Eastern Mediterranean Health Journal [2013; Vol.19, Issue Supp.1]

Contents Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale Volume 19 Supplement 1 / Supplément 1 2013 شرع عساتلا دلجلما 1 فياضلإا ددعلا V olum e 19 Supplem ent 1 2013 Coronavirus particles With the emergence of a novel coronavirus in 2012, WHO convened a meeting of experts in January 2013 to address this new public health threat. This supplement presents papers arising out of the meeting. Editorial Novel coronavirus infection: time to stay ahead of the curve ..................................................................................S3 Perspective Emergence of novel coronavirus: global context ......................................................................................................S5 Country experiences Saudi Arabia and the emergence of a novel coronavirus .........................................................................................S7 Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation ........................................................................................................................................ S12 Reviews The early response to a novel coronavirus in the Middle East ................................................................................ S19 Novel coronavirus: the challenge of communicating about a virus which one knows little about ......................S26 Novel coronavirus infection in the Eastern Mediterranean Region: time to act .....................................................S31 Infection prevention and control measures for acute respiratory infections in healthcare settings: an update ....................................................................................................................................................S39 Emerging respiratory and novel coronavirus 2012 infections and mass gatherings ...............................................S48 Short communications Enhanced surveillance and investigation of coronavirus: what is required? ............................................................ S55 Public health investigations required for protecting the population against novel coronaviruses ...................... S61 Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 .............................................................................................................................. S68 Supplement on Novel Coronavirus Guest Editors Ziad A Memish, MD Jaouad Mahjour, MD, MPH Cover 19 Supplement.indd 1 5/16/2013 1:30:57 PM Subscriptions and Distribution Enquiries regarding subscriptions and distribution of the print edition of EMHJ should be addressed to: Printing and Marketing of Publications at: email: pam@emro.who.int; tel: (+202) 2276 5000; fax: (+202) 2670 2492 or 2670 2494 Permissions Requests for permission to reproduce or translate articles, whether for sale or non-commercial distribution should be addressed to EMHJ at: emhj@emro.who.int Correspondence Editor-in-chief EMHJ WHO Regional Office for the Eastern Mediterranean P.O. Box 7608 Nasr City, Cairo 11371 Egypt Tel: (+202) 2276 5000 Fax: (+202) 2670 2492/(+202) 2670 2494 Email: emhj@emro.who.int EASTERN MEDITERRANEAN HEALTH JOURNAL IS the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas, con‑ cepts, epidemiological data, research findings and other information, with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession, medical and other health educational institutes, interested NGOs, WHO Col‑ laborating Centres and individuals within and outside the Region. LA REVUE DE SANTÉ DE LA MÉDITERRANÉE ORIENTALE EST une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine des ser‑vices de santé ainsi qu’à l’échange d’idées, de concepts, de données épidémiologiques, de résultats de recherches et d’autres informations, se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé, aux membres des instituts médicaux et autres instituts de formation médico‑sanitaire, aux ONG, Centres collabora‑ teurs de l’OMS et personnes concernés au sein et hors de la Région. EMHJ is a trilingual, peer reviewed, open access journal and the full contents are freely available at its website: http://www/emro.who.int/emhj.htm EMHJ information for Authors is available at its website: http://www.emro.who.int/emh-journal/authors/ EMHJ is abstracted/indexed in the Index Medicus and MEDLINE (Medical Literature Analysis and Retrieval Systems on Line) and the ExtraMed‑Full text on CD‑ROM, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), CAB International, Lexis Nexis, Scopus and the Index Medicus for the WHO Eastern Mediterranean Region (IMEMR). ©World Health Organization 2013 All rights reserved Disclaimer The designations employed and the presentation of the material in this publication 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. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The named authors alone are responsible for the views expressed in this publication. ISSN 1020‑3397 Cover designed by Diana Tawadros Cover photograph: Dr Linda Stannard, UCT/Science Photo Library Internal layout designed by Emad Marji and Diana Tawadros Printed by WHO Regional Office for the Eastern Mediterranean ميدقتل برنم ىهو .ةيلماعلا ةحصلا ةمظنمب طسوتلما قشرل ىميلقلإا بتكلما نع ردصت ىتلا ةيمسرلا ةلجلما ىه ةيئابولا تايطعلماو ميهافلماو ءارلآا لدابتلو ،اله جيوترلاو ةيحصلا تامدلخا فى ةديدلجا تاردابلماو تاسايسلا لك لىإ ةهجوم ىهو .طسوتلما قشر ميلقإب اهنم قلعتي ام ةصاخو ،تامولعلما نم كلذ يرغو ثاحبلأا جئاتنو زكارلماو ،ةينعلما ةيموكلحا يرغ تماظنلما اذكو ،ةيميلعتلا دهاعلما رئاسو ةيبطلا تايلكلاو ،ةيحصلا نهلما ءاضعأ .هجراخو ميلقلإا فى ةحصلاب ينمتهلما دارفلأاو ةيلماعلا ةحصلا ةمظنم عم ةنواعتلما طسوتلما قشرل ةيحصلا ةلجلما طسوتلما قشرل ةيلماعلا ةحصلا ةمظنلم ةيميلقلإا ةنجللا ءاضعأ نادلبلا ةيملاسلإا ناريإ ةيروهجم . ايبيل . سنوت . نيرحبلا . ناتسكاب . ةدحتلما ةيبرعلا تاراملإا . ناتسناغفأ . ندرلأا صرم . نانبل . تيوكلا . رطق . ينطسلف . نماُع . قارعلا . لاموصلا . نادوسلا . تيوبيج . نادوسلا بونج . نميلا . ةيروسلا ةيبرعلا ةيروهملجا ةيدوعسلا ةيبرعلا ةكلملما . برغلما Members of the WHO Regional Committee for the Eastern Mediterranean Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . Kuwait . Lebanon Libya . Morocco . Oman . Pakistan . Palestine . Qatar . Saudi Arabia . Somalia . South Sudan Sudan . Syrian Arab Republic . Tunisia . United Arab Emirates . Yemen Membres du Comité régional de l’OMS pour la Méditerranée orientale Afghanistan . Arabie saoudite . Bahreïn . Djibouti . Égypte . Émirats arabes unis . République islamique d’Iran Iraq . Libye . Jordanie . Koweït . Liban . Maroc . Oman . Pakistan . Palestine . Qatar . République arabe syrienne Somalie . Soudan . Soudan du Sud . Tunisie . Yémen Cover 19 Supplement.indd 2 5/16/2013 1:30:58 PM La Revue de Santé de la Méditerranée orientale Eastern Mediterranean Health Journal Vol. 19 Supplement 1 1 فياضلإا ددعلا شرع عساتلا دلجلما•2013• Contents Editorial Novel coronavirus infection: time to stay ahead of the curve Ala Alwan, Jaouad Mahjour and Ziad A. Memish .............................................................................................................................................................................................................................S3 Perspective Emergence of novel coronavirus: global context Keiji Fukuda .....................................................................................................................................................................................................................................................................................................S5 Country experiences Saudi Arabia and the emergence of a novel coronavirus Z.A. Memish, R . Alhakeem and G.M. Stephens ..................................................................................................................................................................................................................................S7 Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation B. Hijawi, M. Abdallat A. Sayaydeh, S. Alqasrawi, A. Haddadin, N. Jaarour, S. Alsheikh and T. Alsanouri ...............................................................................................................S12 Reviews The early response to a novel coronavirus in the Middle East A. Mounts, S. De La Rocque, J. Fitzner, E. Garcia, H.L. Thomas, D. Brown, H. Schuster, K. Vandemaele, H. Esmat, S. Eremin and A. Mafi .................................................S19 Novel coronavirus: the challenge of communicating about a virus which one knows little about G. Härtl ...........................................................................................................................................................................................................................................................................................................S26 Novel coronavirus infection in the Eastern Mediterranean Region: time to act M.R. Malik, A.R . Mafi , J. Mahjour, M. Opoka, M. Elhakim and M.O. Muntasir ..............................................................................................................................................................S31 Infection prevention and control measures for acute respiratory infections in healthcare settings: an update W.H. Seto, J.M. Conly, C.L. Pessoa-Silva, M. Malik and S. Eremin ............................................................................................................................................................................................S39 Emerging respiratory and novel coronavirus 2012 infections and mass gatherings J.A. Al-Tawfiq, C.A.H. Smallwood, K.G. Arbuthnott, M.S.K. Malik, M. Barbeschi and Z.A. Memish ........................................................................................................................S48 Short communications Enhanced surveillance and investigation of coronavirus: what is required? R.G. Pebody, A. Nicoll, U. Buchholz, M. Zambon and A. Mounts .............................................................................................................................................................................................S55 Public health investigations required for protecting the population against novel coronaviruses A. Nicoll ..........................................................................................................................................................................................................................................................................................................S61 Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 C. Joseph, M.R. Malik, A.W. Mounts, A.R . Mafi, S. Briand, Z.A. Memish and the technical working group for the meeting on novel coronavirus .........................................S68 Supplement on Novel Coronavirus Book 19 Supplement.indb 1 5/16/2013 2:27:22 PM Dr Ala Alwan, Editor-in-chief Editorial Board Professor Zulfiqar Bhutta Professor Mahmoud Fahmy Fathalla Professor Rita Giacaman Dr Ziad Memish Dr Sameen Siddiqi Professor Huda Zurayk International Advisory Panel Dr Mansour M. Al-Nozha Professor Fereidoun Azizi Professor Rafik Boukhris Professor Majid Ezzati Dr Zuhair Hallaj Professor Hans V. Hogerzeil Professor Mohamed A. Ghoneim Professor Alan Lopez Dr Hossein Malekafzali Professor El-Sheikh Mahgoub Professor Ahmed Mandil Dr Hooman Momen Dr Sania Nishtar Dr Hikmat Shaarbaf Dr Salman Rawaf Editors Fiona Curlet, Guy Penet Eva Abdin, Alison Bichard, Marie-France Roux Graphics Suhaib Al Asbahi, Hany Mahrous, Diana Tawadros Administration Nadia Abu-Saleh, Yasmine El Sakhawy, Yasmeen Sedky Book 19 Supplement.indb 398 5/16/2013 2:27:22 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S3 Editorial Novel coronavirus infection: time to stay ahead of the curve Ala Alwan,1 Jaouad Mahjour 2 and Ziad A. Memish 3 1Regional Director, World Health Organization Regional Office for Eastern Mediterranean, Cairo, Egypt. 2Director, Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for Eastern Mediterranean, Cairo, Egypt. 3Deputy Minister of Health for Public Health, Ministry of Health, Riyadh; Professor, College of Medicine, Al Faisal University, Riyadh, Kingdom of Saudi Arabia (Correspondence to Ziad A. Memish: zmemish@yahoo.com). In 2003, the World Health Organiza- tion (WHO) steered an unprecedented global response to successfully control severe acute respiratory syndrome (SARS), a new disease caused by a previously unknown coronavirus. This became the first major international health emergency in the 21st century [1]. Almost 10 years later in June 2012, the discovery of another novel strain of SARS-like coronavirus [2] sparked similar alarm. This virus belongs to the same family of viruses that caused SARS in 2003. It also causes unusually severe pneumonia and death in a majority of patients [3]. Because a significant pro- portion of cases have been acquired in our region, it has had a significant impact on the countries of the Eastern Mediterranean. By April 2013, as the number of fa- talities from the Eastern Mediterranean region rose to 9 and with 14 confirmed cases [4], the situation raised some pressing questions. This virus had not been detected in humans or animals previously [5], and although most cases were sporadic, recent evidence of limited person-to-person transmission from in- dex case to family members heightened concerns. The latest cluster involved a United Kingdom (UK) resident who seemed to have acquired his infection in south Asia or the Middle East. Two family members who became ill on his return were subsequently diagnosed with novel coronavirus infection. The fact that neither had travelled outside of the UK provided the first convincing evidence of person-to-person transmis- sion [6]. The origin of this virus remains unknown. Early scientific evidence suggests that the virus might already be widespread in animals [7] but much about this virus remains to be understood. Important questions to be answered include the origins of the outbreak, how widespread it is in na- ture, whether it is a zoonotic infection, and how it emerged in humans as a virulent pathogen. Most important of all is whether infection can be sustained through human-to-human transmis- sion. Its risk to global health will be fully understood once the scale and evolu- tion of this virus is known. Geographic monitoring is a priority, particularly mapping across jurisdictions. In January this year, experts from WHO and other international health bodies assembled in Cairo to discuss what is currently known about this virus. Efforts to answer important questions have been made as shown by Angus Nicoll, Anthony Mounts and colleagues in this issue of the EMHJ. Articles from Richard Pebody, Bassam Hijawi and others have also contrib- uted important new data. The papers published in this issue of the Journal provide a convincing demonstration of the global health community work- ing together to build the evidence base that will guide and inform public health decisions. Our experience with novel corona- virus infection reinforces the benefits of regional engagement amongst WHO Member States. It also highlights the cooperation that is necessary to suc- cessfully combat international health threats within the spirit and framework of International Health Regulations (2005) [8]. WHO and international scientific communities have benefitted from the willingness of countries in our region to share viruses and information immediately. This has allowed timely sequencing studies and the rapid devel- opment of diagnostic tests. Ten years after the world success- fully contained SARS, critical questions remain. How safe is the international community? Are we prepared for an- other global event like SARS? There are mounting concerns over a succession of new pathogens identified since the turn of the century [9]. The world has already experienced the century’s first influenza pandemic. This event was preceded by another outbreak of global importance – avian influenza caused by H5N1 virus. Lessons from avian influenza, pandemic influenza, the recent emergence of novel coronavirus infection in the Middle East and influenza A(H7N9) virus in China [10] demonstrate that all these diseases have in common “known unknowns”. New pandemic diseases will emerge again in the future. Novel microbes that are sustained in nature will eventually spill over again to infect human popu- lations. When this happens, another Book 19 Supplement.indb 3 5/16/2013 2:27:22 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S4 major international health crisis will be announced [11]. The emergence two human patho- gens, novel coronavirus and influenza A(H7N9) virus, within the past few months reminds us that global health is not yet safe. Although these events could not be predicted, we can still gain if we are better prepared through shared and joint defences. This will require constant vigilance, proactive surveillance and targeted response systems across all countries. Such sys- tems should be designed to optimize disease intelligence and to improve risk forecasting. The current priority is to monitor coronavirus infections for evi- dence of sustained human-to-human transmission. While it is important to weigh the evolving risk on a prospective basis, we must stay ahead of the curve. Expecting the unexpected will be the cornerstone for WHO’s vision of global health security. It will also be a test of the global public health community’s col- lective response to this new infectious disease. The global public health community must attempt to understand the public health risk associated with this virus. No one knows how far the disease might spread and its ultimate ramifications for the region and also the world. References 1. Heyman DL, Mackenzie JS, Peiris M. SARS Legacy: out- break reporting is expected and respected. Lancet, 2013, 381:779−781. 2. ProMED-mail. Novel coronavirus − Saudi Arabia: human isolate. Archive number: 20120920.1302733. 20 September 2012 (http://www.promedmail.org/?p=2400:1000, accessed 4 October, 2012). 3. Nuttall I, Dye C. The SARS wake-up call. Science, 2013, 339:1287–1288. 4. World Health Organization. Global alert and response (GAR). Novel coronavirus infection − update. 26 March 2013 [webpage]. (http://www.who.int/csr/don/2013_03_26/en/index.html, accessed 10 April, 2013). 5. Corman VM et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reac- tion. Eurosurveillance, 2012, 17(39):pii 20285 (http://www. eurosurveillance.org/ViewArticle.aspx?ArticleId=20285, ac- cessed 2 May 2013). 6. Update: Severe respiratory illness associated with a novel coronavirus-worldwide, 2012–2013. MMWR Morbidity and Mortality Weekly Report, 2013, 62(10):194–195. 7. Müller MA et al. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replica- tive capability in mammalian cell lines. mBio, 2012, 3e00515-12 (http://mbio.asm.org/content/3/6/e00515-12.long, ac- cessed 2 May 2013). 8. International Health Regulations, 2005, 2nd ed. Geneva, World Health Organization, 2008. 9. Lightfoot N, Rweyemamu M, Heymann DL. Preparing for the next pandemic. BMJ (Clinical Research ed), 2013, 346:f364. 10. Uyeki TM, Cox JN. Global concerns regarding novel influenza A (H7N9) virus infection. New England Journal of Medicine, 2013, DoI: 10.1056/NEJMp1304661 (http://www.nejm.org/ doi/full/10.1056/NEJMp1304661, accessed 2 May 2013). 11. Morse SS et al. Prediction and prevention of the next pan- demic zoonosis. Lancet, 2012, 380:1956–1965. Book 19 Supplement.indb 4 5/16/2013 2:27:22 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S5 Perspective Emergence of novel coronavirus: global context Keiji Fukuda 1 1Assistant-Director General, Health Security and Environment, World Health Organization, Geneva, Switzerland (fukudak@who.int). In the past four decades, the emergence of new infectious diseases has shaped not only medical concepts, but also those of science and public health; affected political responses at global, regional and national levels; had seri- ous economic impact; and influenced the anxieties and expectations of the public. The novel coronavirus (nCoV) discovered in 2012 adds another such disease [1] and its potential impact may best be understood in such a historic and global context. In the 1980s, the emergence of HIV/AIDS had an enormous impact on medicine, science, politics and soci- ety—an impact that is still unfolding. The concerns raised by HIV/AIDS changed the relationship of patients to their disease, treatment and physicians and provided the clearest example to date that a disease has the capacity to become a globally transforming politi- cal issue, affecting national and interna- tional relations [2]. The decade from 2000 to 2010 was an active one for emerging infectious diseases. The emergence of severe acute respiratory syndrome (SARS) demon- strated the speed at which an infectious disease, in this globalized world, can move beyond its local origins to be- come a global crisis affecting the health of people and economies by reducing international travel and trade. The emer- gence of other infectious-disease agents, such as avian influenza A(H5N1) and Nipah virus, further emphasized the in- extricable links between human health, agriculture and the environment. SARS and H5N1 became the driving forces for countries to reshape the International Health Regulations (IHR) and to adopt a revision in 2005. The regulations, which came into force in 2007, are an acknowledgement that all countries are at risk from certain threats, such as a new infectious disease with the potential for international spread [3]. The IHR also stress the need for a proactive approach by affected coun- tries and the need for transparency in reporting. This approach encompasses prevention, containment, investigation and timely reporting of findings. In 2011, a new fundamental public health agreement called the Pandemic Influenza Preparedness (PIP) Frame- work was adopted after more than four years of formal negotiations. This Framework was catalysed by the spread of H5N1, which sharply demonstrated the need for equity among countries [4]. In a strict sense, the PIP Framework pertains only to potential pandemic influenza viruses but reflects the larger concerns of Member States of the World Health Organization (WHO). Under the PIP Framework, coun- tries have agreed that the sharing of potential pandemic influenza viruses as well as the benefits resulting from this sharing, such as diagnostic tests, vaccines and medicines, are of equal importance. The discussions preceding adoption of the Framework highlighted other problematic issues around ac- tivities, such as research, publications, material transfer agreements, and patents and other intellectual prop- erty claims. These issues can become potential impediments to the sharing of critical information, materials and technology. Moreover, it is clear that the full implementation of this Frame- work, similar to the IHR, will take time. Nonetheless, both frameworks clearly point to the directions that the world will need to move if such new diseases and other risks to global health security are to be optimally addressed. The 2009 H1N1 influenza pandem- ic demonstrated that a global outbreak of even a relatively mild disease could overwhelm the capacity of many coun- tries to respond and raised a number of issues. At the beginning of the pan- demic, the naming of the virus raised concerns with respect to fairness and stigmatization. The naming issue, along with the rapid pace of developments and enormous amounts of information and misinformation, aided in particular by social media and the Internet, cre- ated significant levels of distrust and anxiety among countries, the media, the public, individuals and organizations. The pandemic eventually underscored that countries are better prepared than in the past but they still have much to do to be adequately prepared. With the emergence of a novel coro- navirus in 2012, we are once again in a situation both familiar and uncertain. This novel virus is capable of causing severe disease and death. Evidence suggests that limited human-to-human transmission has occurred but its pros- pects for sustained or easy transmission remain unresolved. In addition, the source – presumably an animal – is still unknown, complicating efforts to limit exposure. In short, the future course is uncertain but it is clear that early deci- sions and actions could have profound and global effects. Book 19 Supplement.indb 5 5/16/2013 2:27:22 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S6 When new threats to human health arise, anxiety, needs and expectations are high. Policy-makers require information quickly that will inform risk assessments and potential countermeasures. The public, likewise, demand transparency and trust and assurance that the actions taken by all of those involved, including WHO and its Member States, scientific and public health organizations, and the research community, are guided by overarching concerns about global health and security and commitment to the highest ideals of science, fairness and equity. In short, the principles embodied in both the IHR and the PIP Framework. Just as events such as the emer- gence of a novel pathogen have inter- national consequences, successfully responding to them requires interna- tional cooperation. This includes in- formation sharing and cooperation between animal and human health sectors, between ministries of health in affected countries and between those conducting research and those on the front lines. Bringing diverse expertise and moving information quickly to References 1. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814−1820. 2. De Cock KM et al. Reflections on 30 years of AIDS. Emerging Infectious Diseases, 2011, 17(6):1044−1048. 3. International Health Regulations, 2005, 2nd ed. Geneva, World Health Organization, 2008. 4. Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits. Ge- neva: World Health Organization, 2011. those who need to know to address the critical questions related to the novel pathogen is critical for inform- ing control efforts. The IHR provide both a useful mechanism for report- ing and sharing information through WHO, and a framework for making decisions about what to report. As has been seen in SARS, H5N1, Nipah and countless other emerging pathogens, WHO serves a critical coordinating function, providing a platform for this coordination and collaboration, and synthesizing information into useful guidance for Member States. Book 19 Supplement.indb 6 5/16/2013 2:27:22 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S7 Country experience Saudi Arabia and the emergence of a novel coronavirus Z.A. Memish,1 R. Alhakeem 1 and G.M. Stephens 1 1Ministry of Health, Public Health Directorate, Riyadh, Saudi Arabia (Correspondence to Z.A. Memish: zmemish@yahoo.com). ABSTRACT The novel coronavirus disease outbreak in Saudi Arabia in 2012 predominately affected males and those living in urban areas. Since September and October 2012, when the first 2 cases were published, a total of 15 confirmed cases have been reported. All but 2 have been linked to countries of the Arabian peninsula; Saudi Arabian nationals accounted for a majority, 8 in all, and only 1 case was female. Seven patients had severe pneumonia; 2 survived—1 with mild disease and 1 with significant underlying illness. Although transmission of the virus to health-care workers was suspected in Jordan’s April 2012 outbreak, similar clusters have not been found in Saudi Arabia’s hospitals, nor have additional cases been identified through retrospective tracing of exposed health-care workers. Two family clusters have been identified, 1 in Riyadh and 1 in Manchester, England. A second Riyadh family cluster is being investigated. ديدلجا يجاتلا سويرفلا روهظو ةيدوعسلا ةيبرعلا ةكلملما سنفيتس نيوغ ،ميكلحا تفأر ،شميم دايز رثكأ تباصأ 2012 ماع في ةيدوعسلا ةيبرعلا ةكلملما في تثدح يتلا ديدلجا Coronavirus يجاتلا سويرفلا نع مجانلا ضرلما ةيشاف نإ :ةـصلالخا ، ْنيَتلاح لوأ نع تامولعلما تشرن مانيح ،2012 ربوتكأ/لولأا نيشرتو برمتبس/لوليأ ذنمف ،ةيضرلحا قطانلما في نوشيعي نمو روكذلا تباصأ ام ْنذإ ،ةيبرعلا ةريزلجا هبش نادلبب تطبترا دق تلاالحا عيجم نإف ، ْنيَتنثا ْنيَتلاح ءانثتسابو .ةلاح ةشرع سخم اهنع غلبأ يتلا ةد َّكؤلما تلاالحا عوممج غلب ،ميخو يوئر باهتلاب ضىرم ةعبس بيصأو ،ةدحاو ىثنأ اهنيب نم ناكو ،)تلااح 8( ةيدوعسلا ةيبرعلا ةكلملما ينطاوم نم تلاالحا مظعم ناك يلماعلا لىإ سويرفلا ةياسرب هابتشلاا نم مغرلا لىعو .نأش يذ يفد ضرمب رخآ دحاوو ،فيفط ضرمب ًاباصم ناك مهنم دحاو ،نانثا مهنم اجنو ةيبرعلا ةكلملما تايفشتسم في ةبهاشم ةيدوقنع تاعوممج رهظت لم هنإف ،2012 ليربأ/ناسين في ندرلأا في تعقو يتلا ةيشافلا في ةيحصلا ةياعرلا في ناتيدوقنع ناتعوممج تفشك دقو .ةيحصلا ةياعرلا في يضرعلما يلماعلل يداعتسلاا بقعتلا للاخ نم ةيفاضإ تلااح فشتكت لمو ،ةيدوعسلا .ضايرلا في ةيناث ةيلئاع ةيدوقنع ةعوممج ءاصقتسا ضرالحا تقولا في لصاوتيو .اترلكنإ ،ترسشنام في ىرخأ ةدحاوو ضايرلا في ماهنم ةدحاو ،ناتيلئاع Emergence d'un nouveau coronavirus en Arabie saoudite RÉSUMÉ La flambée d'une infection par le nouveau coronavirus en Arabie saoudite en 2012 a principalement affecté des hommes et des résidents urbains. Depuis septembre et octobre 2012, lorsque les deux premiers cas ont été rendus public, 15 cas confirmés au total ont été notifiés. Tous les cas sauf deux avaient des liens avec des pays de la Péninsule arabique ; les citoyens saoudiens étaient majoritaires avec huit cas et un seul cas de sexe féminin a été observé. Sept patients ont souffert d'une pneumonie sévère ; deux ont survécu, le premier cas étant atteint d'une forme légère de la maladie et le deuxième cas étant porteur d'une maladie sous-jacente importante. Si la transmission du virus aux agents de soins de santé a été suspectée pendant la flambée d'avril 2012 en Jordanie, aucun groupe similaire n'a été observé dans les hôpitaux en Arabie saoudite ; aucun cas supplémentaire n'a été dépisté après le suivi rétrospectif des agents de soins de santé exposés. Deux groupes familiaux ont été identifiés, un à Riyad et un autre à Manchester (Angleterre). Un deuxième groupe familial fait l'objet d'analyses à Riyad. Book 19 Supplement.indb 7 5/16/2013 2:27:22 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S8 Introduction Novel coronavirus (nCoV) was first iso- lated in June 2012 from the respiratory secretions of a businessman in the Bisha area of Saudi Arabia, who subsequently died of pneumonia and renal failure [1]. This discovery, published in September 2012 [2], was accompanied by a full genome sequence deposit and develop- ment of commercial laboratory tests for diagnosing acute cases [3]. Confirma- tion of more cases of nCoV infection followed, including the case of a Qatari national who had been transported to London for treatment of severe pneu- monia [4], and another Saudi Arabian case, a middle-aged teacher in Riyadh, who was the first to survive the infection [5]. The sequencing alignments for the 2 viral genes from these first 3 cases were identical, and confirmed the outbreak of a virulent new coronavirus in the Arabian peninsula [5]. Although there was no immediate evidence of similar illness in the hospital contacts or family contacts of any of these confirmed cases, the clinical presentations were similar to that of severe acute respiratory syn- drome (SARS) pneumonia, prompt- ing the Saudi Arabian government to convene a session of its National Scientific Council to address this new communicable disease risk both for the local population and for inbound Hajj pilgrims, who were already arriving by the tens of thousands at King Abdulaziz international airport and other Saudi Arabian ports of entry. Background The 2003 SARS epidemic had galva- nized global efforts to improve and modernize communicable disease surveillance, and to identify and contain outbreaks of serious respiratory disease as a first priority. Although influenza preparedness programmes had been updated in many jurisdictions by the year 2000, it was a previously unknown human coronavirus that emerged in southern China during the winter of 2002 that would highlight the inher- ent weaknesses of solitary national efforts. Before SARS disappeared the following summer, it had made more than 8000 people ill and killed 774 in some 30 countries. It had also disrupted international trade and compromised the economies of more than a dozen affected jurisdictions, in developed and developing countries alike. The World Health Organization (WHO) follow- up response included an update of its 1969 International Health Regulations in 2005 [6], modifications of treaty obliga- tions that would improve member state accountability and a reorganization that prioritized global surveillance and reporting through the Global Outbreak Alert and Response network. The emer- gence of another nCoV in the Eastern Mediterranean Region is about to test these systems. Cases and laboratory investigations The public health directorate of the Min- istry of Health (MOH) in Saudi Arabia is charged with policy and planning for communicable diseases prevention and control. In September 2012 its surveil- lance and investigation mandates were expanded to identify nCoV cases as a priority, assess transmission to close contacts and investigate the possibility that this was a new zoonotic infectious disease with an animal reservoir on the Arabian peninsula. Case finding Acutely ill individuals who met Saudi Arabia’s case definition (Table 1) were identified through physician, infection control and other institutional reports to the MOH communicable diseases office. Hospitals and medical cities were required to identify patients on ventila- tion to the MOH and submit speci- mens for testing. Specimens submitted for influenza surveillance were screened for nCoV. Hospital laboratories were also required to add nCoV to routine investigations of respiratory illness cas- es. Specimens found to be positive by initial testing at MOH laboratories were forwarded for confirmation to the Unit- ed Kingdom (UK) Health Protection Agency laboratories in Birmingham and Colindale, England, where they were assayed for coinfecting viruses (influ- enza A and B virus, parainfluenza virus, respiratory syncytial virus, adenovirus, human metapneumovirus and seasonal coronaviruses). nCoV confirmation was done by molecular amplification of 3 nCoV genes. Confirmation results were reported to the MOH and by the country’s focal point to WHO. Chart reviews Chart reviews were done for each case to identify clinical features, evaluate comorbidities and risk factors and track the case response to treatment. Family investigations Epidemiologists investigated cases and associated households within their respective administrative jurisdictions. Investigations included a survey of the immediate premises, household inter- views and evaluations of close contacts, in particular family caregivers. Swabs and sera were collected and coded for each family member. Infection control investigations Hospitals and medical cities conducted retrospective investigations according to institutional protocols. Swabs and sera were collected by infection control personnel, coded and referred to the MOH laboratories. Animal studies Surveillance of immediate and neigh- bouring premises was done for each case, along with investigations of ad- joining areas and locales such as rest houses (istirahat) and farms that had Book 19 Supplement.indb 8 5/16/2013 2:27:23 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S9 been visited by cases. This was used to guide specimen collections that were forwarded to reference laboratories for sequencing studies. Summary of findings Confirmed cases Table 2 summarizes the chronology and clinical picture of cases linked to Saudi Arabia. To date, Saudi Arabia has had a total of 8 confirmed cases, including 2 survivors—1 who did not progress to respiratory failure and 1 who survived despite underlying disease and respiratory and renal failure. Only 1 confirmed case was female, the others were males between the ages of 31 and 70 years. The 5 sporadic cases outnum- bered the 3 cases in clusters, although a second family cluster linked to case 15 was identified. All but 2 cases lived in urban Riyadh: case 1 resided in Bisha, an agricultural community located in south-western Asir province, and case 14 lived in Burayda, a city in Al Qassim province, north of Riyadh (Figure 1). Suspected cases In addition to the 8 confirmed cases, Saudi Arabia to date has had 2 suspect- ed cases, both residents of Riyadh. The first was a 16-year-old male, grandson of case 7, son of case 8 and nephew of case 9. All were members of the same household. A second suspected case was the brother of case 15 and the likely index case for his household. Case 10, a 60-year-old UK resident with a history of travel to Pakistan and Saudi Arabia, was reported by the UK Health Protection Agency on 7 February 2013. This case was also associated with subsequent transmission of novel coronavirus to 2 family members, neither of whom had travelled outside the UK [7]. Surveillance before, during and after Hajj Background The Hajj pilgrimage draws 2.5 to 3 million visitors to Saudi Arabia each year, more than half of whom come from overseas countries. Planning for each gathering involves the work of 24 supervising committees that coordi- nate with the Saudi Arabian MOH as the agency with primary oversight of preventive medicine and public health matters. Pilgrims are provided with free health care in 141 centres in or near Hajj venues. This includes 25 hospitals and a total of 4457 beds including 500 critical care and 500 emergency care beds. Around 20 000 specialized health- care workers are deployed to work in these various facilities in a typical year. Ports of entry are managed by public health officers to ensure compliance with MOH regulations. There are addi- tional public health teams, including 21 mobile teams, located in various areas of the Hajj. King Abdulaziz international airport terminal in Jeddah is the port of entry for more than 80% of pilgrims and the site of initial health screening for the vast majority who will enter the holy sites within hours to days of arriving in Saudi Arabia. Public health teams based at the airport and throughout Hajj ven- ues report to a central unit on 9 types of communicable disease: influenza and Table 1 Saudi Arabian case definitions of novel coronavirus Term Saudi Arabian criteria Suspected case • Acute respiratory illness; • Onset includes high fever ≥ 38 °C, cough; • Requires hospitalization; • Evidence of lung parenchymal involvement; • Not explained by other etiology. Probable case • May or may not require hospitalization but otherwise fits criteria for suspected case; • Specimens are not available for testing or patient is not available for testing; • Not explained by other etiology. Confirmed case • Laboratory confirmed. Close contact • Anyone who provided care for the patient; • May include health-care worker or family member; • Anyone who stayed in the same place as a probable or confirmed case while case was symptomatic. Hajj case definition • Meets criteria for suspected, probable or confirmed case; • Symptom onset during Hajj, or 10 days before or 10 days after Hajj; • Located in or near Mecca or Medina cities. Secondary case • Contact with a suspected, probable or confirmed case; • Disease onset within 10 days of index case. Book 19 Supplement.indb 9 5/16/2013 2:27:23 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S10 influenza-like illness, cholera and foodborne illness, menin- gococcal disease, yellow fever, viral haemorrhagic fever, polio and plague [8]. The WHO collaborating Centre for Mass Gatherings Medicine in Saudi Arabia is the repository for data from each Hajj event. Novel coronavirus Hajj 2012 was scheduled to start on 24 October, a month after the first report of the discovery of nCoV. Infectious disease risks were updated and reviewed by the National Sci- entific Committee on 27 September 2012. Evidence of nCoV prevalence in the region was then limited to 2 confirmed cases. Although both cases resembled SARS pneumonias—ful- minant disease in previously healthy adults—there were no symptomatic secondary cases among 64 health-care workers exposed to case 2 in the UK [9] and none were identified at Jeddah or Bisha hospitals where there was exposure to the first case. Family members of both cases remained well. Neither the WHO nor the Saudi Arabian government found compelling reasons to restrict access to the Hajj based on concerns about nCoV. Hajj studies and collaborations To further evaluate the prevalence of nCoV in Saudi Arabia, enhanced surveillance was undertaken at the 2012 Hajj. Individuals who met the Hajj case definition for suspected infection (Table 1) were evaluated by health-care staff and swab specimens were collected and referred to a regional MOH laboratory for testing. Public health staff also monitored health-care facilities and all hospitals in the cities of Mecca and Medina for cases of severe respiratory infection. In addition, Saudi Arabia enabled other governments and nongovern- mental organizations to collect specimens and analyse data on pilgrims returning home. Sample size continues to be an issue for studies of com- municable disease risks at the Hajj; organizing investigations based on a representative selection of pilgrims is particularly challenging given the intensity of the event and a denominator of 2.5 to 3 million people. Nonetheless, the Saudi Arabian MOH confirmed that admissions of respiratory cases to Hajj hospitals had been within the expected range for the 2012 Hajj. Respiratory tract swabs of hospitalized patients—190 from Medina hospitals and another 86 from Mecca hospitals —tested negative for nCoV molecular targets, as did swabs from 154 pilgrims tested on return home to France [10]. More recently the Saudi Arabian MOH, through its leadership of the newly established collaborating Centre for Mass Gather- ings Medicine, will conduct cross-sectional and longitudinal studies on nCoV and other respiratory tract infections for surveillance, prevention and control.Ta bl e 2 D es cr ip ti on o f c on fir m ed c as es o f n ov el c or on av ir us in fe ct io n lin ke d to S au di A ra bi a C as e no . A ge (y ea rs ) Se x D at e of o ns et Re gi on A cu te d ia gn os is O th er di ag no se s O th er ag en ts a Pa st m ed ic al h is to ry O ut co m e Fa m ily cl us te rb 3 60 M al e Ju n 20 12 Bi sh a Re sp ira to ry fa ilu re Re na l f ai lu re N o – D ec ea se d N o 5 49 M al e O ct 2 0 12 Ri ya dh Re sp ira to ry fa ilu re Re na l f ai lu re N o D ia be te s m el lit us , ca rd io va sc ul ar d is ea se A liv e N o 7 70 M al e O ct 2 0 12 Ri ya dh C on ge st iv e he al th fa ilu re ; Re sp ira to ry fa ilu re Re na l f ai lu re N o C on ge st iv e he al th fa ilu re D ec ea se d Ye s 8 39 M al e N ov 2 0 12 Ri ya dh Re sp ira to ry fa ilu re – N o – D ec ea se d Ye s 9 31 M al e N ov 2 0 12 Ri ya dh Pn eu m on ia – N o – A liv e Ye s 13 61 Fe m al e Ja n 20 13 Ri ya dh Re sp ira to ry fa ilu re Re na l f ai lu re N o – D ec ea se d N o 14 65 M al e Fe b 20 12 Bu r Q as si m Re sp ira to ry fa ilu re – N o – D ec ea se d N o 15 37 M al e Fe b 20 12 Ri ya dh Re sp ira to ry fa ilu re – N o – D ec ea se d Ye s a O th er a ge nt s = o th er co in fe ct in g vi ru se s o r b ac te ria l p at ho ge ns ; b Fa m ily c lu st er = m or e th an 1 ca se w ith in a h ou se ho ld . Book 19 Supplement.indb 10 5/16/2013 2:27:23 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S11 Summary The first report of a virulent nCoV in September 2012 has been followed by an extraordinary convergence of References 1. