococcal serogroup through laboratory testing • Monitor thresholds that have been defi ned according to specifi c regional or country epidemiology Health Interventions • Early antibiotic treatment • Conduct vaccination campaigns promptly (according to local epidemiology) • Prophylaxis to close contacts (according to local epidemiology) MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 201 Meningococcal meningitis (MM) is an acute bacterial form of meningitis due to Neisseria meningitidis (N.m), a serious infection of the meninges (brain membranes) • MM is due to the bacteria Neisseria meningitidis. • A variety of other organisms including bacteria, fungi or viruses, can cause meningitis. • MM causes sporadic cases and also very large outbreaks. MM occurs worldwide but its highest burden is in the African meningitis belt • The highest burden is observed in the meningitis belt (26 countries) that stretches across Africa from Senegal to Ethiopia. • The meningitis belt is affected by seasonal endemicity and cyclical large scale epidemics, during the dry season (December to June). Several types of N.m can cause epidemics • Serogroups are named by a letter (A, B, C, etc.). 6 (out of 12) serogroups can cause large epidemics (A, B, C, W, X, Y). Geographic distribution differs according to serogroup. • In the meningitis belt, before 2010, serogroup A meningococcus accounted for an estimated 80–85% of all cases. Since the introduction of a new and very effi cient meningococcal A conjugate vaccine through mass preventive immunization campaigns, the proportion of N. meningitidis A has declined dramatically. • In Europe, the introduction of routine vaccination for N. meningitidis C led to the decline of serogroup C outbreaks. • Independently of the vaccination strategies, the epidemiology of serogroups fl uctuates over time and space for reasons that are not fully understood. 1 2 3 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 202 Humans are the only reservoir of MM, transmitted through direct contact and respiratory droplets • Neisseria meningitidis only infects humans. There is no animal reservoir. • The bacteria can be carried in the throat (asymptomatic carrier). By chance, it can overwhelm the body’s defenses allowing the bacteria to spread through the bloodstream to the brain. • The bacteria are transmitted from person-to-person through droplets of respiratory or throat secretions from carriers. Smoking, close and prolonged contact – such as kissing, sneezing or coughing on someone, or living in close quarters with an infected person (a carrier) – facilitate the spread of the disease. MM can have a fatality rate of up to 50% when untreated • The most common symptoms of the disease are high fever, headaches, stiff neck, vomiting, confusion, sensitivity to light and bulging of the fontanelle in infants. Sometimes, a haemorrhagic rash, ranging from a few petechiae to widespread ecchymoses, occurs as a result of septicaemia. • Even when the disease is diagnosed early and adequate treatment is started, 8–15% of patients die, often within 24 to 48 hours after the onset of symptoms. If untreated, MM is fatal in 50% of cases. • MM may result in brain damage, hearing loss or disability in 10% to 20% of survivors. 4 5 • Asymptomatic carriers can transmit the disease. It is believed that 1% to 10% of the population carries N. meningitidis in their throat in endemic situations. In epidemics, the carriage rate is higher (10% to 25%). • Infants and young adults are the most at risk of getting infected. • The incubation period is 2 to 10 days, usually 3 to 4 days. • Transmission of N. meningitidis is facilitated during mass gatherings (recent examples include the Haj pilgrimage, jamborees, etc.). MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 203 Specifi c vaccines are used for prevention and outbreak response • Vaccines are serogroup specifi c and confer varying degrees of duration of protection. • There are 3 types of vaccines available: - Polysaccharide vaccines are used for outbreak response mainly in Africa: o They are either bivalent (serogroups A and C), trivalent (A, C and W), or tetravalent (A, C, Y and W); o They are not effective before 2 years of age; o They offer a 3-year protection but do not induce herd immunity. - Conjugate vaccines are used in prevention (into routine immunization schedules) and outbreak response: o They confer longer-lasting immunity, prevent carriage and induce herd immunity; o They can be used as soon as one year of age; o Available vaccines include: 6 • Monovalent C and Tetravalent (serogroups A, C, Y, W). Both are currently expensive and mostly used in Canada, United States of America and Europe. • Monovalent A, used for mass preventive campaigns and routine infant immunization. - Protein-based vaccine against N. meningitidis B. It has been used in prevention (into the routine immunization schedule of one country, the UK) and outbreak response. • Reactive vaccination in affected and at- risk populations should be conducted promptly to prevent the spread of the disease. • In Africa, it is essential that a vaccination campaign is conducted within four weeks of crossing the epidemic threshold. • An international stockpile of vaccine has been constituted, that can be accessed by any country facing an outbreak, through a request to the International Coordinating Group on vaccine provision for Meningitis. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 204 Indicative decision tree for meningitis vaccine choice in a reactive vaccination campaign Source: WHO, Managing meningitis epidemics in Africa, Revised 2015 Alert threshold reached meningitis cases available Conduct investigation and obtain specimens no Main pathogen = Nm A Main pathogen = Nm C or W Main pathogen = Nm X Main pathogen = Spn / Hib ≥ 30% of Nm positive are Nm C or W Case management no vaccination yes no If epidemic threshold is crossed ACW containing vaccine Men A conjugate vaccine ACW containing vaccine yes REMEMBER If there are NmA cases in the population already vaccinated with MenA conjugate, conduct field investigation. * Confirmation includes a positive result from culture, polymerase chain reaction or rapid diagnostic test. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 205 Laboratory diagnosis is essential to ascertain whether N.m is the pathogen causing Meningitis • Confi rmation of the disease needs a laboratory test performed on Cerebrospinal Fluid (CSF) obtained through lumbar puncture: tests include culture (growing the bacteria), agglutination tests and Polymerase Chain Reaction (PCR). • At the fi eld level, to rapidly identify the N. meningitidis bacteria and the serogroups, rapid point-of-care diagnostic tests should be used. Rapid confi rmation of the pathogen is critical to determine appropriate treatment and epidemic response. Surveillance is critical to detect outbreaks and inform the epidemic response • Surveillance systems should be tailored to detect outbreaks, monitor disease trends and impact of vaccine. • Epidemiological and laboratory data should be linked. • The defi nition of a Meningococcal meningitis outbreak varies from country to country, based on local epidemiology and a comprehensive analysis of surveillance data. • In the African belt, standard case defi nitions are: - Suspected case (based on clinical presentation): any person with sudden onset of fever (>38.5 °C rectal or 38.0 °C axillary) and neck stiffness or another meningeal sign including bulging fontanelle in toddlers; - Probable case (based on non-specifi c laboratory test): any suspected case with macroscopic aspect of CSF turbid, cloudy or purulent; or with a CSF leukocyte count >10 cells/mm3; or with bacteria identifi ed by Gram stain in CSF; 7 8 o In infants: CSF leucocyte count >100 cells/mm3; or CSF leucocyte count 10– 100 cells/ mm3 AND either an elevated protein (>100 mg/dl) or decreased glucose (<40 mg/dl) level. - Confi rmed (based on laboratory test): any suspected or probable case that is laboratory confi rmed by culturing or identifying of Neisseria meningitidis in the CSF or blood. • In the African belt, incidence thresholds that will trigger prevention and control interventions are shown in the table on the following page. MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 206 Incidence thresholds for detection and control of epidemic Meningococcal meningitis (2014) Source: WHO, Managing meningitis epidemics in Africa, Revised 2015 — Inform authorities — Strengthen surveillance — Investigate — laboratory) — Prepare for eventual response inhabitants / week (Minimum of 2 cases in one week) 2 suspected cases in one 100,000 week Or An increased incidence compared to previous non- epidemic years — Mass vaccination within four weeks of crossing the epidemic threshold — Distribute treatment to health centres — Treat according to epidemic protocol — Inform the public inhabitants / week 5 suspected cases in one week Or Doubling of the number of cases in a three-week period (e.g. Week 1: 1 case, Week 2: 2 cases, Week 3: 4 cases) If a neighbouring area to a population targeted for vaccination is considered to be at risk (e.g. cases early in the dry season, no recent relevant vaccination campaign, high population density), it should be included in a vaccination programme. In special situations such as mass gatherings, refugees, displaced prompt mass vaccination. POPULATION Intervention 30,000 – 100,000 Under 30,000 Alert threshold Epidemic threshold 100,000 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 207 Early antibiotic treatment is the most important factor to save life and reduce complications • Prompt treatment (within one hour of diagnosis) is crucial to prevent death and complications: - 5 days ceftriaxone (IV) - 7 days in infants (0-2 months old) - is recommended as a standard treatment during epidemics in the African belt. • Admission to a hospital or health centre is necessary, although isolation of the patient is not necessary. • If there is no improvement of patients’ condition within 48 hours of treatment of if exhibiting convulsions or comatose, they should be transferred to higher-level health facility. 9 Antibiotics reduce transmission risk for close contacts when given promptly• Outside the African meningitis belt, chemoprophylaxis is recommended for close contacts within the household. • In the meningitis belt, chemoprophylaxis for close contacts is recommended in non-epidemic situations. • Ciprofl oxacin antibiotic is the antibiotic of choice, and ceftriaxone an alternative. 10 MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 208 C,W,X,A SEROGROUP SEROGROUP B,C,Y, W B,C,W B,C,W B,C,W,Y A,C B,C,W, A B,C,W B,W,Y The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2018. All rights reserved Source: WHO/IHM, as of 16 February 2018 Invasive Meningococcal Disease – Serogroup distribution, 2018 Most frequent Less frequent MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 209 More information about Meningococcal meningitis: • Meningococcal meningitis WHO webpage: http://www.who.int/csr/disease/meningococcal/en/ • Meningitis WHO MOOC: https://openwho.org/courses/pandemic-epidemic-diseases • Meningococcal meningitis WHO fact sheet: http://www.who.int/mediacentre/factsheets/fs141/en/ • Managing meningitis epidemics in Africa http://www.who.int/csr/resources/publications/HSE_GAR_ERI_2010_4/en/ • International Coordinating Group (ICG) on Vaccine Provision http://www.who.int/csr/disease/icg/en/ MENINGOCOCCAL MENINGITISMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 210

PART III Tool boxes 213 TOOL BOX 1 The role of WHO Example • WHO is: - Working with countries to increase and sustain access to prevention, treatment and care; - Identifying priorities and setting strategies; - Leading and coordinating the health response during emergencies. • Through the International Health Regulations (2005), WHO helps the countries to strengthen their national core capacities for emergency risk management to prevent, prepare for, respond to and recover from health emergencies. WHO mandate – in light of infectious diseases WHO is directing and coordinating authority on international health within the United Nations’ system, by its six mains functions: 1. Providing leadership on matters critical to health and engaging in partnerships where joint action is needed; PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 214 2. Shaping the research agenda and stimulating the generation, translation and dissemination of valuable knowledge; Example • WHO Research & Development Blueprint is a global strategy and pre- paredness plan that allows the rapid activation of R&D activities during epidemics. Its aim is to fast-track the availability of effective tests, vaccines and medicines that can be used to save lives and avert large scale crisis. http://www.who.int/blueprint/en/ • The WHO public health research agenda for infl uenza provides a framework refl ecting public health research priorities for pandemic, zoonotic and seasonal epidemic infl uenza to reduce the risk of emergence of pandemic infl uenza, limit the spread of pandemic, zoonotic and seasonal epidemic infl uenza, minimize the impact of epidemics, optimize the treatment of patients and promote the development of modern public health tools. http://www.who.int/infl uenza/resources/research/en/ • The MERS-CoV research agenda has been developed by WHO to address key unknowns for this virus focusing on fi ve major areas of research: i) virus origin and characteristics, ii) epidemiology and transmission, iii) clinical management and infection prevention and control measures, iv) product development and implementation, and v) impact of interventions and operational research. http://www.who.int/emergencies/mers-cov/en/ TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 215 Articulating ethical and evidence-based policy options; Example • WHO publishes vaccine position papers, providing global vaccine and immunization recommendations that have an international public health impact. WHO position papers follow the recommendations of the WHO Strategic Advisory Group (SAGE) on immunization. The update of vaccine position paper depends on the availability of new scientifi c evidence and public health priorities. http://www.who.int/immunization/documents/positionpapers_intro/en/ 4. TOOL BOX 1 Setting norms and standards and promoting and monitoring their implementation; Example • WHO developed a pocketbook to provide guidance on best management practices for Viral Haemorrhagic Fevers across health care facilities. http://www.who.int/csr/resources/publications/clinical-management-patients/en/ • WHO developed a rapid advance guideline on recommendations for the use of Personal Protective Equipment for use in a fi lovirus disease outbreak http://www.who.int/csr/resources/publications/ebola/personal-protective- equipment/en/ 3. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 216 TOOL BOX 1 Monitoring the health situation and assessing health trends. Example • WHO conducts regular global risk assessments regarding infectious diseases and assesses the risk for any event which could have public health impact. • WHO publishes a summary of epidemiological situation and risk assessments of events that are being monitored through the disease outbreak news. http://who.int/csr/don/en/ • WHO also disseminates epidemiological information on outbreaks and on communicable diseases of public health importance through the Weekly Epidemiological Record. http://www.who.int/wer/en/ 6. Providing technical support, catalysing change, and building sustainable institutional capacity; Example • WHO has developed a web-based platform offering online courses to transfer knowledge on infectious diseases and improve preparedness and response to epidemics. Courses include global knowledge on managing epidemics and public heath interventions, as well as disease-specifi c knowledge. WHO Massive Open Online Courses: https://openwho.org/ 5. