Eliminate yellow fever epidemics (EYE) strategy country toolkit

Eliminate Yellow fever Epidemics (EYE) Strategy country toolkit Eliminate Yellow fever Epidemics (EYE) Strategy Country Toolkit ISBN 978-92-4-009739-1 (electronic version) ISBN 978-92-4-009740-7 (print version) © World Health Organization 2024 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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Girl holds up yellow fever vaccination card after being immunised in Jigawa, Nigeria in 2023 © UNICEF Contents iii EYE Strategy Country Toolkit Introduction 1 Objectives 1 Target audience 1 When to use the Country Toolkit 2 Structure of the Country Toolkit 2 Acknowledgements 2 1 - The global Eliminate Yellow fever Epidemics (EYE) Strategy 3 Yellow fever (YF) 3 EYE’s vision, mission and strategic objectives 5 The keys to EYE Strategy success 7 The EYE Strategy governance structure 7 Further reading 9 2 - Yellow fever risk evaluation at the global and country levels 10 The rationale for yellow fever risk evaluation 10 YF transmission patterns 10 The key factors influencing YF risk 11 The risk of urban outbreaks 11 At the global level: risk classification of countries 12 At the country level 14 Further reading 14 3 - Yellow fever vaccines and vaccination 15 When to use yellow fever vaccines 15 When fractional dose YF vaccination is indicated 16 The importance of monitoring for adverse events following immunization (AEFIs) for all YF vaccination activities 17 Further reading 18 4 - Tailoring yellow fever activities to reach vulnerable and marginalized at-risk populations 19 The importance of tailoring yellow fever activities to reach vulnerable and at-risk populations 19 How to define vulnerable and at-risk populations 19 How to identify vulnerable and at-risk populations 19 Specific actions to reach vulnerable and at-risk populations 20 Further reading 21 5 - Assessing coverage from yellow fever vaccination campaigns 22 Why assess coverage from yellow fever vaccination campaigns 22 Rapid convenience monitorting (RCM) 22 How to assess vaccine coverage 24 Further reading 25 Contents iv EYE Strategy Country Toolkit 6 - Advocacy, social mobilization and communication for yellow fever campaign vaccination activities 26 The need for strong advocacy, social mobilization and communication 26 How to implement advocacy, social mobilization and communication strategies 26 How to tailor a communication and social mobilization plan in the context of preventive mass vaccination campaigns (PMVCs) 30 Communication and social mobilization activities in specific situations 30 Monitoring and evaluating impact 32 Further reading 32 7 - Monitoring the quality of vaccination campaigns 33 The rationale for monitoring yellow fever vaccination campaigns 33 Pre-PMVC indicators 34 Monitoring indicators during PMVCs 34 Post-PMVC monitoring indicators 35 Further reading 36 8 - Routine immunization (RI) for yellow fever 37 The importance of high-performing routine immunization 37 Who should be vaccinated 38 Current issues with YF RI in high-risk countries 38 How to ensure continuous vaccine supplies 38 How to achieve and sustain high RI coverage 39 Support available for YF vaccine introduction (technical and financial) 40 Why conduct PMVCs and catch-up activities 41 How to monitor YF RI activities and performance 42 Further reading 43 9 - Yellow fever preventive mass vaccination campaigns 44 Why conduct preventive mass vaccination campaigns 44 How to set priorities at the subnational level 45 The key elements of a successful PMVC 46 Aiming for early planning and effective coordination 48 Developing an appropriate waste management plan 49 Design and implementation of proper monitoring and evaluation activities 50 Ensuring proper campaign logistics 52 Further reading 53 10 - Logistics of preventive mass vaccination campaigns 54 What to consider for preventive mass vaccination campaign logistics 54 The core components 54 Contents v EYE Strategy Country Toolkit 11 - Preventing the international spread of yellow fever 60 The new approaches needed to prevent the international spread of yellow fever 60 Applying the International Health Regulations (IHR) 60 Protecting high-risk workers 61 Building resilient urban centres 63 The key people to contact and data sources to support these activities 64 Further reading 65 12 - Strengthening surveillance and laboratory capacities 66 Why surveillance and laboratory capacities matter 66 The difference between a presumptive positive sample and a probable case 70 How to interpret complex laboratory diagnostics results 70 Performance indicators for surveillance quality and YF lab diagnostics 70 Further reading 72 13 - Yellow fever outbreak investigation 73 The importance of timely and detailed investigation of yellow fever outbreaks 73 How to conduct an efficient and effective YF outbreak investigation 73 Further reading 78 14 - Response to yellow fever outbreaks 79 The importance of responding appropriately to yellow fever outbreaks 79 What is included in each core activity of a comprehensive outbreak response 79 Checking whether a single case of YF is an outbreak requiring a response 82 Documenting campaign progress and impact 84 Further reading 85 15 - Access to yellow fever vaccine stockpiles for emergency response 86 The International Coordinating Group (ICG) on Vaccine Provision for yellow fever 86 The conditions required to access the YF vaccine stockpile 86 How to apply for the YF vaccine in the ICG stockpile 87 The requirements for a successful ICG request 87 The criteria for release of YF vaccine by the ICG 89 The cost 90 The reporting requirements for reactive campaigns supplied by the ICG 90 Further reading 90 1The Eliminate Yellow fever Epidemics (EYE) Strategy Country Toolkit was developed in recognition of the importance of having readily available country-centred tools to inform practical implementation of yellow fever (YF) prevention and control activities. The Guide represents a consolidation of the expertise and operational insights from many partners and agencies committed to eliminating YF epidemics globally by 2026. The EYE Secretariat would like to thank all the contributors who added their voices to the development process – from the time of inception to preliminary work during the regional kick-off meeting of the EYE Strategy in Abuja, Nigeria, May 2018; inputs from the EYE Strategy Annual Partners’ Meeting in Dakar, September 2018; and the International Coordinating Group (ICG) YF meeting, September 2018. The content was further refined following the African Regional Immunization Technical Advisory Group (RITAG) meeting in January 2019. The EYE Strategy Country Toolkit aims to provide practical, ready-to-use guidance on topics relating to boosting population immunity, YF case detection and investigation, and outbreak response including prevention of international spread. These tools offer a consolidation of information and links to more detailed resources. The content is intended to inform country- level activities to prevent and control YF epidemics successfully. Objectives Target audience This document is intended primarily for public health professionals, surveillance officers and immunization programme managers who are directly involved in YF detection and control activities. These include, for example, staff working at ministries of health, public health institutions, United Nations agencies including the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) country offices, and partners including nongovernmental organizations (NGOs). Introduction Provide ready-to-use practical guidance to support activities to eliminate the risk of YF epidemics. Promote awareness about sources of support for YF prevention and outbreak response. Highlight best practice for planning, preparedness, implementation and monitoring of YF control activities. EYE Strategy Country Toolkit 2When to use the Country Toolkit The Country Toolkit is intended to offer a comprehensive suite of guidance on YF control. It consists of a series of short topics that provide information to be used: • to strengthen population immunity and YF vaccination coverage; • to support detection, investigation and verification of suspected YF cases; • to develop a response plan and access vaccines when a YF outbreak is suspected; and • to organize and monitor the response during a YF outbreak. Structure of the Country Toolkit The Country Toolkit is composed of a series of standalone documents. The structure of each document consists of the following: • general topic overview and rationale; • key information and content; and • list of resources and references for further detail and support. Acknowledgements Many people from many partners and agencies contributed their valuable time and expertise to the development of the different sections of this country toolkit. The development of this project was led by the WHO Eliminate Yellow fever Epidemics Secretariat under the leadership of Laurence Cibrelus. WHO gratefully acknowledges the following individuals for their contributions to the development and finalization of this document: Elise Guillermet, Isabelle Delrieu, Philippe Jaillard, and Philippe Cavailler who were contracted to develop the draft versions of the Country Toolkit; as well as Chikwe Ihekweazu (Nigeria Centre for Disease Control; current affiliation: WHO), Nwachukwu William and Nwando Mba (Nigeria Centre for Disease Control); Oyewale Tomori (former Vice Chancellor, Redeemer’s University Nigeria and former President for the Nigeria National Academy of Science); Carlos Campelo de A. e Melo (Pan American Health Organization); Yodit Sahlemariam and Hans Christiansen (United Nations Children’s Fund (UNICEF)); Chantal Reusken (Centre for Infectious Disease Control, Kingdom of the Netherlands); Duane Gubler (Duke-NUS Medical School, Singapore); Tatiana Guimarães de Noronha (Fiocruz, Brazil); Cristina Domingo (Robert Koch Institute, Germany); Jane Basile, Rebecca Cassey and Terri Hyde (United States Centers for Disease Control and Prevention (CDC); Tina Lorenson (Bill & Melinda Gates Foundation); Cassandra Quintanilla and Lee Hampton (Gavi, the Vaccine Alliance); and Dhamari Naidoo, Madhava Ram Balakrishnan, Corinne Ponce, Carmen Dolea, Raman Velayudhan, Jennifer Horton, Marie-Eve Raguenaud and Jean-François Lemaire (WHO). Declaration of interests: No interests were identified upon review by the WHO EYE Secretariat of declaration of interests submitted by external contributors. Methods: The EYE Secretariat hosted by the WHO Health Emergencies Programme led and coordinated the development of the product. Several drafts were first developed by independent contractors and by a consulting firm specialized in developing evidence-based health products for low- and middle-income countries. After review of these drafts by the WHO yellow fever technical team, specific chapters were shared with external contributors of the EYE partner network for inputs in their area of expertise. The process included a review of each chapter before final editing and design work. EYE Strategy Country Toolkit 3Yellow fever Yellow fever (YF) is an acute viral disease of humans and other primates1 that is transmitted by many different types of mosquitoes, including Aedes spp., Haemagogus spp. and Sabethes spp.2 The disease is endemic to tropical areas of Africa and Central and South America. YF is a multifaceted and high-impact epidemic-prone disease that cannot be eradicated because of the existence of a wildlife reservoir, and that can spread internationally and threaten global health security. However, outbreaks can be eliminated because YF is preventable by vaccination and vector control. A single dose of vaccine is effective in more than 95% of recipients and provides lifelong immunity, with protective antibodies appearing 7–10 days after immunization. If sufficient levels of population immunity are maintained indefinitely through vaccination, epidemics can be eliminated. After early successes in outbreak prevention and control in the mid-20th century, attributable mainly to mass vaccination campaigns3, waning population immunity led to a re-emergence of outbreaks in West Africa in the early 2000s and to the launch of the Yellow Fever Initiative in 2006. This collaborative initiative targeted countries in West Africa where YF is endemic and introduced the YF vaccine into routine childhood immunization programmes and preventive mass vaccination campaigns (PMVCs). The three-pronged strategy that began in 2005 included the introduction of the YF vaccine into routine child immunization programmes in endemic countries; implementation of PMVCs in at-risk areas to boost immunity in most or all age groups; and the setting up of a global vaccine stockpile to permit for rapid response to outbreaks, administered by the International Coordinating Group (ICG) on Vaccine Provision4. Between 2005 and 2015, more than 114 million people were vaccinated in West Africa, leading to a steady reduction in the number of YF outbreaks; in 2015, no outbreaks were reported in the WHO African Region (Fig. 1)5. However, immunity remained low in other countries, including Nigeria, and in countries in East and Central Africa that were not covered by PMVCs. There was a subsequent re-emergence of YF outbreaks in West Africa in late 2020 1 - The global Eliminate Yellow fever Epidemics (EYE) Strategy EYE Strategy Country Toolkit 1 For a comprehensive list of African and South American vertebrate host species of YF virus, see Vainio J, Cutts F. Yellow fever. Geneva: World Health Organization; 1998 (https://apps.who.int/iris/handle/10665/64455, accessed 24 July 2023). 2 In South America, Haemagogus spp. mosquitoes are the main vector in the sylvatic cycle. 3 Global health partners mobilize to counter yellow fever. Geneva: World Health Organization; 2007 (https://apps.who.int/iris/ handle/10665/73958, accessed 24 July 2023). 4 International Coordinating Group (ICG) on Vaccine Provision: yellow fever. In: World Health Organization [website]. Geneva: World Health Organization; 2023 (https://www.who.int/groups/icg/yellow-fever, accessed 24 July 2023). 5 See details in the WHO Weekly Epidemiological Record: Weekly Epidemiological Record. 2016;91(32):381–8 (https://apps.who.int/ iris/handle/10665/254474, accessed 24 July 2023). 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 4 1 in areas with suboptimal population immunity due to low vaccination and population movements, underscoring the importance of maintaining high population immunity.6 People with YF disease may present with nonspecific symptoms, and many cases are not confirmed by existing surveillance and laboratory structures. A modelling study based on African data sources estimated that the annual burden of YF during 2013 was 51 000 to 380 000 cases and 19 000 to 180 000 deaths.7 There is urgent need for improved detection and rapid response to YF cases. In 2016, Angola experienced an unprecedented YF urban outbreak that spread to neighbouring countries and generated local transmission, including in Kinshasa, the capital of the Democratic Republic of the Congo. The epidemic created an urgent need for more than 28 million doses of YF vaccine, exhausting the existing global supply. It also diverted public health authorities from tackling other public health issues with an impact on health systems. These events triggered increased awareness of the need for a global YF programme, and resulted in the development of the global EYE Strategy.8 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 10 9 8 7 6 5 4 3 2 1 0 Year 1 country 5 countries 6 countries 60 to 80% <60% ≥80% No . o f Y F ou tb re ak s Number of YF outbreaks in West African countries with campaigns through the Yellow Fever Initiative Average national routine immunization coverage for YF in West African countries with campaigns through the Yellow Fever Initiative Source: Proceedings of the 2018 annual meeting of partners to Eliminate Yellow fever Epidemics (EYE), Dakar, Senegal. Weekly Epidemiological Record. 2019;94(6):68– 78 (https://apps.who.int/iris/handle/10665/281713, accessed 24 July 2023). 6 For details on outbreaks in Guinea and Senegal in 2020–2021, see details in the WHO Weekly Epidemiological Record: Weekly Epidemiological Record. 2021;96(33):377–92 (https://apps.who.int/iris/handle/10665/344322, accessed 24 July 2023). 7 Garske T, Van Kerkhove MD, Yactayo S, Ronveaux O, Lewis RF, Staples JE et al. PLoS Med. 2014;11(5):e10011638. 