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814–1820. 2. Novel coronavirus—Saudi Arabia: human isolate. ProMed, 2012, archive number 1302733:20. 3. Corman VM et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Eurosurveillance, 2012, 17(39):pii 20285. 4. Bermingham A et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United King- dom from the Middle East, September 2012. Eurosurveillance, 2012, 17(40):pii 20290. 5. Albarrak AM et al. Recovery from severe novel coronavirus infection. Saudi Medical Journal, 2012, 33:1265–1269. 6. International health regulations (2005), 2nd ed. Geneva, World Health Organization, 2005. 7. Novel coronavirus 2012 in the UK: situation as at 19 February 2013. Health Protection Report, 2013, 7(8). 8. Al-Tawfiq JA, Memish ZA. The Hajj: updated health hazards and current recommendations for 2012. Eurosurveillance, 2012, 17(41):pii 20295. 9. Pebody RG et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coro- navirus in September 2012. Eurosurveillance, 2012, 17(40):pii 20292. 10. Gautret P et al. Lack of nasal carriage of novel corona virus (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms. Clinical Microbiology and Infection, 2013, Feb 11 (doi: 10.1111/1469- 0691.12174). global expertise focused on this agent and on the countries of the Eastern Mediterranean Region that have been linked to it. Ten years ago it was anoth- er virulent coronavirus—SARS—that compelled the first truly international effort aimed at containing an incipient virus pandemic. That legacy is evident now; scientific collaborations have produced full genome sequences, laboratory tests to quickly diagnose infection and a body of knowledge that supports a technology-driven search for an animal reservoir. Perhaps the most important legacy of SARS is the International Health Regulations 2005, with new rules to compel rapid, coordinated case reporting and en- able an informed evaluation of global risks [6]. This information is now disseminated to a global audience in real time. Whether nCoV disappears suddenly, as did the SARS coronavirus in 2003, remains to be seen. To date, there is limited evidence to support a pandemic risk, although transmission to close contacts is now established with certainty. Whether we are watch- ing an epidemic in progress remains to be seen. Collaborations and partner- ships with local disease experts have been slow to evolve, yet they remain essential if we are to have a better un- derstanding of the epidemiology of nCoV. Figure 1 Map of Saudi Arabia showing the location of cases Book 19 Supplement.indb 11 5/16/2013 2:27:23 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S12 Country experience Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation B. Hijawi,1 M. Abdallat 2 A. Sayaydeh,2 S. Alqasrawi,2 A. Haddadin,3 N. Jaarour,2 S. Alsheikh 2 and T. Alsanouri 3 1Primary Health Care Administration; 2Directorate of Communicable Diseases; 3Laboratory Directorate, Ministry of Health, Jordan (Correspondence to S. Alqasrawi: sultanmabdalla@yahoo.com). ABSTRACT In April 2012, an outbreak of acute respiratory illness occurred in a public hospital in Zarqa city, in Jordan; 8 health care workers were among the 11 people affected, 1 of who later died. The cause of the outbreak was unknown at the time and an epidemiological investigation including laboratory testing carried out immediately after the outbreak was inconclusive. Following the discovery of novel coronavirus infection (nCoV) in the Arabian peninsula in September 2012, stored respiratory and serum samples of patients from this outbreak were retested and the diagnosis of nCoV was confirmed in 2 deceased patients. This paper describes the epidemiological findings of retrospective investigation carried out in November 2012 and highlights the likelihood of nosocomial transmission of nCoV infection in a health-care setting. A total of 2 laboratory-confirmed and 11 probable cases were identified from this outbreak of whom 10 were HCWs and 2 were family members of cases. ةيداعتسلاا تايصقتلل ةيئابولا جئاتنلا :2012 ناسين ندرلأا في ديدلجا يجاتلا سويرفلاب ىودعلا يروناسلا قراط ،خيشلا حماس ،يرورعج ىوجن ،نيدادح مثكأ ،يواسركلا ناطلس ،هديايص بويأ ،ّتلادبعلا دممح ،يوا َّجِح ماسب الهلاخ بيصأو ،ندرلأا في ءاقرزلا ةنيدم في ةيمومعلا تايفشتسلما ىدحإ في ّدالحا سيفنتلا ضرلما نم ةيشاف تعلدنا ،2012 ليربأ/ناسين في :ةـصلالخا اهنع ترفسأ يتلا جئاتنلاف ،كاذنآ ًافورعم ةيشافلا ببس نكي لمو .كلذ دعب مهدحأ تامو ،ًاباصم شرع دحأ يب نم ةيحصلا ةياعرلا في يلماعلا نم ةينماث ةريزلجا في ديدلجا يجاتلا سويرفلاب ىودعلا فاشتكا دعبو .ةعطاق نكت لم ةيشافلا علادنا روف تيرجأ ةيبرتمخ تارابتخا تن َّمضت يتلاو ةيئابولا تايصقتلا صيخشت د َّكأتف ،ةيشافلا كلت في ضىرلما نم اهنيزتخ مت يتلا ةيلصلماو ةيسفنتلا تانيعلا لىع ًاددمج تارابتخلاا تيرجأ ،2012 برمتبس/لوليأ في ةيبرعلا /نياثلا نيشرت في تيرجأ يتلا ةيداعتسلاا تايصقتلل ةيئابولا جئاتنلا ةساردلا هذه فصتو . ْنيَيفوتم ْنيَضيرم ىدل ديدلجا يجاتلا سويرفلاب ىودعلا ًايبرتمخ ْنيَتد َّكؤم ْنيَتلاح فشك مت دقف .ةيحصلا ةياعرلا عقاوم في يجاتلا سويرفلاب تايفشتسلما ىودع ةياسر لماتحا لىع ءوضلا يقلُتو ،2012 برمفون .تلاالحاب يباصلما َسرُأ دارفأ نم نانثاو ةيحصلا ةياعرلا في يلماعلا نم ةشرع ابه يباصلما يب نم ناكو ،ةيشافلا كلت في ةلمتمح ةلاح ةشرع ىدحإو Infections par le nouveau coronavirus en Jordanie, avril 2012 : résultats épidémiologiques d'une étude rétrospective RÉSUMÉ En avril 2012, une flambée de maladies respiratoires aiguës a été observée dans un hôpital public de la ville de Zarqa (Jordanie) ; huit agents de soins de santé faisaient partie des onze personnes affectées, et l'un d'eux est décédé ultérieurement. La cause de cette flambée était inconnue à l'époque et l'étude épidémiologique menée immédiatement après la flambée, comprenant des analyses de laboratoire, n'a pas permis de tirer de conclusions. Après la découverte d'une infection par le nouveau coronavirus dans la péninsule arabique en septembre 2012, des échantillons respiratoires et sériques prélevés chez des patients de cette flambée, et qui avaient été conservés, ont été réanalysés et le diagnostic d'infection par le nouveau coronavirus a été confirmé chez deux patients décédés. Le présent article présente les résultats épidémiologiques de l'étude rétrospective menée en novembre 2012 et souligne la probabilité d'une transmission nosocomiale de l'infection par le nouveau coronavirus en milieu de soins. Au total, deux cas confirmés en laboratoire et onze cas probables ont été identifiés à partir de cette flambée ; dix de ces patients étaient des agents de soins de santé et deux patients des membres de la famille de cas. Book 19 Supplement.indb 12 5/16/2013 2:27:23 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S13 Introduction In April 2012, an outbreak of acute respiratory illness was reported by the Ministry of Health (MOH) in Jordan in an intensive care unit (ICU) of a hospital in Zarqa. Among the 11 people affected were 7 nurses and 1 internist; 1 of the nurses later died [1]. All cases were reported to have had high fever and acute lower respiratory symptoms. An epidemiological investigation, in- cluding laboratory tests carried out in the immediate aftermath of this out- break, was inconclusive and the cause of this outbreak remained unknown. In September 2012, novel coronavi- rus (nCoV) infection was identified in a patient from Saudi Arabia and later in a patient from Qatar [2–4]. In October 2012, after the discovery of the nCoV and following reports of patients with nCoV infections presenting with similar acute lower respiratory symptoms, the Ministry of Health decided to retest the samples from this outbreak for nCoV at the United States Naval Medical Research Unit-3 (US NAMRU-3) in Cairo, a World Health Organiza- tion (WHO) collaborating centre for emerging infectious diseases. Samples were tested by conventional universal pan-corona virus primers and specific reverse transcription real-time polymer- ase chain reaction (RT-PCR) for the nCoV using reagents from the United States Centers for Disease Control and Prevention. Bronchioalveolar lavage and nasal swab extracts from a case, who was a health-care worker (HCW)—an intensive care unit (ICU) nurse—and a convalescent serum sample from a second case, who was a student, tested positive for nCoV by RT-PCR. Accord- ingly 2 laboratory-confirmed cases of nCoV infections were officially notified to WHO by the Ministry of Health in Jordan [5] Following these positive test re- sults, the MOH Jordan, together with WHO, fielded a team in Zarqa from 28 November to 7 December 2012 to conduct a retrospective investigation of this outbreak. This paper presents the epidemiological findings of this out- break investigation. Methods Settings The field investigation was carried out in Zarqa, which is the second largest city in Jordan with a population of about 1 million. The city is located 25 km north- east of the capital, Amman. There are 3 public and 3 private hospitals in the city, of which the Zarqa hospital is the oldest and largest public hospital, with a capacity of 300 beds including 6 beds in the coronary care unit (CCU) and 6 beds in the ICU. Epidemiological investigations Case definition For the purpose of retrospective in- vestigation a probable case definition was developed, defined as “any case admitted in Zarqa hospital or their close contacts, who complained of fever and dry cough with radiological evidence of pneumonia during the period from 15 March to 30 April [2012]”. For the pur- pose of the investigation, a close contact was defined as “anyone who provided care to a laboratory-confirmed case, including a HCW or family member, or who had other similarly close physical contact”, as recommended in the WHO interim surveillance recommendations for human infection with nCoV [6]. Patient interviews The team visited the Zarqa public hospital as well as 2 other hospitals to which patients were referred during the outbreak in April 2012. Medical records were retrieved and reviewed for all patients with severe acute lower respiratory infections admitted to ei- ther the ICU or CCU in Zarqa hospital from 15 March to 30 April. During the visit, interviews were conducted with all the probable cases, HCW and some of the close contacts of both the laboratory-confirmed and probable cases, and key epidemiological and clinical information were collected including their history of contact with other laboratory-confirmed cases. The investigation was targeted at potential modes of acquisition of the infection. The questionnaire contained questions about the early course of disease, social status, living conditions, profession, hobbies and regular activities, exposure to animals, eating habits and contact with individuals with respiratory ill- ness in the 10 days before the onset of illness. Contact investigations The family members of the 2 laboratory- confirmed cases could not be contacted and no information was collected on the duration or frequency of contact with the laboratory-confirmed cases. Laboratory investigations The hospital laboratory was searched for availability of any other stored res- piratory or blood samples from the ad- ditional cases reported in this outbreak in April 2012. No such samples were available. Results Epidemiological investigation of the initial cluster For the description of this outbreak, all listed cases from the outbreak were considered as probable if no laboratory conformation were available. A total of 13 cases were identified that matched the case definition developed for this investigation. The total number of laboratory-confirmed cases was 2, while the remaining 11 cases were defined as probable. Of these 13 cases, 10 were HCW in the CCU or ICU, medical or emergency ward in the Zarqa public hospital (Table 1). The 3 non HCWs were a student, a brother of the de- ceased female nurse and the mother of a male nurse. Book 19 Supplement.indb 13 5/16/2013 2:27:23 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S14 The investigation and the epidemic curve suggested 2 phases to the out- break (Figure 1). The initial phase con- sisted of 4 cases: 2 laboratory-confirmed cases (who died) and 2 probable cases (who recovered from their illness). For investigation purposes, emphasis was put on the initial phase in order to better understand the potential origin of the disease. Case 1 and exposure history Based on the reported date of onset of symptoms case 1 was a 25-year-old university student who had onset of symptoms on 21 March 2012. He was among the 4 cases identified in the initial phase of this outbreak. He had cough for a week followed by fever and shortness of breath. He was admitted to the regular medical ward in Zarqa public hospital on 4 April with an ini- tial diagnosis of pneumonia. His X-ray showed right lung consolidation and he was later treated for pericarditis. He was then transferred to the CCU a day after admission and later transferred to Prince Hamzah hospital in Amman for further treatment, where he was admit- ted to the CCU and then to the ICU isolation room on the second day of his arrival and was intubated. His condi- tion deteriorated and he eventually died on 25 April. The patient had no travel history and had no reported direct con- tact with animals or with persons with severe respiratory illness in the 10 days before the onset of his illness. A total of 3 close contacts of case 1 were identified (1 household and 2 HCW contact). The household contact, who was the patient’s mother, did not report any respiratory symptoms, while 2 HCW developed respiratory symptoms (here- after referred as case 2 and case 3) that progressed to severe illness requiring hospitalization. Case 2 and contacts Case 2 was a 30-year-old male CCU nurse in Zarqa hospital with an esti- mated onset of symptoms on 29 March 2012. This was a probable case, who recovered. The patient had no travel history and no reported contact with animals in the 10 days before the onset of illness. It was reported that he was in direct contact with case 1 as he was caring for him in the CCU; however, it was not clear why his date of onset of symptoms was 5 to 6 days before case 1 was admitted in the hospital. He was admitted to the CCU of Zarqa hospital on 8 April with shortness of breath and bilateral pneumonia. He was transferred to the CCU of Islamic hospital on 12 April and was discharged in good condition on 23 April. A total of 2 close contacts (household contacts) were identified for case 2. One was the mother of case 2 (hereafter referred to as case 13) and developed respiratory symptoms which required hospitaliza- tion. The other household contact, who was a brother of case 3, had also cared for him but did not report any respiratory symptoms in the 10 days post-exposure. Case 3 and contacts Case 3 was a 40-year-old female ICU nurse at the Zarqa hospital with on- set of symptoms on 2 April 2012 and was a laboratory-confirmed case who later died. From the limited information Table 1 Line list of confirmed and probable cases of novel coronavirus (nCoV) infection in Zarqa, Jordan, March to May 2012 Case no. Age (years) Sex Date of onset Date of admission Date of discharge/ death Occupation Outcome Classification 1 25 Male 21 Mar 4 Apr 25 Apr Student Deceased Confirmed case 2 30 Male 30 Mar 8 Apr 23 Apr Nurse Alive Probable case 3 40 Female 2 Apr 9 Apr 19 Apr Nurse Deceased Confirmed case 4 60 Male 2 Apr Refused admission – Physician, internist Alive Probable case 5 29 Male 11 Apr 15 Apr 21 Apr Nurse Alive Probable case 6 33 Male 12 Apr 14 Apr 21 Apr Nurse Alive Probable case 7 28 Male 13 Apr 17 Apr 21 Apr Nurse Alive Probable case 8 45 Male 14 Apr 17 Apr 24 Apr Road technician (brother of case 3) Alive Probable case 9 46 Male 15 Apr 16 Apr 21 Apr Nurse Alive Probable case 10 25 Male 15 Apr 18 Apr 21 Apr Nurse Alive Probable case 11 53 Male 18 Apr 21 Apr 23 Apr Physician, internist Alive Probable case 12 28 Female 19 Apr Refused admission – Nurse Alive Probable case 13 60 Female 26 Apr 1 May 5 May Housewife (mother of case 2) Alive Probable case Book 19 Supplement.indb 14 5/16/2013 2:27:23 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S15 available, there was no travel history or contact with animals in the 10 days before the onset of her illness. She was admitted to the ICU of Zarqa hospital on 9 April with right-sided pneumo- nia. She was transferred to the ICU of Islamic private hospital in Amman on 14 April, was intubated the following day and died on 19 April with a dissemi- nated coagulopathy. A total of 4 close contacts of case 3 were identified (all household contacts), one of whom was a brother of case 3 (hereafter referred to as case 9) and developed pneumonia in the 10 days post-exposure. Case 4 and contacts Case 4 was a 65-year-old medical doc- tor, head of the internal ward, a probable case who recovered. The onset of symp- toms was on 2 April 2012 with fever and fatigue. There was no travel history or contact with animals in the 10 days before the onset of his illness His chest X-ray showed bilateral pneumonia. He refused admission to the hospital and took self-care at home. No respiratory disease was reported in any of his house- hold contacts. Epidemiological investigation of the secondary phase The secondary phase consisted of 9 probable cases who all developed pneu- monia? and recovered (Figure 2). March to May 2012 The onset of symptoms was between 11–19 April 2012 for 8 cases and was 26 April for the last reported probable case. Seven of these probable cases were HCW (2 CCU nurses, 1 internist, 1 nurse in the internal ward and 2 nurses working in the emergency ward) and 2 cases were relatives of HCW (mother of case 2 and brother of case 3). Based on the available information all of them were likely to have had significant con- tact with at least 1 of the 2 confirmed cases, apart from the mother of the probable case 2, for whom a contact to a confirmed case was not documented in the 10 days before onset of symptoms. To prevent stigmatization of patients the HCW reported that they did not use any personal protective equipment apart from gloves when caring for the patients. Investigation for additional cases The initial outbreak investigation report stated that there was no unusual pattern of community-acquired respiratory dis- ease noted in the community or other hospitals. It was not possible to validate this information during the investiga- tion. Review of the ICU admission log book in Zarqa hospital revealed 6 other cases for whom admission could have been due to respiratory symptoms and whose files were reviewed. While 5 cases were discarded due to irrelevant symp- toms, only 1 case, a 22-year-old patient with Down syndrome, had signs of an acute respiratory infection at admis- sion and later died. His date of onset of symptoms was at the end of March 2012. No laboratory results for nCoV were performed for this case. Interviews with nurses from the CCU revealed 2 other non-Jordanian patients with signs of respiratory infection. Review was only possible for 1 of them and this did not show any documented acute respiratory disease. All admitted cases identified in this cluster were transferred from Zarqa hospital to 2 other hospitals in Amman (Islamic hospital and Prince Hamzah hospital). The 2 referral hospitals were asked to analyse their discharge statis- tics (using International Classification of Diseases, version 10 codes) for the month of March to May 2012 and 2011. The information retrieved from one of the referral hospitals (Islamic hospital) suggested an increase in the number of visits to that hospital of pa- tients with pneumonia, with 74 cases in April 2011 compared with 205 cases recorded in April 2012. No further in- formation was available explaining this apparent rise in cases of severe acute respiratory infection. Exposure of the patients Some information on exposure from the initial phase of the outbreak was available for the 3 HCW and not for the deceased patient. All of the HCW had no history of travel or contact with animals. The only known fact was that case 3, with onset of symptoms Number of Cases Lab confirmed and deceased Probable and recovered First Wave Second Wave 3 2 3 8 1 12 2 1 5 4 7 9 6 10 11 13 20 21 22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 March April May Date of Onset of Symptoms Figure 1 Epidemic curve of confirmed and probable cases of novel coronavirus infection, Zarqa, Jordan, 20 March to 4 May 2012 Book 19 Supplement.indb 15 5/16/2013 2:27:24 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S16 Fi gu re 2 T im el in e of 1 3 ca se s of n ov el c or on av ir us in fe ct io n, Z ar qa , J or da n, M ar ch to M ay 2 0 12 (C C U = c ri ti ca l c ar e un it) co nt ac t w it h ca se 2 Ca se 1 3 m ot he r of c as e 2 Ca se 1 2 N ur se Ca se 1 1 In te rn is t Ca se 1 0 N ur se E m er ge nc y W ar d Se co nd er y ph as e co nt ac t w it h ca se 6 Ca se 9 CC U N ur se co nt ac t w it h ca se 3 Ca se 8 br ot he r o f c as e 3 Ca se 7 N ur se E m er ge nc y W ar d co nt ac t w it h ca se 1 , 2 , 3 Ca se 6 N ur se C CU Ca se 5 N ur se In te rn al w ar d co nt ac t w it h ca se 1 Ca se 4 In te rn is t Ca se 3 N ur se IC U In iti al p ha se Ca se 2 st af f C CU Ca se 1 st ud en t 20 21 22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 M ar ch A pr il M ay D at e of O ns et o f S ym pt om s M ild ly il l ( ho m e si ck ) A dm it ti on to w ar d Za rq a H os pi ta l C CU H am za H os pi ta l C CU Is la m ic H os pi ta l C CU Po ss ib le c on ta ct p er io d D ea th H CW H ea lt h Ca re w or ke r ss Book 19 Supplement.indb 16 5/16/2013 2:27:24 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S17 on 2 April 2012, had her sister visiting from Saudi Arabia 1 month before the onset of symptoms. No information was available regarding residence and or health status of the visiting sister. The 2 probable cases in the initial phase of this outbreak had contact with the laboratory-confirmed cases in the CCU of Zarqa hospital, while the 2 other probable cases in the second phase of this outbreak—case 13 and case 8— were the household contacts of cases 2 and 3 respectively. It was also possible that the 7 HCWs who were the prob- able cases in the second phase of this outbreak had some contacts with the 2 laboratory-confirmed cases of the first phase; however, the investigation could not establish this link. Age and sex The median age of patients was 33 years (range 25–65 years). Males accounted for 77% of the 13 cases. Clinical picture The earliest date of onset of symptoms was 21 March 2012 and most cases (70%) were described as having cough followed by high fever. The duration of admission for admitted patients (2 patients refused admission) ranged from 3–17 days with a mean of 9 days. The white blood cell count in a major- ity of cases was disproportionately low considering the extent of infection and body temperature of the patients. The chest X-rays showed evidence of single- lobular, bi-lateral or multi-lobular pneu- monias. No sequelae were reported in the recovered patients. No case had renal failure. Case 1 had a pericarditis with huge fluid accumulation. Laboratory investigations: patient samples During the outbreak of acute respira- tory illnesses in April 2012, the US NAMRU-3, Cairo, was requested to support the laboratory investigation of cases reported from this out- break. Nasopharyngeal swabs and 1 bronchoalveolar lavage from 9 patients were tested at US-NAMRU-3 by RT- PCR for coronaviruses (229E, HKU1, NF69, OC), parainfluenza viruses 1–3, adenovirus, human metapneumovirus and for severe acute respiratory syn- drome (SARS) virus by nested PCR, using published sequences. Except for case 1, where the RNA extracts from na- sopharyngeal swabs were weakly posi- tive for CV 229E by RT-PCR, all other cases were negative for all viruses tested. Following the discovery of nCoV, an- other set of these stored samples (5 serum samples and 2 nasopharyngeal swabs and 2 bronchoalveolar lavages) were sent to US NAMRU-3 for retest- ing in October 2012. No additional samples from the outbreak were avail- able for nCoV testing in during the autumn in 2013. The US NAMRU-3 also tested another 234 nasopharyngeal samples that were collected from the severe acute respiratory infection sen- tinel surveillance sites from April and October 2012 and all samples tested negative for nCoV. Discussion In this report of the Jordan 2012 nCoV outbreak we present evidence of limited person-to-person transmis- sion of nCoV following contact but it seems that transmission did not occur frequently. The secondary cases that were detected had a putative incuba- tion period within 10 days of reported contact with cases. The secondary cases were mostly HCW, who most likely acquired the infection in health-care set- tings. However, nCov was not detected among the close contact of the index case or among the 4 close contacts of the 2 other cases reported in the initial phase. These findings suggest that al- though person-to-person infection is possible, there is no evidence at present of sustained person-to-person transmis- sion of nCoV in relation to this cluster. For the index case of this outbreak, we had 2 main hypotheses. Case 1, who was a student and admitted with pneumonia and pericarditis, was the first nCoV patient and case 2, who was a HCW became infected from him. How- ever, there remained the question how the HCW was exposed, as the index case’s admission was after the 2 HCW had already developed symptoms. It is possible that there might have been contact between the index case and any of these HCW in the outpatient clinic before the index patient’s admission or that each case had different exposure histories that could not be identified or established. Another hypothesis was that case 2 was the initial case and that he infected his colleagues as well as case 1, who he was caring for. The HCW was present at work while he was already symptomatic with cough and fever. He also would have been in contact with cases 3 and 4 at his workplace. This would suggest that case 1 was admitted due to signs and symptoms of a different disease and had acquired the infection while in the CCU at Zarqa hospital. If this is the case, the question then is: from where did case 2 contract the infection and why were only HCW infected (beside the 1 patient and relatives)? The hospital set-up, as well as the stated contact of the HCW while caring for symptomatic cases (i.e. without using precautions to prevent transmission) means that human–human transmission was very likely to have occurred. Further pos- sibilities are that there was a common source of infection outside the hospital, but again we would expect more cases outside the hospital, or that there was yet another patient who would have infected the HCW as well as case 1. For the secondary phase, person- to-person transmission in health-care settings seemed very likely, and close contact with respiratory secretions seems to be the most likely route of transmission, despite the limited infor- mation available. Based on the available Book 19 Supplement.indb 17 5/16/2013 2:27:24 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S18 References 1. Severe respiratory disease of unknown origin—Jordan—out- break in ICU. Communicable Disease Threats Report, week 18, 29 April–May 2012 (http://www.ecdc.europa.eu/en/publi- cations/Publications/CDTR%20online%20version%204%20 May%202012.pdf, accessed 9 May 2013). 2. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814–1820. 3. Severe respiratory illness associated with a novel coronavirus- -Saudi Arabia and Qatar, 2012. Morbidity and Mortality Weekly Report, 2012, 61(40):820–820. 4. Bermingham A et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United King- dom from the Middle East, September 2012. Eurosurveillance, 2012, 17(40): pii: 20290. 5. Novel coronavirus infection—update. 30 November 2012. World Health Organization [online] http://www.who. int/csr/don/2012_11_30/en/index.html, accessed 7 May 2013). 6. World Health Organization. Interim surveillance recom- mendations for human infection with novel coronavirus as of 18 March 2013 (http://www.who.int/csr/disease/corona- virus_infections/InterimRevisedSurveillanceRecommenda- tions_nCoVinfection_18Mar13.pdf, accessed 9 May 2013) 7. Albarrak AM et al. Recovery from severe novel coronavirus infection. Saudi Medical Journal, 2012, 33:1265–1269. 8. Health Protection Agency (HPA) UK NCoV Investigation team. Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, Feb- ruary 2013. Eurosurveillance, 2013, 18(11):pii 20427. 9. Buchholz U et al. Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October–November 2012. Eurosurveillance, 2013, 18(8):pii 20406. information, the outbreak seems to have been limited to the direct contacts of patients (brother and mother). It is unclear if there might have been more cases with less severe presentations that were not admitted to the hospital and eventually might have been excluded from the list of probable cases, as the definition for the probable case did not include those who presented with mild illness and were not admitted. The lim- ited transmissibility is consistent with the data available to date, with 2 other reports of small, self-limited clusters of severe disease in the Eastern Mediter- ranean Region in a household setting [7] and in the United Kingdom in a household setting [8]. Furthermore, intensive follow-up of the close contacts of 2 other cases imported to European countries has failed to demonstrate on- ward transmission [8,9]. Our investigation had some impor- tant limitations. The main limitation was recall bias, as the epidemiological investigation was conducted 7 months after the outbreak. The complexity of social perceptions made access and data collection from the relatives and other contacts extremely difficult. Other factors were the death of 2 possible in- dex cases, the unavailability of stored respiratory specimens for the majority of patients to be tested for nCoV, the absence of serological tests for confir- mation of previous infection with nCoV and the case definition of the outbreak which excluded patients without radio- logical evidence of pneumonia. Conclusion and recommendations This outbreak of nCoV, with evidence of likely transmission in a health-care setting, together with our observation of limited secondary transmission, highlights the importance of ongoing vigilance and rapid investigation of cases or clusters of severe respiratory illness, including HCW, with pneumo- nia from any area that match the cur- rent case definition from WHO [6]. Further work is required to determine how widely nCoV is circulating in the area. To establish the final links and to investigate the risk factors for transmis- sion, a seroepidemiological study needs to be conducted in various population groups—HCW, among families and the community—to understand the extent of this outbreak. Until that time, it is important to strengthen both the epidemiological and virological surveil- lance for severe acute respiratory infec- tions in Zarqa hospitals and to detect any changes over time. Acknowledgements The Jordan Ministry of Health expresses it is appreciation and thanks to the World Health Organization Regional Office for the Eastern Mediterranean, the World Health Organization Jordan country of- fice, the United States Naval Medical Re- search Unit-3 in Cairo and the Centers for Disease Control and Prevention, Atlanta, Georgia for their assistance and support. Book 19 Supplement.indb 18 5/16/2013 2:27:24 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S19 Review The early response to a novel coronavirus in the Middle East A. Mounts,1 S. De La Rocque,2 J. Fitzner,1 E. Garcia,3 H.L. Thomas,4 D. Brown,5 H. Schuster,6 K. Vandemaele,1 H. Esmat,7 S. Eremin 8 and A. Mafi 9 1Global Influenza Programme; 2 IHR Monitoring, Procedure and Information; 3 Alert and Response Operations; 8Infection Prevention and Control in Health Care, World Health Organization, Geneva, Switzerland (Correspondence to A. Mounts: mountsa@who.int). 4Field Epidemiology Training Programme; 5Virus Reference Department, Public Health England, London, United Kingdom. 6Public Health England, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 7Public Health Laboratory Unit, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt. 9Pandemic and Epidemic Disease, Division of Communicable Disease Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt. ABSTRACT The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to- human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission as the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community. طسولأا قشرلا في ديدج يجات سويرفل ةركابلا ةهجاولما ،تمصع ةلاه ،لييامدناف تاك ،ترسوش تومله ،نوارب ديفيد ،ساموت سيول ،ايسراغ اكيريإ ،رنزتيف ايلوج ،يكورلا يد نافيتس ،ستنوام نيوطنأ فياعم اضر ليع ،يمريإ يغيرس لماتحلا ةي ِّدج قلق نماكم ةراثإ لىإ 2012 ماع رخاوأ في ةيبرعلا ةريزلجا هبش نم ضىرم ىدل ديدج Coronavirus يجات سويرف فشك ىَّدأ :ةـصلالخا تاردقللو تايطعملل ةعجارم ءارجإ في ةهماسملل ةيلماعلا ةحصلا ةمظنم نم تاثعب ةرثأتلما ةثلاثلا نادلبلا في ةحصلا ءارزو اعد دقو .ةيلود ةيشاف ثودح لاقتنلاا لوح ةمسالحا ةلئسلأا نع ةباجلإل تاءاصقتسلاا لوح تايصوت رادصإ لعفلاب مت دقو .اله ةباجتسلااو تلاالحا نم ديزلما فشكل ةمزلالا يّرتح ءارجإ في تاردقلا باستكا للاخ نم د ُّصترلا تاردق يسحتل ىرخأ تايصوت تردص ماك .سويرفلل فيارغلجا ىدلما لوحو ناسنلإ ناسنإ نم نياويح يدارُف لاقتنا عم سويرفلل فورعم يرغ نياويح عدوتسم دوجو لىإ يرشت يتلا ةرفاوتلما تانِّيبلا لصاوتتو .تامزلاتلما د ُّصرت زيزعتو تاسويرفلا .عمتجلما في ٌماَدَت ْنسُم هنأ ودبي لا - هثودح ناكمإ نم مغرلا لىع وهف ،ناسنلإ ناسنإ نم لاقتنلاا امأ .لاقتنلال ليولأا يئابولا طمنلا هرابتعاب ردصلما Riposte rapide au nouveau coronavirus au Moyen-Orient RÉSUMÉ La détection d'un nouveau coronavirus chez des patients de la Péninsule arabique à la fin de l'année 2012 a soulevé de graves inquiétudes concernant une possible flambée internationale. Les ministères de la Santé des trois pays affectés ont invité des missions de l'Organisation mondiale de la Santé à participer à une revue des données et à un examen des capacités pour dépister les cas à venir et y riposter. Des recommandations ont été formulées pour les recherches visant à répondre aux questions critiques sur la transmission interhumaine et la propagation géographique du virus. Des recommandations supplémentaires ont été effectuées afin d'améliorer les capacités de surveillance en développant la capacité de détection du virus et en renforçant la surveillance syndromique. Les données dont nous disposons semblent toujours indiquer un réservoir animal viral inconnu avec un mode de transmission zoonotique sporadique comme principal modèle épidémiologique de transmission. La transmission interhumaine, si elle est possible, ne semble pas soutenue au sein de la communauté. Book 19 Supplement.indb 19 5/16/2013 2:27:24 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S20 Background The detection of a novel coronavirus in two patients from the Arabian Penin- sula in late 2012 captured the attention of the global public health community for a number of reasons. The virus was of the same family that was responsi- ble for a large multinational outbreak of severe acute respiratory syndrome (SARS) in 2003 and while the novel virus was not closely related genetically, the clinical syndrome associated with the early confirmed cases was severe [1,2]. In addition, the first two reported cases had a history of having been in the area around Mecca and Medina in the weeks before their illnesses and the second case occurred close in time to the Hajj. The subsequent retrospective confirmation of an outbreak among health care workers (HCW) in Jordan with two confirmed and a number of probable cases raised concerns that the virus could be transmissible between humans. The appearance of the virus in three widely separated areas over at least a six-month period further demon- strated the virus’ persistence and wide distribution. These concerns prompted the ministries of health of all three coun- tries (Saudi Arabia, Qatar and Jordan) to invite teams of international experts to review their data and capacity to de- tect and respond to a serious outbreak of a novel pathogen. Primary questions At the outset, the working hypothesis regarding the emergence of the novel coronavirus was that it had a zoonotic origin with animal host(s) and sporadic spill-over into humans. However, the evidence for this was entirely circum- stantial. If this was not a zoonosis, the sporadic appearance of severe human cases with long periods of time between them and the wide area over which the virus was apparently distributed would have required unrecognized ongoing transmission in the human population to explain the pattern of occurrence. Furthermore, early comparisons with other known coronaviruses suggested a similarity to viruses previously de- scribed in bats, although this may only reflect the paucity of coronavirus se- quences available in public databases for comparison [3]. Finally, it has been demonstrated that the virus could be easily grown in a number of widely used cell lines [4], and therefore would have likely been detected earlier through routine diagnostic testing if circulating widely in human populations over a long period of time. However, the use of cell culture as a standard diagnostic tool has decreased markedly in the past decade in favour of polymerase chain reaction (PCR), which is much less likely to detect novel pathogens. The appearance of a novel patho- gen can have serious public health and economic impacts but the immediate concern is to assess its potential interna- tional implications as described in the International Health Regulations, 2005 [5]. As such, the primary questions to be addressed early in the course of an event include: i) does the pathogen transmit from human to human, if not, ii) what is its geographic distribution and iii) what are the risk factors for ac- quiring infection. For a pathogen to have truly pandemic potential it would need to be easily transmissible from hu- man to human. However, even if non- transmissible among humans, a zoono- sis that is widespread in an animal popu- lation could cause widespread disease among humans, particular if contact between human and animal is frequent or transmission is easy. Answering these critical questions requires thor- ough field investigation to determine the exposure(s) that result in infection, investigate whether human-to-human transmission has occurred, search for unrecognized cases and detect signals that may represent previously unrecog- nized circulation of the novel pathogen in the community (Table 1). Initial missions The initial assessment by the World Health Organization (WHO) was aimed primarily at reviewing the data already collected during investigations by the respective ministries of health in Saudi Arabia, Qatar and Jordan to evaluate the possibility that this event constituted a Public Health Emergency of International Concern (PHEIC) as defined in the IHR (2005). In addition, the WHO missions sought to support the ministries by assisting in a review of their capacity to detect and respond to potential further emergence of the novel pathogen. The information re- viewed included: • The histories given by the cases of exposures to animals, potential en- vironmental sources, and other sick humans in the days before infection, including a history of travel outside of the area where illness first occurred. • Data from investigations of close con- tacts of the known cases, including members of the household, close so- cial contacts and HCWs exposed in the hospital. • Historical trends in data from hos- pital and intensive care unit admis- sions for severe respiratory infections, mortality from pneumonia and the occurrence of severe respiratory dis- ease reported to sentinel surveillance systems. • Hospital infection control policies and procedures. • Respiratory disease surveillance system procedures, policies and ca- pacity, including the capacity to in- corporate testing for novel viruses in the laboratory. Answering the critical questions Several recommendations were made by the missions to specifically address the critical questions (Table 1). Book 19 Supplement.indb 20 5/16/2013 2:27:25 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S21 Human-to-human transmission The first clue to both the source of infection and the presence of human- to-human transmission will often occur in the initial interview with the patient and family. Patients or their proxies should be carefully questioned using memory prompts such as calendars, menus, travel records, etc. about recent travel, exposure to sick individuals, expo- sure to animals, activities, hobbies, and consumption of