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 217 WHO and the International Health Regulations (IHR) creation: A need for global cooperation in public health The Cholera epidemics that overran Europe between 1830 and 1847 were catalysts for intensive infectious disease diplomacy and multilateral cooperation in public health. They showed that collaboration between countries was needed to control the spread of dangerous diseases across the world. This led to the fi rst International Sanitary Conference in Paris in 1851. In 1948, the WHO Constitution entered into force and in 1951, WHO Member States adopted the International Sanitary Regulations, which were replaced by and renamed the International Health Regulations in 1969. The 1969 Regulations were subject to minor modifi cations in 1973 and 1981. The IHR were primarily intended to monitor and control six serious infectious diseases: Cholera, Plague, Yellow fever, Smallpox, Relapsing fever and Typhus. Under the IHR (1969), only Cholera, Plague and Yellow fever remain notifi able, meaning that States are required to notify WHO if and when these diseases occur on their territory. Increase in cross-border travel and trade, the development of information and communication technologies, the resurgence of some well-known epidemic diseases, such as Cholera and Plague and the emergence of new infectious agents such as Ebola virus disease, as well as the limitations of IHR (1969) (narrow scope of three diseases and dependence on offi cial country notifi cations), led to their revision. The World Health Assembly adopted the IHR (2005) on 23 May 2005 and they entered into force on 15 June 2007. The International Health Regulations (2005) represent a binding international legal agreement involving 196 countries across the globe. They aim to prevent, protect against, control and respond to the international spread of disease while avoiding unnecessary interference with international traffi c and trade. Questions & Answers 1. What are the major changes between IHR (1969) and IHR (2005)? • The scope of the IHR (2005) is purposely broader and more inclusive in respect of the public health event to which they have application in order to maximize the probability that all such events that could have serious international consequences are identifi ed early and promptly reported by States Parties to WHO for assessment. • The IHR (2005) explicitly allow WHO to take into account information from sources other than offi cial notifi cations and consultations, and, after assessment, to seek verifi cation of specifi c events from the concerned States Parties. 2. What are the general obligations of States under the IHR 2005? Under the IHR (2005), States parties are required to: • Designate a National IHR Focal Point (it may be a team). Focal points are required to be available on a 24-hour basis, 7 days a week. • Assess events occurring in their territory and to notify WHO of all events that may constitute a public health emergency of international concern using the decision instrument. • Respond to requests for verifi cation of information regarding events that may constitute a public health emergency of international concern, to respond to public health risks which may spread internationally. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 218 • Develop, strengthen and maintain the capacity to detect, report and respond to public health events; to provide routine facilities, services, inspections and control activities at designated international airports, ports and ground crossings to prevent the international spread of disease. • Report to WHO evidence of a public health risk identifi ed outside their territory which may cause international disease spread, manifested by exported/imported human cases, vectors carrying infection or contamination, contaminated goods. • Respond appropriately to WHO- recommended measures. • Collaborate with other States Parties and with WHO on IHR (2005) implementation. OR Yes NoNo No Yes Yes Is the public health impact of the event serious? NoYes Is the event unusual or unexpected? Is the event unusual or unexpected? NoYes Is there a significant risk of international spread? Is there a significant risk of international spread? NoYes 1 As per WHO case definitions. 2 The disease list shall be used only for the purposes of these Regulations. OR EVENT SHALL BE NOTIFIED TO WHO UNDER THE INTERNATIONAL HEALTH REGULATIONS Not notified at this stage. Reassess when more information becomes available. • Is there a significant risk of inter- national travel or trade restrictions? Events detected by national surveillance system An event involving the following diseases shall always lead to utilization of the algorithm, because they have demonstrated the ability to cause serious public health impact and to spread rapidly internationally: • Cholera • Pneumonic plague • Yellow fever • Viral haemorrhagic fevers (Ebola,Lassa,Marburg) • West Nile fever • Other diseases that are of special national or regional concern, e.g. dengue fever, Rift Valley fever,and meningococcal disease. A case of the following diseases is unusual or unexpected and may have serious public health impact, and thus shall be notified 1, 2: • Smallpox • Poliomyelitis due to wild-type poliovirus • Human influenza caused by a new subtype • Severe acute respiratory syndrome (SARS). Any event of potential international public health concern, including those of unknown causes or sources and those involving other events or diseases than those listed in the box on the left and right shall lead to utilzation of the algorithm. OR Decision instrument for the assessment & notifi cation of events that may constitute a public health emergeny of international concern Source: Annex 2, International Health Regulations (2005) TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 219 3. What events should States Parties notify to WHO? Under the IHR, States Parties are required to notify WHO of all events that are assessed as possibly constituting a Public Health Event of International Concern (PHEIC), taking into account the context in which an event occurs. A decision instrument, provided in Annex 2 of the Regulations, identifi es four criteria that States Parties must follow in their assessment of events within their territories and their decision as to whether an event is notifi able to WHO: • Is the public health impact of the event serious? • Is the event unusual or unexpected? • Is there a signifi cant risk of international spread? • Is there a signifi cant risk of international restriction(s) to travel and trade? 4. What if States Parties have diffi culties to assess an event? State Parties have an option of initiating confi dential consultations with WHO and seeking advice on evaluation, assessment and appropriate health measures to be taken, in case they are unable to complete a defi nitive assessment. 5. How and when to report these events? • These notifi cations must occur within 24 hours of assessment by the country. • Notifi cations must be followed by ongoing communication of detailed public health information on the event, including, where possible, case defi nition, laboratory results, source and type of the risk, number of cases and deaths, conditions affecting the spread of the disease and the health measures employed. 6. What States Parties should do if they identify a public health risk outside their territory? States Parties must inform WHO through the National IHR Focal Point within 24 hours of receipt of evidence of a public health risk identifi ed outside their territory that may cause international disease spread, as manifested by imported or exported human cases, vectors which carry infection or contamination, or by contaminated goods. 7. Can WHO require more information to States Parties about events unoffi cially reported? States Parties are required under the IHR to respond to WHO Requests for Verifi cation. WHO has an express mandate to obtain verifi cation from States Parties concerning unoffi cial reports or communications, received from various sources, about events arising within their territories which may constitute a PHEIC. States Parties must acknowledge verifi cation requests by WHO within 24 hours and provide public health information on the status of the event, followed, in a timely manner. 8. What are the diseases that should be mandatorily notifi ed to WHO? Under the IHR (2005), all cases of four diseases must be automatically notifi ed to WHO: Smallpox, Poliomyelitis due to wild- type poliovirus, SARS and cases of human Infl uenza caused by a new subtype. 9. What are the core capacities? • Under the IHR (2005), each State Party is required to develop, strengthen and maintain core public health capacities for surveillance and response. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 220 • Public health capacity under the IHR (2005) is defi ned as the indispensable, fundamental actions that are the primary responsibility of each State Party for achieving the goal of national health security, i.e. to prevent the spread of diseases and to detect and investigate health risks in the community by effi cient multisectoral action (e.g. integrated disease surveillance systems, laboratory services and national, regional and global networks). • Core capacities at the local (community), intermediate and national levels, as well as key sanitary and health services needed at designated international airports, ports and ground crossings are described in Annex 1 of the IHR (2005). 10. What are the specifi c requirements for Yellow fever? • A proof of vaccination or prophylaxis against Yellow fever may be required for travellers as a condition of entry to a State. • States Parties must designate at least one Yellow fever vaccination centre. 11. Why developing the necessary public health capacities at points of entry will limit the spread of public health hazards? Today’s high traffi c at airports, ports and ground crossings – points of entry, can play a key role in the international spread of diseases through persons, conveyances and goods. This is why countries should be prepared to detect and respond to any health event that may be of international concern and contain risks at source, limiting unnecessary health-based restrictions on international traffi c and trade and protecting the health of travellers and populations. 12. What are the guiding principles for preparedness at points of entry? • Simplicity; • Proportionality and practicality: one size does not fi t all; • Minimal disruption; • Collaboration: multisectoral approach; • (Risk) Communication. For more information: • International Health Regulations (2005) http://www.who.int/ihr/ publications/9789241580496/en/ • More information about IHR http://www.who.int/ihr/about/en/ • More information about implementing IHR http://www.who.int/ihr/procedures/ implementation/en/ • More about public health at points of entry: http://www.who.int/ihr/ports_airports/ en/ • Joint External Evaluation Tool and Process Overview http://apps.who.int/iris/ bitstream/10665/252755/1/WHO-HSE- GCR-2016.18-eng.pdf?ua=1 TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 221 WHO management of events under the Emergency Response Framework (ERF) The ERF is an internal WHO tool that outlines a set of procedures to better respond to emergencies. The ERF provides WHO staff with essential guidance on how the Organization manages the assessment, grading and response to public health events and emergencies with health consequences, in support of Member States and affected communities. TOOL BOX 1 Ungraded Grade 1 Grade 2 A public health event or emergency that is being monitored by WHO but that does not require a WHO operational response. A single country emergency requiring a limited response by WHO, but that still exceeds the usual country-level cooperation that the WHO Country Office (WCO) has with the Member State. Most of the WHO response can be managed with in-country assets. Organizational and/or external support required by the WCO is limited. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office. A single country or multiple country emergency, requiring a moderate response by WHO. The level of response required by WHO always exceeds the capacity of the WCO. Organizational and/or external support required by the WCO is moderate. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office. An Emergency Officer is also appointed at headquarters to assist with the coordination of Organization-wide support. Grade 3 A single country or multiple country emergency, requiring a major/maximal WHO response. Organizational and/or external support required by the WCO is major and requires the mobilization of Organization-wide assets. The provision of support to the WCO is coordinated by an Emergency Coordinator in the Regional Office(s). An Emergency Officer is also appointed at headquarters, to assist with the coordination of Organizationwide inputs. On occasion, the WHE Executive Director and the Regional Director may agree to have the Emergency Coordinator based in headquarters. For events or emergencies involving multiple regions, an Incident Management Support Team at headquarters will coordinate the response across the regions. Levels for graded emergencies Source: Emergency Response Framework, second edition, WHO PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 222 WHO internal grading of events • Once an event is detected or notifi ed to WHO, it will be verifi ed and analysed. Risk assessment would be conducted if the event is confi rmed. Risk assessment by WHO team may result in: - Monitoring, mitigation, preparedness and readiness if the risk is low or very low; - Grading the event and activating the Incident Management System and scaled response if the risk is high or very high. • Grading an event is a WHO internal process which purpose is to defi ne the level of operational response required by WHO. Grading takes into consideration 5 criteria: scale, complexity, urgency of the event, capacity to respond at local and national levels and reputational risk for WHO. • They are four levels for graded emergencies shown here at left. TOOL BOX 1 Linking risk assessment and situation analysis to WHO grading and operational response Source: Emergency Response Framework, second edition, WHO Discard Discard Close event WHO response required; Repurposing WCO WHO response required and/or high/very high risk Graded Emergency: G1 – G3 Ungraded / Pre-grading Ungraded / Pre-grading For acute events and emergencies, grading occurs within 24 hours of risk assessment/situation analysis Suspected public health event Monitoring, mitigation, prepardness & readiness Monitoring, mitigation, prepardness & readiness IMS activation & scaled response Risk assessment: low – very high Emergency Verification Grading Situation analysis Detection PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 223 WHO operational response through the ERF • Grading will trigger WHO emergency procedures and activities for the management of the response. It will activate the Incident Management System (IMS). The IMS is recognized best practice for emergency management. It is simple, fl exible and adaptable to any scenario: it may be applied in small, simple, or large, complex incidents. Scaling up or down the response can be quickly done to suit the changing needs. • The IMS is the combination of facilities, equipment, personnel, procedures and communications operating within a common organizational structure. It enables: - Common terminology and structure that enhance interoperability; - Clarifi cation of roles and responsibilities; - Flow of information and resources; - Rapid mobilization, deployment and tracking of resources. • The IMS implies: - Determining the overarching objectives (e.g. stop transmission of an infectious agent); - Establishing specifi c and measurable objectives for various functional activities; - Developing strategies and issuing plans, directions, procedures, and protocols; - Assigning tasks; - Establishing an evaluation process. • WHO has adapted the Incident Management System to consist of six critical functions: Leadership, Partner Coordination, Information and Planning, Health Operations and Technical Expertise, Operations Support and Logistics, and Finance and Administration. • WHO applies a no regret