8 Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Geneva: World Health Organization; 2018 (https://www. who.int/publications/i/item/9789241513661, accessed 24 July 2023). EYE Strategy Country Toolkit Fig. 1. Routine vaccination must be strengthened to prevent YF from re-emerging in West Africa 5EYE’s vision, mission and strategic objectives The global EYE Strategy was validated by the Strategic Advisory Group of Experts on Immunization (SAGE) in October 2016 and approved by the Board of Gavi, the Vaccine Alliance, in December 2016. The Strategy will succeed if there is strong coordination and engagement with countries and multidisciplinary partners, as no country or institution can tackle the global issue of YF epidemics alone. Vision The EYE Strategy aims to vaccinate more than 1 billion people in Africa and the Americas against YF and to eliminate YF epidemics globally by 2026. It is a comprehensive, long-term (2017–2026) plan that targets the most vulnerable countries and involves many international partners, such as the United Nations Children’s Fund (UNICEF) and Gavi, the Vaccine Alliance. It addresses the global risk of YF by building resilience in urban centres and in areas with outbreak potential and ensures reliable and sustainable vaccine supply. Mission The EYE Strategy coordinates international action and helps at-risk countries prevent YF outbreaks and prepare for those that may occur, minimizing suffering, damage and spread by early and reliable detection and a rapid and appropriate response. Strategic objectives The EYE Strategy consists of three strategic objectives built on lessons learned during recent outbreaks: PROTECT AT RISK POPULATIONS PREVENT INTERNATIONAL SPREADCONTAIN OUTBREAKS RAPIDLY The scaled-up strategy for accelerated YF prevention and control is global and comprehensive, extends beyond the established endemic areas in Africa and the Americas, and utilizes all the public health tools available to manage risk beyond vaccination. As such, the EYE Strategy also emphasizes the strengthening of surveillance and laboratory capacity, the application of the International Health Regulations (2005) (IHR) and the involvement of the private sector, especially the mining and forestry industries, as well as agricultural industries (Fig. 2 overleaf). RESPOND NOW SUPPLY READY DETECT EARLY EYE Strategy Country Toolkit 1 6EYE Strategy Country Toolkit Fig. 2. Multisector approach to control the risk of YF effectively International Health Regulations (IHR) Vaccination (Campaigns, routine) Early detection, surveillance and Dx Heightened risk of YF epidemics Vector surveillance and control Non-human primates surveillance (PAHO) Urban Health Clinical management To achieve and maintain population-level immunity with a security threshold to ensure adequate protection (at a recommended 80% or higher), several vaccination strategies have to be combined (Fig. 3), including: • introduction of YF vaccine into routine child immunizations and strengthening of these activities; • PMVCs, typically nationwide and for most or all age groups, in countries without previous campaigns of this type; and • targeted catch-up activities to close immunity gaps, in specific geographical areas and/or targeting selected age groups and/or subpopulations where unprotected populations are identified. Fig. 3. Population protected by routine immunization, PMVC and combined vaccination strategy 1 10 20 30 40 (A) Routine child immunization (C) Combined vaccination strategy: Routine childhood immunization (B) Preventive mass vaccination campaign 100 90 80 70 60 50 40 30 20 10 0 1 10 2.3 22.8 45.6 68.4 91.2 20 30 Pr op or tio n (% ) o f p op ul at io n pr ot ec te d 40 100 90 80 70 60 50 40 30 20 10 0 1 10 80.0 55.1 26.6 0 0 20 30 40 82.3 77.9 72.2 91.2 68.4 100 90 80 70 60 50 40 30 20 10 0 Vaccine coverage security threshold Number of years after the intervention Number of years after the intervention Number of years after the intervention + one preventive mass vaccination campaign 1 Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 7EYE Strategy Country Toolkit The YF vaccine has been introduced successfully into routine immunization programmes for children at the scheduled age of 9–12 months in most high-risk countries at the national level since the late 1970s. The EYE Strategy aims to introduce the YF vaccine in the routine immunization schedule of the remaining high-risk countries of Ethiopia and South Sudan, and to achieve continuous high vaccination coverage each year and in all districts. Prior to 2016, PMVCs were conducted in many West African countries. Furthermore, large parts of Angola and areas in the Democratic Republic of the Congo benefited from reactive and pre-emptive campaigns in the course and aftermath of the 2016 outbreaks. Nevertheless, at the time the EYE Strategy began, PMVCs remain uncompleted in some countries (such as Ghana, Nigeria and Sudan). Accounting for both the logistic capacity of countries to conduct very large national PMVCs and the global supply of the YF vaccine, countries have been prioritized based on risk, and national PMVCs in large countries will be spread throughout several years. In addition, the Strategy will provide for reactive and pre-emptive campaigns in outbreak situations. The global emergency vaccine stockpile is currently maintained at a magnitude of 6 million doses at all times, and is annually reassessed by the ICG to ensure that the size is fit for purpose. The keys to EYE Strategy success In order to achieve the objectives and goal of eliminating YF epidemics, the EYE Strategy addresses the following areas: • access to affordable vaccines and a sustained vaccine market; • strong political commitment at the global, regional and country levels; • robust governance and long-term partnerships; • synergies with other programmes and sectors; and • research and development for better tools and practices. The EYE Strategy governance structure The EYE Strategy is a global plan with involvement of stakeholders at the global, regional and national levels. It has a governance structure that includes membership of core partners (WHO, UNICEF and Gavi, the Vaccine Alliance) that provide high-level oversight through the leadership group and programme management through the programme management group, which supports technical and coordination issues using an objective evidence-informed approach. Regional and country support needs are managed through the regional focal points, who communicate regularly with the EYE Secretariat and programme management group to ensure smooth coordination and implementation of activities in accordance with global vaccine supply and support availability. The EYE Strategy regional focal points (Africa) In the WHO Regional Office for Africa, there are two specialized focal points who support in-country activities related to YF. The focal points are available to travel regularly to priority countries to support initiatives to strengthen routine immunization for YF, as well as to support the planning and preparation for preventive and reactive campaigns. The focal points may assist with event and outbreak investigations and risk assessments when necessary. They also support linkages of countries to other resources where available, and support coordination with the overarching EYE Strategy governance structure. 1 8EYE Strategy Country Toolkit The EYE Secretariat The EYE Secretariat provides organizational support and ensures the smooth and efficient running of all activities of the leadership group, the programme management group and the contributing partners. It is based at WHO headquarters and hosts the EYE Strategy dashboard, a publicly accessible platform to provide updates on key progress and outcome indicators. The Secretariat also provides a monthly newsletter update. Synergies with other public health and vaccination programmes The EYE Strategy’s efficiency and sustainability can be optimized through integration to other existing programmes/initiatives, including: • measles/rubella strategy, for vaccination activities; • vector-borne disease activities such as vector control activities and research, community engagement/ behavioural change and social mobilization strategies; • integrated disease surveillance, for laboratory testing of samples from patients presenting with haemorrhage and/or jaundice; • resilient cities programmes such as those steered by the Rockefeller Foundation, which could serve as platforms to develop urban readiness plans; • IHR-related activities to enhance consistency between IHR maps and EYE Strategy risk assessment, and improve YF vaccination status control at land-border crossings; • collaboration between occupational health units and the private sector; • collaboration between health systems and immunization strengthening programmes such as Immunization Agenda 2030, to address health inequities, discrepancies identified between YF and first dose of measles- containing vaccine or third dose of diphtheria, tetanus toxoid and pertussis-containing vaccine, and to improve overall routine immunization performance and build capacity. Contacting the EYE focal points for assistance • Technical assistance and general guidance to implement EYE Strategy activities • Support for monitoring and evaluation of EYE Strategy implementation • Assistance to raise awareness at the country level • Recommendations for improvement of vaccination coverage • Technical guidance and support for PMVCs, routine immunization, outbreak response and risk assessments • Information on financial support applications • Support to conduct lessons learned exercises and advice for improvement For more information Contact: EYE.Strategy@who.int 1 9EYE Strategy Country Toolkit Further reading 9 Communication and social mobilization in yellow fever mass vaccination campaigns: 10 points from field experience. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/156053). Framework for implementing the global strategy to Eliminate Yellow fever Epidemics (EYE), 2017–2026 in the African Region. Brazzaville: WHO Regional Office for Africa; 2017 (AFR/RC67/8; https://iris.who.int/handle/10665/334311). GAVI Support Guidelines. Geneva: Gavi, the Vaccine Alliance; 2021 (https://www.gavi.org/our-support/guidelines). Immunization in practice: a practical guide for health staff. Geneva: World Health Organization; 2015 (https://iris.who.int/ handle/10665/193412). Increasing immunization coverage at the health facility level. Geneva: World Health Organization; 2002 (https://iris.who.int/ handle/10665/67791). Investigation of yellow fever epidemics in Africa: field guide. Geneva: World Health Organization; 2008 (https://iris.who.int/ handle/10665/69874). Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://iris.who.int/handle/10665/330568). Practical guide for the design, use and promotion of home-based records in immunization programmes. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/175905). Risk assessment on yellow fever virus circulation in endemic countries: working document from an informal consultation of experts: a protocol for risk assessment at the field level. Geneva: World Health Organization; 2014 (https://iris.who.int/handle/10665/112751). Surveillance standards for vaccine-preventable diseases, second edition. Geneva: World Health Organization;2018 (https://iris.who.int/ handle/10665/275754). Yellow fever: strategic response plan June–August 2016. Geneva: World Health Organization; 2017 (https://iris.who.int/ handle/10665/246103). Yellow fever surveillance and outbreak response: revision of case definitions, October 2010. Weekly Epidemiological Record. 2010;85(47):465–72 (https://iris.who.int/handle/10665/241676). 9 All references accessed 24–27 July 2023. 1 10 2 - Yellow fever risk evaluation at the global and country levels EYE Strategy Country Toolkit Yellow fever risk evaluation at the global and country levels The rationale for yellow fever risk evaluation Evaluation of the yellow fever (YF) risk at the global and country levels is crucial to implement tailored preventive strategies. A comprehensive risk assessment methodology has been designed and applied in a number of countries in the past five years. Country risk assessments are used to guide preventive interventions and recommend preventive campaigns or introduction of the YF vaccine into the routine Expanded Programme on Immunization. In some contexts, additional assessment may be needed to ensure that the remaining vulnerable population is reached. YF transmission patterns The most frequent YF virus transmission patterns are as follows (Fig. 4) Jungle (Sylvatic) Urban Intermediate (Africa) Sylvatic transmission occurs when the animal reservoir living in the forest or jungle infects mosquitoes, which in turn bite humans who enter the forest. The sylvatic cycle may be propagated by different species of mosquitoes, including Haemagogus spp., Aedes spp. and Sabethes spp. Urban transmission is effected by Aedes aegypti mosquitoes, which are highly competent vectors capable of direct human-to- human transmission, and which amplify YF outbreaks rapidly. Intermediate transmission occurs when various mosquito species moving between the forest and human settlements are involved, and humans living in rural villages and small towns serve as the hosts. Fig. 4 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 11 EYE Strategy Country Toolkit The key factors influencing YF risk Occurrence of YF outbreaks is a multicomponent process. The key factors to be considered are vectors, environmental risk and human risk. • The primary vector responsible for urban outbreaks is Aedes spp. mosquitoes. Aedes spp. are also associated with other arbovirus outbreaks (such as chikungunya, dengue and Zika virus). Presence of arboviral disease and outbreaks should alert countries to the possibility that YF virus could also be transmitted successfully in their communities. • Humans enter the environments of forest and jungle to hunt or work (in mining, oil extraction and forestry), and move back rapidly to cities or large settlements, thus contributing to the rapid spread of YF virus. Risk- amplification factors include deforestation, urbanization, large population movements, climate change and increasing exposure of workers to infected mosquitoes in jungles and forests. • Under-immunized human populations are at risk of infection and spread of the virus. Movement of populations (such as for commerce, work or major worship events, or due to civil unrest, health or humanitarian emergencies) can lead to situations where a susceptible population encounters the virus. If there is a large influx of unvaccinated populations into a high-risk area, they will be at risk of infection and spread. Conversely, if infected people move to an area with an under-immunized population, the virus has the potential to spread quickly if the vector is present. The risk of urban outbreaks In recent outbreaks in past decades, the YF virus transmission cycle has been increasingly short-circuited from a sylvatic cycle to an urban, inter-human transmission cycle. Additionally, the intermediate pattern observed in Africa can lead to an “emergence zone” in rural settlements, and can progress to large outbreaks if infected people from these settlements travel to urban centres. The urban cycle, propagated by Aedes spp. mosquitoes, is characterized by rapid amplification. Urban outbreaks are particularly deadly, disruptive and fast-moving, and have easy capacity for international spread. Major specific risk factors for the occurrence of an urban outbreak include population density, crowding, low levels of population immunity, daily population movements in and out of – and around – the city, and mosquito breeding sites leading to high mosquito vector density (Fig. 5). Climate Change Risk of emergence in other refgions Intensified population movements Rampant informal urbanization African cities connected to areas with YF potential Fig. 5. Increased risk of urban outbreaks with international spread 2 12 EYE Strategy Country Toolkit Responding to outbreaks in large urban settings is challenging and costly, and can have major impacts on public health, travel and trade. It is essential to investigate early and respond promptly. At the global level: risk classification of countries Approaches within the Eliminate Yellow fever Epidemics (EYE) Strategy differ in type and extent, in line with a country’s probability of experiencing YF outbreaks and the associated risk. Specific criteria were applied to classify countries (mostly in Africa) and propose preventive strategies accordingly, as follows: Crude risk of YF transmission was estimated. Crude risk represents the likelihood of YF disease cases occurring if the population is inadequately vaccinated. Countries fulfilling at least one of the following criteria were classified as high risk: • YF outbreaks reported between 1990 and 2016; • YF cases (with local transmission) reported between 2011 and 2016; • national mass vaccination campaigns conducted prior to the Yellow Fever Initiative; and • evidence of YF circulation from serosurveys in vaccination-naive populations. Other countries with suitable vector mosquito populations were classified as moderate risk or potential risk, according to circulation of arboviruses requiring similar conditions to YF (such as chikungunya, dengue and Zika virus), and on their inclusion in previous YF strategies. As a result, 27 African countries were classified as high risk and a further 8 as moderate risk.10 (Fig 6). Figure 7 shows yellow fever risk classification by country in the Americas. Step 1 10 Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Geneva: World Health Organization; 2018 (https://www.who. int/publications/i/ item/9789241513661, accessed 29 November 2023). Figure 6: Yellow fever risk classification by country, Africa 2 Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who. int/handle/10665/279723. 13 EYE Strategy Country Toolkit Figure 7. Yellow fever risk classification by country in the Americas. Actual risk of YF disease cases and urban outbreaks was estimated. This was based on the crude risk of YF circulation (step 1) and data on population immunity (the proportion of people likely to be protected against YF by previous vaccination). Countries’ prioritization was calculated, based on their perceived level of risk (such as the history of outbreaks, virus circulation or low vaccine immunity in the country). Step 2 Step 3 2 Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 14 At the country level A comprehensive risk assessment methodology has been designed and applied in a number of countries in the past five years.11 With 40 endemic countries at high risk of YF disease, it has been essential to prioritize immunization activities. To address the vaccine demand for preventive mass vaccination campaigns (PMVCs) in a context where demand was exceeding supply, periodic risk prioritization among high-risk countries was needed to optimize vaccine allocation and maximize impact. Subnational risk assessment is a further step that may be required to guide the identification of which administrative unit PMVCs should prioritized, particularly in highly populated countries. The risk assessment tool includes three domains: risk of disease, epidemic risk, and mitigation. Further reading 12 Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Weekly Epidemiological Record. 2017;92(16):193–204 (https://apps. who.int/iris/handle/10665/255374). Framework for implementing the global strategy to Eliminate Yellow fever Epidemics (EYE), 2017–2026 in the African Region. Brazzaville: WHO Regional Office for Africa; 2017 (AFR/RC67/8; https://iris.who.int/handle/10665/334311). Jentes ES, Poumerol G, Gershman MD, Hill DR, Lemarchand J, Lewis RF et al. The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever. Lancet Infectious Diseases. 2011;11(8):622–32. doi:10.1016/S1473-3099(11)70147-5. Yellow fever: strategic response plan June–August 2016. Geneva: World Health Organization; 2017 (https://iris.who.int/ handle/10665/246103).Yellow fever surveillance and outbreak response: revision of case definitions, October 2010. Weekly 11 Risk assessment on yellow fever virus circulation in endemic countries: a protocol for risk assessment at the field level. Geneva: World Health Organization; 2014 (https://apps.who.int/iris/handle/10665/112751, accessed 24 July 2023). 