unprocessed foods and beverages. Questions should initially be open-ended and broad in scope but may become more specific as hypotheses are generated about possible sources of in- fection. Ultimately, exposures of interest identified during the interview process can be tested for significance through carefully designed case–control studies comparing rates of exposure in the cases to rates in similar randomly selected indi- viduals from the community. Members of the household and others with close physical contact should be asked about symptoms occurring around the same time as the known case. If symptoms are reported, virological testing can be used to diagnose infection, if the time frame is appropriate; if the window of oppor- tunity for virological testing has passed, serological testing will be required. There are several challenges to de- termining whether cases or clusters of cases have acquired infection through human-to-human transmission. Pri- mary among these is the fact that a clear history of exposure to potential sources of virus may not be remembered, cases are often incapacitated or dead, and in household clusters, the majority of the members of a household will likely share common environmental expo- sures. Investigation of the first reported case was complicated by the fact that he had died many months prior to discov- ery of the virus that caused his illness. The second case, however, offered a unique opportunity to tease out poten- tial sources of infection and help clarify the incubation period. His history il- lustrates the utility of household inves- tigations. The patient had travelled with select members of his household to Mecca and Medina, the same location where the first case may have acquired infection, two to four weeks prior to illness onset. He then returned home to Doha but also made a visit with other members of his household to a family farm outside the city. Different members of his household had three different types of exposure: exposure to the same environment in Mecca/ Medina, exposure to the household environment in Doha but not Mecca and not the farm, and exposure to the farm but not Mecca /Medina or Doha (farm workers). Because of the challenges in disen- tangling potential sources of infection in household investigations, HCWs car- ing for patients with the novel infection may provide the best first evidence of human-to-human transmission. Care- ful exposure histories using standard questionnaires to document duration and intensity of exposure and the use of personal protective equipment are important. If carried out prospectively, PCR testing can be used to test symp- tomatic workers exposed to the patient. However, the more likely scenario will involve retrospective investigations of workers exposed before recognition of the novel agent and subsequent im- plementation of enhanced infection control. In this situation, serological assays are used to confirm infection. As acute and convalescent sera may not be possible and diagnosis may rely on single sera, the use of control groups chosen from a similar group of unex- posed workers will enable investiga- tors to control for rates of background seropositivity and exposures occurring external to the health care environment. Is the agent a novel pathogen? While a newly recognized agent is presumed to be a novel pathogen, nonspecific clinical presentation and the absence of pre-existing labora- tory tests require a careful search for Table 1 Critical initial questions to address in the initial stages of investigation of a novel pathogen Question Investigation Does human-to-human transmission occur? • Survey of exposed health care workers with serological and virological testing • Contact tracing of exposed family and social contacts supported by serological testing What exposures result in infection? • Interview of cases or proxies; case–control study of exposures What is the source of the novel pathogen? • Virological and serological testing of animals, food stuffs; environmental sampling • Seroepidemiological surveys of specific human risk groups • Testing of stored animal clinical specimens Is the pathogen new? When did it first appear? • Review of recent surveillance data, admission records and vital statistics data for the relevant clinical syndrome • Retrospective testing of stored clinical specimens from studies, surveillance or health care facility archives Book 19 Supplement.indb 21 5/16/2013 2:27:25 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S22 evidence of previous circulation to confirm that it is indeed novel. In the case of nCoV, the most commonly rec- ognized clinical presentation is severe respiratory disease. However, even in prospective studies, the etiology of most community acquired pneumonias are not proven and patients are very often treated empirically [6,7]. Consequently, single, sporadic infections with novel respiratory pathogens may be undetect- able if not investigated as thoroughly as the first diagnosed case of nCoV. However, the appearance of a novel transmissible agent may cause a de- monstrable increase in background rates of respiratory disease. A review of temporal trends in hospital admissions, deaths in the community and cases reported to surveillance systems, such as the sentinel system for Severe Acute Respiratory Infection (SARI), can pro- vide clues as to the timing of the first appearance of novel respiratory patho- gens. In addition, stored specimens previously collected from similar cases either as part of specific studies or ongo- ing surveillance programmes can be tested retrospectively for the presence of the virus. Such strategies have been used to push back the time of first ap- pearance of human immunodeficiency virus (HIV) in Africa. [8]. Retrospec- tive testing of specimens collected in an earlier outbreak of respiratory disease in Jordan demonstrated that the nCoV had been present longer than initially thought. However, review of pneumo- nia admission records, admissions to intensive care for respiratory disease, vital statistics data and data from the SARI surveillance system all indicated that background rates of respiratory disease in the three affected countries had been stable in recent years and had not increased notably since the first appearance of the virus. This would in- dicate that either the agent has not been previously circulating in the community or that the number of cases has been low enough or mild enough that they are lost in the “background noise” of disease caused by a wide variety of pathogens. The absence of a post-introduction surge in cases does provide reassurance that the virus was not transmitting with the same degree of frequency as seen in SARS. Retrospective testing of stored SARI specimens indicated that the virus had not been widely circulating prior to the recognition of the first cases [Jordan Ministry of Health unpublished data] Source of the virus Several recent zoonotic outbreaks have indicated how complicated transmis- sion from a zoonotic source to humans can be. In SARS, the endemic source of the virus was ultimately discovered to be horseshoe bats. However, palm civets were initially implicated as the source of transmission to humans and human− bat exposure likely did not play a direct role in the outbreak [9,10]. Likewise, the Nipah virus has displayed circuitous transmission routes from bat to human. In Malaysia, swine acted at the interme- diary vector and amplifier of infection [11]. In Bangladesh, raw palm sap con- taminated with bat guano has served as a vector [12]. In the nCoV event, both of the first two reported cases had a history of having visited farms with a va- riety of animals in the two weeks prior to illness. However, no direct exposure to animals was reported and no illness was reported in the animals on the farms. In addition, many thousands of animals are imported into the region every year both for consumption and for ritual sac- rifice, and an animal reservoir need not exist in the country where the cases were reported in order to result in exposure. Finding the animal source of a zo- onotic virus can be even more com- plicated when associated with wildlife and a clear route of transmission can be difficult to find as demonstrated by the example of Nipah virus in Bangladesh noted above. However, capture and testing of animals from the environment of cases is often the first step in identify- ing the reservoir of a novel agent. In addition, retesting of stored diagnostic specimens from animal health laborato- ries or from importation screening can provide evidence of both the species of animal and the geographic origin of the virus if external to the country where the cases have occurred, once an appropri- ate test is developed. Secondary investigations Even before the public health impor- tance of a novel pathogen is completely understood, there are a number of criti- cal secondary questions that need to be addressed in order to be adequately prepared to respond in case of accel- erating transmission (Table 2). These are questions that will inform control measures and include the incubation period, mode of transmission, degree of transmissibility, the spectrum of disease severity, and natural history of infection. The data related to these characteristics of the novel pathogen will determine the need for and duration of isolation and quarantine, inform case definitions for case finding and other containment strategies, such as social distancing, if they are needed. Recommendations for system enhancements There are also several areas in which enhancements are likely to be needed to existing systems in order to monitor for future cases and enable appropriate management (Table 3). Surveillance The primary goal of surveillance en- hancements in the context of a novel pathogen should be to monitor for the occurrence of human-to-human or ac- celerating transmission. Two situations that can be useful indicators are clusters of cases with a compatible clinical pres- entation and the occurrence of disease in HCWs. Tight clusters of severe Book 19 Supplement.indb 22 5/16/2013 2:27:25 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S23 Table 2 Important secondary investigations to describe key characteristics of novel pathogens Key questions Investigations/Studies Transmissibility • Period of infectivity and duration of viral shedding • Serial interval • Ro (basic reproductive rate) • Secondary attack rate • Mode of transmission and types of exposure Outbreak investigations including: • Investigations of contacts in health-care settings, households, other institutions. Define attack rates based on exposures within the institutions, time intervals from last exposure to onset of illness. Define types of exposures based on surveys. Use serology in addition to PCR/culture to identify mild and asymptomatic cases. • Community transmission studies. Rates of increase in outpatient visits and admissions to hospital. Phone surveys to monitor rates of change in illness in the community • Enhanced syndromic surveillance • In the event of widespread community transmission, serological surveys before and after transmission (may need to identify archived pre-transmission sera) • Serial testing of confirmed cases to determine duration of viral shedding • Animal studies of transmission and shedding Clinical presentation and course Detailed chart review with data extraction: • Signs, symptoms, laboratory and X-ray findings at initial presentation of confirmed cases • Risk factors for severe vs mild infection • Course of illness including changes in key laboratory parameters, development of complications and interventions needed • Duration of illness • Follow-up of patients for long term sequelae • Development of case definition. Clinical management best practices Detailed chart review documenting treatment modalities and outcomes Morbidity, mortality and case-fatality rate • SARI surveillance data • Hospital/ICU trend data on pneumonia (perhaps also renal or multi-organ failure) • Pneumonia and influenza mortality rates • All-cause mortality rates • Proportion of probable and confirmed cases that die • Proportion of admitted cases that die • Serological survey of exposed population to determine attack rate • Community death surveys Source of virus Animal studies to identify reservoir: • Animal capture surveys • Surveys of markets, farms, etc. • Testing of archived materials from animal diagnostic laboratories, food and importation screening Laboratory diagnosis, sensitivity and specificity • Define different PCR targets to be used according to type of specimen and timing from onset of illness. • Development of sensitive and specific serological test • Validation of PCR sensitivity/specificity • Best specimen for testing • Best timing of collection • Production of control material • Serological testing of symptomatic cases with comparison to PCR/culture from multiple sites (e.g. nasopharyngeal, oropharyngeal, sputum, lower airway, stool) • Community serosurveys and/or seroprevalence in stored sera Virological characteristics • Duration of survival in environment and viability • Receptor distribution • Genetic characterization: degree of variation between viruses, relatedness to other viruses • Sensitivity to disinfectants • Antiviral sensitivity • Laboratory characterization • Comparison of genomic sequences • Viral culture in range of cells from different species ICU = intensive care unit; SARI = Severe Acute Respiratory Infection; PCR = polymerase chain reaction Book 19 Supplement.indb 23 5/16/2013 2:27:25 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S24 respiratory disease occurring in small groups of individuals such as a family or classroom are an unusual event outside of chronic care facilities and gener- ally represent an event of public health importance [13]. Pneumonia related to seasonal influenza, pneumococci, haemophilus influenza infections and other commonly recognized pathogens typically does not occur in multiple members of the same family, classroom or work place in a short period of time. As such, clusters always deserve inves- tigation. Indeed, the occurrence of a family cluster was the first indication of the appearance of influenza A(H7N90) in China in April 2013. HCWs likely acquire pneumonias at a similar rate as other adults of similar age and health status. However, due to the fact that they may have a higher risk of exposure to human sources of infection and are not from the same home environment as the cases for whom they care, they may provide a useful marker of human- to-human transmission for novel patho- gens. The presence of a pre-existing surveillance system for SARI greatly facilitates the establishment of a system to monitor for widespread community transmission and real-time detection of a sudden surge in cases. These systems are usually established for influenza moni- toring and use molecular techniques to test for influenza viruses as part of the system [14]. They provide baseline data on the occurrence of respiratory disease Table 3 Recommendations for enhancing detection capacity and preparedness for response to novel pathogens Domain Enhancement Surveillance • Implement monitoring for clusters, health care workers and/or cases fitting case definition • Introduce laboratory testing for novel agent • Review quality of routine surveillance monitoring systems Infection control • Ensure implementation of standard precautions and appropriate specific measures aimed at novel pathogen (e.g. droplet precautions in the case of a respiratory pathogen) • Review patient triage and flow processes in health care facilities to ensure appropriate handling of potential cases • Voluntary quarantine of exposed contacts and isolation of cases, depending on available epidemiological data in the community and can be adapted for monitoring nCoV by the incorpora- tion of specific testing into the operating procedures. In the case of nCoV, limited evidence from early cases indicated that the virus might be more easily detected in lower respiratory tract specimens ne- cessitating a slight adjustment of speci- men collection practice in the existing system [15]. The addition of testing for nCoV as a routine diagnostic tool for community acquired pneumonias used at the discretion of the treating clinician in areas where the virus is thought to be present can also provide additional monitoring. Enhancing laboratory capacity in the age of molecular techniques such as PCR is often a matter of incorporation of new primers into existing testing panels. However two important considerations are required in the context of a novel pathogen. The first is biosecurity in the extraction of RNA. With a novel agent, especially one known to cause severe and fatal disease, at least a BSL2 facility including use of a microbiological safety cabinet (class 1, 2, or 3) is required for the handling of potentially infec- tious materials. While this is beyond the capacity of most routine virological diagnostic laboratories, the facility may be available in laboratories handling tuberculosis specimens. In addition, the widespread use of multiplex PCR platforms may complicate the introduc- tion of new primers for novel agents. The interplay between different primers and reagents in a multiplex PCR plat- form requires a great deal of testing and validation. The primers for novel agents will initially have to be tested in a separate PCR to determine optimal cycling conditions before being incor- porated in the multiplex PCR. Finally, the interpretation of PCR results can be problematic as their sensitivity and rela- tionship to actual infection is generally unknown early in the course of an event with a novel pathogen. Without actual culture and the support of serology to document seroconversion, it may prove difficult to clearly know that infection has in fact occurred with a positive PCR. Infection control Health care facilities played an impor- tant role in the transmission of SARS in the 2003 outbreak and the imple- mentation of rigorous infection control practices was critical to breaking chains of transmission. The successful preven- tion of amplification of nCoV infections associated with health care facilities will depend on the full implementation of all core components for infection preven- tion and control (IPC) programmes 16]. Most nosocomial transmissions occur in the absence of basic IPC pre- cautions and before a specific infection is suspected or confirmed, hence the routine application of standard IPC precautions and additional measures to prevent spread of acute respiratory infections (ARI) when caring for symp- tomatic patients is essential to reduce the spread of any ARI in health-care Book 19 Supplement.indb 24 5/16/2013 2:27:25 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S25 References 1. Corman V et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Eurosurveillance, 2012, 17(39):pii 20285. 2. Zaki A et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367(19):1814–1820. 3. Public Health England. Health Protection Agency. Genetic se- quence information for scientists about the novel coronavirus 2012 (http://www.hpa.org.uk/Topics/InfectiousDiseases/ InfectionsAZ/NovelCoronavirus2012/, accessed 6 May 2013). 4. Müller MA et al. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. mBio, 2012, 3(6):1–5. 5. International Health Regulations, 2005, 2nd ed. Geneva, World Health Organization, 2005:43. 6. Mandell LA et al. Infectious Diseases Society of America/ American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases, 2007, 44(Suppl. 2):S27–S72. 7. Bartlett JG et al. Practice guidelines for the management of community-acquired pneumonia in adults. Clinical Infectious Diseases, 2000, 31:347–382. 8. Zhu T et al. An African HIV-1 sequence from 1959 and implica- tions for the origin of the epidemic. Nature, 1998, 391:594–597. 9. Guan Y et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science, 2003, 302(5643): 276–278. 10. Li W et al. Bats are natural reservoirs of SARS-like coronavi- ruses. Science, 2005, 310(5748):676–679. 11. Parashar UD et al. Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998–1999 outbreak of severe encephalitis in Malay- sia. Journal of Infectious Diseases, 2000, 181:1755–1759. 12. Luby SP et al. Foodborne transmission of Nipah virus, Bang- ladesh. Emerging Infectious Diseases, 2006, 12(12):1888–1894. 13. Puro VGE. Clustered cases of pneumonia among healthcare workers over a 1-year period in three Italian hospitals: applying the WHO SARS alert. Infection, 2006, 34(4):219–221. 14. Interim epidemiological surveillance standards for influenza. Geneva, World Health Organization, 2012. 15. Bermingham A et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United King- dom from the Middle East, September 2012. Eurosurveillance, 2012, 17(40):pii 20290. 16. Core components of infection prevention and control pro- grammes in health care. Aide-memoire. Geneva, World Health Organization, 2011 (Aide-memoire) (http://www.who.int/csr/ resources/publications/AM_CoreCom_IPC.pdf, accessed 6 May 2013). 17. Seto WH et al. Infection prevention and control measures for acute respiratory infections in healthcare settings: an update. Eastern Mediterranean Health Journal, 2013, 19(Suppl.):S39–S47 18. Flu and the Mexican economy; a painful tune. The Economist, 1 May 2009. settings. These as well as the additional precautions to be applied when caring for patients with probable or confirmed infection with nCoV are discussed in detail in the accompanying article in this issue of EMHJ by Seto et al. on infection prevention and control measures [17]. Conclusions Early investigations into the appearance of a novel coronavirus in the Middle East indicated that sustained commu- nity transmission was not occurring. Re- view of the available data suggested that while nosocomial human-to-human transmission might have occurred in Jordan in April 2012, transmission did not appear to occur frequently or easily. Enhancements to surveillance includ- ing acquiring the appropriate prim- ers for diagnosing infection with the novel agent have enabled the affected countries to detect further cases which have not markedly changed the initial assessment. However, further vigilance is needed along with expanded testing to determine the full geographic extent of the virus. The source of the virus re- mains a mystery that urgently needs to be solved. The appearance of a novel patho- gen carries many inherent risks over and above those to global public health that create a reluctance by national au- thorities to announce its appearance. The economic impact can be substantial as demonstrated in Mexico when the novel influenza A(H1N1) virus first ap- peared [18]. As such, the risk to global public health from a novel pathogen with unknown potential for international spread must be balanced with the risk to local economies from an exagger- ated and unnecessary response from a concerned public. The most effective way to mitigate the negative impact of an emerging novel pathogen is through rapid investigation and response with the support of international partners, as needed. The International Health Regu- lations ratified by WHO Member States in 2005 established a mechanism for the confidential sharing of information be- tween WHO and other Member States early in an event before its significance is even fully evaluated. This greatly reduces disincentives to information sharing and facilitates global cooperation. The SARS experience of 2003 taught many lessons about how to respond to global crises. The elements that made the response successful included the open sharing of information internationally, the rapid deployment of teams to support and sup- plement manpower in affected countries, and the global coordination of research activities and the sharing of results be- fore their publication so that they could inform response efforts. Answering the critical questions around this novel pathogen will require similar efforts Book 19 Supplement.indb 25 5/16/2013 2:27:25 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S26 Review Novel coronavirus: the challenge of communicating about a virus which one knows little about G. Härtl1 1Coordinator, Department of Communications, World Health Organization, Geneva, Switzerland (hartlg@who.int). ABSTRACT Following the severe acute respiratory syndrome (SARS) event in 2002/2003, the World Health Organization (WHO) developed outbreak communications guidelines. With the emergence in September 2012 of a novel coronavirus, WHO’s public communications response was initiated and planned in light of these guidelines and 5 principles of trust, transparency, announcing early, listening and planning. This review describes WHO’s communication response to the novel coronavirus event and its efforts to provide early, accurate information via various media to keep the public appraised of the situation, and its commitment to continued communication on an ongoing basis. هنع تامولعلما ردنت سويرف لوح يملاعلإا لصاوتلا يدتح لتراه يروغيرغ لصاوتلل ةيداشرإ لئلاد ةيلماعلا ةحصلا ةمظنم ت َّدعأ ،2013/2012 ْنيَماع في )سراس( ةميخولا ةدالحا ةيسفنتلا ةمزلاتلما ثودح دعب :ةـصلالخا ةيلماعلا ةحصلا ةمظنم ةباجتسا تقلطنا ،2012 برمتبس/لوليأ في ديدلجا Coronavirus يجاتلا سويرفلا علادنا عمو ،تايشافلا لوح يملاعلإا عماتسلااو ركابلا نلاعلإاو ةيفافشلاو ةقثلا يهو ةسملخا ئدابلماو ،ةيداشرلإا لئلادلا ءوض لىع اهطيطتخ متو روهملجا عم يملاعلإا لصاوتلل ةمظنلما اهتلذب يتلا دوهلجاو ديدلجا يجاتلا سويرفلا لوح يملاعلإا لصاوتلا في ةيلماعلا ةحصلا ةمظنم ةباجتسا ةساردلا هذه فصتو .طيطختلاو رارمتسلااب ةمظنلما مازتلا بناج لىإ ،عاضولأا لىع علاّطا لىع سانلا مومع ءاقبإ ةَي ْنغُب ةيملاعلإا لئاسولا فلتمخ برع ةقيقدو ةركاب تامولعم ميدقتل .عطقني لا ٍوحن لىع يملاعلإا لصاوتلا في Nouveau coronavirus : difficultés de communication sur un virus encore mal connu RÉSUMÉ Suite à l'épisode du syndrome respiratoire aigu sévère en 2002/2003, l'Organisation mondiale de la Santé a élaboré des lignes directrices sur la communication lors des flambées de maladies. Après l'émergence d'un nouveau coronavirus en septembre 2012, l'Organisation mondiale de la Santé a lancé des actions de communication publique à la lumière de ces recommandations et des cinq principes de confiance, de transparence, d'annonce précoce, d'écoute et de planification. Le présent article décrit les actions de communication menées par l'Organisation mondiale de la Santé face à l'émergence du nouveau coronavirus, les efforts pour fournir rapidement des informations exactes par l'intermédiaire de divers médias afin de tenir le public au courant de la situation. Il présente également l'engagement de l'OMS pour une communication continue et régulière. Book 19 Supplement.indb 26 5/16/2013 2:27:26 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فىاضلإا ددعلا S27 Introduction The experience of communicating and the lessons learned during the severe acute respiratory syndrome (SARS) event led the World Health Organi- zation (WHO) to develop the WHO Outbreak Communications Guidelines [1]. These Guidelines stipulated that all acute public health event communica- tions should be planned, organized and executed in keeping with the 5 princi- ples: trust, transparency, announcing early, listening and planning. Since the SARS event 10 years ago, WHO has communicated during acute public health events according to these tenets. WHO has also conducted considerable training—both of its own and of Ministry of Health staff around the world—in the art of communicat- ing quickly and effectively, according to these 5 principles. The benefits of early, transparent and effective outbreak communications have been seen in nu- merous instances, as have the pitfalls of not communicating using these 5 principles. Of the 5 principles, trust is the key. It is the hardest to build and the easiest to lose. Trust is earned over long pe- riods by being open and honest with one’s audiences, while trust is easily lost when those same audiences believe that the communicator is hiding or being economical with the truth. The first goal, therefore, of any and all commu- nications during an acute public health event must be to build and retain trust, for only when audiences trust the com- municator, will they listen to and take the protective public health actions which the public health spokesperson is recommending. The public communications efforts of the WHO during the novel corona- virus event were initiated and planned in this light: it was the Organization’s in- tention to communicate openly about what it did and did not know concern- ing this virus so that it became a trusted source of information and its audiences would follow its public health advice. WHO’s communication response WHO was notified on 22 September 2012 of a Qatari national, in the United Kingdom in the intensive care unit of a London hospital, who had been found to be infected with a novel coronavi- rus genetically almost identical to that found in a Saudi Arabian patient in June 2012. Very little further information was available at this time. Within WHO, a communications team was immediately established as a key component of the larger response team. The operational team consisted both of public communications and information management profession- als: a communications coordinator, a full-time communications staff member seconded to the response team, 2 social media professionals monitoring the event in various media channels and putting out information via those same channels as needed, an information management manager, a report writer and an intern (the Director of Commu- nications was a member of the Senior Policy Group on Novel Coronavirus and took decisions in policy areas when needed but was not involved in the day- to-day operational team). The first communications actions were to monitor what was being said in public about the event, issue a Dis- ease Outbreak News (DON), and then tweet the same information as had been released in the DON via social media channels. A dedicated website on the novel coronavirus soon followed, where all information known about the virus and the cases, and relevant guidance was posted in a single place [2]. According to the first DON posting on the novel coronavirus, on 23 Sep- tember 2012, WHO had been notified by the authorities in the United King- dom, where the patient then was, of a 49 year-old Qatari national with acute respiratory syndrome and renal failure who had a travel history to Saudi Arabia and Qatar. The clinical sample collected from the 49 year-old Qatari patient was compared with that of a virus sequenced previously by the Erasmus University Medical Centre, Netherlands from lung tissue of a fatal case earlier in 2012 in a 60-year-old Saudi national. WHO was able to confirm that the 2 virus samples were 99.5% identical, but no further information was available [3]. Social media, Twitter in particu- lar, have become the main means for WHO to get news out quickly. WHO’s first experience with social media came during the influenza pandemic in 2009–2010, when WHO tweeted out the daily increases in case numbers and also monitored what was being said about WHO in the social media sphere, but at that time the organization’s en- gagement did not go beyond that: it had no policy, and little experience, of how to deal with social media and how to respond when WHO was mentioned or, worse, criticised in this medium. However, this was to change when the recommendations of the International Health Regulations Review Committee on the performance of WHO during the influenza pandemic noted that one of the areas where WHO needed sub- stantial strengthening was social media/ communications. As a result, WHO established a dedicated social media function at the start of 2012, and what had been 500 followers of WHO’s Twitter feed in April 2009 had grown into more than 600 000 by the start of 2013. Many of the most active followers of WHO are journalists and public health experts and practitioners. A priority, therefore, was to re-transmit the news contained in the DON via WHO’s Twitter feed: Some of the most prominent of the bloggers and tweeters who engaged with WHO and re-tweeted WHO on Book 19 Supplement.indb 27 5/16/2013 2:27:26 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S28 the novel coronavirus issue from the outset included Mike Coston, Maryn McKenna, Helen Branswell, Tom “Treyfish” Watkins, Crawford Killian and Henry Niman. General media interest was also high and, predictably, journalists grabbed onto the fact that the novel coronavirus is from the same family as SARS. A typi- cal lead paragraph was the one from the BBC’s online article of 24 September 2012: “A new respiratory illness similar to the Sars virus that spread globally in 2003 and killed hundreds of people has been identified in a man who is being treated in Britain” [4]. The headlines and leads were disturbing from a public health point of view because a) very little was known about this virus; and b) what information was being relayed by media was misinformation: what public health officials did know did not indicate that the transmissibility was at all like that of the SARS virus, or that nearly as many people had been infected. WHO, with its public partners, had to move quickly to correct these mis- perceptions before incorrect and inap- propriate, and potentially-damaging, public health and other measures were taken in the belief that the world was facing a new SARS. On 25 September 2012, the Head of Media for WHO briefed Geneva-based journalists, emphasizing on numerous occasions during the press conference that the only similarity between the coronavirus and SARS were that they were from the same family. Similarities, e.g, epidemiological, ended there. In addition, to reinforce this message that novel coronavirus was not like SARS, a second DON was issued on 25 Sep- tember with this message (and others, including an interim case definition) [5], and WHO’s social media team distributed this information via social media channels. A third DON was issued on 28 September. Because of the severity of the first 2 cases, WHO and its partners remained on high alert, and investiga- tions continued, but the fact that there had not been any new cases by this date led WHO to state that the novel coro- navirus could not be transmitted easily from person-to-person [6]. By this date, with no new cases, and apparently no growing story, media interest began to wane. Behind the scenes, WHO contin- ued to work to try gain more infor- mation on the virus: much about its origins, its transmissibility, its virulence, its geographic spread and how it spread, remained unknown. In fact, on 10 Oc- tober 2012, in the next DON which WHO published [7], it was stated that the governments of Saudi Ara- bia, Qatar and the United Kingdom, supported by WHO, were continuing to try to gain a better understanding of the disease and the likely source of infection. Despite WHO and other organizations having deployed teams to Saudi Arabia and Qatar, and even after careful follow-up of close contacts of the 2 confirmed cases, and with a heightened state of global surveillance in place, there was no evidence of human-to-human transmission of the virus, or even of more cases. While public interest in general in the virus had died down (as judged by the number of stories written on the topic), some of the more specialized health journalists who were pursuing the story now turned from simply fol- lowing the story to asking the ques- tions which WHO and its partners so far had not been able to answer. Richard Knox of National Public Ra- dio, on 5 October, speculated in an article entitled Arabian Coronavirus: Plot Thickens but Virus Lies Low [8] that, given the fact that 1 of the 2 cases was from Riyadh, Saudi Arabia, whilst the other was from Qatar, the virus had to be widespread and that public health investigators weren’t picking up what had to be more cases. Knox went on to do what no one else had so far done: give a name to the virus. With no new cases, and no develop- ments to report on from the laboratory and field investigations, the 10 October 2012 DON seems, however, to have acted as a summary to an event which apparently was increasingly being re- garded as waning, or closed, or having no more media interest, because between 15 October and 20 November, not one article appeared in the English-language mainstream media on the subject. In light of these events, the WHO operational team was wrapped up. This was all to change rapidly, how- ever, with the announcement to WHO on 23 November of a new family cluster in Saudi Arabia and an additional case in Qatar. WHO responded publicly by issuing a DON [9], sending an email notification to journalists and alerting its over 600 000 Twitter subscribers to the DON and its contents—as can be seen in the jump in Twitter activity on 23 November (Figure 1). Internally, WHO reconvened its rapid response team, and the Com- munications Team was once again a key part of this team. The Saudi Arabian/Qatari cases were followed rapidly by the notifica- tion to WHO of cases in Jordan: WHO issued a DON on 30 November 2012 alerting the world to the fact that Jordan had, through retrospective investiga- tion, found 2 cases of novel coronavirus infection that had occurred in April [10]. Throughout that week, however, traditional media interest remained small. Conversation on social media, on the other hand, picked up pace, with public health commentators and health journalists carrying on a discussion around WHO’s announcements. Espe- cially after the cases in Jordan were an- nounced, journalists started to ask how widespread the virus was, and wondered both how likely it was that the disease could spread to other countries and even other continents, and how good the world’s surveillance systems were. Book 19 Supplement.indb 28 5/16/2013 2:27:26 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فىاضلإا ددعلا S29 Traditional media interest between 20 November 2012 and 15 December 2012 was not as extensive as it had been in September and October. Was this because the pattern of infection was no different from the cases seen originally in Saudi Arabia and Qatar? Or was it be- cause there was no sustained human-to- human transmission, no large events? Were the infections, and the cases, too distant and too sporadic to care about? With no sign of human-to-human transmission, maybe the cases would be isolated and people outside the region would not be affected, contrary to what the situation had been during the SARS event? The event seems to have followed the same pattern in November and December as it had in September and October: a flurry of cases and activity, with the setting up of an internal WHO operational team, which was then stood down as no new cases were found. WHO again stood down its operational team. Media chatter, i.e. interest in novel coronavirus continues, however: in January and February 2013, numer- ous scientific and specialist journalists continued to write about the virus and what is known about it. For example, Yanzhong Huang wrote in the blog of the Council of Foreign Relations on 4 February 2013 that, “SARS has had a lasting impact on our collective psyche. In September 2012, a novel coronavirus was identified in 2 patients from the Middle East, raising the spectre of a new SARS-like outbreak” [11]. Medscape cites the 9 cases and 5 deaths through 2012, and warns that, “this might turn out to be a very limited and unimpor- tant outbreak in the global scheme of infectious diseases. However, we are reminded that SARS was also a coro- navirus of zoonotic origin that, with the help of a super spreader, became the source of a large global epidemic” [12]. Conclusion The fact that interest is still there, that the public continues to associate novel coronavirus with SARS, and that people want answers, should serve as a remind- er to WHO and its partners: the more answers public health experts can pro- vide now, the greater the public’s trust in these institutions will be if and when the virus should become easily transmis- sible between humans and cause more widespread morbidity and mortality. WHO, for its part, will continue to give communications primacy as a public health tool and advocate amongst its partners for gaps in information to be filled and the results of epidemiological, laboratory and other work on the virus to be communicated publicly and in a timely manner. The more WHO and its partners can communicate on an ongoing basis, even when this (or any) event is not in an acute phase, the bet- ter WHO and its partners will be able to build and maintain trust and thus be more effectively listened to when giving public health advice in the heat of an acute public health event. Good outbreak communications practices in and outside of acute public health events make communications a more effective public health tool. References 1. WHO Outbreak communications guidelines. Geneva, World Health Organization, 2005 (http://www.who.int/infectious- disease-news/IDdocs/whocds200528/whocds200528en. pdf, accessed 8 May 2013) . 2. Coronavirus infections. Geneva, World Health Organization, Global Alert and Response (GAR), 2013 (http://www.who.int/ csr/disease/coronavirus_infections/en/index.html, accessed 8 May 2013). 3. Novel coronavirus infection in the United Kingdom. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http://www.who.int/csr/don/2012_09_23/en/index. html, accessed 8 May 2013). 4. Roberts M. New 'Sars-like' coronavirus identified by UK officials. BBC news website, 2012 (http://www.bbc.co.uk/news/ health-19698335, accessed 8 May 2013). 5. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_09_25/en/index.html, ac- cessed 8 May 2013). 6. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_09_28/en/index.html, ac- cessed 8 May 2013). 1,200,000 1,000,000 800,000 600,000 400,000 200,000 0.0 12:00 am 4:00 am 8:00 am 12:00 pm 4:00 pm 8:00 pm Reach: 2,005,172 people Exposure: 20,362,896 impressions Activity: 2,560 tweets Contributors: 1,615 users Figure 1 Twitter activity for 23 November 2012 (top hashtag was #coronavirus) Book 19 Supplement.indb 29 5/16/2013 2:27:26 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S30 7. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_10_10/en/index.html, accessed 8 May 2013). 8. Knox R. Arabian coronavirus: plot thickens but virus lies low. Washingto, NPR (website), 2012 (http://www.npr.org/blogs/ health/2012/10/05/162394086/arabian-coronavirus-plot- thickens-but-virus-lies-low, accessed 8 May 2013). 9. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_11_23/en/index.html, accessed 8 May 2013). 10. Novel coronavirus infection – update. Geneva, World Health Organization, Global Alert and Response (GAR), 2012 (http:// www.who.int/csr/don/2012_11_30/en/index.html, accessed 8 May 2013). 11. Hang Y. Ten years after SARS: five myths to unravel. New York, Council on Foreign Relations, Asia Unbound (blog), 2013 (http://blogs.cfr.org/asia/2013/02/04/ten-years-after-sars- five-myths-to-unravel/, accessed 8 May 2013). 12. Bartlett JG. 2012’s top 10 stories in infectious disease that will change practice. Novel coronavirus: another SARS? Medscape Today News, 24 January 2013 (http://www.medscape.com/ viewarticle/777952_6, accessed 11 May 2013). Book 19 Supplement.indb 30 5/16/2013 2:27:26 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S31 Review Novel coronavirus infection in the Eastern Mediterranean Region: time to act M.R. Malik,1 A.R. Mafi ,1 J. Mahjour,2 M. Opoka,1 M. Elhakim 1 and M.O. Muntasir 1 1Pandemic and Epidemic Disease, Department of Communicable Disease Prevention and Control. World Health Organization. Regional Office for Eastern Mediterranean (Correspondence to M.R. Malik: malikm@who.int). 2Department of Communicable Disease Prevention and Control. World Health Organization. Regional Office for Eastern Mediterranean. ABSTRACT The Eastern Mediterranean Region of World Health Organization has been an emerging focus for global health after the discovery of a novel coronavirus infection in some countries in the Region. The Region has already witnessed a number of emerging zoonoses with epidemic potential. In view of this new virus, there is now an urgent need for strong public health vigilance and monitoring of the evolution of the virus in the Region. The situation will challenge and test the national health authorities’ resilience and ability to respond in a timely manner. This review summarizes the evidence related to the emergence in the Region of new epidemic diseases of predominantly zoonotic origin and the challenges posed by the discovery of the novel coronavirus infection, and outlines recommendations for the countries for early detection, prevention and control of public health threats from this novel coronavirus infection. لمعلا ناوأ نآ :طسوتلما قشر ميلقإ في ديدلجا يجاتلا سويرفلاب ىودعلا صرتنم دممح ،ميكلحا دممح ،اكوبوأ نترام ،روجمح داوج ،فيام اضر ليع ،كلام رانومام Coronavirus يجاتلا سويرفلاب ىودعلا فاشتكا دعب لماعلا في ةحصلل مماتهلاا ةرؤب ةيلماعلا ةحصلا ةمظنلم طسوتلما قشر ميلقإ حبصأ :ةـصلالخا لظ فيو .ةئبولأا ببست نأ نكمي يتلا ةدجتسلما ردصلما ةيناويلحا ضارملأا نم ًاددع لعفلاب ميلقلإا دهش دقف .ميلقلإا نادلب ضعب في ،ديدلجا هذه نإ لب .ميلقلإا في سويرفلا اذه روطت ةعباتلم ةيمومعلا ةحصلا لامج في ييوق دصرو ظ ُّقيت لىإ نلآا ةجالحا ستم ،ديدلجا سويرفلا اذه دوجو تاذ تانِّيبلل ًاصيخلت ةعجارلما هذه م ِّدقتو .بسانلما تقولا في ةباجتسلاا لىع اتهردقو اهتنورمو ةيحصلا تاطلسلل ًارابتخاو ًاي ِّدتح لثتم عاضولأا يجاتلا سويرفلاب ىودعلا فاشتكا نع ةجمانلا تايدحتلاو ،ردصلما ةيناويح نوكت نأ بلغي ةديدج ةيئابو ضارمأ نم ميلقلإا في رَهَظ ماب ةلصلا ىودعلا نع ةئشانلا ةيمومعلا ةحصلا لىع تاديدهتلل ةحفاكلماو ةياقولاو ركابلا فشكلا لجأ نم نادلبلل ةهّجولما تايصوتلا ضرعتستو ،ديدلجا .ديدلجا يجاتلا سويرفلا اذبه Infection par le nouveau coronavirus dans la Région de la Méditerranée orientale : l'heure est à l'action RÉSUMÉ La Région de la Méditerranée orientale de l'Organisation mondiale de la Santé est progressivement devenue un centre d'attention en matière de santé mondiale après la découverte d'une infection par un nouveau coronavirus dans certains pays de la Région. La Région a déjà connu un certain nombre de zoonoses émergentes à potentiel épidémique. Face à ce nouveau virus, une grande vigilance en matière de santé publique et une surveillance de l'évolution du virus dans la Région sont maintenant nécessaires de manière urgente. Cette situation risque de mettre à l'épreuve les capacités de résilience et de riposte rapide des autorités sanitaires nationales. Le présent article synthétise les données concernant l'émergence dans la Région de nouvelles maladies épidémiques, principalement d'origine zoonotique, et les difficultés découlant de la découverte de cette infection par un nouveau coronavirus. Il esquisse en outre des recommendations à l'intention des pays pour le dépistage précoce et la prévention de l'infection par le nouveau coronavirus et l'endiguement de la menace qu'elle représente pour la santé publique. Book 19 Supplement.indb 31 5/16/2013 2:27:27 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S32 Introduction The Eastern Mediterranean Region of the World Health Organization (WHO) comprises 22 Member States and the occupied Palestinian territory and is home to over 583 million people [1]. The Region extends from Pakistan in the east to Morocco in the west and as far south as Somalia and as far north as the Islamic Republic of Iran (Figure 1). Although the countries of the Re- gion share many common elements of history and culture, the Region abounds with sociopolitical contrast and contra- dictions. There is wide variation in the gross national income (GNI) per capita among the countries [2]. Such variation and income disparities have a major in- fluence on overall health spending and a significant impact on current health achievements in the Region. The geopolitical situation of the Re- gion is extremely challenging since many countries are in a state of protracted humanitarian emergencies or recover- ing from conflict. Providing emergency medical assistance to these countries has become a normative function of the WHO’s Regional Office for Eastern Mediterranean in recent years [3]. Over the past decade, the Region has faced repeated outbreaks from emerging in- fectious diseases as a result of various factors [4]. International travel either for tourism, business or religious reasons, globalization and the varying capacity of surveillance systems in the countries in the Region to detect and diagnose early an unknown pathogen are signifi- cant risk factors for rapid international spread of any emerging infections once such infections or diseases emerge in the Region. Certain disease amplifiers, such as population movement, frag- mented health systems, weak response and laboratory diagnostic capacity, and disruption of routine public health services in crisis-affected countries, have also contributed considerably to the surge of emerging infectious diseases in the Region [5]. In this paper, we summarize the evidence related to emergence of new epidemic diseases in our Region that are predominantly zoonotic in origin and the challenges posed by the discov- ery of a novel coronavirus infection in the Region, and outline some specific recommendations for the countries for early detection and prevention of public health threats from this novel coronavi- rus infection. Emerging infectious disease in EMR The Region presents daunting health challenges in the field of emerging zoonoses. Evidence shows that over 60% of the emerging infectious diseases !( !( !( !(!( !( !( !( !( !( !(!( !(!( !( !( !( !( !( !( !( !( !( !( !( !(!(!( !( !( !( !( !(!( !( !(!( !( !( !( !( !( !( !( !(!( !( !( !( !( !( !(!(!(!(!( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !(!( !( !( !( !( !( !( !(!( !( !( !(!(!( !( !( !(!( !( !( !( !( !( !(!( !( !( !( !( !(!( !( !( !( !( !( !(!(!(!( !( !( !( !(!(!( !(!( !(!(!( !(!( !( !(!( !( !( !( !(!( !( !( !( !( !(!( !( !( !(!( !( !( !(!( !( !( !(!(!( !( !( !( !( !(!( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( South Sudan United Arab Emirates Qatar Yemen Saudi Arabia Tunisia Syria Somalia Pakistan Oman Morocco Libya Lebanon Jordan Iraq Iran Egypt Djibouti Kuwait Afghanistan Islamabad As- Sulaymaniyah Kirkuk Samarra Ba qubah Ar- Ramadi Karbala' Al-Kut Al- Hillah Ad DiwaniyahAn Najaf Al 'Amarah As- Samawah An- Nasiriyah Al Mafraq Az Zarqa' At Tafilah Irbid Najran Al Karak Ma'an Hawalli Al- Jahrah Al-Ahmadi SidonNabatiyet et Tahta Zahle B'abda DarnahAz Zawiyah Al Khums MisratahGharyan Benghazi Ajdabiya Sabha Oujda Fes MeknesCasablanca Marrakech Agadir Jidd Hafs Ar RifaSitrah Peshawar Lahore Quetta Karachi An Nabk Ar'ar Sakakah Tabuk Ha'il Buraydah Ad Damman Jaizan Abha Laascaanood Boosaaso Ceerigaabo Hargeysa Burao Garoowe Gaalkacyo Dhuusa Mareeb Beledweyne Xuddur Garbahaarey Baydhabo Jawhar Marka Bu'aale Kismaayo Dongola El Fasher Malakal Wau Al- Hasakah Ar RaqqahIdlib Al Ladhiqiyah Dayr az ZawrHamahTartus Al Qunaytirah As SuwaydaDar'a Ra's Al- Khaymah Umm Al QaywaynAjman Sharjah Dubai Fujairad L'Ariana Sousse Gafsa Gabes Sa'Dah Hajjah Marib Al MukallaAl Hudaydah Dhamar 'Ataq Al BaydaIbb Ta'izz Lahij Jalabad Zareh Sharan Feyzabad TaloqanKonduz Mazar-E SharifSheberghan Aybak BaghlanMeymaneh Mahmud- E Eraqi Charikar Qal eh-ye AsadabadBamian Mehtar Lam Chaghcharan Mayda Shahr Herat Baraki Barak Gardez Ghazni Tarin Kowt Farah Qalat Kandahar Lashkar Gah Zaranj ObockTadjoura Ali Sabieh Dikhil El'Arish El Tur Dumyat Marsa Matruh Port Said Kafr el Sheikh El Mansura Damanhur Tanta Shibin el Kom Ismailia Zagizig Benha El Faiyum Beni Suef El Minya Al GhurdaqahAsyut Sohag Qena El- Kharga Aswan Tabriz Orumiyeh Rasht Zanjan Sari Mashhad Semnan Sanandaj Hamadan Kermanshah Ilam Khorramabad EsfahanShahr- E Kord Yazd Ahvaz Yasuj Kerman Shiraz Zahedan Bushehr Bandar- E Abbas Arak As-Salt Dahuk Arbil Tehran Mogadishu Cairo Djibouti Kabul San'a Tunis Abu Dhabi Damascus Khartoum Riyadh Doha Al Manamah Muscat Rabat Tripoli Beirut Kuwait Amman Baghdad Sudan Greece Turkey Algeria United Arab Emirates Niger Guinea-Bissau Sudan EthiopiaNigeria Chad Benin Central African Republic Togo Cameroon Gabon Equatorial Guinea Congo Uganda Kenya Rwanda India Maldives Malta Cyprus Sao Tome & Principe Belarus Germany Netherlands Kazakhstan Poland Belgium Czech RepublicLuxembourg Ukraine Moldova Slovakia Austria Switzerland Liechtenstein Italy Slovenia Hungary France Romania Eritrea Monaco Georgia Bulgaria Kyrgyzstan Andorra Macedonia Uzbekistan Vatican City Azerbaijan Albania Croatia Bosnia & Herzegovina Portugal Congo, DRC Burundi Tanzania Gibraltar Mauritania Senegal Mali Burkina Faso The Gambia Sierra Leone Guinea Ghana Serbia & Montenegro Cote d'Ivory Liberia Spain United Kingdom Ireland Guernsey TurkmenistanArmenia Tajikistan China Russia San Marino !(!(!( !( !( !( !( !( !( !( !( !( !( !( !( !( !(!( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !( Bahrain Iran Oman Qatar United Arab Emirates Saudi Arabia Al-Muharraq Jidd Hafs Ar Rifa Sitrah Umm Al Qaywayn Ajman Sharjah Dubai Al Manamah Doha Abu Dhabi !( !( !( !( !( !( !( !( !( !( !( !(!( !( !( !( !( !( !( !( !( !( !(!( !( !( !( !( !( !( !( !( !( !( !( !( !( !( !(!( !( !( !(!( !( !( !( !( !( !( !( !( !( !( !( Palestine Egypt Jordan Lebanon Syria Saudi Arabia Al Mafraq Az Zarqa' At Tafilah Irbid As-Salt Al Karak Sidon Nabatiyet et Tahta ZahleB'abda An Nabk Al Qunaytirah As Suwayda Dar'a El'Arish Amman Beirut Damascus Disclaimer: The presentation of material on the maps contained herein does 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 areas or its authorities of its frontiers or boundaries Dotted lines on maps represent approximate border lines for which there may not yet be full agreement Production Date Source February 19th, 2012 WHO / EMRO GIS & Health Informatics Support Evidence-based Health Situation & Trend Assessment Produced by © WHO 2012. Al l r ights r eser ve d !( National capital !( Provincial capital Major Rivers Disputed borders EMR Countries Non EMR Countries 0 400 800 1,200 1,600200 KM !( Juba !( El Madina !( Makkah !( Jedah Figure 1 Map of the countries in the Eastern Mediterranean Region of the World Health Organization Book 19 Supplement.indb 32 5/16/2013 2:27:36 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S33 that have been identified since 1940 are zoonotic [6] and thus the Region continues to witness both sporadic and epidemic occurrence of emerging zoon- oses (Table 1). The Region has recently seen out- breaks of yellow fever in Sudan [7], Chikungunya in Yemen [8], West Nile fever in Tunisia [9] and Q fever in Afghanistan [10,11 ] and Iraq [12]. The region is home to a number of arbo and filoviruses. While outbreaks from Crimean–Congo haemorrhagic fever (CCHF) occur periodically in Afghanistan [13], Islamic Republic of Iran [14] and Pakistan [15–18], noso- comial outbreaks of the disease have been reported in recent years as a sea- sonal surge in Iraq [16], United Arab Emirates [18] and Sudan [19–21]. Viral haemorrhagic fevers are perpetual risks in the Region. Ebola haemorrhagic fever in South Sudan in 2004 was the only viral haemorrhagic fever caused by a filovirus seen the Region [22,23]. The sudden expansion of Rift Valley fever, endemic in sub-Saharan Africa, along the animal trade routes to Yemen [24], Saudi Arabia [25,26] and Sudan [27], is a characteristic example of geographic expansion of emerging zoonoses in the Region. The highly pathogenic avian influ- enza spread rapidly through the Region in 2006 with large epizootics reported in a number of countries while human infections occurred in Djibouti [28], Iraq [29], Pakistan [30] and Egypt [31]. Avian influenza is now presumed en- trenched in Egypt with a low level of transmission throughout the year [32]. In 2009, the influenza A (H1N1)pdm 09 of swine origin affected all countries in the Region [33]. Other emerging zo- onotic diseases have occurred in the Re- gion and, while rare, can still cause high morbidity. These include monkey pox [34], sandfly fever [35] and plague [36]. As illustrated by the Alkhurma virus, this Region is also home to newly emerging pathogens of zoonotic origin [37–39]. In the midst of the occurrence of these old and new infectious diseases seen by the world in the past decade, severe acute respiratory syndrome (SARS) was the only emerging zoonoses that did not strike the Region in 2003. Novel coronavirus infections in EMR As if to remind the Region that emerg- ing zoonoses can occur anywhere anytime and that no country is immune to the threats of these diseases, human infection with a novel coronavirus (nCoV) arose in the Region in 2012 and rapidly focused global attention on this new virus [40]. First detected in a Saudi Arabian national in September 2012 who had died of acute respiratory illness in June, it was soon confirmed in a patient from Qatar in London in Oc- tober 2012 with similar illness [41]. In November, two laboratory-confirmed cases were reported retrospectively by diagnosis of stored respiratory and serum specimens of two deceased pa- tients in Jordan with an occurrence date in March–April 2012 from a cluster of healthcare workers whose initial di- agnosis was inconclusive [42]. On 26 March 2013, Germany notified WHO of an imported case of novel corona- virus infection from the United Arab Emirates [43]. By the end of March 2013, of the 17 laboratory-confirmed cases of nCoV infections, including 10 deaths, that were reported to WHO globally [43], 14 cases (82%), including 9 deaths (90%), were reported from four countries in the Region (Jordan, Saudi Arabia, Qatar and the United Arab Emirates) (Figure 2). It is unclear where the initial infec- tion occurred. In the cluster of health- care workers in Jordan, the date of onset of symptoms of a confirmed case was in March 2012, while at least three other cases reported in 2013 had a history of travel to another country (including Pakistan and Egypt) where cases have not been reported previously [44]. The majority of cases reported in the Region are male (12 out of 14) and the cases reported so far show preponderance among older age groups (Table 2). Most cases have been sporadic. However, by March 2013, limited human-to-human transmission had been noted within a household setting in Saudi Arabia and in a healthcare set- ting in Jordan [44]. Risk assessment and mitigation The appearance of a new disease in the Region that had not been seen before and about which little was known of its origin or mode of transmission [44] may constitute a serious worldwide threat with profound implications for global health security. The Region, especially the countries where these novel coronavirus infections occurred, is a favourite destination for millions of tourists and religious pilgrims com- ing from outside the Region and hence represents a substantial risk and major conduit for the global spread of diseases as has been seen with the outbreak of meningococcal meningitis W135 in 2000 and 2001 [45] and cholera in 1984–1986 [46]. Religious mass gatherings like the Hajj pilgrimage in Saudi Arabia is the largest annual religious mass gathering worldwide with over 3 million people performing the Hajj every year [44]. Also over six million Umrah pilgrims visit Saudi Arabia every year. The coun- tries reporting the nCoV infections are also home to large numbers of migrant populations from Asia and Africa. A more cautious approach is therefore needed to understand fully the global threat posed by this novel virus for inter- national spread. Of the total cases reported in the Re- gion, five were sporadic with no second- ary transmission, while the remainder occurred in two clusters, two cases in one cluster in an intensive care unit in Jordan [42] and others in a family clus- ter in Saudi Arabia [44]. Investigations Book 19 Supplement.indb 33 5/16/2013 2:27:36 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S34 Table 1 Selected outbreaks from emerging zoonoses in the Eastern Mediterranean Region of World Health Organization, 2000-March 2013 Disease Country Period Host/reservoir Human health impact References Casesa Deaths Rift Valley fever Yemen 10 Sep– 19 Oct 2000 Cattle, sheep, goats; Aedes mosquitoes (vector) 653 80 24 Saudi Arabia 26 Aug 2000– 22 Sep 2001 886 123 25,26 Sudan 18 Oct 2007– 15 Jan 2008 747 230 27 CCHF Pakistanb 2000–2012 Wild and domestic animals (cattle, goats and sheep); Hyalomma ticks 585 113 15-18 Iran (IR)b 2000–2011 3235 122 14 Afghanistanb 2007–2012 104 15 13 Sudanc 2007-2011 19-21 Yellow fever Sudan Sep–Dec 2005 Primates (mainly monkeys); Aedes mosquitoes (vector) 605 163 59 02 Sep–24 Dec 2012 849 171 7 South Sudan May-Jun 2003 178 27 60 Ebola haemorrhagic fever South Sudan 24 May–26 Jun 2004 Monkeys 17 7 22, 23 Monkey pox Sudan, Unity State 20 Sep 2005– 31 Jan 2006 Unknown but rodents, sun squirrels, even monkeys are implicated 49 0 34 Al-Khurma haemorrhagic feverd Saudi Arabia 2001–2009 Camels and sheep; Mammalian ticks 37–39 Sandfly fever Lebanon 01 Jul–18 Sep 2007 Phlebotomine sandflies 800 – 35 Avian influenza (H5N1)e Iraq Jan–Mar 2006 Poultry, birds, wild fowl 3 2 29 Djibouti 23 Apr 2006 1 – 28 Pakistan 29 Oct–21 Nov 2007 4 2 30 Egypt Jan 2006–Mar 2013 172 62 32 Plague Libya 09–18 Jun 2009 Rodents; fleas 5 1 36 Pandemic influenza All countries 25 May 2009– 6 Aug 2010 Birds; pigs 1019 33 Q feverf Afghanistan 29 May–02 Jun 2011 Domestic animals (sheep, cattle, goats); birds 147 f Chikungunya Yemen Oct 2010–Mar 2011 Monkeys; Aedes mosquitoes (vector) 1657 0 8 West Nile virus fever Tunisia 14 Aug–14 Nov 2012 Birds; mosquitoes (vector) 63 10 9 Novel coronavirus infection Saudi Arabia, Qatar, Jordan, UAE 21 Mar 2012–30 Apr 2013 Unknown but bats are suspected 14 9 43 aSuspected cases including those laboratory-confirmed. bCases reported during the outbreak are included. cNosocomial transmission. dSporadic cases have continued to be reported since 2001. eLaboratory-confirmed cases. fWorld Health Organization. Eastern Mediterranean Regional Office. Weekly Epidemiological Monitor, 2011, 5(28 & 29). CCHF = Crimean–Congo haemorrhagic fever; UAE = United Arab Emirates. Book 19 Supplement.indb 34 5/16/2013 2:27:37 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S35 around previous clusters and cases have not demonstrated onward transmission or increases in rates of severe disease in the area [47]. The fact that this is a new virus and an animal origin is presumed [41,47] and that the mortality rate was high amongst the confirmed cases, it appears that people of all ages may have little protective immunity. As such, the global pandemic threat associated with this virus should not be understated. The ability of this virus to spread be- yond first or second generation should be closely monitored and tracked. The mild presentation and the uncertainty around exposure raise concern that oth- er mild infections and links might have been missed. It is not clear if or when the low levels of sporadic transmission cur- rently seen with this virus will change. In the current situation, there is a need to constantly assess and monitor the evolving threats from this new disease. The only way this can be achieved is through early detection of any unusual patterns in the disease manifestations that can spread on a global scale and by adequate and timely sharing of such disease patterns. Surveillance From the public health perspective, all countries of the Region need to enhance their surveillance for severe acute respiratory infections (SARI). In countries where routine surveillance for SARI may be too resource-intensive, an alternative “best buy” can be a sentinel- based surveillance system for SARI in a geographically representative area com- bined with appropriate strategies for routine collection and rapid laboratory testing of samples to confirm or rule out any circulating nCoV and immediate notification of WHO of any new or untypeable respiratory pathogen. Any unusual cluster of acute respiratory disease needs to be reported to WHO promptly as well. The countries of the Region where cases have occurred or have been linked to in the past need to establish case-based surveillance for SARI and conduct universal screen- ing of SARI patients for nCoV using the latest WHO case definition [48] to determine if the virus is still circulat- ing and the extent of its distribution. From the global perspective, the key would be to detect early any event that signals sustained secondary or tertiary transmission in the community. Laboratory tests The prompt recognition of nCoV infec- tions will largely depend on the labora- tory capacity of the countries to detect and identify such novel pathogens in a timely manner. Epidemiological surveil- lance for SARI will be meaningful only when the laboratory can test the pa- tient’s respiratory specimens routinely Table 2 Characteristics of 14 confirmed cases of nCoV including 9 deaths in the Eastern Mediterranean Region, March 2012– March 2013 Age group (years)a Sex Acute renal failureb Comorbiditiesc Outcome Male Female Died Recovered Still hospitalized 25–34 2 1 1 35–44 2 1 1 3 45–54 3 2 2 2 1 55–64 1 1 1 2 65+ 4 2 1 3 1 Total 12 2 6 3 9 4 1 aNo cases have been found in people under 25 years of age. bInformation for the remaining cases are not available. cComorbidities include pre-existing chronic health conditions such as diabetes, chronic kidney disease, heart disease, lung disease, multiple myeloma, etc. First case reported from Jordan (diagnosed retrospectively), 21 March First case reported from Saudi Arabia, 6 June First case reported from Qatar, 3 September First case reported from United Arab Emirates, 8 March N um be r o f c as es Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Date of onset (month) 2012 2013 Died Survived 6 5 4 3 2 1 Figure 2 Epidemic curve of confirmed cases of novel coronavirus infection in the Eastern Mediterranean Region, March 2012–March 2013 Book 19 Supplement.indb 35 5/16/2013 2:27:37 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S36 and detect any emerging new pathogen. Specific laboratory testing procedures for nCoV have been published [49]. Capacities need to be increased rapidly in all countries for routine confirmation of cases of novel coronavirus infection. Investigation of cases and close contacts A standardized approach for full-scale epidemiological investigation needs to be instituted as soon as any case is con- firmed. The close contacts (households or healthcare provider) need to be identified and followed up for at least 10 days, which is the putative incubation period for nCoV infection. If respira- tory illness occurs within the 10 days after last exposure in a close contact, the contact should be investigated urgently for nCoV infection. Such investigation is important to help understand the spectrum of illness and risk of infection in those exposed. Infection prevention and control during healthcare The current global knowledge on the risk of transmission of nCoV in healthcare settings is limited and based on a small number of cases reported so far globally. However as there is now evidence of limited human-to- human transmission, in at least two healthcare settings possibly involving different modes of transmission [50], strict infection control measures need to be rapidly applied to prevent on- ward transmission that may be associ- ated with health care. The successful prevention of amplification of nCoV infections associated with health care will depend on the full implementation of the core components for Infection Prevention and Control programmes [51] including standard precautions. Additional precautions while caring for patients with probable or confirmed infection with nCoV should depend on risk assessment especially when aerosol-generating procedures are be- ing performed. Clinical care No recognized effective treatment is yet available for nCoV infection [50]. Possible interventions that need to be investigated include convalescent plasma from recovered cases. The premise of this approach is based on some evidence from the treatment of cases with severe acute respiratory virus infection caused by SARS-CoV [52], highly pathogenic avian influenza A (H5N1) [53] and most recently by the 2009 pandemic influenza virus [54]. This will require that affected countries, WHO and the WHO Col- laborating Centres work together to establish an international novel coro- navirus convalescent plasma centre that can strengthen the Region’s public health preparedness against this infection. The countries may also benefit from the interim rapid advice document published by WHO [53] for care of patients, which may need to be adapted to the local settings. Transparency in sharing information The emergence of any new infectious disease, particularly one with the capac- ity to transmit from person-to-person, creates several challenges. Transpar- ency of the countries where nCoV cases have occurred or are likely to occur in the future will be central to our understanding of how this virus tran- scends into a pandemic threat. Greater understanding of the epidemiology of and disease manifestations caused by the virus can only help to determine the evolving risk to global health as- sociated with this novel virus. As such information is critical to global health security, countries need to use to the full all the mechanisms enshrined in the framework of the International Health Regulations (IHR) (2005) [55] for their benefit. The IHR (2005) also un- derscores the importance of minimiz- ing adverse publicity effects or unfair and unwarranted treatment of affected countries. Risk communication The initial days surrounding any out- break of a novel disease is challenging as knowledge about its epidemiology is minimal, accurate predictions are diffi- cult and have to rely on historical events that parallel the diseases as closely as possible [56]. As these days are usually marked by confusion, uncertainty and a sense of urgency, good and effective communication is with the media as well as the general public in order to increase public trust and confidence on the measures taken by the national health authorities to protect the health of their population. Risk communication needs to an integral part of control efforts be- cause with good communication, sup- port can be galvanized, the public can be reassured and information that may save lives can be provided. As much as good communication can mobilize public support and increase credibility, there have been numerous communication failures that have delayed outbreak con- trol and as a result prolonged economic and social turmoil [56]. Seroepidemiological studies Many questions about this novel coronavirus remain unanswered. One assumption that the virus was circu- lating in one or more animal groups, yet remained unrecognized for some time, and is transmitted sporadically to humans as a zoonotic infection [44,50] needs to be studied in-depth. Although all cases to date have had some connec- tion with the Arabian Peninsula, more information is needed about the full geo- graphical extent of the virus. Serological studies for the virus are urgently needed to accurately assess sub-clinical infec- tion rates (both mild and asymptomatic infections) in countries where cases have occurred, and large multicountry serosurveys need to be conducted to better understand the epidemiology and geographic extent of the infection. Controlled studies of cases and con- tacts can also give a clue to the source of infection [44]. Several laboratories Book 19 Supplement.indb 36 5/16/2013 2:27:37 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S37 References 1. World Health Organization. Eastern Mediterranean Regional Office. About us. Available from http://www.emro.who.int/ entity/about-us/. 2. World Bank. World Development Indicators. Available from http://data.worldbank.org/ 3. Shaping the future of health in the WHO Eastern Mediterranean Region: reinforcing the role of WHO. Cairo, World Health Or- ganization Regional Office for the Eastern Mediterranean, 2012 (http://applications.emro.who.int/dsaf/EMROPUB_2012_ EN_742.pdf, accessed 9 May 2013). 4. Report on the Meeting on establishing an outbreak alert and response network in the Eastern Mediterranean Region Casa- blanca, Morocco 21–23 October 2012. Cairo, World Health Organization Regional Office for the Eastern Mediterranean, 2013 (http://applications.emro.who.int/docs/IC_Meet_ Rep_2013_EN_14863.pdf, accessed 9 May 2013). 5. Growing threat of viral haemorrhagic fevers in the Eastern Medi- terranean Region: a call for action. World Health Organization Regional Office for the Eastern Mediterranean (Technical paper EM/RC54/5) (http://applications.emro.who.int/docs/ EM_RC54_5_en.pdf, accessed 9 May 2013). 6. Jones KE, Patel N, Levy M, et al. Global trends in emerging infectious diseases. Nature 2008, 451:990–994. 7. Markoff, L. Yellow fever outbreak in Sudan. New England Jour- nal of Medicine, 2013, 368(8):689–691. 8. Zayed A et al. Detection of Chikungunya virus in Aedes aegypti during 2011 outbreak in Al Hodayda, Yemen. Acta Tropica, 2012, 123(1):62–66. 9. Report of new health events occurring inside the Episouth area. Tunisia. EpiSouth Weekly Epi Bulletin, No. 243 (7 November–14 No- vember 2012) (http://www.episouthnetwork.org/sites/default/ files/bulletin_file/eweb_243_15_11_12.pdf, accessed 9 May 2013). 10. Aronson NE. Infections Associated with War: the American Forces Experience in Iraq and Afghanistan. Clinical Microbiol- ogy Newsletter, 2008, 30(18):135–140. 11. Hartzell JD et al. Atypical Q fever in US soldiers. Emerging Infec- tious Diseases, 2007, 13(8):1247–1249. 12. Leung-Shea C, Danaher PJ. Q Fever in Members of the United States Armed Forces Returning from Iraq. Clinical Infectious Diseases, 2006, 43(8):e77–e82. 13. Mofleh J, Ahmad AZ. Crimean–Congo haemorrhagic fever outbreak investigation in the Western Region of Afghani- stan in 2008. Eastern Mediterranean Health Journal, 2012, 18(5):522–526. 14. Chinikar S et al. Crimean–Congo Hemorrhagic Fever (CCHF). In: Lorenzo-Morales J, ed. Zoonosis. InTech, 2012 (http://www.intechopen.com/books/zoonosis/crimean- congo-hemorhagic-fever-, accessed 10 May 2013) (DOI: 10.5772/38851). 15. Sheikh AS et al. Bi-annual surge of Crimean–Congo haemor- rhagic fever (CCHF): a five-year experience. International Jour- nal of Infectious Diseases, 2005, 9:37–42. 16. Athar MN et al. Crimean–Congo hemorrhagic fever outbreak in Rawalpindi, Pakistan, February 2002: contact tracing and risk assessment. American Journal of Tropical Medicine and Hygiene, 2005, 72:471–473. 17. Rai MA et al. Crimean–Congo hemorrhagic fever in Pakistan. Journal of medical virology, 2008, 80:1004–1006. 18. Mofleh JA, Ashgar RJ, Kakar RS. Nosocomial outbreak of Crimean–Congo hemorrhagic fever in Holy Family Hospital, Rawalpindi, Pakistan, 2010. Journal of Public Health and Epide- miology, 2013, 5(4):173–177. 19. Aradaib I et al. Multiple Crimean–Congo hemorrhagic fever virus strains are associated with disease outbreaks in Sudan, 2008–2009. PLoS Neglected Tropical Diseases, 2011, 5(5):e1159. 20. Elata A et al. A nosocomial transmission of Crimean–Congo hemorrhagic fever to an attending physician in north Kordu- fan, Sudan. Virology Journal, 2011, 8(1):303. 21. Aradaib I et al. Nosocomial outbreak of Crimean–Congo hemorrhagic fever, Sudan. Emerging Infectious Diseases, 2010, 16:837–839. 22. Onyango CO et al. Laboratory diagnosis of Ebola hemorrhagic fever during an outbreak in Yambio, Sudan, 2004. Journal of Infectious Diseases, 2007, 196(Suppl. 2):S193–S198. are currently working to develop and validate serological assays for nCoV. Two approaches for serological testing have recently been published [57,58]. Further validated assays and protocols for serosurvey need to be developed and applied in all countries in a standard way. Conclusion and future perspective The Region has borne the brunt of several emerging infectious diseases of zoonotic origin and is now a focus for global health after the discovery of nCoV. A lesson of this experience is that emerging infectious diseases that are of zoonotic origin are unexpected and unpredictable events. Another les- son that has been learned is that any disease outbreak anywhere today could be a problem for the world tomorrow. These novel diseases will continue to confront and challenge national health authorities’ resilience and responsive- ness. Likewise, the ability of regional and global communities to cooperate to control these diseases that cross na- tional boundaries will be a real test for global health security. What is important now is not to lower our guard and to continue to as- sess the risk of global threats associated with emergence of this novel virus. This will involve close regional collabora- tion between the countries where cases have occurred, WHO and other international health bodies who are also responsible for global health. While the global efforts should continue to fill the current gaps in knowledge associated with this virus, much greater regional cooperation is needed to protect the health of the people living in the Region. From the regional perspective, the pre- sent situation should not be treated as just a sequel to the long list of epidemic zoonotic diseases that the Region has witnessed in the past decade or so. It should trigger a clear need for the detec- tion, prevention and control of this and other emerging zoonoses in the Region that may cross borders. In the mean time, one can only hope that this new virus does not unfold into one that is easily transmissible between humans. Book 19 Supplement.indb 37 5/16/2013 2:27:38 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S38 23. World Health Organization. Global Alert and Response (GAR). Ebola haemorrhagic fever in South Sudan – update 8. 6 July 2004 [webpage] (http://www.who.int/csr/don/2004_07_06/en/ index.html, accessed 9 May 2013). 24. World Health Organization. Global Alert and Response (GAR). Rift Valley fever in Yemen –update 4. 26 October 2000 [web- page] (http://www.who.int/csr/don/2000_10_26/en/index. html, accessed 9 May 2013). 25. Rift Valley fever, Saudi Arabia. August–October 2000. Weekly Epidemiological Record, 2000, 75:370–371. 26. Madani TA et al. Rift Valley fever epidemic in Saudi Arabia: epidemiological, clinical, and laboratory characteristics. Clini- cal Infectious Diseases, 2003, 37(8):1084–1092. 27. Hassan OA et al. The 2007 Rift Valley fever outbreak in Sudan. PLoS Neglected Tropical Diseases, 2011, 5(9):e1229. 28. World Health Organization. Global Alert and Response (GAR). Avian influenza – situation in Djibouti, 12 May 2006 [webpage] (http://www.who.int/csr/don/2006_05_12/en/index.html, accessed 9 May 2013). 29. World Health Organization. Global Alert and Response (GAR). Avian influenza – situation in Iraq – update 5. 19 September 2006 [webpage] (http://www.who.int/csr/don/2006_09_19/en/ index.html, , accessed 9 May 2013). 30. World Health Organization. Global Alert and Response (GAR). Avian influenza – situation in Pakistan – update 2. 3 April 2008 [webpage] (http://www.who.int/csr/don/2008_04_03/en/ index.html, accessed 9 May 2013). 31. World Health Organization. Influenza at the human–animal interface. Summary and assessment as of 26 April 2013. http:// www.who.int/influenza/human_animal_interface/Influen- za_Summary_IRA_HA_interface_26Apr13.pdf, accessed 9 May 2013). 32. New cases of avian influenza A(H5N1) in Egypt. Weekly Epide- miological Monitor, 2012, 6(15 and 16) (http://applications. emro.who.int/dsaf/epi/2013/Epi_Monitor_2013_6_15-16.pdf, accessed 9 May 2013). 33. World Health Organization. Eastern Mediterranean Regional Office. Report on Pandemic H1N1 and progress on the re- sponse. ( http://applications.emro.who.int/docs/RC_techni- cal_papers_2011_inf_doc_7_14208.pdf, accessed 10 May 2013) 34. Formenty P et al. Human monkeypox outbreak caused by novel virus belonging to Congo Basin clade, Sudan, 2005. Emerging Infectious Diseases, 2010, 16:1539–1545. 35. Sandfly fever in Lebanon (July 2007–September 2007). Week- ly Epidemiological Monitor, 2008, 1(5) (http://applications. emro.who.int/dsaf/epi/2008/Epi_Monitor_2008_1_5.pdf, accessed 9 May 2013). 36. Cabanel N et al. Plague outbreak in Libya, 2009, unrelated to plague in Algeria. Emerging Infectious Diseases, 2013, 19:230– 236. 37. Madani TA. Alkhumra virus infection, a new viral hemorrhagic fever in Saudi Arabia. Journal of Infection, 2005, 51:91–97. 38. Madani TAet al. Alkhumra (Alkhurma) virus outbreak in Najran, Saudi Arabia: epidemiological, clinical, and laboratory charac- teristics. Journal of Infection, 2011, 62(1):67–76. 39. Memish Z et al Alkhumra haemorrhagic fever: case report and infection control details. British Journal of Biomedical Science, 2005, 62:37–39. 40. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814–1820. 41. Malik M et al. Emergence of novel human coronavirus: public health implications in the Eastern Mediterranean Region. East- ern Mediterranean Health Journal, 2012, 18:1084–1085. 42. World Health Organization. Global Alert and Response (GAR). Novel coronavirus infection – update. 30 November 2012 [webpage] (www.who.int/csr/don/2012_11_30/en/index. html, accessed 9 May 2013). 43. World Health Organization. Global Alert and Response (GAR). Novel coronavirus infection – update. 26 March 2013 [web- page] (http://www.who.int/csr/don/2013_03_26/en/index. htm, accessed 9 May 2013). 44. McCloskey B et al. Applying lessons from SARS to a newly iden- tified coronavirus. The Lancet Infectious Diseases, 13(5):384–385. 45. Ahmed QA, et al. Health risks at the Hajj. Lancet. 2006 Mar 25;367(9515):1008-15 46. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: the Saudi perspective. International Journal of Antimicrobial Agents, 2003, 21:96–101. 47. The Health Protection Agency (HPA) UK Novel Coronavirus Investigation team. Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Eurosurveillance, 2013, 18(11):pii 20427 (http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20427, accessed 9 May 2013). 48. World Health Organization. Interim surveillance recom- mendations for human infection with novel coronavirus as of 18 March 2013 (http://www.who.int/csr/disease/corona- virus_infections/InterimRevisedSurveillanceRecommenda- tions_nCoVinfection_18Mar13.pdf, accessed 9 May 2013) 49. WHO Laboratory testing for novel coronavirus (Available from http://www.who.int/csr/disease/coronavirus_infections/en/ index.html, accessed 10 May 2013). 50. Pebody R, Zambon M, Watson J. Novel coronavirus: how much of a threat? BMJ, 2013, 346:f1301. 51. Core components of infection prevention and control programmes in health care. Geneva, World Health Organization, 2011 (Aide- memoire). (http://www.who.int/csr/resources/publications/ AM_CoreCom_IPC.pdf, accessed 9 May 2013). 52. Cheng Y et al. Use of convalescent plasma therapy in SARS pa- tients in Hong Kong. European Journal of Clinical Microbiology and Infectious Disease, 2005, 24(1):44–46. 53. Zhou B et al. Treatment with convalescent plasma for influenza A (H5N1) infection. New England Journal of Medicine, 2007, 357(14):1450–1451. 54. Hung IF et al. Convalescent plasma treatment reduced mor- tality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clinical Infectious Diseases, 2011, 52(4):447–456. 55. International Health Regulations, 2005. Geneva, World Health Organization, 2005. 56. Tabbaa D. Emerging zoonoses: responsible communication with the media – lessons learned and future perspective. In- ternational Journal of Antimicrobial Agents, 2010, 36S:S80-S83. 57. Corman VM et al. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillace, 2012, 17(49):pii 20334 (http://www.eurosurveillance.org/ ViewArticle.aspx?ArticleId=20334, accessed 9 May 2013). 58. Reusken C et al. Specific serology for emerging human corona- viruses by protein microarray. Eurosurveillance, 2013;18(14):pii 20441. (http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20441, accessed 9 May 2013 59. Gould LH et al. An outbreak of yellow fever with concurrent chikungunya virus transmission in South Kordofan, Sudan, 2005. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2008, 102(12):1247–1254. 