policy which affi rms that “it is better to err on the side of over-resourcing the critical functions rather than risk failure by under-resourcing”. In terms of fi nancial resources, the WHO representative and/or the Incident Manager has increased authority to approve expenditure. Immediate access to funds, for the fi rst three months of an acute emergency, is provided from either the Contingency Fund for Emergency (CFE) or the Regional Offi ce’s rapid response accounts. TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 224 WHO’s Incident Management System organizational structure: critical functions and sub-functions Source: Emergency Response Framework, second edition, WHO IMS critical functions IMS sub-functions Leadership / Incident management Partner coordination Staff health, wellbeing & security Risk communication & community engagement External relations Liaison ProcurementField support Human resources & surge Health logistics EOC Management Health & intersectoral coordination Prevention & control measures Health service delivery Training of health staff Technical expertise, science & research Planning Finance, budget / grants management Supply chain managementInformation • Risk & needs assessment • Early warning & surveillance • Monitoring & evaluation • Information products • Strategic & operational planning • Project management Communications Information & planning Finance & administration Operations support & logistics Health operations & technical expertise PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 225 For more information: • Emergency Response Framework: http://www.who.int/hac/about/erf/en/ WHO monitoring of the response: a criteria for success • It is critical to evaluate the response to an event and learn the lessons from past responses, improving things that could have gone better and enforcing best practices. • During grade 2 and 3 emergencies, WHO performance standards and key performance indicators are monitored. - Performance standards should be monitored with the ERF Monitoring Tool. The responsibility for completing the ERF Monitoring Tool is with the Country Offi ce, with oversight from the Regional Offi ce. - Key performance indicators (not more 8) are agreed upon on a case-by-case basis for each response (e.g. case fatality ratio; vaccination coverage, etc.). TOOL BOX 1 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 226 TOOL BOX 2 The International Coordinating Group (ICG) on vaccine provision What is the ICG? • The International Coordination Group (ICG) was established in 1997, following major outbreaks of Meningitis in Africa, as a mechanism to manage and coordinate the provision of emergency vaccine supplies and antibiotics to countries during major outbreaks. • The ICG monitors its vaccine security global stock levels for Cholera, Meningitis and Yellow fever to ensure availability of suffi cient supply to respond to disease outbreaks when they occur. • The ICG brings partners together to improve cooperation and coordinating of epidemic preparedness and response. • The ICG also works on forecasting vaccine stocks, negotiating vaccine prices through its networks or partners, evaluating interventions and standard protocols for managing diseases. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 227 Why is such mechanism needed? Though outbreaks of Meningitis, Yellow fever and Cholera are unpredictable events, they can each be controlled by the timely use of vaccine. Vaccine-preventable diseases typically affect people in vulnerable settings who have limited access to vaccines. But vaccines can take months to manufacture, and they are not always readily available in the amounts needed during emergencies. The resulting shortages have raised diffi cult issues about how limited supplies should be allocated during periods of high demand. That is why, after public health organizations found themselves unprepared to respond in a timely manner to a large-scale outbreak of Meningitis in Nigeria, the ICG mechanism was created in 1997. What is the ICG mandate? • The core mandate of the ICG is to make available and ensure equitable access to vaccines for Cholera, Meningitis, and Yellow fever during outbreaks. • The ICG mechanism seeks to ensure timely and targeted deployment so that vaccines can be used as effective outbreak responses where they are most needed. • The ICG also manages the global emergency vaccine stockpiles and, working with manufacturers, determines their size and composition with the goal of ensuring that adequate stocks of emergency supplies are accessible for emergency response. What are the guiding principles of the mechanism? Three principles guide the mechanism: • Equity: distribution of vaccine based on public health priorities; • Rapid and timely access: delivery of vaccine within a defi ned timeframe to control outbreaks; • Independence: decisions made independent of any political or economic infl uences with the sole goal of improving public health. TOOL BOX 2 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 228 Who are the ICG’s partners? The ICG is made up of four member agencies: • International Federation of the Red Cross and Red Crescent Societies (IFRC) - Has strong country presence for community health promotion, local social and resource mobilization and provides support to states during disasters and epidemics. • Médecins sans Frontières (MSF) - An independent, fi eld-based NGO that provides health care to vulnerable populations in emergency settings. • United Nations Children’s Fund (UNICEF) - Conducts wide scale vaccine procurement and shipment, and provides technical support on campaign planning and implementation in country focusing specially on social mobilization and cold chain. • World Health Organization (WHO) - Provides global public health advice and technical support to countries. During outbreaks, WHO focuses on vaccine stockpile management, surveillance, preparedness and response to disease outbreaks. Additional expertise and technical advice is provided on a case-by-case basis from partners including: Agence de Médecine Preventive, Epicentre, GAVI the Vaccine Alliance, WHO Collaborating Centres, the US Centers for Disease Control (CDC) and the European Community Humanitarian Offi ce (ECHO). Vaccine manufacturers, vaccine equipment providers and fi nancial donor institutions are also engaged in the ICG operations. Which vaccine stockpiles are available through the ICG? ICGs have been established to provide access to vaccines for Cholera, Meningitis and Yellow fever. TOOL BOX 2 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 229 For more information: • General information on the ICG: http://www.who.int/csr/disease/icg/en/ • Application forms and guidelines for Cholera: http://www.who.int/csr/disease/icg/ cholera/en/ • Application forms and guidelines for Meningitis: http://www.who.int/csr/disease/ meningococcal/icg/en/ • Application forms and guidelines for Yellow fever: http://www.who.int/csr/disease/icg/ yellow-fever/en/ Lead time for request reception to vaccine delivery How a country can access emergency vaccine stockpiles? • Vaccine security stocks can be accessed by ANY country facing an epidemic ANYWHERE in the world, as long as the country’s request fulfi lls ICG’s criteria for release of vaccine stocks. • As a fi rst step, a country must complete and submit a request to the ICG Secretariat using the standard application form. • The ICG Secretariat at WHO then circulates this request to the partners for review and assessment. Additional requests for information are sent back to the country, if needed. Following a rapid consultation and evaluation process, the decision to release vaccines and other supplies is communicated to the requesting country within 48 hours, once all necessary information has been provided. • If approved, UNICEF procures vaccines and injection materials and organizes delivery of vaccines to the country, ideally within 7 days. • Requests are evaluated taking into account the epidemiological situation, vaccination strategy, pre-existing stocks in the country and operational aspects of the epidemic response. TOOL BOX 2 1 day ICG Sec. ICG core members Procurement agency, ICG Secretariat Request Circulation Decision Delivery 2 working days 7 days PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 230 TABLE 1: Specimen collection and storage TOOL BOX 3 Tables for laboratory diagnosis & shipment of infectious substances Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Diarrhoeal Syndrome Cholera • Liquid stool specimen; • Rectal swab; • Culture isolates. • Container for stool specimen; • Cary-Blair transport medium for the swab; • Filter paper if Cary-Blair is not available, liquid stool sample may be blotted on fi lter paper. • Room temperature up to 4hrs, refrigerated if longer; • Sample in Cary-Blair can be stored at room temperature; • Sample on dry fi lter paper can be stored at room temperature; • Sample on moistened fi lter paper can be stored at room temperature; • Isolated strains from culture: • solid non selective culture medium in test tubes stored at room temperature for a few days; • In Stock Culture Agar at room temperature. Acute Haemorrhagic Fever Crimean-Congo haemorrhagic fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissue. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 231 TABLE 1: Specimen collection and storage, (continued) TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Haemorrhagic Fever Dengue • Whole blood (serum/plasma – 1ml). • Serum separator tubes; • Citrate and heparin plasma can be tested by RT-PCR; • EDTA may cause interference of PCR reagents and testing. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Ebola virus disease • Whole blood (1ml) collected on EDTA (alternative serum); • Oral fl uid collected from deceased patients; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Heparin can cause interference with PCR reagents and tests; • Dacron/polyester swab with fl ocked tip stored in universal transport medium. • < 24 hours: room temperature ; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Lassa fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissues For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 232 TABLE 1: Specimen collection and storage, (continued) TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Haemorrhagic Fever Marburg virus disease • Whole blood (2.5ml) collected on EDTA (alternative serum); • Oral fl uid collected from deceased patients; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Rift Valley fever • Whole blood (2.5ml) collected on EDTA (alternative serum); • Frozen tissue specimens; • Other: formalin-fi xed tissue or paraffi n-embedded tissues. For serology, testing of acute and convalescent specimens is strongly recommended. • EDTA tubes; • Serum separator tubes; • Heparin can cause interference with PCR reagents and tests. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Yellow fever • Whole blood (serum – 1ml); • Other: urine (10ml) has been recommended but is not a validated specimen type. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • < 24 hours: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Acute Jaundice Syndrome Leptospirosis • Whole blood (250 uL); • Serum (250 uL); • Cerebrospinal fl uid (CSF - 250 uL); • Urine (10ml); • Isolate and media inoculated with clinical specimens (blood, tissue and urine). • Blood specimens should be collected in EDTA or Sodium Citrate tubes; • Blood specimens collected in heparin are not acceptable. • Cultures should be stored at room temperature; • Clinical specimens to be kept frozen at -20°C; • Serum to be stored at 4°C. * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 233 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Neurological Syndrome Meningococcal meningitis • Blood (Adult: 5-10ml / Child: 1-3ml); • Cerebrospinal fl uid (CSF – 3ml); • Aspirate or biopsy of any normally sterile site (e.g. cardiac fl uid) and/ or purpuric skin lesion. • CSF: - 1 dry tube and 1 Cryotube (for PCR); - If dry tube cannot be processed in <2 hours, inoculate into trans- isolate (T-I) medium; • Blood: Collected blood should be diluted in blood culture broth in order to obtain blood cultures. Specimens should be immediately inoculated (within one minute) into a blood culture bottle. • CSF in dry tube: room temperature; • CSF in Cryotube: stored at refrigerator temperature and transported in cold chain; • CSF isolates: stored frozen at -20°C to allow further testing; • Trans-isolate (TI) media vials should never be frozen. Before inoculation TI vials should be kept in the refrigerator. Once inoculated, TI vials should be kept at room temperature. Inoculated TI vials must be ventilated if not transported the same day; • Inoculated blood culture media should be protected from temperature extremes (<18°C or >37°C) with a transport carrier and thermal insulator (such as extruded polystyrene foam); • Inoculated blood culture bottles should not be placed in the refrigerator. Acute Respiratory Syndrome Anthrax • Whole blood; • Skin lesion exudates; • Pleural fl uid; • Cerebrospinal fl uid (CSF); • Rectal swab; • Ascites fl uid; • Tissues from biopsy or autopsy. • Blood specimens should be collected in EDTA or Sodium Citrate tubes (not heparin); • Tissues for Immunohistochemistry (IHC) should be formalin-fi xed. • Most samples can be sent 2-8°C; • Fresh tissue should be sent frozen and fi xed tissue can be sent at room temperature. TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 234 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Respiratory Syndrome Infl uenza • Virus isolates; • Respiratory clinical specimens (i.e. nasopharyngeal swabs, nasal swabs, throat swabs, nasal aspirates, nasal washes, lower respiratory tract specimens, broncho lavage); • Nucleic acid. (1ml) For suspected avian infl uenza samples: collect lower respiratory tract specimens in addition to upper respiratory tract specimens • Dacron or polyester fl ocked swabs with universal transport medium • Dacron orSpecimens received cold should be stored refrigerated (2°–8°C) for up to 72hrs before processing. • Dacron orStore any residual specimens at ≤ -70°C. • Dacron orAlthough optimal performance is met when testing fresh specimens within 72hrs of collection, performance has been demonstrated with frozen specimens: - If testing of a fresh specimen is not possible within 72 hours storage at 2–8°C, the specimen may be frozen at ≤ -70°C and tested at a later time; - Specimens received frozen should be stored at ≤ -70°C until processing; - Store any residual specimens at ≤ -70°C; - Ship extracted RNA and frozen specimen on dry ice. Plague • Bubonic plague: bubo aspirate plus, swabs in bacterial transport media (e.g. Cary-Blair); • Pneumonic plague: sputum plus swabs in bacterial transport media (e.g. Cary-Blair); • Blood for serology. Specimens should be collected during the acute phase of illness and ideally before commencement of antibiotic treatment • Fresh or frozen: swab, biopsy, touch prep slides, formalin-fi xed, paraffi n block; • Swabs should be made of nylon, polyester, or Dacron material. • Storage at 2-8°C TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 235 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Respiratory Syndrome MERS • Lower respiratory tract: - Sputum; - Aspirate; - Lavage; • Upper respiratory tract: • Naso-pharyngeal and Oro- pharyngeal swabs; • Naso-pharyngeal • wash / naso-pharyngeal aspirate; • Serum. (1ml) Collection of both upper and lower respiratory tract specimens is recommended • Dacron, polyester swabs with universal transport medium; • Blood: EDTA. • < 24 hrs: room temperature; • > 24hrs-72hrs: 0-4°C; • Long term storage: -20°C or -70°C (preferable). Acute Dermatological Syndrome Cutaneous anthrax • Skin lesion exudates; • Tissues from biopsy or autopsy; • Other: - Whole blood; - Pleural fl uid; - Cerebrospinal fl uid (CSF); - Rectal swab; - Ascites fl uid. • Blood specimens should be collected in EDTA or Sodium Citrate tubes (not heparin); • Tissues for immunohistochemistry (IHC) should be formalin-fi xed. • Most samples can be sent 2-8°C; • Fresh tissue should be shipped frozen; • Fixed tissue should be shipped at room temperature. Monkeypox • Lesion fl uid and/or material: - Vesicle/pustule skin or fl uid; - Scab, crust; • Optional but not preferred: blood. (0.5ml for fl uids) • Swabs without individual holders may be stored in a sterile container; • Dry swabs are preferred but a minimal amount of viral transport media may be added. • Storage at 4°C, shipments within 72hrs TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 236 TOOL BOX 3 Information to be recorded: Patient information, EPID number, date of sample collection, laboratory ID number, and clinical/epi information SYNDROME DISEASE PREFERRED SPECIMEN TYPES & SPECIMEN VOLUMES (minimum)* SPECIMEN COLLECTION MATERIALS STORAGE OF SPECIMENS Acute Dermatological Syndrome Smallpox • Cutaneous lesion scabs; • Pustule fl uid. (0.5ml for fl uids) • Swabs without individual holders may be stored in a sterile container; • Dry swabs are preferred but a minimal amount of viral transport media may be added. • Storage at 4°C, shipments within 72hrs Acute Fever and Rash Chikungunya • Whole blood, serum (4-5ml venous blood); • Other: urine has been recommended but is not a validated specimen type; • CSF in meningoencephalitis cases: - Synovial fl uid in arthritis with effusion; - Autopsy material – serum or available tissues. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • Storage at 0 to 4ÐC Zika • Whole blood, serum, plasma (4- 5ml venous blood); • Urine; • Cerebrospinal fl uid (CSF – 0.25ml); • Other: semen. • EDTA tubes; • Serum separator tubes; • Sterile urine collection tube. • Storage at 4ÐC; • >48hrs, serum should be separated. TABLE 1: Specimen collection and storage, (continued) * For detection, specimens should be collected during the acute phase of illness. Test results are highly dependent on timing of specimen collection in relation to disease onset; therefore, multiple specimens are required to confi rm/exclude diagnosis. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 237 TABLE 2: Laboratory diagnosis and shipment of infectious substances TOOL BOX 3 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Diarrhoeal Syndrome Cholera • RDT for fi eld use (needs additional confi rmation); • PCR, MLVA, sequencing; • Culture; • Antibiotic susceptibility testing. • PCR: 24-48hrs; • Culture and susceptibility testing: up to 8 weeks. • Amoebic Dysentery • Cryptosporidiosis • Giardiasis • Shigellosis • E.coli (enterotoxigenic and enterohaemorrhagic) • Viral gastroenteritis (Norwalk-like and rotavirus) • Salmonellosis • Campylobacter • UN3373 - Biological Substance • Packing Instruction 650 Acute Haemorrhagic Fever Syndrome Crimean-Congo haemorrhagic fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Antigen detection; • Serum neutralization; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Dengue • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Antigen detection: IgM, IgG, RDTs; • Serology; IgM, RDTs; • Virus isolation. • PCR: 24hr;s • ELISA: 72hrs. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 238 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Haemorrhagic Fever Syndrome Ebola virus disease • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Antigen detection (RDT); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Lassa fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 Marburg virus disease • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 72hrs. • UN2814 - Infectious Substance affecting humans • Packing Instruction 620 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 239 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Haemorrhagic Fever Syndrome Rift Valley fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Virus isolation by cell culture. • PCR:24hrs; • ELISA: 72hrs. • Hantaviruses • South American arenaviruses • Tick-borne fl aviviruses • Chikungunya • West Nile • Sindbis • Invasive Meningococcal Disease • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Yellow fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Neutralization assays; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 10 days; • PRNT: up to 2 weeks. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Acute Jaundice Syndrome Leptospirosis • Serology: MAT-micro agglutination; • Molecular: Polymerase Chain Reaction (PCR); • Microscopy. • 2 weeks; • Primary isolation from clinical specimens takes up to 6 months. • Hepatitis A-E • CMV • EBV • Other fl aviviruses • UN3373 - Biological Substance • Packing Instruction 650 Yellow fever • Reverse transcriptase polymerase chain reaction (RT-PCR) assay; • Enzyme-linked immunosorbent assay (ELISA); • Neutralization assays; • Virus isolation by cell culture. • PCR: 24hrs; • ELISA: 10 days; • PRNT: up to 2 weeks. • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 240 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Neurological Syndrome Meningococcal meningitis • Culture; • PCR. • PCR: 48hrs; • Culture: 4-5days. • H.infl uenzae • Strep. Pneumoniae • Enteroviral meningitis • Malaria • Poliomyelitis • Rabies and other lyssaviruses • African trypanosomiasis • Meningoencephalitis • Tick-borne encephalitis viruses • Japanese encephalitis • UN3373 - Biological Substance • Packing Instruction 650 Acute Respiratory Syndrome Anthrax • Culture; • PCR; • Immunohistochemistry (IHC); • Toxin detection. • PCR: 24hrs; • Culture, toxin detection: 2 weeks. • Diphtheria • Hantavirus Pulmonary Syndrome • Mycoplasma • Legionellosis • Respiratory syncytial virus • Pertussis • Other respiratory viruses • Cultures: - UN2814- Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Infl uenza • PCR; • Virus isolation; • HAI (Hemagglutination Inhibition Test). • PCR: 24hrs; • HAI: 72hrs; • Culture: 1-2 weeks. • Cultures of avian infl uenza and suspected avian/ pandemic infl uenza: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimen: - UN3373 - Biological Substance - Packing Instruction 650 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 241 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Respiratory Syndrome Plague • Rapid dipstick test; • PCR; • ELISA IgM; • culture; • DFA. • PCR: 24hrs; • Culture: 1 week. • Diphtheria • Hantavirus Pulmonary Syndrome • Mycoplasma • Legionellosis • Respiratory syncytial virus • Pertussis • Other respiratory viruses • Cultures: - UN2814 - Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 MERS • Molecular: PCR positive on at least two gene targets: Screening assay (e.g. up E or N gene NAAT) and Confi rmatory assay (e.g. ORF 1a, ORF 1b or N gene NAAT); • Serology: immunofl uorescence assays, serum neutralization assays, protein microarray technology, recombinant nucleocapsid (N) and spike (S) protein-based indirect enzyme-linked immunosorbent (ELISA), and a neutralization test based on retroviral pseudoparticles. • PCR: 24hrs; • IFA: 24hrs; • ELISA and microneutralization: 1-3 days. • UN3373 - Biological Substance • Packing Instruction 650 TABLE 2: Laboratory diagnosis and shipment of infectious substances, (continued) * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 242 TOOL BOX 3 SYNDROME DISEASE TYPE OF TEST FOR CONFIRMATION* AVERAGE TEST RESULTS TURNAROUND TIME DIFFERENTIAL DIAGNOSIS SHIPMENT CLASSIFICATION BASED ON INTERNATIONAL SHIPMENTS** Acute Dermatological Syndrome Cutaneous anthrax • Culture; • PCR; • Immunohistochemistry (IHC); • Toxin detection. • 2 weeks • Chickenpox • Herpes • Enterovirus • Measles • Medication-associated allergies • Bacterial skin infections • Cultures: - UN2814- Infectious Substance affecting humans - Packing Instruction 620 • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Monkeypox • PCR • 24hrs • UN2814- Infectious Substance affecting humans • Packing Instruction 620 Smallpox • PCR • 24hrs • UN2814- Infectious Substance affecting humans • Packing Instruction 620 Acute Fever and Rash Chikungunya • PCR; • Serology; • Viral culture. • PCR: 24hrs; • ELISA: 2-5 days; • Virus isolation ≤ 8 days. • Leptospirosis, • Alphavirus infections • Dengue • Malaria • Meningitis • Post-infectious arthritis (incl. rheumatic fever) • Invasive Meningococcal Disease • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 Zika • PCR; • Serology; • Neutralization tests. • PCR: 24hrs; • ELISA: 2-5 days. • Diagnostic clinical specimens: - UN3373 - Biological Substance - Packing Instruction 650 * Consideration must be given to the design and performance of the diagnostic products to ensure that testing is safe and effective ** Safety measures remain the same for national shipments PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 243 TOOL BOX 4 Transport of infectious substances Infectious substances: defi nition For the purposes of transport, infectious substances are defi ned as substances which are known or are reasonably expected to contain pathogens. Pathogens are defi ned as microorganisms (including bacteria, viruses, rickettsiae, parasites, fungi) and other agents such as prions, which can cause disease in humans or animals. This tool box highlights some important features of the Guidance on regulations for the Transport of Infectious Substance 2017-2018 1, World Health Organization, 2017. 1 The full guidance can be found on: http://www.who.int/ihr/publications/WHO-WHE-CPI-2017.8/en/ Laboratory diagnosis Patient Specimen collection National laboratory International laboratory The defi nition is applied to all specimens except those explicitly exempted: • Cultures; • Patient specimens; • Biological products; • Genetically modifi ed microorganisms (GMMOs) and organisms (GMOs); • Medical or clinical wastes. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 244 Classifi cation Infectious substances are classifi ed in Division 6.2 of the Dangerous Goods Regulations and assigned to proper shipping names according to their hazard classifi cation and their composition (UN 2814, UN 2900, UN 3291 or UN 3373). Infectious substances are divided into the following categories: • Category A - An infectious substance which is transported in a form that, when exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal disease in otherwise healthy humans or animals. • Category B - An infectious substance which does not meet the criteria for inclusion in Category A. • Exemptions. General preparation of shipments for transport Because of the differences in the hazards posed by Category A infectious substances (UN 2814 and UN 2900) and Category B infectious substances (UN 3373), there are variations in the packaging, labelling and documentation requirements for the two categories. Note 1: Hand carriage of Category A and Category B infectious substances and transport of these materials in diplomatic pouches are strictly prohibited by international air carriers. Note 2: Inner packaging containing infectious substances shall not be consolidated with inner packaging containing unrelated types of goods. Shippers of infectious substances shall ensure that packages are prepared in such a manner that they arrive at their destination in good condition and present no hazard to persons or animals during transport. Basic triple packaging system This system of packaging shall be used for all infectious substances. It consists of three layers as follows: • Primary receptacle. A primary watertight, leak-proof receptacle containing the specimen. The receptacle is packaged with enough absorbent material to absorb all fl uid in case of breakage or leakage. • Secondary packaging. A second durable, watertight, leak-proof packaging to enclose and protect the primary receptacle(s). Several cushioned primary receptacles may be placed in one secondary packaging, but suffi cient additional absorbent material shall be used to absorb all fl uid in case of breakage or leakage. • Outer packaging. Secondary packagings are placed in outer shipping packagings with suitable cushioning material. Outer packagings protect their contents from outside infl uences, such as physical damage, while in transit. The smallest overall external dimension shall be 10 x 10 cm. Each completed package is normally required to be correctly marked, labelled and accompanied with appropriate shipping documents (as applicable). There are specifi c packaging, labelling and documentation requirements for infectious substances in Category A and with lesser constrains for substances in Category B. Overpacks • For both categories it is possible to use overpacks. • “Overpack” is the term used when several packages are combined to form one unit and sent to the same destination by a single shipper. When refrigerants are used to protect contents, the overpacks may comprise insulated vessels or fl asks. Whenever an overpack is used, the required marks and labels shown on the outer packaging must be repeated on the outermost layer of the overpack. This requirement applies to infectious substances in Categories A and B. Overpacks are also required to be marked with the word “overpack”. • It is very important not to reproduce UN specifi cations mark on the overpack. TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 245 Reusing packaging materials Shipping packages can be reused. If the shipper plans on reusing a package, it must be appropriately disinfected. Before reusing a package, the shipper must make sure all marks and labels refl ect the substances actually being shipped. If the shipper plans on shipping an empty package, all non-applicable marks and labels must be removed or covered. Before an empty package is returned to the shipper, or sent elsewhere, it must be appropriately disinfected or sterilized to nullify any hazard. Any label or mark indicating that it had contained an infectious substance shall be removed or covered. Refrigerants • Refrigerants may be used to stabilize infectious substances in Categories A and B during transit. • Packed infectious substances requiring cooling meet the appropriate requirements as described in the guidance on regulations for the Transport of Infectious Substances 2017-2018. Trainings • The Dangerous Goods Regulations require all personnel involved in transport to undergo appropriate training. • For the transport of Category A infectious substances, personnel must undergo training in accordance with the modal requirements. This can involve attendance at approved courses and passing examinations. • For the transport of Category B infectious substances, there is a requirement that clear instructions on the use of the packaging are supplied to the user; this is regarded as suffi cient “training” for the shipping of these substances. However, if such specimens are consigned with other dangerous goods (e.g. fl ammable liquids, radioactive materials, liquefi ed gases, etc.), then personnel must be trained in the proper procedures for their transport. TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 246 Transport • It is the responsibility of the shipper to ensure the correct classifi cation, packaging, labelling, and documentation of all infectious substances destined for transport. • The effi cient transport and transfer of infectious substances requires good coordination between the sender, the carrier and the receiver to ensure that the material is transported safely and arrives on time and in good condition. Such coordination depends upon well-established communications and a good working relationship between the three parties. Main actors in the infectious substance transport chain are: • The shipper; • The carrier; • The receiver. Descriptions of their respective responsibilities and duties can be found in the guidance on regulations for the Transport of Infectious Substances 2017-2018. For more information on the transport of infectious substances: • Guidance on regulations for the transport of infectious substances 2017–2018, World Health Organization, 2017: http://www.who.int/ihr/publications/WHO-WHE- CPI-2017.8/en/ TOOL BOX 4 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 247 TOOL BOX 5 Vector control Prevention of Vector-Borne Diseases and control measures against vectors during epidemic situations Some epidemic diseases are transmitted by arthropods vectors, such as ticks and insects. To prevent the transmission of these infectious diseases called Vector-Borne Diseases (VBDs), actions can be taken to protect human beings from the vectors and/or to eliminate or reduce vectors population. These actions include community engagement, personal protection and vector control operations. Recommendations and deployment of the available tools are modulated according to the level of the transmission of the disease, which can range from sporadic to endemic levels and fi nally to epidemic level. Coordination of the deployment of the different tools at different levels is aided by having a preparedness plan and trained staff. Countries are recommended to have national preparedness plans for the prevention and control of VBDs, as well as a training program for staff engaged in vector control activities. Regional coordination is also necessary as most of the VBDs cross borders. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 248 TOOL BOX 5 Below is a list of epidemic-prone VBDs that are included in the handbook. These are transmitted by different vectors but share the common transmission mode, via the bite (in other VBDs such as Chagas disease and Typhus, other transmission modes are found): These different vectors have different ecologies, behaviors, biting times and transmission cycles. The bionomics of the vectors affects the type of actions taken to prevent and control these diseases. In all situations, there are four key actions: a. Personal protection tools: Table 1 summarizes the biting behavior of the different vectors and the type of personal protection available. b. Vector control operations implemented by public and/or private agencies and deployed at the community level. Table 2 summarizes vector control tools available for each vector type. c. Community engagement, essential for outbreak response. d. Communication of the different actions, as an essential component for success. Public Health recommendations must take into account social and cultural factors. • The Crimean-Congo haemorrhagic fever virus (CCHFV) is transmitted by ticks of the family Ixodidae, mainly by Hyalomma genus. In the Mediterranean and Middle Asia regions, the most prominent vector is Hyalomma marginatum. • The Yellow fever (YFV), Zika (ZIKV) and Chikungunya (CHIKV) viruses are transmitted by mosquitoes, through different cycles from sylvatic (wild), rural, peri-urban and urban, with different vector species according to the cycle. Zoonoses can occur in sylvatic transmission involving various vector species, whereas epidemics are found to occur in rural and urban environments, with the main vector being Aedes aegypti, and an emerging secondary vector being Aedes albopictus. • The Plague is a bacterial disease transmitted by fl eas into wild cycles in which rodents’ fl eas are playing a major role. For epidemics in domiciliary environments, the rodent’s fl eas, such as the most known Xenopsylla cheopis, are the major vectors. However, the association between the disease caused by Yersinia pestis and the fl eas species is not very specifi c, thus many fl eas species can act as plague vectors. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 249 TABLE 1: Personal protection tools according to the type of vectors Type of vector (VBDs) Vectors bionomics Personal Protection tools Natural environment Biting time Need animal cycle Bednet Repulsive Window screen Insecticide Sprays Electric devices Elimination of domestic breeding sites Forest, wild Day Yes - ++ + + - - Ticks (CCHFV) Aedes mosquitoes (YFV, CHIKV, ZIKAV) Fleas (PLAGUE) Domestic, rural & urban Day No + +++ +++ +++ ++ +++ Domestic, wild All day Yes / No - ++ - ++ - +++ The vector control activities are deployed at the community level to eliminate the vectors and larvae as much as possible, in order to prevent or control the transmission of VBDs. The operationalization of vector control varies according to the type of vector and transmission intensity. • Vector control strategies should address all life stages of the Aedes mosquito from the egg, to larva and adult. • Among the control measures, insecticide applications are the most frequently used, either on the animal bearing the vectors, such as the ticks and the fl eas, or in the breeding places to kill vectors’ larvae, and fi nally, as adulticide- spraying to eliminate adult female mosquitoes. • Other vector control activities include: - Environmental measures through sanitation, habitat management and livestock management; - Mechanical measures with trapping of vectors; - Biological tools using natural enemies and biological larvicides for mosquitoes; - Other chemicals such as the use of mimics of natural hormones to stop the insect development; - A new generation of vector control products is also arriving with genetically modifi ed organisms (e.g. bacteria Wolbachia). TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 250 TABLE 2: Vector control tools according to the type of vectors Type of vector (VBDs) Endemic situation Epidemic situation Insecticide against larvae Insecticide against adults Animal sprayed Physical elimination of all breeding sites (public and domestic) Mechanical trapping Environmental measures Insecticide against larvae Insecticide against adults Animal sprayed Physical elimination of all breeding sites (public and domestic) Mechanical trapping Environmental measures + + Yes + + + +++ +++ Yes + + + Ticks (CCHFV) Aedes mosquitoes (YFV, CHIKV, ZIKAV) Fleas (PLAGUE) +++ + No +++ + ++ +++ +++ No +++ +++ +++ +++ +++ Yes +++ ++ +++ +++ +++ Yes +++ +++ +++ • Vector control tools can be used alone or in combination, through an Integrated Vector Management (IVM) approach (WHO, 2012) 1. The deployment, effi ciency and results of the vector control activities require Monitoring and Evaluation (M&E), but the methods to perform this M&E, both at the level of the vector population, and in terms of disease transmission, are often lacking. • Mosquito surveillance is part of vector control and helps improve timeliness of decisions to control mosquito populations and prevention disease. Both larval and adult vector populations should be targeted for surveillance. Epidemiological and entomological surveillance/indicators should be collected and analyzed in close collaboration. This surveillance will include: - Mosquitoes densities and geographical distribution; - Contacts with human hosts; - Effectiveness of control tools (e.g. susceptibility of resistance to insecticides). TOOL BOX 5 1 WHO, Handbook for integrated vector Management, 2012 http://apps.who.int/iris/ bitstream/10665/44768/1/9789241502801_eng.pdf PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 251 Disease-specifi c approaches based on the vectors’ ecology and control options The Crimean-Congo haemorrhagic fever virus (CCHFV) is transmitted by Hyalomma marginatum ticks. • These ticks blood feed at all stages from the 6-legged larval stage to the adult stage to complete their development and mature their eggs. In addition to being transmission vectors, ticks fulfi l the role of reservoir of CCHFV. • The larval stages usually feed on small animals, and the adult stages feed on larger animals such as deer, sheep and cattle. The ticks do not have feeding preference for the host and humans are considered as accidental hosts. The CCHFV circulates into animal populations without causing diseases (except in ostriches) and humans are considered as dead-end hosts. • In the regions with transmission risks, where animals are infected by the CCHFV, the main objective is to inform the public and the local communities how to promote practices that decrease transmission of the disease. - Such practices would include preventing contacts with the blood of virus-infected animals (e.g. slaughtering activities), preventing tick bites, and preventing the transmission during care at home or during funerals. TOOL BOX 5 Key behavioral interventions Animal settings Home settings Health care settings • Reduce ticks in the environment and decrease tick infestations on animals or in stables/barns. The tick vectors are numerous and widespread and tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well-managed livestock production facilities. • Implement quarantine for animals before they enter slaughterhouses or routine treatment of ruminants with pesticides 2 weeks prior to slaughter. This activity will decrease the risk for animal to be viraemic during its slaughtering. • Wear personal protective equipment (masks, gloves and gowns) when slaughtering and butchering animals in slaughterhouses or at home. This will prevent skin contact with infected animal tissue or blood. • Wear protective clothing (long leaves, long pants, etc.) and light colored clothing (to allow easy detection of ticks on the clothes). • Avoid of areas where tick vectors are abundant, when they are active (spring to fall). • Regular examination of clothing and skin for ticks. • Use of repellents on the skin (e.g. DEET) and clothing (e.g. permethrin). • Remove ticks safely from the skin. • Seek early treatment for fever after a history of tick bites or contacts with CCHF patients. • Avoid any direct unprotected contact with blood or body fl uids when managing patients. • Wash hands with soap and clean water regularly. • Organise safe and dignifi ed funerals. PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 252 • Current vector control measures are not fully satisfactory: - Chemical methods produce resistant ticks, food contamination, and environmental pollution. Furthermore, chemical tick control is only realistic for well-managed and suffi ciently resourced livestock production facilities that are rare in most affected countries; - Physical methods (e.g. heavy grazing, burning of grasslands) have an important environment negative impact; - Biological methods (e.g. use of hormones and growth regulators, use of predators, bacteria, nematodes, and fungi) have not demonstrated full effi cacy. • Vaccination is considered a promising alternative to control tick infestations. An animal vaccine effective against Hyalomma ticks that prevent the tick-animal-tick cycle would decrease tick population, decrease CCHF prevalence in animals, and therefore decrease human exposure, being a cost effective CCHF prevention measure. • The virus cannot be amplifi ed into humans and thus directly transmitted into a human cycle. It needs amplifying hosts (domestic and wild animals) to provide blood meals to support tick populations. The Yellow fever (YFV), Zika (ZIKV) and Chikungunya (CHIKV) viruses are transmitted at an epidemic level by mosquitoes belonging to the species Aedes aegypti and Aedes albopictus. The Aedes mosquitoes also transmit the Dengue virus (DENV). • Although these viruses can be transmitted by other mosquito vectors species in sylvatic environments and potentially cause zoonoses, only the Aedes species are responsible for epidemics as they have adapted to urban settings and can lay eggs in any kind of recipient containing water in and around houses and other human dwellings in urban and scattered rural areas. • The development of the larvae can be very short, less than a week, and thus the increase of the mosquito population can be exponential if the conditions are favorable (temperatures and water) in the absence of any vector or larvae control. • It is thus strongly recommended to maintain regular control of these mosquito populations through the physical elimination of all breeding sites, in private and public spaces, and through the use of larvicides in breeding places that cannot be eliminated. The biological larvicide with Bacillus thuringiensis var. israelensis toxins are recommended because of the lack of resistance and no environmental drawback. TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 253 • During an epidemic situation, all tools to protect humans from mosquito bites (Table 1), as well as all available tools to eliminate adult mosquitoes are recommended, with reinforcement of the elimination of breeding sites, use of larvicide and use of adulticide 2. - The effi cacy of the products needs to be monitored in advance with tests on resistance and, if necessary, an integrated resistance management plan must be developed. - The spraying of adulticides must be done on a daily basis until the mosquito populations are cut down under the necessary Breteau Index (BI) (that is the number of positive containers in 100 houses) which should be less than 1 3. - Community engagement is also a very important component for controlling Ae. aegypti and Ae. albopictus populations. Through participative actions, such as recommendations for personal protection in the working places and schools, elimination of breeding sites, installation of window screens, and overall surveillance of the environment to make it less favorable for mosquitoes, are some of the major actions that can be taken by communities. • Vector control against Ae. aegypti and Ae. albopictus, the main vectors of urban arboviruses have not been reported as effi cient as it is required due to many factors (including unplanned urbanization and lack of resources). However, these tools are the only ones available in many situations and will result in controlling the transmission if well applied. Plague circulates into mammals, especially rodents, in almost all regions of the world. • The humans are affected by Plague epidemics according to two main transmission modes. At the beginning of an epidemic, rodents are affected by the disease with fl eas as vectors, then the fl eas leave the dying rodents and move on to humans. At this stage, the Plague is called bubonic because bubonic abscesses are the main clinical symptoms. With the spread of the bacterial into the lungs, humans can directly transmit the Plague bacteria to other human beings, and the Plague is called pneumonic. • The fl eas are host-specifi c and animal fl eas bit human rather by accident. • Sanitation and rat control are the best practices to prevent human Plague. When Plague cases are reported, control measures must fi rst target fl eas and secondarily rodents, because the use of raticide may result in the adverse effect, with fl eas leaving the dead rats and moving onto humans. • Depending on environmental context, large deployment of insecticide baited traps for rats can be recommended. • Environmental measures to repel rat population as well as strong disinsectisation of places where rats are installed can also be applied. • The community engagement is also very important for coordinated rat control activities, management of wastes and domestic environment. 2 WHO, Pesticide and their application for the control of vectors and pests of public health importance, 2006. http://apps.who.int/iris/bitstream/10665/69223/1/WHO_CDS_NTD_WHOPES_GCDPP_2006.1_eng.pdf 3 Bowman LR,Runge-Ranzinger S and McCall PJ. Assessing the Relationship between Vector Indices and Dengue Transmission: A Systematic Review of the Evidence. PLoS Negl Trop Dis. 2014 May; 8(5): e2848. doi: 10.1371/ journal. pntd.0002848 TOOL BOX 5 PART III: TOOL BOXESMANAGING EPIDEMICS | KEY FACTS ABOUT MAJOR DEADLY DISEASES 254