12 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 2 15 When to use yellow fever vaccines One dose of the yellow fever (YF) vaccine provides a lifelong immunity against the disease. The YF vaccine should be administered to everyone aged 9 months and over in high-risk settings.13 The YF vaccine is not recommended for people aged over 60 years, as the risk of adverse effects is higher, and the overall risk of YF infection remains low for this age group. Women who are pregnant or lactating require special consideration. Since YF is a live-attenuated vaccine, a risk–benefit assessment should be undertaken on an individual basis for all such women. In endemic areas, the benefits of YF vaccination are likely to far outweigh the risk of potential transmission of vaccine virus to the fetus or the infant. • Pregnant women and nursing mothers should be counselled on the potential benefits and risks of vaccination so that they can make an informed decision. • Vaccination activities should be implemented with care for equitable access – if pregnant or lactating women defer administration, there is a need to provide a barrier-free opportunity for catch-up vaccination at a later time. There are very few contraindications to YF vaccination. The YF vaccine is contraindicated in children under 6 months of age, and is not recommended for those aged 6–8 months (infants younger than 9 months old being at higher risk of vaccine-associated encephalitis). YF vaccine may be administered with other vaccines either simultaneously on separate vaccination sites (such as the antero-lateral deltoid areas of both arms) or at an interval of four weeks. Oral polio vaccine may be given at any time in relation to YF vaccination. YF vaccination cards are lifelong vaccination documentation records that are directly connected with the process of obtaining an International Health Regulations (2005) (IHR) card for international travellers. These cards should be kept indefinitely. The global supply of YF vaccine is improving. At present, three manufacturers globally produce WHO pre- qualified YF vaccines in large quantities. Country needs are expected to be met over time, accounting for programmatic considerations. 3 - Yellow fever vaccines and vaccination EYE Strategy Country Toolkit 13 Vaccines and vaccination against yellow fever: WHO Position Paper – June 2013. Weekly Epidemiological Record. 2013;88(27):269–84 (https://apps.who.int/iris/handle/10665/242089, accessed 24 July 2023). 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 16 EYE Strategy Country Toolkit When fractional dose YF vaccination is indicated YF fractional dose works to interrupt transmission and should be considered in response to an emergency situation, and in the context of vaccine shortage and acute demand. According to the last Strategic Advisory Group of Experts on Immunization (SAGE) recommendations, only Bio Manguinhos YF vaccine should be considered in the perspective of fractional dosing utilization. Fractional dose should not be used for routine immunization or preventive mass vaccination campaigns (PMVCs). As soon as the vaccine supply situation normalizes, off-label fractional dose use should be replaced by full dose vaccination. Advice should be sought at the WHO country office. Fractional dose of YF vaccine is as safe and effective as the full dose of the vaccine. There is no evidence of increased serious adverse effects when using a fractional dose. Studies show that the YF vaccine given at one fifth of the regular dose still provides full immunity against the disease for at least 12 months and likely longer. A full dose of vaccine should be offered preferentially during emergency campaigns to children younger than 2 years old, pregnant women, lactating mothers and HIV-infected individuals. Fractional dosing is currently used for administration of inactivated polio, rabies and Bacillus Calmette-Guérin (BCG) vaccines. After administration of a fractional dose of the YF vaccine, the need for re-vaccination has yet to be determined, and therefore YF vaccination requirements under the IHR have not been met. Proof of vaccination for international travel currently requires re-vaccination with a standard full dose. When the YF vaccine is administered in a fractional dose the following applies: • Preference should be given to administration of the vaccine according to the standard route, subcutaneously or intramuscularly, using the appropriate auto-disable syringes (i.e. 0.1 ml), as the huge logistic bottleneck remains the stock limitation for the 0.1 ml syringes. • The minimal potency should preferentially be equal to 3000 IU/per dose, but should not be less than 1000 IU/ dose, and the minimum administration should be not less than 0.1 ml. • Guidance should be sought from the WHO country office regarding the determination of the most suitable volume (i.e. one fifth of the standard dose). • Multidose vials containing more than 10 standard 0.5 ml doses should not be used for fractional dose administration in order to avoid the increased risk of contamination through large numbers of punctures of the vial septum. Vaccination with fractional doses should be recorded using personal registries for the purpose of safety and effectiveness monitoring. Such information might be useful in assessing eventual re-vaccination needs with a full dose, for which there is currently no recommendation. Social mobilization and communication made to the community should be fine-tuned, with an emphasis on the key issue of use of fractional doses (i.e. that experience to date has confirmed fractional dosing as safe and effective to stop outbreaks). Specific messages need to be tailored for communication at the national and district levels. Rumour tracking, including on social media platforms, is important. Social mobilizers must be trained in particular to understand and communicate messages in the local languages properly. Even though preliminary results are encouraging, follow-up studies on immunogenicity and vaccine failures are needed to provide additional evidence to guide further practice of YF fractional dose. 3 17 EYE Strategy Country Toolkit The importance of monitoring for adverse events following immunization (AEFIs) for all YF vaccination activities YF is a live attenuated vaccine that is very safe. It has been used for more than 70 years in endemic countries and for international travellers. Occurrence of AEFIs is always a possibility. The procedures for AEFI monitoring are described in the 2010 WHO field guide.14 All personnel providing immunization services should be educated and given tools to support clinical management and reporting to district and national levels of any serious AEFIs. Serious AEFIs can present shortly after vaccination (for example, severe allergy or anaphylaxis) or in the days following immunization (for example, vaccine-associated viscerotropic disease and vaccine-associated neurotropic disease). Generally mild systemic reactions caused by hypersensitivity to the vaccine components are occasionally observed. In a recent eight-country study (38 million people vaccinated between 2010 and 2013) examining the issue,15 the reported frequencies of severe adverse outcomes were as follows: • severe allergic reaction: 0.29 per million vaccine doses administered (giving an incidence of 0.029 per 100 000); • YF vaccine-associated neurologic disease: 0.16 per million vaccinations (incidence of 0.016 per 100 000); • YF vaccine-associated viscerotropic disease): 0.13 per million vaccinations (incidence of 0.013 per 100 000). More AEFIs are detected during mass campaigns. This is not related to the vaccine itself but due to the large number of vaccinations performed during a short period of time, and the possibility, for some vaccination teams, of reduced compliance with safe injection practices due to high workload and demand. Careful AEFI monitoring during campaigns is also a possible contributing factor. Early planning of vaccine safety before the campaign should take place through the appointment of an AEFI national committee, development of technical documents adapted from the WHO global guidelines (for the definition, monitoring and management of AEFIs),16 appropriate sensitization of the community (with the message “YF is effective and safe”) and training of health personnel. During the campaign, vaccine safety activities include: • passive surveillance supplemented by active detection of serious AEFIs; • management and reporting of AEFIs according to standard protocols; and • appropriate communication (addressing any rumours or misinformation). 14 Yellow fever: surveillance of adverse events following immunization against yellow fever – field guide for staff at the central, intermediate and peripheral levels. Geneva: World Health Organization; 2010 (https://apps.who.int/iris/ handle/10665/70216, accessed 24 July 2023). 15 Breugelmans JG, Lewis RF, Agbenu E, Veit O, Jackson D, Domingo C et al. Adverse events following yellow fever preventive vaccination campaigns in eight African countries from 2007 to 2010. Vaccine. 2013; 31(14):1819–29. doi:10.1016/j. vaccine.2013.01.054. 16 Global manual on surveillance of adverse events following immunization, 2016 update. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/206144, accessed 24 July 2023). 3 18 Further reading 17 Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response – WHO Secretariat information paper. Geneva: World Health Organization; 2016 (WHO/YF/SAFE/16.1; https://iris.who.int/handle/10665/246236). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Yellow fever vaccine: WHO position on the use of fractional doses – June 2017. Weekly Epidemiological Record. 2017;92(25):345–50 (https://iris.who.int/handle/10665/255754). EYE Strategy Country Toolkit 17 All references accessed 24–27 July 2023. 3 19 The importance of tailoring yellow fever activities to reach vulnerable and at-risk populations Vaccinating all eligible populations at risk of yellow fever (YF) is key to the success of the Eliminate Yellow fever Epidemics (EYE) Strategy. During an outbreak, reaching and vaccinating every eligible person is crucial for outbreak control. In routine and preventive activities, sustaining routine vaccination in underserved, hard-to- reach populations and ensuring that every child and eligible person is reached will help prevent cases of YF disease and possible outbreaks. Some subpopulations may be more challenging to reach in terms of vaccination efforts, owing to a variety of cultural, gender, geographical and socioeconomic factors. They may have specific communication needs or reservations about formal public health interventions, or they might be difficult to identify or locate. Creating tailored strategies to reach all at-risk populations will facilitate optimal vaccine coverage rates and reduce the risk of outbreaks. How to define vulnerable and at-risk populations Vulnerable, marginalized and at-risk populations include specific groups with low vaccination coverage and/ or high risk of infection. These populations could be mobile (for example, nomadic or migrant populations, or refugees) or stationary (for example, remote, hard-to-reach or underserved communities; groups that are marginalized or have limited access because of sex or gender; unregistered people; people in informal settlements, such as children in slums; or prisoners). High-risk workers engaged by informal employment in extractive industries and their families are an example of an at-risk population. Gender is a crucial consideration to ensure that outreach strategies can reach all people equitably. People living in fragile, conflict and vulnerable contexts should be identified as at-risk populations that have unique complexities, requiring tailored approaches. How to identify vulnerable and at-risk populations In vaccine-implementing countries, a risk-mapping exercise is necessary to identify possible vulnerable and at- risk populations. The most vulnerable populations can be defined through the following actions: Epidemiological data and socioeconomic indicators should be collected during the investigation of any suspected YF case. Indicators collected should include gender, origin, ethnicity, reason for mobility, movement and displacement – including routes and congregation points to anticipate routes for widespread YF outbreaks. 4 - Tailoring yellow fever activities to reach vulnerable and marginalized at-risk populations EYE Strategy Country Toolkit 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 20 Risk-mapping exercises should be conducted with partner organizations and experts in vulnerability, including: • the United Nations Children’s Fund (UNICEF), UN Women and nongovernmental organizations (NGOs) for children (street children, orphaned and vulnerable children, migrants) and marginalized gender(s); • the International Organization for Migration (IOM), United Nations High Commissioner for Refugees (UNHCR) and Médecins Sans Frontières (MSF) for migrants and refugees or activities in fragile, conflict or vulnerable contexts; • the private sector for vulnerable workers (in the oil extraction, mining, forestry and fishery industries and involved in cross-border trade, among others); • experts in vulnerabilities (such as mobility, social inequities and health access); and • other ministries. Coordinating rapid risk assessments at the district level (via the ministry of health) is essential, with a focus on populations with limited access to health services and vaccines despite satisfactory official statistics. Specific actions to reach vulnerable and at-risk populations Once defined, the target populations can be reached through: • establishing YF vaccination guidance for the inclusion of vulnerable, marginalized, mobile and displaced populations in at-risk areas; • facilitation of a specific working group for equitable access to YF vaccination for all at-risk populations, with dedicated partners (such as UNICEF, UNHCR, IOM and MSF) and experts to define the guidance (vaccination as standard practice), reach a decision about priorities and draw lessons learned from special activities used by programmes for other antigens and integrated outreach activities (such as those for polio and measles); • defining a plan for immunization per category of vulnerable population – routine immunization, preventive mass vaccination campaign (PMVC) or catch-up activities – including the timeline, roles and responsibilities, estimated doses and process to request vaccines if needed (such as via the International Coordinating Group (ICG) on Vaccine Provision); • determination of whether special strategies to offer vaccination are useful, and designing how to implement them (such as via special outreach or mobile teams, after-hours booths or allied health partners engaged with subpopulations in fragile, conflict and vulnerable contexts). Implementing immunization strategies involves: • developing tailored communications and outreach strategies to address the needs and concerns of each identified special population, including use of targeted outreach with multiple antigen activities where indicated; • ensuring barrier-free access to vaccination (such as flexibility to vaccinate people without formal registration or identification, sensitivity to sociocultural norms and accommodation for equitable access for all genders and subpopulations); • applying specific strategies to protect high-risk workers and their families, including sensitization to YF risks and vaccination; • developing specific data collection tools for each method of immunization implementation to tally uptake by special populations (such as fixed post, special outreach or mobile teams, after-hours booths); • establishing reporting mechanisms to record numbers vaccinated through alternative routes (organizations working with vulnerable, marginalized and displaced populations). EYE Strategy Country Toolkit 4 21 Conducting ongoing monitoring and technical support involves: • ongoing monitoring and technical support for organizations working with vulnerable, marginalized and displaced populations in at-risk areas; • regular meetings with the working group to update risk assessments, microplans and priorities for immunization strategies following the arrival of new migrants, set-up of new informal urban settings and development of new at-risk working areas (such as oil extraction, mining, forestry and fishery industries and cross-border trade); • proactive monitoring and transparent reporting on vaccination by age, gender, locality and specific subgroup (when acceptable) through both qualitative and quantitative sources (such as tally sheets, supportive supervision and independent monitors); • ensuring that course-corrective steps are taken if trends suggesting low uptake in specific groups are identified through quantitative or qualitative feedback. Tailoring implementation of YF prevention measures Most risk-reduction approaches need to be national in scope to account for population movement, feasibility, efficiency, consistency and sustainability. When a localized vulnerability, age or gender-specific risk is documented, some interventions might be targeted at a subnational level or to a specific population (such as PMVCs or catch-up activities). For practical considerations, such as programmatic issues in countries with large target populations, some national interventions can also be implemented by subnational increments – based on risk analysis, existing vulnerabilities and ecological criteria. National advocacy, social mobilization and communications subcommittees (and district-level equivalents), including community leaders, should be established at the district level or equivalent to facilitate interventions. EYE Strategy Country Toolkit Further reading 18 Communication and social mobilization in yellow fever mass vaccination campaigns: 10 points from field experience. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/156053). Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://iris.who.int/handle/10665/330568). Reaching every district (RED): a guide to increasing coverage and equity in all communities in the African Region. Brazzaville: WHO Regional Office for Africa; 2017 (https://apps.who.int/iris/handle/10665/260112). 18 All references accessed 24–27 July 2023. 4 22 Why assess coverage from yellow fever vaccination campaigns It is critical to have a clear understanding of the impact of a campaign to measure its quality and ascertain that equitable access was achieved during implementation. Monitoring helps to identify areas that require targeted approaches or adjusted strategies to achieve high population immunity. Such information is also important for reporting to stakeholders. Yellow fever (YF) vaccination campaigns are unique for coverage assessment purposes because they target a gender-inclusive population across a wide age bracket representing different life stages, from child to adolescent and adult. Methodologies to measure coverage should be modified accordingly, with well-designed data collection tools adapted for the age group covered by the campaign, including subanalysis by gender. All surveyors should be well trained and aware of the need to focus on all ages covered by the campaign. A separate guidance document on the different options to assess coverage following a reactive vaccination campaign for YF is available. Countries are encouraged to refer to it. In this document, we present the two main types of coverage monitoring and assessment. 