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Yellow fever: strategic response plan, June-August 2016

21 июня 2016 г. Всемирная организация здравоохранения

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YELLOW FEVER Strategic Response Plan JUNE–AUGUST 2016

JUNE 2016

World Health Organization

Yellow Fever Strategic Response Plan 20/06/2016 WHO/YF/ENB/16.2

© World Health Organization 2016 All rights reserved. Publications of the World Health Organization are available on the WHO website (http://www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: bookorders@ who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO website (http://www. who.int/about/licensing/copyright_form/en/index.html). 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 and dashed 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. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. 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 expressed 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.

TABLE OF CONTENTS STRATEGIC RESPONSE FRAMEWORK The strategic response framework at a glance �� 04 Situation overview �� 05 Strategic objectives �� 08 Response strategy �� 09 Response coordination �� 16 Response monitoring �� 17 Summary of requirements �� 18

JOINT OPERATIONS PLAN Strategic objective 1 �� 21 Strategic objective 2 �� 27 Strategic objective 3 �� 28 Strategic objective 4 �� 30 ANNEX �� 32

at a glance

AT A GLANCE

THE STRATEGIC RESPONSE FRAMEWORK

This document is intended to guide the international response to the 2016 yellow fever outbreak in Angola and Democratic Republic of the Congo, and a concurrent yellow fever outbreak in Uganda, including preparedness for the importation of cases in non-affected countries, in a coordinated approach to interrupt the chain of transmission is informed by lessons learned over the past six months. This document provides an overview of the current situation, and outlines the response strategy for the rapid containment of current outbreaks and the prevention of international spread, including a Joint Operations Plan that provides further detail of how WHO and its partners are and will continue to meet the framework’s strategic objectives. The overview and strategy were developed with input from WHO’s regional office for Africa, the WHO Country Offices of Angola, the Democratic Republic of the Congo, and Uganda, and from partners including Médecins Sans Frontières, the Prevention and Control Program of the Communicable Disease Control Directorate of the Department of Health, Western Australia, UNDP, UNHCR, UNICEF regional offices for West and Central Africa (WCARO) and East and Southern Africa (ESARO), UNICEF headquarters, and from The University of Texas Medical Branch (UTMB Health).

GOAL End yellow fever outbreaks in affected countries and limit international spread

COORDINATION

04 STRATEGIC OBJECTIVE 1 End outbreaks in currently affected countries through targeted vaccination and other public health measures STRATEGIC OBJECTIVE 2 Prevent morbidity and reduce mortality through early case detection and strengthened case management STRATEGIC OBJECTIVE 3 Prevent international spread US$ 6.9 M US$ 5.2 M US$ 60 M

SURVEILLANCE AND RISK ASSESSMENT VACCINATION

COUNTRY CONTEXTS • Countries with a current outbreak Countries that share a border with a country experiencing a yellow fever outbreak, and all other countries in which yellow fever is endemic Other countries at risk of importation through international travel and trade, and at risk of an outbreak due to the presence of Aedes spp. mosquitoes

CASE MANAGEMENT VECTOR CONTROL SOCIAL MOBILIZATION AND RISK COMMUNICATION

•

TOTAL REQUIREMENT STRATEGIC OBJECTIVE 4 Prioritize research to improve access to yellow fever vaccine, and to improve the effectiveness of other prevention and control interventions US$ 0.29 M

US$ 72.35 M

Situation Overview

SITUATION OVERVIEW Background Yellow Fever is endemic in tropical areas of Africa and Central and South America. Thirty four (34) countries in Africa and thirteen (13) in Central and South America are either endemic for, or have regions that are endemic for, yellow fever.1 On 21 January 2016 WHO received official notification through the International Health Regulations (2005) of a yellow fever outbreak in Angola.2 The first suspected cases were reported in late December from Luanda – the country’s capital city and main trade and travel hub, with a population of over 6 million people. The disease, which is transmitted in urban settings by the Aedes aegypti mosquito, spread rapidly in Luanda. From there, cases were exported to the rest of the country (figure 1). By early May, all 18 of Angola’s provinces had reported suspected cases of yellow fever; 6 provinces had confirmed local

mosquito-borne transmission (figure 2). Cases of yellow fever have also been exported from Angola to China3 and Kenya4 (figure 1; table 1). On 22 March the Democratic Republic of the Congo (DRC), which borders Angola to the south, confirmed the detection of imported cases of yellow fever in areas bordering Angola by analysis at the Kinshasa National Institute of Bio-medical Research (INRB) and Pasteur Institute Dakar (IPD).5 By 15 June over 63 confirmed cases had been reported in districts bordering Angola (figure 1), including evidence of local mosquito-borne transmission in the capital, Kinshasa, and the country’s main seaport Matadi. Together these two large urban settlements have a population of over 11 million people and are well connected to international travel and trade routes. On 21 May 2016 The Republic of Congo reported a probable case of yellow fever in the town of Madingou, located close to the border with DRC and Angola. WHO provided immediate

1. WHO. Yellow fever Fact sheet: http://www. who.int/mediacentre/ factsheets/fs100/en/ (last accessed 24 May 2016). 2. WHO disease outbreak news: http://www.who. int/csr/don/12-february2016-yellow-feverangola/en/ (last accessed 24 May 2016) 3. WHO disease outbreak news: http://www.who. int/csr/don/22-april2016-yellow-fever-china/ en/ (last accessed 24 May 2016). 4. WHO disease outbreak news: http://www.who. int/csr/don/6-april-2016yellow-fever-kenya/en/ (last accessed 24 May 2016). 5. WHO disease outbreak news: http://www.who. int/csr/don/11-april2016-yellow-fever-drc/ en/ (last accessed 24 May 2016).

Table 1 | Total yellow fever cases and deaths as of 15 June 2016 Total confirmed, probable, and suspected cases of yellow fever Local transmission plus imported cases Angola DRC Uganda* Brazil* Peru* Imported cases only China Kenya 11 2 3137 1044 68 1 54 Total deaths from confirmed,

probable, and suspected yellow fever

345 71 3 1 6

0 1

*Not epidemiologically linked to the outbreak that originated in Angola. Investigations are ongoing into suspect cases (not epidemiologically linked to the Angola outbreak) reported in Ethiopia (22 cases), Ghana (4 cases), Chad (1 case), and Colombia (1 case).

Situation Overview Republic Of Congo Kinshasa

Democratic Republic Of The Congo

Figure 1 | National and international spread of yellow fever as of 8 June 2016

Districts reporting confirmed cases with autochthonous transmission Districts reporting confirmed cases imported from other areas Luanda*

Angola

Number of confirmed cases ≤2 3–5 6–10 11–25 26–150 151–500

06 As of 15 June, three countries have reported confirmed cases of yellow fever imported from Angola: • 11 cases in China • 57 cases in the Democratic Republic of the Congo • 2 cases in Kenya

Namibia

WHO received official notification of a yellow fever outbreak in Angola on 21 January 2016. As of 15 June over 3137 suspected cases and over 847 confirmed cases have been reported, with 345 deaths. On 22 March the Democratic Republic of The Congo (DRC) reported cases of yellow fever imported from Angola. As of 15 June 63 confirmed and probable cases had been reported in districts bordering Angola, including evidence of local mosquito-borne transmission in the capital, Kinshasa, and the country’s main seaport Matadi. The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement.

On 26 March WHO received official notification of a yellow fever outbreak in Uganda. As of 15 June, 68 suspected cases and 7 confirmed cases have been reported from 3 districts. Analysis of the genetic sequence of the circulating virus indicates that the Ugandan outbreak is not linked to the outbreak in Angola. *Data shown for the province of Luanda.

Situation Overview

technical assistance to the Congolese Ministry of Health, and is currently undertaking full field investigations to determine the nature and possible source of infection. Resources have been mobilised to strengthen local surveillance and diagnostic capacity. In addition to the yellow fever outbreak taking place in and around Angola, on 26 March WHO received official notification of a yellow fever outbreak in Uganda. By 15 June, 61 suspected and 7 confirmed cases had been reported from three districts. Analysis of the genetic sequence of the circulating virus indicates that the Ugandan outbreak is not linked to the outbreak in Angola. Further unrelated outbreaks in 2016 have been reported from Peru in April and Brazil in May (table 1), and Ethiopia (22 cases), Ghana (4 cases), Chad (1 case), and Colombia (1 case) in June. These outbreaks are under investigation, and appear to be limited to non-urban areas. Response Since the beginning of the outbreak, WHO and partners have supported the governments of Angola, DRC, and Uganda in their ongoing efforts to rapidly interrupt yellow fever transmission and strengthen measures to prevent spread across borders. WHO and its partners in the International Coordinating Group (ICG) for Vaccine Provision are managing an emergency stockpile supported by the Global Alliance for Vaccine and Immunization (GAVI). As of 20 May 2016, WHO has facilitated the procurement and delivery of over 14 million doses of yellow fever vaccine allocated through the ICG mechanism, for mass vaccination campaigns in Angola, DRC and Uganda. Funds amounting to approximately $US 2.24 million have been disbursed from the WHO Contingency Fund for Emergencies to further support national response efforts in affected countries. The response in Angola has also been supported by the Central Emergency Fund of the United Nations (CERF).6 Further CERF proposals are in process for DRC and Uganda. However, despite reactive mass vaccination campaigns in the Angolan capital Luanda and the provinces of Benguela and Huambo, new cases continue to be reported throughout Angola and around the border area with DRC and the Republic of Congo. By 15 June continued spread of yellow fever in Angola, including on the border with DRC, and the confirmation of autochthonous transmission in Kinshasa, DRC, prompted WHO to initiate a rapid, large-scale vaccination campaign to prevent further spread.