Acknowledgements The Managing epidemics handbook is a WHO collective endeavour with the involvement of the WHO Health Emergencies Programme (WHE) departments and, in particular, many Infectious Hazard Management (IHM) experts at HQ, Regional and Country levels. It has also been developed in collaboration with other departments within the WHO: The Special Programme for Research and Training in Tropical Diseases (TDR), Health Emergency Information & Risk Assessment (HIM), Emergency Operations (EMO), Country Health Emergency Preparedness & IHR (CPI), Information Evidence and Research (IER), Polio Eradication (POL), and Control of Neglected Tropical Diseases (NTD) departments. 256 Authors & contributors WHO acknowledges the contributions given by the following individuals who have provided inputs and/or contributed to the drafting, review and/or production of the handbook: Aysheshim Ademe, Hernando Agudelo, Kate Alberti, Sylvain Aldighieri, Yahaya Ali Ahmed, Sophie Allain Ioos, Yokouide Allarangar, Inacio Alvarenga, Javier Aramburu, Richelot Ayangma Mouko, Jean-Christophe Aze, Freddy Banza Mutoka, Cecile Barbou des Courieres, Mady Ba, Maurizio Barbeschi, Philippe Barboza, Jennifer Barragan, Ahmadou Barry, Rodrigue Barry, Bienvenu Baruani Ngoy, Marie Roseline Darnycka Belizaire, Luisa Belloni, Simeon Bennett, Justus Benzler, Isabelle Bergeri, Eric Bertherat, Terry Besselaar, Aphaluck Bhatiasevi, Viviane Bianco, Bonkoungou Boukaré, Anna Bowman, Rick Brennan, Sylvie Briand, Caroline Brown, Gisèle Bwende Kasungi, Jorge Castilla, Andersen Chimusoro, Stella Chungong, Laurence Cibrelus, Ian Clarke, Peter Clement, Rudi Coninx, Alejandro Costa, Ana Paula Coutinho Rehse, Fernando Da Silveira, Arsene Daizo, Farah Dakhlallah, Lucia Dell Amura, Ghyllain Demba Lubambo, Janet Diaz, Heidi Divecha, Devika Dixit, Mamoudou Harouna Djingarey, Sabelo Dlamini, Emmanuel Douba, Patrick Drury, Kara Durski, Amgad Abdalla Elkholy, Nedret Emiroglu, Rocío Escobar, Anthony Eshofonie, Socé Fall, Ana Fernandes, Katya Fernandez, Johanna Fihman, Julia Fitzner, Pierre Formenty, Florence Fouque, Mara Frigo, Florence Fuchs, Caroline Fuhrer, Christian Fuster, Gaya Gamhewage, Erika Garcia, Sandra Garnier, Semere Gebregiorgis, Yohannes Ghebrat, Carolina Gomes, Philip Gould, Peter Graaff, Michael Griffi n, Mary-Anne Groepe, Aspen Hammond, Alexandra Hill, Siddhivinayak Hirve, Daniel Hougendobler, Khelifi Houria, Stéphane Hugonnet, Poonam Huria, Anne Huvos, Benido Impouma, Christian Itama Mayikuli, Yurie Izawa, Alpha Jallow, Sandrine Joucla, Hilary Kagume Njenge, Arnaud Kahn, Lingawako Kalinde Mangachi, Ebba Kalondo, Masaya Kato, Erin Kenney, Joyce Kerubo Onsongo, Asheena Khalakdina, Moakofhi Kentse, James Kojo Teprey, Davi Kokou Mawulé, Innocent Komackech, Alexandra Kontic, Thomas d’Aquin Koyazegbe, Eve Lackritz, Andersson Latt, Sharmila Lareef-Jah, Anaïs Legand, Dominique Legros, Ellen Leroy, Ailan Li, Francois Libama, Maja Lievre, Clement Lingani, Jennifer Linkins, Daniel Lucey, André Lukusa, Nuha Mahmoud, Kevin Makadzange, Mamunur Malik, Awandha Mamahit, Koria Mankampa, Stephen Maphosa, Rima Marrouch, Christian Massidi, Humphreys Masuku, Margaux Mathis, Petrus Mhata, Ruhana Mirindi Bisimwa, Ann Moen, Vital Mondonge Makuma, Oliver Morgan, Sylvie Mortier, Amadou Mouctar Diallo, Mireille Flore Mouele, Ahamada Msa Mliva, Kelias Msymbaoza, Martin Muita, Marjorie Mupandare, Robert Musoke, Abrahams Mwanamwenge, Dhamari Naidoo, Michel N’da Konan Yao, Miriam Nanyunga, Jérôme Ndaruhutse, Charlotte Faty Ndiaye, Jean-Bosco Ndihokubwayo, Landry Ndriko Mayigane, Bla François Nguessan, Tim Nguyen, Dorit Nitzan, Lionel Nizigama, Ian Norton, Deo Nshimirimana, Alex Ntale Gasasira, Innocent Nzeyimana, Roderico Ofrin, Sally-Ann Ohene, Ifeanyi Okudo, Babatunde Olowokure, David Olson, Catherine Oswald, Heather Papowitz, Cyr Passi-Louamba, Scott Pendergast, William Augusto Perea Caro, Anne Perrocheau, Arturo Pesigan, Lorenzo Pezzoli, Marcia Poole, Jukka Tapani Pukkila, Arthur Rakotonjanabelo Lamina, Otim Patrick Cossy Ramadan, Bardan Jung Rana, João Rangel De Almeida, Peter Rehse, Bertrand Renaud, Tatiana Resnikoff, Amelie Rioux, Guenael Rodier, Jose Rovira Vilaplana, Olivier Ronveaux, André Rusanganwa, Florence Rusciano, Michael Ryan, Massambou Sacko, Grace Saguti, Niang Saidou Doro, Mohamed Sainda, Peter Salama, Rosine Sama Kanembe, Gina Samaan, Magdi Samaan, Ravi Santhana Gopala Krishnan, Nikki Shindo, Véronique Sicilia, Raphael Slattery, Catherine Smallwood, Vincent Sodjinou, Peter Songolo, Mary Stephen, Oliver Gerd Stucke, Ute Ströher, Aka Tano Bian, Israel Tareke, Joanna Tempowski, Michel Thieren, Desta Tiruneh, Ciro Ugarte Casafranca, Heini Utunen, Maria Van Kerkhove, Katelijn Vandemaele, Reinhilde Van De Weerdt, Raman Velayudhan, Sirenda Vong, Christèle Wantz, Sergio Yactayo, Sanyang Yaya, Daniel Yota, Zebulon Yoti, Wenqing Zhang, Ursula Zhao, Weigong Zhou. The development of the handbook was led by Sylvie Briand, Director of the Department of Infectious Hazard Management, and Margaux Mathis in collaboration with the experts mentioned above. Edited by: Thomson Prentice Design & layout by: Vivian Lee Illustrations by: Sam Bradd (Drawing Change) 257

Key facts about major deadly diseases Managing epidemics World Health Organization 20 Avenue Appia CH-1211 Geneva 27 Switzerland ISBN 978-92-4-156553-0

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W?OY=SH?[DEFAIPLQK==L KLH%#@@@M@K?MNOL#T=RNIP=OLC=#AIPLQK==LQ#AQ!(!#=O# &†-‡ Ã' 书１５６　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 鼠疫 你应该知道的 １０个关键事实 １ 肺鼠疫会引发广泛流行且难以控制。 ２ 最常见的鼠疫类型———腺鼠疫，不会在人与人之间传播。 ３ 早诊断早治疗对存活至关重要。 ４ 健康教育、感染预防和控制、媒介和啮齿动物控制是预防和处理流行的关键。 ５ 应举行安全和庄严的葬礼以避免进一步传播。 ６ 鼠疫的早期症状无特异性，难以与其他急性发热性疾病相鉴别。 ７ 潜在的鼠疫自然疫源地分布于世界各地，并正在扩大。 ８ 鼠疫是一种通常严重影响脆弱人群的疾病。 ９ 除腺鼠疫和肺鼠疫外，还有第三种鼠疫，即细菌进入血液循环时出现的败血症型鼠疫。 １０ 鼠疫是由细菌引起的人兽共患病，通常发生于小型哺乳动物（主要是啮齿动物）。 鼠疫 １５７　 鼠疫应对提示 协调应对者  与合作伙伴和社区合作，在地方性流行区控制 媒介 风险沟通  鼓励卫生当局： － 在地方性流行区开展健康教育和社区参与以 控制媒介  关键信息： － 鼠疫是可治的：如出现相关症状或暴露于疾 病，应该接受治疗 － 腺鼠疫和肺鼠疫的传播方式是不同的 － 肺鼠疫可通过呼吸道飞沫在人与人之间发生 传播 － 腺鼠疫患者没有传染性 － 对于腺鼠疫，应采取预防措施防止跳蚤叮咬， 不接触动物尸体 健康信息  对腺鼠疫有稳定的灵敏的快速诊断检测  发现传染源以便采取有针对性的控制措施  按《国际卫生条例》（２００５）要求，向世界卫生组 织报告病例 卫生干预  尽早使用抗生素治疗  确保安全和有尊严的葬礼  对于肺鼠疫： － 密切追踪密切接触者，并为其提供预防措施， 持续 ７天 － 医护人员预防性服药 － 感染预防和控制：标准预防措施和飞沫预防 措施（个人防护装备，ＰＰＥ）  对于腺鼠疫： － 控制媒介和啮齿动物。 － 为与腺鼠疫患者共同居住的人提供预防性服药 － 感染预防和控制（标准预防措施） １５８　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 １ 肺鼠疫会引发广泛流行且难以控制  肺鼠疫可以通过空气中的飞沫 （咳嗽、呼吸道分泌物）在人与人 之间传播，因此具有很强的流行 性，是最难控制的鼠疫类型。  肺鼠疫是一种毒力最强的鼠疫： 潜伏期最短为 ２４ 小时，如不治 疗，很可能死亡。  肺鼠疫可由晚期腺鼠疫发展所 致，当鼠疫杆菌通过血流或直接 吸入感染的呼吸道飞沫到达肺 部时，即可引发肺鼠疫。  对肺鼠疫患者应进行隔离，从而 使患者不会通过呼吸道飞沫传 染他人。应该由经培训的医务 人员照料患者。医务人员应穿 戴个人防护装备，并可以预防性 服药以防止院内传播。  对密切接触者必须进行医学观 察，并用抗生素进行预防性服 药，持续 ７天。  对任何疑似病例应进行治疗。  肺鼠疫在人与人之间传播的潜 伏期通常为 １ ～ ３ 天。随后突然 发热、头痛、寒颤、疼痛、乏力、胸 部不适、呼吸浅促、咳嗽、有时还 伴有血痰或黏液痰。 ２ 最常见的鼠疫类型———腺鼠疫，不会在人与人之间传播  腺鼠疫是最常见的鼠疫类型，除 非接触了化脓性腹股沟的脓液， 否则不会在人与人之间传播。  大约 １０％的腺鼠疫患者会发展 为肺鼠疫。  腺鼠疫可由跳蚤叮咬，或鼠疫杆 菌感染的物质或体液（院内感染 最多见）直接污染了开放性皮损 组织所致。如未采取合适的保 护措施来处理死亡动物，则会引 发感染。感染的细菌通过淋巴 系统传播到附近的淋巴结，并在 　 淋巴结进行繁殖。然后淋巴结出现 发炎、肿胀、疼痛，称之为“腹股沟淋 巴结炎”。在感染晚期，发炎的淋巴 结可变为化脓性开放性溃疡。  腺鼠疫在潜伏期 ２ ～ ６ 天后，突然发 病，出现头痛、寒颤、发热、乏力和受 累局部淋巴结疼痛。腺鼠疫在颈部 和腹股沟等处可出现淋巴结炎、炎 症和肿胀。  控制腺鼠疫流行的措施包括：对患 者的共同居住者进行预防性服药、 控制媒介和啮齿动物。 　 　 　 　 鼠疫 １５９　 ３ 早诊断早治疗对存活至关重要 鼠疫是可以治疗的。 常用抗生素治疗和支持疗法对治愈 人类鼠疫非常有效，但其效果取决 于早期给药，这就需要及早发现病 例。这对肺鼠疫特别重要，因为该 病传染性极强，患者 ２４ 小时内就可 死亡，如不治疗非常容易致命。如 果患者及时接受治疗，腺鼠疫和肺 鼠疫的恢复率都很高。  治疗鼠疫所推荐的抗生素如下： － 治疗腺鼠疫推荐使用：四环素、多 西环素、氯霉素。 － 治疗肺鼠疫或败血症型鼠疫推荐 使用：氨基糖苷类、氟喹诺酮类。 － 暴露后推荐的假定性治疗（ｐｒｅ ｓｕｍｐｔｉｖｅ ｔｒｅａｔｍｅｎｔ）：四环素、多西 环素、磺胺甲 唑 ／甲氧苄啶。  早期治疗需要早期做出诊断。鼠疫的 确诊需要实验室检测。最好的方式是 从腹股沟淋巴腺炎脓液、血液或痰标本 中检出鼠疫耶尔森菌。可通过下列多 种技术检测鼠疫杆菌： － 使用显微镜：染色、荧光抗体试验。 － 分离法：菌落形态检查、生化反应、噬 菌体裂解。 － 抗原 ／抗体检测：酶联免疫吸附试验 （ＥＬＩＳＡ）、荧光抗体试验、聚合酶链 反应（ＰＣＲ）。  有一种使用方便、稳定可靠、灵敏的快速 诊断腺鼠疫的方法（试纸法），能够在 １５ 分钟内检出抗原并提供可靠结果，极大提 升了防控能力。可在所有地方性流行区 推荐使用这种快速诊断检测方法。 １６０　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 　 ４ 健康教育、感染预防和控制、媒介和啮齿动物控制是预防和处理流行的关键  在鼠疫地方性流行区，对人们宣传有关 疾病、症状和传播方式至关重要。当环 境中有动物鼠疫发生时，应当告知当地 公众，建议采取预防措施以防止跳蚤叮 咬，不要接触动物尸体。  避免接触死亡的动物。在地方性流行 区衣服和皮肤涂上驱虫剂有助于预防 腺鼠疫。  避免近距离（２ｍ以内）接触有咳嗽症状的 疑似肺鼠疫患者，有助于预防肺鼠疫。  鼠疫被称为“黑死病”，过去造成了数百 万人死亡，因此是一种非常可怕的疾病。 所以，健康教育对防止在鼠疫暴发期间 的恐慌特别重要。  应该明确告知医疗卫生工作者有关感染 预防控制方面的信息，并对其进行培训。 应该为他们提供合适的个人防护装备，并 对有关如何使用这些装备进行培训。  在鼠疫疫区腺鼠疫暴发期间，必须控制 跳蚤和贮存宿主（通常为啮齿动物）。 ５ 应举行安全和庄严的葬礼以避免进一步传播  鼠疫患者死亡后其体液中的细 菌会成为人的传染来源，人们 在葬礼期间与其接触后可发生 传染。必须实施安全的丧葬， 并尊重当地文化和宗教信仰。 鼠疫 １６１　 ６ 鼠疫的早期症状无特异性，难以与其他急性发热性疾病相鉴别  经过 １～７天的潜伏期，鼠疫感染者开 始出现非特异性症状。典型症状是起 病急骤、发热、寒颤、头痛、全身酸痛、 乏力、呕吐和恶心。这些症状很难与 其他常见的地方性流行病相鉴别。  腺鼠疫期间，淋巴结会出现疼痛和继 发炎症。  肺鼠疫在感染后短时间内（有时不到 ２４小时）出现症状。症状包括严重呼 吸道症状，如呼吸浅促、咳嗽、往往痰 中带血。  鼠疫临床表现的特异性不强，误诊率 较高。因此，快速诊断检测对于快速 诊断和早期治疗非常重要。 ７ 潜在的鼠疫自然疫源地分布于世界各地，并正在扩大  虽然在马达加斯加、刚果民主共和 国和秘鲁，鼠疫是很常见的，但潜在 的鼠疫自然疫源地（细菌、动物储 存宿主和媒介）分布于世界各地。  目前发现在一些鼠疫已消失的地区 又重新出现了鼠疫，一些从未发生 过鼠疫的地方也出现了鼠疫。  鼠疫的自然疫源地也在扩大。主要 原因如下： 　 － 环境改变（如砍伐森林）。 　 － 黑鼠（一种贮存宿主）的持续 侵占。 　 － 国内和国际的交流不断增加。 　 － 失控的城市化进程。  此外，在有地方性流行的国家， 昆虫学和动物学监测活动的费 用高且维持困难。在没有人间 病例的情况下，往往会被忽视， 很难获得有关自然疫源地的状 况或变化的详细信息。 １６２　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 ８ 鼠疫是一种通常严重影响脆弱人群的疾病  鼠疫是一种通常严重影响脆弱人 群的疾病，因为鼠疫往往发生在 卫生条件差、医疗卫生服务不足、 拥挤的地方。  鼠疫暴发的发生往往与内乱、战争 以及医疗基础设施和机构遭到损 毁有关。  因此应加强卫生体系建设以减少 流行风险。 ９ 除腺鼠疫和肺鼠疫外，还有第三种鼠疫，即细菌进入血液循环时出现的败血症型鼠疫  败血症型鼠疫是第三种鼠疫，这种 鼠疫为细菌进入血流扩散所致。  败血症型鼠疫由跳蚤叮咬，通过皮 肤裂口直接接触感染物质，或继发 于腺鼠疫所引起。败血症型鼠疫 可导致肺鼠疫。 鼠疫 １６３　 １０ 鼠疫是由细菌引起的人兽共患病，通常发生于小型哺乳动物（主要是啮齿动物）  鼠疫是由鼠疫耶尔森菌引起的人兽共患疾 病，通常常见于小型哺乳动物（主要是啮 齿类动物）。该病通过跳蚤在动物之间传 播。  在鼠疫自然疫源地（细菌、动物储存宿主、 生物媒介）和人群共存的地区，都有发生 人间鼠疫的风险。  根据感染的临床表现，鼠疫主要分为三种 类型：腺鼠疫、败血症型鼠疫和肺鼠疫。通 过感染的跳蚤叮咬，直接接触感染物质，或 吸入肺鼠疫患者的传染性呼吸道飞沫，均 可引起人类感染。  院内感染风险极大，尤其是肺鼠疫。  人间鼠疫是一种烈性传染病，根据鼠疫的 临床类型，病死率可达 ３０％～１００％。  但是，如鼠疫得到快速诊断并及时治疗，则 使用抗生素治疗效果良好，病死率可降至 １５％以下。  非洲、亚洲和南美洲曾发生鼠疫流行。自 ２０世纪 ９０ 年代以来，大多数人间鼠疫病 例发生在非洲。鼠疫流行最严重的三个国 家为马达加斯加、刚果民主共和国和秘鲁。 １６４　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 关于鼠疫的更多信息：  ＷＨＯ Ｆａｃｔ ｓｈｅｅｔ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｍｅｄｉａｃｅｎｔｒｅ ／ ｆａｃｔｓｈｅｅｔｓ ／ ｆｓ２６７ ／ ｅｎ ／  Ｐｌａｇｕｅ ＷＨＯ ｗｅｂｐａｇｅ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｐｌａｇｕｅ ／ ｅｎ ／  Ｐｌａｇｕｅ ＷＨＯ ＭＯＯＣ ｈｔｔｐｓ：／ ／ ｏｐｅｎｗｈｏ ｏｒｇ ／ ｃｏｕｒｓｅｓ ／ ｋｎｏｗｌｅｄｇｅｒｅｓｏｕｒｃｅｓｐｌａｇｕｅ  Ｐｌａｇｕｅ ｍａｎｕａｌ：ｅｐｉｄｅｍｉｏｌｏｇｙ，ｄｉｓｔｒｉｂｕｔｉｏｎ，ｓｕｒｖｅｉｌｌａｎｃｅ ａｎｄ ｃｏｎｔｒｏｌ ｈｔｔｐ：／ ／ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｒｅｓｏｕｒｃｅｓ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ｐｌａｇｕｅ ／ ＷＨＯ ＿ ＣＤＳ ＿ ＣＳＲ ＿ ＥＤＣ＿９９＿２＿ＥＮ ／ ｅｎ ／ （王孝忠 译） 钩端螺旋体病 １６５　 钩端螺旋体病 你应该知道的 １０个关键事实 １ 钩端螺旋体病是一种通常在热带或亚热带气候自然灾害后出现的疾病。 ２ 虽然啮齿动物是钩端螺旋体（引起钩端螺旋体病的病原体）的主要储存 宿主，但各种哺乳动物可以在人间传播中起重要作用。 ３ 人通过直接或间接接触受感染动物的尿液而感染。 ４ 在某些行为和社会经济情况下，感染风险会增加。 ５ 早期给予常用抗生素，对治疗钩端螺旋体病有效。 ６ 钩端螺旋体病会被漏诊，且往往被误诊为其他疾病。 ７ 实验室诊断具有挑战性，但对确诊钩端螺旋体病至关重要。 ８ 预防和控制措施应针对传染源、传播途径和人间疾病。 ９ 气候变化和城市化将增加暴发的频次和强度。 １０ 多部门联防和整体考虑对预防控制至关重要。 １６６　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 钩端螺旋体病应对提示 协调应对者  让动物卫生部门参与 风险沟通  鼓励卫生当局： － 让社区参与 － 确保对临床医生的培训，以便及早发现和治疗 － 帮助医院做好接收需要重症监护的严重病例 的准备  关键信息： － 人通过直接或间接接触受感染动物的尿液而 感染 － 避免与啮齿动物接触 － 可通过接触受污染的水而暴露 － 对所有皮肤损伤要立即消毒，避免接触未经 处理的水 － 如果出现症状，应尽早进行治疗 健康信息  确保对疑似病例的实验室确诊 卫生干预  早期发现病例  为所有可能病例提供经验性治疗（抗生素）  为人群提供经处理的水  为高危人群（救援人员、污水处理人员和环境卫 生人员）提供有针对性的化学预防和防护设备 钩端螺旋体病 １６７　 １ 钩端螺旋体病是一种通常在热带或亚热带气候自然灾害后出现的疾病  钩端螺旋体病是一种由钩端螺旋体引 起的传染病。  在世界范围内都有钩端螺旋体病发生， 但在热带和亚热带地区发病最多。  病例常呈季节性分布，随着强降雨或高 温而增加。  经常发生与自然灾害（特别是洪水）有 关的暴发。 ２ 虽然啮齿动物是钩端螺旋体（引起钩端螺旋体病的病原体）的主要储存宿主，但各种哺乳动物可以在人间传播中 起重要作用  啮齿动物被认为是人的主要传染源。  几乎所有野生哺乳动物和家养哺乳动物 都能携带钩端螺旋体（存在于肾脏和生殖 道中），并成为人和其他动物的传染源。  牛、水牛、马、羊、山羊、猪和犬也被认为是 钩端螺旋体的常见宿主，这种病原体可引 起钩端螺旋体病。  该病的自然史取决于当地的生态条件。 １６８　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 ３ 人通过直接或间接接触受感染动物的尿液而感染  钩端螺旋体病是一种人兽共患病，可直接或 间接从动物传给人。  人通过直接接触受感染动物的尿液或被尿 液污染的环境而感染。  钩端螺旋体可通过皮肤上割伤或擦伤的伤 口，或通过口腔、鼻子和眼部黏膜进入体内。  暴露于被感染动物尿液污染的水是最常见 的感染途径。钩端螺旋体病偶尔也可通过 饮用水，或摄入被感染动物尿液污染的食 物，以及处理受感染的动物组织而传播。  在人与人之间的传播非常罕见。 ４ 在某些行为和社会经济情况下，感染风险会增加 感染的风险取决于暴露程度。有些人接触被啮齿动物或其他家畜污染的水的机会更多。  人们可因职业暴露而感染：职业人员包括户外作 业人员和农民（如种植水稻和甘蔗的人员）、屠宰 场工人、兽医、肉类加工人员、宠物店员工、下水 道工人等。  人们也可以通过娱乐活动、游泳或划独木舟等水 上运动而暴露。自然灾害（如洪水）的幸存者也 是感染的高危人群。 钩端螺旋体病的临床表现 可能混淆的疾病 轻型 疟疾、登革热、流感 发热出血型 病毒性出血热 严重肺炎 鼠疫 黄疸发热 黄热病或肝炎 钩端螺旋体病 １６９　 ５ 早期给予常用抗生素，对治疗钩端螺旋体病有效 钩端螺旋体病可以用抗生素治 疗，应尽可能在疾病早期使用， 最好在发病后第 ５天使用。  在使用抗生素治疗前，临床医 生不用等待实验室检查结果。  治疗方案包括抗生素，如阿莫 西林、四环素、氨苄西林和多西 环素等。  严重病例需住院治疗。对这些 严重病例，应该使用大剂量青 霉素静脉注射治疗。在肾衰竭 的情况下，需要进行腹膜或血 液透析。对有肺出血表现者， 可使用机械通气。由于严重病 例需要重症监护，如在暴发情 况下处理病例，则后勤安排会 变得更加复杂。 ６ 钩端螺旋体病会被漏诊，且往往被误诊为其他疾病  由于钩端螺旋体病症状多变，临床表 现为非特异性，且与许多其他传染病 相似，故往往被误诊。  通常的临床表现是急性起病，突然发 热、头痛、肌痛（特别是腓肠肌）、虚 弱，并伴有下列症状 ／体征：结膜充血、 无尿或少尿、黄疸、咳嗽、咯血和呼吸 困难、出血（在某些地区肠道、肺部出 血是非常明显的）、脑膜刺激征、心律 失常或心功能衰竭，以及皮疹。其他 常见的症状包括恶心、呕吐、腹痛、腹 泻和关节痛。  钩端螺旋体病的潜伏期通常为 ５ ～ １４ 天，可达 ２ ～ ３０ 天。尽管钩端螺旋体 病是一种自限性疾病，且大部分感染 者往往不出现临床症状，但在未治疗 的病例中，有 ５％ ～１５％可能会发展为 更严重且可能致命的阶段。  钩端螺旋体病有四大临床类别： － 轻型流感样疾病。 － Ｗｅｉｌ 综合征（黄疸、肾衰竭、出 血、心肌炎）。 － 脑膜炎。 － 肺出血和呼吸衰竭。  出现上述症状的患者，如果有暴 露于感染动物或可能被动物尿液 污染环境的职业史或游玩史，则 对钩端螺旋体病的怀疑会进一步 增加。临床医生在洪水后对发热 性疾病做鉴别诊断时考虑到钩端 螺旋体病也非常重要。  误诊或延误诊断具有重要的临床 意义，因为钩端螺旋体病的早期 治疗对降低发病率和死亡率以及 及时采取控制措施至关重要。 １７０　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 钩端螺旋体病的典型病程 钩端螺旋体病 １７１　 ７ 实验室诊断具有挑战性，但对确诊钩端螺旋体病至关重要  由于病原体的复杂性，实验室诊断 并不容易：有 ２５ 个血清群，分为 ２５０个血清型。  实验室支持是必需的： － 确认诊断并与其他疾病相鉴别。 － 确定感染的血清型，这将有助于 指导控制策略。  目前对实验室检测的建议如下： － 血清学：显微镜凝集试验（ＭＡＴ） 特异性高，是血清学试验的金标 准。 － 聚合酶链反应（ＰＣＲ）。  可使用酶联免疫吸附试验（ＥＬＩＳＡ） 检测 ＩｇＭ，但在感染后到能检测到 抗体前，有一个间隔期。由于检测 方法的灵敏度和特异度不同，解释 结果需要谨慎。 ８ 预防和控制措施应针对传染源、传播途径和人间疾病  控制传染源（通常是当地的动物 贮存宿主）的措施包括：减少某 些动物贮存宿主数量；将动物贮 存宿主与人类居住区隔开（通过 栅栏和屏障）；对犬和牲畜实施 免疫；清除垃圾并保持人居住区 清洁；处理家畜排泄物时避免污 染环境；鼓励人们不要在周围环 境留下食物，特别是在可能有老 鼠的休闲区域；改善生活条件和 卫生系统等。  通过避免接触动物尿液、感染的 动物或污染的环境来防止传播， 采取的措施包括：穿防护服；用 防水敷料覆盖皮损表面；防止接 触已知的或怀疑的被污染水体， 并发出适当的警告；接触溢洒的 尿、污染的土壤或水后，要进行 清洗或淋浴；冲洗和清洁伤口； 在照料或处理所有动物期间严 格实施卫生措施；在可行的情况 下，对污染的区域进行消毒（清 理马厩、肉食店、屠宰场的地面 等）；饮用干净的饮用水等。  人类宿主层面的干预措施包括： － 提高公众和高危人群的意识。人 们需要了解疾病以及如何避免风 险，但及时用药也是有益的。在 某些情况下，医生和兽医应将钩 端螺旋体病作为鉴别诊断的一部 分。 － 如果知道已发生暴露（如由于实 验室事故或其他高危的暴露）， 应使用抗生素预防。 － 不推荐对人使用疫苗。疫苗不会 诱导对感染的长期保护，并且对 其他钩端螺旋体血清型不产生交 叉保护性免疫（仅对所用特定疫 苗中存在的血清型产生保护性抗 体）。  在流行情况下，战略性控制措施包 括： － 早期发现病例。 － 为所有可能病例提供经验性治 疗。 － 为人群提供经处理的水。 － 为极高危人群（救援人员、污水处 理人员和环境卫生人员）提供有 针对性的化学预防和防护设备。 － 在这个阶段控制啮齿动物和对动 物接种疫苗是无效的。 １７２　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 ９ 气候变化和城市化将增加暴发的频次和强度  钩端螺旋体病感染与环境密切相关，气 候变化将导致全球钩端螺旋体病增加： － 由于海平面上升以及海洋和陆地表面 的温度上升，气候变化可望会增加强 降雨和洪水的发生以及热带气旋和风 暴的强度。 － 自然灾害还会破坏卫生服务和基础设 施，破坏水源和卫生网络，从而增加了 发生传染病的风险。  城市化进程也增加了钩端螺旋体病的发 病率和流行强度。快速城市化通常伴随 着城市贫民窟的出现，城市贫民窟因过 度拥挤、卫生条件差、医疗保健差、贫困、 大量老鼠和其他动物贮存宿主而成为感 染的危险因素。 钩端螺旋体病 １７３　 １０ 多部门联防和整体考虑对预防控制至关重要  钩端螺旋体病仍然是一种未知的疾病：对其 传播动力学知之甚少，其症状不特异，实验室 诊断复杂，往往无法获得实验室确诊。  全健康（Ｏｎｅ Ｈｅａｌｔｈ）方法对预防和控制影响 人和动物的环境疾病至关重要： － 需要考虑动物、人与生态系统之间的关系， 以更好地了解和处理疾病。 － 研究和控制工作需要一种真正综合的、多 学科的和相互协调的方法，来改进钩端螺 旋体病暴发的预测、检测、预防和应对。 １７４　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 关于钩端螺旋体病的更多信息：  ＷＨＯ Ｆａｃｔ ｓｈｅｅｔ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｍｅｄｉａｃｅｎｔｒｅ ／ ｆａｃｔｓｈｅｅｔｓ ／ ｆｓ２６７ ／ ｅｎ ／  Ｐｌａｇｕｅ ＷＨＯ ｗｅｂｐａｇｅ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｐｌａｇｕｅ ／ ｅｎ ／  Ｐｌａｇｕｅ ＷＨＯ ＭＯＯＣ ｈｔｔｐｓ：／ ／ ｏｐｅｎｗｈｏ ｏｒｇ ／ ｃｏｕｒｓｅｓ ／ ｋｎｏｗｌｅｄｇｅｒｅｓｏｕｒｃｅｓｐｌａｇｕｅ  Ｐｌａｇｕｅ ｍａｎｕａｌ：ｅｐｉｄｅｍｉｏｌｏｇｙ，ｄｉｓｔｒｉｂｕｔｉｏｎ，ｓｕｒｖｅｉｌｌａｎｃｅ ａｎｄ ｃｏｎｔｒｏｌ ｈｔｔｐ：／ ／ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｒｅｓｏｕｒｃｅｓ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ｐｌａｇｕｅ ／ ＷＨＯ ＿ ＣＤＳ ＿ ＣＳＲ ＿ ＥＤＣ＿９９＿２＿ＥＮ ／ ｅｎ ／ （易晋华 译） 脑膜炎球菌性脑膜炎 １７５　 脑膜炎球菌性脑膜炎 你所知道的 １０个关键事实 １ 脑膜炎球菌性脑膜炎是由脑膜炎奈瑟菌引起的急性细菌性脑膜炎，即脑膜的严重感染。 ２ 脑膜炎球菌性脑膜炎呈全球性分布，但在非洲流行带的疾病负担最重。 ３ 脑膜炎奈瑟菌的多种血清群可引起流行。 ４ 人类是脑膜炎球菌性脑膜炎的唯一宿主，可通过直接接触和呼吸道飞沫传播。 ５ 如不治疗，脑膜炎球菌性脑膜炎的病死率可高达 ５０％。 ６ 接种特异性疫苗可用来预防和控制暴发。 ７ 实验室诊断对确定脑膜炎奈瑟菌是否是导致脑膜炎球菌性脑膜炎的病原体至关重要。 ８ 监测对识别暴发并为流行病学应对提供信息是至关重要的。 ９ 尽早使用抗生素治疗是挽救生命和减少并发症的最重要因素。 １０ 尽早给予抗生素可减少密切接触者的传播风险。 １７６　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 脑膜炎球菌性脑膜炎应对提示 协调应对者  在流行季节来临前，确保对流行的防备和成立 应对委员会  联系世界卫生组织 ／国际协调小组获取应急疫 苗和抗生素 风险沟通  确保对人群接种疫苗以预防这种疾病  关键信息如下： － 可通过呼吸道飞沫或咽喉分泌物在人与人之 间传播 － 无症状携带者可传播疾病 － 做好手卫生和呼吸道卫生 － 尽早使用抗生素治疗可降低病死率和减少并 发症，因此患者应尽早就医 卫生信息  通过实验室检测确定脑膜炎球菌血清群  要监测根据特定区域或国家的流行病学确定警 戒阈值 健康干预  尽早使用抗生素治疗  及早开展疫苗接种运动（根据当地的流行病学 特征）  对密切接触者实施预防性措施（根据当地流行 病学特征） 脑膜炎球菌性脑膜炎 １７７　 １ 脑膜炎球菌性脑膜炎是由脑膜炎奈瑟菌引起的急性细菌性脑膜炎，即脑膜的严重感染  脑膜炎球菌性脑膜炎是由脑膜 炎奈瑟菌引起的。  各种其他微生物（包括细菌、真 菌或病毒）也可引起脑膜炎。  脑膜炎球菌性脑膜炎可导致散 发病例，也可引起大规模暴发。 ２ 脑膜炎球菌性脑膜炎呈全球性分布，但在非洲流行带的疾病负担最重  在跨越非洲从塞内加尔到埃塞 俄比亚的非洲流行带（包括 ２６ 个国家），脑膜炎球菌性脑膜炎 的疾病负担最重。  非洲脑膜炎球菌性脑膜炎流行 带在干旱季节（１２ 月至次年 ６ 月）呈季节性地方性流行和周期 性大规模流行。 ３ 脑膜炎奈瑟菌的多种血清群可引起流行  血清群以字母命名（Ａ、Ｂ、Ｃ 等）。１２个血清群中的 ６ 个可 引起大规模流行（Ａ、Ｂ、Ｃ、Ｗ、 Ｘ、Ｙ）。地理分布随血清群不 同而异。  ２０１０ 年前在脑膜炎流行带，脑 膜炎奈瑟菌血清群 Ａ占总病例 的 ８０％ ～ ８５％。自新的和非常 有效的脑膜炎奈瑟菌血清群 Ａ 结合疫苗用于大规模预防性免 疫接种运动以来，脑膜炎奈瑟 菌血清群 Ａ的比例明显降低。  在欧洲，常规接种脑膜炎奈瑟 菌 Ｃ 群疫苗后导致血清群 Ｃ 暴发减少。  随着时间和空间的不同，血清 群流行病学会发生变化，其原 因还不完全清楚，但与疫苗接 种策略无关。 １７８　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 ４ 人类是脑膜炎球菌性脑膜炎的唯一宿主，可通过直接接触和呼吸道飞沫传播  脑膜炎奈瑟菌只感染人类，无动 物储存宿主。  细菌可以寄居在咽喉，成为无症状 带菌者。偶尔会突破机体防御系 统，细菌侵入血流到达大脑。  通过带菌者的呼吸道飞沫或咽喉 分泌物，细菌在人与人之间传播。 吸烟，长期和密切的接触（如接 吻、喷嚏或咳嗽），与感染者（带菌 者）共同居住在密闭的房子，都会 促进该病的传播。  无症状带菌者可传播疾病。在地方 性流行情况下，人群咽喉带菌率达 １％～１０％。在流行情况下，带菌率更 高，达 １０％～２５％。  婴幼儿和年轻人是感染的高危人群。  潜伏期为 ２～１０天，通常为 ３～４天。  在大规模集会期间易引起脑膜炎奈 瑟菌的传播（例如朝圣、童子军大会 等）。 ５ 如不治疗，脑膜炎球菌性脑膜炎的病死率可高达 ５０％  该病最常见的症状是高热、头痛、 颈项强直、呕吐、意识模糊、畏光、 婴儿囟门隆起。有时，可出现败 血症所导致的出血性皮疹，从少 数瘀点到广泛的瘀斑不等。  即使对疾病能做出早期诊断，并 开始合适的治疗，但仍有 ８％ ～ １５％的患者发生死亡。往往在出 现症状后 ２４ ～ ４８ 小时内发生死 亡。如不治疗，脑膜炎球菌性脑 膜炎的病死率高达 ５０％。  在 １０％～２０％幸存者中，脑膜炎球 菌性脑膜炎可导致脑损伤、耳聋 或失能。 脑膜炎球菌性脑膜炎 １７９　 ６ 接种特异性疫苗可用来预防和控制暴发  疫苗有特定的血清群，且产生的保护时 间长短不一。  现有 ３种疫苗可以获得： － 多糖疫苗主要用于非洲的暴发应对： ○ 多糖疫苗有二价（血清群 Ａ 和 Ｃ）、三价（血清群 Ａ、Ｃ和Ｗ）或四 价（血清群 Ａ、Ｃ、Ｙ和 Ｗ）。 ○ ２岁前使用多糖疫苗是无效的。 ○ 多糖疫苗可提供 ３ 年的保护时 间，但不会诱生群体免疫。 　 － 结合疫苗用于预防（纳入常规免疫程 序）和控制暴发： ○ 结合疫苗可产生持久免疫力，防 止携带和诱生群体免疫。 ○ 结合疫苗可以在 １周岁使用。 ○ 现有结合疫苗包括：  单价 Ｃ 和四价（血清群 Ａ、Ｃ、Ｙ、Ｗ）。 目前这两种疫苗价格昂贵，主要在加拿 大、美国和欧洲使用。  单价 Ａ用于群体免疫接种运动和婴儿 常规免疫。 － 基于蛋白质的脑膜炎奈瑟菌血清群 Ｂ疫苗用于预防（纳入英国常规免疫 程序）和控制暴发。  对受累人群和高危人群应及早进 行反应性疫苗接种，以阻止疾病 的蔓延。  在非洲，非常有必要在超过流行 阈值后 ４周内开展疫苗接种运动。  现已建立了国际疫苗储备，任何 面临暴发的国家都可以向脑膜炎 疫苗供应国际协调小组提出要 求，并获得脑膜炎疫苗。 １８０　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 　 反应性疫苗接种运动中脑膜炎球菌疫苗的决策树 　 脑膜炎球菌性脑膜炎 １８１　 ７ 实验室诊断对确定脑膜炎奈瑟菌是否是导致脑膜炎球菌性脑膜炎的病 原体至关重要  实验室确诊脑膜炎球菌性 脑膜炎需要对腰穿获得的 脑脊液（ＣＳＦ）标本进行检 测。