5 - Assessing coverage from yellow fever vaccination campaigns EYE Strategy Country Toolkit Rapid convenience monitoring (RCM) is conducted during or immediately following the campaign. It aims to identify areas or subpopulations with low coverage to facilitate targeted interventions to boost vaccination coverage (such as course-corrective actions during campaign or mop-up vaccination activities). Post-campaign vaccination surveys are conducted shortly after the campaign is completed. These aim to provide statistically valid estimated vaccination coverage in the target area. The survey methodology requires careful design by skilled personnel with statistical training and familiarity with methods such as WHO vaccination coverage cluster surveys. Planning and budgeting for monitoring activities including RCM and vaccination coverage surveys should be incorporated from the inception and initial organization of the campaign. Reporting on the outcomes of monitoring activities should be shared in a timely manner with regional focal points, who will facilitate reporting to the Eliminate Yellow fever Epidemics (EYE) Strategy programme management group. Rapid convenience monitoring The most important objective of RCM is to identify unvaccinated people to improve the quality of the campaign. Additional goals include identifying reasons for non-vaccination and planning and executing rapid corrective 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 23 action. RCM data provide information on the general performance of a preventive mass vaccination campaign (PMVC) or reactive vaccination campaign (RVC). The data suggest ways to refine strategies to include the hardest-to-reach subpopulations and ensure equitable coverage. RCM produces a pass/fail assessment of the areas surveyed, not a coverage assessment. RCM data are collected using methods that are not designed to be representative of the population targeted for the campaign; they therefore do not produce valid coverage estimates. RCM should be used while the campaign is ongoing (referred to as intra-campaign RCM). Post-campaign independent monitoring using RCM can be used to highlight at-risk areas with inadequate coverage, although such monitoring will not provide reliable coverage estimates. A well-designed post-campaign vaccination coverage survey should be planned at the inception phase of the campaign. Intra-campaign RCM is designed to inform rapid course-corrective action during the campaign. Such monitoring therefore requires rapid analysis and provision of summaries to field operatives so that communication and vaccination activities can be adjusted to improve coverage. Intra-campaign RCM should start with in-house monitoring, selecting geographical areas – such as neighbourhoods or villages – where unvaccinated people (in the target age group, typically 9 months to 60 years of age) are more likely to be found. A direction is selected at random, and monitoring is started with the first household. If the household contains eligible people, the in-house monitoring form should be completed, indicating whether they received vaccination during the current campaign and, if not, the reasons for being unvaccinated. The survey should be continued until 15 households containing at least one eligible person have been interviewed. The assessment should be complemented by out-of-house monitoring in areas where people may congregate (such as markets or playgrounds). This should document the immunization status of up to 10 campaign-eligible people. Lastly, school monitoring should be considered when a significant proportion of the campaign target age group are enrolled in schools, and when schools are used as temporary vaccination posts, as is typically the case in YF campaigns. Post-campaign independent monitoring occurs immediately after all vaccination campaign activities have been completed. It should be conducted using RCM methodology in all areas where initial data (coverage and intra-campaign RCM) or local knowledge suggest poor coverage. The main objective of post-campaign independent monitoring is to provide details of areas that may have pockets of unvaccinated people and require further campaign activities or mop-up vaccinations, and the characteristics of these populations. For example, if unvaccinated people are identified, they can be targeted during mop-up vaccination activities 1–2 weeks after the campaign. In addition, such monitoring provides independent and critical information on campaign performance that will be useful for future campaigns. The same principles apply to both PMVC and RVC monitoring; however, the PMVC preparation schedule allows greater time for planning. Extensive guidance on vaccination coverage surveys can also be found in the WHO reference manual for cluster surveys.19 EYE Strategy Country Toolkit 19 World Health Organization vaccination coverage cluster surveys: reference manual. Geneva: World Health Organization; 2018. (https://extranet.who.int/iris/restricted/handle/10665/272820, accessed 27 July 2023). 5 24 EYE Strategy Country Toolkit How to assess vaccine coverage The vaccine coverage figure is the percentage of people in the target age group who have been immunized during a vaccination campaign. It can be calculated for the entire target population and also by gender, age group and location, based on administrative data (for example, projected age structure and target populations). Administrative coverage should always be complemented by well-planned coverage assessments or surveys. Vaccine coverage (%) = Number of doses administered during vaccination campaign Total number of people in target age group × 100 Administrative vaccine coverage Administrative vaccine coverage is estimated during the campaign based on the data collected each day on the tally sheets and census data. Although quite informative, significant limitations exist with these estimates. First, reliable and updated figures for the demographic data (denominator) are not always available. Second, some of the people living outside the target area might have been vaccinated during vaccination campaign, leading to an underestimation of the true coverage. The information included in the tally sheets facilitates the calculation of the vaccine utilization rate. This quality indicator is equal to the number of doses administered divided by the number of doses used. It is calculated by team, by day and by site, based on the information included in the tally sheets. An abnormal utilization rate (either less than 85% or more than 100%) should be checked immediately. Vaccination coverage surveys Vaccination coverage surveys are essential for demonstrating the impact of vaccination campaigns and for helping to fulfil reporting requirements for reactive and preventive campaigns. Such surveys yield more reliable numbers and provide crucial information on the quality of vaccination campaign activities, such as reasons for non-vaccination and proportion of invalid doses (doses administered to people outside the target age group or outside the target area). Various methods can be used to estimate vaccine coverage (such as cluster sampling and lot quality assurance surveys). Very detailed granular vaccination coverage surveys require a high investment of planning and resources. The choice of method depends on the objectives and available resources. Countries with campaigns funded by Gavi, the Vaccine Alliance, should ensure that their choice of survey design meets current guidance standards for design and implementation. The WHO reference methods for the estimation of vaccination coverage were updated in 2018,20 and provide in-depth guidance on how to design and implement high-quality vaccination coverage surveys. The design should take into account the diversity of subpopulations present in the coverage area, and should include data collection on key variables such as age, gender and relevant sociodemographic indicators. 20 World Health Organization vaccination coverage cluster surveys: reference manual. Geneva: World Health Organization; 2018 (https://iris.who.int/handle/10665/272820, accessed 28 November 2023). 5 25 Probability-based sampling and two-stage design WHO recommends probability-based sampling at each stage of vaccination coverage survey design. Two-stage designs may be used for coverage surveys. They require a random sample of units (such as households) to be selected from each primary sampling unit – typically a census enumeration area such as a town or settlement. All eligible people in the selected households should be interviewed, and the results compiled on standardized questionnaires by skilled trained interviewers. It is recommended not to restrict the sample based on residency status (for example, visitors and recent arrivals should be included). In YF campaigns, a vaccination card is provided. Adults should be asked for their vaccination card and checked for name and identifying details such as gender and age. For children, the principal caregiver is requested to show the vaccination card, and the child is then recorded as vaccinated or unvaccinated in a standard questionnaire. Specific statistical packages are needed to calculate the point estimates of coverage in the sample, which are then used to obtain confidence intervals. Although cluster surveys are easier to conduct, they have important limitations in terms of data analysis (for example, their design does not facilitate identification of areas with low coverage, and is not powerful enough to conduct multistratified analyses). Importantly, special populations such as refugees or internally displaced people should be taken into account during the planning stages, as they may have an impact on the design of high-quality vaccination coverage surveys. Further reading 21 Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://www.who.int/publications/i/item/9789241511254). Training for mid-level managers (MLM): module 7: the EPI coverage survey. Geneva: World Health Organization; 2008 (https://www.who. int/publications/i/item/9789241511254). 21 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 5 26 The need for strong advocacy, social mobilization and communication The presence of yellow fever (YF) cases and transmission may raise community fears. Similarly, the planning and implementation of a large vaccination response necessitates good communication and engagement with communities to ensure success, with equitable access and uptake across genders and among all at-risk subgroups. Advocacy at all levels, from national to community, helps to ensure that all partners are engaged, and that messages are commonly understood and agreed upon. At subnational and community levels, methods of communication and social mobilization activities help to build trust and momentum to engage people and ensure the success of YF vaccination efforts. Tailored messaging and engagement strategies are particularly important in helping to reach special population groups that may have barriers and/or hesitancy to accepting and accessing vaccination. All communication and social mobilization activities should consider the local context and use appropriate tools, language and media to convey messages. How to implement advocacy, social mobilization and communication strategies Field procedures for advocacy, social mobilization and communication, along with community engagement and behaviour change, are summarized below. Advocacy Advocacy activities should be carried out by national advocacy, social mobilization and communication subcommittees. Key messages in support of the preventive mass vaccination campaign (PMVC) should be developed. These should be simple, clear and easy to understand for the target population, and pre-tested before dissemination in local languages. Political leaders, goodwill ambassadors and local celebrities should be engaged and briefed to influence opinion leaders. Appropriate influential media channels should be used to reinforce the commitment of decision-makers to the vaccination campaigns. 6 - Advocacy, social mobilization and communication for yellow fever campaign vaccination activities EYE Strategy Country Toolkit 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 27 Examples of social mobilization actors include: • district communication focal points: the key people responsible for the organization, coordination and monitoring of social mobilization activities, who identify and train social mobilizers; • mobilizers, who are recruited based on their residence, credibility and legitimacy to provide information in the target community, their oral and communication skills adapted to their community, and their experience in similar fieldwork; • key partners and stakeholders, including community health workers, local authorities, community and religious leaders, town criers, civil society groups, local media, nongovernmental organizations (NGOs), health committees, professional associations, the private sector, schools, opinion leaders and religious groups; • town criers, who adapt the information to their local context and travel where the mobilizers cannot go, can speak the local language and are known and trusted by the population. Examples of social mobilization activities include: • training of focal points, mobilizers and town criers on key messages, activities and use of communication materials and channels; • activities undertaken by mobilizers, including focal points, such as: • planning and coordinating activities; • identifying and communicating with local partners; • fixing monitoring indicators, timelines and responsibilities; • organizing meetings with local leaders and stakeholders; • mobilizing social networks, including town criers; • obtaining input from locals, with care to consider specific needs or considerations for communication with different age groups and genders; • helping to prepare and display communication materials; and • identifying and implementing communication strategies for hard-to-reach populations; • organization of meetings and workshops, ensuring community acceptance and support, and adapting solutions to a specific local situation; • monitoring and evaluating the effectiveness of social mobilization activities at the community level to inform future strategies; • in the case of school involvement in social mobilization, obtaining an agreement between the ministries of health and education. Social mobilization Social mobilization brings together community members and other stakeholders to strengthen community participation for sustainability and self-reliance. It generates dialogue, negotiation and consensus among a range of players. Social mobilization should be designed to reach all members of the community through the traditional channels of social networks. A social mobilization checklist should be used, including attributes of high-quality community engagement activities (such as key messages used, community leaders or influencers attending/ presiding at meetings, opportunities for audience questions) to help monitoring and tracking activities. EYE Strategy Country Toolkit 6 28 Communication Planning for any communication or engagement activity starts at the national level, after political commitment and consensus on the core programmatic aspects of the PMVC are agreed upon. There are four critical components of communications planning: • establishing or reinvigorating a national advocacy, social mobilization and communications subcommittee (and district-level equivalent), with a focus on specific communication needs for YF; • developing a communications and demand-generation plan (based on a needs assessment and specific, measurable, attainable, relevant and time-bound (SMART) criteria); • preparing for management of issues (such as negative publicity, rumours and adverse events following immunization) through early engagement and consultation with key immunization stakeholders and community leaders, including development of a crisis communication plan; • planning monitoring and evaluation of the effectiveness of the communications activities (especially among populations at higher risk of not being vaccinated) and the reasons for non-vaccination during the campaign, to inform any mop-up vaccination activities. Main messages should be communicated to the population, tailored to circumstances. It is recommended that core content should cover what YF is and why it is a concern, what vaccination activity is occurring, and how people can protect themselves and access vaccination. Examples include the following: Specific or support messages should be designed – such as safety, mode of administration (including fractional dose use), tailored outreach (for example, specific age or gender cohorts if appropriate, marginalized groups, informal settlements) and the vaccination calendar. These should be based on a rapid assessment of the barriers to YF vaccine uptake, and on the vaccination context (for example, whether reactive or routine vaccination). Health-care workers, vaccinators and medical staff at the district level are additional targets for communication – this is especially important when a fractional dose strategy is employed. Messages should include the topics described for the population and specific points such as product characteristics and administration, the importance of reporting and notifications, and rumour tracking. EYE Strategy Country Toolkit YF is a serious disease that is spread by infected mosquitoes. It can cause jaundice and result in death. YF disease can be prevented by a safe and effective vaccine. Get vaccinated at the nearest health centre or vaccination post at no cost, and be protected for life. Almost everyone should be vaccinated (all children older than 9 months and most adults to the age of 60 years). Protect yourself and your family from mosquito bites and remove mosquito breeding sites (such as water collecting in discarded vehicle tyres). Seek medical care if you experience symptoms of YF. There is a YF vaccination campaign from_____ to _____. 