Rationale for a global response strategy The continued spread of yellow fever in Angola, evidence of local transmission in DRC, and the threat of further international spread triggered WHO to activate its organizationwide incident management system on 22 April 2016. A reallocation of vaccine stocks through ICG mecahnisms has provided a temporay boost to vaccine availability; however, current vaccine stocks are insufficient to respond to multiple simultaneous urban outbreaks. In the context of a constrained global supply of yellow fever vaccine there is an urgent need for a coordinated global response in order to end current yellow fever outbreaks. Failure to intervene decisively now may result in further large-scale urban outbreaks in at-risk areas, and a consequent inability to meet the demand for vaccine. The strategic framework set out in this document provides the basis for WHO’s continued response to the yellow fever outbreak, and for strengthened coordination and collaboration with partners to ensure that national and international response activities are supported. The Yellow Fever Emergency Committee gathered under the International Health Regulations (2005) convened by WHO on 19 May 2016 emphasized the seriousness of the national and international risks posed by urban yellow fever outbreaks and made the following recommendations: • In Angola and DRC, accelerate surveillance, mass vaccination, risk communication, community mobilization, vector control and case management measures • For travelers to and from Angola and DRC ensure travellers, especially migrant workers, are vaccinated against yellow fever • In at-risk countries and countries that share land borders with affected countries, intensify surveillance and preparedness activities, including the verification of yellow fever vaccination of travelers and risk communication • Identify and manage imported cases rapidly • Evaluate the effectiveness of the response • Rapidly expand yellow fever diagnostic and confirmatory capacity • Apply the policy of 1 lifetime dose of yellow fever vaccine7 • Undertake a rapid evaluation of dosesparing strategies through the WHO Strategic Advisory Group of Experts (SAGE) on Immunization 6. CERF Funding by Country (2016) Project Detail Angola (01/01/2016 to 24/05/2016; last accessed 24 May 2016). 7. World Health Assembly Resolution WHA 67.13.

Objectives

OBJECTIVES

STRATEGIC

1 • • •

To achieve the over-arching goal of ending yellow fever outbreaks in affected countries and limiting international spread, WHO will coordinate with partners to support countries to attain the following strategic objectives: End outbreaks in currently affected countries through vaccination and other public health measures Country context The implemention of interventions should be tailored to three country contexts (Table 2 and below). Countries with a current outbreak: Angola, Democratic Republic of the Congo (DRC), and Uganda. Countries that share a border with a country experiencing a yellow fever outbreak, and all other countries in which yellow fever is endemic Other countries at risk of importation through international travel and trade, and at risk of an outbreak due to infestation by Aedes spp. mosquitoes Current yellow fever outbreak Endemic or adjacent to At risk of importation and outbrealk Aedes spp present

Prevent morbidity and reduce mortality through early case detection and strengthened case management

Prevent international spread

Prioritize research to improve access to yellow fever vaccine, and to improve the effectiveness of other prevention and control interventions

Table 2 | Recommended yellow fever response interventions by country context Surveillance and risk assessment Assess the risk of the spread or start of an outbreak* Prepare for the importation of (more) cases from another area or country Ensure prompt and open information sharing in country and with the WHO and members states at risk through the IHR focal person. Strengthen case detection and reporting, including laboratory diagnostic capabilities Monitor the course of the epidemic and the outcome of interventions Vaccination Undertake reactive mass vaccination in areas where it is still likely to have an impact on the course of the outbreak, primarily in urban settings† Consider halting yellow fever vaccination provided through the expanded program of immunization, in order to prioritize the use of available vaccine for mass vaccination Case management Prevent excess mortality among suspected and confirmed cases

Social mobilization and risk communication Community engagement and social mobilization Risk communication Vector control Intensify vector surveillance and control

strategy

STRATEGY Achieving the strategic objectives will require coordinated implementation of a broad range of interventions, grouped here into: surveillance and risk assessment; vaccination; case management; social mobilization and risk communication; and vector control. Coordination with member states and partners remains essential to enable the implementation of all response activities. WHO will continue to monitor trends in affected and unaffected countries, and will adapt the strategic response framework on the basis of changing needs. WHO will support the implementation of preparedness activities in priority and at-risk countries at national and sub-national levels, and will support the assessment of surveillance and response capacity. Surveillance and risk assessment Effective yellow fever surveillance8 is critical to ensure that new cases and newly affected areas are identified quickly and that all data are transmitted to decision makers in a timely manner, which in turn enables the rapid implementation of response measures to contain outbreaks. Access to yellow fever vaccine from the ICG stockpile depends on laboratory confirmation of a case according to the standard case definition. Integrated arboviruses surveillance (epidemiological and laboratory) is a must where several mosquitoborne diseases are being transmitted especially when clinical presentation at the start is none-specific. Robust systems for transmission and managment of data, including links between case investigation information and laboratory results are required. Approximately 25 laboratories are able to test for Yellow Fever in Africa. In addition, there are two (2) international reference laboratories for Yellow Fever: the Pasteur Institute Dakar, Senegal, and the Arbovirus Branch at the Centers for Disease Control in Fort Collins, USA. WHO will coordinate technical support to countries through the Global Outbreak Alert and Response Network (GOARN) and WHO collaborating laboratories to strengthen national surveillance capacity, and harness support from the Inter Agency Standing Committee Cluster System as required. Areas of support will include technical support for surveillance, case investigation and risk assessment; provision of reagents, personnel, and equipment; sample transport logistics; and the deployment of mobile laboratories where needed to expedite laboratory testing. Additionally, coordination structures will be established and strengthened to support national government efforts at national and subnational levels in areas with ongoing outbreaks. Panel 1 | Yellow fever case definition A suspected case is confirmed when, in the absence of recent yellow fever vaccination, yellow-fever-specific IgM is found in the serum, or when a fourfold or greater rise in IgG levels is found in PAIRED acute AND convalescent sera, or when yellow fever virus is isolated in cell culture or laboratory animals, or in case of positive postmortem liver histopathology, or when yellow fever antigens are detected in tissues by immunohistochemistry, or when yellow fever virus genomic sequences are detected in blood or organs by molecular diagnostic techniques such as Reverse Transcription Polymerase Chain Reaction (RTPCR).

RESPONSE

Preparedness strengthening activities, including risk assessments for spread, will target priority countries at risk of yellow fever importation from countries with ongoing outbreaks. As of end of May 2016, the countries at risk of cross-border importation from epidemic countries, either through mosquitoe infestation or human travel and trade are: • • • Neighbouring Angola : western Zambia, northern Botswana, and northern Namibia Neighbouring Congo: Gabon Neighbouring affected areas in DRC: the south of the Republic of Congo

8. WHO-recommended surveillance standard of yellow fever: http://www. who.int/immunization/ monitoring_surveillance/ burden/vpd/surveillance_ type/passive/ YF_standards/en/ (last accessed 24 May 2016).

strategy • 9. WHO Yellow fever vaccine safety: http:// www.who.int/ith/ vaccines/yf/en/ (last access 24 May 2016).

Neighbouring affected areas in Uganda: eastern DRC, northern Rwanda, and northern Tanzania (through boat travel across lake Victoria)

•

Risk assessments for yellow fever outbreaks must be carried out regularly and be based on the findings of case and outbreak investigation and of entomological investigations. Recommendations should account for local surveillance and response capacity, and set prioritise interventions and resource allocation on the basis of national and local context. In countries experiencing an outbreak • Yellow fever case-based surveillance should be implemented and/or strengthened. Synergy with the existing polio surveillance network should be sought where appropriate. Case-based investigation aims to establish vaccination status, differentiate between local transmission (autochthonous transmission) and imported cases, and document travel history and information regarding location of exposure. • As per the requirements of the IHR (2005), affected countries should monitor yellow fever vaccination status of travelers through entry points. • Reporting of yellow fever cases and the geographical extent of the outbreak should be done in accordance with the requirements of the IHR 2005. • WHO and partners will support: ◊ Dissemination and use of the standard case definition. ◊ Case-based surveillance. ◊ Strengthening of national or regional reference laboratories to improve capacity for diagnostic testing and reporting, and the shipment of specimens for validation and quality control. ◊ Strengthen laboratory capacity in countries where they are limited ◊ Support implementation of intercountry cooperation mechanisms for crossborder surveillance and outbreak investigation. In countries that share a border with a country experiencing a yellow fever outbreak, and all other countries where yellow fever is endemic • WHO and partners will support countries to heighten their surveillance for yellow fever, especially in areas that border countries experiencing an outbreak. Case investigations should seek to distinguish between imported cases and cases of local transmission, and should facilitate rapid risk assessment to determine the risk and possible extent of

•

further spread. WHO and partners will support countries to establish and strengthen surveillance and reporting procedures at major entry points where requested including airports and ports. As per the requirements of the IHR (2005), countries should monitor yellow fever vaccination status of travelers through entry points.