60. Onyango CO et al. Yellow fever outbreak, southern Sudan, 2003. Emerging Infectious Diseases, 2004, 10(9):1668–1670. Book 19 Supplement.indb 38 5/16/2013 2:27:38 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S39 Review Infection prevention and control measures for acute respiratory infections in healthcare settings: an update W.H. Seto,1 J.M. Conly,2 C.L. Pessoa-Silva,3 M. Malik 4 and S. Eremin 3 1Department of Community Medicine, School of Public Health, University of Hong Kong, Hong Kong, People's Republic of China. 2Departments of Medicine, Microbiology, Immunology and Infectious Diseases, Calvin, Phoebe and Joan Synder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Canada. 3Department of Pandemic and Epidemic Diseases, World Health Organization, Geneva, Switzerland (Correspondence to S. Eremin: eremins@who.int). 4Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt. ABSTRACT Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARIs is through large droplets, but transmission through contact (including hand contamination with subsequent self- inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as “opportunistic” airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting high- risk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus. تامولعملل ثيدتح :ةيحصلا ةياعرلا عقاوم في اهتحفاكمو ةدالحا ةيسفنتلا ىوادعلا نم ةياقولا يربادت يمريإ يغيرس ،كلام نحمرلا نومأم ،افليس اوسيب نمراك ،لينوك نوج ،وتيس غنوه غنيو رثكأو .ماع لك ييلام 4 زواجتت تايفول يِّدؤتو ،يلماعلا ديعصلا لىع ةدالحا ةيسفنتلا ىودعلا تلااح مظعم نع ةلوؤسم تاسويرفلا نإ :ةـصلالخا ًايلاح تانِّيبلا يرشتو .يدغلا سويرفلاو ،ازنولفنلإا ةيرظنو ،سيفنتلا يولخلما سويرفلاو ،ازنولفنلإا :يه اهرتاوت قفو ًةبترم ًاعويش تاسويرفلا هذه ثولت كلذ في ماب( ةسملالما للاخ نم لاقتنلاا نأ لاإ ،مجلحا ةيربكلا تايرطقلا للاخ نم يه ةدالحا ةيسفنتلا ىودعلا لاقتنلا سييئرلا طمنلا نأ لىإ لاقتنلاا حلطصم اهيلع قلطيو( ةيرصقلا تلااجلما فيو اهماجحأ فلتخمب ىودعلل ةلمالحا ةيسفنتلا بئابضلاو ،)ةيتاذ ىودع نم هولتي امو نيديلا تاءارجلإا في ًاضيأ ءاولهاب لوقنلما يزاهتنلاا لاقتنلاا ثديح دقو ،ضارملأل ةبِّبسلما لماوعلا ضعبل ثديح نأ نكمي ،)ءاولهاب لوقنلما يزاهتنلاا يربادتلا نوثحابلا ضرعتسا دقو .عقاولما كلت في ءاولهاب ةلوقنلما ىودعلا نم تاطايتحا بلطتي امم ،راطتخلاا ةعفترم بئابض جاتنإ لىإ يدؤت يتلا بِّبسلما يجاتلا سويرفلا كلذ في ماب ةعئاشلا تاسويرفلا ضعب اوشقانو ،ةيسفنتلا ةيسويرفلا ىودعلا تلااح عيجم في ةلا َّعفلا ىودعلا ةحفاكلم ةماعلا .ًاثيدح فشُتكا يذلا ،Coronavirus يجاتلا سويرفلاو ،)سراس( ةميخولا ةدالحا ةيسفنتلا ةمزلاتملل Prévention des infections et mesures de lutte contre les infections respiratoires aiguës en milieu de soins : le point sur la situation RÉSUMÉ Les virus sont responsables de la majorité des infections des voies respiratoires aiguës dans le monde avec une mortalité supérieure à quatre millions de décès par an. Les virus les plus fréquents sont, par ordre décroissant, celui de la grippe, le virus respiratoire syncytial, le virus paragrippal et l'adénovirus. Les données actuellement disponibles laissent penser que les grosses gouttelettes constituent le principal mode de transmission des infections des voies respiratoires aiguës, mais que la transmission par le contact (notamment la contamination par les mains suivie par une auto-inoculation) et par des aérosols respiratoires infectieux de différentes tailles et de courte portée (appelées transmissions par voie aérienne « opportunistes ») peut aussi se produire pour certains agents pathogènes. Une transmission par voie aérienne opportuniste peut survenir lors de l'utilisation de procédures générant des aérosols impliquant un risque élevé. Dans ce cas, des précautions contre une transmission aérienne sont requises. Des mesures de lutte anti-infectieuses générales efficaces contre toutes les infections respiratoires virales font l'objet d'un examen puis de discussions concernant certains virus courants, notamment le coronavirus du syndrome respiratoire aigu sévère et le nouveau coronavirus découvert récemment. Book 19 Supplement.indb 39 5/16/2013 2:27:38 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S40 Introduction Acute respiratory infections (ARIs) cause widespread diseases globally and are responsible for over 4 million deaths each year [1]. The incidence of ARIs is especially high among infants, children, and the elderly and is more pronounced in low- and middle-income countries [1,2]. ARIs may affect either or both the upper or lower respiratory tract and infections involving the lower respiratory tract may be especially severe. Although bacteria are significant pathogens, the most common etiologies of ARIs are viral and they are frequent causes of hospital admissions and nosocomial outbreaks. Determining the magnitude of the extent of disease due to ARIs has been difficult because of the lack of laboratory diagnos- tic capabilities, but in recent years many hospital laboratories have established rapid viral diagnostic capabilities. In Hong Kong, for example, the capacity for both rapid diagnosis and viral culture has existed for the public sector since 1995, covering 90% of hospital beds in the ter- ritory. Laboratory data from Hong Kong identified influenza A and influenza B as accounting for about 50% of the patients diagnosed with viral respiratory infec- tions, followed by respiratory syncytial virus (RSV) at about 20%, and parainflu- enza and adenovirus at about 15% each. Rhinovirus accounts for about 3%, but this is probably an underestimate since specimens are less frequently submitted for these cases, which generally have mild symptoms [3]. The practice of infection control for patients with ARIs has its own par- ticular challenges. The present review focuses mainly on infection prevention and control measures that are consid- ered effective in healthcare settings, and discusses the relevance of these meas- ures during health care for probable or confirmed case of novel coronavirus infections. Of special pertinence are 4 related systematic reviews recently commissioned by the World Health Organization [4–7] and a World Health Organization guideline released on this subject [8] which covers infec- tion control recommendations on key issues which are summarized later in this article. General infection control measures for ARIs in healthcare settings To develop effective strategies for infection control, it is critical to first understand the mode of transmission of these viruses. As these pathogens infect the respiratory tract and the virus can be disseminated into the air by coughing, it had been assumed in the past that the airborne route of trans- mission was important. Research over the years has provided evidence that this is not the case. Though knowledge of transmission modes continues to evolve, current evidence indicates that the major mode of transmission of most ARIs is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infec- tious respiratory aerosols of various sizes and at short range may also occur for some pathogens [9]. In an infected individual, a cough would generally produce large droplets, in the order of 10 μm in diameter or larger, and these large droplets would generally fall to ground within 1 metre of the patient [10]. This distance of 1 metre for viral droplets was first identified for RSV in a study by Hall and Douglas [11]. Large droplets of this size, because of their weight and size, generally cannot remain suspended in the air [9]. Conse- quently, infection control precautions will only be necessary when the health- care worker comes within 1 metre of the patient. This is the rationale behind the recommendations under “droplet precautions”, which will be discussed below. Some respiratory viruses, notably RSV, parainfluenza, and adenovirus, may be emitted in large quantities in respiratory secretions. With extensive contamination of the patient’s environ- ment, contact transmission can occur. Contact transmission refers to transfer of viruses and other microbes resulting from direct physical contact between infectious secretions from an infected or colonized person or via hands, envi- ronmental surfaces or inanimate objects which are contaminated by infectious secretions [9]. The isolation measure for these settings is designated “con- tact precautions”, which will also be discussed below. In these settings with viruses associated with large droplet and contact transmission (including metapneumovirus [12] because of its similarity to RSV) a patient generally will not cough out droplet nuclei of < 5 µ and therefore infectious material will not be disseminated for long distances through the air. Thus “airborne precau- tions” are generally not necessary. At present, none of these acute respiratory viral pathogens is classified as airborne [13]. However it should be noted that those respiratory viruses typically as- sociated with large droplet and con- tact transmission may spread by the airborne route under special circum- stances. Thus modes of transmission are not mutually exclusive and there may be settings or circumstances where transi- tions between modes of transmission may occur. This mode of transmission is described as “opportunistic airborne transmission” by Roy and Milton [14], who also stressed that such infections would not require “airborne infection isolation”. Rather, one should be alert to settings and circumstances where this “opportunistic airborne transmission” may occur, such as with aerosol generat- ing procedures. Airborne or aerosol transmission refers to dissemination of microorgan- isms by aerosolization, and occurs when microorganisms are contained in drop- let nuclei of a size < 5–10 μm, that result Book 19 Supplement.indb 40 5/16/2013 2:27:38 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S41 from evaporation of large droplets or in dust particles that remain suspended in the air [9]. Airborne transmission may occur over long distances (> 1 metre) and the microorganisms usually settle in the lower respiratory tract [14]. Administrative controls and measures for early recognition and isolation Infection control measures can only be effectively implemented in healthcare facilities when administrative controls are in place; this includes including es- tablishing sustainable infrastructure and activities to maintain infection control practices, clear policies on early recogni- tion of ARIs of potential concern, and access to prompt laboratory testing for identification of the etiologic agents. The healthcare facilities should also have adequate patient-to-staff ratios, provide adequate staff training, and es- tablish appropriate staff vaccination and prophylaxis programmes [8]. Given the ongoing spread of viral respiratory infections globally, the World Health Organization (WHO) released a guideline in 2007 entitled Infection prevention and control of epi- demic- and pandemic-prone acute respira- tory infections in health care [8]. It will be referred to as the “ARI guideline” in subsequent discussion. This guideline recommends that in all hospitals, ad- ministrative measures should be taken to set up a system for patients with ARI so that they are managed in a coordinat- ed manner with timely reporting to the public health authorities. The decision tree algorithm is shown in Figure 1 [8]. When a patient is first seen in the hospital or other healthcare site, usu- ally in an outpatient setting, a system should be established for clinical triage where patients are screened for specific signs and symptoms of ARI. The mo- ment these symptoms are detected, the infection control measures shown in the upper box of Figure 1 should be implemented. They are basically general infection control measures but include accommodating patients at least 1 me- tre away from other patients. Both epidemiological and clinical clues should be obtained from patients. The emergence of severe, novel viral respiratory infections of public health concern such as a new pandemic influ- enza strain should prompt an appropri- ate travel and occupational history. A contact history with any known case or cluster of ARIs of public health concern should be elucidated. Clinical clues, such as the patient having severe respiratory illness after exposure to a cluster of ARI of unknown etiology but with a high mortality rate, may also be important. If these clues suggest that the patient has an ARI of public health concern, he/she should be isolated in a single, well-ventilated room if possible. However if it is a new virus, and the mode of transmission is still unclear, an airborne precaution room is recom- mended. The details surrounding the case may also be reported to the public health authorities depending on local policies. Relevant specimens should be submitted to the laboratory and once a specific etiologic diagnosis is made (Figure 1), the specific infection control measures, as recommended in the guidelines or in Table 1, should be followed. General measures within healthcare settings Surveillance is extremely useful so that hospitals are alerted to outbreaks cir- culating in the community and will be an aid to early diagnosis and isolation of patients. A system to alert infection control personnel, e.g when there are ≥ 3 patients with influenza-like illnesses from a single ward, is also extremely use- ful. Immediate assessment of the possi- bility of an outbreak should be initiated, so that early isolation or discharge of patients can be undertaken [8]. Once admitted into the healthcare facility, the essential general infection control measures include rigorous hand hygiene, standard precautions and respir- atory hygiene. Hand hygiene is extremely important and every hospital should implement the WHO hand hygiene guideline that has been introduced world- wide [15]. It has been demonstrated that alcohol hand rubs are effective against all the respiratory viruses. Standard precautions are the measures initially introduced for all patients to reduce the risk of blood-borne pathogens. It also covers respiratory viral infections and as part of standard precautions, healthcare workers must utilize surgical masks and eye protection when there is significant risk of contamination from patients with profuse acute respiratory symptoms. For the person with a cough, “respiratory hy- giene” is a measure to contain respiratory secretions by providing them with tissues for covering the mouth and nose while coughing or providing surgical masks for the patients [13]. The 2 main isolation precautions for acute viral respiratory infections are droplet and contact precautions. It is important to stress that standard pre- cautions and strict hand hygiene are integral parts of all of these precautions. The key element of droplet precautions is wearing a surgical mask whenever healthcare workers come within 1 metre of the patient; for contact precautions, it is wearing a gown and gloves on enter- ing the patient’s room and removing them on leaving [8]. Recent systematic reviews [5,6] have shown the effective- ness of these measures. “Quarantine” is an infection control measure recommended for some infec- tious diseases, but it should be noted that there is no such recommendation in any guidelines for the present list of acute viral respiratory infections [8]. Quarantine involves the segregation of healthy contacts and it was the policy for severe acute respiratory syndrome (SARS) in many countries. Such a dras- tic measure for SARS was carried out Book 19 Supplement.indb 41 5/16/2013 2:27:38 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S42 for the sake of caution, but the present evidence does not support the need for quarantine because subclinical infec- tion is shown to be almost nonexist- ent [16] and even mildly symptomatic cases have not been reported [17]. Cohorting is the process of isolat- ing patients with the same diagnosis in the same isolation room and since significant surges of these viral respira- tory infections do occur, especially in the winter months, it often is needed. Many hospitals have the problem of admitting large numbers of patients with infectious respiratory syndromes, especially among paediatric patients, and where there is insufficient isola- tion capacity to place them in separate rooms before a specific viral diagnosis is available. A possible solution, suggested in the ARI guideline is to place all of these patients on droplet precautions in the same room but ensuring that all beds are at least 1 metre apart and having healthcare workers wear medical masks whenever they are within 1 metre of the patient [8]. There is no sharing of specific patient care equipment, such as stethoscopes, and patient medical records are not placed by the bedside but at the nursing station. Patients are advised not to leave their beds without permission, which is especially impor- tant for paediatric patients, and also the common play area found in most pae- diatric wards. When an etiologic diag- nosis is established, infected patients are taken from this area and placed under the appropriate precautions as shown in Table 1. Such modified cohorting of respiratory illnesses has been reported to be successful in reducing nosocomial respiratory viral infections in paediatric units [18,19]. For adult wards, such measures may also be adapted with care, but when toilets are shared, it is impor- tant to ensure proper disinfection and adequate hand hygiene after use [8]. Figure 1 Decision-tree for infection prevention and control (IPC) measures for patients known or suspected to have an acute respiratory infection (ARI) [8] (PPE = personal protective equipment) Patient Infection control measures - HCWs should perform adequate hand hygiene, use medical mask and, if splashes onto eyes are anticipated, eye protection (goggles/face shield) (Table 2.1) - Pediatric patients with clinical symptoms and signs indicating specific diagnosis (e.g. croup for parainfluenza, acute bronchiolitis for respiratory syncytial virus), especially during seasonal outbreaks, may require isolation precautions (Table 2.1) as soon as possible - Encourage respiratory hygiene (i.e. use of medical mask or tissues when coughing or sneezing followed by hand hygiene) by the patient in the waiting room - If possible, accommodate patients at least 1 m away from other patients - HCWs should use PPE (medical mask, eye protection, gown and gloves) and perform adequate hand hygiene (Table 2.1) - Use separate adequately ventilated or Airborne Precautionb room (Table 2.1) - If no separate room available, cohort patients with same laboratory-confirmed etiological diagnosis - If etiology cannot be laboratory confirmed and no separate room, adopt special measuresc Patient enters triage with symptoms of acute febrile respiratory illness plus clinical and epidemiological clues for ARI of potential concerna Patient diagnosed with ARI of potential concerna Other diagnosis IPC precautions (Table 2.1) to remain in place for the duration of symptomatic illness (see Section 2.2.4) Reassess IPC precautions (Table 2.1) Report to public health authorities Book 19 Supplement.indb 42 5/16/2013 2:27:39 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S43 Ta bl e 1 I nf ec ti on p re ve nt io n an d co nt ro l p re ca ut io ns fo r h ea lt h- ca re w or ke rs (H C W ) an d ca re gi ve rs p ro vi di ng c ar e fo r p at ie nt s w it h ac ut e re sp ir at or y in fe ct io n (A RI ) a nd tu be rc ul os is (T B) Pr ec au ti on N o pa th og en id en ti fie d, n o ri sk fa ct or fo r T B or A RI of p ot en ti al c on ce rn (e .g . I LI w it ho ut ri sk fa ct or fo r A RI o f po te nt ia l c on ce rn ) Pa th og en Ba ct er ia l A RI a , in cl ud in g pl ag ue TB O th er A RI v ir us es (e .g . p ar ai nfl ue nz a RS V, a de no vi ru s) In flu en za v ir us w it h su st ai ne d hu m an -t o- hu m an tr an sm is si on (e .g . se as on al in flu en za , pa nd em ic in flu en za ) N ew in flu en za vi ru s w it h no s us ta in ed hu m an -t o- hu m an tr an sm is si on (e .g . av ia n in flu en za ) SA RS N ov el A RI b H an d hy gi en e Ye s Ye s Ye s Ye s Ye s Ye s Ye s Ye s G lo ve s Ri sk a ss es sm en t Ri sk a ss es sm en t Ri sk as se ss m en t Ye s Ri sk a ss es sm en t Ye s Ye s Ye s G ow n Ri sk a ss es sm en t Ri sk a ss es sm en t Ri sk as se ss m en t Ye s Ri sk a ss es sm en t Ye s Ye s Ye s Ey e pr ot ec tio n Ri sk a ss es sm en t Ri sk a ss es sm en t Ri sk as se ss m en t Ri sk a ss es sm en t Ri sk a ss es sm en t Ye s Ye s Ye s M ed ic al m as k fo r H C W s an d ca re gi ve rs Ye s Ri sk a ss es sm en t N o Ri sk a ss es sm en t / Ye sc Ye s Ye s Ye s N ot ro ut in el yb Pa rt ic ul at e re sp ira to r fo r H C W s an d ca re gi ve rs fo r r oo m en tr y N o N o Ye s N o N o N ot ro ut in el y N ot ro ut in el y Ye s w ith in 1 m o f pa tie nt N o N o Ye s N o N o N ot ro ut in el y N ot ro ut in el y Ye s fo r a er os ol - ge ne ra tin g pr oc ed ur es Ye s Ye s Ye s Ye s Ye s Ye s Ye s Ye sb M ed ic al m as k fo r p at ie nt w he n ou ts id e is ol at io n ar ea s Ye s Ye s Ye s Ye s Ye s Ye s Ye s Ye s A de qu at el y ve nt ila te d se pa ra te ro om Ye s, if a va ila bl e N o N o Ye s, if a va ila bl e Ye s, if a va ila bl e Ye s Ye s N ot ro ut in el yb A irb or ne p re ca ut io n ro om N o N o Ye s N o N o N ot ro ut in el y N ot ro ut in el y Ye s Su m m ar y of is ol at io n pr ec au ti on s fo r r ou ti ne pa ti en t c ar e, e xc lu di ng ae ro so l- ge ne ra ti ng pr oc ed ur es St an da rd St an da rd St an da rd St an da rd St an da rd St an da rd St an da rd St an da rd D ro pl et -- -- D ro pl et D ro pl et D ro pl et D ro pl et -- -- -- -- C on ta ct -- C on ta ct C on ta ct C on ta ct -- -- A ir bo rn e -- -- -- -- A ir bo rn e Ia B ac te ria l A RI re fe rs to co m m on b ac te ria l r es pi ra to ry in fe ct io ns ca us ed b y or ga ni sm s s uc h as S tr ep to co cc us p ne um on ia e, H ae m op hi lu s i nfl ue nz ae , C hl am yd op hi la sp p. a nd M yc op la sm a pn eu m on ia e. b W he n a no ve l A RI is n ew ly id en tifi ed , t he m od e of tr an sm is si on is u su al ly u nk no w n. Im pl em en t t he h ig he st a va ila bl e le ve l o f I PC p re ca ut io ns , u nt il th e si tu at io n an d m od e of tr an sm is si on is c la rifi ed . c A de no vi ru s A RI m ay re qu ire u se o f m ed ic al m as k. IL I = in flu en za -li ke il ln es s; R SV = re sp ira to ry sy nc yt ia l v iru s; S AR S = se ve re a cu te re sp ira to ry sy nd ro m e. Book 19 Supplement.indb 43 5/16/2013 2:27:39 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S44 Aerosol generating procedures As mentioned previously, ARIs are gener- ally not transmitted by air but aerosols of < 5 μ may be generated in certain pro- cedures labelled as “aerosol generating procedures” and transmitted at short dis- tance. The risk of “opportunistic” airborne transmission will then be a real possibility, and airborne precautions will be required in these settings. There is intense debate on the list of aerosol generating procedures that are associated with increased risk of infec- tion transmission. Recently the Canadian Agency for Drugs and Technologies in Health completed a systematic review [4] which demonstrated that tracheal intu- bation was most consistently associated across multiple studies with an increased risk of SARS transmission to health-care workers, or was a risk factor for trans- mission of SARS. Four cohort studies revealed a pooled odds ratio [OR] of 6.6 [95% confidence interval (CI): 2.3–18.9], and 4 case–control studies revealed a pooled OR of 6.6 (95% CI: 4.1–10.6), which were remarkably consistent. No other procedures emerged with such a clear association. There were 2 studies re- ported for non-invasive ventilation which demonstrated a pooled OR of 3.1, but they were low quality studies in which the association in one was not statistically significant [20] and the other was also not significant after multivariate analysis [21]. On the basis of the review, the WHO has made a strong recommendation in the recently revised ARI guideline that identi- fies intubation for special attention as a procedure associated with risk of trans- mission of respiratory viruses [8] (see recommendations 6 and 7 in Table 2). Recommendations for infection control in the WHO ARI guideline Based on the systematic reviews, the WHO has updated recommendations on 10 key issues in the recently revised ARI guideline, illustrated in Table 2 [8]. Synthesizing the evidence and formu- lating the recommendations was done using the GRADE (Grading of Recom- mendations Assessment, Development and Evaluation) framework according to the WHO Handbook for Guideline Development [22]. Measures for specific viral infections The measures for specific viral infec- tions that are commonly encountered are summarized in Table 1, adapted from the 2007 guideline [8]. Key is- sues for the various viral infections are discussed below. Influenza Controversy surrounds the mode of transmission of influenza, especially with an outbreak report suggesting that it could be airborne [23]. How- ever, recent reviews suggest that the basic mode of transmission is still considered to be via droplets [24–26]. Currently, influenza as listed in the Centers for Disease Control and Pre- vention guidelines requires droplet precautions [13], and, similarly, the World Health Organization (WHO) recommends that standard precau- tions and droplet precautions suffice for caring for patients infected with influenza [8]. Annual vaccination with trivalent in- activated (the most common) vaccine is the primary means of prevention and control of seasonal influenza, and is one of the recommendations in Table 2. A systematic review has been conducted which supports the recommendation for vaccinating healthcare workers but the quality of evidence is actually low [7]. The WHO guideline recommends both standard and droplet precautions, which includes the use of a medical mask rather than a facial particulate respirator for the healthcare worker. Use of the particulate respirators is only recommended for aerosol generating procedures such as intubation [27]. A study published in 2012 demon- strated the effectiveness of the WHO pandemic infection control guideline. When the WHO guideline was adopt- ed, there was no significant difference in the infection rate of clinical staff who were exposed to pH1N1 2009-infected patients compared to non-clinical staff who do not see patients at all [28]. Avian influenza There is now general consensus that the mode of transmission for avian in- fluenza is via droplet, and studies have shown that human-to-human spread is possible but is a rare event [29] and sustained, efficient, human-to-human transmission has not been reported to date. The WHO recommends droplet and contact precautions in their ARI guideline [8] and the first community outbreak of avian influenza reported in Hong Kong in 1997 [30] was success- fully controlled in hospital clusters using such precautions. Severe acute respiratory syndrome (SARS) and coronavirus infections When SARS was first reported, the emotional response was intense and widespread. This is understandable, be- cause it was a new disease and more than 1700 healthcare workers were infected. Subsequently, studies conducted in Hong Kong and elsewhere clearly dem- onstrated that infection control meas- ures are effective. A case–control study on staff providing direct patient care to 11 proven SARS patients was reported comparing the infection control precau- tions of the 241 non-infected staff with the 13 infected staff [31]. Four specific measures were expressly studied: (1) the washing of hands and the wear- ing of (2) masks, (3) gowns, and (4) gloves. The results showed that if proper droplet and contact precautions were undertaken by the staff, they would be protected [31]. Although standard infection control measures will prevent transmission of Book 19 Supplement.indb 44 5/16/2013 2:27:39 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S45 the SARS coronavirus (SARS-CoV), the correct practices must be inculcated in a properly organized programme for the entire hospital. The importance of leadership, intensive surveillance, and intense education of healthcare work- ers with adequate logistics cannot be overemphasized [32,33]. There was controversy in the lit- erature regarding the transmission of SARS-CoV as to whether it was air- borne, but this issue was addressed by Seto and Tang [34]. The outbreak in the Amoy Garden in Hong Kong published by Yu et al. used computerized fluid dynamic modelling and suggested that SARS-CoV could be transmitted by the airborne route [35]. It was an elegant study but it was a simulation, and pre- sents a level of evidence not comparable to actual epidemiological comparative studies involving real patients with con- comitant controls. The authors correctly point out in their conclusions that their study only “supports the probability of an airborne spread of SARS in the out- break in Amoy Gardens.” In an editorial regarding the article by Yu et al., Roy and Milton stated that “Hydraulic aerosol experiments combined with aerosol and epidemiologic modelling clearly impli- cated airborne transmission within the apartment complex” [14]. However, this “should not be considered to represent evidence that airborne infections neces- sarily cause explosive outbreaks” [14]. There are now reports supporting this contention, and that the use of medical masks when working within 1 metre of the patient is effective in preventing the transmission of SARS [36,37]. Infection prevention and control recommendations The emergence of a novel strain of coronavirus in September 2012 raised a global health alert as this novel virus belonged to the same family Coronaviri- dae as the SARS-CoV was [38]. There is now clear evidence [39] of limited, not Table 2 Ten WHO recommendations for infection prevention and control (IPC) and of acute respiratory infections (ARIs) Recommendations Overall ranking 1. Use clinical triage for early identification of patients with ARIs to prevent the transmission of ARI pathogens to HCWs and other patients. Strong 2. Respiratory hygiene (i.e. covering the mouth and nose during coughing or sneezing with a medical mask, tissue, or a sleeve or flexed elbow followed by hand hygiene) should be used in persons with ARIs to reduce the dispersal of respiratory secretions containing potentially infectious particles. Strong 3. Maintain spatial separation (distance of at least 1 m) between each ARI patient and others, including HCWs (without the use of PPE), to reduce the transmission of ARI. Strong 4. Consider the use of patient cohorting (i.e. the placement of patients infected or colonized with the same laboratory-identified pathogens in the same designated unit, zone or ward). If cohorting is not possible apply special measures (i.e. the placement of patients with the same suspected diagnosis – similar epidemiological and clinical information – in the same designated unit, zone or ward) within a health-care setting to reduce transmission of ARI pathogens to HCWs and other patients. Conditional 5. Use appropriate PPE as determined by risk assessment (according to the procedure and suspected pathogen). Appropriate PPE when providing care to patients presenting with ARI syndromes may include a combination of the following: medical mask (surgical or procedure mask), gloves, long- sleeved gowns and eye protection (goggles or face shields). Strong 6. Use PPE, including gloves, long-sleeved gowns, eye protection (goggles or face shields) and facial mask (surgical or procedure mask, or particulate respirators) during aerosol-generating procedures that have been consistently associated with an increased risk of transmission of ARI pathogens.1 The available evidence suggests that performing or being exposed to endotracheal intubation either by itself or combined with other procedures (e.g. cardiopulmonary resuscitation or bronchoscopy) is consistently associated with increased risk of transmission. Conditional 7. Use adequately ventilated single rooms when performing aerosol-generating procedures that have been consistently associated with increased risk of ARI transmission. Conditional 8. Vaccinate HCWs caring for patients at high risk of severe or complicated influenza disease, to reduce illness and mortality among these patients. Strong 9. Considerations for Ultraviolet Germicidal Irradiation – no recommendations possible. – 10. Implement additional IPC precautions at the time of admission and continue for the duration of symptomatic illness, and modify according to the pathogen and patient information. Always use Standard Precautions. There is no evidence to support the routine application of laboratory tests to determine the duration of IPC precautions. Conditional When a novel ARI is identified and the mode of transmission is unknown, it may be prudent to implement the highest level of IPC precautions whenever possible, including the use of fit tested particulate respirators, until the mode of transmission is clarified. Patient information (e.g. age, immune status and medication) should be considered in situations where there is concern that a patient may be infectious for a prolonged period. HCW = health-care workers; PPE = personal protective equipment. Book 19 Supplement.indb 45 5/16/2013 2:27:39 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S46 sustained, human-to-human transmis- sion, possibly involving different routes of transmission such as droplet and contact transmission, but the informa- tion on transmission and other fea- tures of the novel coronavirus (nCoV) is based on a small number of cases reported globally so far. Further stud- ies are required to understand better the transmission dynamics associated with this nCoV infection. Based on currently available in- formation, however, it does not seem rational to change the current recom- mendations on infection, prevention and control (IPC) measures which have proven to be effective for SARS and other coronaviruses. The success- ful prevention of further amplifica- tion of nCoV infections associated with health care will depend on the maturity of IPC programmes and the implementation of administrative and engineering and environmental controls. Droplets and contact pre- cautions and eye protection should be added to standard precautions for health-care workers or visitors in close contact when caring for patients with probable or confirmed nCoV infec- tion in healthcare settings. Additional precautions should also be applied when performing aerosol-generating procedures that are thought to be as- sociated with an increased risk of infec- tion transmission. The experience with SARS-CoV has clearly shown that it is crucial that health-care workers are provided with the appropriate pro- tection for caring for nCoV-infected patients and followed up if exposure has occurred. The detailed IPC recom- mendations are available in the ARI guideline and on the WHO Coronavi- rus web page [8,40]. The current scientific knowledge on the duration of infectivity of nCoV infection is limited. Based on currently available information, the isolation precautions need to be applied con- sistently during the duration of symp- tomatic illness and continued for not less than 24 hours after the resolution of symptoms. Until the epidemiology of the nCoV is better understood, and also considering other factors, test- ing for viral shedding could assist in decision-making, when available. On the other hand, a positive result for viral shedding does not necessarily imply effective infection transmission, and the epidemiological studies are the cornerstone for better informed decision making. Patient information (e.g. age, immune status and medi- cation) should also be considered in situations where there is concern that a patient may be shedding the virus for a prolonged period. In such situations a more cautious approach, such as a longer duration of IPC precautions, may be necessary References 1. The world health report 2004: changing history. Geneva, World Health Organization, 2004 (http://www.who.int/whr/2004/ en/, accessed 7 May 2013). 2. Nair H et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet, 2011, 378:1917–1930. 3. Seto W, Ho J. Healthcare-associated respiratory viral infec- tions. In: Jarvis W, ed. Bennett and Brachman’s hospital infec- tions, 6th ed. (In press). 4. Tran K et al. Aerosol generating procedures and risk of trans- mission of acute respiratory infections to healthcare workers: a systematic review. PLoS ONE, 2012, 7:e35797. 5. Jefferson T et al. Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review. BMJ, 2008, 336:77. 6. Lee K et al. Physical interventions to interrupt or reduce the spread of respiratory viruses - resource use implications: a systematic review. CADTH Technology Overviews, 2012, 2(3):e2302. 7. Dolan GP et al. Vaccination of health care workers to protect patients at increased risk for acute respiratory disease. Emerg- ing Infectious Diseases, 2012, 18:1225–1234. 8. Infection prevention and control of epidemic-and pandem- ic-prone acute respiratory diseases in health care. Geneva, World Health Organization, Global Alert and Response, 2007 (WHO/CDS/EPR/2007.6) (http://www.who.int/csr/ resources/publications/swineflu/WHO_CD_EPR_2007_6/ en/index.html, accessed 7 May 2013). 9. Hall CB. The spread of influenza and other respiratory viruses: complexities and conjectures. Clinical infectious disease, 2007, 45(3):353–359. 10. Rabenau HF et al. Efficacy of various disinfectants against SARS coronavirus. Journal of Hospital Infection, 2005, 61:107–111. 11. Hall CB, Douglas RG Jr. Modes of transmission of respiratory syncytial virus. Journal of Pediatrics, 1981, 99:100–103. 12. Crowe JEJ Jr. Human metapneumovirus as a major cause of human respiratory tract disease. Pediatric Infectious Disease Journal, 2004, 23(Suppl.):S215–S221. 13. Siegel JD et al., and the Healthcare Infection Control Practices Advisory Committee. 2007 Guideline for isolation precautions: preventing transmission of infectious agents in healthcare set- tings. Atlanta, Georgia, Centers for Disease Control, 2007 (http://www.cdc.gov/hicpac/2007ip/2007isolationprecauti ons.html, accessed 7 May 2013). 14. Roy CJ, Milton DK. Airborne transmission of communicable in- fection–the elusive pathway. New England Journal of Medicine, 2004, 350:1710–1712. 15. WHO guidelines on hand hygiene in health care. Geneva, World Health Organization, 2009 (http://www.who.int/gpsc/5may/ tools/9789241597906/en/index.html, accessed 7 May 2013). 16. Leung GM et al. SARS-CoV antibody prevalence in all Hong Kong patient contacts. Emerging Infectious Diseases, 2004, 10:1653–1656. 17. Leung GM et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Annals of Internal Medicine, 2004, 141:662–673. 18. Karanfil LV et al. Reducing the rate of nosocomially transmit- ted respiratory syncytial virus. American Journal of Infection Control, 1999, 27:91–96. 19. Mlinarić-Galinović G, Varda-Brkić D. Nosocomial respiratory syncytial virus infections in children’s wards. Diagnostic Micro- biology and Infectious Disease, 2000, 37:237–246. Book 19 Supplement.indb 46 5/16/2013 2:27:39 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S47 20. Fowler RA et al. Transmission of severe acute respiratory syn- drome during intubation and mechanical ventilation. Ameri- can Journal of Respiratory and Critical Care Medicine, 2004, 169:1198–1202. 21. Raboud J et al. Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada. PLoS ONE, 2010, 5:e10717. 22. WHO Handbook for Guideline Development. Geneva, World Health Organization, 2010 (http://www.who.int/hiv/topics/ mtct/grc_handbook_mar2010_1.pdf, accessed 7 May 2013. 23. Moser MR et al. An outbreak of influenza aboard a commercial airliner. American Journal of Epidemiology, 1979, 110:1–6. 24. Salgado CD et al. Influenza in the acute hospital setting. Lancet Infectious Diseases, 2002, 2:145–155. 25. Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: implications for control in health care settings. Clinical infec- tious diseases, 37(8):1094–1101. 26. Stott DJ, Kerr G, Carman WF. Nosocomial transmission of influenza. Occupational Medicine (Oxford, England), 2002, 52:249–253. 27. Human infection with pandemic (H1N1) 2009 virus: updated interim WHO guidance on global surveillance. Geneva, World Health Organization, 2009 (http://www.who.int/csr/disease/ swineflu/WHO_case_definition_swine_flu_2009_04_29.pdf, accessed 7 May 2013). 28. Seto WH et al. Clinical and nonclinical health care workers faced a similar risk of acquiring 2009 pandemic H1N1 infection. Clinical infectious diseases, 2011, 53(3):280–283. 29. Buxton Bridges C et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influ- enza A (H5N1), Hong Kong. Journal of Infectious Diseases, 2000, 181:344–348. 30. Yuen KY, Wong SS. Human infection by avian influenza A H5N1. Hong Kong Medical Journal, 2005, 11(3):189–199. 31. Seto WH et al.; Advisors of Expert SARS group of Hospital Au- thority. Effectiveness of precautions against droplets and con- tact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet, 2003, 361:1519–1520. 32. Seto WH, Ching PTY, Ho PL. Infection control for SARS: evidence for efficacy of good practice and description of a successful model. In: Perris M, ed. Severe acute respiratory syn- drome. Oxford, England, Blackwell Publishing, 2005:176–183. 33. Ho PL, Tang XP, Seto WH; HO. SARS: hospital infection control and admission strategies. Respirology (Carlton, Vic.), 2003, 8(Suppl.):S41–S45. 34. Tong TR, Tsang D. SARS infection control. Lancet, 2003, 362:76–77, author reply 76–77. 35. Yu ITS et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. New England Journal of Medi- cine, 2004, 350:1731–173. 36. Peck AJA et al.; SARS Pennsylvania Case Investigation Team. Lack of SARS transmission and U.S. SARS case-patient. Emerg- ing Infectious Diseases, 2004, 10:217–224. 37. Park BJ et al. Lack of SARS transmission among healthcare workers, United States. Emerging Infectious Diseases, 2004, 10:244–248. 38. Malik M et al. Emergence of novel human coronavirus: public health implications in the Eastern Mediterranean Region. East- ern Mediterranean Health Journal, 2012, 18:1084–1085. 39. The Health Protection Agency (HPA), UK Novel Coronavirus Investigation Team. Evidence of person-to-person trans- mission within a family cluster of novel coronavirus infec- tions, United Kingdom, February 2013. Eurosurveillance, 2013, 18(11):pii 2042 (http://www.eurosurveillance.org/images/ dynamic/EE/V18N11/art20427.pdf, accessed 7 May 2013). 