6 29 EYE Strategy Country Toolkit Communication tools and channels The appropriate media channel mix depends on the traditional channels, language and tools, target population, characteristics of the epidemiologic situation (such as outbreaks) and communication budget. It may include: • town criers; • spots on local radio channels; • local press releases; • text (SMS) and audio messaging; • social media posts; • folk media output (roadside shows, street dramas, community events, events in places of worship); • community meetings (such as chief meetings, church meetings, women’s groups, civil society meetings); and • visual materials, such as leaflets/brochures distributed in communities; posters in health centres, vaccination posts and other public places (for example, schools, places of worship and markets); and banners in health centres, vaccination posts and/or on the main road. In the case of joint/combined campaigns with different target age groups, communication should be tailored. Rumour tracking should be employed to monitor uptake and community perceptions of any YF vaccination campaigns. Community engagement The aim of community engagement efforts is to establish a two-way dialogue that serves to empower communities to identify and adapt solutions that are specific to their local situation. Close engagement with local communities – especially with community and religious leaders – will contribute to resolving any context-specific barriers to access and uptake. Meetings should be organized at the province and districts levels. All the district managers, communication focal points, community and religious leaders, relevant NGOs, educational staff, health staff and mobilizers should be invited to the provincial meetings. All the key community leaders and representatives, including the leaders of marginalized groups, religious leaders, NGOs, educational staff, women and youth social groups, health staff, mobilizers and town criers should be invited to the district meetings. Behaviour change communication Behaviour change communication aims to change knowledge, attitudes and practices among target audiences to promote uptake of vaccination. It is also helpful to address the concerns of groups of people who may be hesitant to accept the YF vaccine. A rapid assessment of perceptions of the YF vaccine and the delivery strategy prior to a campaign can identify potential barriers to vaccine uptake. The communication focal point or social scientists should be involved in such an evaluation. Communication efforts geared towards communities require careful research, design and adaptation to specific populations through appropriate channels and messages. Messages should address knowledge gaps, misperceptions and issues of concern. 6 30 Vaccination with YF fractional doses When an emergency situation occurs and the vaccine supply is insufficient, countries may decide to use fractional doses of the vaccine to contain the epidemic. Characteristics of fractional doses and the reasons for administering partial instead of full doses must be explained clearly to vaccinators, medical staff, health-care workers and social mobilizers, in order to correctly inform the population. EYE Strategy Country Toolkit How to tailor a communication and social mobilization plan in the context of preventive mass vaccination campaigns (PMVCs) The district communications focal point should be identified. The main messages and supporting messages should be defined. Messages and materials should be pre-tested with target audiences representing a broad scope of ages and genders, and should be updated prior to production based on feedback. Messages and materials should be disseminated through appropriate communication channels such as radio programmes, social media such as WhatsApp, social mobilization, home visits, town criers and interpersonal communications. Identification of social mobilizers by the communication focal point may take into account the credibility and respectability of the mobilizers. This is particularly important for hard-to-reach or marginalized populations. The social mobilizers must be carefully trained on the main and specific messages in order to disseminate accurate and documented information. Communication and social mobilization activities in specific situations Reactive vaccination in the context of a YF outbreak During an outbreak, people’s behaviour is a critical factor, and efforts should be made to provide information and mobilize communities as part of the outbreak response. In high-risk countries, it is essential to plan a risk communication strategy in the event of a future outbreak. A district communications focal point should be identified in advance or quickly after the onset of the outbreak. The information must be relayed to the community quickly by the identified stakeholders and influencers. Specific pre-defined key messages should be ready at the national level, and tailored with the focal point to fit local requirements in the event of an outbreak (for example, language, type of population and environment). Main messages should at the very least address the following: • that an outbreak has been detected in the area or an area nearby; • what YF is, and how it is transmitted; • the need to get vaccinated, with dates, place and targets of the vaccination campaign; • the fact that YF vaccine is safe, effective and free of charge; • how to protect people from mosquito bites and reduce mosquito breeding sites (in discarded waste items such as vehicle tyres, tins and jars); and • where to seek medical care in case of symptoms. 6 31 EYE Strategy Country Toolkit Specific messages include the following: • Fractional doses of YF vaccine are as safe and effective as full dose vaccines to provide protection during an outbreak. • The fractional dose is efficient against the outbreak, but people may need to be re-vaccinated with a full dose in the future to obtain full and long-term protection. Rumour-tracking activities by national or regional health promotion or communication officers can help with anticipating and responding to false and harmful information regarding vaccination with fractional doses. Communication regarding serious adverse events following immunization Given the devastating impact of misinterpretation and miscommunication of vaccine safety issues on vaccination programmes, it is critical that national technical and social mobilization committees develop strong training and communication materials on adverse events following immunization (AEFIs) during the preparatory phase. Although serious AEFIs due to YF vaccination are extremely rare, coincidental occurrence of a serious event and sensational media coverage have the ability to undermine immunization activities seriously. Vaccine administration error-related reactions can also occur, and can negatively affect the programme if not addressed immediately and effectively. Specific messages include the following: • The YF vaccine is safe and well tolerated. • As with all vaccines, side-effects may occur after vaccination and can be serious in very rare instances. • Medical advice should be sought in the case of unexpected symptoms after vaccination. Communication regarding YF in non-human primates In areas with large non-human primate (NHP) populations and unusual patterns of sickness or death in the NHP population (in the Americas), there may be a need to communicate messages to discourage the unnecessary killing of NHPs. While YF is a disease that can affect both humans and NHPs, there is no benefit to killing NHPs to control YF outbreaks. People in areas at risk of YF can be protected through vaccination, and additional measures to reduce exposure to mosquitoes are a complementary activity that can reduce risks in outbreak settings. Specific messages include the following: • Vaccination is the first line of protection from YF. • Taking steps to reduce the likelihood of mosquito bites can complement vaccination strategies in high-risk outbreak settings (such as urban areas). • Killing or attempting to reduce populations of NHPs is not recommended, and does not stop YF outbreaks. 6 32 Monitoring and evaluating impact Documentation and analysis of the impact, successes and challenges encountered are core components of communication and social mobilization strategies. Variables that are useful to track include the scale and description of communication and social mobilization activities undertaken, the degree of penetration in vulnerable at-risk communities, and any rumours and reasons for non-vaccination, with a breakdown by age, gender and any relevant descriptors (such as specific sociocultural groups). Lessons learned should be documented to inform future vaccination activities, including any other vaccination activities with other antigens. Further reading 22 Adverse events following immunization (AEFI) communication [online course]. New York: United Nations Children’s Fund; 2017 (https://agora.unicef.org/course/info.php?id=10708). Communicating about vaccine safety: guidelines to help health workers communicate with parents, caregivers, and patients. Washington DC: Pan American Health Organization; 2020 (https://iris.paho.org/handle/10665.2/53167). Communication and social mobilization in yellow fever mass vaccination campaigns: 10 points from field experience. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/156053). Communication for Development (C4D) [online course]. New York: United Nations Children’s Fund; 2023 (https://agora.unicef.org/ course/info.php?id=11146). Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://iris.who.int/handle/10665/330568). Reaching every district (RED): a guide to increasing coverage and equity in all communities in the African Region. Brazzaville: WHO Regional Office for Africa; 2017 (https://apps.who.int/iris/handle/10665/260112). WHO, USAID, UNICEF. Communication for polio eradication and routine immunization : checklists and easy reference guides. Geneva: World Health Organization; 2002 (https://iris.who.int/handle/10665/67220). 22 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 6 33 Fig. 8. Stages of PMVC preparation and implementation The rationale for monitoring yellow fever vaccination campaigns The quality of a yellow fever (YF) preventive mass vaccination campaign (PMVC) is determined by its impact on disease incidence, assessed through disease surveillance. It is critical to monitor the quality of the PMVC throughout the process of preparation and implementation to understand any challenges and bottlenecks undermining its quality, and to use the information to improve future PMVCs and routine immunization. After completion of the PMVC, reporting on administrative coverage and a validated vaccination coverage survey 23 are used to measure the impact of the campaign to boost population immunity. At all stages of PMVC preparedness and implementation (Fig. 8), monitoring helps to identify challenges and best practices that can be used to trigger corrective actions and document successes. The results of monitoring are reviewed by the Eliminate Yellow fever Epidemics (EYE) Strategy to help inform useful supports and lessons learned. Monitoring also helps with assessment of whether quality indicators and targets have been developed for use by countries for activities carried out before, during and after the PMVC. Countries may wish to focus on a few of the indicators or add other indicators that are more relevant to their situation. Indicators provide information on the quality of different aspects of the PMVC (such as training, monitoring, supervision and logistics), and highlight specific issues, thereby increasing accountability. A suggested list of indicators for the different phases of the PMVC that should be monitored is included in the WHO field guide Planning and implementing high- quality supplementary immunization activities for injectable vaccines,24 and is summarized below. 7 - Monitoring the quality of vaccination campaigns                               23 World Health Organization vaccination coverage cluster surveys: reference manual. Geneva: World Health Organization; 2018 (https://extranet.who.int/iris/restricted/handle/10665/272820, accessed 27 July 2023). 24 Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://extranet.who.int/iris/ restricted/handle/10665/330568, accessed 24 July 2023). EYE Strategy Country Toolkit 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 34 Pre-PMVC indicators Data for monitoring the following indicators can be obtained from programme information and PMVC readiness assessment data. These indicators can be monitored at the national level, and should be communicated through regular timely updates to the regional level. EYE Strategy Country Toolkit Indicators include: • approval of donor funding at the national level (target: budget available at the national level at least nine months prior to the planned PMVC date); • approval of local/government funding at the national level (target: budget available at the national level at least nine months prior to the planned PMVC date); • timing of orders of bundled vaccines and supplies (target: orders made at least 9–12 months prior to the PMVC); • availability of operational funds at the district level (target: budget available at the district level at least four months prior to the planned PMVC date in all districts); • completion of a national PMVC logistics plan (target: plan completed and approved six months before the PMVC at the latest); • completion of district-level microplanning workshops (target: workshops completed by all districts at least six months prior to the planned PMVC date); • levels of PMVC readiness assessed at the national level, using a readiness checklist, 12, 9, 6, 3 and 2 months prior to the start date of the PMVC (target: national-level PMVC readiness information documented 12, 9, 6, 3 and 2 months before the PMVC); • percentage of districts conducting a readiness assessment at least twice within the eight weeks prior to the PMVC (target: 30% of districts); • percentage of districts with planned quantities of vaccine and devices at least two weeks prior to the start of the PMVC (target: all districts); • number and percentage of households surveyed within the two weeks prior to the start of the PMVC who can identify the target disease, campaign dates, venues and target age groups (target: 95% of households). Monitoring indicators during PMVCs Data for monitoring the following indicators can be obtained from vaccine coverage data and monitored at the district level before they are sent to the national level. Such data should be communicated through regular timely updates to the regional level throughout the campaign. Indicators include: • percentage of vaccination posts assessed by supervisors or monitors during the PMVC (target: 100%); • percentage of vaccination sites assessed with no shortfalls of vaccines and equipment (target: 95%); • percentage of permanent fixed vaccination sites assessed with proper cold chain – refrigerators monitored daily and temperatures between 2 °C and 8 °C (target: 100%); • percentage of vaccine vials seen with vaccine vial monitor stage 3 or 4 (target: 0%); 7 35 EYE Strategy Country Toolkit • percentage of vaccination sites assessed where used syringes are placed immediately in safety boxes (target: 100%); • percentage of vaccination sites assessed where tally sheets are filled in correctly (target: 100%); • percentage of vaccination sites where vaccinators know and apply AEFI reporting procedures (target: 100%); • percentage of districts reporting daily information on the number of vaccine doses administered (target: 100%); • percentage of unvaccinated people (eligible for vaccination) detected during intra-campaign monitoring by district (target: <10%); • percentage of people (eligible for vaccination) monitored through in-house rapid convenience monitoring (RCM) who were not aware of the PMVC or timing and location of vaccination posts (target: <5%). Post-PMVC monitoring indicators A post-campaign summary report is a core product for measuring the impact of the campaign, documenting the challenges and successes, and meeting reporting requirements. Data for monitoring the following indicators can be obtained from intra- and post-campaign data, and can be monitored at the district level, with data sent to the national level. Such data should be communicated to the regional level within six weeks of completion of the campaign. There is also a requirement to report on vaccine utilization and AEFIs, as well as lessons learned. Indicators include: • number and percentage of targeted districts that have at least one area monitored through RCM during or after the PMVC (target: 100%); • number and percentage of unvaccinated people detected during post-campaign independent RCM, by district (target: <10%); • analysis of the numbers of unvaccinated people by age and gender, relative to the estimated proportions in the target population – in areas with specific subpopulations vulnerable to inequities, the analysis is recommended to consider coverage in different subgroups; • number and percentage of monitored areas not meeting the minimal level of people/households vaccinated that had remedial action taken within one week of the end of the PMVC (target: 100%); • number of people vaccinated and administrative vaccination coverage by district (target: at least 85%); • percentage of districts with vaccination coverage of at least 85%; • survey vaccination coverage by unit surveyed (target: at least 80%); • number of serious AEFIs by district; • vaccine utilization report according to most current recommendations and including wastage and number of doses remaining in-country at the end of campaign activities; • summary of lessons learned, key implementation challenges and documentation of best practices from the campaign. Fig. 9 sets out the key phases for the three stages of monitoring. 7 36 EYE Strategy Country Toolkit Fig. 9. Key phases for PMVC monitoring Readiness Pre-implementation (6 months prior to the start of the campaign) • Readiness assessment checklist (monthly, then weekly) • Microplanning, including adverse event following immunization (AEFI) monitoring, waste management, training and social mobilization • Cold-chain capacity assessment and logistics plan Quality assessment During implementation (throughout vaccination activities) • Intra-campaign independent monitoring • Comprehensive supportive supervision • AEFI reporting and response • Daily tally sheet updates and session reviews to guide course correction and mop-up vaccination activities Impact Post-implementation (within three months of campaign completion) • Post-campaign independent monitoring or lot quality assurance surveys • Vaccine utilization and AEFI summary • Post-campaign vaccination coverage survey assessment • Campaign report and lessons learned • Disease incidence (mid- to longer term) Further reading 25 Training for mid-level managers (MLM): module 7: the EPI coverage survey. Geneva: World Health Organization; 2008 (https://iris.who. int/handle/10665/337065). 25 All references accessed 24–27 July 2023. 7 Source: Adapted from World Health Organization. (2016). Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. World Health Organization. https://iris.who.int/handle/10665/330568 37 The importance of high-performing routine immunization Yellow fever (YF) cannot be eradicated. Routine immunization (RI) coverage is critical for YF control and should be pursued indefinitely. The YF vaccine is a safe and effective live attenuated vaccine. One dose provides lifelong immunity against YF. Vaccine coverage greater than 80% is necessary to interrupt local transmission of YF virus within a community, and ensure that sporadic unvaccinated cases do not generate secondary cases. However, with RI alone, it takes about 30 years to build population immunity to adequate levels to stop large-scale outbreaks. This is the reason preventive mass vaccination campaigns (PMVCs) are recommended, as these facilitate quick population protection, which is then maintained with RI (Fig. 10). 8 - Routine immunization (RI) for yellow fever EYE Strategy Country Toolkit 100 90 80 70 60 50 40 30 20 10 0 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 2.3 22.8 45.6 68.4 91.2 Pr op or tio n (% ) o f p op ul at io n pr ot ec te d Years after the intervention Years after the intervention Years after the intervention 100 90 80 70 60 50 40 30 20 10 0 80.0 55.1 26.6 0 0 82.3 77.9 72.2 91.2 68.4 100 90 80 70 60 50 40 30 20 10 0 (A) Routine childhood immunization (B) Preventative mass vaccination campaign Vaccine coverage security threshold (C) Combined vaccination strategy: Routine childhood immunization + one preventive mass vaccination campaign Fig. 10. Benefits of combining RI with PMVCs Low YF vaccine coverage poses an epidemic threat. High population immunity is required in all at-risk areas and populations to prevent YF epidemics (sporadic cases may continue to occur in unvaccinated individuals, but no epidemic amplification should occur). Pockets of unprotected individuals are at risk of epidemic amplification, with potential for spread in non- epidemic areas with favourable ecosystems. The root causes of low YF RI coverage are multiple and often non-YF-specific. These causes should be analysed carefully and addressed using systematic, integrated approaches for health system strengthening. RI is a long-term activity, and high vaccine coverage must be achieved and maintained indefinitely in all districts. 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 38 Special efforts and plans are needed to reach underserved populations and hard-to-reach communities (such as migrants, displaced people and children living in poor urban areas), as they represent potential sources of amplification and/or spread if they are unprotected (see Section 4 for more detailed guidance). Who should be vaccinated The YF vaccine should be administered to everyone aged 9 months and above in high-risk countries 26 (see Section 3 for more details). There are very few contraindications. The YF vaccine is contraindicated in children under 6 months of age, and is not recommended for those aged 6–8 months (infants under 9 months old being at higher risk of vaccine- associated encephalitis). Current issues with YF in routine immunization in high-risk countries There remain areas high-risk countries where not all children receive YF vaccination. In the WHO African Region, 25 countries at high risk have already introduced YF vaccine into their national RI schedule; 2 countries are expected to do so before the end of the EYE Strategy (as of December 2023). Coverage often remains low, however, with significant discrepancies from district to district. The main challenges for successful implementation of YF in RI include the following: • lack of political will; • limitations in continuous supply and cold chain facilities at peripheral sites; • missed opportunities for vaccination and challenges to assure equitable access – particularly for hard-to-reach populations, and those in urban slums, informal settlements, and fragile, conflict and vulnerable contexts; • difficulty in keeping records and inconsistent reporting practices; • insufficient funding; and • competing priorities and other vaccine introduction plans. How to ensure continuous vaccine supplies At the global level, there should not be a shortage of YF vaccine for RI. It is crucial that continuous supply of YF vaccines exists in all centres providing vaccination. To meet this goal, the following are required: • accurate forecasting of annual vaccine requirements; • timely placing of orders at the central level or to manufacturers; • receipt and distribution of vaccines at the peripheral level; and • monitoring and timely reporting of vaccine stocks at all levels to avoid any stock-outs. EYE Strategy Country Toolkit 26 Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Geneva: World Health Organization; 2018 (https:// www.who.int/publications/i/item/9789241513661, accessed 24 July 2023).iris/restricted/handle/10665/330568, accessed 24 July 2023). 8 39 How to achieve and sustain high RI coverage The reasons for low coverage need to be analysed, addressed and monitored carefully. They may include: • overly rigid vaccination practices routinely observed in some settings (for example, not giving the vaccine after 12 months, unwillingness to open a 10- or 20-dose vial for only one child, reluctance to administer several antigens at the same time); • a delay in administering the YF vaccine due to minor illnesses; and • in some sites, weak vaccine management. Mechanisms to address these include policy changes and refresher training opportunities for health-care workers involved in vaccinations. Regional and national technical advisory groups play a critical role in supporting countries during YF vaccine introduction and increasing equity of access. Countries are encouraged to seek advice from these groups. It is important to monitor RI coverage regularly (at least once a month) and intervene at the lowest level possible (at the district level at a minimum). Even if it is not included in the standard list of indicators, countries are encouraged to monitor YF vaccine coverage at the district level, in addition to diphtheria tetanus and pertussis and measles vaccine coverage, to assess performance of the RI programme. Catch-up strategies should be offered where applicable; for example, using the strategies outlined in the WHO handbook on the second year of life platform or other approaches.27 WHO recommends several strategies to maintain high RI coverage, including: • ensuring reliable YF vaccine stock and a regular supply of health facilities; • increasing political commitment and ensuring that children are vaccinated; • linking prevention of measles and YF, and improving all RI antigens coverage; • ensuring a catch-up strategy for missed opportunities, such as school checks and second year of life activities or other opportunities through adulthood and lifecourse; • close coordination with health implementing partners to ensure sustained RI delivery, including YF vaccine, in fragile, conflict and vulnerable contexts; • improving awareness among health personnel of the importance of YF vaccination; • achieving strong community engagement (through active and efficient communication and social mobilization efforts); and • using mass vaccination campaigns as opportunities also to strengthen RI systems. 27 A practical handbook for planning, implementing and strengthening vaccination in the second year of life. Geneva: World Health Organization; 2018 (https://extranet.who.int/iris/restricted/handle/10665/311642, accessed 28 July 2023). handle/10665/330568, accessed 24 July 2023). EYE Strategy Country Toolkit 8 40 Support available for YF vaccine introduction (technical and financial) Countries that are eligible for Gavi support should liaise early with the Gavi Senior Country Manager to request support. Gavi provides support for a one-dose routine vaccination schedule, as well as associated injection supplies. Countries are encouraged to introduce YF vaccination into RI prior to initiating the PMVC. Countries should ensure that their target vaccine introduction date and plans for preparatory activities are compatible with the timelines for the likely receipt of Gavi funds and vaccines. It will usually not be feasible for a country to introduce a vaccine less than 15–18 months after the Gavi application submission deadline. A vaccine introduction grant (VIG) is one-off financial support for countries eligible for Gavi support using the YF vaccine for the first time in the routine schedule. VIG funds are equivalent to US$ 0.80 per child in the birth cohort for the year of introduction, or a lump sum of US$ 100 000 (whichever is higher). The aim is to facilitate timely and effective implementation of critical activities in the national vaccine introduction plan in advance of a new vaccine introduction. Activities supported under VIGs or Campaign Operational Support (Ops) for reactive vaccination campaigns can be found in the Gavi support guidelines.28 Countries should refer to this document when planning and developing their budget for VIGs/Ops. The VIG may include – but is not limited to – health worker training, education, communication and social mobilization, microplanning, expansion or rehabilitation of cold chain equipment and additional vehicles if needed, and modifications to surveillance systems. Targeted country assistance (TCA) is financial support to countries for technical assistance to ensure quality planning and implementation of vaccination programmes. Technical assistance is intended to be targeted and tailored to countries’ needs – driven by the Expanded Programme on Immunization; to ensure country focus, transparency, accountability and differentiation; and to support vaccine and health system strengthening investments. TCA can be provided through core partners (WHO, United Nations Children’s Fund (UNICEF), United States Centers for Disease Control and Prevention (CDC) and the World Bank), and expanded partners including local institutions. Countries can identify their challenges and express their TCA needs through the joint appraisal, an annual review of Gavi’s support to each country. TCA complements the support that countries receive from Gavi for vaccines and health system strengthening. Regardless of Gavi eligibility, it is crucial that the country, WHO and UNICEF offices are contacted early for planning purposes and to support requests for: • conducting risk assessment, planning, organizing and implementing high-quality immunization activities; • building national capacity for social and behavioural communication to improve YF vaccine coverage, including public demand for quality YF immunization; • ensuring an equity lens to guarantee that all genders, and hard-to-reach and marginalized populations – including those living in fragile, conflict and vulnerable contexts – are considered in developing immunization service planning; and • identifying local and international partners and their potential roles, including technical assistance and social mobilization. 28 GAVI support guidelines [website]. Geneva: Gavi, the Vaccine Alliance; 2022 (https://www.gavi.org/our-support/guidelines, accessed 29 November 2023). EYE Strategy Country Toolkit 8 41 Why conduct PMVCs and catch-up activities PMVCs are the most efficient approach to increase population immunity rapidly in high-risk areas and eliminate the risk of epidemics on a short-term basis. However, protection induced by the vaccine wanes rapidly, becoming nonexistent after 25 or 30 years. Therefore, an optimal, sustained public health impact can be achieved when PMVCs are combined with RI. Catch-up activities should enable to reach undervaccinated cohorts or pockets of populations where there is documented low RI coverage or gaps in population immunity related to one of the following situations: • delayed introduction of YF vaccine in RI; • underperforming RI; or • potential dilution of the effect of PMVCs due to population movements. Catch-up activities should not be a substitute for a well-functioning RI system, but can mitigate and close immunization gaps in high-risk countries. Activities should target age-specific vaccination gaps or geographical areas where population immunity is low (Fig. 11 A and B). Catch-up activities are resource-intensive; they need to be planned, and require the same coordination efforts and fixed costs as large-scale PMVCs. It is necessary to access high-quality vaccine coverage data to determine target areas. It is crucial to develop a plan to overcome potential challenges for successful catch-up activities – particularly regarding barriers to vaccine access of the targeted populations, waste management and monitoring of adverse effects following immunization. Ongoing monitoring and evaluation of vaccine coverage and addressing implementation challenges to build on lessons learned are key to implementing successful catch-up activities. 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 Years after the intervention Years after the intervention Years after the intervention Years after the intervention Years after the intervention (A) Routine childhood immunization (B) Preventative mass vaccination campaign (A) Routine childhood immunization (B) Preventative mass vaccination campaign 2.3 12.8 25.6 52.2 74.5 80.0 45.1 26.6 82.3 77.9 72.2 74.5 62.2 (C) Combined vaccination strategy with delayed introduction of routine immunization : The population immunity gap is filled by a catch-up campaign 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 2.3 22.8 36.6 49.4 54.2 P ro po rt io n (% ) o f p op ul at io n pr ot ec te d P ro po rt io n (% ) o f p op ul at io n pr ot ec te d 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 80.0 55.1 26.6 0 0 0 0 82.3 77.9 63.4 75.2 70.4 Vaccine coverage security threshold Vaccine coverage security threshold (C) Combined vaccination strategy with underperforming routine immunization: The population immunity gap is filled by a catch-up campaign 1 10 20 30 40 Years after the intervention Fig. 11A. Benefits of filling population immunity gaps with catch-up campaigns EYE Strategy Country Toolkit 8 Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 42 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 1 10 20 30 40 Years after the intervention Years after the intervention Years after the intervention Years after the intervention Years after the intervention (A) Routine childhood immunization (B) Preventative mass vaccination campaign (A) Routine childhood immunization (B) Preventative mass vaccination campaign 2.3 12.8 25.6 52.2 74.5 80.0 45.1 26.6 82.3 77.9 72.2 74.5 62.2 (C) Combined vaccination strategy with delayed introduction of routine immunization : The population immunity gap is filled by a catch-up campaign 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 2.3 22.8 36.6 49.4 54.2 Pr op or ti on (% ) o f p op ul at io n pr ot ec te d P ro po rt io n (% ) o f p op ul at io n pr ot ec te d 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 80.0 55.1 26.6 0 0 0 0 82.3 77.9 63.4 75.2 70.4 Vaccine coverage security threshold Vaccine coverage security threshold (C) Combined vaccination strategy with underperforming routine immunization: The population immunity gap is filled by a catch-up campaign 1 10 20 30 40 Years after the intervention Fig. 11B. Benefits of filling population immunity gaps with catch-up campaigns How to monitor YF RI activities and performance For YF coverage, historical coverage data should be monitored and compared with surveillance data, or any available serosurvey data. It is vital to ensure that the YF vaccine is included in fully immunized child estimates, and to monitor measles rubella-containing vaccine relative to YF vaccination coverage. It is recommended that YF vaccination is monitored using home-based vaccination records for the following reasons: • to track and document immunization services (and additional health interventions received by individuals), because these records are valid for life and are linked to a process for obtaining the International Health Regulations (2005) (IHR) card for international travel; • to reinforce public health monitoring and reporting; • to help to improve caregivers’ awareness and knowledge of the schedule; and • to facilitate communication between health workers and caregivers. In addition, WHO encourages use of computerized tools for district data monitoring. Adverse events following immunization (AEFIs) should be monitored. Rare but possibly serious, AEFI incidence should be monitored at all levels. The procedures for AEFI monitoring are described in a WHO field guide 29 (see Section 3 for more details). EYE Strategy Country Toolkit 8 WHO has developed key indicators for monitoring RI performance. These should be monitored at various levels, including: • national-level indicators on the proportion of districts achieving at least 80% YF routine vaccination coverage of the annual infant cohort; • district-level indicators on the proportion of the eligible infant population vaccinated against YF in newly introduced RI programmes at the district level, and the proportion of the eligible infant population vaccinated against YF in established RI programmes at the district level. Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 43 Further reading 30 Establishing and strengthening immunization in the second year of life: practices for vaccination beyond infancy. Geneva: World Health Organization; 2018 (https://iris.who.int/handle/10665/260556). GAVI support guidelines Geneva: Gavi, the Vaccine Alliance; 2022 (https://www.gavi.org/our-support/guidelines). Immunization in practice: a practical guide for health staff. Geneva: World Health Organization; 2015 (https://iris.who.int/ handle/10665/193412). Increasing immunization coverage at the health facility level. Geneva: World Health Organization; 2002 (https://iris.who.int/ handle/10665/67791). Introduction and implementation of new vaccines: field guide. Washington DC: Pan American Health Organization; 2010 (https://iris. paho.org/handle/10665.2/49176). New vaccine introduction: checklist for planning communication and advocacy: World Health Organization vaccine safety supporting document. Copenhagen: WHO Regional Office for Europe; 2017 (https://iris.who.int/handle/10665/346171). Practical guide for the design, use and promotion of home-based records in immunization programmes. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/175905). Planning guide to reduce missed opportunities for vaccination. Geneva: World Health Organization; 2017 (https://iris.who.int/ handle/10665/259202). Principles and considerations for adding a vaccine to a national immunization programme: from decision to implementation and monitoring. Geneva: World Health Organization; 2014 (https://iris.who.int/handle/10665/111548). Reaching every district (RED): a guide to increasing coverage and equity in all communities in the African Region. Brazzaville: WHO Regional Office for Africa; 2017 (https://apps.who.int/iris/handle/10665/260112). Robertson S. The immunological basis for immunization series – module 8: yellow fever. Geneva: World Health Organization; 1993 (https://nccvmtc.org/PDF1/1_034.pdf). Vaccines and vaccination against yellow fever: WHO Position Paper – June 2013. Weekly Epidemiological Record. 