In other countries at risk of importation through international travel and trade, and at risk of an outbreak due to infestation by Aedes spp. mosquitoes Ad-hoc surveillance measures should be strengthened, especially in countries that have regular flight, road and boat connections with countries and cities affected by outbreaks. Entry screening of yellow fever vaccination status may be implemented at entry points for travelers coming from affected countries.

Vaccination Vaccination is the most important measure for preventing yellow fever. The vaccine is safe, affordable, and provides effective immunity within 10 days for more than 90% of people vaccinated and within 30 days for 99% of people vaccinated. A single dose confers sustained immunity and life-long protection. Side-effects are rare and serious adverse events are rarely reported.9 The International Certificate of Vaccination is valid 10 days after vaccination. In a non-epidemic situation all individuals above 9 months are eligible to be vaccinated with the exception of women who are pregnant and/or breastfeeding, individuals who are severely allergic to egg or another vaccine component, and immunocompromised individuals. In an epidemic situation eligibility for vaccination is extended to infants aged 6 months and above and to women who are pregnant and/or breastfeeding. WHO and its partners in the ICG for Vaccine Provision have activated the ICG mechanism for release of yellow fever vaccine from the emergency stockpile. Despite the reallocation of vaccine from the Expanded Programme on Immunization (EPI) to the global stockpile, stocks are insufficient to respond to several simultaneous urban outbreaks. Vaccine producers have been requested to accelerate vaccine production, and WHO will continue to work with partners to: • • • prioritize the release of vaccine according to risk validate and adopt dose-sparing strategies to increase vaccine availability carry out other research and development related to vaccines

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strategy WHO is developing a strategy on how best to prioritise the use of vaccines in the event of simultaneous urban outbreaks and a depletion of global stocks. Meanwhile, national strategies for vaccination may include either reactive mass vaccination campaigns, preventive mass campaign based on risk assessment (e.g. in high-risk areas located near the affected countries), or targeted vaccination of travelers, depending on the country’s risk of an outbreak. In the event that vaccine stocks approach exhaustion, routine vaccination activities against yellow fever as part of the expended program of immunization (EPI) may have to be deferred. In countries experiencing an outbreak • WHO is collaborating with partners to support affected countries to rapidly implement reactive mass vaccination campaigns in combination with other response and prevention measures. In addition to reactive vaccination, WHO will prioritise unaffected, high-risk areas for the implementation of pre-emptive vaccination campaigns to mitigate spread within the affected countries and across borders. Priority will be given to high-risk border areas and other non-border areas that are at high risk due to high levels of economic migration and trade activity. WHO will engage in discussions with ICG and other partners to rationalise the use of limited vaccine stocks and mobilise additional logistical capacity. WHO and UNICEF may recommend a temporary suspension of national routine childhood yellow fever immunization programs in order to prioritize vaccines for reactive mass vaccination campaigns In case of multiple large outbreaks priority will be given to the control of urban and peri-urban outbreaks. Vaccination cards must be distributed to vaccinated individuals to facilitate surveys of vaccination coverage, and to enable the individuals concerned to travel internationally. Yellow Fever vaccination activity should include surveillance for adverse effect and adverse events following immunization (AEFI) against yellow fever should be implemented according to WHO guidance.10 Strict border control measures must include checking of yellow fever vaccination cards for all outgoing and in-coming travelers. Dose-sparing strategies may be considered in the context of limited vaccine availability. In countries that share a border with a country experiencing a yellow fever outbreak, and in all other countries where yellow fever is endemic • • Countries should enforce the vaccination of travelers. WHO will work with countries to map areas at highest risk of importation, and prioritise areas for pre-emptive vaccination to mitigate this risk. In the context of limited availability of vaccines where the yellow fever immunization coverage is below 80%, preventive vaccination11 may have to be postponed until the global vaccine stock is adequately replenished, unless the assessed outbreak risk is estimated to be high. Micro plans for emergency mass vaccination should address the logistical organization of the campaign, crowd control, safe waste disposal, resources mobilization, social mobilization/risk communication, daily monitoring of outcome of the campaign and monitoring of Adverse Events Following Immunization (AEFI). WHO will support the implementation of preparedness activities at national and sub-national levels, and the assessment of surveillance and response capacity. National/regional checks must monitor vaccine availability, injection/safety material availability, the availability of vaccination cards, the capacity of active and passive cold chain, and report findings to the yellow fever partnership. Strict border control measures must be implemented to verify the yellow fever vaccination status of all passengers who have travelled to countries with a yellow fever outbreak in the past 2 weeks.12

10. WHO. Surveillance of adverse events following immunization against yellow fever. Field Guinde for staff at the central, intermediate and peripheral level. January 2010: http://www. who.int/csr/resources/ publications/HSE_GAR_ ERI_2010_1ENw.pdf. 11. WHO. Yellow fever Fact sheet: http://www. who.int/mediacentre/ factsheets/fs100/en/ (last accessed 24 May 2016). 12. US Centers for Disease Control and Prevention: http:// wwwnc.cdc.gov/travel/ yellowbook/2016/ infectious-diseasesrelated-to-travel/yellowfever (last accessed 24 May 2016). 13. WHO. Yellow fever risk mapping and recommended vaccination for travellers : http://www.who.int/ ith/yellow-fever-riskmapping/risk_mapping/ en/ (last access 24 May 2016).

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In other countries at risk of importation through international travel and trade, and at risk of an outbreak due to infestation by Aedes spp. Mosquitoes • Countries that implement yellow fever vaccination as part of the routine EPI program and receive vaccine through UNICEF, will receive staggered shipments to prevent the exhaustion of national vaccine stocks. Countries will receive shipments one month prior to depletion of vaccine stocks. Such shipments will include enough supply to cover 2 months of use. All countries are at risk of importation through international travel and trade. Therefore, travelers planning to visit yellow fever endemic and epidemic countries or returning from affected countries, should be vaccinated at least ten (10) days before

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strategy

14. WHO. Recommended insecticides for space spraying against mosquitoes: http:// www.who.int/whopes/ Space_Spray_products_ February_2016.pdf (last accessed 23 May 2016.) 15. WHOPESrecommended compounds and formulation for control of mosquito larvae: http://www.who.int/ whopes/Mosquito_ larvicides_Feb_2016.pdf (Last accessed 23 May 2016.) 16. WHO. Clinical management of patients with viral haemorrhagic fever. A pocket guide for the front-line health worker. http://www. who.int/csr/resources/ publications/clinicalmanagement-patients/ en/ (last accessed 24 May 2016.) 17. Heymann. D.L. Control of Communicable diseases Manual. 20th Edition.

to travel to the affected country or at least ten (10) days prior to return to a non-affected country.13 Dose-sparing strategy Dose-sparing, also known as fractional dosing, is under consideration as a short-term measure, in the context of a potential vaccine shortage for use in emergencies. WHO Strategic Advisory Group of Experts (SAGE) on Immunization reviewed existing evidence that demonstrates that using a fifth of a standard vaccine dose would still provide protection against the disease for at least 12 months and possibly much longer. More research is needed to find out whether fractional doses would be effective in young children, who may have a weaker immune response to yellow fever vaccine. Practical issues on administering the reduced doses need further investigation, including obtaining the necessary supply of suitable syringes.

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Clinical management Symptoms of yellow fever are non-specific and resemble other tropical febrile diseases, making diagnosis in the absence of laboratory testing challenging at all phases of the disease. Around 15% of cases suffer relapse after an initial phase. The case-fatality rate in severe cases can reach 50%. There is no specific cure for yellow fever. Case management is based on supportive care and provision of insecticide-impregnated mosquito nets, including for daytime use, to prevent transmission to other patients via infected mosquitoes at the site of treatment. Symptom relief can include therapies to control fever and pain (paracetamol), but non-steroidal antiinflammatory agents such as salicylates (aspirin) should not be used to limit the risk of bleeding in severely affected patients. Treatment of patients with severe yellow fever disease is resource intensive, requiring additional medical supplies and trained medical staff. Further recommendations for the management of patients suffering bleeding signs can be found in WHO guidance for the clinical management of patients with haemorrhagic fever16 and more general guidance for clinical management of yellow fever patients are included in reference communicable disease manuals.17 The WHO-coordinated Emerging Diseases Clinical Assessment and Response Network (EDCARN) has been mobilised, and will provide technical support, training and mentoring of the health workers involved in the yellow fever response. In countries experiencing an outbreak

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12 18. IASC. Removing user fees for primary health care services during humanitarian crises. http:// www.who.int/hac/ global_health_cluster/ about/policy_strategy/ EN_final_position_ paper_on_user_fees. pdf (last accessed 24 March 2010).