40. Coronavirus infections. Geneva, World Health Organization, Global Alert and Response, 2013 (http://www.who.int/csr/ disease/coronavirus_infections/en/index.html, accessed 7 May 2013). Book 19 Supplement.indb 47 5/16/2013 2:27:39 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S48 Review Emerging respiratory and novel coronavirus 2012 infections and mass gatherings J.A. Al-Tawfiq,1 C.A.H. Smallwood,2 K.G. Arbuthnott,2 M.S.K. Malik,3 M. Barbeschi 2 and Z.A. Memish 4 1Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia. 2Alert and Response Operations, Global Capacities, Alert and Response, World Health Organization, Geneva, Switzerland. 3Pandemic and Epidemic Disease, Regional Office for the Eastern Mediterranean, World Health Organization, Cairo, Egypt. 4Ministry of Health, Riyadh, Saudi Arabia; College of Medicine, Al Faisal University, Riyadh, Saudi Arabia (Correspondence to Z.A. Memish: zmemish@yahoo.com). ABSTRACT Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview of the literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 (nCoV), an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts. ةدشالحا تاعمجتلاو 2012 ديدلجا يجاتلا سويرفلاو ةئشانلا ةيسفنتلا ىوادعلا شميم دايز ،شييبراب ويزيرام ،كلام رانومام ،تونثبرأ نيرثاك ،دوو لومس نيرثاك ،قيفوتلا رفعج ةماعلا ةحصلا لىع ةداح رطامخ ثودح لماتحا نم قلقلا يرثي امم لماعلا ءاجرأ ىتش نم روضلحا نم ةيرفغ ًادادعأ ةدشالحا تاعمجتلا دهشت :ةـصلالخا ةثعبنلما ضارملأاو ةدجتسلما ضارملأا اهنيب نمو ،ةيراسلا ضارملأا رطاخلما كلت نمو .دشالحا ع ُّمجتلا نوفيضتسي نيذلا ناكسلا في ًةداع فداصت لا مث ،ةدشالحا تاعمجتلا في ةيسفنتلا ىوادعلا لوح ِشرُن ام عوممج ةلاقلما هذه في نوثحابلا ضرعتسيو .نيرئازلا ناكسلا فيو يفيضتسلما ناكسلا في اذه نأ نم مغرلا لىعو .دشالحا ع ُّمجتلل تادادعتسلاا لىع ،ًايسفنت ًاضرم ببسي ديدج سويرف وهو ،2012 ّدجتسلما يجاتلا سويرفلا رثأ نوفصي حضاولا نمو ،سويرفلا كلذب ىودعلاب اوباصي نأ نود مهرئاعش ءادأ اولمكتسا دق جاّجلحا نإف ،2012 جلحا مسوم لبق رهظ دق ديدلجا سويرفلا ثدلحا اذه لثم لوح ةارجلما ثوحبلا مءاوتت نأ متحلما نم لعتج ةيلودلا ةحصلا لىع رطامخ نم هلمتح دق امو ةدشالحا تاعمجتلل ةيلماعلا ةعيبطلا نأ .لماعلا في ءابرلخا فلتمخ لَبِق نم ةينواعت دوهج ةليصح نوكت نأو ،تاقايسلا فلتمخ عم هتلجاعلم ةمزلالا ةيداشرلإا لئلادلاو Infections respiratoires émergentes, nouveau coronavirus 2012 et rassemblements de masse RÉSUMÉ Les rassemblements de masse réunissent un public de plus en plus mondial et soulèvent par conséquent des inquiétudes concernant des risques aigus potentiels pour la santé publique que la population hôte ne connaît pas habituellement. Les maladies transmissibles font partie des risques aigus potentiels pour la santé au niveau de l'individu et de la population. Les risques liés aux maladies transmissibles comprennent les affections émergentes ou réémergentes dans les populations hôtes et de passage. Dans la présente revue, nous proposons un aperçu de la littérature sur les infections respiratoires lors de rassemblements de masse, puis nous décrivons l'impact du nouveau coronavirus 2012, un virus respiratoire émergent, sur les préparatifs des rassemblements de masse. Toutefois, le nouveau coronavirus a sévi avant la saison du pèlerinage du Hadj de 2012 et les musulmans ont accompli leurs obligations religieuses sans contracter d'infection par ce virus. En clair, la nature mondiale des rassemblements de masse et les risques potentiels pour la santé internationale rendent impératif que la recherche sur de tels événements et les recommandations pour leur prise en charge soient adaptées aux divers contextes et soient le résultat d'une concertation d'experts mondiaux. Book 19 Supplement.indb 48 5/16/2013 2:27:40 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S49 Risks of infectious disease at mass gatherings With the advent of more widely avail- able air travel, mass gatherings are attended by an increasingly global audi- ence [1]. This, combined with poten- tially increased crowd numbers, raises the concern of possible acute public health risks. Some risks are common to most mass gatherings, but others are specific to a given gathering or crowd. The potential acute risks to individual and population health range from non- communicable disease concerns, such as crush injuries [2], to infectious agents [3]. Minimizing the risk of communica- ble diseases at mass gathering is there- fore an important part of global health security. A mass gathering is defined by the World Health Organization (WHO) as an occasion that “attracts a sufficient number of people to strain the planning and response resources of a community, state or nation” [4]. It follows that mass gathering can be planned or spontaneous, and can be diverse in purpose, from music festivals and protests to large-scale religious events. At mass gatherings, communi- cable disease risks include emerging and re-emerging diseases in host and visiting populations. The possible impact of such outbreaks during mass gathering is serious, potentially resulting in the dissemination of the disease to different countries upon the return of attendees to their countries of origin [5]. Concerns about communicable dis- ease spread at a given mass gathering are focused on the problems of crowding, lack of sanitation and temporary food stalls, travel and movement of popula- tion groups. Communicable disease threats may arise from pathogens with different modes of transmission, such as faeco–oral, vector-borne, zoonotic, sexually transmitted and bloodborne pathogens and these risks have been reviewed elsewhere [3]. One concern among host countries is the spread of respiratory disease. The risk of respira- tory pathogen spread may, among other factors, depend on crowd density and length of stay, in addition to hygiene facilities and the capacity for diagnostics and appropriate isolation. The type of respiratory disease risk will be influ- enced by the endemic disease patterns in the host and visiting nations, and by seasonality or climate [6]. The ability to detect and diagnose specific respiratory pathogens at mass gatherings depends on the participants seeking health care, ready access to health-care treatment facilities, and the availability of rapid lab- oratory diagnostics to the health-care clinicians. The probability of a specific pathogen causing an epidemic among the participants at mass gathering de- pends on the population immunity to the pathogen, the incubation period of a particular infectious agent before symp- toms of disease emerge and the length of time the mass gathering participants are in close contact with each other. If an outbreak were to occur at a mass gather- ing, there are potential implications for international public health and for the revised International Health Regulations [7]. Under Annex 2, the revised Regula- tions outline criteria for the assessment and notification of potential public health events of international concern. These criteria may be influenced by the occurrence of a mass gathering. To better prepare for the increased communicable disease threats, public health preparations for all mass gath- erings should include a specific focus on enhanced disease surveillance and risk assessment. This extends from the local level of the mass gathering, to the national and international levels. For example, additional diseases, which are non-endemic in the host country but endemic in the visitors’ countries, may be included on “priority condition” lists for reporting. Furthermore, surveillance sites may be implemented at additional geographical locations, for example at ports of entry or around the mass gathering location. Laboratory capacity may also be strengthened to accommo- date surge capacity and for diagnosis of non-endemic diseases. A number of large mass gatherings took place in 2012, including the Olym- pic Games in London, annual events such as the Hajj pilgrimage in Mecca and many spontaneous political rallies in countries of the Eastern Mediterra- nean Region. The discovery of the novel coronavirus (nCoV), with evidence of human cases appearing approximately 1 month before Hajj 2012, necessitated an iterative approach to risk assessment and management before, during and after the event. Objectives of the review This review, based on information up to March 2013, presents some of the issues surrounding emerging respiratory infections at mass gatherings, with a par- ticular focus on nCoV and the Hajj. An overview of the literature on respiratory infections at mass gatherings is present- ed, followed by a narrative describing the impact of nCoV, an emerging respira- tory disease, on the preparations before, during and after Hajj 2012. Viral respiratory infections at Hajj and other mass gatherings The Hajj takes place during the 12th month of the Islamic calendar, and according to Islam, every able Mus- lim must undertake the pilgrimage to Mecca once in their lifetime. Just as for any international mass gathering, the potential for large epidemics dur- ing Hajj has been, and will continue, to present a considerable challenge to attending pilgrims and the local com- munities. The risks, comprehensively described in other publications, arise from the attendance of close to 4 million Book 19 Supplement.indb 49 5/16/2013 2:27:40 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S50 pilgrims from more than 180 countries [8]. The number of foreign pilgrims attending Hajj is increasing every year (Figure 1). This change in population attendance may affect the disease risks present at Hajj. It has been argued that the potential for respiratory tract infections during mass gatherings is related to the large number of people coming from different parts of the world. Intense crowding of people in limited spaces facilitates the transmission of disease, especially that of airborne infections [8]. The congested conditions of the Hajj and the crowded nature of the accommodation contrib- ute to the transmission of communica- ble diseases at the pilgrimage [9]. Influenza outbreaks during mass gathering have been described previ- ously [10–13]. A modelling study by Shi et al. has suggested that mass gathering could be associated with a 10% increase in the attack rate of influenza if they oc- cur within 10 days before an influenza pandemic [14]. Studies on the occur- rence of influenza during mass gatherings were also undertaken during the 2002 Winter Olympics in Salt Lake City in the United States and during World Youth Day 2008 in Sydney, Australia [12,13]. Among the total 188 patients tested at the World Youth Day 2008, influenza A and B were diagnosed in 19% [13]. Dur- ing World Youth Day 2008, a number of influenza strains were identified and these included oseltamivir-resistant and -sensitive influenza A(H1N1) viruses, in- fluenza A(H3N2) viruses and influenza B lineages (B/Florida/4/2006-like virus and B/Malaysia/2506/2004-like virus) [13]. The presence of multiple viruses among those attending mass gathering may increase the opportunity for the emergence of novel reassortment viruses [13]. In a third study describing the occur- rence of influenza during a rock festival in Hungary, among the total attendants of 390 000 young people, 14 individu- als were examined at St Margareta hos- pital and 8 (57.1%) tested positive for influenza A(H1N1)pdm09 by real-time polymerase chain reaction (PCR) assay [15]. The incidence was 3.7 times the overall European value, and may have been higher since attendees may not have sought medical treatment [15]. Dur- ing the inauguration of the Asian Youth Games in Singapore in 2009, 66 suspect- ed cases of influenza H1N1 virus were screened; 6 were confirmed for influenza A(H1N1)pdm09 and were admitted to hospital for isolation and treatment [16]. In Serbia, a few influenza A(H1N1) cases were identified among participants attending 2 mass gatherings and it was not possible to assess their impact on local populations [17]. Transmission of influenza A(H1N1) was inevitable, but preparations were put in place to mitigate the situation, including detection, isola- tion options and treatment of cases [17]. Further studies on respiratory viruses at mass gatherings have been related to the Hajj [10,11]. A range of respiratory vi- ruses have been described among pilgrims attending the annual Muslim pilgrimages in Saudi Arabia [18–25]. In these studies, the prevalence of parainfluenza virus was 1%–7.4% [19,23], adenovirus was 5.4% [23], influenza A(H1N1) was 2.5%– 21.8% [18], influenza B was 0.8%–2.6% [10,11] and influenza was 0.2%–37.4% [10,11,19,21–23]. The difference in the detection rates in these studies were re- lated to the study design and the included population. For example, using a PCR as- say, influenza was detected in 10%–12% of symptomatic pilgrims [11,22] versus 1% among a sample of Egyptian return- ing pilgrims without the mention of any specific symptoms [21]. In another study of 305 pilgrims arriving at Shiraz airport, Islamic Republic of Iran, pandemic 2009 influenza A(H1N1) virus was detected in 1.6% pilgrims and other influenza A viruses were detected in 2.6% [26]. A recent study reviewed respiratory tract infections during the annual Hajj with comments on the potential risks [27]. Emergence of novel coronavirus infections prior to Hajj 2012 The first recorded infections with the 2012 nCoV occurred only a few months before the Hajj season in 2012 and were only reported publicly a few weeks ahead of the pilgrimage [28]. The first reported infection with nCoV 2.0 1.8 1.6 1.4 1.2 1.0 0.8 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 Year N o. o f fo re ig n vi si to rs (m ill io n) Figure 1 Annual counts of foreign visitors to the Hajj, 1996 to 2011 (Source: Ministry of Health, Saudi Arabia) Book 19 Supplement.indb 50 5/16/2013 2:27:40 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S51 was identified in the Saudi Arabian port city of Jeddah, in a Saudi Arabian male who died in June 2012 [29,30]. A second case was reported in a Qatari male with a history of travel to Saudi Arabia in late September 2012 [31,32]. The emergence of this virus in humans came at a time when Muslims from around the world were preparing to converge on Saudi Arabia for the Hajj pilgrimage given that the first reported case occurred in Jeddah, where Hajj pilgrims assemble, risks to Hajj had to be considered by Saudi authorities, by WHO, and by the national authorities of countries of the participating pilgrims [29]. Figure 2 illustrates the timing of initial infections with nCoV and Hajj 2012. The first 2 reported cases of nCoV sparked significant media interest in the implications of a new virus that was of the same family as the severe acute respiratory syndrome (SARS) coronavirus. Studies of the 2003 SARS outbreak found that the SARS virus was not easily transmitted between humans and required close contact or facilitated transmission by aerosol production [33]. As attention turned to the possible implications of nCoV infections for the Hajj, the available information about the virus was extremely limited. Geneti- cally, it closely resembled other coro- naviruses associated with bats, but the reservoir, the mechanism of acquisition and its spread were not known. Based on the initial information provided by the first reported cases of nCoV, no human-to-human transmission had oc- curred [32] and, as such, there were no travel restrictions to areas with reported cases. Risks of novel coronavirus to public health at Hajj 2012 Preparations leading to Hajj 2012 As described above, evidence exists for sustained communicable disease trans- mission at mass gathering such as Hajj. The discovery of nCoV infections in the location of the Hajj meant that the late stages of planning for Hajj 2012 had to account for this new disease. A unique component of Saudi Arabia’s approach to managing public health risks to pil- grims is the preparation and revision on an annual basis of the recommendations and health requirements for the period of the pilgrimage. Once developed by the Ministry of Health of Saudi Arabia, these requirements are shared through national and international platforms, including WHO’s Weekly Epidemiologi- cal Record. Since 2009, the Weekly Epi- demiological Record has communicated different types of information to the international community. This ranges from general advice to target popula- tions, to requirements at points/ports of entry, to vaccination obligations for all pilgrims. For instance, during pan- demic influenza A(H1N1) 2009, Saudi Arabia recommended that immuno- compromised, extremely overweight or pregnant individuals defer travel plans to another year [34]. In 2000 and 2001, coinciding with Hajj, an international outbreak of disease was caused by a rare strain of Neisseria meningitidis, se- rogroup W135. This prompted Saudi 13–24 June Saudi case presents with symptoms and dies 3 September Qatari case onset of symptoms in Qatar Hajj 2012 takes place from 10–30 October Mid July Erasmus Medical Centre tests samples and obtains virus culture 20 and 23 September Pro Med/WHO report infections. First annoucement of the virus 23 November Saudi Arabia reports family cluster of nCoV cases. Qatar reports additional case. 30 November Jordan reports 2 retrospec- tive cases from a hospital cluster 11 February 2013 onwards Further cases of nCoV detected Figure 2 Timeline of novel coronavirus (nCoV) infections Book 19 Supplement.indb 51 5/16/2013 2:27:41 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S52 Arabian health authorities to introduce a mandatory vaccination requirement of quadrivalent ACWY meningitis vac- cine for Hajj 2002 [35]. Requirements and recommenda- tions for Hajj seasons are also revised on an ad hoc basis as and when acute public health events are judged by Saudi Arabian authorities to present a risk to Hajj attendees. In July 2012, preliminary recommendations and requirements for Hajj were issued and published in the Weekly Epidemiological Record [36]. Viral respiratory infections were ad- dressed within specific recommenda- tions for seasonal influenza vaccination for national and international pilgrims. In addition, the 2012 recommendations made specific reference to the impor- tance of routine vaccinations, especially for measles and rubella due to the recent resurgence of these diseases around the globe [36]. Initial information for Hajj 2012 did not include specific recom- mendations to infections due to nCoV as in July 2012 the disease had yet to emerge as a public health risk. In October 2012, Saudi Arabia up- dated information on health hazards and recommendations for Hajj 2012 in an article published in Eurosurveillance [28]. These revisions provided further requirements for Hajj pilgrims coming from Uganda, the Democratic Republic of the Congo and Sierra Leone on the basis of ongoing outbreaks of commu- nicable disease at that time. The paper also recommended specific measures to reduce the risk of transmission of viral respiratory infections, including those associated with nCoV but it did not issue any travel restrictions with respect to nCoV infections. Saudi Arabia reminded pilgrims to “practice proper hand hygiene, protective be- haviours and cough etiquette to further decrease the occurrence of respiratory diseases”. Other countries also issued nCoV guidance to their nationals visit- ing Saudi Arabia for the Hajj, such as Britain [37] and the United States [38]. Some countries advised their nationals to seek medical attention if, on return from Hajj, they developed acute respira- tory symptoms. Public health measures adopted during the Hajj pilgrimage Public health efforts to maintain a high level of excellence during the Hajj are coordinated by 24 supervisory commit- tees [39]. To enhance the effectiveness of activities, an electronic surveillance system is used by public health teams and teams at points of entry. This en- hanced surveillance targets influenza, influenza-like illness, meningococcal disease, food poisoning, viral haemor- rhagic fevers, yellow fever, cholera, polio and plague [39]. In line with Saudi Ara- bia’s policy of providing free access to health care during the Hajj, there were 25 hospitals offering 4964 beds includ- ing 547 critical care beds [28]. Health care was also provided through 141 medical centres in the Hajj area [28]. The Saudi Arabian Ministry of Health case definition for nCoV was published in Eurosurveillance [28]. A suspected case was defined as a per- son requiring hospitalization with community-acquired acute respiratory syndrome with symptoms of: fever (≥ 38 °C) and cough; and confirmed lower airways involvement (clinical and radiological evidence of pneumonia) not explained by any other infection or other etiology. A confirmed case was defined as a person with laboratory- confirmed infection with nCoV [28]. The current WHO definitions for case finding include the definition for a confirmed case (a person with labora- tory confirmation of infection with the nCoV) and a probable case [40]. A probable case is defined as a person with an acute respiratory infection with clinical, radiological or histopathologi- cal evidence of pulmonary parenchy- mal disease (e.g. pneumonia or acute respiratory distress syndrome); and no possibility of laboratory confirmation for nCoV either because the patient or samples are not available for testing; and close contact with a laboratory- confirmed case [40]. The lack of information or evidence on the severity and transmissibility of this novel virus in mass gathering situa- tions raised concerns for the Hajj. As for other viruses in the coronavirus family, the infection was thought to spread by aerosol droplets [41]. The pattern of transmission of nCoV in overcrowded and congested settings, such as those of Hajj, posed a big “unknown” to the international community as well as to the Saudi national health authorities. The risk of international nCoV spread as a result of imported cases from returnee pilgrims was also unknown. Examples of this had been previous documented, as seen in the 2000 and 2001 outbreaks of meningococcal men- ingitis W135 [9,42]. This prompted the Saudi Arabian national health authori- ties to consult with international health partners, including WHO, to rapidly develop and put into practice an appro- priate strategy for detection of suspect nCoV cases among pilgrims. The annual Hajj took place from 10–31 October 2012 and approximate- ly 4 million pilgrims took part. Pilgrims came from 187 countries and visited the main religious sites of Saudi Arabia in Mecca and Medina. The Hajj of 2012 was declared by Saudi Arabia as free from any public health event and not a single case of nCoV infection was de- tected through the national surveillance system. Over 300 sick pilgrims were tested for nCoV infections and all were found to be negative [43]. Screening of returnee pilgrims was also carried out in Europe and else- where. No imported cases of nCoV infections were reported to WHO from these countries. In a cohort of 154 French pilgrims returning from Hajj 2012, 83.4% had respiratory symptoms and 41% had influenza-like illness [44]. All the pilgrims screened tested negative for nCoV by real-time PCR assays [44]. Book 19 Supplement.indb 52 5/16/2013 2:27:41 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S53 Impact of further cases on future mass gatherings At the time of writing (March 2013), WHO had been informed of a total of 15 confirmed cases of human infection with nCoV, including 9 deaths [45]. Eight of these cases including 6 deaths were reported from Saudi Arabia. The majority of cases presented with severe illness. Limited, but not sustained, human-to-human transmission has also been reported in cases in the United Kingdom [46] and in Jordan. The cases in Jordan were detected retrospectively [47]. A Saudi investigation into a fam- ily cluster of 3 confirmed and 1 prob- able case—conducted after the Hajj in 2012—remained inconclusive but the dates of onset of symptoms of this family cluster of cases appeared to be consist- ent with human-to-human transmission [46]. Given new information on the transmission and the reported incidence of the virus following the Hajj in 2012, the epidemiological potential for an outbreak of nCoV infections during this year’s Hajj in 2013 may be more likely. The occurrence of nCoV infections and the possible evolving patterns of trans- mission should be closely monitored and assessed by the international com- munity and Saudi authorities ahead of this year’s Hajj in October 2013. Another factor related to nCoV that may impact on the Hajj in 2013 is the epidemiology of this emerging disease. If populations susceptible to nCoV are found to be demographically similar to those attending Hajj, the risks posed to the Hajj may be increased. Global public health vigilance will be important to see how the public health risk associated with this novel virus unfolds. International collabora- tions will be crucial to protect global health as Hajj and mass gathering in the face of a potentially deadly virus that may seriously affect global health security. Importance of international collaborations As part of this international collabora- tion to prevent any global spread of nCoV infection through spread of Hajj-related infections, teams of disease experts converged on Saudi Arabia immediately before the Hajj. These included epidemiologists from WHO and the United States Centers for Dis- ease Control in Atlanta, virologists from the Center for Infection and Immunity at Columbia University in New York and experts in the control of zoonotic diseases from EcoHealth, a New York city-based international organization for ecology and health. These specialists were invited by the Saudi Arabian gov- ernment. The Saudi Arabian National Committee for Infectious Diseases worked with WHO to rapidly develop a case definition and protocol for detecting and testing pilgrims who de- veloped a respiratory infection [40]. An investigation of potential environmen- tal and animal sources of the nCoV was carried out by the team from Columbia University. In addition to international col- laboration with regards to nCoV, the global nature of mass gathering and potential risks to international health and security, make it imperative that the research and guidelines produced are relevant to diverse contexts and are a collaborative effort between global experts and centres. This is important, not only as emergence of new patho- gens is a continued threat with implica- tions for transmission and international spread at mass gathering, but to foster a culture of sharing of knowledge and expertise more generally across the field. This should extend to areas as diverse as communicable and noncommunicable diseases and to ensure a legacy of practi- cal knowledge transfer and sharing of lessons learned. There are many centres and indi- viduals with academic and practical expertise in this mass gathering and a current commitment exists to bring such organizations and individuals to- gether through formal and informal networks and collaborations. Examples of these networks include the WHO virtual interactive advisory group on mass gatherings, the newly formed Global Mass Gatherings Network and the developing network of WHO col- laborating centres on mass gatherings. References 1. Al Rabeeah AA et al. Mass gatherings medicine and global health security. Lancet, 2012, 380:3–4. 2. Steffen R et al. Non-communicable health risks during mass gatherings. Lancet Infectious Diseases, 2012, 12:142–149. 3. Abubakar I et al. Global perspectives for prevention of infec- tious diseases associated with mass gatherings. Lancet Infec- tious Diseases, 2012, 12:66–74. 4. Communicable disease alert and response for mass gatherings. Technical workshop, Geneva, Switzerland, 29–30 April 2008. Geneva, World Health Organization, 2008 (WHO/HSE/ EPR/2008.8). 5. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: the Saudi perspective. International Journal of Antimicrobial Agents, 2003, 21:96–101. 6. Altizer S et al. Seasonality and the dynamics of infectious dis- eases. Ecology Letters, 2006, 9:467–484. 7. International health regulations (2005), 2nd ed. Geneva, World Health Organization, 2005. 8. Al-Tawfiq JA, Memish ZA. Mass gatherings and infectious dis- eases: prevention, detection, and control. Infectious Disease Clinics of North America, 2012, 26:725–737. Book 19 Supplement.indb 53 5/16/2013 2:27:41 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S54 9. Ahmed QA, Arabi YM, Memish ZA. Health risks at the Hajj. Lancet, 2006, 367:1008–1015. 10. Balkhy HH et al. Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination. Journal of Travel Medicine, 2004, 11:82–86. 11. El Bashir H et al. Influenza among UK pilgrims to hajj, 2003. Emerging Infectious Diseases, 2004, 10:1882–1883. 12. Gundlapalli AV et al. Influenza, Winter Olympiad, 2002. Emerging Infectious Diseases, 2006, 12:144–146. 13. Blyth CC et al.; World Youth Day 2008 Influenza Study Group. Influenza outbreaks during World Youth Day 2008 mass gath- ering. Emerging Infectious Diseases, 2010, 16:809–815. 14. Shi P et al. The impact of mass gatherings and holiday traveling on the course of an influenza pandemic: a computational model. BMC Public Health, 2010, 10:778. 15. Botelho-Nevers E et al. Travel-related influenza A/H1N1 infec- tion at a rock festival in Hungary: one virus may hide another one. Journal of Travel Medicine, 2010, 17:197–198. 16. Van Hal SJ et al. Influenza outbreak during Sydney World Youth Day 2008: the utility of laboratory testing and case definitions on mass gathering outbreak containment. PLoS ONE, 2009, 4:e6620. 17. Loncarevic G et al. Public health preparedness for two mass gathering events in the context of pandemic influenza (H1N1) 2009—Serbia, July 2009. Eurosurveillance, 2009, 14:pii 19296. 18. Mandourah Y et al. Clinical and temporal patterns of severe pneumonia causing critical illness during Hajj. BMC Infectious Diseases, 2012, 12:117 19. Alborzi A et al. Viral etiology of acute respiratory infections among Iranian Hajj pilgrims, 2006. Journal of Travel Medicine, 2009, 16(4):239–242. 20. Alherabi AZ. Impact of pH1N1 influenza A infections on the otolaryngology, head and neck clinic during Hajj, 2009. Saudi Medical Journal, 2011, 32:933–938. 21. Kandeel A et al. Pandemic (H1N1) 2009 and Hajj pilgrims who received predeparture vaccination, Egypt. Emerging Infectious Diseases, 2011, 17:1266–1268. 22. Rashid H et al. Influenza and respiratory syncytial virus infec- tions in British Hajj pilgrims. Emerging Health Threats, 2008, 1:e2. 23. Rashid H et al. Viral respiratory infections at the Hajj: compari- son between UK and Saudi pilgrims. Clinical Microbiology and Infection, 2008, 14:569–574. 24. El-Sheikh SM et al. Bacteria and viruses that cause respiratory tract infections during the pilgrimage (Haj) season in Makkah, Saudi Arabia. Tropical Medicine and International Health, 1998, 3:205–209. 25. Memish ZA et al. Detection of respiratory viruses among pil- grims in Saudi Arabia during the time of a declared influenza A(H1N1) pandemic. Journal of Travel Medicine, 2012, 19:15–21. 26. Lim HC et al. The influenza A (H1N1–2009) experience at the inaugural Asian Youth Games Singapore 2009: mass gathering during a developing pandemic. British Journal of Sports Medi- cine, 2010, 44:528–532. 27. Al-Tawfiq JA, Zumla A, Memish ZA. Respiratory tract infections during the annual Hajj: potential risks and mitigation strategies. Current Opinion in Pulmonary Medicine, 2013, 19:192–197. 28. Al-Tawfiq JA, Memish ZA. The Hajj: updated health hazards and current recommendations for 2012. Eurosurveillance, 2012, 17:pii 20295. 29. Novel coronavirus—Saudi Arabia: human isolate. ProMed, 2012, archive number 1302733:20. 30. Corman VM et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Eurosurveillance, 2012, 17:pii 20285. 31. Novel coronavirus infection—update. 25 September 2012. World Health Organization [online] (http://www.who.int/csr/ don/2012_09_25/en/index.html, accessed 7 MAY 2013). 32. Bermingham A et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United King- dom from the Middle East, September 2012. Eurosurveillance, 2012, 17:pii 20290. 33. Skowronski DM et al. Severe acute respiratory syndrome (SARS): a year in review. Annual Review of Medicine, 2005, 56:357–381. 34. Health conditions for travellers to Saudi Arabia for the pilgrim- age to Mecca (Hajj). Weekly Epidemiological Record, 2009, 84:477–480. 35. Al-Tawfiq JA, Clark TA, Memish ZA. Meningococcal disease: the organism, clinical presentation, and worldwide epidemiol- ogy. Journal of Travel Medicine, 2010, 17(Suppl.):3–8. 36. Health conditions for travellers to Saudi Arabia for the pilgrim- age to Mecca (Hajj). Weekly Epidemiological Record, 2012, 87:277–280. 37. Novel coronavirus—advice for travellers, including Hajj pilgrims. Clinical updates, 15 October 2012. National Travel Health Net- work and Centre [online] (http://www.nathnac.org/pro/ clinical_updates/coronavirus_151012.htm, accessed 7 May 2013). 38. Severe respiratory illness associated with a novel coronavirus— Saudi Arabia and Qatar, 2012. MMWR Morbidity and Mortality Weekly Report, 2012, 61(40):820–820. 39. Memish ZA. The Hajj: communicable and non-communicable health hazards and current guidance for pilgrims. Eurosurveil- lance, 2010, 15:pi 19671. 40. Revised interim case definition for reporting to WHO—novel coro- navirus. 19 February 2013. World Health Organization [online] (http://www.who.int/csr/disease/coronavirus_infections/ case_definition/en/index.html, accessed 7 May 2013). 41. Malik M et al. Emergence of novel human coronavirus: public health implications in the Eastern Mediterranean Region. East- ern Mediterranean Health Journal, 2012, 18:1084–1085. 42. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: the Saudi perspective. International Journal of Antimicrobial Agents, 2003, 21:96–101. 43. Novel coronavirus—Eastern Mediterranean (03): Saudi com- ment, 12 February 2013. ProMed, 2013, archive number 20130212.1540011. 44. Gautret P et al. Lack of nasal carriage of novel corona virus (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms. Clinical Microbiology and Infection, 2013, Feb 11 (doi: 10.1111/1469- 0691.12174 ). 45. Novel coronavirus infection in the United Kingdom. 23 September 2012, update 12 March 2013. World Health Organization [on- line] (http://www.who.int/csr/don/2013_03_12/en/index. htmlhttp://www.who.int/csr/don/2012_09_23/en/index. html, accessed 7 May 2013). 46. Novel coronavirus infection—update. 16 February 2013. World Health Organization [online] (http://www.who.int/csr/ don/2013_02_16/en/index.html, accessed 7 May 2013). 47. Novel coronavirus infection—update. 30 November 2012. World Health Organization [online] http://www.who.int/csr/ don/2012_11_30/en/index.html, accessed 7 May 2013). Book 19 Supplement.indb 54 5/16/2013 2:27:41 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S55 Short communication Enhanced surveillance and investigation of coronavirus: what is required? R.G. Pebody,1 A. Nicoll,2 U. Buchholz,3 M. Zambon1 and A. Mounts4 1Public Health England, London, United Kingdom (Correspondence to R.G. Pebody: richard.pebody@phe.gov.uk). 2European Centre for Disease Prevention and Control, Stockholm, Sweden. 3Robert Koch Institute, Berlin, Germany. 4Global Influenza Programme,World Health Organization, Geneva, Switzerland. ABSTRACT Following the discovery in September 2012 of 2 patients, both with links to the Eastern Mediterranean Region, with serious respiratory illness due to novel coronavirus, all countries have instigated surveillance and laboratory activities to detect further cases, with intensive case−contact investigations undertaken on laboratory confirmation of cases. A total of 30 cases, of whom 18 have died, and at least 3 clusters have been detected to date (1 cluster among health-care workers and another 2 clusters among family members). To date, transmission studies have shown a low risk of onward human transmission, with clinical presentation remaining severe for the majority. Many questions remain including the zoonotic source and geographical extent of infection. Surveillance has been extended to include clusters of cases or health-care workers with severe, undiagnosed respiratory illness regardless of travel history. Environmental studies, on-going surveillance and linked case− contact investigations will provide a critical role in answering some of these issues. ؟بولطلما وه ام :يجاتلا سويرفلل ِّيصقتلاو د ُّصترلا زيزعت ستنوام .أ ،نوبماز .م ،زلوهشُب .أ ،لوكين .أ ،يدَبِيب .ر Coronavirus يجاتلا سويرفلا نع مجانلا ميخولا سيفنتلا ضرلماب ْنيَباصم ،طسوتلما قشر ميلقإب ةلص ماله يضيرم فاشتكا دعب :ةـصلالخا ةز َّكرم تايصقت ذا ِّتخا بناج لىإ ،تلاالحا نم ديزلما فشكل ةمزلالا تابرتخلماو د ُّصترلا ةطشنأ نادلبلا عيجم تز َّزع ،2012 برمتبس/لوليأ في ديدلجا تاعوممج ثلاث فاشتكا عم ،ةافولاب تهتنا 18 اهنم ،30 تلااحلل ليكلا ددعلا غلبو .تلاالحا نم يبرتخلما د ُّكأتلا لجأ نم تلااحلل يطلاخملل انموي ىتحو )ةسرلأا ءاضعأ يب ناتيدوقنع ناتعوممجو ،ةيحصلا ةياعرلا في يلماعلا يب ةدحاو ةيدوقنع ةعوممج( نلآا ىتح لقلأا لىع ةيدوقنع ةميخو لازتلا ةيريسر تماس عم ،لبقتسلما في ناسنلإل ناسنلإا نم لاقتنلال ًاضفخنم ًاراطتخا ىودعلا لاقتنا لىع ةارجلما تاساردلا ترهظأ ،اذه لمشيل د ُّصترلا قاطن عيسوت مت دقو .ىودعلل فيارغلجا ىدلماو ،ىودعلل نياويلحا ردصلما اهنيب نم ،ةديدع ةلئسأ كانه لازتلاو .تلاالحا مظعم في فوسو .رفسلا خيرات نع رظنلا ضغب ص َّخشم يرغ ميخو سيفنت ضرمب يباصلما ةيحصلا ةياعرلا في يلماعلا وأ تلااحلل ةيدوقنعلا تاعومجلما .