检验方法包括细菌培 养、凝集试验和聚合酶链 反应（ＰＣＲ）。  为了在现场快速鉴定脑膜 炎奈瑟菌及血清群，应使 用快速床边诊断试验。快 速鉴定病原体对确定合适 的治疗方法和流行病学应 对是非常重要的。 ８ 监测对识别暴发并为流行病学应对提供信息是至关重要的  监测系统应能识别暴发、监测疾病 流行趋势和接种疫苗的影响。  应将流行病学和实验室数据结合 起来。  脑膜炎球菌性脑膜炎暴发的定义 是根据当地流行病学特征和监测 数据的综合分析作出的，因此各国 的脑膜炎球菌性脑膜炎暴发的定 义是不同的。  在非洲脑膜炎流行带，标准病例定 义如下： － 疑似病例（根据临床表现）：任 何人有突起发热（肛门体温 ＞ ３８ ５℃或腋下＞３８ ０℃）且颈项 强直，或伴有其他脑膜炎体征， 如婴儿前囟隆起。 　 － 可能病例（根据非特异性实验室检测）： 任何疑似病例出现脑脊液在显微镜下呈 浑浊、米汤样或脓样，或脑脊液白细胞计 数＞１０×１０６ ／ Ｌ，或脑脊液革兰氏染色检出 细菌。 ○ 婴儿：脑脊液白细胞计数＞１００×１０６ ／ Ｌ， 或脑脊液白细胞计数（１０ ～ １００）×１０６ ／ Ｌ，且伴有蛋白含量增高（＞１ｇ ／ Ｌ）或葡 萄糖降低（＜０ ４ｇ ／ Ｌ）。 　 － 确诊病例（根据实验室检测）：任何疑似 病例或可能病例，并从其血液或脑脊液培 养出或检出脑膜炎奈瑟菌。  在非洲脑膜炎流行带，启动预防和控制干预 措施的发病率阈值见下表。 １８２　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 脑膜炎球菌性脑膜炎流行的发现和控制的发病率阈值（２０１４） 人口数 干预 ３０ ０００～１００ ０００ ＜３０ ０００ 警戒阈值 － 报告当局 － 加强监测 － 调查 － 确诊（包括实验室） － 准备最终应对措施 ■ ３例疑似病例 ／ １００ ０００居民 ／周 （１周至少 ２例病例） ■ １周内 ２例疑似病例 或 ■ 与以前非流行年相比，发病率升高 流行阈值 － 达到流行警戒阈值后 ４周内开展大规模疫苗接种活动 － 下发治疗药物给卫生中心 － 根据流行病学方案治疗 － 告知公众相关信息 ■ １０例疑似病例 ／ １００ ０００居民 ／周 ■ １周内 ５例疑似病例 或 ■ ３ 周内病例数每周成倍增长（如第 １ 周 １ 例， 第 ２周 ２例，第 ３周 ４例） 如果接种的目标人群相邻区域感染风险高（如病例发生在干旱季节早期、最近未开展疫苗接种活动 和人口密度大），也应开展疫苗接种活动 在特殊情况下（如群众聚会、难民、流离失所者或封闭的场所），如 １ 周内发生 ２ 例确诊病例，则应尽 早开展大规模疫苗接种 脑膜炎球菌性脑膜炎 １８３　 ９ 尽早使用抗生素治疗是挽救生命和减少并发症的最重要因素  及时治疗（诊断后 １ 小时内）对 预防死亡和并发症至关重要： － 在非洲流行带流行期间推荐的 标准治疗方案为：头孢曲松 （静脉注射），持续 ５ 天；婴儿 （０～２月龄），持续 ７天。  虽然没有必要隔离患者，但入住 医院或卫生中心治疗是必要的。  假如患者治疗 ４８ 小时后病情没 有改善，或仍出现惊厥或昏迷， 应转送到更高级别的卫生机构 治疗。 １０ 尽早给予抗生素可减少密切接触者的传播风险  在非洲脑膜炎流行带以外的地区， 家庭密切接触者可推荐使用化学药 物进行预防。  在非洲脑膜炎流行带，在非流行情 况下可推荐密切接触者使用化学药 物进行预防。  抗生素首选环丙沙星，也可用头孢 曲松。 １８４　 第二部分　 熟知内情———１５种致死性传染病的 １０个关键事实 有关脑膜炎球菌性脑膜炎的更多信息：  Ｍｅｎｉｎｇｏｃｏｃｃａｌ ｍｅｎｉｎｇｉｔｉｓ ＷＨＯ ｗｅｂｐａｇｅ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｍｅｎｉｎｇｏｃｏｃｃａｌ ／ ｅｎ ／  Ｍｅｎｉｎｇｉｔｉｓ ＷＨＯ ＭＯＯＣ： ｈｔｔｐｓ：／ ／ ｏｐｅｎｗｈｏ ｏｒｇ ／ ｃｏｕｒｓｅｓ ／ ｐａｎｄｅｍｉｃｅｐｉｄｅｍｉｃｄｉｓｅａｓｅｓ  Ｍｅｎｉｎｇｏｃｏｃｃａｌ ｍｅｎｉｎｇｉｔｉｓ ＷＨＯ ｆａｃｔ ｓｈｅｅｔ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｍｅｄｉａｃｅｎｔｒｅ ／ ｆａｃｔｓｈｅｅｔｓ ／ ｆｓ１４１ ／ ｅｎ ／  Ｍａｎａｇｉｎｇ ｍｅｎｉｎｇｉｔｉｓ ｅｐｉｄｅｍｉｃｓ ｉｎ Ａｆｒｉｃａ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｒｅｓｏｕｒｃｅｓ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ＨＳＥ＿ＧＡＲ＿ＥＲＩ＿２０１０ ＿４ ／ ｅｎ ／  Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｃｏｏｒｄｉｎａｔｉｎｇ Ｇｒｏｕｐ（ＩＣＧ）ｏｎ Ｖａｃｃｉｎｅ Ｐｒｏｖｉｓｉｏｎ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｉｃｇ ／ ｅｎ ／ （李万仓 译） １８５　 第三部分 工具箱 １８６　 第三部分　 工具箱 工具箱 １ 世界卫生组织的作用 世界卫生组织的职责———在传染病方面 世界卫生组织根据下列 ６项主要任务，指导和协调联合国系统内的国际卫生管理机构： １ 在健康关键问题上发挥领导作用和参与需要共同行动的伙 　 　 　 伴关系。 例如  世界卫生组织： － 与各国共同努力增加和维持预防、治疗和保健的获得。 － 确定优先项目和制订策略。 － 领导和协调突发事件期间的卫生应对。  通过《国际卫生条例》（２００５），世界卫生组织帮助各国增强应 急风险管理的国家核心能力，来预防、防备、应对突发公共卫 生事件并使之恢复。 工具箱 １　 世界卫生组织的作用 １８７　 工具箱 １ 　 　 ２ 制定研究议程和促进有价值知识的产生、翻译和传播。 例如  世界卫生组织研发计划是一项全球战略和防备计划，该计划允许 在疾病流行期间快速启动研发活动。其目的是快速跟踪有效检 测、疫苗和药物的可获得性，从而挽救生命，避免大规模危机。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｂｌｕｅｐｒｉｎｔ ／ ｅｎ ／  世界卫生组织的流感公共卫生研究议程提供了反映大流行流感、 动物源性流感和季节性流感流行的公共卫生研究优先项目，以减 少出现大流行流感的风险，遏制大流行流感、动物源性流感和季节 性流感的传播，减少流行产生的影响，优化患者的治疗并促进现代 公共卫生工具的开发。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｉｎｆｌｕｅｎｚａ ／ ｒｅｓｏｕｒｃｅｓ ／ ｒｅｓｅａｒｃｈ ／ ｅｎ ／  由世界卫生组织制定的中东呼吸综合征冠状病毒（ＭＥＲＳＣｏＶ）研究 议程旨在解决该病毒的未知问题，主要集中在 ５个主要研究领域：① 病毒的起源与特性；② 流行病学与传播；③临床管理与感染预防控 制措施；④产品开发与应用；⑤干预的影响和操作性研究。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｅｍｅｒｇｅｎｃｉｅｓ ／ ｍｅｒｓｃｏｖ ／ ｅｎ ／ １８８　 第三部分　 工具箱 工具箱 １ 　 　 ３ 制订规范和标准，促进和监督其实施。 例如  世界卫生组织编写了一本袖珍手册，提供了医疗保健机构病毒性 出血热的最佳管理实践指南。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｒｅｓｏｕｒｃｅｓ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ｃｌｉｎｉｃａｌｍａｎａｇｅｍｅｎｔ ｐａｔｉｅｎｔｓ ／ ｅｎ ／  世界卫生组织编写了关于在丝状病毒病暴发期间使用个人防护用 品的快速建议指南。 ｈｔｔｐｓ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｒｅｓｏｕｒｃｅｓ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ｅｂｏｌａ ／ ｐｅｒｓｏｎａｌｐｒｏ ｔｅｃｔｉｖｅｅｑｕｉｐｍｅｎｔ ／ ｅｎ ／ 　 　 ４ 阐明基于伦理和证据的政策选项。 例如  世界卫生组织发表疫苗立场文件，提供全球疫苗和免疫建议，具有 国际公共卫生的影响力。世界卫生组织立场文件遵循世界卫生组 织免疫战略咨询小组（ＳＡＧＥ）的建议。疫苗立场文件的更新是根 据所获得的新的科学证据和公共卫生优先事项。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｉｍｍｕｎｉｚａｔｉｏｎ ／ ｄｏｃｕｍｅｎｔｓ ／ ｐｏｓｉｔｉｏｎｐａｐｅｒｓ ＿ ｉｎｔｒｏ ／ ｅｎ ／ 工具箱 １　 世界卫生组织的作用 １８９　 工具箱 １ 　 　 ５ 提供技术支持，促进变化，并建立可持续的机构能力。 例如  世界卫生组织开发了一个网络平台，提供在线课程，传播传染病知 识，改善对流行的防备和反应。课程包括管理流行和公共卫生干 预的全球知识，以及特定疾病的知识。 世界卫生组织大规模开放网络课程： ｈｔｔｐｓ：／ ／ ｏｐｅｎｗｈｏ ｏｒｇ ／ 　 　 ６ 监测健康状况和评估健康趋势。 例如  世界卫生组织对传染病进行定期的全球风险评估，评估任何能产 生公共卫生影响的事件的风险。  世界卫生组织发布通过监测疾病暴发信息所获得的事件的流行病 学情况和风险评估的摘要。 ｈｔｔｐ：／ ／ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｏｎ ／ ｅｎ ／  世界卫生组织还通过流行病学周报发布有公共卫生意义的暴发和 传染病的流行病学信息。 ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｗｅｒ ／ ｅｎ ／ １９０　 第三部分　 工具箱 工具箱 １ 世界卫生组织和《国际卫生条例》的建立：全球公共卫生合作的需要 １８３０—１８４７年欧洲蔓延的霍乱流行是强化传染病外交和公共卫生多边合作的催化剂。他们 展示了需要国家间的合作来控制全世界危险疾病的传播，从而导致了 １８５１年在巴黎召开的第一次 国际卫生会议。世界卫生组织宪章于 １９４８年生效，１９５１年世界卫生组织会员国通过了 Ｉｎｔｅｒｎａｔｉｏｎ ａｌ Ｓａｎｉｔａｒｙ Ｒｅｇｕｌａｔｉｏｎｓ，在 １９６９该条例被取代，并更名为 Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｈｅａｌｔｈ Ｒｅｇｕｌａｔｉｏｎ（《国际卫生 条例》）。世界卫生组织于 １９７３年和 １９８１年对《国际卫生条例》进行了较小的修订。 《国际卫生条例》的主要目的是监测和控制 ６ 种严重传染病，包 括霍乱、鼠疫、黄热病、天花、回归热和斑疹伤寒。根据《国际卫生条 例》（１９６９），只有霍乱、鼠疫和黄热病仍为法定报告传染病，表示这些 疾病在成员国领土上发生，则需要报告世界卫生组织。 随着跨境旅行和贸易的增加，信息和通信技术的发展，霍乱和鼠 疫等古老传染病的死灰复燃，一些新的传染病（如埃博拉病毒病）的 出现，以及受《国际卫生条例》（１９６９）的限制（仅局限于 ３ 种疾病，对 国家官方报告的依赖性），需要修订条例。世界卫生大会于 ２００５年 ５ 月 ２３日通过了《国际卫生条例》（２００５），并于 ２００７ 年 ６ 月 １５ 日生 效。《国际卫生条例》（２００５）是对全球 １９６ 个国家有约束力的国际法律协议。其目的是预 防、控制和应对疾病的国际传播，同时避免不必要的对国际交通和贸易的干涉。 问题和解答： １ 《国际卫生条例》（１９６９）与《国际卫 生条例》（２００５）的主要变化是什么？  就公共卫生事件而言，《国际卫生条 例》（２００５）的范围更广泛，包含的内容 更多，所有可能导致严重国际后果的 这些事件能被世界卫生组织缔约国尽 早发现，并迅速报告给世界卫生组织 进行评估，从而使这种可能性最大化。  《国际卫生条例》（２００５）明确允许世 界卫生组织考虑来自除官方通报和咨 询以外来源的信息，以及评估后寻找 有关缔约国对特殊事件的核实。 ２ 根据《国际卫生条例》（２００５），国家的 一般义务是什么？ 《国际卫生条例》（２００５）要求缔约国：  指定 ＩＨＲ国家归口单位（可以是一个 团队）。需要一周 ７ 天，每天 ２４ 小时 在岗。  使用决策工具评估其领土内发生的事 件，并向世界卫生组织报告可能构成 国际关注的所有突发公共卫生事件。  对于可能构成国际关注的突发公共卫 生事件，应该对要求核实信息的请求 做出回应，并对可能国际传播的公共 卫生风险作出应对。 工具箱 １　 世界卫生组织的作用 １９１　 工具箱 １  建立、加强和维持监测、报告和应对公共卫生事 件的能力；在指定的国际机场、港口和陆地过境 点提供日常设施、服务、监督和控制活动来防止 疾病的国际传播。  向世界卫生组织报告在其领土以外的地方发现 可导致国际疾病蔓延的公共卫生风险的证据， 其特征包括输出 ／输入人类病例、携带感染或污 染的媒介、被污染的货物等。  适当实施世界卫生组织推荐的措施。  与其他缔约国和世界卫生组织合作并实施《国 际卫生条例》（２００５）。 １９２　 第三部分　 工具箱 　工具箱 １ ３ 缔约国应向世界卫生组织通报 哪些事件？ 根据国际卫生条例，缔约国要 向世界卫生组织报告所有被评估为 可能构成国际关注的公共卫生事件 （Ｐｕｂｌｉｃ Ｈｅａｌｔｈ Ｅｖｅｎｔ ｏｆ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｃｏｎｃｅｒｎ，ＰＨＥＩＣ），同时要考虑事件 发生的背景。 条例的附录 ２提供的决策工具， 确定了缔约国在评估其领土范围内 的事件以及决定是否向世界卫生组 织报告时必须遵循的四项标准：  事件的公共卫生影响是否严重？  事件不寻常或出乎预料吗？  是否存在重大的国际传播危险？  是否有采取国际旅行和贸易限 制措施的严重危险？ ４ 如果缔约国评估风险有困难，怎 么办？ 缔约国有权与世界卫生组织发 起保密磋商和征求有关评价、评估 和要采取适当卫生措施的意见，以 防他们无法完成权威性的评估。 ５ 怎样报告以及何时报告这些事件？  报告的事件必须经过国家评估后 ２４ 小时内完 成报告。  报告后还必须对有关事件的详细公共卫生信 息持续进行沟通，在可能的情况下，应该包括 病例定义、实验室结果、风险的来源和类型；病 例数和死亡数、影响疾病传播的条件和采取的 卫生措施。 ６ 如果缔约国确定了在其领土之外的公共卫生 危险，应该怎么办？ 缔约国在收到其领土外发现有公共卫生危险 的证据后，必须 ２４小时内通过《国际卫生条例》国 家归口单位向世界卫生组织报告，这些危险可导 致国际疾病传播，表现为输入和输出人类病例，可 携带感染或污染的媒介，或被污染的物品。 ７ 世界卫生组织 能要求缔约国提供更多未报道 事件的信息吗？ 根据《国际卫生条例》，缔约国需要对世界卫生 组织的事件核实请求做出回应。世界卫生组织有 明确的授权，可从缔约国获得有关对非官方报告或 通讯的核实情况，并从不同来源收集关于其领土内 可能构成国际关注的公共卫生事件。缔约国必须 在 ２４小时内确认世界卫生组织提出的核实要求， 并及时提供有关事件状况的公共卫生信息。 ８ 有哪些疾病应强制向世界卫生组织 报告？ 根据《国际卫生条例》（２００５），天花、 野生型脊髓灰质炎病毒引起的脊髓灰质 炎、严重急性呼吸综合征和新亚型病毒 引起的人流感等 ４种疾病的所有病例都 必须主动向世界卫生组织报告。 ９ 何谓核心能力？  根据《国际卫生条例》（２００５），每个 缔约国都需要发展、加强和维护核心 公共卫生能力，以进行监测和响应。  根据《国际卫生条例》（２００５），公共卫 生能力的定义是为实现国家卫生安全 目标，每个缔约国将采取的必不可少 的、根本性的行动作为其主要责任，如 　 　 　 工具箱 １　 世界卫生组织的作用 １９３　 　工具箱 １ 　 通过有效的多部门行动来预防疾病传 播，发现和调查社区的健康风险（如综 合疾病监测系统、实验室服务以及国 家、区域和全球网络）。  当地（社区）、中层和国家层面的核心能 力，以及在指定的国际机场、港口和陆地 过境点（ｇｒｏｕｎｄ ｃｒｏｓｓｉｎｇｓ）所需的主要卫生 服务，见《国际卫生条例》（２００５）附件 １。 １０ 对黄热病的具体要求有哪些？  作为进入一个国家的条件，旅行者可 能需要提供预防接种或黄热病预防措 施的证据。  缔约国必须指定至少一个黄热病疫苗 接种中心。 １１ 为什么在入境点发展必要的公共卫生 能力会减少公共健康危害的蔓延？ 目前机场、港口和陆地过境点———入境 点繁忙的交通，可通过人员、运输工具和货 物在疾病的国际传播中起关键作用。这就 是为什么各国应做好准备，发现和应对任何 可能引起国际关注的卫生事件，控制源头风 险，限制有关国际旅行和贸易方面不必要的 卫生限制，保护旅行者和人类的健康。 １２ 在入境点做好防备的指导原 则是什么？  简单。  比例性和实用性，要因地制宜。  最小干扰。  协作：多部门合作的方法。  （风险）沟通。 更多的信息：  Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｈｅａｌｔｈ Ｒｅｇｕｌａｔｉｏｎｓ（２００５） ｈｔｔｐ：／ ／ ｗｗｗ． ｗｈｏ． ｉｎｔ ／ ｉｈｒ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ９７８９２４１５８０４ 　 ９６ ／ ｅｎ ／  Ｍｏｒｅ ｉｎｆｏｒｍａｔｉｏｎ ａｂｏｕｔ ＩＨＲ ｈｔｔｐ：／ ／ ｗｗｗ． ｗｈｏ． ｉｎｔ ／ ｉｈｒ ／ ａｂｏｕｔ ／ ｅｎ ／  Ｍｏｒｅ ｉｎｆｏｒｍａｔｉｏｎ ａｂｏｕｔ ｉｍｐｌｅｍｅｎｔｉｎｇ ＩＨＲ ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｉｈｒ ／ ｐｒｏｃｅｄｕｒｅｓ ／ ｉｍｐｌｅｍｅｎｔａ ｔｉｏｎ ／ ｅｎ ／  Ｍｏｒｅ ａｂｏｕｔ ｐｕｂｌｉｃ ｈｅａｌｔｈ ａｔ ｐｏｉｎｔｓ ｏｆ ｅｎｔｒｙ： ｈｔｔｐ：／ ／ ｗｗｗ． ｗｈｏ． ｉｎｔ ／ ｉｈｒ ／ ｐｏｒｔｓ＿ａｉｒｐｏｒｔｓ ／ ｅｎ ／  Ｊｏｉｎｔ Ｅｘｔｅｒｎａｌ Ｅｖａｌｕａｔｉｏｎ Ｔｏｏｌ ａｎｄ Ｐｒｏｃｅｓｓ Ｏｖｅｒｖｉｅｗ ｈｔｔｐ：／ ／ ａｐｐｓ． ｗｈｏ． ｉｎｔ ／ ｉｒｉｓ ／ ｂｉｔｓｔｒｅａｍ ／ １０６６５ ／ ２５２７５５ ／ １ ／ ＷＨＯＨＳＥＧＣＲ２０１６． １８ｅｎｇ． ｐｄｆ？ｕａ＝ １ １９４　 第三部分　 工具箱 工具箱 １ 世界卫生组织紧急应对框架下的事件管理 紧急应对框架（Ｅｍｅｒｇｅｎｃｙ Ｒｅｓｐｏｎｓｅ Ｆｒａｍｅｗｏｒｋ， ＥＲＦ）是世界卫生组织的一个内部工具，概述了更好应 对突发事件的一套程序，紧急应对框架为世界卫生组 织工作人员提供了如何管理评估和分级，以及应对有 健康后果的公共卫生事件和突发事件的基本指导，来 支持成员国和受影响的社区。 突发事件等级 未分级 由世界卫生组织监测但不需要世界卫生组织操作响应的公共卫生事件或突 发事件。 一级 单一的国家突发事件需要世界卫生组织做出有限的反应，需要世界卫生组 织驻成员国代表处（ＷＨＯ Ｃｏｕｎｔｒｙ Ｏｆｆｉｃｅ，ＷＣＯ）与成员国之间的合作，但仍 然超出通常国家层面的合作。世界卫生组织的大多数应对可以用国内资产 进行管理。ＷＣＯ要求的组织支持和（或）外部支持是有限的。向ＷＣＯ提供 的支持由地区办事处的紧急协调员协调。 二级 一个国家或多个国家的突发事件，需要世界卫生组织作出适度的反应。世 界卫生组织要求的反应水平总是超过ＷＣＯ的能力。ＷＣＯ要求的组织支持 和（或）外部支持是适度的。向 ＷＣＯ提供的支持由地区办事处的应急协调 员来协调。总部还任命了紧急事务官员来协助组织范围内的支持。 三级 一个国家或多个国家的突发事件需要世界卫生组织作出重大的 ／最大的响 应。ＷＣＯ所要求的组织支持和 ／或外部支持是重要的，需要动员组织范围 内的资产。向 ＷＣＯ提供的支持由地区办事处的应急协调员来协调。总部 也任命了应急人员来帮助协调组织范围内的投入。有时，世界卫生组织的 卫生应急规划部（ＷＨＥ）执行主任和区域主任可以同意在总部设立应急协 调员。对于涉及多个区域的事件或突发事件，总部的事件管理支持小组将 协调跨区域的应对。 工具箱 １　 世界卫生组织的作用 １９５　 工具箱 １ 　 将风险评估和事态分析与世界卫生组织分级和操作性应对相关联 世界卫生组织的事件内部分级  一旦发现事件并向世界卫生组织报告，应对其核 实和分析。如果事件得到证实，要进行风险评 估。世界卫生组织团队的风险评估可能导致下 列情况： － 如果风险低或极低，要进行监测、减缓、防范和 准备。 － 对事件进行分级，启动事件管理系统；如果风 险高或极高，应提高响应级别。  事件分级是世界卫生组织的内部过程，其目的是 确定世界卫生组织所需的操作性应对水平。分 级考虑了 ５ 个标准：事件规模、复杂性、紧迫性、 在地方和国家层面的应对能力、世界卫生组织的 声誉风险。  突发事件分为四级，见左图。 １９６　 第三部分　 工具箱 工具箱 １ 世界卫生组织通过 ＥＲＦ 的操作响应  评分将触发世界卫生组织应急 程序和响应管理活动。评分将 启动事件管理系统（Ｉｎｃｉｄｅｎｔ Ｍａｎａｇｅｍｅｎｔ Ｓｙｓｔｅｍ，ＩＭＳ），该 系统是公认的应急管理最佳实 践。它简单、灵活，适用于任何 情况：可以应用于小的、简单的 事件，也可以适用于大规模的 复杂事件。提升或降低响应的 措施应迅速，以适应不断变化 的需求。  事件管理系统是在普通组织结 构内操作的机构、设备、人员、 程序和通信的组合。它具有： － 提高互操作性的共同术语和 结构。 － 澄清角色和责任。 － 信息流和资源。 － 快速动员、资源部署和跟踪。  事件管理系统包括： － 确定首要目标（如阻断病原 体的传播）。 　 － 为各项职能活动制定具体 的、可测量的目标。 　 － 制定战略和发布计划、指 南、程序和协议。 　 － 分配任务。 　 － 建立评价过程。  世界卫生组织 已将事件管理 系统调整为 ６ 个关键功能： 领导、伙伴协调、信息和规 划、卫生管理和技术知识、管 理支持和后勤、财务和行政。  世界卫生组织应用“无悔”政 策（ｎｏ ｒｅｇｒｅｔ ｐｏｌｉｃｙ），就是“宁 愿在关键功能方面因使用资 源过多而导致错误，也不要因 资源过少而冒失败之风险”。 就金融资源而言，世界卫生组 织代表和（或）事件管理者增 加了批准支出的权限。在发 生突发事件的头 ３个月，可从 突发事件应急基金（Ｃｏｎｔｉｎ ｇｅｎｃｙ Ｆｕｎｄ ｆｏｒ Ｅｍｅｒｇｅｎｃｙ， ＣＦＥ）或者地区办事处快速 应对账户立即获得资金。 工具箱 １　 世界卫生组织的作用 １９７　 　 　 　 世界卫生组织的事件管理系统组织结构：关键功能与子功能 １９８　 第三部分　 工具箱 工具箱 １ 世界卫生组织 对应对的监控：成功的标准  评估对事件的应对，从过去的应对中吸取教训，改 进可能做得更好的事情并加强最佳实践是至关重 要的。  对 ２级和 ３级突发事件，应监测世界卫生组织的绩 效标准和关键绩效指标。 － 应该使用紧急应对框架监测工具来监测绩效标 准。使用 ＥＲＦ监测工具的任务由驻成员国办事 处负责，并由地区办事处监督。 － 对每个应对项目的关键绩效指标（不超过 ８ 项） 进行逐案商定（如病死率，疫苗接种覆盖率等）。 更多的信息：  Ｅｍｅｒｇｅｎｃｙ Ｒｅｓｐｏｎｓｅ Ｆｒａｍｅｗｏｒｋ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｈａｃ ／ ａｂｏｕｔ ／ ｅｒｆ ／ ｅｎ ／ （邹艳 译） 工具箱 ２　 疫苗供应国际协调小组 １９９　 工具箱 ２ 疫苗供应国际协调小组 什么是国际协调小组？  国际协调小组（Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｃｏｏｒｄｉｎａｔｉｏｎ Ｇｒｏｕｐ，ＩＣＧ）于 １９９７ 年成立，是继非 洲重大脑膜炎暴发后作为一种机制，来管理和协调在重大暴发期间向各国提 供应急疫苗和抗生素。  ＩＣＧ监测霍乱、脑膜炎和黄热病疫苗的安全全球库存水平，以确保在发生暴 发时能提供足够的疫苗以应对疾病暴发。  ＩＣＧ与合作伙伴一起，改进流行防备和应对的合作和协调。  ＩＣＧ致力于预测疫苗库存，通过其网络或合作伙伴协商疫苗价格，评价干预 措施和处理疾病的标准协议。 ２００　 第三部分　 工具箱 工具箱 ２ 为什么需要这样的机制？ 虽然脑膜炎、黄热病和霍乱的暴发是不可预知的事件，但这些疾病可以通过及 时使用疫苗来控制。疫苗可预防的疾病通常会影响高危地区的人群，因为他们获得 疫苗会受到限制。疫苗可能需要几个月才能生产出来，而且在紧急情况下所需的疫 苗数量并不一定能得到保障。由此产生的疫苗短缺对在需求高峰期如何分配有限 的疫苗带来了难题。对尼日利亚大规模脑膜炎暴发后的及时应对，公共卫生组织发 现自己没有准备好，这就是为什么在 １９９７年建立 ＩＣＧ机制的原因。 ＩＣＧ 的任务是什么？  ＩＣＧ的核心任务是在暴发期间确保能公平地获 得霍乱疫苗、脑膜炎疫苗、黄热病疫苗。  ＩＣＧ 机制旨在确保及时和有针对性地使用疫 苗，以便在最需要时将疫苗作为有效的暴发应 对措施。  ＩＣＧ 还管理全球应急疫苗储备，并与生产商合 作，确定其规模和构成，目标是确保应急物资有 充足的库存供应急应对之用。 ＩＣＧ 机制的指导原则是什么？ 有三项原则来指导机制：  公平：基于公共卫生优先权的疫苗分配。  快速和及时的获得：在既定时间范围内分发疫 苗来控制暴发。  独立性：所作的决定独立于任何政治或经济，而 以改善公共卫生为唯一目标。 工具箱 ２　 疫苗供应国际协调小组 ２０１　 工具箱 ２ 谁是 ＩＣＧ 的合作伙伴？ ＩＣＧ由 ４个成员机构组成。  红十字会与红新月会国际联合会（Ｉｎｔｅｒｎａ ｔｉｏｎａｌ Ｆｅｄｅｒａｔｉｏｎ ｏｆ ｔｈｅ Ｒｅｄ Ｃｒｏｓｓ ａｎｄ Ｒｅｄ Ｃｒｅｓｃｅｎｔ Ｓｏｃｉｅｔｉｅｓ，ＩＦＲＣ）——— 在促 进社区健康、动员当地社会和资源方面有强 有力的国家影响力，并在灾害和流行病期间 向各国提供支持。  无国界医生（Ｍéｄｅｃｉｎｓ ｓａｎｓ Ｆｒｏｎｔｉèｒｅｓ， ＭＳＦ）———是一个独立的、基于现场的非政 府组织，在紧急情况下为弱势人群提供医疗 保健。  联合国儿童基金会（Ｕｎｉｔｅｄ Ｎａｔｉｏｎｓ Ｃｈｉｌ ｄｒｅｎ’ｓ Ｆｕｎｄ，ＵＮＩＣＥＦ）——— 进行大规模 疫苗采购和运送，并在特别注重社会动员和 冷链的国家提供行动规划和实施方面的技 术支持。  世界卫生组织———为各国提供全球公共卫 生咨询和技术支持。在疾病暴发期间，世界 卫生组织专注于疫苗储备管理、监测、防备 和对疾病暴发的应对。 　 　 额外的专业知识和技术建议由下列合作 伙伴分别提供，包括预防医学机构（Ａｇｅｎｃｅ ｄｅ ｍéｄｅｃｉｎｅ ｐｒｅｖｅｎｔｉｖｅ，ＡＭＰ）、Ｅｐｉｃｅｎｔｒｅ 公司、 ＧＡＶＩ疫苗联盟、世界卫生组织合作中心，美国 疾病预防控制中心（ＵＳ Ｃｅｎｔｅｒｓ ｆｏｒ Ｄｉｓｅａｓｅ Ｃｏｎ ｔｒｏｌ，ＣＤＣ）和欧洲共同体人道主义办公室（Ｅｕ ｒｏｐｅａｎ Ｃｏｍｍｕｎｉｔｙ Ｈｕｍａｎｉｔａｒｉａｎ Ｏｆｆｉｃｅ，ＥＣＨＯ）。 疫苗制造商、疫苗设备供应商和捐赠机构也参 与 ＩＣＧ运行。 通过 ＩＣＧ 可以获得哪些疫苗储备？ 　 　 现已建立了 ＩＣＧ旨在提供霍乱、脑膜炎和 黄热病的疫苗。 霍乱 脑膜炎 黄热病 ２０２　 第三部分　 工具箱 工具箱 ２ 一个国家如何获得紧急疫苗储备？  世界上任何国家面临任何疾病的流行时，国家的要求能满足 ＩＣＧ 发放疫苗库存 的标准，则可获得疫苗安全库存。  第一步，国家必须填写标准申请表并向 ＩＣＧ秘书处提出请求。  然后世界卫生组织 ＩＣＧ秘书处将此请求分发给合作伙伴进行审查和评估。必要 时，会向请求国发回要求报告额外的信息。一旦提供了所有必要的信息，在快速 咨询和评估过程后，会在 ４８小时内将提供疫苗和其他物品的决定通知请求国。  如果获得批准，联合国儿童基金会采购疫苗和注射材料，并组织向该国运送疫苗， 最好在 ７天内实施。  评估请求时要考虑到流行病学情况、疫苗接种战略、当事国已有的库存和流行应 对措施的操作方面。 更多的信息：  Ｇｅｎｅｒａｌ ｉｎｆｏｒｍａｔｉｏｎ ｏｎ ｔｈｅ ＩＣＧ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｉｃｇ ／ ｅｎ ／  Ａｐｐｌｉｃａｔｉｏｎ ｆｏｒｍｓ ａｎｄ ｇｕｉｄｅｌｉｎｅｓ ｆｏｒ Ｃｈｏｌｅｒａ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｉｃｇ ／ ｃｈｏｌｅｒａ ／ ｅｎ ／  Ａｐｐｌｉｃａｔｉｏｎ ｆｏｒｍｓ ａｎｄ ｇｕｉｄｅｌｉｎｅｓ ｆｏｒ Ｍｅｎｉｎｇｉ ｔｉｓ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｍｅｎｉｎｇｏｃｏｃ ｃａｌ ／ ｉｃｇ ／ ｅｎ ／  Ａｐｐｌｉｃａｔｉｏｎ ｆｏｒｍｓ ａｎｄ ｇｕｉｄｅｌｉｎｅｓ ｆｏｒ Ｙｅｌｌｏｗ ｆｅ ｖｅｒ： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｃｓｒ ／ ｄｉｓｅａｓｅ ／ ｉｃｇ ／ ｙｅｌｌｏｗ ｆｅｖｅｒ ／ ｅｎ ／ （邹艳 译） 工具箱 ３　 实验室诊断和感染性物质运输表 ２０３　 工具箱 ３ 实验室诊断和感染性物质运输表 表 １　 标本采集和保存 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性腹泻综合征 霍乱  腹泻标本  直肠拭子  培养分离物  粪便标本容器  拭子的 Ｃａｒｙ Ｂｌａｉｒ转运培养基  如果没有 Ｃａｒｙ Ｂｌａｉｒ，可用滤纸， 将腹泻样本涂在滤纸上  室温下可置 ４ 小时，冷藏时可储 放更长  Ｃａｒｙ Ｂｌａｉｒ样本可常温保存  在干燥滤纸上的标本可在室温下 储存  在湿润滤纸上的标本可在室温下 储存  分离培养物的菌株：  试管中的固体非选择性培养基可 在室温下储存几天  库存琼脂培养基在室温下培养 急性出血热 克里米亚刚果 出血热  用 ＥＤＴＡ收集全血（２ ５ｍｌ）（替代血清）  冷冻组织标本  其他：甲醛固定的组织或石蜡包埋的组织 对于血清学检测，强烈推荐急性期和恢复期 标本  ＥＤＴＡ管  血清分离管  肝素可干扰 ＰＣＲ试剂和试验  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） ２０４　 第三部分　 工具箱 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息：患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性出血热 登革热  全血（血清 ／血浆－１ｍｌ）  血清分离器管  ＲＴＰＣＲ 检测可采用枸橼酸盐和肝素抗凝血浆  ＥＤＴＡ可干扰 ＰＣＲ试剂和检测  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 埃博拉病毒病  用 ＥＤＴＡ收集全血（１ｍｌ）（替代血清）  从死亡患者收集唾液  其他：甲醛固定的组织或石蜡包埋的组织 对于血清学检测，强烈推荐急性期和恢复期标本  ＥＤＴＡ试管  肝素可干扰 ＰＣＲ试剂和试验  涤纶 ／聚酯拭子，棉签头部储存在通用运送培养基中  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 拉沙热  用 ＥＤＴＡ收集全血（２ ５ｍｌ）（替代血清）  冷冻组织标本  其他：甲醛固定的组织或石蜡包埋的组织 对于血清学检测，强烈推荐急性期和恢复期标本  ＥＤＴＡ试管  血清分离管  肝素可干扰 ＰＣＲ试剂和试验  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 马尔堡病毒病  用 ＥＤＴＡ收集全血（２ ５ｍｌ）（替代血清）  从死亡患者收集唾液  其他：甲醛固定的组织或石蜡包埋的组织 对于血清学检测，强烈推荐急性期和恢复期标本  ＥＤＴＡ试管  血清分离管  肝素可干扰 ＰＣＲ试剂和试验  ＜２４小时：室温  ＞２４小时～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 裂谷热  用 ＥＤＴＡ收集全血（２ ５ｍｌ）（替代血清）  冷冻组织标本  其他：甲醛固定的组织或石蜡包埋的组织 对于血清学检测，强烈推荐急性和恢复期标本  ＥＤＴＡ试管  血清分离管  肝素可干扰 ＰＣＲ试剂和试验  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 黄热病  全血（血清－１ｍｌ）  其他：推荐采集尿液（１０ｍｌ），但尿液不是已验证的标本类型  ＥＤＴＡ试管  血清分离管  无菌尿收集管  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） 工具箱 ３　 实验室诊断和感染性物质运输表 ２０５　 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性黄疸综合征 钩端螺旋体病  全血（２５０μｌ）  血清（２５０μｌ）  脑脊液（２５０μｌ）  尿液（１０ｍｌ）  分离物和接种临床标本的培养基（血 液、组织和尿液）  血液标本应收集在 ＥＤＴＡ 或枸 橼酸钠管中  采集的血液标本加肝素是不可 接受的  培养物应存放在室温下  临床标本应在－２０℃下冷冻保存  血清储存在 ４℃ 急性神经系统综 合征 脑膜炎球菌脑 膜炎  血液（成人：５～１０ｍｌ；儿童：１～３ｍｌ）  脑脊液（－３ｍｌ）  任何正常无菌部位（心包液）和 ／或紫 癜性皮肤病变的抽吸物或活检  脑脊液： － １ 只干燥试管和 １ 只冰冻管 （ＰＣＲ检测用） － 如果干燥试管在 ２ 小时内不 处理，则接种到 ＴＩ培养基  血液：采集的血液在血液肉汤增 菌液中稀释，以获得血液培养 物。应将标本立即接种在血液 培养瓶内（１分钟内）  脑脊液用干燥管保存：室温  脑脊液用冷冻管保存：冷藏，用冷链 运送  ＣＳＦ分离物：在－２０℃冷藏，以做进 一步检测  ＴＩ培养基瓶不应冷冻。在接种前， 应将 ＴＩ 培养基瓶放在冰箱里冷 藏。一旦接种，ＴＩ瓶应保持在室温 下。如果接种的 ＴＩ 瓶当天不运送， 则必须通气  应保护接种的血液培养基，通过运 输载体和热绝缘体（如挤塑聚苯乙 烯泡沫塑料）防止温度过低或过高 （＜１８℃或＞３７℃）  接种的血培养瓶不应放置在冰箱中 ２０６　 第三部分　 工具箱 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性呼吸综合征 炭疽病  全血  皮肤病变渗出物  胸腔积液  脑脊液（ＣＳＦ）  直肠拭子  腹水  活检或尸检组织  血液标本应收集在 ＥＤＴＡ 或枸 橼酸钠管中（不含肝素）  用甲醛固定组织做免疫组化法 （ＩＨＣ）检测  大多数标本可在 ２～８℃运送  新鲜组织应冷冻运送，固定的组 织可在室温下运送 流行性感冒  病毒分离株  呼吸道临床标本（如鼻咽拭子、鼻拭子、 咽拭子、鼻抽提物、鼻冲洗物、下呼吸道标 本、支气管灌洗液）  核酸（１ｍｌ） 对疑似禽流感患者的标本：除上呼吸道标本 外，还应收集下呼吸道标本  涤纶 ／聚酯拭子与通用运送培养 基  收到冷藏的涤纶拭子或标本在处 理前可冷藏（２～８℃）达 ７２小时  涤纶拭子和任何残留标本储放在 －７０℃以下  涤纶拭子或尽管在采集 ７２ 小时 内检测新鲜标本易于检出，但冷 冻标本也可以检出： － 如果在 ２ ～ ８℃储存 ７２ 小时内 不可能对新鲜标本进行检测， 则该样品可在≤－７０℃下冷冻， 待检 － 收到冷冻的标本，应存放在≤ －７０℃直至处理 － 将任何残留标本存放在≤ －７０℃ － 用干冰运送提取的 ＲＮＡ 和冷 冻标本 工具箱 ３　 实验室诊断和感染性物质运输表 ２０７　 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性呼吸综合征 鼠疫  腺鼠疫：腹股沟淋巴结炎抽提物，细菌运 送培养基中的拭子（如 Ｃａｒｙ Ｂｌａｉｒ 培养 基）  肺鼠疫：痰液，细菌运送培养基拭子（如 Ｃａｒｙ Ｂｌａｉｒ培养基）  用于血清学检测的血液 标本应在疾病急性期采集，最好在抗生素治 疗开始前采集  新鲜或冷冻：拭子、活组织检查、涂片 标本（ｔｏｕｃｈ ｐｒｅｐ ｓｌｉｄｅ）、甲醛固定的 组织或石蜡块  拭子用尼龙、聚酯或涤纶材料制成  在 ２～８℃储存 中东呼吸综合征  下呼吸道： － 痰 － 抽吸物 － 灌洗液  上呼吸道： － 鼻咽和口咽拭子 － 鼻咽部冲洗液 － 鼻咽部抽吸物  血清（１ｍｌ） 建议采集上呼吸道和下呼吸道标本  涤纶、聚酯拭子，通用运送培养基  血液：ＥＤＴＡ  ＜２４小时：室温  ＞２４～７２小时：０～４℃  长期储存： 　 －２０℃或－７０℃（首选） ２０８　 第三部分　 工具箱 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性皮肤综合征 皮肤炭疽  皮损渗出物  活检或尸检组织  其他： － 全血 － 胸膜液 － 脑脊液（ＣＳＦ） － 直肠拭子 － 腹水  将血液标本收集在 ＥＤＴＡ 或枸橼酸 钠管中（不含肝素）  用甲醛固定组织做组织免疫组化 （ＩＨＣ）检查  大多数标本可在 ２～８℃运送  新鲜组织应冷冻运送  固定的组织应在室温下运送 猴痘  病变组织的液体和（或）材料： － 疱疹 ／脓疱疹或其液体 － 痂，痂皮  可选但不首选：血液（０ ５ｍｌ）  非手持端拭子可存放在无菌容器中  首选干拭子，但可以加入小量病毒运 送培养基  ４℃保存，７２小时内运送 天花  皮损痂  脓疱液（０ ５ｍｌ）  非手持端拭子可存放在无菌容器中  首选干拭子，但可以加入小量病毒运 送培养基  ４℃保存，７２小时内运送 工具箱 ３　 实验室诊断和感染性物质运输表 ２０９　 工具箱 ３ 表 １　 标本采集和保存（续） 需记录的信息： 患者信息、流行病学 ＩＤ编号、样品采集日期、实验室 ＩＤ号和临床 ／流行病学信息 综合征 疾病 首选标本类型和样本体积（最小） 标本采集材料 标本保存 急性发热和皮疹 基孔肯雅热  全血、血清（静脉血 ４～５ｍｌ）  其他： － 推荐采集尿标本，但并非已验证的标本 类型 － 脑膜脑炎病例的脑脊液 － 关节炎积液伴滑膜液 － 尸体解剖材料———血清或可用组织  ＥＤＴＡ管  血清分离管  无菌尿收集管  ０～４℃保存 寨卡病毒病  全血、血清、血浆（静脉血 ４～５ｍｌ）  尿  脑脊液（０ ２５ｍｌ）  其他：精液  ＥＤＴＡ管  血清分离管  无菌尿液收集管  ０～４℃储存  ＞４８小时，血清应分离 　 　 应在急性期采集标本供检测用。