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Patients with suspected yellow fever with progressive or severe symptoms should be hospitalized and receive good supportive care. Presumptive treatment should be guided by local disease epidemiology (e.g. malaria) to eliminate other common causes of similar symptoms, and laboratory diagnosis should be prioritized. Care/supportive treatments for patients with suspected and confirmed yellow fever should be made available free of charge.18 Trained health workers at all levels should be provided with the case definition to detect cases early, provide initial supportive care, and to refer to appropriate follow up. The disease-management strategy should assess the presence of co-infections with other similar debilitating conditions that may include malaria or other arboviruses such as dengue. Where needed malaria and dengue rapiddetection tests should be made available to support differential diagnosis. Although isolation of patients infected with yellow fever is not part of usual recommendations (no human-to-human transmission has been described), case management can be optimized through the creation of designated specialized health units. Insecticide-impregnated mosquito nets should be provided in clinical settings and for people who rest during the day (pregnant women, infants, sick or bedridden individuals), especially in countries neighboring those currently experiencing yellow fever outbreaks. Malaria and dengue rapid detection tests should be made available to support differential diagnosis. WHO and partners will support the dissemination of emergency guidance for clinical management, supply needs, train staff and support case management activities in reference health facilities, as well as the organization of referral and contra-referral strategies. Where requested, WHO will assist in securing additional international clinical management capacity.

In countries that share a border with a country experiencing a yellow fever outbreak, and in all other countries where yellow fever is endemic • • Clinical management standards should be reiterated to all health practitioners. Care/supportive treatments for patients with suspected and confirmed yellow fever should be made available free of charge. Insecticide-impregnated mosquito nets should be provided in clinical settings and for people

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strategy

who rest during the day (pregnant women, infants, sick or bedridden individuals), especially in countries neighboring those currently experiencing epidemics. Malaria and dengue rapid detection tests should be made available to support differential diagnosis. All other countries • All countries may be at risk of importation through international travel and trade. Those with infestation by Aedes spp. mosquitoes are further at risk of local transmission. Therefore all countries should be ready to detect cases of yellow fever and to transfer patients with suspected yellow fever (either from country entry point or from health facility of first admission) to pre-identified infectious disease health units competent to manage yellow fever cases. The WHO yellow fever vaccination recommendations for travelers should be enforced, and travelers returning from countries affected by yellow fever informed to report to the health authorities in case of a febrile event with suspected signs within a week from return, especially if the patient had not been vaccination against yellow fever prior to travel to or through an affected country or area.

Practice (KAP) surveys should be implemented to support work to understand barriers to applying interventions, especially prior to mass vaccination campaigns, but should not delay intervention. WHO, UNICEF and key operational partners should coordinate their messages and, wherever possible, activities for greater effect and consistency. Evidence-based risk communication can build confidence and trust in yellow fever vaccination and the health system in case any accident or adverse event occurs during mass vaccination. Depending on the country context, messages may address various issues, from disease presentation to the vaccination to travelers. In countries experiencing an outbreak • If they do not exist, health authorities should set up mechanisms to communicate risk and mobilise society, and continuoually assess the effectiveness of community engagement strategies, focusing on analysing public concerns and knowledge gaps with regards to the ongoing outbreak, and on sound monitoring of both implementation and results. Micro-plans should integrate risk communication and social mobilisation activities at local level. Activities should target groups most affected and most at risk. The approaches for different contexts (urban, peri-urban, and rural) will differ due to population density, infrastructure, work and daily routines, and access to services, communications and media. This should be documented and incorporated into microplanning and wider coordination Communication materials should be adapted to local cultural perceptions and languages, and community health workers, mobilisers, volunteers and health workers should be trained on key messages and, if needed, on interpersonal communication skills. Supervision of and reporting by actors engaged in risk communication activities should be ensured. Partners should facilitate the development and implementation of community-led action plans and community monitoring mechanisms, in priority areas at a minimum, and not limited to the period of the vaccination campaign. Vector-control communication should engage communities, families and individuals through health education and social mobilization informed by KAP assessment to tailor strategies and messages. Vaccine and vaccination campaigns messages should be based whenever possible on the results of KAP surveys, focus group discussions, and rumor monitoring to identify and address vaccine hesitancy. Key stakeholders include

•

Social mobilization and risk communication Populations need and have a right to information about yellow fever (including symptoms, mode of transmission, need for vaccination, possible adverse effect following immunization, the need to seek medical care early, and other personal and environmental protective strategies) adapted to local contexts, providing realistic recommendations, and translated into local languages. Access to essential care, supplies, and advice should be ensured. It is essemtial to engage community influencers, and to implement mechanisms to identify and address misinformation and rumors. Community mobilisation approaches for engagement in surveillance and vector control should be adopted, and efforts made to sustain the effects beyond the period of the vaccination campaign especially in the border areas. Risk-communication strategies should be based on an analysis of socio-cultural barriers to adopting interventions (e.g. vaccine hesitancy or refusal, vector control, seeking medical care) and on consultations with the communities. They should segment audiences, clearly define results and activities for each of them, and set the monitoring and evaluation framework, process and tools. Preferably, operational research utilizing rapid qualitative and Knowledge, Attitude and

•

• •

•

strategy

communities, families and individuals, influential individuals, community leaders, community based organizations (CBOs), religious groups, civil society organizations (CSOs) and professional groups, services providers and local authorities. In countries that share a border with a country experiencing a yellow fever outbreak, and in all other countries where yellow fever is endemic • Preparedness plans and materials used for social mobilization should be reviewed urgently, especially in countries neighbouring those experiencing an outbreak. • Information should be made available to communities at each entry point in the country in local language(s), and should address clinical presentation, health seeking behavior, and the need for travellers to be vaccinated. All other countries • Authorities should assess the pertinence of developing contingency plans and ensure that information is made available at main entry points at a minimum. Travelers to affected countries should be made aware of the compulsory requirement for vaccination at least 10 days prior to departure. Travelers returning from affected countries should be informed of how to recognize signs and symptoms, the importance of case notification and how to seek treatment in case of suspected infection.

Countries can be categorized on the basis of their entomological situation as follows: A: Ongoing yellow fever outbreak AND Aedes present AND intense yellow fever transmission in humans B: Neighbouring a country with an ongoing outbreak AND Aedes present AND limited yellow fever transmission in humans (a small number of imported or autochthonous cases reported) C: Other country AND Aedes present NO YF human transmission Different targeted interventions are recommended depending on which category a country falls in (table 2), but in all countries, community mobilization should start to eliminate/cover urban and peri-urban standing water mosquito breeding sites around homesteads. Countries in categories A and B • Vector-control measures should come as a package, addressing the control of adult mosquitoes and larvae, the removal of eggs, and the prevention of mosquito bites through personal protection. Personal protection methods are advised for patients who are being treated for yellow fever and for members of affected communities. Targeted residual spraying is the primary vector-control intervention for immediate response. During outbreaks of vector borne diseases authorities should implement space spraying to kill adult vectors so as to reduce virus transmission. An appropriate WHOPES-recommended insecticide should be selected.14,15 Control measures to target breeding sites should be immediately intensified, especially when an outbreak occurs in urban areas. These control measures must be complemented with long-term monitoring of mosquito population density.

•

Vector control The yellow fever virus is transmitted to humans by Aedes species mosquitoes that also spread dengue, Chikungunya and Zika viruses. The implementaion of vector control measures and the prioritization of interventions in the case of a yellow fever outbreak should follow the guidance set out in the WHO guidance document Vector control operations framework for Zika, which will be published shortly. Well-implemented vector control can effectively reduce the transmission of vectorborne diseases if significant resources are available and communities fully engaged. Vector control is a cross sectoral approach requiring the investment and coordination of several ministries (e.g. health, sanitation and environment, education). WHO and partners will support efforts to intensify existing national Aedes mosquitoe vector surveillance and control programs, especially for Aedes spp., and improve access to larvicides and monitor insecticide resistance in countries with an ongoing outbreak.

•

Countries in category C • WHO and partners will support governments to play a direct and pre-emptive role in implementing vector surveillance and vector control at the scale needed to prevent transmission. To be most effective, action must be taken before human cases of yellow fever occur.

Vector-control activities should be guided by an assessment of population immunity, vaccination coverage, mosquito density, and access to care and to control measures.

strategy

Table 3 | Recommended yellow fever response interventions by country classification

Vector surveillance and risk assessment Intensification of entomological surveillance, assessing the density of Aedes mosquitoes around residences of detected cases (400 m radius), yellow fever patient treatment sites, and in areas where there is known to be a high risk of mosquito proliferation Intensification of entomological surveillance, assessing the density of Aedes mosquitoes around residences of detected cases, yellow fever patient treatment sites, and in areas where there is known to be a high risk of mosquito proliferation Monitoring of ports of entry Monitoring of insecticide resistance of Aedes mosquitoes where insecticide-based interventions are being used or planned Monitoring and evaluation of the quality and impact of control measures

Vector control Adaptation of vector control strategies to the intensity of virus transmission and to the timing of the mosquito breeding season, including source reduction Provision of insecticide-impregnated mosquito nets as part of the management of suspected yellow fever cases, and where needed, to affected communities Distribution and appropriate use of mosquito repellents

Implementation of vector control measures integrated with surveillance

Conduct adult vector control, including indoor space spraying in identified hot spots

Application of larvicides in targeted areas not amenable to source reduction

Specific social mobilization interventions Community mobilization with source reduction

Risk communication and promotion of personal protection *Few imported or autochthonous cases reported.