ةلئسلأا كلت ضعب نع ةباجلإا في مساح رود ابه ةطبترلما تلااحلل يطلاخملل ةرمتسلما تاي ِّصقتلاو رمتسلما د ُّصترلاو ةيئيبلا تاساردلل نوكي Surveillance et recherche renforcées pour le coronavirus : quels sont les besoins ? RÉSUMÉ Suite à la découverte en septembre 2012 de deux patients atteints d'une maladie respiratoire sévère imputable à un nouveau coronavirus, tous deux ayant des liens avec la Région de la Méditerranée orientale, tous les pays ont initié des activités de laboratoire et de surveillance afin de dépister d'autres cas, et notamment des recherches de cas-contacts intensives pour les cas confirmés en laboratoire. Sur 30 cas au total, 18 sont décédés, et au moins trois groupes ont été identifiés à ce jour (un groupe chez des agents de soins de santé et deux autres groupes chez les membres des familles). À ce jour, les études de transmission ont démontré que le risque de future transmission interhumaine était faible, mais que le tableau clinique demeurait sévère pour la majorité des cas. Il reste de nombreuses questions en suspens, notamment la source zoonotique et la propagation géographique de l'infection. La surveillance a été élargie à ces groupes de cas ou aux agents de soins de santé atteints de maladies respiratoires sévères non diagnostiquées indépendamment de leurs voyages passés. Des études environnementales, une surveillance continue et des recherches reliant des cas-contacts seront essentielles pour répondre à certaines de ces questions. Book 19 Supplement.indb 55 5/16/2013 2:27:41 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S56 Introduction The discovery of a novel coronavirus (nCoV) in a patient hospitalized with severe respiratory illness reported in September 2012 in Saudi Arabia [1] was shortly followed by the laboratory confirmation of nearly identical virus in a second individual in a hospital in Lon- don, United Kingdom [2]. This further, unlinked case had been transferred for medical care from Qatar following on- set of a severe respiratory illness [3]. The detection of these 2 cases, both infected with a novel respiratory virus from the same genus as severe acute respiratory syndrome (SARS)-CoV, led to a global alert about the emergence of a new virus with possible SARS-like properties, with the experience of SARS at the forefront of response planning. The appearance of a previously un- recognized virus, most closely related to beta corona viruses in bats and which resulted in severe respiratory illness in humans, raised a series of important public health questions. These are sum- marized in the accompanying article by Nicoll et al. [4]. What was the likely ani- mal reservoir of this virus? What were the risk factors for animal-to-human infection? What was the ability of the virus to spread from person-to-person? What was the extent of infection in the human population? And what was the spectrum of illness associated with in- fection in humans? The answers to all of these questions were unknown based on the experience of only 2 cases, 1 of which was fatal. What role can surveillance play in helping to answer these questions? Surveillance was originally described by Langmuir as “the systematic collec- tion, collation, analysis of data and dis- semination of information on a specific disease to inform public health action” [5]. Latterly the epidemic intelligence role of surveillance, with timely alerting, analysis and dissemination of informa- tion, has gained greater prominence and is enshrined in the 2005 revision of the World Health Organization (WHO) International Health Regulations [6,7]. The detection of the 2 initial cases, both of whom required intensive care support and who acquired their infec- tion in the Eastern Mediterranean Region, together with the rapid devel- opment and availability of a sensitive and specific polymerase chain reaction (PCR) diagnostic tool for the detec- tion of viral genetic material while virus shedding was still occurring [8], allowed the development of surveillance strat- egies to find further nCoV cases [9]. Relatively specific clinical case defini- tions were developed initially to provide a moderately good predictive value and ensure an efficient use of limited public health and laboratory capacity. The hi- erarchical case definitions developed by WHO and national organizations such as the Centers for Disease Control in the United States, Public Health Eng- land (formerly the Health Protection Agency) in England, the Robert Koch Institute in Germany and the Euro- pean Centre for Disease Prevention and Control for the European Union [9–13] focused on the detection of individuals with severe undiagnosed respiratory illness with a history of travel from countries where indigenously acquired cases had been detected dur- ing the putative incubation period of nCoV. Such “patients under investiga- tion” were recommended for nCoV testing (Table 1). Detailed laboratory algorithms needed to be established with a first-line sensitive assay to detect the virus, followed by a second-line as- say to confirm virus detection, to avoid false conclusions about the incidence of disease Early detection and isolation of laboratory-confirmed cases of symp- tomatic illness allows the rapid imple- mentation of measures to limit potential spread of infection to close contacts. Case ascertainment also provides an opportunity for an in-depth epidemio- logical, clinical and virological investiga- tion of the first cases and their close contacts using approaches developed during the 2009 influenza pandemic [11]. Collection of detailed information from cases (or their families when cases have died or were seriously unwell) al- lows a description of the demographic and clinical characteristics of cases and the development of hypotheses about risk factors for human infection from an as yet unknown reservoir. Describing laboratory-confirmed cases by time and place enables the epidemic curve and geographical distribution of this appar- ent emerging public health problem to be elaborated. Finally, the identification and follow-up of close contacts of con- firmed cases provides the opportunity for detailed case-contact investigations that may provide clues to key epidemio- logical questions. These investigations involve intensive prospective follow-up of contacts for evidence of respiratory disease, together with virological and serological sampling. The availability of newly developed virological and se- rological assays provides the ability to detect secondary infections [14] and to measure the full disease spectrum among infected contacts [15]. These surveillance approaches, together with follow-up of an increas- ingly large number of close contacts, has resulted in 30 laboratory confirmed cases of nCoV being reported globally in the 6 months to 8 May 2013 [16]. Of the 30 confirmed cases, the majority have had severe respiratory disease, with 18 cases having died to date, a high case fatality rate. There is, however, a sugges- tion of a wider disease spectrum, with a small number of milder cases, detected through intense contact tracing activi- ties [14], although active virological and serological follow-up of case-contacts regardless of symptoms has to date failed to uncover a significant hidden “iceberg” of mild or asymptomatic cas- es. The majority (24/30) of cases have been detected in the Eastern Mediter- ranean Region, with 6 cases diagnosed in Europe (the United Kingdom and Germany). Four of these latter 6 cases Book 19 Supplement.indb 56 5/16/2013 2:27:42 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S57 Table 1 Definitions of patients and situations requiring public health investigation and testing for novel coronavirus (nCoV) Organization [reference] Patient under investigation Other situations under investigation World Health Organization [9] A person with an acute respiratory infection, which may include history of fever or measured fever ≥ 38 °C (100.4 °F) and cough; AND Suspicion of pulmonary parenchymal disease (e.g. pneumonia or acute respiratory distress syndrome), based on clinical or radiological evidence of consolidation; AND Residence in or history of travel to the Arabian peninsula or neighbouring countriesa within 10 days before onset of illness; AND Not already explained by any other infection or etiology, including all clinically indicated tests for community-acquired pneumonia according to local management guidelines. It is not necessary to wait for all test results for other pathogens before testing for nCoV. Ill contacts Individuals with acute respiratory illness of any degree of severity who, within 10 days before onset of illness, were in close physical contact with a confirmed or probable case of nCoV infection while the case was ill. Any person who has had close contact with a probable or confirmed case while the probable or confirmed case was ill should be carefully monitored for the appearance of respiratory symptoms. If symptoms develop with the first 10 days after contact, the individual should be considered a “patient under investigation”, regardless of the severity of illness, and investigated accordingly. Clusters Any cluster of severe acute respiratory infection, particularly clusters of patients requiring intensive care, without regard to place of residence or a history of travel; AND Not already explained by any other infection or etiology, including all clinically indicated tests for community- acquired pneumonia according to local management guidelines. Health-care workers Health-care workers who care for patients with severe acute respiratory infections, particularly patients requiring intensive care, who develop unexplained pneumonia without regard to place or residence or history of travel. Centers for Disease Control [10] A person with an acute respiratory infection, which may include fever ≥ 38 °C (100.4 °F) and cough; AND Suspicion of pulmonary parenchymal disease (e.g. pneumonia or acute respiratory distress syndrome based on clinical or radiological evidence of consolidation); AND History of travel from the Arabian peninsula or neighbouring countriesa within 10 days; AND Not already explained by any other infection or etiology, including all clinically indicated tests for community-acquired pneumoniab according to local management guidelines. Persons who develop severe acute lower respiratory illness of known etiology within 10 days after travel from the Arabian peninsula or neighbouring countriesa but do not respond to appropriate therapy; OR Persons who develop severe acute lower respiratory illness who are close contacts of a symptomatic traveller who developed fever and acute respiratory illness within 10 days after travel from the Arabian Peninsula neighbouring countriesa. Close contact is defined as providing care for the ill traveller (e.g. a health-care worker or family member), or having similar close physical contact; or stayed at the same place (e.g. lived with, visited) as the traveller while the traveller was ill. Clusters of severe acute respiratory illness In addition, any clusters of severe acute respiratory illness in health-care workers in the United States should be thoroughly investigated. Occurrence of a severe acute respiratory illness cluster of unknown etiology should prompt immediate notification of local public health for further notification and testing. Health Protection Agency [11] Any person with severe acute respiratory infection: Symptoms of fever ≥ 38 ºC or history of fever and cough; AND With evidence of pulmonary parenchymal disease (e.g. pneumonia or acute respiratory distress syndrome) based on clinical or radiological evidence; AND Not already explained by any other infection or etiology; AND History of travel to or residence in an area where infection with nCoV 2012 has recently been reported or where transmission could have occurred in the 10 days before onset of illness. Health-care worker based in intensive care unit (ICU) caring for patients with severe acute respiratory infection; OR Close contact (i.e. prolonged face-to-face contact) during the 10 days before onset of illness with a confirmed case of nCoV infection while the case was ill. Cluster Two or more cases of severe acute respiratory infection requiring ICU admission, regardless of history of travel; AND Not already explained by any other infection or etiology. Book 19 Supplement.indb 57 5/16/2013 2:27:42 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S58 Table 1 Definitions of patients and situations requiring public health investigation and testing for novel coronavirus (nCoV) (concluded) Organization [reference] Patient under investigation Other situations under investigation Robert Koch Institute [12] Patient with respiratory symptoms independent of its severity; AND “epidemiological exposure A” (close contact); OR Patient with “clinical picture” and “epidemiological exposure B”. Clinical picture Patients with acute respiratory syndrome (with or without fever ≥ 38 °C) and (with or without cough) for whom based on clinical or radiological signs of an inflammatory infiltrate it is suspected that the lower respiratory tract is affected (e.g. pneumonia or acute respiratory distress syndrome); AND Symptoms not explained by another cause of infection or disease including causes of community-acquired pneumonia (e.g. Streptococcus pneumoniae, Haemophilus influenzae type B, Legionella pneumophila, other bacterial, pneumonia virus, influenza virus type A or B, respiratory syncytial virus). Epidemiological exposure Within the last 10 days before onset of illness: (A) Close contact: With a patient, in particular by medical personnel, or family members; OR Stay in the same place (e.g. living together, visit) as a case, while they were symptomatic. (B) Stay (travel or residence) in the Arabian peninsula or in adjacent countriesc. Medical personnel meeting the clinical picture after close contact with ICU-treated patients meeting the clinical picture and needing intensive care INDEPENDENT of epidemiological exposure. Two or more persons treated in ICU meeting the clinical picture, with onset of symptoms within the same 2 -week period and within the same classroom, workplace, household, extended family, hospital, other residential facility, barracks or camps INDEPENDENT of epidemiological exposure. European Centre for Disease Prevention and Control [13] A person with an acute respiratory infection, which may include history of fever and cough and indications of pulmonary parenchymal disease (e.g. pneumonia or acute respiratory infection), based on clinical or radiological evidence of consolidation, who requires admission to hospital; AND Has exposure in the Middle East within 10 days before onset of illness, unless another aetiology has been identifiedd. A person with an acute respiratory infection, which may include history of fever and cough and indications of pulmonary parenchymal disease (e.g. pneumonia or acute respiratory infection), based on clinical or radiological evidence of consolidation, who requires admission to hospital; AND any of the following: • Is in a cluster that occurs within a 10-day period, without regard to place of residence or history of travel, unless another aetiology has been identifiedd. • Occurs in a health-care worker who has been working in an environment where patients with severe acute respiratory infections are being cared for, particularly patients requiring intensive care, without regard to place of residence or history of travel, unless another aetiology has been identifiedd. aCountries considered in the Arabian peninsula and neighbouring include: Bahrain, Iraq, Islamic Republic of Iran, Israel, Jordan, Kuwait, Lebanon, Oman, Palestinian territories, Qatar, Saudi Arabia, Syrian Arab Republic the United Arab Emirates and Yemen. bExamples of respiratory pathogens causing community-acquired pneumonia include influenza A and B, respiratory syncytial virus, Streptococcus pneumoniae and Legionella pneumophila. cYemen, Qatar, Kuwait, Oman, Saudi Arabia, United Arab Emirates and Iraq, Jordan, Bahrain, Syrian Arab Republic, Lebanon, Islamic Republic of Iran, Palestinian Territories, Israel. dNotes that dual infection has been demonstrated in at least 1 case and so that detection of another pathogen should not exclude testing for nCoV where the first pathogen is unlikely to explain the clinical presentation). Book 19 Supplement.indb 58 5/16/2013 2:27:42 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S59 had travelled from the Eastern Mediter- ranean Region during the 10-day puta- tive incubation period. The remaining 2 cases were both family members of one of the imported cases, who were infected following contact in the UK, one in a household setting, the other seemingly in a hospital setting [14]. Al- though the majority of cases have been sporadic, follow-up and investigation of close contacts of cases has identified likely evidence of non-sustained per- son-to-person transmission of virologi- cally confirmed infection on at least 3 occasions. One cluster (of 2 confirmed cases and 11 probable cases) of severe respiratory illness among health care workers in a hospital in Jordan was iden- tified based on retrospective testing; a second cluster (of 3 confirmed and 1 probable case) was identified in a family in Saudi Arabia and a third cluster (of 2 confirmed cases plus the index case) was found among family contacts of one of the confirmed cases imported to the UK. Investigation of each cluster did not demonstrate evidence of on-going person-to-person transmission. In May 2013, 13 confirmed cases were reported from Saudi Arabia to WHO and are currently under investigation [16]. The current picture is thus most likely of a severe, zoonotic infection with occasional transmission to humans, with limited person-to-person transmis- sion. These preliminary and limited data suggest that the surveillance strategies implemented following the detection of the initial 2 cases are generally ap- propriate, with a focus on severe rather than mild disease to maintain optimum specificity and sensitivity, although many gaps in knowledge remain. Al- though onward infection in the human population has been limited to date, experience with SARS illustrated the possibility for super-spreading events to take place [17], highlighting the impor- tance of ensuring timely detection of new cases through physician awareness and early testing and implementation of prevention and control measures. The ongoing detection of new cases linked (directly or indirectly) to the Eastern Mediterranean Region, highlights the importance of continuing surveillance for cases of severe respiratory disease with a history of travel from countries where sporadic cases have been re- ported (Table 1). Global and national nCoV surveillance and investigation activities have evolved based on the emerging epidemiological picture. WHO has adapted nCoV surveillance guidelines with a focus on detecting the full geographical extent of cases and to detect evidence of person-to-person transmission. Key changes to the case definition will allow the full geographi- cal “reach” of the infection in the human population to be better delineated by extending previous surveillance case definitions to include clusters of severe undiagnosed respiratory disease and severe undiagnosed respiratory disease in health-care workers regardless of his- tory of travel (Table 1). Continuing to undertake case-contact transmission studies of new cases and follow-up of contacts of newly confirmed cases is essential to detect evidence of person- to-person transmission. Investigation protocols and guidelines for these case-contact investigations have been developed [11] and should be deployed for future confirmed cases [11,18]. The emergence of nCoV has also high- lighted the importance of international collaboration between laboratories and countries where suspect cases have oc- curred. This has allowed the technol- ogy transfer of real-time PCR diagnostic tools. The serological diagnostics for nCoV remain technically challenging, and the importance of a global reference laboratory will remain vital. Such surveillance activities need to be supported by applied epidemio- logical studies to answer more specific questions and which should be under- taken in a standardized fashion to allow global pooling of results [13]. Other studies include: environmental and animal studies to identify the source of the infection; serological studies in a range of potentially exposed popula- tions; case–control studies to identify and quantify risk factors for animal-to- person transmission and retrospective testing of sample repositories from cases of severe undiagnosed respira- tory illness in a range of geographical settings. These studies should provide answers to the source of nCoV, whether nCoV is occurring in other settings, how long it has been around and what burden of illness it is responsible for. Such information is key to informing the revision and optimization of public health prevention and control measures to reduce the burden of disease due to this novel infection. References 1. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814–1820. 2. Bermingham A et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United King- dom from the Middle East, September 2012. Eurosurveillance, 2012, 17(40):pii 20290. 3. Pebody RG et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012. Eurosurveillance, 2012, 17(40):pii 202922. 4. Nicoll A. Public health investigations required for protecting the population against novel coronaviruses. Eastern Mediter- ranean Health Journal, 2013, 19(Suppl.):S61–S67. 5. Langmuir AD. The surveillance of communicable diseases of national importance. New England Journal of Medicine, 1963, 268:182–192. 6. International health regulations (2005), 2nd ed. Geneva, World Health Organization, 2005. 7. Heymann D, Mackenzie J, Peiris M. SARS legacy: outbreak re- porting is expected and respected. Lancet, 2013, 381:779–781. Book 19 Supplement.indb 59 5/16/2013 2:27:42 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S60 8. Corman VM et al. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance, 2012, 17(39):pii 20285. 9. Interim surveillance recommendations for human infection with novel coronavirus (28 November 2012). Geneva, World Health Organization, 2012 (http://www.who.int/csr/disease/coro- navirus_infections/InterimRevisedSurveillanceRecommenda- tions_nCoVinfection_20121128.pdf, accessed 6 May 2013). 10. Coronavirus. Update, case definitions, and guidance. Centers for Disease Control and Prevention [online factsheet] (http:// www.cdc.gov/coronavirus/ncv/case-def.html#case, accessed 6 May 2013). 11. The first few hundred (FF100). Enhanced case and contact protocol v4.0. Epidemiological protocols for comprehensive assessment of early novel coronavirus cases and their close contacts in the United Kingdom. London, Health Protection Agency, 2012 (http://www.hpa.org.uk/webc/HPAwebFile/ HPAweb_C/131713630080, accessed 6 May 2013). 12. Schwere respiratorische Erkrankungen in Verbindung mit einem Neuartigen Coronavirus. Falldefinition zur Fallfindung, Meldung und Übermittlung. Aktualisierte Version vom 12.12.201 [Severe respiratory disease in conjunction with a novel coronavirus. Case definition for case finding, reporting and communication. Updat- ed version 12.12.201]. Berlin, Robert Koch Institute, 2012 (http:// www.rki.de/DE/Content/InfAZ/C/Corona/Corona_Falldefi- nition.pdf?__blob=publicationFile, accessed 6 May 2013). 13. Rapid risk assessment. Severe respiratory disease associated with a novel coronavirus. 19 February 2013. Stockholm, European Centre for Disease Control and Prevention, 2013 (http://www. ecdc.europa.eu/en/publications/Publications/novel-coro- navirus-rapid-risk-assessment-update.pdf, accessed 6 May 2013). 14. Health Protection Agency (HPA) UK NCoV Investigation team. Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, Feb- ruary 2013. Eurosurveillance, 2013, 18(11):pii 20427. 15. Buchholz U et al. Contact investigation of a case of human novel coronavirus infection treated in a German hospital, Oc- tober–November 2012. Eurosurveillance, 2013, 18(8):pii 20406. 16. Novel coronavirus infection—update. 8 May 2013. World Health Organization [online] (http://www.who.int/csr/disease/ coronavirus_infections/update_20130508/en/index.html, accessed 8 May 2013). 17. Peiris JS et al. The severe acute respiratory syndrome. New Eng- land Journal of Medicine, 2003, 349:2431–2441. 18. Van Kerkhove M et al. The consortium for the standardiza- tion of influenza seroepidemiology (CONSISE): a global partnership to standardize influenza seroepidemiology and develop influenza investigation protocols to inform public health policy. Influenza and Other Respiratory Viruses, 2013, 7(3):231–234. Book 19 Supplement.indb 60 5/16/2013 2:27:42 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S61 Short communication Public health investigations required for protecting the population against novel coronaviruses A. Nicoll 1 1Influenza and Other Respiratory Viruses Programme, European Centre for Disease Prevention and Control, Stockholm, Sweden (Correspondence to A. Nicoll: Angus.Nicoll@ecdc.europa.eu). ABSTRACT There have been many laboratory-based investigations since the emergence of the novel coronaviruses in the autumn of 2012, but most of the parameters required for establishing scientifically the control measures that will protect against them have yet to be determined. Equally, the global distribution of the viruses in their animal reservoir has yet to be established. The experience of investigating and controlling another novel coronavirus, SARS, in 2003 shows how national and local investigations can come together as an international coalition and successfully avert epidemics. A menu of studies that need to be undertaken, especially in the countries experiencing transmission, is presented here. ديدلجا يجاتلا سويرفلا نم سانلا ةيمالح ةمزلالا ةيمومعلا ةيحصلا تاي ِّيصقتلا لوكين سوغنأ متي لم هنأ لاإ ،2012 ماع فيرخ في ديدلجا Coronavirus يجاتلا سويرفلا روهظ ذنم تابرتخلما لىع زكترت ةيرثك تاي ِّصقت ترهظ دقل :ةـصلالخا عيزوتلا في كلذ لثم ْنلُقو .سويرفلا كلذ نم سانلا يمتح ثيحب ةيملع سسأ لىع ةحفاكلما يربادت ةماقلإ ةبولطلما تاتباثتلما مظعم ديدتح نلآا ىتح رخآ ديدج سويرف ةحفاكمو ءاصقتسا نم ةدافتسلما ةبرلخا ترهظأ دقو .نلآا ىتح اهديدتح متي لم يتلا ةيناويلحا اتهاعدوتسم في تاسويرفلل يلماعلا نأ نكمي ةيلحلماو ةينطولا تايصقتلا نأ فيك 2003 ماع في )سراسلا( ةميخولا ةدالحا ةيسفنتلا ةمزلاتلما سويرف وهو ،ةيجاتلا تاسويرفلا نم ةياسر نم نياعت يتلا نادلبلا في ماَّيسلاو ،ابه مايقلا يغبني يتلا تاساردلاب ةمئاق ةلاقلما ضرعتو .ءابولا يدافت في حجنتل ليود فلاتح نمض ًاعم لمعت .تاسويرفلا Etudes de santé publique requises pour la protection de la population contre les nouveaux coronavirus RÉSUMÉ Depuis l'émergence de nouveaux coronavirus pendant l'automne 2012, de nombreuses études ont été menées en laboratoire, mais la plupart des paramètres requis pour l'établissement scientifique de mesures de lutte qui soient capables de protéger contre ces virus restent à définir. De plus, la répartition mondiale de ces virus dans leur réservoir animal doit encore être établie. En 2003, l'expérience de la recherche sur un autre nouveau coronavirus, le syndrome respiratoire aigu sévère, et de la lutte contre ce virus a démontré comment des recherches nationales et locales permettent de mettre en place un front commun au sein d'une coalition internationale et d'éviter efficacement les épidémies. Les études qui doivent être menées, en particulier dans les pays où la transmission est active, sont répertoriées dans le présent article. Book 19 Supplement.indb 61 5/16/2013 2:27:42 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S62 Introduction Concerns have been raised globally by the appearance in 2012 of a novel coronavirus (nCoV) causing severe respiratory disease within some coun- tries in the Middle East and in patients transferred for medical care in Europe [1–3]. The fact that a significant pro- portion of the confirmed cases have died and that the cause is a coronavirus of presumed animal origin has revived memories of the severe acute respira- tory syndrome (SARS) epidemics of 2003 [3–5]. Patients who survive the initial infection often require prolonged artificial respiratory support (me- chanical ventilation or extra corporeal membrane oxygenation), so even a few cases impact significantly on higher- level clinical services. A case travelling to Europe on a commercial flight and then infecting others indicates how easily the infection might spread in- ternationally, as seen with the SARS coronavirus [6,7]. The purpose of this short com- munication is to summarize thinking on priorities for surveillance, applied epidemiological studies, and public health research and development activities. The approach taken is to highlight particular questions that need to be answered for the purposes of preventing or treating these infec- tions and diseases—the what and the why of each specific question. This is followed by an explanation of the mechanisms by which each question can be answered (the how) leading to a list of the specific studies required to achieve this. Controlling and protecting against novel coronaviruses The new viruses have been genetically sequenced [8,9]. Bats are considered to be the hosts for animal coronavi- ruses and these novel viruses affecting humans are similar to a number of bat coronaviruses isolated in both the old and the new world [10]. While they bear some relationship to the SARS-CoV virus which caused severe acute respiratory syndrome (SARS), they are also sufficiently different to preclude the assumption that they will behave in the same way as SARS-CoV [9]. Indeed the signature characteristic of SARS outbreaks in humans—super spreading events—have not been described so far [3,5,7]. Analytic viro- logical studies of nCoV have appeared with impressive speed in peer reviewed journals and some of the conclusions reached are concerning [9,11–13]. The virus may have the potential to spread in a range of mammalian cells; binds to a receptor that is preserved across a number of species, including humans [11,13]; it can also infect and replicate with cytopathic effect in a wide range of cell-lines across various human tissue types and from other species [12]. However virological in- vestigations alone cannot predict how the virus will behave, its pathogenic action or how it should be treated or controlled [14]. At present (April 2013), there is still a lack of much of the information that would be needed to inform on how to control nCoV infection; prevent initial infections; interrupt any human- to-human transmission; and manage and treat human infections (Table 1). Table 1 Information required from investigations for control or mitigation of a novel respiratory virus affecting humans – the “known unknowns” for influenza and other respiratory viruses (including novel zoonotic coronaviruses) Information required Reservoir of infections: animal, human, environmental Modes of transmission to humans and effective prevention of transmission Survival of the viruses in infectiousness doses in the environment Method of spread: human-to-human Setting when infections are take place and procedures associated with transmission Those at risk of infection: risk factors for transmission Those most likely to transmit Those at highest risk of severe disease Population susceptibility Incubation period When cases are infectious and how this relates to symptoms Reproductive number and serial interval Clinical presentation and clinical spectrum Antiviral susceptibility if any Effectiveness of specific treatment and care strategies Proportionate and effective infection control procedures Book 19 Supplement.indb 62 5/16/2013 2:27:43 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S63 Equally, it is unclear what (and where) the natural and more recent reservoirs of infection are. SARS for example had both a reservoir in bats and an intermediary host in southern China [15]. Similarly, it is unclear whether humans are occasionally being in- fected outside the Middle East. It can be argued that the simplest response would be to assume that the parameters for control of the nCoVs would be the same as those for SARS and apply the same measures. How- ever, these measures cannot be under- taken lightly because some of those which were effective in controlling SARS were resource-intensive and disruptive to societies and, especially, health-care economies [3]; therefore the parameters for control of nCoV infection need to be determined speedily. This uncertainty and the need for speedy action led the WHO Regional Office for the Eastern Medi- terranean to convene a consultation in Cairo in January 2013 attended by the countries experiencing cases in the Middle East and Europe; the relevant European laboratories [the Erasmus Medical Centre, Health Pro- tection Agency (since April 2013 now called Public Health England) and the University of Bonn]; and the public health authorities from Germany and the United Kingdom (Robert Koch Institute and Public Health England, respectively). This ECDC staff mem- ber also attended and presented an earlier version of this paper. Extensive epidemiological investi- gations have been undertaken around the few cases that have come to Eu- rope. Rapid publications from these are reassuring on transmissibility and appear to contradict some of the more worrying interpretations of the labo- ratory studies [6,16,17]. In Europe the novel viruses are not behaving in the same way as the SARS viruses did in countries outside Europe in 2003 (Table 1)[18]: to date, testing of over 200 close contacts of the first 2 imported cases have not revealed a single transmission (serological re- sults are pending for the United King- dom contacts) [16,17,]. Yet a third case who travelled on a commercial flight resulted in unsustained human- to-human transmission after arrival in the United Kingdom. There were 2 secondary transmissions: one in a family setting, the other a nosocomial infection in hospital [1,6]. This same cluster of 3 cases included the first confirmed mild case and another case with dual infection of the new virus and a seasonal influenza virus [6]. It would be unwise to base global guidance on the experience in a single country or region, even in an area as large as Europe. One of the notable features of the SARS coronaviruses in 2003 was the diversity of experience which arose seemingly by chance [7]. While some countries with imported cases had no transmissions, others experienced considerably transmis- sion, often in association with super- spreading events [5,7]. European Union/European Economic Area countries experienced only 32 prob- able SARS cases in 2003 (0.4% of the global total), with 1 death and no further transmissions [18]. So far, the experience with the nCoV in 2012– 2013 looks very similar to that with SARS in Europe in 2003 when there were imported confirmed cases but no sustained human-to-human trans- mission [1,7,19]. Hence, the 2012– 2013 European data alone do not provide a sufficient basis to conclude that the intense local transmission that happened in Hanoi, Vietnam, Hong Kong, Singapore and Toronto, Canada could not be reproduced with the new coronavirus [5,7]. It is instructive to consider how the measures that were effective in controlling SARS were determined in 2003. Essentially, the scientific basis for these measures (Table 2) was determined by the countries in which infection and transmission took place—Canada, China, Hong Kong, Singapore, Taiwan and Viet Nam—working together with WHO. Information from detailed field inves- tigations undertaken around the cases in those countries was shared openly, starting with a global video confer- ence meeting on 16–17 May 2003 [5]. The measures that were agreed on that basis in May 2003 were: general surveillance of respiratory illnesses; case finding and investigation; triage of persons with febrile illness; selec- tive quarantine; isolation of cases and close contacts of SARS cases; inten- sive infection control and cleaning in health-care setting and public and professional education (Table 2) [5]. These measures were effective and subsequent reviews indicated that this early sharing and publishing of the results did not prejudice any publica- tions from the countries [19,20,]. Conclusions It may be concluded that nCoV requires rapid field research studies combining epidemiological, clinical, serological and virological data to complement the published virologi- cal studies. These would be a series of studies carried out around the natu- rally-occurring cases as was done at speed in 2003 (Table 3) [5,19–26]. An advantage now is the availability of prepared protocols ready for adapta- tion by the countries that wish to un- dertake the work [21–25]. Serological techniques have been developed but await both use and validation in the countries experiencing transmission as well as an indication from the International Health Regulations (Article 6) that these and other sorts of studies should be undertaken and the results communicated in a timely manner[3,16, 21–27]. Book 19 Supplement.indb 63 5/16/2013 2:27:43 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S64 Table 2 The parameters that were used for controlling SARS – and how they were determined, 2003 [5,19,20] Parameter Findings Implications for control Modes of transmission Person-to-person via respiratory route; Direct (and indirect) contact of mucous membranes with respiratory secretions, including fomites; Aerosol-generating procedures were associated with “super-spreading events” Strict infection control and respiratory hygiene, especially in health-care settings; Regular and high levels of environmental cleaning in health-care settings; Avoid aerosol-generating procedures and undertake scrupulous infection control procedures when they are essential Method of spread Air travel especially important for international spread; Movement of infected patients between hospitals for local spread Persons with febrile respiratory illnesses should delay travel; Exit screening for febrile respiratory illness for those leaving a country where transmission was taking place regularly; Reduction in movement and transfer of certain patients in complex local health economies Those at risk of infection Health care workers Patients in hospital Adult family members Children were only rarely infected themselves or infected others Particular emphasis on infection control in health care settings including emergency rooms and health care waiting rooms No reason to take more than the normal precautions with children Setting when infections take place Mostly health-care settings including emergency rooms Some transmissions in other closed settings such as aircraft Some unusual super-spreading events in Hong Kong in one hotel and one apartment complex Particular emphasis on infection control in health care settings including emergency rooms and health care waiting rooms Initial triage of febrile patients and those with respiratory symptoms seeking care Avoid aerosol generating procedures and undertake scrupulous infection control procedures when they are essential Incubation period 2 to 10 days Ten days a reasonable period for quarantine and for judging whether or not a person was likely to have SARS if symptomatic and had been in a country where transmission was taking place regularly When infectious Low in first few days of symptoms, maximal in second week Early self-isolation was found to be especially effective Reproductive number Best estimate was R = 1–3 Most infections did not result in further infections but super-spreading events took place Particular emphasis on infection control in health care settings including emergency rooms and health care waiting rooms Clinical presentation Acute, febrile respiratory illness, could be difficult to notice in persons with other respiratory illness and post- operative cases In a country where transmission was taking place regularly focus efforts on case-finding among those with acute, febrile respiratory illness: so-called fever clinics and initial triage of those presenting for care to prevent transmission in waiting areas and emergency rooms Effective control measures Intensive surveillance for respiratory infections and aggressive case finding where cases were occurring; Early isolation of putative cases Contact tracing around confirmed cases; Triage of persons with acute febrile respiratory illnesses Reduce movement and transfer of patients Those at highest risk of severe disease Persons with chronic underlying conditions; Pregnant women Particular protection of these groups Book 19 Supplement.indb 64 5/16/2013 2:27:43 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S65 Table 3 Specific public health questions needing answered for the novel coronaviruses – the what, why and how What do we need to know? Why do we need to know it? How will we find out? Types of studies and notes 1. Where geographically are the human infections occurring worldwide? Determining the level of threat: is this an infection only occurring in 1 locality in 1 sub-region or is it more widespread? Alternatively is this an older infection that has been around some time and simply unrecognised? To inform decisions on which patients to test among those who come to Europe with respiratory infections or who subsequently develop respiratory infections within a certain time Case-finding virologic testing of people fitting the case definition for severe cases and others; Prospectively, among the people fitting the Persons Under Investigation (PUI) definitions in any clusters and outbreaks of severe respiratory disease Applied epidemiological and laboratory research studies in a number of countries testing patients with unexplained severe lower respiratory tract infection, either using retrospective contemporaneous archives of suitable stored specimen or as prospective planned studies. The ECDC/WHO laboratory survey of European Union countries gives a mechanism by testing people fitting the PUI-with symptoms definition but need to distinguish the different groups therein: • People with severe disease + geographical risk • People with severe disease without geographical risk • Exposed health-care workers Question: Do we need to know the animal reservoir? Question: Have Koch’s postulates been demonstrated? Need to think beyond the Middle East and consider the trade/people movements from the Middle East especially migrant workers from South Asia who work in the Middle East Serological surveys to agreed protocols with local adaptations [21,22,24]. It should be possible to develop the tools but the importance will be validation and quality assurance from the CONSISE and earlier experience. It will be especially important to include validation with ‘sticky’ sera from middle East countries remembering the initial HIV serological experience where tests developed and validated in one region lost specificity in another settinga What is the reservoir of the virus infection? As for point 1 Environmental and animal surveillance and testing around sporadic unexplained cases Environmental and animal studies 2. The estimated incubation period (from exposure to symptoms) and serial interval? Informing on who to test: “all people developing severe acute respiratory infections within a certain number days of coming from countries X, Y, Z” Determining potential for explosive spread. Comparing infections like influenza (short incubation period and serial interval: impossible to control) and SARS and smallpox (long incubation period and serial interval: possible to control) Observing and investigating clusters to agreed protocols with local adaptations [21,22]. Book 19 Supplement.indb 65 5/16/2013 2:27:43 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S66 Table 3 Specific public health questions needing answered for the novel coronaviruses – the what, why and how (concluded) What do we need to know? Why do we need to know it? How will we find out? Types of studies and notes 3. How infectious are these cases and what are the sources of infectious virus? Informing on infection control measures and their stringency Reviewing the outcome of the case finding around the recognised cases especially in health care staff and household/family contacts In SARS most cases did not transmit to secondary cases, but 10%–20% transmitted to many secondary (and higher order) cases: super-spreading events [7,19,20]. 4. When are these cases infectious to others Informing on the duration of infection control measures and the stringency of control measures, as well as possible advice on quarantine of exposed persons Studies of when and at what levels are the viruses detectable compared to the symptoms and to default cases of influenza and SARS There are some data from this from Germany (Robert Koch Institute). Note: a positive feature of SARS was that the cases were really not infectious before developing symptoms (c.f. influenza) making quarantine and early isolation of cases especially effective [5]. 5. Are there any super- spreading events? Informing on infection control measures and the stringency of control measures Reviewing the outcome of the case finding around the recognised cases especially in health care staff and household/family contacts Watch for these especially in health- care settings. What actually happened in the clusters in Jordan and Saudi Arabia? 6. What do cases look like? Who are the high risk groups? Informing on who to test and understanding the scope of illness manifestations; Understanding the frequencies and severity of organ involvement and secondary bacterial infections to assist in clinical management Review of the confirmed cases; Serological testing of contacts, especially those with milder symptoms, and virologic testing of contacts exposed in future events [21]. Note: a problem with SARS was that infectious cases were not always recognised in a timely manner. Some were inapparent for example in those hospitalised for other reasons (e.g. post major surgery, people with multiple pathology). In a sense this has happened in the cases that were imported into Germany and the United Kingdom without thinking they might represent serious imported infections. 7. How best to manage and treat the patients To optimise care and to avoid doing harm from certain medical interventions Preparing and agreeing protocols, and those caring for patients applying these and sharing experience and results in real time Suitable protocols have now been agreed between ISARIC members and approved by WHO [25]. 