检测结果与从发病到采集标本的时间高度相关。因此，需要采集多份标本来证实 ／排除诊断。 ２１０　 第三部分　 工具箱 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性腹泻综合征 霍乱  现场使用的 ＲＤＴ（需要 额外的确认）  ＰＣＲ、多位点可变数目串 联重复序列分析 　 （ＭＬＶＡ）、测序  培养  抗生素敏感性试验  ＰＣＲ：２４～４８小时  培养和敏感性试验：可 达 ８周  阿米巴痢疾  隐孢子虫病  贾第虫病  志贺菌病  大肠杆菌（肠产毒性和肠 出血性）  病毒性胃肠炎（诺瓦克样 病毒和轮状病毒）  沙门菌病  弯曲杆菌  ＵＮ３３７３生物学物质  包装说明 ６５０ 急性出血热综合征 克里米亚刚果 出血热  反转录聚合酶链反应 （ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验 （ＥＬＩＳＡ）  抗原检测  血清中和试验  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时 登革热  反转录聚合酶链反应 （ＲＴＰＣＲ）  抗原检测  血清学：ＩｇＭ、ＲＤＴｓ  病毒分离  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时  汉坦病毒  南美沙粒病毒  蜱传黄病毒  基孔肯雅热病毒  西尼罗病毒  辛德毕斯病毒  侵袭性脑膜炎球菌病  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０  培养： － ＵＮ２８１４ － 感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３ － 生物物质 － 包装说明 ６５０ 工具箱 ３　 实验室诊断和感染性物质运输表 ２１１　 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输（续） 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性出血热综合征 埃博拉病毒疾 病  反转录聚合酶链反应 （ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验 （ＥＬＩＳＡ）  抗原检测（ＲＤＴ）  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时 拉沙热  反转录聚合酶链反应 （ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验 （ＥＬＩＳＡ）  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时 马尔堡病毒病  反转录聚合酶链反应 （ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验 （ＥＬＩＳＡ）  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时  汉坦病毒  南美沙粒病毒  蜱传黄病毒  基孔肯雅热病毒  西尼罗病毒  辛德毕斯病毒  侵袭性脑膜炎球菌病  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０ ２１２　 第三部分　 工具箱 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输（续） 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性出血热综合征 裂谷热  反转录聚合酶链反应（ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验（ＥＬＩＳＡ）  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：７２小时 黄热病  反转录聚合酶链反应（ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验（ＥＬＩＳＡ）  中和试验  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：１０天  蚀斑减少中和试验（ＰＲＮＴ）：可达 ２周  汉坦病毒  南美砂粒病毒  蜱传黄病毒  基孔肯雅热病毒  西尼罗病毒  辛德毕斯病毒  侵袭性脑膜炎球菌病  培养： － ＵＮ２８１４感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０  培养： － ＵＮ２８１４感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０ 急性黄疸综合征 钩端螺旋体病  血清学：显微镜凝集试验（ＭＡＴ）———微凝集试验  分子：聚合酶链反应（ＰＣＲ）  显微镜检查  ２周  从临床标本初步分离需要长达 ６个月 黄热病  反转录聚合酶链反应（ＲＴＰＣＲ）  酶 联 免 疫 吸 附 试 验（ＥＬＩＳＡ）  中和试验  通过细胞培养分离病毒  ＰＣＲ：２４小时  ＥＬＩＳＡ：１０天  蚀斑减少中和试验（ＰＲＮＴ）：可达 ２周  甲型———戊型肝炎  巨细胞病毒  ＥＢ病毒  其他黄病毒  ＵＮ３３７３生物物质  包装说明 ６５０  培养： － ＵＮ２８１４感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０ 工具箱 ３　 实验室诊断和感染性物质运输表 ２１３　 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输（续） 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性神经系统综 合征 脑膜炎球菌脑 膜炎  细菌培养  ＰＣＲ  细菌培养：４～５天  ＰＣＲ：４８小时  流感嗜血杆菌  肺炎球菌  肠道病毒性脑膜炎  疟疾  脊髓灰质炎  狂犬病和其他狂犬病毒属病毒  非洲锥虫病  脑膜脑炎  蜱传脑炎病毒  流行性乙型脑炎  ＵＮ３３７３生物物质  包装说明 ６５０ 急性呼吸综合征 炭疽  细菌培养  ＰＣＲ  免疫组化法（ＩＨＣ）  毒素检测  ＰＣＲ：４８小时  细菌培养、毒素检测： １ ～ ２ 周 流行性感冒  ＰＣＲ  病毒分离  血凝抑制试验（ＨＡＩ）  ＰＣＲ：２４小时  血凝抑制试验：７２ 小时  病毒培养：１～２周  白喉  汉坦病毒肺综合征  支原体  军团菌病  呼吸道合胞病毒  百日咳  其他呼吸道病毒  培养： － ＵＮ２８１４感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０  禽流感和疑似禽流感 ／大流行流感的病毒培养 － ＵＮ２８１４感染人类的感染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０ ２１４　 第三部分　 工具箱 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输（续） 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性呼吸综合征 鼠疫  快速试纸条法  ＰＣＲ  ＥＬＩＳＡ ＩｇＭ  细菌培养  直接免疫荧光法（ＤＦＡ）  ＰＣＲ：２４小时  细菌培养：１周 中东呼吸综合 征  分子：至少 ２ 个基因靶 点 ＰＣＲ 阳性：筛选试验 （如上游 Ｅ 或 Ｎ 基因 ＮＡＡＴ）和确证试验（如 ＯＲＦ １ａ，ＯＲＦ １ｂ 或 Ｎ 基 因 ＮＡＡＴ）  血清学：免疫荧光试验、 血清中和试验、蛋白质微 阵列技术、基于重组核衣 壳（Ｎ）和突起蛋白（Ｓ）的 间接酶联免疫吸附试验 （ＥＬＩＳＡ）和基于反转录 病毒假颗粒的中和试验  ＰＣＲ：２４小时  间 接 免 疫 荧 光 法 （ＩＦＡ）：２４小时  酶联免疫吸附试验和 微量中和试验：１～３天  白喉  汉坦病毒肺综合征  支原体  军团菌病  呼吸道合胞病毒  百日咳  其他呼吸道病毒  培养 － ＵＮ２８１４感染人类的感 染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０  ＵＮ３３７３生物物质  包装说明 ６５０ 工具箱 ３　 实验室诊断和感染性物质运输表 ２１５　 工具箱 ３ 表 ２　 感染性物质的实验室诊断和运输（续） 综合征 疾病 确证检测类型 平均检测结果周转时间 鉴别诊断 运输分类：基于国际运输货物分类 急性皮肤综合征 皮肤炭疽  细菌培养  ＰＣＲ  免疫组化法（ＩＨＣ）  毒素检测  ２周 猴痘  ＰＣＲ  ２４小时 天花  ＰＣＲ  ２４小时  水痘  疱疹  肠道病毒  麻疹  药物过敏  细菌性皮肤感染  培养 － ＵＮ２８１４感染人类的感 染性物质 － 包装说明 ６２０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０  ＵＮ２８１４感染人类的感染 性物质  包装说明 ６２０ 急性发热和皮疹 基孔肯雅热  ＰＣＲ  血清学  病毒培养  ＰＣＲ：２４小时  ＥＬＩＳＡ：２～５天  病毒分离：≤８天 寨卡病毒病  ＰＣＲ  血清学  中和试验  ＰＣＲ：２４小时  ＥＬＩＳＡ：２～５天  钩端螺旋体病  α病毒感染  登革热  疟疾  脑膜炎  感染后关节炎（如风湿热）  侵袭性脑膜炎球菌病  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０  临床诊断标本： － ＵＮ３３７３生物物质 － 包装说明 ６５０ 　 　 必须考虑诊断产品的设计和性能，以确保试验是安全和有效的。  国家运输安全措施不变 （邹艳 译） ２１６　 第三部分　 工具箱 工具箱 ４ 感染性物质的运输 这个工具箱强调了关于 ２０１７—２０１８年感染性物质运输规章指导的一些重要特征１ （世界卫生组织，２０１７）。 感染性物质：定义 出于运输目的，感染性物质是指那些已知或有理由认为含有病原体的物质。病原 体是指能引起人或动物疾病的微生物（包括细菌、病毒、立克次体、寄生虫、真菌）和其 他病原体（如朊毒体）。 这个定义适用于所有标本，但明确排除的标本除外：  培养物。  患者标本。  生物学产品。  遗传修饰微生物和生物体。  医疗或临床废弃物。 　 　 １全文可见：ｈｔｔｐ：／ ／ ｗｗｗ． ｗｈｏ． ｉｎｔ ／ ｉｈｒ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ＷＨＯ－ＷＨＥ－ＣＰＩ－２０１７． ８ ／ ｅｎ ／ 工具箱 ４　 感染性物质的运输 ２１７　 　 工具箱 ４ 分类 《危险品条例》（Ｄａｎｇｅｒｏｕｓ Ｇｏｏｄｓ Ｒｅｇｕｌａ ｔｉｏｎｓ）第 ６ ２款中有感染性物质分类，并根据 危害分类及其组成确定合适的运输名称（ＵＮ ２８１４，ＵＮ ２９００，ＵＮ ３２９１或 ＵＮ ３３７３）。 感染性物质分为以下几类：  Ａ 类 以某种形式运输的感染性物质，当 发生暴露时，可造成健康的人或动物发生 永久性残疾、威胁生命或致死性疾病。  Ｂ类 不符合 Ａ类标准的感染性物质。  例外的情况。 运输货物的一般准备 由于 Ａ 类感染性物质（ＵＮ ２８１４ 和 ＵＮ ２９００）和 Ｂ 类感染性物质（ＵＮ ３３７３） 造成的危害不同，对这两类物质的包装、 标签和单据要求也有差异。 注 １：国际航空公司承运人严格禁止 徒手运送 Ａ 类和 Ｂ 类感染性物质和使用 外交邮袋运送此类物质。 注 ２：含有感染性物质的内包装不得 与含有不相关货物的内包装固定在一起。 感染性物质的托运人应确保所准备 的包装能使感染性物质完好地到达目的 地，并在运输过程中不会对人员或动物造 成危害。 基本的三重包装系统 这个包装系统应用于所有感染性物 质，包括以下三层：  主容器。一种防水、防漏的主容器。容 器用足够的吸收性材料包裹，可以吸收 所有在破损或泄漏情况下的液体。  中层包装。中层用耐用、防水、防漏的 包装，把容器装入其中并对其提供保护 作用。可将几个加缓冲衬垫的主容器 放置在中层包装中，但应使用足够的其 他吸收性材料，以便在破损或泄漏情况 下可以吸收所有液体。  外包装。中层包装放置在外部运 输包装中，并加用合适的缓冲材 料。外包装应能保护其内容物在 运输途中不受外界影响，如遭受物 理损伤。外包装最小总尺寸为 １０ｃｍ×１０ｃｍ。 每个完整的包裹通常需要有正确 的运输标记、标签，必要时还应附上相 应的装运单据。对 Ａ 类感染性物质 有专门的包装、标签和单据要求，对 Ｂ 类物质限制较小。 合装  对于这两个类别，都可以使用合 装。  “合装”这一术语是指将多个包组 合成一个单元，并由单个托运人发 送到同一目的地。当制冷剂用于 保护内容物时，合装件可包括绝热 容器或保温瓶。当采用合装时，外 包装上应标明所需的标记和标签， 并必须在合装件的最外层上重复 标明。这一要求适用于 Ａ 类和 Ｂ 类的感染性物质。合装件上还需 标上“合装”字样。  不能仿制合装件上的联合国规范 标识，这一点非常重要。 ２１８　 第三部分　 工具箱 工具箱 ４ 包装材料的再利用 运输包装可以重复使用。如果托运 人计划重新使用包裹，必须经过严格消 毒。在重复使用包装前，托运人必须确 保所有的标记和标签都符合实际装运的 货物。如果托运人计划装运空包装，则 所有不适用的标记和标签必须被移除或 覆盖。在空包装返回给托运人前，或发 送到别处，必须经过适当的消毒或灭菌， 以杜绝任何危害。如有标签或标记表明 含有感染性物质，应予以清除或覆盖。 制冷剂  在运输过程中，制冷剂可用于稳定 Ａ 类和 Ｂ类的感染性物质。  需要冷藏包装的感染性物质应符合 ２０１７—２０１８年感染性物质运输规章 指导中所述的相应要求。 培训  《危险货物条例》要求所有参与运输的 人员接受适当的培训。  对于 Ａ类感染性物质的运输，相关人员 必须按照示范要求接受训练。培训可以 包括参加批准的课程学习和通过考试。  对于 Ｂ类感染性物质的运输，要求向用 户提供关于包装使用的明确说明；这被 认为是对这些物质运输的充分“培 训”。然而，如果这些标本与其他危险 货物（如可燃液体、放射性物质、液化 气）一起运送，相关人员必须在正确的 运输过程方面接受训练。 工具箱 ４　 感染性物质的运输 ２１９　 工具箱 ４ 转运  托运人有责任确保所有待运感染性物 质进行正确的分类、包装、标签和记 录。  对感染性物质的高效运输和转运需要 发货人、承运人和收货人之间的良好 协调，以确保这些物质能安全运输，并 准时、完好地到达。这种协调有赖于 完善的沟通机制以及三方之间已建立 的良好工作关系。 感染性物质运输链的主要参与者 是：  发货人  承运人  收货人 各自责任和义务说明可从 ２０１７— ２０１８年感染性物质运输规章指导中找 到。 有关传染物质运输的更多信息：  Ｇｕｉｄａｎｃｅ ｏｎ ｒｅｇｕｌａｔｉｏｎｓ ｆｏｒ ｔｈｅ ｔｒａｎｓｐｏｒｔ ｏｆ ｉｎｆｅｃｔｉｏｕｓ ｓｕｂｓｔａｎｃｅｓ ２０１７２０１８，Ｗｏｒｌｄ Ｈｅａｌｔｈ Ｏｒｇａｎｉｚａｔｉｏｎ，２０１７： ｈｔｔｐ：／ ／ ｗｗｗ ｗｈｏ ｉｎｔ ／ ｉｈｒ ／ ｐｕｂｌｉｃａｔｉｏｎｓ ／ ＷＨＯＷＨＥＣＰＩ２０１７ ８ ／ ｅｎ ／ （邹艳 译） ２２０　 第三部分　 工具箱 工具箱 ５ 媒介控制 媒介传播疾病的预防以及疾病流行期间对生物媒介的控防措施 有些流行性疾病是通过节肢动物媒介（如蜱和昆虫）传播的。防止这些媒 介传播疾病（ＶＢＤｓ）的传播，应该采取措施如防止接触生物媒介和（或）消除或 减少生物媒介来保护人类。这些措施包括社区参与、个人保护和媒介控制操 作。 可用工具的推荐和使用可根据疾病的传播水平来调整，疾病的传播水平可 从散发到地方性流行以及最终到流行水平不等。通过预案和训练有素的员工 来协调不同级别所使用的不同工具。 建议各国制定预案来预防和控制媒介传播疾病，为从事媒介控制活动的员 工制定培训规划。区域协调也是必要的，因为大多数的媒介传播疾病会跨越国 境。 工具箱 ５　 媒介控制 ２２１　 工具箱 ５ 以下是本手册中易流行的媒介传播疾病列表。这些疾病通过不同的媒介传播，但 有共同的传播模式，即通过叮咬（在其他媒介传播疾病，如美洲锥虫病和斑疹伤寒，也 存在其他传播模式）： 　 　 这些不同的媒介具有不同的生态、行为、叮 咬时间和传播循环。媒介的生态学对预防和控 制这些疾病所采取的行动类型造成影响。在所 有情况下，有四个关键行动： ａ 个人防护工具：表 １ 概括了不同媒介的叮咬 行为以及现有的个人防护类型。 ｂ 媒介控制操作：由公共机构和 ／或私人机构 实施，并在社区层面开展行动。表 ２ 总结了 用于每种媒介的媒介控制工具。 ｃ 社区参与：这对暴发应对至关重要。 ｄ 沟通：不同行动的沟通是成功的重要组成部 分。公共卫生建议必须考虑社会和文化因 素。 ２２２　 第三部分　 工具箱 工具箱 ５ 表 １　 不同媒介类型的个人防护工具 媒介类型 （媒介传播疾病） 蜱 （克里米亚 刚果出血热病毒） 伊蚊 （黄热病病毒、寨卡病毒 和基孔肯雅热病毒） 跳蚤 （鼠疫） 媒介生态学 自然环境 森林，野生动物 家中，城市和农村 家中，野生动物 叮咬时间 白天 白天 全天 需要动物生命周期 是 否 是 ／否 个人防护工具 蚊帐 － ＋ － 驱避剂 ＋＋ ＋＋＋ ＋＋ 纱窗 ＋ ＋＋＋ － 杀虫剂喷洒 ＋ ＋＋＋ ＋＋ 电子设备 － ＋＋ － 消除家里的孳生地 － ＋＋＋ ＋＋＋ 　 　 在社区层面开展媒介控制活动，尽可能地消除媒介和幼虫，预防和控制媒介传播疾病的传播。媒介控制的实际操作要根据媒介类型和传播强度而定。  媒介控制策略应针对伊蚊的所有生命阶段（从卵到幼虫和成蚊）。  在控制措施中，杀虫剂的应用是最常见的，既可以用于携带媒介（如蜱、蚤）的动物，也可用于孳生地以杀死媒介的幼虫，最后可作为杀虫剂喷雾来消灭雌性成蚊。  其他媒介控制活动包括： － 环境措施：通过卫生管理、栖境管理和家畜管理来改善。 － 机械措施：诱捕媒介。 － 生物工具：使用天敌和生物杀灭蚊子的幼虫。 － 其他化学物质：如使用天然激素的模拟物来阻止昆虫发育。 － 基因修饰的生物带来了新一代媒介控制产品（如沃巴体细菌）。 工具箱 ５　 媒介控制 ２２３　 工具箱 ５ 表 ２　 不同媒介类型的媒介控制工具 媒介类型（媒介传播疾病） 蜱（克里米亚刚果出血热病毒） 伊蚊（黄热病病毒、寨卡病毒和基孔肯雅热病毒） 跳蚤（鼠疫） 地方性流行状况 幼虫杀虫剂 ＋ ＋＋＋ ＋＋＋ 成虫杀虫剂 ＋ ＋ ＋＋＋ 动物喷雾 是 否 是 物理消除所有孳生地（公共场所和家庭） ＋ ＋＋＋ ＋＋＋ 机械诱捕 ＋ ＋ ＋＋ 环境措施 ＋ ＋＋ ＋＋＋ 流行状况 幼虫杀虫剂 ＋＋＋ ＋＋＋ ＋＋＋ 成虫杀虫剂 ＋＋＋ ＋＋＋ ＋＋＋ 动物喷雾 是 否 是 物理消除所有孳生地（公共场所和家庭） ＋ ＋＋＋ ＋＋＋ 机械诱捕 ＋ ＋＋＋ ＋＋＋ 环境措施 ＋ ＋＋＋ ＋＋＋  媒介控制工具可以通过综合媒介管理（Ｉｎｔｅｇｒａｔｅｄ Ｖｅｃｔｏｒ Ｍａｎａｇｅｍｅｎｔ，ＩＶＭ）方法（世界卫生组织，２０１２）单独或组合使用１。媒介控制活动的开展、效率和结果需要监测和评价，但是，这种监测和评价的方法无论是在媒介种群水平上还是在疾病传播方面往往都是缺乏的。  蚊子监测是媒介控制的一部分，有助于提高控制蚊子种群和预防疾病决策的及时性。幼虫和成虫的媒介种群都是监测的对象。应密切合作来收集和分析流行病学和昆虫学监测 ／指标。监测包括： － 蚊虫密度和地理分布。 － 与人类宿主接触。 － 控制工具的有效性（如对杀虫剂的耐药性）。 １ ＷＨＯ，Ｈａｎｄｂｏｏｋ ｆｏｒ ｉｎｔｅｇｒａｔｅｄ ｖｅｃｔｏｒ Ｍａｎａｇｅｍｅｎｔ， ２０１２ ｈｔｔｐ：／ ／ ａｐｐｓ． ｗｈｏ． ｉｎｔ ／ ｉｒｉｓ ／ ｂｉｔｓｔｒｅａｍ ／ １０６６５ ／ ４４７６８ ／ １ ／ ９７８９２４１５０２８０１＿ｅｎｇ． ｐｄｆ ２２４　 第三部分　 工具箱 工具箱 ５ 基于媒介生态学和控制方案的疾病 特异性方法 　 　 克里米亚刚果出血热病毒通过边缘璃眼 蜱传播。  这些蜱从六足幼虫阶段到成虫阶段的所有阶 段都以吸血为生，以完成它们的生长发育和 产卵。除了作为传播媒介外，蜱还是克里米 亚刚果出血热病毒的宿主。  幼虫期通常以小动物为食，成虫阶段以较大 的动物为食，如鹿、羊和牛。蜱不具有宿主偏 好，而人类被认为是偶然宿主。克里米亚刚 果出血热病毒进入动物种群循环而不引起疾 病（除鸵鸟外），人类被认为是终宿主。  在有传播风险的地区，动物可感染克里米亚 刚果出血热病毒，故主要目标是告知公众和 当地社区如何改善行为，减少疾病传播。 － 这些行为包括防止与感染病毒的动物有血 液接触（如屠宰动物）、防止蜱叮咬、防止 在家庭治疗或葬礼期间的传播。 关键行为干预 动物环境  减少环境中的蜱，减少蜱对动物的侵扰，或减少马厩 ／谷仓里的蜱侵扰。 媒介蜱众多，分布广泛，使用杀螨剂（旨在杀死蜱的化学品）控制蜱虫仅 是管理良好的牲畜养殖场的现实选择  在进入屠宰场前对动物实施检疫，或者在屠宰前 ２ 周用杀虫剂对反刍动 物进行常规处理。这项措施可降低动物在屠宰过程中发生病毒血症的 风险  在屠宰场或家中屠宰动物时，请穿戴个人防护用品（口罩、手套和防护 服），以防止皮肤接触受感染的动物组织或血液 家庭环境  穿防护服（长袖衣服、长裤等）和浅色衣服（使之容易发现衣服上的蜱）  在蜱活跃期（春季到秋季），避免进入蜱多的区域  定期检查衣服和皮肤上是否有蜱  将驱虫剂用于皮肤（如 ＤＥＥＴ）和衣物（如氯菊酯）上  安全地去除皮肤上的蜱 卫生保健机构  有蜱叮咬史或与克里米亚刚果出血热病毒患者接触后应及早就医  在治疗患者时，避免无保护地直接接触血液或体液  经常用肥皂和清洁水洗手  组织安全和有尊严的葬礼 工具箱 ５　 媒介控制 ２２５　 工具箱 ５  目前的媒介控制措施并不完全令人满意： － 化学方法能使蜱产生抗药性、污染食物和环境。此外，化学方法控制蜱仅仅适用 于管理良好和资源充足的家畜养殖机构，而这些机构在大多数受影响国家是罕 见的。 － 物理方法（如过度放牧、草地焚烧）对环境有重要的负面影响。 － 生物学方法（如使用激素和生长调节剂、使用捕食性天敌、细菌、线虫和真菌）尚 未完全证明有效。  疫苗接种被认为是控制蜱侵扰的一种有前途的选择方案。一种能有效预防蜱动 物蜱循环的动物疫苗可以减少璃眼蜱的数量，减少动物中克里米亚刚果出血热的 流行，从而可减少人类暴露，是一种有成本效益的克里米亚刚果出血热病毒预防 措施。  病毒不能在人之间传播，而是偶尔感染人类。病毒需要扩增宿主（家畜和野生动 物）提供血液以支持蜱类生长。 黄热病病毒、寨卡病毒和基孔肯雅热病毒的流行是通过埃及伊蚊和白纹伊蚊传播 的。伊蚊也传播登革热病毒。  虽然这些病毒在森林环境中可以由其他蚊子传播，并可能引起人畜共患病，但只有 伊蚊才会导致流行，因为它们已经适应了城市环境，并且可以在城市和分散的农村 地区的室内外以及其他人类住所中有积水的容器中产卵。  幼虫的发育时间可以非常短，不到 １ 周，因此如果未采取任何媒介或幼虫控制措 施，且条件（温度和水）合适，蚊子数量可呈指数增长。  因此，强烈建议在私人和公共场所通过物理方法消除所有孳生地，并对不能消除的 孳生地使用杀幼虫剂，以持续控制这些蚊子。苏云金芽孢杆菌以色列变种毒素无 耐药性和环境污染，因此推荐使用苏云金芽孢杆菌以色列变种毒素这一生物杀幼 虫剂。 ２２６　 第三部分　 工具箱 工具箱 ５  在流行期间，推荐使用保护人类免遭蚊子叮咬的所有工具（表 １），以及所有杀灭 成蚊的现有工具，同时强化消除孳生地，使用杀幼虫剂和杀成蚊剂２。 － 对产品的有效性进行监测时需要事先检测耐药性，必要时必须制定综合性耐药 性管理计划。 － 必须每天喷洒杀成蚊剂，直到蚊子密度减少到必须达到的布雷图指数（ＢＩ）（每 １００户中的阳性容器数）１以下３。 － 社区参与也是控制埃及伊蚊和白纹伊蚊的重要组成部分。社区可以采取的一 些主要行动包括通过参与性行动，如建议在工作场所和学校进行个人保护、消 除孳生地、安装纱窗、全面监测环境，使之不利于蚊子生长繁殖。  埃及伊蚊和白纹伊蚊是城市虫媒病毒的主要媒介，对这些伊蚊的控制因许多因 素（包括计划外的城市化和资源匮乏）的影响而没有达到预期的效果。然而，这 些工具在许多情况下是唯一可用的，如果应用得当，可以控制传播。 ２ ＷＨＯ，Ｐｅｓｔｉｃｉｄｅ ａｎｄ ｔｈｅｉｒ ａｐｐｌｉｃａｔｉｏｎ ｆｏｒ ｔｈｅ ｃｏｎｔｒｏｌ ｏｆ ｖｅｃｔｏｒｓ ａｎｄ ｐｅｓｔｓ ｏｆ ｐｕｂｌｉｃ ｈｅａｌｔｈ ｉｍｐｏｒｔａｎｃｅ，２００６． ｈｔｔｐ：／ ／ ａｐｐｓ． ｗｈｏ． ｉｎｔ ／ ｉｒｉｓ ／ ｂｉｔｓｔｒｅａｍ ／ １０６６５ ／ ６９２２３ ／ １ ／ ＷＨＯ＿ＣＤＳ＿ＮＴＤ＿ＷＨＯＰＥＳ＿ＧＣＤＰＰ＿２００６． １＿ｅｎｇ． ｐｄｆ ３ Ｂｏｗｍａｎ ＬＲ，Ｒｕｎｇｅ－Ｒａｎｚｉｎｇｅｒ Ｓ ａｎｄ ＭｃＣａｌｌ ＰＪ． Ａｓｓｅｓｓｉｎｇ ｔｈｅ Ｒｅｌａｔｉｏｎｓｈｉｐ ｂｅｔｗｅｅｎ Ｖｅｃｔｏｒ Ｉｎｄｉｃｅｓ ａｎｄ Ｄｅｎｇｕｅ Ｔｒａｎｓｍｉｓｓｉｏｎ： Ａ Ｓｙｓｔｅｍａｔｉｃ Ｒｅｖｉｅｗ ｏｆ ｔｈｅ Ｅｖｉｄｅｎｃｅ． ＰＬｏＳ Ｎｅｇｌ Ｔｒｏｐ Ｄｉｓ． ２０１４ Ｍａｙ；８（５）：ｅ２８４８． ｄｏｉ：１０． １３７１／ ｊｏｕｒｎａｌ． ｐｎｔｄ． ０００２８４８ 　 　 鼠疫　 几乎在世界所有地区都可传播到 哺乳动物，特别是啮齿动物。  鼠疫流行通过两种主要传播方式影响人类。 在流行初期，啮齿动物通过蚤作为媒介感染疾 病，然后蚤离开死亡的啮齿动物，并转移到人 类身上。在这个阶段，鼠疫被称为腺鼠疫，因 为腹股沟淋巴结脓肿是主要临床症状。随着 细菌传播到肺，人可以直接将鼠疫杆菌传染给 其他人，这时的鼠疫称为肺鼠疫。  蚤具有宿主特异性，动物跳蚤叮咬人是偶然的。  改善卫生设施和鼠类控制是预防人类鼠疫 的最佳做法。在报告鼠疫病例时，控制措 施必须首先针对蚤，其次是啮齿动物，因为 使用灭鼠剂可能导致副作用，会导致蚤离 开死鼠，并转移到人身上。  根据环境条件，可以推荐大范围使用诱捕 老鼠的捕鼠器。  也可采取环境措施驱除鼠类以及在鼠类出 没的地方灭鼠。  社区参与对于协调鼠类控制活动、废物管 理和家庭环境也非常重要。 （邹艳 译） 致谢 ２２７　 致谢 这本流行控制手册是世界卫生组织卫生应急规划部（Ｈｅａｌｔｈ Ｅｍｅｒｇｅｎｃｉｅｓ Ｐｒｏ ｇｒａｍｍｅ，ＷＨＥ），特别是在总部、地区和国家层面的许多感染危害管理（Ｉｎｆｅｃｔｉｏｕｓ Ｈａｚ ａｒｄ Ｍａｎａｇｅｍｅｎｔ，ＩＨＭ）专家集体奉献的成果。此外，还有世界卫生组织内的其他部门 参加编写： 热带疾病研究和培训特别规划（Ｒｅｓｅａｒｃｈ ａｎｄ Ｔｒａｉｎｉｎｇ ｉｎ Ｔｒｏｐｉｃａｌ Ｄｉｓｅａｓｅｓ，ＴＤＲ）、 卫生应急信息和风险评估（Ｈｅａｌｔｈ Ｅｍｅｒｇｅｎｃｙ Ｉｎｆｏｒｍａｔｉｏｎ ＆ Ｒｉｓｋ Ａｓｓｅｓｓｍｅｎｔ，ＨＩＭ）、应 急管理 （Ｅｍｅｒｇｅｎｃｙ Ｏｐｅｒａｔｉｏｎｓ，ＥＭＯ）、国家卫生应急准备和世界卫生条例（Ｃｏｕｎｔｒｙ Ｈｅａｌｔｈ Ｅｍｅｒｇｅｎｃｙ Ｐｒｅｐａｒｅｄｎｅｓｓ ＆ ＩＨＲ，ＣＰＩ）、信息证据与研究 （Ｉｎｆｏｒｍａｔｉｏｎ Ｅｖｉｄｅｎｃｅ ａｎｄ Ｒｅｓｅａｒｃｈ，ＩＥＲ）、脊髓灰质炎根除（Ｐｏｌｉｏ Ｅｒａｄｉｃａｔｉｏｎ，ＰＯＬ）、被忽视的热带病（Ｎｅｇ ｌｅｃｔｅｄ Ｔｒｏｐｉｃａｌ Ｄｉｓｅａｓｅｓ，ＮＴＤ）控制等部门。 ２２８　 作者和贡献者 　 　 世界卫生组织感谢下列人员为本书编写、 审阅和出版所作的贡献： Ａｙｓｈｅｓｈｉｍ Ａｄｅｍｅ，Ｈｅｒｎａｎｄｏ Ａｇｕｄｅｌｏ，Ｋａｔｅ Ａｌｂｅｒｔｉ，Ｓｙｌｖａｉｎ Ａｌｄｉｇｈｉｅｒｉ，Ｙａｈａｙａ Ａｌｉ Ａｈｍｅｄ，Ｓｏ ｐｈｉｅ Ａｌｌａｉｎ Ｉｏｏｓ，Ｙｏｋｏｕｉｄｅ Ａｌｌａｒａｎｇａｒ，Ｉｎａｃｉｏ Ａｌ ｖａｒｅｎｇａ，Ｊａｖｉｅｒ Ａｒａｍｂｕｒｕ，Ｒｉｃｈｅｌｏｔ Ａｙａｎｇｍａ Ｍｏｕ ｋｏ，ＪｅａｎＣｈｒｉｓｔｏｐｈｅ Ａｚｅ，Ｆｒｅｄｄｙ Ｂａｎｚａ Ｍｕｔｏｋａ， Ｃｅｃｉｌｅ Ｂａｒｂｏｕ ｄｅｓ Ｃｏｕｒｉｅｒｅｓ，Ｍａｄｙ Ｂａ，Ｍａｕｒｉｚｉｏ Ｂａｒｂｅｓｃｈｉ，Ｐｈｉｌｉｐｐｅ Ｂａｒｂｏｚａ，Ｊｅｎｎｉｆｅｒ Ｂａｒｒａｇａｎ， Ａｈｍａｄｏｕ Ｂａｒｒｙ，Ｒｏｄｒｉｇｕｅ Ｂａｒｒｙ，Ｂｉｅｎｖｅｎｕ Ｂａｒｕａｎｉ Ｎｇｏｙ，Ｍａｒｉｅ Ｒｏｓｅｌｉｎｅ Ｄａｒｎｙｃｋａ Ｂｅｌｉｚａｉｒｅ，Ｌｕｉｓａ Ｂｅｌｌｏｎｉ，Ｓｉｍｅｏｎ Ｂｅｎｎｅｔｔ，Ｊｕｓｔｕｓ Ｂｅｎｚｌｅｒ，Ｉｓａｂｅｌｌｅ Ｂｅｒｇｅｒｉ，Ｅｒｉｃ Ｂｅｒｔｈｅｒａｔ，Ｔｅｒｒｙ Ｂｅｓｓｅｌａａｒ，Ａｐｈａｌｕｃｋ Ｂｈａｔｉａｓｅｖｉ，Ｖｉｖｉａｎｅ Ｂｉａｎｃｏ，Ｂｏｎｋｏｕｎｇｏｕ Ｂｏｕｋａｒé， Ａｎｎａ Ｂｏｗｍａｎ，Ｒｉｃｋ Ｂｒｅｎｎａｎ，Ｓｙｌｖｉｅ Ｂｒｉａｎｄ， Ｃａｒｏｌｉｎｅ Ｂｒｏｗｎ，Ｇｉｓèｌｅ Ｂｗｅｎｄｅ Ｋａｓｕｎｇｉ，Ｊｏｒｇｅ Ｃａ ｓｔｉｌｌａ，Ａｎｄｅｒｓｅｎ Ｃｈｉｍｕｓｏｒｏ，Ｓｔｅｌｌａ Ｃｈｕｎｇｏｎｇ，Ｌａｕ ｒｅｎｃｅ Ｃｉｂｒｅｌｕｓ，Ｉａｎ Ｃｌａｒｋｅ，Ｐｅｔｅｒ Ｃｌｅｍｅｎｔ，Ｒｕｄｉ Ｃｏｎｉｎｘ，Ａｌｅｊａｎｄｒｏ Ｃｏｓｔａ，Ａｎａ Ｐａｕｌａ Ｃｏｕｔｉｎｈｏ Ｒｅ ｈｓｅ，Ｆｅｒｎａｎｄｏ Ｄａ Ｓｉｌｖｅｉｒａ，Ａｒｓｅｎｅ Ｄａｉｚｏ，Ｆａｒａｈ Ｄａｋｈｌａｌｌａｈ，Ｌｕｃｉａ Ｄｅｌｌ Ａｍｕｒａ，Ｇｈｙｌｌａｉｎ Ｄｅｍｂａ Ｌｕｂａｍｂｏ，Ｊａｎｅｔ Ｄｉａｚ，Ｈｅｉｄｉ Ｄｉｖｅｃｈａ，Ｄｅｖｉｋａ Ｄｉｘｉｔ， Ｍａｍｏｕｄｏｕ Ｈａｒｏｕｎａ Ｄｊｉｎｇａｒｅｙ，Ｓａｂｅｌｏ Ｄｌａｍｉｎｉ， Ｅｍｍａｎｕｅｌ Ｄｏｕｂａ，Ｐａｔｒｉｃｋ Ｄｒｕｒｙ，Ｋａｒａ Ｄｕｒｓｋｉ， Ａｍｇａｄ Ａｂｄａｌｌａ Ｅｌｋｈｏｌｙ，Ｎｅｄｒｅｔ Ｅｍｉｒｏｇｌｕ，Ｒｏｃíｏ Ｅｓｃｏｂａｒ，Ａｎｔｈｏｎｙ Ｅｓｈｏｆｏｎｉｅ，Ｓｏｃé Ｆａｌｌ，Ａｎａ Ｆｅｒ ｎａｎｄｅｓ，Ｋａｔｙａ Ｆｅｒｎａｎｄｅｚ，Ｊｏｈａｎｎａ Ｆｉｈｍａｎ，Ｊｕｌｉａ Ｆｉｔｚｎｅｒ，Ｐｉｅｒｒｅ Ｆｏｒｍｅｎｔｙ，Ｆｌｏｒｅｎｃｅ Ｆｏｕｑｕｅ，Ｍａｒａ Ｆｒｉｇｏ，Ｆｌｏｒｅｎｃｅ Ｆｕｃｈｓ，Ｃａｒｏｌｉｎｅ Ｆｕｈｒｅｒ，Ｃｈｒｉｓｔｉａｎ Ｆｕｓｔｅｒ，Ｇａｙａ Ｇａｍｈｅｗａｇｅ，Ｅｒｉｋａ Ｇａｒｃｉａ，Ｓａｎｄｒａ Ｇａｒｎｉｅｒ，Ｓｅｍｅｒｅ Ｇｅｂｒｅｇｉｏｒｇｉｓ，Ｙｏｈａｎｎｅｓ Ｇｈｅｂｒａｔ， Ｃａｒｏｌｉｎａ Ｇｏｍｅｓ，Ｐｈｉｌｉｐ Ｇｏｕｌｄ，Ｐｅｔｅｒ Ｇｒａａｆｆ，Ｍｉ ｃｈａｅｌ Ｇｒｉｆｆｉｎ，ＭａｒｙＡｎｎｅ Ｇｒｏｅｐｅ，Ａｓｐｅｎ Ｈａｍ ｍｏｎｄ，Ａｌｅｘａｎｄｒａ Ｈｉｌｌ，Ｓｉｄｄｈｉｖｉｎａｙａｋ Ｈｉｒｖｅ，Ｄａｎｉｅｌ Ｈｏｕｇｅｎｄｏｂｌｅｒ，Ｋｈｅｌｉｆｉ Ｈｏｕｒｉａ，Ｓｔéｐｈａｎｅ Ｈｕｇｏｎｎｅｔ， Ｐｏｏｎａｍ Ｈｕｒｉａ，Ａｎｎｅ Ｈｕｖｏｓ，Ｂｅｎｉｄｏ Ｉｍｐｏｕｍａ， Ｃｈｒｉｓｔｉａｎ Ｉｔａｍａ Ｍａｙｉｋｕｌｉ，Ｙｕｒｉｅ Ｉｚａｗａ，Ａｌｐｈａ Ｊａｌ ｌｏｗ，Ｓａｎｄｒｉｎｅ Ｊｏｕｃｌａ，Ｈｉｌａｒｙ Ｋａｇｕｍｅ Ｎｊｅｎｇｅ，Ａｒ ｎａｕｄ Ｋａｈｎ，Ｌｉｎｇａｗａｋｏ Ｋａｌｉｎｄｅ Ｍａｎｇａｃｈｉ，Ｅｂｂａ Ｋａｌｏｎｄｏ，Ｍａｓａｙａ Ｋａｔｏ，Ｅｒｉｎ Ｋｅｎｎｅｙ，Ｊｏｙｃｅ Ｋｅｒｕｂｏ Ｏｎｓｏｎｇｏ，Ａｓｈｅｅｎａ Ｋｈａｌａｋｄｉｎａ，Ｍｏａｋｏｆｈｉ Ｋｅｎｔｓｅ， Ｊａｍｅｓ Ｋｏｊｏ Ｔｅｐｒｅｙ，Ｄａｖｉ Ｋｏｋｏｕ Ｍａｗｕｌé，Ｉｎｎｏｃｅｎｔ Ｋｏｍａｃｋｅｃｈ，Ａｌｅｘａｎｄｒａ Ｋｏｎｔｉｃ，Ｔｈｏｍａｓ ｄ’Ａｑｕｉｎ Ｋｏｙａｚｅｇｂｅ，Ｅｖｅ Ｌａｃｋｒｉｔｚ，Ａｎｄｅｒｓｓｏｎ Ｌａｔｔ，Ｓｈａｒｍｉｌａ ＬａｒｅｅｆＪａｈ，Ａｎａｓ Ｌｅｇａｎｄ，Ｄｏｍｉｎｉｑｕｅ Ｌｅｇｒｏｓ，Ｅｌｌｅｎ Ｌｅｒｏｙ，Ａｉｌａｎ Ｌｉ，Ｆｒａｎｃｏｉｓ Ｌｉｂａｍａ，Ｍａｊａ Ｌｉｅｖｒｅ， Ｃｌｅｍｅｎｔ Ｌｉｎｇａｎｉ，Ｊｅｎｎｉｆｅｒ Ｌｉｎｋｉｎｓ，Ｄａｎｉｅｌ Ｌｕｃｅｙ， Ａｎｄｒé Ｌｕｋｕｓａ，Ｎｕｈａ Ｍａｈｍｏｕｄ，Ｋｅｖｉｎ Ｍａｋａｄｚａｎｇｅ， Ｍａｍｕｎｕｒ Ｍａｌｉｋ，Ａｗａｎｄｈａ Ｍａｍａｈｉｔ，Ｋｏｒｉａ Ｍａｎｋａｍ ｐａ，Ｓｔｅｐｈｅｎ Ｍａｐｈｏｓａ，Ｒｉｍａ Ｍａｒｒｏｕｃｈ，Ｃｈｒｉｓｔｉａｎ Ｍａｓｓｉｄｉ，Ｈｕｍｐｈｒｅｙｓ Ｍａｓｕｋｕ，Ｍａｒｇａｕｘ Ｍａｔｈｉｓ，Ｐｅ ｔｒｕｓ Ｍｈａｔａ，Ｒｕｈａｎａ Ｍｉｒｉｎｄｉ Ｂｉｓｉｍｗａ，Ａｎｎ Ｍｏｅｎ， Ｖｉｔａｌ Ｍｏｎｄｏｎｇｅ Ｍａｋｕｍａ，Ｏｌｉｖｅｒ Ｍｏｒｇａｎ，Ｓｙｌｖｉｅ Ｍｏｒｔｉｅｒ，Ａｍａｄｏｕ Ｍｏｕｃｔａｒ Ｄｉａｌｌｏ，Ｍｉｒｅｉｌｌｅ Ｆｌｏｒｅ Ｍｏｕｅｌｅ，Ａｈａｍａｄａ Ｍｓａ Ｍｌｉｖａ，Ｋｅｌｉａｓ Ｍｓｙｍｂａｏｚａ， Ｍａｒｔｉｎ Ｍｕｉｔａ，Ｍａｒｊｏｒｉｅ Ｍｕｐａｎｄａｒｅ，Ｒｏｂｅｒｔ Ｍｕｓｏ ｋｅ，Ａｂｒａｈａｍｓ Ｍｗａｎａｍｗｅｎｇｅ，Ｄｈａｍａｒｉ Ｎａｉｄｏｏ，Ｍｉ ｃｈｅｌ Ｎ’ｄａ Ｋｏｎａｎ Ｙａｏ，Ｍｉｒｉａｍ Ｎａｎｙｕｎｇａ，Ｊéｒｍｅ Ｎｄａｒｕｈｕｔｓｅ，Ｃｈａｒｌｏｔｔｅ Ｆａｔｙ Ｎｄｉａｙｅ，ＪｅａｎＢｏｓｃｏ Ｎｄｉｈｏｋｕｂｗａｙｏ，Ｌａｎｄｒｙ Ｎｄｒｉｋｏ Ｍａｙｉｇａｎｅ，Ｂｌａ Ｆｒａｎｏｉｓ Ｎｇｕｅｓｓａｎ，Ｔｉｍ Ｎｇｕｙｅｎ，Ｄｏｒｉｔ Ｎｉｔｚａｎ，Ｌｉｏ ｎｅｌ Ｎｉｚｉｇａｍａ，Ｉａｎ Ｎｏｒｔｏｎ，Ｄｅｏ Ｎｓｈｉｍｉｒｉｍａｎａ，Ａｌｅｘ Ｎｔａｌｅ Ｇａｓａｓｉｒａ，Ｉｎｎｏｃｅｎｔ Ｎｚｅｙｉｍａｎａ，Ｒｏｄｅｒｉｃｏ Ｏｆｒｉｎ，Ｓａｌ ｌｙＡｎｎ Ｏｈｅｎｅ，Ｉｆｅａｎｙｉ Ｏｋｕｄｏ，Ｂａｂａｔｕｎｄｅ Ｏｌｏｗｏｋｕｒｅ，Ｄａ ｖｉｄ Ｏｌｓｏｎ，Ｃａｔｈｅｒｉｎｅ Ｏｓｗａｌｄ，Ｈｅａｔｈｅｒ Ｐａｐｏｗｉｔｚ，Ｃｙｒ Ｐａｓ ｓｉＬｏｕａｍｂａ，Ｓｃｏｔｔ Ｐｅｎｄｅｒｇａｓｔ，Ｗｉｌｌｉａｍ Ａｕｇｕｓｔｏ Ｐｅｒｅａ Ｃａｒｏ，Ａｎｎｅ Ｐｅｒｒｏｃｈｅａｕ，Ａｒｔｕｒｏ Ｐｅｓｉｇａｎ，Ｌｏｒｅｎｚｏ Ｐｅｚｚｏｌｉ， Ｍａｒｃｉａ Ｐｏｏｌｅ，Ｊｕｋｋａ Ｔａｐａｎｉ Ｐｕｋｋｉｌａ，Ａｒｔｈｕｒ Ｒａｋｏｔｏｎｊａｎａ ｂｅｌｏ Ｌａｍｉｎａ，Ｏｔｉｍ Ｐａｔｒｉｃｋ Ｃｏｓｓｙ Ｒａｍａｄａｎ，Ｂａｒｄａｎ Ｊｕｎｇ Ｒａｎａ，Ｊｏｏ Ｒａｎｇｅｌ Ｄｅ Ａｌｍｅｉｄａ，Ｐｅｔｅｒ Ｒｅｈｓｅ，Ｂｅｒｔｒａｎｄ Ｒｅｎａｕｄ，Ｔａｔｉａｎａ Ｒｅｓｎｉｋｏｆｆ，Ａｍｅｌｉｅ Ｒｉｏｕｘ，Ｇｕｅｎａｅｌ Ｒｏｄｉ ｅｒ，Ｊｏｓｅ Ｒｏｖｉｒａ Ｖｉｌａｐｌａｎａ，Ｏｌｉｖｉｅｒ Ｒｏｎｖｅａｕｘ，Ａｎｄｒé Ｒｕ ｓａｎｇａｎｗａ，Ｆｌｏｒｅｎｃｅ Ｒｕｓｃｉａｎｏ，Ｍｉｃｈａｅｌ Ｒｙａｎ，Ｍａｓｓａｍｂｏｕ Ｓａｃｋｏ，Ｇｒａｃｅ Ｓａｇｕｔｉ，Ｎｉａｎｇ Ｓａｉｄｏｕ Ｄｏｒｏ，Ｍｏｈａｍｅｄ Ｓａｉｎ ｄａ，Ｐｅｔｅｒ Ｓａｌａｍａ，Ｒｏｓｉｎｅ Ｓａｍａ Ｋａｎｅｍｂｅ，Ｇｉｎａ Ｓａｍａａｎ， Ｍａｇｄｉ Ｓａｍａａｎ，Ｒａｖｉ Ｓａｎｔｈａｎａ Ｇｏｐａｌａ Ｋｒｉｓｈｎａｎ，Ｎｉｋｋｉ Ｓｈｉｎｄｏ，Ｖéｒｏｎｉｑｕｅ Ｓｉｃｉｌｉａ，Ｒａｐｈａｅｌ Ｓｌａｔｔｅｒｙ，Ｃａｔｈｅｒｉｎｅ Ｓｍａｌｌｗｏｏｄ，Ｖｉｎｃｅｎｔ Ｓｏｄｊｉｎｏｕ，Ｐｅｔｅｒ Ｓｏｎｇｏｌｏ，Ｍａｒｙ Ｓｔｅ ｐｈｅｎ，Ｏｌｉｖｅｒ Ｇｅｒｄ Ｓｔｕｃｋｅ，Ｕｔｅ Ｓｔｒｈｅｒ，Ａｋａ Ｔａｎｏ Ｂｉａｎ， Ｉｓｒａｅｌ Ｔａｒｅｋｅ，Ｊｏａｎｎａ Ｔｅｍｐｏｗｓｋｉ，Ｍｉｃｈｅｌ Ｔｈｉｅｒｅｎ，Ｄｅｓｔａ Ｔｉｒｕｎｅｈ，Ｃｉｒｏ Ｕｇａｒｔｅ Ｃａｓａｆｒａｎｃａ，Ｈｅｉｎｉ Ｕｔｕｎｅｎ，Ｍａｒｉａ Ｖａｎ Ｋｅｒｋｈｏｖｅ，Ｋａｔｅｌｉｊｎ Ｖａｎｄｅｍａｅｌｅ，Ｒｅｉｎｈｉｌｄｅ Ｖａｎ Ｄｅ Ｗｅｅｒｄｔ，Ｒａｍａｎ Ｖｅｌａｙｕｄｈａｎ，Ｓｉｒｅｎｄａ Ｖｏｎｇ，Ｃｈｒｉｓｔèｌｅ Ｗａｎｔｚ，Ｓｅｒｇｉｏ Ｙａｃｔａｙｏ，Ｓａｎｙａｎｇ Ｙａｙａ，Ｄａｎｉｅｌ Ｙｏｔａ，Ｚｅ ｂｕｌｏｎ Ｙｏｔｉ，Ｗｅｎｑｉｎｇ Ｚｈａｎｇ，Ｕｒｓｕｌａ Ｚｈａｏ，Ｗｅｉｇｏｎｇ Ｚｈｏｕ． 本手册的编写工作由感染危害管理部主任 Ｓｙｌｖｉｅ Ｂｒｉａｎｄ及 Ｍａｒｇａｕｘ Ｍａｔｈｉｓ 领导，并与上述专家合作完 成。 编辑：Ｔｈｏｍｓｏｎ Ｐｒｅｎｔｉｃｅ 封面和版式设计：Ｖｉｖｉａｎ Ｌｅｅ 插图：Ｓａｍ Ｂｒａｄｄ （Ｄｒａｗｉｎｇ Ｃｈａｎｇｅ）