E in pid hu ten em m se ic an y A N s ell D ow A fe ede N ve s e pr ig r t pr h e tr s b ra es an en o ns en sm t uri m tA A n is ND g is N si si D on li epi on m d o e in ite m O f y e d ic no the l h A l ow u N hu r c m ou fe ma D A an nt ve n e r de r* y tr s an A N sm D A is e si de on s of pr ye ese llo n w tA fe ND ve r

coordination

COORDINATION An effective response depends on effective national and international coordination. WHO will continue to keep member states informed through IHR focal points and in its public communications, and to mobilize technical experts through the Global Outbreak Alert and Response Network (GOARN). WHO will also support the mobilization of other resources (financial, logistical or other), in addition to the resources being provided bi-laterally by other partners or through a health sector/cluster coordination mechanism. In countries experiencing an outbreak • WHO and partners will support national and local health authorities to continue leading the coordination of all stakeholders. The national coordination mechanism should include an appropriate structure and management, and a framework for the collection of information, decision making, and for action implementation. Leadership should also design and implement a framework for response monitoring so as to adapte interventions to the evolving situation Intersectoral collaboration at governmental level is recommended to help mobilize national and local ministries involved in health, environmental health, and in education, social development and tourism sectors, communication sectors, and entry points (ports, airports, ground entry points). Public practitioners and community health workers, private practitioners and traditional healers must all be engaged in response and prevention activities. In parallel, local, national, and international partners, non-governmental organizations (NGOs), the donor community, community leaders and private entities should be encouraged to engage in response and prevention interventions. Domain-specific working groups within the wider national and subnational coordination mechanisms (e.g. a risk communication and social mobilization sub-group) should be established. Cross-border coordination with surrounding countries at risk should be established WHO and partners should be ready to mobilize self-sufficient multidisciplinary and readyto-operate teams (epidemiologists; public and media communication officers; social mobilization and community engagement officers; logistician, laboratories, case management vector control, administration staffs) for large-scale assistance. In countries that share a border with a country experiencing a yellow fever outbreak, and in all other countries where yellow fever is endemic • National and sub-national coordination capacity across all response pillars should be reviewed as soon as possible. Health authorities should be familiar with the ICG procedures and criteria for the deployment of vaccines from the global emergency stockpile and the related ICG vaccine request forms. A coordination structure or disease taskforce should be created to coordinate and/or conduct risk assessments, prepare and plan on the basis of those assessments, and convene partners to assess needs and mobilise resources. Health authorities should be familiar with the response capacity of the main external health actors present in country (e.g. NGOs, donors, presence or not of the Cluster system of the Inter-Agency Standing committee, and UN agencies), and have defined how the response to an outbreak would be coordinated (who is doing what, lines of reporting, roles and responsibilities.

RESPONSE

•

16 •

•

All other countries • National and local health authorities should review coordination mechanisms, and assess the risk of an outbreak in case of a yellow fever importation.

• •

Monitoring

Table 4| Global yellow fever response monitoring indicators (priority indicators in bold) Domain Activity Availability of vaccines for urban outbreaks Vaccination Monitoring of adverse event following immunization (AEFI) with yellow fever vaccine % of mass vaccination campaigns where active and passive daily AEFI monitoring is being carried out 100% National reports to the ICG, reports from responsible entity/agency

MONITORING Indicator

RESPONSE

Target

Information source

% of request of vaccine supply complying with ICG criteria responded to within 1 week

100%

ICG activity report

Weekly number of new countries reporting yellow fever cases

Surveillance reports

Weekly number of new epidemic countries

Surveillance reports

Weekly number of new provinces reporting yellow fever cases in affected* countries Global level surveillance Weekly number of suspected and confirmed cases reported by country, and in total

Surveillance reports

Weekly number of suspected and confirmed deaths reported by country, and in total

Surveillance reports

Human-disease surveillance Specimen shipment and processing

Weekly number of confirmed cases by status, imported versus autochthonous, by country and in total

Surveillance reports

% of international requests for laboratory support (equipment, reagent, mobile laboratory) from epidemic countries that where effectively supported within 2 weeks from request

100%

Situation reports

% of affected countries complying with the IHR obligations for notification†

100%

IHR reports

% of countries carrying out entry screening for yellow fever vaccination proof, on main entry points, on travelers coming from epidemic countries Health Security and International Health Regulation Weekly number travelers reported not carrying a valid yellow fever vaccination card while entering country, per epidemic country, and in total

100%

Situation reports

Weekly number of travelers vaccinated upon entry to country, per epidemic country, and in total

Situation reports

Vector control

Vector surveillance

Weekly number of new priority areas identified for vector control per country†

Surveillance, situation and other reports

Case identification

% of affected* countries having disseminated an appropriate case definition

100%

Assessment

Case management Case management

Weekly number of newly admitted YF cases in epidemic countries

Country specific

Specific monitoring

Weekly number of specialized bed in YF ad-hoc facilities per province in epidemic countries

Country specific

Specific monitoring

% of countries with updated risk communication/social mobilization strategies/plans Risk communication and social mobilization

100%

Situation and other reports

Risk communication and social mobilization

% of epidemic countries and neighboring countries where risk communication and community engagement plans and material in local languages are available

100%

Situation and other reports

% of epidemic countries and neighboring countries where risk communication and community engagement material is available in appropriate international and local languages at main official points of entry/exit

100%

Assessment

% of epidemic and neighboring countries with sub-national coordination frameworks and response plans for yellow fever outbreaks

100%

WHO situation up dates

% of epidemic countries with national coordination frameworks and response plans in affected provinces

100%

WHO situation up dates

International coordination

Number and list of partners supporting YF national response per domain (surveillance, vaccination, cases management, vector control, social mobilization, coordination) per country and globally

Country specific

4Ws, countries reports, WHO situation reports, Health sector/cluster reports

Total number of international technical experts deployed by week from GOARN partners

Country specific

GOARN reports

Total number of WHO staff by week supporting the response at sub-national, national and international levels

Country specific

WHO situation up dates

*Any country reporting yellow fever cases, including sporadic sylvatic cases. †See International Health Regulation (2015) Third edition; Part II-information and public health response; Article 6 Notification.

requirements

Rationale for response monitoring Effective response operations depend on continuous, regular and detailed surveillance and response monitoring, analysis and reporting. Surveillance and response monitoring data and analysis provide an overview of trends, and are used to adjust needs, targets and funding requirements. Response monitoring data and analysis also enable leadership to review the progress of the overall response and make adjustments where necessary. WHO is working to provide Member States with recommendations on strengthening surveillance and

reporting systems in the context of current yellow fever outbreaks. WHO also encourages and requests partners to regularly report on their response activities at the global, regional and national levels through an online portal currently in development. The overall yellow fever response strategy is being continually reassessed to respond to changing circumstances. WHO publishes a global situation report on a weekly basis through the WHO website.

REQUIREMENTS 18 WHO is currently working with all partners to consolidate needs and requirements across the response based on the strategic response framework. The budget requirements identified to date by WHO are summarized below (table 5). WHO headquarters, the WHO regional office for Africa, and the relevant country offices have a consolidated requirement of US$ 69 762 864 (table 5). For all activities conducted by WHO there is a total need of approximately US$ 59.2 million. There is a total request of approximately US$ 10.5 million for human resources. There is a total partner requirement of US$ 2.59 million (table 6) on behalf of those partners who have informed WHO of their needs so far. Most activities are taking place either in, or in support of, the African regional office and affected countries. Response activities and related human resource requirements across all levels have been aligned to the four strategic objectives of this response framework. To support the ongoing response, existing funds have been matched against some requirements for Yellow Fever activities: • US$ 3 200 000 from ICG revolving fund for procurement of YF vaccine • •

SUMMARY OF

REQUIREMENTS (US$)

72.35M

US$ 500 000 from USAID for Angola outbreak and response activities US$ 2 200 000 from Contingency Fund for Emergencies, which will need to be reimbursed to the CFE

Additionally other funding to support vaccination activities in Angola, DRC and Uganda WHO is also working on a model to examine budget estimates for epidemic preparedness in at-risk countries/locations neighbouring currently affected countries. Based on ongoing preparedness work, usual costs are between US$ 2.5 and 4 million per country for a hazard-specific preparedness and response contingency plan, and around US$ 10 million for an annual all-hazard preparedness plan (which ranges from US$ 6 to 15 million in the African region). Of the yellow fever affected and surrounding countries, only Uganda, DRC, and Tanzania currently have ongoing preparedness programmes in place.

requirements

Table 5| WHO yellow fever response resource requirements by office and strategic objective WHO office and objective Headquarters 1. End outbreaks in currently affected countries 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread 4. Prioritize research to improve access to yellow fever vaccine, and to improve the effectiveness of other prevention and control interventions WHO Regional Office for Africa 1. End outbreaks in currently affected countries 3. Prevent international spread WHO Country Office: Angola 1. End outbreaks in currently affected countries 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO Country Office: Democratic Republic of The Congo 1. End outbreaks in currently affected countries 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO Country Office: Uganda 1. End outbreaks in currently affected countries 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO Country Office: Republic of the Congo 1. End outbreaks in currently affected countries 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread Total

Total funding requirement (US$) 2 843 750 1 169 281

1 090 112

289 356 295 000 30 444 805 25 025 000 5 419 805 18 608 587 16 909 389 1 260 838 438 359 2 960 864 1 324 289 1 387 125 249 450 13 227 358 12 279 793 762 856 184 709 1 677 500 843 875 632 250 201 375 69 762 864

requirements Table 6| Yellow fever response resource requirements by partner Partner Total funding requirement (US$)

UNICEF

2 205 000

Save the Children

385 000

US CDC

TBD

ECDC

TBD

Tephinet/REDSUR

TBD

Total

2 590 000

This information will be regularly updated with new partner information. More partners will be added in due course.