2013;88(27):269–84 (https://apps.who.int/iris/handle/10665/242089). 29 Yellow fever: surveillance of adverse events following immunization against yellow fever – field guide for staff at the central, intermediate and peripheral levels. Geneva: World Health Organization; 2010 (https://apps.who.int/iris/ handle/10665/70216, accessed 24 July 2023). 30 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 8 44 Why conduct preventive mass vaccination campaigns Preventive mass vaccination campaigns (PMVCs) are a key strategy for yellow fever (YF) control. High vaccination coverage (i.e. >80%) is necessary to interrupt local transmission (human–mosquito–human) of the YF virus within the community, and to ensure that sporadic unvaccinated cases do not generate secondary cases. A PMVC is the most efficient approach to increase population immunity rapidly in high-risk areas and eliminate the risk of epidemics on a short-term basis. However, protection from PMVCs diminishes rapidly in populations if birth cohorts are not vaccinated continually. Without continual routine immunization (RI), population immunity becomes nonexistent after 25–30 years. Therefore, an optimal, sustained public health impact can be achieved when PMVCs are combined with RI (Fig. 12). 9 - Yellow fever preventive mass vaccination campaigns Years after the intervention Years after the intervention Years after the intervention (A) Routine childhood immunization (B) Preventative mass vaccination campaign P ro po rt io n (% ) o f p op ul at io n pr ot ec te d 1 10 20 30 40 Vaccine coverage security threshold 1 10 20 30 40 100 90 80 70 60 50 40 30 20 10 0 1 10 2.3 22.8 45.6 68.4 91.2 20 30 40 100 90 80 70 60 50 40 30 20 10 0 80.0 55.1 26.6 0 0 82.3 77.9 72.2 91.2 68.4 100 90 80 70 60 50 40 30 20 10 0 (C) Combined vaccination strategy: Routine childhood immunization + one Preventative mass vaccination campaign Fig. 12. Benefits of combining RI with PMVCs EYE Strategy Country Toolkit It is important to plan for nationwide rather than subnational PMVCs. Current patterns of YF transmission, with frequent exchanges between sylvatic and rural areas, are such that subnational PMVCs do not seem a reasonable control strategy, and only national approaches provide comprehensive risk mitigation. Efforts should be made to complete PMVCs in as short a time as possible, to boost immunity nationwide and decrease the risk of outbreaks. 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles Source: World Health Organization. (2018). Eliminate Yellow Fever Epidemics (EYE): strategy partners meeting report: Geneva, Switzerland, 9–10 May 2017. World Health Organization. https://iris.who.int/handle/10665/279723. 45 EYE Strategy Country Toolkit Campaign phasing should be developed on a country-by-country basis, based on: • risk analysis: looking at the risk of amplification and spread, RI coverage, history of reactive and preventive campaigns and their coverage; • existing vulnerability: population density and movement, transportation hubs, areas with low vaccination coverage, barriers to access or insecurity, and so on; and • ecological criteria: areas of moist savannah that are the zones of YF emergence in Africa, and forested areas where the YF virus circulates should be given priority to protect populations at the source. Programmatic issues such as national and local capacity, logistics for vaccine distribution (such as transportation, cold chain management and storage) and competing priorities are important considerations in the perspective of successful PMVC implementation. While planning and preparation must be tailored to the unique elements of a YF vaccination activity, efficiencies may be realized through complementary planning and preparation with other mass interventions, such as measles campaigns (for example, some training activities could serve both types of campaign and include tailored messages to each). 31 Technical resources for improving immunization coverage and equity [online database]. Geneva: World Health Organization; 2021 (https://www.technet-21.org/en/library/main/7095-technical-resources-for-improving-immunization- coverage-and-equity, accessed 27 July 2023). 32 Vaccines and vaccination against yellow fever: WHO Position Paper – June 2013. Weekly Epidemiological Record. 2013;88(27):269–84 (https://apps.who.int/iris/handle/10665/242089, accessed 24 July 2023). 33 Cibrellus L, Lingani C, Fernadez K, Djingarey MH, Perea WA, Hugonnet S. Risk assessment and meningococcal A conjugate vaccine introduction in Africa: the District Prioritization Tool. Clinical Infectious Diseases. 2015;61(Suppl 5):S442–50. PMVCs should include a special plan to protect hard-to-reach communities and underserved populations (such as migrants, displaced people and children living in poor urban areas), as they represent potential sources of amplification and/or spread if unprotected (see Section 3 for more guidance). Planning for inclusion of these subpopulations and reducing any barriers to access can be supported by the resources in WHO’s technical resources for improving immunization coverage and equity.31 YF vaccines One dose of the YF vaccine provides lifelong immunity against the disease.32 The YF vaccine should be administered to everyone aged 9 months to 60 years, with special consideration for pregnant and lactating women (see Section 3 for more details). YF vaccination cards are lifelong records that are directly connected to the process of obtaining an International Health Regulations (2005) (IHR) card for international travellers. These cards should be kept indefinitely. How to set priorities at the subnational level In countries with large target populations, national PMVCs are mounted in multiple phases of subnational increments over several years, in a similar way to the introduction of the meningococcal meningitis A vaccine.33 In those circumstances, in-country prioritization is required. In-country prioritization based on YF epidemic risk will not be necessary in countries where PMVCs will be conducted within a year (even if conducted in successive phases). 9 46 Pragmatic considerations should be incorporated in the decision-making process for campaign phasing, as follows: • Except during emergencies, PMVCs may not be feasible in some areas during the rainy season (e.g. because of physical constraints to access). • Capital cities located near the YF emergence zones (moist savannah) have an increased risk of urban outbreaks and should be prioritized. • The organization of joint vaccination campaigns is recommended to help achieve efficiencies and support access to other health services. This is of particular import for hard-to-reach or underserved populations, and the approach may be leveraged to help build community trust. Multiantigen or health intervention activities require careful planning and training to ensure smooth implementation and maximal uptake, and to avoid administration errors. • Timing of PMVCs relative to other vaccination campaigns is recommended with an interval of four weeks between campaigns with live attenuated vaccines (e.g. measles) or a minimum of two weeks for other antigens (e.g. coronavirus disease (COVID-19) vaccine). • Opportunities and mechanisms should be used to tailor PMVCs for specific underserved and hard- to-reach contexts, including implementation in urban slums or fragile conflict-affected areas. The key elements of a successful PMVC The main lessons learned, which are also valid for other mass vaccination campaigns, include the following (Table 1). The team should: • aim for early planning and effective coordination; • develop appropriate waste management plans; • design and implement proper monitoring and evaluation activities (including monitoring of adverse events following immunization (AEFIs) and assessment of vaccine coverage); • conduct efficient advocacy, social mobilization and communication, with particular care to ensure that all target age groups, genders and relevant subpopulations are reached; and • ensure proper campaign logistics. EYE Strategy Country Toolkit 9 47 EYE Strategy Country Toolkit Table 1. Timing of activities for a successful PMVC Timing Activities Scoping and application for funding (18–24 months before the campaign) • Review the country context and risk assessment to scope the planned PMVC, including target age group and geographical scope (national or subnational) • Gavi-eligible countries: prepare and submit an application at least 18–24 months before planned implementation • Non-Gavi-eligible countries: determine sources of internal and external funding and complete any associated planning and proposal activities Macroplanning (9–15 months before the campaign) • Review lessons learned from previous campaigns, situation analyses • Define the target population • Estimate the budget • Establish national subcommittees, and seek political endorsement Microplanning (6–9 months before the campaign) • Define technical and budget requirements • Define human resources and logistics needs (including cold chain, transportation, waste management, vaccination teams) • Train staff • Conduct community and social mobilization • Mobilize equipment and resources Pre-implementation (1–6 months before the campaign) • Plan for AEFI monitoring • Develop a waste management plan • Train staff • Raise awareness, conduct social mobilization and prepare for crisis communication • Prepare operations and conduct pre-campaign supervision and monitoring PMVC implementation • Ensure operation of vaccination posts • Conduct supervision and monitoring • Undertake early identification and remediation of areas or groups with suboptimal coverage Waste management • Ensure proper elimination of waste Monitoring and evaluation (during and close follow-up of PMVC) • Implement post-campaign independent monitoring • Conduct mop-up vaccination activities • Evaluate vaccine coverage and monitor quality • Review the campaign, write a report and disseminate results to the Eliminate Yellow fever Epidemics (EYE) Strategy and partners 9 48 EYE Strategy Country Toolkit Aiming for early planning and effective coordination Costing and financing A budget reflecting the campaign costs and financing sources should be developed early. It should include key activities related to monitoring of vaccine safety, management of campaign waste, campaign monitoring and evaluation, social mobilization and communication for community sensitization, and mop-up vaccination activities in underserved areas during and after the campaign. In Gavi-eligible countries, the budget should be discussed early with the Senior Country Manager. In all countries, the team should consult early on with WHO and the United Nations Children’s Fund (UNICEF) about possible avenues for support. Linkages with other interventions and addressing unique subpopulation needs YF mass vaccination campaigns can provide a platform to deliver additional public health and nutrition interventions, and optimize the use of resources. Effective integration between programmes can contribute to increasing vaccination coverage by reducing missed opportunities for vaccination, reducing vaccine hesitancy and increasing access to hard-to-reach populations. These can be of particular importance when planning for activities in underserved and hard-to- reach populations. The most common integrated interventions include other vaccinations (measles, polio), vitamin A or other vitamins and mineral supplementation, deworming, health promotion activities, and provision of health services. The decision to integrate other health interventions in a YF preventive campaign should be made on a case-by- case basis. It will mainly depend on whether the added activities contribute to the campaign’s main objective of reaching unvaccinated people, and whether they do so at an affordable cost and efficiency. The complexity of integrated interventions must be accounted for in planning (for example, the measles vaccine is often targeted at children younger than 10 years old, while YF vaccination campaigns typically target people aged 9 months to 60 years). Planning should consider how to address the different target age groups and social groups or genders for each type of intervention (for example, adolescents and adults may warrant different strategies; social norms may require careful consideration of how to ensure that married woman can access vaccination in a socially acceptable manner; certain subpopulations such as young men may require tailored messaging, and so on). Building on a strong and inclusive partnership In Gavi-eligible countries, the Senior Country Manager should be contacted early to request support. Gavi-eligible countries can receive support for preventive campaigns on a one-dose vaccination schedule, as well as associated supplies. To receive this support, countries must have already introduced YF into the national RI schedule, or must plan to do so no later than 12 months following the campaign. Countries should ensure that their target vaccine introduction date and plans for preparatory activities are compatible with the timelines for the likely receipt of Gavi funds and vaccines. In particular, it will usually not be feasible for a country to introduce the YF vaccine in less than 15–18 months of the Gavi application submission deadline. The Gavi application (where applicable, a joint PMVC–RI application) should be submitted at least 18–24 months before PMVC implementation. Following approval by the Gavi Independent Review Committee, a decision letter is issued, and is valid for a certain number of doses over a two-year period. The application includes a plan of action (macroplanning) and budget. Microplanning is initiated after issuance of the decision letter, which will also trigger the issuance of a purchase order for UNICEF. 9 49 Targeted country assistance (TCA) is financial support to countries for technical assistance to ensure quality planning and implementation. Technical assistance is intended to be targeted and tailored to countries’ needs – driven by the Expanded Programme on Immunization; to ensure country focus, transparency, accountability and differentiation; and to support vaccine and health system strengthening investments. TCA can be provided through core partners (WHO, UNICEF, United States Centers for Disease Control and Prevention (CDC) and the World Bank), and expanded partners, including local institutions. Countries identify their challenges and express their TCA needs through the joint appraisal – an annual review of Gavi’s support to each country. TCA complements the support that countries receive from Gavi for vaccines and health system strengthening. Regardless of Gavi eligibility, the WHO and UNICEF country offices should be contacted early for planning purpose and to request support for: • risk assessment, planning, organizing and implementing high-quality immunization activities; • building national capacity for social and behavioural communication to improve YF vaccine coverage, including public demand for quality YF immunization; and • identification of local and international partners and their potential roles, including technical assistance and social mobilization. Developing an appropriate waste management plan Inadequate management of waste generated by mass campaigns, such as sharps and infectious non-sharp waste, can cause direct negative health impacts on the community and the personnel working during and after a campaign. In addition, pollution due to inadequate treatment and disposal of this waste can cause indirect negative health impacts in the community, and affect the environment. Details about development, implementation and evaluation of a proper waste management plan can be found in WHO-specific guidelines 34 and are summarized in Fig. 13. EYE Strategy Country Toolkit Fig. 13. Waste management planning STEP 1 Assess current situation and estimate needs PLANNING IMPLEMENTATION STEP 1 Estimate needs and define infrastructure STEP 2 Define a general strategy for waste management STEP 3 Allocate resources and provide material STEP 4 Raise awareness and assign responsibilities STEP 2 Raise awareness and assign responsibilities STEP 3 Define a waste tracking system STEP 4 Ensure protective measures for staff STEP 5 Set up daily routines STEP 6 Carry out final evaluation STEP 6 Ensure periodic field control STEP 7 Carry out final evaluation STEP 5 Set up a monitoring system -12 -10 -8 -4-6 -2 0 1 PHASE Ensure coordination Provide tools Give feedback Level M on th s CE N TR AL LO CA L EVALUATION 9 Source: Adapted from World Health Organization. (2016). Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. World Health Organization. https:// iris.who.int/handle/10665/330568 50 Strategies to reduce the operational burden of campaign waste management The safe disposal of high volumes of vaccination campaign waste can be a stress on a country’s health system. Options to reduce this burden can help to improve the quality of the campaign and to minimize the impact on other health services. Options include use of foundries or cement plants for disposal of waste. In order to cope with the significant production of immunization waste generated during the short period of the campaign, some countries have opted to use foundries or cement plants for the disposal of waste. The transport of waste can also be outsourced from the district to a large destruction site. The use of private operators requires development of agreements that specify the services to be provided, the means mobilized for the provision of these services, and the deadlines and costs, on the basis of specifications developed by the country. The contract must include a performance monitoring and evaluation framework. Design and implementation of proper monitoring and evaluation activities AEFI monitoring AEFIs are rare but can be serious. AEFI incidence should be monitored at all levels. The procedures for AEFI monitoring are described in a WHO field guide.35 For more detail, refer to Sections 3 and 6. The risk of AEFI is higher during the campaign. This is related not to the vaccine itself, but to the large number of vaccinations performed during a short period of time, and the possibility – for some vaccination teams – of reduced compliance with safe injection practices due to high workload and demand. Early planning of vaccine safety before the campaign is needed, through the appointment of an AEFI National Committee, development of technical documents adapted from the WHO global guidelines (for the definition, monitoring and management of AEFIs), appropriate sensitization of the community (“YF is effective and safe”) and training of health personnel. During the campaign, this entails: • passive surveillance, supplemented by active detection of serious AEFIs; • management and reporting of AEFIs according to standard protocols; and • appropriate communication tailored to the affected community (building trust, addressing any rumours or misinformation). 