8. How extensive is patient movement from the Middle East to Europe? Looking for cases and determining which clinicians to inform; Considering the risk to those caring for patients in transit WHO Member States asking the referral centre; Work with people who look at transport trends and patient export importations Note for the cases that came to other countries the long time between the arrival and considering testing for novel infections. aWhen HIV serological tests validated in Europe and North America were applied in Africa in the 1980s without local validation and the consequent publication of analyses suggesting substantial levels of population prevalence in East Africa which were due to cross-reaction with other antibodies (to malaria) [26]. ECDC = European Centre for Disease Prevention and Control. WHO = World Health Organization. CONSISE = consortium for the standardization of influenza seroepidemiology. HIV = human immunodeficiency virus. SARS = severe acute respiratory syndrome. ISARIC = International Severe Acute Respiratory and Emerging Infection Consortium. Book 19 Supplement.indb 66 5/16/2013 2:27:43 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S67 References 1. Rapid risk assessment: severe respiratory disease associ- ated with a novel coronavirus, 19 February 2013. Stockholm, European Centre for Disease Prevention and Control, 2013 (http://ecdc.europa.eu/en/publications/Publications/nov- el-coronavirus-rapid-risk-assessment-update.pdf, accessed 11 May 2013). 2. Danielsson N, on behalf of the ECDC Internal Response Team. Catchpole M. Novel coronavirus associated with severe res- piratory disease: Case definition and public health measures. Eurosurveillance, 2012, 17(39):pii 20282. 3. Heymann D, Mackenzie J, Peiris M. SARS legacy: out- break reporting is expected and respected Lancet, 2013, 381(9869):779–781. 4. Eurosurveillance editorial team. Note from the editors: A new virus bringing back memories from the past. Eurosurveillance, 2012, 17(39):pii 20284. 5. Consensus document on the epidemiology of severe acute respira- tory syndrome. Geneva, World Health Organization, Depart- ment of Communicable Disease Surveillance and Response 2003 (WHO/CDS/CSR/GAR/2003.11) (http://www.who.int/ csr/sars/en/WHOconsensus.pdf, accessed 11 May 2013). 6. Health Protection Agency (HPA) UK, Novel Coronavirus Investigation team. Evidence of person-to-person transmis- sion within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Eurosurveillance, 2013;18(11): pii 20427 7. Update: Outbreak of Severe Acute Respiratory Syndrome — Worldwide, 2003. Morbidity and Mortality Weekly Report (MMWR), 2003, 52(12):241–248. 8. Genetic sequence information for scientists about the novel coronavirus 2012. Whole Genome Sequence – Added 18th February 2013. London, Public Health England, Health Pro- tection Agency 2013 (http://www.hpa.org.uk/Topics/In- fectiousDiseases/InfectionsAZ/NovelCoronavirus2012/ respPartialgeneticsequenceofnovelcoronavirus/) accessed 11 May 2013. 9. Cotten M et al. Full-genome deep sequencing and phylo- genetic analysis of novel human betacoronavirus. Emerging Infectious Diseases, 2013, 19(5) (http://wwwnc.cdc.gov/eid/ article/19/5/13-0057_article.htm, accessed 11 May 2013). 10. Annan A et al. Human betacoronavirus 2c EMC/2012–related viruses in bats, Ghana and Europe.[Internet]. Emerging Infec- tious Diseases, 2013, 19:456–459. 11. Raj VS et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 2013, 495:251– 254 (http://www.nature.com/nature/journal/v495/n7440/ pdf/nature12005.pdf , accessed 11 May 2011). 12. Chan JP et al. Differential cell line susceptibility to the emerg- ing novel human betacoronavirus 2c EMC/2012: implications on disease pathogenesis and clinical manifestation. Journal of Infectious Diseases. (2013) 207(11):1743–1752. 13. Müller M et al. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. mBio, 2012, 3(6) (http:// mbio.asm.org/content/3/6/e00515-12.long, accessed 11 May 2013). 14. Mackintosh K. A new virulent human coronavirus: How much does tissue culture tropism tell us? Journal of Infectious Diseases (Advance Access), 2013 (http://jid.oxfordjournals.org/con- tent/early/2013/03/24/infdis.jit125.full.pdf+html, accessed 11 May 2013). 15. Li W et al. Bats are natural reservoirs of SARS-like coronavi- ruses. Science, 2005, 310:676–679. 16. Buchholz U et al. Contact investigation of a case of hu- man novel coronavirus infection treated in a German hos- pital, October–November 2012. Eurosurveillance, 2013, 18(8):20406 (http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20406, accessed 11 May 2013). 17. Pebody RG et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coro- navirus in September 2012. Eurosurveillance, 2012, 17(40):pii 20292. 18. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 (Based on data as of the 31 De- cember 2003.). Geneva, World Health Organization, Global Health and Response, 2003 (http://www.who.int/csr/sars/ country/table2004_04_21/en/index.html, accessed 11 May 2013). 19. Anderson RM et al. Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 2004, 359:1091–1105. 20. Peiris JS et al. The severe acute respiratory syndrome. New England Journal of Medicine, 2003, 349:2431–2441. 21. “The First Few Hundred (FF100)” Enhanced Case and Contact Protocol v4.0. Epidemiological protocols for comprehensive assessment of early novel coronavirus cases and their close contacts in the United Kingdom. London, Health Protection Agency, 2012 (http://www.hpa.org.uk/webc/HPAwebFile/ HPAweb_C/1317136300809, accessed 11 May 2013). 22. Van Kerkhove M et al. on behalf of the CONSISE steering com- mittee. The consortium for the standardization of influenza seroepidemiology (CONSISE): a global partnership to stand- ardize influenza seroepidemiology and develop influenza in- vestigation protocols to inform public health policy. Influenza and Other Respiratory Viruses, 2012, 7(3). 23. Reusken C et al.Specific serology for emerging human coro- naviruses by protein microarray.Eurosurveillance, 2013, 18:pii 20441.) 24. Van Kerkhove M. CONSISE and avian influenza H7N9. CONSISE Working Draft Protocols for influenza. London, CONSISE The Consortium for the Standardization of Influenza Seroepide- miology, 2013 (http://consise.tghn.org/articles/consise-and- avian-influenza-h7n9/, accessed 11 May 2013). 25. Longuère K-S. ISARIC and WHO SARI and Natural History Pro- tocols. Oxford, ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium), 2013 (http://isaric.tghn. org/articles/isaric-and-who-sari-and-natural-history-proto- cols/, accessed 11 May 2013). 26. Biggar RJ et al. Regional variation in prevalence of anti- body against human T-lymphotropic virus types I and III in Kenya. East Africa International Journal of Cancer, 1985, 35(6):763–767 (http://onlinelibrary.wiley.com/doi/10.1002/ ijc.2910350611/abstract, accessed 11 May 2013). 27. International Health Regulations, 2005, 2nd ed. Geneva, World Health Organization, 2008 (http://whqlibdoc.who.int/pub- lications/2008/9789241580410_eng.pdf, accessed 11 May 2013). Book 19 Supplement.indb 67 5/16/2013 2:27:44 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S68 Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 C. Joseph,1 M.R. Malik,2 A.W. Mounts,1 A. R. Mafi,2 S. Briand,1 Z.A. Memish 3,4 and the technical working group for the meeting on novel coronavirus 1Global Influenza Programme, Department of Pandemic and Epidemic Disease. World Health Organization, Geneva, Switzerland. 2Pandemic and Epidemic Disease, Department of Communicable Disease Prevention and Control, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt (Correspondence to M.R. Malik: malikm@who.int). 3Ministry of Health, Riyadh, Saudi Arabia. 4College of Medicine, Al Faisal University, Riyadh, Saudi Arabia. ABSTRACT The emergence of a novel strain of coronavirus in the Arabian Peninsula raised a global health concern in 2012, partly because the majority of human infections were fatal and partly due to its presumed animal origin. An urgent meeting of scientific and public health experts was convened by WHO in January 2013 in view of the limited knowledge available on the epidemiological and natural history of infection with this novel virus. The meeting reviewed current evidence and identified critical knowledge gaps to improve better understanding of the public health risk associated with the virus so as to improve preparedness and to safeguard and protect global health. نوناك 16-14 ،صرم ،ةرهاقلا ؛ديدلجا يجاتلا سويرفلاب ىودعلا لوح ينقتلا يرواشتلا عماتجلاا نم تاصلاخو تافطتقم 2013 رياني/نياثلا يجاتلا سويرفلا ةياور لىع عماتجلال لماعلا قيرفلا ،شميم دايز ،دنايرب يفليس ،فياعم اضر ليع ،تنوام نياو نيوطنأ ،كلام رانومام ،فيزوج لراك ماع يلماعلا ديعصلا لىع يحصلا قلقلا ةراثإ لىإ ةيبرعلا ةريزلجا هبش في Coronavirus يجاتلا سويرفلا نم ةديدج ةيرذ روهظ ىدأ دقل :ةـصلالخا تدقع دقو .ضَترفُي ام لىع نياويح ردصم نم انهأ لىإ ًاضيأ ًايئزج دوعي ماك ،ةتيمم تناك ةيشربلا ىودعلا تلااح مظعم نأ لىإ ًايئزج دوعي كلذو ؛2012 اذبه ىودعلل ةيئابولاو ةيعيبطلا قباوسلا لوح ةحاتلما ةليئضلا تامولعلما لظ في ًلاجاع ًاعماتجا ،2012 رياني/نياثلا نوناك في ةيلماعلا ةحصلا ةمظنم رطاخلم لضفأ ٍمهف لىإ لوصولا يسحتل ةمزلالاو فراعلما في ةمسالحا تاوجفلا د َّدحو ،ةنهارلا تانِّيبلا عماتجلاا ضرعتسا دقو .ديدلجا سويرفلا .لماعلا في ةحصلا ةياقوو ةياحم متت ماك بهأتلا يستح متي ثيحب سويرفلا اذه قفارت يتلا ةماعلا ةحصلا Faits marquants et conclusions de la réunion de consutlation technique sur l'infection par le nouveau coronavirus, Le Caire (Égypte), 14 - 16 janvier 2013 RÉSUMÉ L'émergence d'une nouvelle souche de coronavirus dans la Péninsule arabique a soulevé des inquiétudes sanitaires à l'échelle mondiale en 2012, d'une part parce que la majorité des infections humaines ont été mortelles et d'autre part parce qu'une origine animale était suspectée. L'Organisation mondiale de la Santé a invité des experts en santé publique et scientifiques à une réunion urgente en janvier 2013, étant donné les connaissances limitées disponibles sur l'évolution épidémiologique et naturelle de l'infection par ce nouveau virus. Pendant la réunion, les données disponibles ont été examinées et des lacunes critiques dans les connaissances ont été identifiées en vue d'améliorer la compréhension du risque pour la santé publique associé à ce virus, d'intensifier la préparation et de préserver et de protéger la santé mondiale. Book 19 Supplement.indb 68 5/16/2013 2:27:44 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S69 Introduction In 2012, a multi-country outbreak of severe acute respiratory disease in the Arabian Peninsula, caused by a novel coronavirus (nCoV), raised a global health alert [1–3]. In light of the severity of illness seen amongst the laboratory- confirmed cases reported to the World Health Organization (WHO) by Janu- ary 2013, where the mortality rate was over 55% [4], the discovery of this new virus triggered unprecedented global attention. This novel virus brought back mem- ories of the global epidemic of severe acute respiratory syndrome (SARS) in 2003 as this new virus was presumed to be of animal origin and also belonged to the same family of Coronoviridae as that of the SARS virus (SARS–CoV). Clini- cal symptoms caused by nCoV infection also matched the clinical picture of acute primary viral pneumonia seen in many patients suffering from SARS [5]. The genetic sequence data indicated that this new coronavirus was a beta- coronavirus similar to bat coronaviruses, but not similar to any other coronavirus previously described in humans, includ- ing the coronavirus that caused SARS in 2003 [6–8]. The available evidence related to this nCoV continued to sug- gest a zoonotic origin for the virus, and experience with the SARS–CoV also showed that any novel virus that is zo- onotic in origin has the potential to effi- ciently transmit from person to person, especially in healthcare settings, and to cause a global pandemic of severe human illness. An urgent meeting of scientific and public health experts involved in the national and global investigations of this nCoV infection was convened by WHO at its Eastern Mediterranean Re- gional Office in Cairo, Egypt, from 14 to 16 January 2013. The meeting brought together WHO, national experts who had been involved in investigations around the cases that have occurred, scientists who had been involved with the study of the origin of the virus, and experts who had participated in the global public health response to SARS and the avian influenza epidemic. The purpose of this meeting was to review and discuss the scientific and public health understanding of the emer- gence of nCoV to date, identify critical knowledge gaps in understanding the current risk and identify the next steps to improve knowledge and close up the research gap for public health ac- tion at the national and international level. The meeting was organized in 5 thematic sessions and in each of these sessions, available scientific informa- tion and up-to-date evidence on nCoV were presented and discussed by the participants. The sessions included (i) epidemiological information; (ii) virological and animal investigation; (iii) development of tests for nCoV; (iv) experience from SARS; and (v) risk communication and preparedness. The final session of the meeting on “knowledge gaps and priorities for re- search” reviewed the currently available scientific evidence and identified the critical knowledge gaps that needed to be addressed in order to improve global understanding of the risk associated with this novel virus. This paper summa- rizes the currently available information on the virus, knowledge gaps and the priority public health research activities that were discussed in the meeting in order to improve global preparedness for any potential pandemic caused by this novel virus. Highlights Environmental and epidemiological investigation By December 2012, 6 laboratory- confirmed cases of nCoV, including 3 deaths, had been reported from Saudi Arabia. Three (3) cases occurred sporadically and 3 were part of a fam- ily cluster. The dates of onset for the 3 sporadic cases were 6 June—10 Oc- tober. The dates of onset for the cases within the family cluster were sequen- tial and ranged from 5 October to 3 November, consistent with human-to- human transmission. No community transmission was reported. The investigation of potential en- vironmental and animal sources of the nCoV carried out in the Bisha area of Saudi Arabia in September 2012 was not conclusive. Bats and dates were the main focus of investigation. Bats were targeted because of the genetic relatedness of the nCoV to coronaviruses previously found in bats in Mexico and elsewhere [9]. Bat CoVHKU9, bovine respiratory CoV and Kenya Idoline bat viruses were detected among the 755 oral, rectal and serological samples from insectivorous bats collected in the Bisha area of Saudi Arabia and tested in the United States of America (USA) in October. Sequenc- ing by nested polymerase chain reaction (PCR) showed that Saudi bat virus was genetically indistinguishable from the nCoV identified by the Erasmus Medi- cal Center (EMC) of Rotterdam in the Netherlands. No virus was cultured from the Bisha bats. No microbiological or environmental link was made between date farming and date consumption for the first confirmed case of nCoV infec- tion and no tests were carried out on camels or goats. Though the inability to culture the virus or extend the sequence makes interpretation of the results dif- ficult, it did suggest that the virus may have been in the environment at very low frequency and concentration. It remained unknown whether the virus was in livestock or another intermediate host, nor how it may have been transmit- ted to humans. The first case reported from Qatar had onset of illness on 3 September with a travel history to Mecca from 29 July to 18 August. He had no known contact with sick people. He owns a farm with camels and sheep which he visited once on his return from Mecca. The patient was transferred to the United Kingdom Book 19 Supplement.indb 69 5/16/2013 2:27:44 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S70 (UK) on 12 September where the nCoV was identified through culture and PCR. Genetic sequencing indi- cated that the virus was the same as that previously found in the patient in Saudi Arabia. An investigation of health- care workers exposed to the patient identified 4 who became symptomatic after exposure, but laboratory reports were negative for all these cases when tested at the Health Protection Agency (HPA) in London. The UK Health Protection Agency (now known as Public Health Eng- land) confirmed on 22 September 2012 infection with a novel coronavi- rus in a patient in a London hospital who had been transferred from Qa- tar 11 days previously. Following the institution of strict respiratory isola- tion, infection control procedures and enhanced surveillance as a response to this imported case from Qatar, 64 contacts (56 health-care workers and 8 family and friends) were identified. Ten days after last exposure, none of the 64 had developed severe disease; 13 of them had reported mild respiratory symptoms during the 10-day follow- up period. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested. The health-care work- ers had a variety of exposures, includ- ing some during an aerosol generating procedure. Preliminary results of se- rological testing found no evidence of a serological response consistent with infection among close contacts of the confirmed case. The second case from Qatar was a single male and owns a camel and goat farm. He had no contact with the animals, had no history of travel, and no known contact with sick people. He was treated in 2 hospitals in Qatar from 12 to 24 October. Respiratory samples— nasal swabs and an endotracheal tube (ETT) aspirate were collected from the patient on 13 and 17 October and were negative when tested for a standard panel of respiratory viruses in Qatar. The ETT sample sent to the HPA in London tested positive for nCoV. The patient was transferred to Germany on 24 October. The estimated number of health-care workers and family con- tacts associated with the case was 85. Respiratory and serum samples were collected from 20 of these contacts and the nCoV was not detected in any of the respiratory samples. An investigation of 123 contacts (120 hospital and 3 out-of-hospital con- tacts) of the first nCoV case identified in Germany was conducted in November 2012 at the Robert Koch Institute in Berlin, Germany, to evaluate human- to-human transmission. The case was a patient with acute respiratory distress syndrome of unknown origin and symptom onset on 5 October who was transferred from Qatar to a specialist lung clinic in Germany. Eighty-five con- tacts provided blood for a serological test and analysis was performed using a 2-stage approach with an initial immu- nofluorescence assay as a screening test, followed by recombinant immunofluo- rescence assays and an nCoV-specific serum neutralisation test. None of the contacts tested positive for antibodies to the nCoV, indicating that no trans- mission had occurred to contacts after 20 days post exposure. A cluster of severe acute respiratory infections occurred in April 2012 in a health-care setting in Zarqa, Jordan. In November 2012, retrospective labora- tory investigation of a stored specimen of bronchoalveolar lavage and a serum sample confirmed nCoV infection in 2 patients, both of whom died. Addition- ally, 11 probable cases were identified through a retrospective epidemiological investigation. Ten of the 13 persons in this cluster were health-care workers. No sustained community transmission was observed. Virological and animal investigations Pathogenesis of nCoV A study conducted at the Univer- sity of Bonn found that the cellular receptor for nCoV is different from that used by the SARS–CoV, which also causes Severe Acute Respiratory Syndrome [10]. It has been previously shown that changes in the spike pro- tein (S1) of the coronavirus are an important means by which the virus adapts to a new host. The S1 protein as the presumed binding site in nCoV was cloned and tested for binding to target cells and was found to bind to human cells, and in animal models. The dipeptidyl peptidase 4 (DPP4) protein, an enzyme expressed on the surface of some cells, has now been identified as a receptor to which the S1 virus protein binds in human and bat cells. Further studies are now going on in the animal model related to patho- genic potential of nCoV in human respiratory tissues Sequencing studies The complete genome sequence of the nCoV-EMC/2012 virus has been published [8]. By January 2013, only 2 viruses were fully sequenced: the nCoV-EMC from Saudi Arabia and the one from Qatar sequenced by the HPA in London (England1_CoV). The analysis of 3 sequenced genomic fragments showed that the genetic structure of the virus isolate in Germa- ny was identical to the virus isolated from the patient in Qatar in the UK. Methods for detecting nCoV by 2 real-time, reverse-transcription PCR assays (real-time RT-PCR) were published in September 2012 [6]. Two target regions were chosen for screening, confirmation and sequenc- ing of the nCoV; the Upstream of the E gene (UpE) for screening and ORF1b for confirmation. A 700-nucleotide segment of the N gene of the virus from one of the cases in Jordan sequenced at the United States Naval Medical Research Unit- 3 (NAMRU-3) had 99% homology to the EMC and London viruses. Book 19 Supplement.indb 70 5/16/2013 2:27:44 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S71 Development of laboratory tests for nCoV Tests by real-time PCR The current WHO interim guidance on PCR testing for nCoV states that a positive PCR test should be followed by a confirmatory test with the 1A as- say or by sequencing target sites within the nucleocapsid protein region of the genome [11]. Positive control materials developed by the University of Bonn are available for the upE and 1A tests. Two new assays for sequencing, particularly where an insertion/deletion polymor- phism might exist, as is the case between the EMC virus and the London virus, were also made available in December 2012. The assays are now available commercially worldwide and have been provided to some of the countries of the WHO Eastern Mediterranean Region where cases have occurred. The Cent- ers for Disease Control and Preven- tion (CDC), USA, has developed two nucleocapsid assays for detection of nCoV. These assays were distributed to Saudi Arabia and Jordan, and were used by NAMRU-3 to confirm the cases in Jordan. Serological tests Two immunofluorescent antibody (IFA) detection assays have been de- veloped; one using conventional IFA methods and the other a rapid method. Confirmatory tests for positive IFA results are carried out through recom- binant subunit assays, plaque reduction neutralization tests, and western blot to rule out false positive results [6]. Tests for sensitivity and cross-reactivity against other coronaviruses and other respiratory viruses with the nCoV- EMC found no cross-reactivity using these confirmatory methods. Further validation studies are needed and the IFA test is not suitable for broad popula- tion screening of asymptomatic indi- viduals. Many serological samples are in storage from the 9 nCoV cases and their contacts and these could be used to further validate the IFA tests. The UK HPA tested 124 sera samples from family and health-care worker contacts of the imported case from Qatar. The sera were screened for reactivity to coronavirus NL63 (CoV gp1), OC43 (CoV gp2a), SARS (CoV gp2b) and nCoV England/1 2012 (CoV gp2c). No reactivity with the nCoV England 1 antigen was detected. When recombinant assays were tested for cross-reactivity with these strains and bat CoV strains from groups 1, 2a, 2b, 2c and 2d, the group 2c bat strains were reactive to the London patient sera. These results were part of work in progress, and further studies will be needed to interpret the data. Cross- reactivity, particularly in older people who have been exposed to different coronaviruses over time, can be natu- ral. Cross reactions might also occur when detecting low titres that might be a result of past infection combined with a fresh infection of a different CoV. A wide range of tests are required to fully understand these issues. Ecological studies Ecological studies have shown that bats are natural hosts of 2b and 2c beta- coronavirus subgroups. Extensive bat sampling has been carried out in Africa and Europe, where a high percentage of bats among the Nycteris (25%) and Pipistrellus (36%) genera were found to be positive with CoV of the 2c clade. The pipistrellus bats inhabit the Ara- bian Peninsula but also migrate to Africa and other continents. The knowledge that insectivorous bats are natural hosts for betacoronaviruses, and that coronaviruses have been detected in a significant proportion of bats, does not in itself provide definitive evidence that they are the source of infection for the cases of nCoV detected in the Arabian Peninsula. More studies are needed to ascertain whether a virus even more closely related to nCoV-EMC might be found in other species and whether other animals might be sources or car- riers of the novel human coronavirus. Experience from SARS The global experience from SARS was a stark reminder of how a novel virus can cause a global public health emergency, from a few sporadic cases to a world- wide epidemic. The SARS-CoV spread to 5 countries within a 24-hour period, before international public health meas- ures were in place to identify, control and prevent the spread of infection. The importance and challenges in the implementation of public health meas- ures such as strict hospital infection control measures, case identification, and comprehensive identification and quarantine of contacts cannot be over- emphasized. Sharing of information at the local, national and international level was key to managing public and professional fear and anxiety. The les- sons learned from the SARS outbreak in 2003 emphasized the need to strength- en international health regulations, have national plans in place to handle similar future outbreaks, maintain public health epidemiological and microbiological capacity and keep ahead of the curve. Risk communication and preparedness The national and international public health organizations have kept the public fully apprised of the emergence and investigation of the nCoV cases on their websites through regular bul- letins and updates, question and answer sheets, or through publications such as the rapid reports in Eurosurveillance. The WHO has 3 main communica- tion channels: the Event Information Site (EIS), a password-protected rapid reporting system; the disease outbreak news (DON), which is a public system; and traditional media through its web- site and publications. The important lessons learned were mainly related to timely and adequate dissemination of information—the more informa- tion the better—to help the affected country, to help other neighbouring countries, and to help the world be bet- ter prepared. Book 19 Supplement.indb 71 5/16/2013 2:27:44 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S72 Gap analysis and priorities for future research and investigation of novel coronavirus A number of key knowledge gaps were identified to better understand the evo- lution and public health risk associated with this nCoV. The most important ones were the source of the virus, the exposures that resulted in human infec- tion, and the mode of transmission. Those areas where more information is needed to characterize the current and future risk posed to global health by this novel virus are: • source of the infection and its animal reservoir(s), • extent of geographical spread, • route(s) of transmission, • transmissibility of infection and de- gree of infectiousness, • exposure patterns, • incubation periods, • pathogenesis including age and gen- der determinants, • clinical spectrum of severe illness and evidence of mild infections, • what further diagnostic tests should be developed for detection of virus, • interpretation of test results. Four key areas were highlighted for guiding future efforts in further- ing the global understanding and knowledge of nCoV. These included (i) defining the geographic extent of virus transmission, (ii) detecting any escalation in incidence, (iii) improving the case definition; and (iv) identify- ing the source of infection. A number of recommended actions were also proposed and future steps were identi- fied for WHO’s role. Table 1 presents a summary of these priority research areas and the suggested recommended actions to improve the current knowl- edge gaps. Conclusion and next steps The emergence of new, infectious, global threats in the past 4 decades (e.g. AIDS, avian influenza A/H5N1 and SARS) has reshaped thinking at both national and international levels on the nature and level of public health responses needed for these threats. The International Health Regulations (2005) have emphasized that all countries are at risk from new infections and therefore need to collaborate on in- formation sharing and data exchange when they occur [12]. In the current age of immediate and ongoing access to world-wide digital information, there are high expectations globally that everything is being done to de- tect and control an emerging disease threat. Uncertainties as to how a newly discovered disease is going to evolve means that preparations have to be determined at both the national and the global level. During the Cairo meeting, all cur- rent knowledge about the cases of nCoV infection and about what has shaped priorities for future actions at the national and the international level was evaluated. After consolidating in- formation on current scientific activities ongoing at the global level, the delegates identified activities that would advance knowledge about this infection in the immediate and long term. These in- clude: • preparing an inventory of current nCoV virological research activities in European, American and other na- tional laboratories; • encouraging cooperation in the de- velopment of virological studies; • preparing an inventory of training op- portunities for laboratory staff testing for nCoV; • preparing an inventory of laboratories developing nCoV serological tests and list which laboratories are using which tests; • preparing an inventory of countries willing to test cases of severe acute respiratory infection (SARI) for nCoV; • liaising with the animal research group to strengthen collaborative studies and coordinate future stud- ies into the reservoir of infection for nCoV; • itemizing all collaborating resources and identifying where capacity build- ing is required; • ensuring that risk assessment guide- lines, infection control guidelines and other documents are regularly re- viewed and communicated to those that need to know. Technical working group members The members of the technical work- ing group include: Christian Drosten, Walter Ian Lipkin, Ron Fouchier, Udo Buchholz, Keiji Fukuda, Jaouad Mahjour, Hala Esmat, Dalia Samhouri, Gregory Hartl, Agnus Nicoll, Richard Pebody, Maria Zambon, Theresa Tam, Barbara Raymond, Hamad Eid Al- Romaihi, Said Hamed Al Dhahry and Sultan Mabdalla. Book 19 Supplement.indb 72 5/16/2013 2:27:44 PM طسوتلما قشرل ةيحصلا ةلجلماشرع عساتلا دلجلما 1 فياضلإا ددعلا S73 Table 1 Priority research area and recommended actions to improve global understanding and knowledge on novel coronavirus infection Priority research area Recommended actions Next steps, with support from WHO Defining the spectrum of disease severity (extent of virus transmission) • Develop a standardized and sensitive approach for seroepidemiological studies to identify severely and mildly ill persons, including those who may have been exposed to the virus but remained well. The studies should focus on: • patients with SARI; • close contacts of cases who become symptomatic; • clusters of SARI occurring in occupational groups, particularly health care workers; • Standardize and validate laboratory methods for serological assays (IFA or ELISA) to be used for screening for more specific and conclusive results. • Create a study group and framework for designing appropriate studies using standardized epidemiological methods. • Identify and prioritize groups for testing. • Develop protocols for standardized serological methods. • Encourage sharing of clinical samples between countries and laboratories. • Initiate serosurveys of contacts and probable cases to elucidate the full clinical spectrum of the disease, mindful of cross reaction. issues in serological studies. • Initiate laboratory training programmes for using standard methods. Detecting any increase or decrease in incidence of infection • Establish hospital baselines for pneumonia and monitor any unexplained rise in trend. • Enhance surveillance within groups such as case contacts, health care workers and clusters of patients with severe respiratory illness. • Prospectively collect and test sputum specimens from SARI patients and their close contacts. • Develop standard surveillance tools for monitoring changes in rates of pneumonic illness or detection of illness in selected population groups. • Develop a standard protocol for guidance on types of specimens to collect from selected population groups. • Ensure countries test single cases of unexplained severe respiratory illness and report positives to WHO. Improving the case definition • Collect more data on the clinical spectrum and natural history of nCoV to inform changes to the case definition (implementing a 2-stage case definition of initial screening followed by closer examination of cases that meet specific criteria can be considered). • Utilize protocols from the SARS epidemic to develop risk factor studies. • Contact affected countries to request data to better define key clinical features of known cases. • Obtain clinical information on known cases: pool all information from affected countries using a standardized extraction form. • Develop a global case definition for reporting. • Continue to monitor the effectiveness of the case definition and revise when relevant. Identifying the source of infection • Conduct animal studies to inform sources; (protocols from the studies carried out for the SARS epidemic could be utilized for developing risk factor studies into nCoV infection). • Include animal studies in the framework. ELISA = enzyme-linked immunosorbent assay; IFA = immunofluorescence assay; nCoV = novel coronavirus; SARI = severe acute respiratory infection; SARS = severe acute respiratory syndrome; WHO = World Health Organization. Book 19 Supplement.indb 73 5/16/2013 2:27:45 PM EMHJ  •  Vol. 19  Supplement 1 2013 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale S74 References 1. Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012, 367:1814–1820. 2. Pebody RG et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coro- navirus in September 2012. Eurosurveillance, 2012, 17(40):pii 20292. 3. Albarrak AM et al. Recovery from severe novel coronavirus infection. Saudi Medical Journal, 2012, 33:1265–1269. 4. Novel coronavirus infection-update (30 November 2012). Geneva, Switzerland, World Health Organization, Global alert and response (GAR), 2013 (http://www.who.int/csr/ don/2012_11_30/en/index.html, accessed May 10 2013). 5. Malik M et al. Emergence of novel human coronavirus: public health implications in the Eastern Mediterranean Region. East- ern Mediterranean Health Journal, 2012, 18:1084–1085. 6. Corman VM et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Eurosurveillance, 2012, 17(39):pii 20285. 7. Perlman S, Zhao J. Human coronavirus EMC is not the same as severe acute respiratory syndrome coronavirus. mBio, 2013, 4(1). 8. Van Boheemen S et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory dis- tress syndrome in humans. mBio, 2012, 3(6). 9. Anthony SJ et al. Coronaviruses in bats from Mexico. Journal of General Virology, 2013, 94:1028–1038. 10. Müller M et al. Human coronavirus EMC does not require the SARS-Coronavirus receptor and maintains broad replicative capability in mammalian cell lines. mBio, 2012 3(6). 11. Laboratory testing for novel coronavirus. Interim recommenda- tions. Geneva, World Health Organization, 2012 (http:// www.who.int/csr/disease/coronavirus_infections/Laborat oryTestingNovelCoronavirus_21Dec12.pdf, accessed 10 May 2013). 12. International health regulations (2005), 2nd ed. Geneva, World Health Organizati0n, 2008 (http://whqlibdoc.who.int/pub- lications/2008/9789241580410_eng.pdf, accessed 10 May 2013). Book 19 Supplement.indb 74 5/16/2013 2:27:45 PM Subscriptions and Distribution Enquiries regarding subscriptions and distribution of the print edition of EMHJ should be addressed to: Printing and Marketing of Publications at: email: pam@emro.who.int; tel: (+202) 2276 5000; fax: (+202) 2670 2492 or 2670 2494 Permissions Requests for permission to reproduce or translate articles, whether for sale or non-commercial distribution should be addressed to EMHJ at: emhj@emro.who.int Correspondence Editor-in-chief EMHJ WHO Regional Office for the Eastern Mediterranean P.O. Box 7608 Nasr City, Cairo 11371 Egypt Tel: (+202) 2276 5000 Fax: (+202) 2670 2492/(+202) 2670 2494 Email: emhj@emro.who.int EASTERN MEDITERRANEAN HEALTH JOURNAL IS the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas, con‑ cepts, epidemiological data, research findings and other information, with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession, medical and other health educational institutes, interested NGOs, WHO Col‑ laborating Centres and individuals within and outside the Region. LA REVUE DE SANTÉ DE LA MÉDITERRANÉE ORIENTALE EST une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine des ser‑vices de santé ainsi qu’à l’échange d’idées, de concepts, de données épidémiologiques, de résultats de recherches et d’autres informations, se rapportant plus particulièrement à la Région de la Méditerranée orientale. 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ISSN 1020‑3397 Cover designed by Diana Tawadros Cover photograph: Dr Linda Stannard, UCT/Science Photo Library Internal layout designed by Emad Marji and Diana Tawadros Printed by WHO Regional Office for the Eastern Mediterranean ميدقتل برنم ىهو .ةيلماعلا ةحصلا ةمظنمب طسوتلما قشرل ىميلقلإا بتكلما نع ردصت ىتلا ةيمسرلا ةلجلما ىه ةيئابولا تايطعلماو ميهافلماو ءارلآا لدابتلو ،اله جيوترلاو ةيحصلا تامدلخا فى ةديدلجا تاردابلماو تاسايسلا لك لىإ ةهجوم ىهو .طسوتلما قشر ميلقإب اهنم قلعتي ام ةصاخو ،تامولعلما نم كلذ يرغو ثاحبلأا جئاتنو زكارلماو ،ةينعلما ةيموكلحا يرغ تماظنلما اذكو ،ةيميلعتلا دهاعلما رئاسو ةيبطلا تايلكلاو ،ةيحصلا نهلما ءاضعأ .هجراخو ميلقلإا فى ةحصلاب ينمتهلما دارفلأاو ةيلماعلا ةحصلا ةمظنم عم ةنواعتلما طسوتلما قشرل ةيحصلا ةلجلما طسوتلما قشرل ةيلماعلا ةحصلا ةمظنلم ةيميلقلإا ةنجللا ءاضعأ نادلبلا ةيملاسلإا ناريإ ةيروهجم . ايبيل . سنوت . نيرحبلا . ناتسكاب . ةدحتلما ةيبرعلا تاراملإا . ناتسناغفأ . ندرلأا صرم . نانبل . تيوكلا . رطق . ينطسلف . نماُع . قارعلا . لاموصلا . نادوسلا . تيوبيج . نادوسلا بونج . نميلا . ةيروسلا ةيبرعلا ةيروهملجا ةيدوعسلا ةيبرعلا ةكلملما . برغلما Members of the WHO Regional Committee for the Eastern Mediterranean Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . Kuwait . Lebanon Libya . Morocco . Oman . Pakistan . Palestine . Qatar . Saudi Arabia . Somalia . South Sudan Sudan . Syrian Arab Republic . Tunisia . United Arab Emirates . Yemen Membres du Comité régional de l’OMS pour la Méditerranée orientale Afghanistan . Arabie saoudite . Bahreïn . Djibouti . Égypte . Émirats arabes unis . République islamique d’Iran Iraq . Libye . Jordanie . Koweït . Liban . Maroc . Oman . Pakistan . Palestine . Qatar . République arabe syrienne Somalie . Soudan . Soudan du Sud . Tunisie . Yémen Cover 19 Supplement.indd 2 5/16/2013 1:30:58 PM Contents Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale Volume 19 Supplement 1 / Supplément 1 2013 شرع عساتلا دلجلما 1 فياضلإا ددعلا V olum e 19 Supplem ent 1 2013 Coronavirus particles With the emergence of a novel coronavirus in 2012, WHO convened a meeting of experts in January 2013 to address this new public health threat. This supplement presents papers arising out of the meeting. Editorial Novel coronavirus infection: time to stay ahead of the curve ..................................................................................S3 Perspective Emergence of novel coronavirus: global context ......................................................................................................S5 Country experiences Saudi Arabia and the emergence of a novel coronavirus .........................................................................................S7 Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation ........................................................................................................................................ S12 Reviews The early response to a novel coronavirus in the Middle East ................................................................................ S19 Novel coronavirus: the challenge of communicating about a virus which one knows little about ......................S26 Novel coronavirus infection in the Eastern Mediterranean Region: time to act .....................................................S31 Infection prevention and control measures for acute respiratory infections in healthcare settings: an update ....................................................................................................................................................S39 Emerging respiratory and novel coronavirus 2012 infections and mass gatherings ...............................................S48 Short communications Enhanced surveillance and investigation of coronavirus: what is required? ............................................................ S55 Public health investigations required for protecting the population against novel coronaviruses ...................... S61 Meeting report Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14–16 January 2013 .............................................................................................................................. S68 Supplement on Novel Coronavirus Guest Editors Ziad A Memish, MD Jaouad Mahjour, MD, MPH Cover 19 Supplement.indd 1 5/16/2013 1:30:57 PM