[In development: to be regularly revised with partners’ inputs]

JOINT OPERATIONS PLAN

REQUIREMENTS (US$)

STRATEGIC OBJECTIVE 1 End outbreaks in currently affected countries through targeted vaccination and other public health measures 21

60M

Vaccination (reactive and pre-emptive) Mass vaccination campaigns are critical in the control of a yellow fever epidemic. The earlier a mass vaccination campaign begins, the more will cases of disease be prevented. Vaccination has been initiated in the affected countries with varying coverage ranging from 30% to 96% in Angola and Uganda respectively. However, many at risk districts and provinces require urgent vaccination to create a sufficient cordon sanitaire around areas reporting locally transmitted cases. When all high risk areas have been covered by the vaccination campaign and subject to availability of vaccines, vaccination will be expanded outward into adjacent areas, to include all areas at risk. If vaccines and resources are limited, vaccination will be targeted to the age groups with the highest attack rates i.e. ages 6 months to 45 years. Due to emerging concerns about the spread northwards through Angola to DRC, and the potential impact this may have on large urban centres, a pre-emptive vaccination campaign will be carried out during July 2016 in areas that are presently the epicentre of the epidemic or remains at greatest risk. The identification of risks, target populations and areas is being informed by current disease epidemiology, and modelling to determine risk levels: 1. A 75-100km belt spanning the border between Angola and DRC 2. Other high risk in-land areas associated with local mining areas, and big markets attracting large migrant populations and population movements to and from Angola 3. Reactive vaccination of at risk populations around confirmed cases of local transmission and a phased preemptive vaccination of the entire population of Kinshasa to mitigate further spread within and internationally. According to vaccine supply and emerging priorities it will also be assessed further whether there are communities outside the proposed 100km belt that should be factored into the pre-emptive campaign in order to prevent further spread of the disease. As areas are vaccinated the coordinated recording of coverage will be documented accurately and shared appropriately to inform ongoing planning. The unit cost of implementing such a campaign is approximately two US dollars per vaccine administered, which is inclusive of all costs, broken down into approximately one dollar for the vaccine itself and one dollar for the operational costs of vaccine delivery. As DRC is GAVI eligible, and pre-emptive vaccination campaigns are funded through this mechanism during an emergency, these costs will be covered through the existing GAVI mechanism. However, the cost per vaccine provided by GAVI is 25 cents per vaccine for operational cost, and allowing for the increased cost of delivering vaccinations in a complex urban environment such as Kinshasa, one dollar per vaccine administered will need to be raised for DRC. Angola is not covered by GAVI, but the Angolan Government has committed to funding half the vaccination costs during the current outbreak. Therefore one dollar for each vaccine administered will need to be raised for Angola. In view of this strategic re-orientation there is a need to scale up the human resources for each country and for the WHO Africa Regional Office to facilitate robust micro-planning and logistical preparation required to deliver such a vaccination programme. The human resource cost for implementing this can be found within the section relating to strategic objective three below. There are limited vaccine stocks immediately available for the pre-emptive campaign in July 2016, and therefore prioritization will be required in the micro-planning, along with synchronising the approach between DRC and Angola, and trying to achieve the vaccinations in as short a time as is realistic and as vaccine supplies with associated logistics allow.

WHO recommends the use of dose fractioning of the vaccine in order to get greater coverage from the limited stock available. Practical issues that need further consideration include sourcing of appropriate syringes, ensuring reconstituted vials are kept cool (4-8 °C) and used within 6 hours of opening, training of health workers on vaccine reconstitution/use and developing messages on the new approach to ensure community acceptance. Dose sparing would be more challenging in rural areas, and cannot be performed in children under two years old. Lastly, there are slightly different recommendations for the product of each vaccine manufacturer which need to be taken into account for any dose sparing strategy. Pre-emptive vaccination across the border of Angola and DRC In collaboration with the Imperial College of London and the University of Oxford-KEMRI Wellcome Trust Programme, the WHO and partners have used the available data on incidence, recent vaccination activities, vector distribution, past occurrence of yellow fever and population movement patterns to model the risk of spread and help identify areas 1 to target the available vaccine resources on the border of Angola and DRC . The risk is ranked from 1 to 5, and category five is the highest risk (Table 1). It is proposed to vaccinate the higher risk districts falling inside this 100km corridor, using the risk scores to prioritize which districts should be targeted first. Within this approach there are two courses of action possible. The first will be to vaccinate the entire population, while the second will be to vaccinate only the urban population within each district. Regional and country experts advise that the minimum functional unit for vaccination is the district. Due to the logistical challenges involved in rural areas, dose fractioning would not be proposed in this area. WHO would recommend using full doses of yellow fever vaccine in these settings.

Table 1 | Angola and DRC population in 100km belt Country Angola Risk Category 5 4 3 2 1 DRC 5 4 3 2 1 Total Total Population 86,000 1,769,400 749,800 164,800 675,300 1,241,500 1,173,600 818,700 3,453,100 4,692,800 14,825,000 Urban Population 39,700 817,400 199,300 30,500 196,300 721,200 495,300 494,800 2,235,000 2,546,000 7,775,500

Fig 1. | Urban population

Table 2 | Population in proposed 100km belt Total population numbers AGO Phase 1 Phase 2 Phase 3 Country-level total 2.3 1.1 0.2 3.6 DRC 2.9 3.4 2.6 8.9 Total 5.2 4.4 2.9 13.7 Urban population numbers only

AGO 1.1 0.2 0.1 1.4

DRC 1.4 2.3 1.4 5.2

Total 2.5 2.5 1.6 6.6

Jean K, Hamlet A, Garske T. Target populations for preventive vaccination in the Angola/DRC border area. Confidential Report to WHO, Imperial College. 2016.

Targeting Kinshasa Population estimates vary significantly, but the total population for the purposes of this plan is approximately 7,270,400. Attempts to reduce this number to focus only on ‘urban’ areas result in a very slightly smaller figure of 7 266 800. However, estimates vary significantly for this population, up to 12 million people, which needs to be factored into any plans, therefore an estimate of the total population targeted will be 9.7 million. WHO recommends considering dose fractioning as a way to extend a limited stock of vaccine to cover the entire city in a phased approach. This method would be more feasible in an urban setting than in a remote rural area.

Fig 3. | Cases in Kinshasa

Fig 2. | Urban area of Kinshana highlighting areas of cases of Yellow Fever

The total requirements for the pre-emptive vaccination campaign are show in Table 3.

Table 3 | Cross border belt and Kinshasa populations, and cost of vaccination Approach Cross-border belt Angola Cross-border belt DRC Kinshasa Total Population Total 3,600,000 8,900,000 9,700,000 22,200,000 Cost of vaccination $3,445,300 $11,379,700 $9,700,000 $24,525,000 Population Urban 1,400,000 5,200,000 9,700,000 16,300,000 Cost of vaccination $1,283,200 $6,492,300 $9,700,000 $17,475,500

Further to the above analysis, it is possible to stratify Kinshasa into a three phase approach as follows, based on the risk stratification conducted by Imperial College. At the time of writing the total number of vaccines in stock is approximately four million, with an expected 13 million by the end of July due to an increase in production. If a decision is made to use dose fractioning, both the cross-border belt approach and the Kinshasa approach could be done simultaneously, phasing each by priority geographies, with the suggested timing for the campaign being mid- to end-July. Implementation of a dose-fractioning strategy would require more resources and logistics in terms of appropriate syringes and cold chain, including training and close monitoring of the campaigns. Organizations will work in collaboratively with the Ministries of Health of the affected countries to link with and support existing vaccination campaigns. The human resource costs for implementing this vaccination plan are stipulated under strategic objective three below. WHO is collaborating with its international partners in the area of vaccination in the following ways: UNHCR recommends that all asylum seekers and refugees be included in national preparedness and response plans and programs including micro-planning for vaccine procurement needs. Support provided to countries by partners should include consideration of asylum seekers and refugees. This applies to countries with ongoing outbreak, surrounding countries and others. CDC is contributing to implement targeted vaccination campaigns and support program management, operations and implementation. UNDP is providing technical support to the National Directorate of Public Health in Luanda in the Ministry of Health. The objective is to support the Directorate in the preparation and implementation of the current response to the Yellow Fever Outbreak in Angola and to extend the vaccination campaign to all districts in Luanda and eventually to other provinces in the country, focusing on the coordination of the response, and strategic and operations planning. This work includes the development of estimates of needs for human resources, vaccine and injection supplies, vaccination cards, registration material and overall financial resources required, disaggregating by the conditions and needs of the 17 provinces still unvaccinated. Also included in the support are strategic gap analysis, human resource planning and deployment support, plan performance monitoring and technical advice on surveillance systems development.

Fig. 4 | Map of Kinshasa with phased approach

Risk Communication and Community Engagement When a yellow fever epidemic has been declared, there is likely to be widespread public concern and media attention. Therefore, efforts to reach communities with key messages about the outbreak have to be instituted and sustained throughout the epidemic. The strategy will support the deployment of social scientists including anthropologists to explore local beliefs about disease transmission and conduct operational research to understand barriers. Knowledge, Attitude and Practice (KAP) surveys will be conducted to measure the understanding and application of this key information. This will allow the messages to be culturally relevant, to be communicated through channels which maximize their impact and will assist in dispelling misconceptions. It will be critical for media campaigns to be conducted in multiple local languages to maximize the reach they have. Multiple channels will also be key in ensuring the reach and impact of the messaging; including national and international media, television, leaflets, social media, and the development of an Android/iOS phone application. Activities mobilizing community organizations and networks will include training community workers in inter-personal communication for yellow fever prevention, as well as dynamic and interactive community-based approaches in high risk villages. Outreach to the public will prioritize evidence based channels such as: meetings with the community, religious and political leaders, presentations at markets, health centres, schools, religious centres and house-to-house visits. Partner organizations like CDC and UNICEF are also supporting community outreach to improve the effectiveness of prevention and control interventions Together these risk communication and community engagement methods will aim to both raise general awareness, whilst also providing specific, clear information on: 1. 2. 3. 4. 5. 6. Why they should be vaccinated when and where to go for vaccination; why it is important for travellers to present a valid yellow fever vaccination card at borders and points of entry when and where to seek medical attention; how yellow fever is spread; and how to reduce mosquitoes and their breeding sites.

In any setting where dose fractioning is considered, community engagement and risk communication will be very important in order to gain health worker and community acceptance. People will need to be informed that fractional dosing does not mean partial efficacy or an inferior vaccine.

Vector Control Eliminating adult and larval mosquito populations and potential mosquito breeding sites reduces the vector that transmits yellow fever. Mosquito control efforts are most effective when the major vector is a peri-domestic mosquito such as Aedes Aegypti. In such cases, both the management of individual homes (using insecticide sprays and protecting water containers) and community-based programs can have substantial impact on the size of infected mosquito populations. Significant resource will be allocated to integrated vector control as part of this strategy, and in addition countries will be provided technical support in vector control activities, including WASH expertise. A number of entomologists will be deployed and vector control field assessments will be supported in high risk areas. Communities will also be supported to use mosquito nets, especially on the beds of ill patients. Consequently, the scale up plan below has costed the HR needs to deploy vector control experts in the provinces and the districts.

REQUIREMENTS (US$)

STRATEGIC OBJECTIVE 2 Prevent morbidity and reduce mortality through early case detection and strengthened case management 26

5.1M

Surveillance & Risk Assessment Coordinating the collection, analysis and dissemination or communication of vital information is critical in early case detection and in strengthening case management. Assessing the health risks, the needs, the response of the sector and the identified gaps will also be key in allocating resources appropriately to prevent morbidity and reduce mortality. Diagnosis and reporting of new cases will be based on standard case definitions and laboratory confirmation, and risk assessment requires comprehensive investigation of all confirmed cases informing the basis of timely vaccine allocation and the implementation of vaccination campaigns. The standard case definitions will be widely disseminated. All health facilities will be required to send daily and weekly reports on the number of cases and deaths. All districts will prepare summary reports of health facility data and submit them to the provincial level. These reports will include: the period of time covered by the report, the number of health facilities that reported (including the health facilities that reported no cases of suspected yellow fever), the total number of health facilities in the district, the total number of suspected yellow fever cases and deaths during the reporting period and the number of vaccinations planned and the number given. Such reports will be consolidated by developing and maintaining a global laboratory and enhanced epidemiological database to allow the appropriate monitoring, tracking, verification and mapping of yellow fever. Risk mapping and specific field risk assessments will also be conducted in high risk areas to guide further response planning. It will be important to strengthen surveillance at the provincial level to ensure completeness and quality of reporting. Support in case investigations, case classification and in assessment of surveillance quality at the provincial level will be prioritized to improve the early detection, reporting and referral of suspected cases through active surveillance and investigation. The strengthening of disease surveillance in the city of Kinshasa and Kongo Central Province in the Democratic Republic of Congo is seen as a priority and will be supported through: investigation of mission alerts; strengthening the capacity of laboratories; conducting active research; and through logistics training. Laboratory capacity, and capacity for specimen collection, packaging and shipment for confirmation are important components of surveillance and risk assessment. The laboratory capacity should also include the ability to rule out or determine co-infections, including differential diagnosis for negative cases meeting suspect case definition for Yellow Fever. For maximizing testing capacity, the option of deploying mobile laboratories is also being explored. WHO will coordinate updates on epidemiology and on laboratory results and will conduct modelling on yellow fever risk and a global risk assessment. In terms of partner support, the Centre for Disease Control will strengthen case management capacity through data collection and analysis. They will help expedite surveillance, reporting and case investigation and develop in-country lab services to encourage early case detection.

Case Management Although there is no specific curative therapy for yellow fever, such as antiviral drugs, adequate supportive care is imperative. This strategy and scale up plan will ensure the wide dissemination of simplified case management emergency guidance for yellow fever, as well as retraining of health workers in clinical case management to cover early recognition, management, and referral of severe cases. Support will be provided for case management, including required logistical support and in the clinical management of suspected, probable and confirmed cases. Laboratory facilities will be strengthened to support clinical management including PCR, IgM and test evaluation services.

REQUIREMENTS (US$)

STRATEGIC OBJECTIVE 3 Prevent international spread 27

6.9M

Coordination and Leadership The WHO at all three levels (HQ, Regional Office and Country Offices) shall support the objectives through:     providing technical guidance to countries to conduct rapid assessments, prepare plans, mobilize financial and other resources, and provide advice on implementation; establishing regional mechanisms for international/cross national actions; establishing a regional dashboard system with member states to monitor the implementation and progress with these strategies; and partner coordination to ensure synergy of the response actions through strategic planning.

In order to ensure that the epidemic is rapidly controlled, the WHO will specifically:     strengthen leadership and coordination frameworks using the Incident management system (IMS) at all levels of the organization and in synchrony with national coordination structures at country level; coordinate, mobilize and deploy staff with appropriate expertise from member states, in collaboration with regional and international partners; The GOARN network, and other partners will be mobilized as necessary; deploy specialized staff and resources in the affected districts; and establish standard operating procedures (SOPs) for response actions.

Advocacy is needed for the response at all levels from the global to the local, requiring strong political engagement. Advocacy for adequate domestic financial resources needs to be pursued to contribute for the operational costs. Response teams will be placed in all the provinces and districts for better support to the local authorities. In Kinshasa and at the field level in DRC, WHO will organize coordination meetings and will ensure the coverage of needs and identification of gaps are filled by partners in the health sector. For the purposes of coordination and leadership to the response, the Incident Management System in Angola, DRC, Uganda and AFRO will be strengthened to fulfil the required functions and expectations. The support to these structures will continue to be drawn from a variety of sources, with tight coordination needed between all three levels of the Incident Management System (led by AFRO) to identify gaps in the recruitment to each IMS, especially in light of the pre-emptive vaccination campaign and required micro-planning.

Table 4 | Incident management structure augmentation requirements in AFRO, Angola and DRC IMS AFRO Position Planning and resource forecasting Case management Logistic Epi SHOC Vector control Requirement 1 senior person 2 additional experts for evaluation, strategy planning and training 2 logisticians 2 senior rapid response epidemiologists 1 expert 1 expert 1 logistician and 1 support person to monitor and facilitate movement of samples across the country, supplies of sampling materials, provide timely feedback to districts and health facilities. 1 data analyst, for support in analysis 1 senior person (could be manager or logistician) to coordinate the scale up process 2 senior rapid response epidemiologists for country support 1 additional logistician for support of coordination of vaccination campaigns 1 additional expert to support coordination of activities at Luanda level 2 additional experts for evaluation, strategy planning and training at Luanda 1 data analyst, for support in analysis 2 senior rapid response epidemiologists for country support 1 expert 1 senior person (could be manager or logistician) to coordinate the scale up process 2 additional experts for evaluation, strategy planning and training 2 logisticians 2 senior rapid response epidemiologists for country support 1 expert

Angola Laboratory support

Data management Planning and resource forecasting Epidemiology Vaccination Social mobilization Case management DRC Data management Epidemiology Field coordination Planning and resource forecasting Case management Logistic Epidemiology Vector control

WHO will work with neighbouring countries (Congo, Namibia and Zambia) to conduct preparedness assessments and to develop preparedness plans and establish minimum preparedness capabilities in readiness for a yellow fever introduction and/or outbreak. A checklist package will be prepared to support countries with preparedness activities. Through preparedness missions to 10 countries including all neighbouring countries over 3-6 month period key preparedness actions shall include the following:       assessing risks, mapping in-country capacities and development of preparedness plans establishing emergency operation centres and strengthening coordination capacity in each country; establishing, training and operationalizing Rapid Response Teams (RRTs); embedding the community engagement and public awareness components of Yellow fever strategies in country preparedness and response plans; reinforce each country’s national epidemiological surveillance capacity; and help to build core capacities for the International Health Regulations (IHR) and Integrated Disease Surveillance and Response (IDSR).

WHO is also working with partners to engender maximum coordination and representation on various operational capacities. UNHCR advocates for ensuring that asylum seekers and refugees are included in national coordination framework and preparedness and response plans. UNDP, resources permitting, in the event of epidemic escalation, could deploy personnel and assets of the Global Fund support programme which focus on fiduciary management, supply chains maintenance, commodities and supply procurement, operations data management and strategic response planning, implementation and monitoring .

Scale up of human resources The WHO and partners will mobilize US $ 4 million for the planned scale up of HR deployments for Yellow Fever surge capacity to Angola and DRC for a period of 60 days. The cost includes per diem, transport for the experts and catalytic operational costs. This requirement will need to be constantly updated and refined in view of the evolving epidemiological data, and how that affects the proposed plan for pre-emptive vaccination.

Table 5 | Scale up plan Angola Field Coordinators Epidemiologists Entomologists Social Mobilization experts Logisticians Risk Communications Vaccination coordinators Vaccination experts Data Managers Total 18 19 6 18 18 2 5 21 18 121 DRC 3 3 3 3 3 1 10 3 3 22 1 1 9 25 22 152 AFRO/WCO AFRO/GOARN Congo 1 2 1 1 1 1 Total 22 24 11 22 22 4 AFRO/WCO AFRO/WCO/GOARN /consultants AFR/GOARN /Consultants AFR/GOARN /consultants AFR/GOARN /Consultants AFRO/HQ/GOARN

REQUIREMENTS (US$)

STRATEGIC OBJECTIVE 4 Prioritize research to improve access to yellow fever vaccine, and to improve the effectiveness of other prevention and control interventions

0.3M Operational Review

A joint technical and operational process review of the yellow fever response in Angola and the DR Congo will commence shortly. This rapid review is in accordance with the recommendations of the IHR yellow fever Emergency Committee. It will include an analysis of the current epidemiology, risk assessment, and will generate recommendations for amending the yellow fever outbreak response to prevent further international spread. In each country, review teams will work with the partners and national counterparts to: 1. Review current status of the disease epidemiology and provide risk assessment for further spread within the country and internationally, including a mapping of priority areas requiring urgent attention; 2. Review the current status of the operational response, to identify gaps and provide recommendations for a scaled up response as well improved operational excellence focusing on early recognition of cases, effective case investigation and risk assessment, case based reporting, vector surveillance and control, planning for and implementation of vaccination campaigns, improved case management, social mobilization and risk communication, cross border interventions to mitigate international spread, and logistic capabilities in support of the response; 3. Review and assess the status of implementation of the YF EC recommendations and recommend solutions; 4. Review the operational organization of the WHO response framework, organizational structure and operations in view of the planned scaled up operations and work with the Country level IMS and WR to recommend feasible solutions to strengthen the WCO IMS in support of the planned scaled up operations; 5. Review the national coordination framework at national and provincial level, including framework for partnerships and provide recommendations to the national government for a scaled up operations to contain the outbreak; and 6. Advocate for and provide evidence based technical and operational guidance for improved and scaled up operations to the MOH, the WHO and partners in respective countries. It is expected that the output of this review will be a report detailing findings and recommendations for: 1. A scaled up operational response and operational excellence at national and sub-national level with a primary focus on the following areas:  Current epidemiology, risks status and priority areas requiring special attention  Gaps and needs in the Incident command / management function, including the HR needs for response operations  Gaps and needs in operational implementation of technical functions  Capacity for planning and forecasting needs  logistics and logistic support  Information Management and sharing  Administration and finance function  Existing partnerships and areas for strengthening 2. Outline of proposed priority interventions for the immediate (first one month), medium (second month), and for the long term (3 months and beyond), agreed upon by national government and all stakeholders 3. Increased political support for the scaled up operational response to the yellow fever outbreak response measured by endorsement of the proposed recommendations for a scaled up operations.

Yellow Fever Dose Fractioning WHO recognizes that further yellow fever outbreaks will strain available vaccine supplies and cannot be met by increasing the production capacity alone. Therefore, innovative solutions to stretch available supplies are being actively investigated by experts recruited for this response. The dose-sparing option especially in the context of limited vaccine supply as well as the need to rationalize and quickly immunize a large population in an urban setting to mitigate risks of potential explosion of an outbreak with further risks of exportation elsewhere, is currently the most promising option if implemented strategically and with proper planning and roll out. The available scientific data from one manufacturer (Bio-Manguinhos) with reduced doses given intramuscularly, and the intradermal administration of a fifth of a dose by another manufacturer (Sanofi Pasteur) provide evidence that the fractional-dose approach is an option to stretch vaccine supplies and ensure that as much of the target population as possible can receive a dose of yellow fever vaccine in case of a further expanding outbreak (i.e., for emergency use). The data have been reviewed by an ad-hoc expert group formed for the response, and will be reviewed in an upcoming SAGE meeting. In parallel, a research agenda is being prepared to ensure that the remaining questions can be addressed expeditiously, including generalizing the dose-sparing to other manufacturers, generating data on children and infants, and addressing regulatory issues (including a potential label change).

Further research A specific research agenda is being developed for yellow fever diagnosis and vaccine. In addition studies on: coinfection of malaria and yellow fever; on vaccine adverse effects; and on differential diagnosis of negatives cases are being conducted. The development of performance indicators for the Incident Management System is also taking place to assess this aspect of the response.

ANNEX A Table of organizations involved Partner name Actionaid Agence de Médecine Préventive Animators without borders Anthrologica BBC Media Action CDAC Network CERF CHINA-CDC Congolese RED CROSS Cuban Brigades ECDC EDCARN Epicentre Federal Ministry of Health, Sudan GAVI Alliance GOAL Grupo Core Harvard IFRC Institut de Veille Sanitaire (InVS) Institut National de Recherches Biomédicales (IRNB) Institute Pasteur of Dakar-mobile unit Instituto Nacional de Saude Publica IOM Lifeline energy MDM MH USAID MSF MSF Belgique MSF-France OCHA Pasteur Institute Dakar (IPD) Pôle santé publique, parquet du tribunal de grande instance de Paris Public Health England REDSUR REDR AUSTRALIA Robert Koch Institute (RKI) Rockefeller foundation Save the Children SIMLab TEPHINET Translator without borders UNAIDS UNDP UNESCO UNFPA UNICEF United Methodist Communications UNV USAID US-CDC Wellcome Trust WORLD BANK WVI

ANNEX B Table of organization’s requirements by objectives Sum of Total Requirement (USD) WHO Africa Regional Office 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO Country Office Angola 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO Country Office Democratic Republic Congo 2,960,864 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread WHO HQ 2,843,750 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread 4. Prioritize research to improve access to yellow fever vaccine, and to improve the effectiveness of other prevention and control interventions WHO Country Office Uganda 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread ECDC REDSUR Save the Children 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures TEPHINET UNICEF (HQ) 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures UNICEF [ESARO] 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread UNICEF [GABON] 1,169,281 1,090,113 289,356 295,000 13,227,358 12,279,793 762,856 184,709 Amount undisclosed Amount undisclosed 385,000 385,000 Amount undisclosed 100,000 100,000 170,000 135,000 10,000 25,000 1,324,289 1,387,125 249,450

32,122,305 25,868,875 632,250 5,621,180 18,608,587 1,640,156 273,359 273,359

205,000 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 2. Prevent morbidity and reduce mortality through early case detection and strengthened case management 3. Prevent international spread UNICEF [WCARO] 1,730,000 1. End outbreaks in currently affected countries through targeted vaccination and other public health measures 3. Prevent international spread US CDC 1,650,000 80,000 Amount undisclosed 170,000 30,000 5,000

Grand Total 72,352,864

Основные сведения

Организация Всемирная организация здравоохранения (ВОЗ / WHO)

Тип документа Technical Documents

Дата принятия 21 июня 2016 г.

Источник Всемирная организация здравоохранения