34 Management of wastes from immunization campaign activities: practical guidelines for planners and managers. Geneva: World Health Organization; 2004 (https://extranet.who.int/iris/restricted/handle/10665/204415, accessed 27 July 2023). 35 Yellow fever: surveillance of adverse events following immunization against yellow fever – field guide for staff at the central, intermediate and peripheral levels. Geneva: World Health Organization; 2010 (https://apps.who.int/iris/ handle/10665/70216, accessed 24 July 2023). EYE Strategy Country Toolkit 9 51 Conducting rapid convenience monitoring The most important objective of rapid convenience monitoring (RCM) is to find unvaccinated people in the target population in order to vaccinate them. Additional goals are to identify reasons for non-vaccination and to plan and execute rapid corrective action. RCM data provide information on the general performance of the PMVC, and suggest how to refine strategies to access the hardest-to-reach people. RCM is a pass/fail assessment of the areas surveyed, not a coverage assessment (see Section 5 for detailed procedures). Assessing vaccine coverage Vaccine coverage is the percentage of people in the target age group who have been immunized during PMVCs. It should be calculated for the entire target population, and also by age group and location. Both administrative vaccine coverage and vaccination coverage surveys should be reported by districts. Coverage surveys should also assess reasons for non-vaccination. Vaccination coverage surveys require careful planning and budgeting early in the preparation phase for the PMVCs. The choice of method depends on the objectives and on the resources available (see Section 5 for more details). Monitoring the quality of a PMVC The quality of a PMVC is determined by its impact on disease incidence assessed through disease surveillance. Monitoring the quality of a PMVC is necessary to understand any challenges and bottlenecks undermining its quality; this information can be used to improve future PMVCs and RI. For quality assessment, a series of indicators (and targets) have been developed for use by countries for activities carried out before, during and after a PMVC. These can be found in specific WHO guidelines36 and are summarized in Section 5. Conducting efficient advocacy, social mobilization and communication Field procedures for advocacy, social mobilization and communication at national and district levels, along with community engagement and behaviour change activities to be conducted in the context of PMVCs, have been developed by WHO,37 and can be found in Sections 4 and 6. They include: • communication planning; • advocacy; and • social mobilization. 36 Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://extranet.who.int/iris/ restricted/handle/10665/330568, accessed 24 July 2023). 37 Planning and implementing high-quality supplementary immunization activities for injectable vaccines using an example of measles and rubella vaccines: field guide. Geneva: World Health Organization; 2016 (https://extranet.who.int/iris/ restricted/handle/10665/330568, accessed 24 July 2023). EYE Strategy Country Toolkit 9 52 EYE Strategy Country Toolkit Communication should be tailored in the case of joint/combined campaigns with different target age groups. At the district level: • the communication focal point should be involved in organizing and coordinating the communication plan; • specific messages should be tailored to address barriers for vaccine uptake, especially in settings with hard-to-reach populations and any subpopulations, or age and/or gender groups that are assessed to be less likely to accept vaccination in the local context; • specific messages should also address misunderstandings about AEFI; • communication should be built on the channels that are the most relevant locally (including social media, radios and town criers); and • social mobilizers should be selected based on their credibility, and should be trained in the main and specific messages. Ensuring proper campaign logistics The quality of PMVC preparation determines its success. This is particularly true for logistics, which must ensure the availability of a quality vaccine and injection materials throughout the campaign and at each vaccination site. Logistics planning should follow a few key principles, including the following: Timely preparation and implementation Logistics planning aims to assess the needs for vaccines, injection equipment and cold chain equipment, and to determine the necessary budget. The deployment of cold chain equipment requires a delay of approximately six months between its ordering and commissioning, and the limited availability of the vaccine on the international market requires its requisition to be anticipated. Planning must begin at least 12 months before the campaign. Monitoring of logistics plan implementation Monitoring the logistical preparation enables implementation of the plan’s activities to be verified, and any problems that may arise to be identified. The resolution of problems sometimes requires implementation of unanticipated corrective action. The plan must allow flexibility to provide necessary resources at all levels of the health system. Immunization safety The specific features of YF vaccination in PMVCs involve strengthening measures to ensure the vaccine’s safety. It is a live attenuated vaccine, administered by injection to a large population during a very short period of time, and generating a large volume of hazardous waste. Logistics must contribute to immunization safety through a controlled and continuous cold chain for vaccine storage and transport, availability of diluents and injection materials, and recording material and effective waste management. Logistics for reaching underserved populations The logistical means to access hard-to-reach populations are often different and sometimes more important than those for easily accessible populations. Logistics should not be planned in a one-size-fits-all fashion: findings from equity and other programmatic assessments must be considered while planning logistics, to ensure the definition of specific interventions and availability of adequate resources. 9 53 Further reading 38 Communication and social mobilization in yellow fever mass vaccination campaigns: 10 points from field experience. Geneva: World Health Organization; 2015 (https://iris.who.int/handle/10665/156053). Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Wkly Epidemiol Rec. 2017;92(16):193–204 (https://apps.who.int/ iris/handle/10665/255374). GAVI support guidelines Geneva: Gavi, the Vaccine Alliance; 2022 (https://www.gavi.org/our-support/guidelines). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Immunization supply chain interventions to enable coverage and equity in urban poor, remote rural and conflict settings. New York: United Nations Children’s Fund; 2020 (https://www.unicef.org/documents/immunization-supply-chain-interventions). Risk assessment on yellow fever virus circulation in endemic countries: a protocol for risk assessment at the field level. Geneva: World Health Organization; 2014 (https://apps.who.int/iris/handle/10665/112751). Vaccination in humanitarian emergencies: implementation guide. Geneva: World Health Organization; 2017 (https://iris.who.int/ handle/10665/258719). 38 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 9 54 EYE Strategy Country Toolkit What to consider for preventive mass vaccination campaign logistics Early planning and effective coordination are key to successful preventive mass vaccination campaigns (PMVCs). 10 - Logistics of preventive mass vaccination campaigns The objectives of high-quality PMVC logistics are to ensure that all elements of an effective vaccination campaign can be implemented safely, including: • yellow fever (YF) vaccine and immunization supplies available and appropriately stored at all vaccine delivery points during the campaign; and • high-quality waste management processes designed, supplied and implemented at all levels for safe and responsible disposal of waste produced by the campaign. The plan for PMVC logistics should include consideration of how to ensure timely supplies and support to underserved populations, and approach planning with the aim of mitigating and reaching zero-dose communities and populations.39 Logistics for supplies and waste management require months of advance planning and should be initiated 9–12 months prior to the campaign. The core components 1. Logistics for availability of vaccine and immunization supplies Advance logistics planning for a PMVC is necessary to ensure that all appropriate actions for an efficient supply chain are completed and the activities of the campaign can proceed smoothly. Steps include detailed assessments to determine vaccine and supply needs at all levels, as well as assessment of cold chain capacity for maintaining the YF vaccine, and distribution systems and processes designed to achieve timely transport and maintain strong accountability. Logistical planning is also necessary to help ensure a safe campaign. Planning must confirm that supplies for managing adverse events following immunization (AEFIs) are available and distributed to all delivery points. 39 Immunization supply chain interventions to enable coverage and equity in urban poor, remote rural and conflict settings. New York: United Nations Children’s Fund; 2020 (https://www.unicef.org/documents/immunization-supply-chain- interventions, accessed 27 July 2023). 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 55 EYE Strategy Country Toolkit 2. Waste management YF PMVCs generate a large amount of immunization waste in a short period of time, exceeding the usual capacity for waste treatment. The estimated volume of hazardous waste generated during the campaign is approximately 5 m3 per 100 000 people vaccinated. It is important that this waste is properly eliminated shortly after the campaign to avoid dissemination of hazardous waste in the environment. Waste management should be planned and implemented as described in Table 2. Table 2. Timelines for planning, preparation and reporting Category Activities Vaccine supply, cold chain logistics and waste management Planning phase 6–12 months before the campaign Technical and budget requirements for vaccines and immunization supplies, cold chain and transport, and waste management should be defined. Estimating vaccine needs Vaccine needs are estimated based on the target population and the vaccine wastage rate. Managers should determine the wastage rate based on wastage rates from previous campaign experience. If no previous vaccine wastage rates are available, a rate of 10% may be used as an estimate. For a wastage rate of 10%, the wastage factor (WF) is 1.11. Required number of vaccine doses = target population × WF The YF vaccine can be supplied in 10 or 20 dose vials. The number of doses to be given should be divided by the number of doses/vials to obtain the required number of vials. Estimating needs for immunization supplies The following supplies are needed: • auto-disable syringes = 1 per vaccine dose • reconstitution syringes = 1 per vaccine vial • safety boxes = 1 per 100 syringes • clean gauze swabs = 0.5 rolls per team per day • soap = 1 bar per vaccination team • trays = 1 per vaccination team • indelible marker pens = 1 per vaccination team per day • AEFI treatment kits = 1 per health centre 10 56 EYE Strategy Country Toolkit Category Activities Estimating cold chain requirements (at least nine months prior to the campaign) A functional cold chain capacity assessment and inventory should be completed. Cold chain assessments should include: conducting an inventory of the cold chain equipment at all levels, including refrigerators, freezers, generators, cold boxes and vaccine carriers; identifying the energy source; and assessing the number and conditions of temperature monitoring devices. To determine the total requirement for coolant packs, the team should estimate the number of coolant packs needed in a single day, and double it (more may be needed if there is insufficient freezing capacity). WHO has developed a tool aiming to estimate the required cold chain capacity at each level and facility, while planning for or expecting significant changes in the national immunization programme such as a PMVC.a To meet the additional demand required during campaigns, cold chain space may be borrowed/rented temporarily from the private sector and/or other ministries or nongovernmental organizations (NGOs). Another way to free up cold chain space is to delay the delivery of vaccines for routine immunization temporarily, if this does not interrupt the programme. Estimating transport requirements Transportation needs and mechanisms to ensure transport should be identified. Depending on the nature of the terrain, use of motorcycles and alternative modes of transport such as aircraft, boats, rafts and animals may be required. Transportation modes needed should be identified before and during the campaign, and the team should ensure that the plan is inclusive of hard-to-reach or underserved areas. An inventory should be conducted of all available transportation resources at the local level. Additional sources of transportation to fill the gaps should be identified (e.g. vehicles from other government departments, NGOs, and private and religious sectors or rented vehicles). Fuel needs should be estimated based on average consumption per vehicle and estimated mileage per day. Costs should be estimated: calculation of costs should include the cost of car rental if needed and the cost of fuel. a Immunization supply chain sizing tool [online tool]. Geneva: World Health Organization; 2021 (https://www.who.int/ publications/m/item/immunization-supply-chain-sizing-tool, accessed 27 July 2023). 10 57 EYE Strategy Country Toolkit Category Activities Estimating waste management requirements The team should assess the current situation and estimate needs. The quantities of waste generated and treated during the campaign should be estimated. Current practices regarding segregation and handling of the sharps should be analysed. The status and location of health-care waste management should be reviewed. The capacity of the local system to cope with additional quantities of waste generated during the campaign should be analysed, incorporating consideration of different methods of management depending on the local context, and including strategies for hard-to-reach or access-limited areas. Additional material, financial and human resource needs should be evaluated. A strategy for waste management should be defined. Treatment and disposal options should be determined and waste transportation defined. National regulations should be checked, and a strategy outlined for the campaign (including initial assessment, plan of action and timeline). The document to should be submitted to national/local authorities. Resources should be allocated and materials provided. Financial and human resources should be allocated according to the strategy. Safety boxes and leak-proof containers or bags for waste packaging should be supplied. Personal protective equipment for waste handling and treatment should be provided. Infrastructure should be built/rehabilitated and equipment for waste management and disposal supplied. Waste management Pre-implementation phase (six months prior to the campaign) Waste management Awareness-raising activities should be undertaken, and responsibilities assigned. Key contact should be established with health authority representatives. Responsibilities for the supervision of health-care facilities should be allocated. Instructions should be given to mobile team leaders. 10 58 EYE Strategy Country Toolkit Category Activities Waste management (cont.) A monitoring system should be set up. Central monitoring should track sharps along the waste stream until final disposal. The team should ensure follow-up of stock positions of vaccines, syringes and safety boxes. Registration forms should be provided to health-care facilities and mobile teams for self-monitoring and accountability. Vaccine supply and cold chain logistics Pre-implementation phase two months to one day before the campaign Vaccine and immunization supplies The team should prepare to transfer vaccines and supplies from the central store to the district with vaccine storage capacity. Vaccines should be transferred to health facilities one or two days before the campaign. Cold chain equipment Back-up cold chain capacity should be organized for national and provincial cold rooms, including generators and spares. A reliable power supply must always be ensured. At the health facility level, supervisors and logisticians must undertake the following actions: • ensure that cold chain technicians visit all the health centres at least four weeks before the campaign, and that at least one refrigerator is working in each health centre; • ensure there is also a detailed plan for hard-to-reach or high-need areas that require an alternative approach due to power supply and/or access limitations, including details of when replenishment will occur and how temperatures will be maintained; • take temperature readings twice a day and refer to vaccine vial monitors to ensure that vaccines have not been exposed to excessive temperatures; • ensure that batteries for solar refrigerators are in good condition and that solar panels are clean; • ensure that there are enough cold boxes, vaccine carriers and coolant packs in good working order (freezing of water packs should begin 7–10 days before the first day of the supplementary immunization activity); • ensure that the vaccine storekeeper/manager knows how to condition water packs properly prior to packing; • if necessary, ensure that cold-chain space has been borrowed/ rented from other sectors (private, NGOs); • ensure establishment of contingency plans at all levels with bulk or central stock of vaccine supplies. 10 59 Category Activities Transport The stock remaining (if any) at the district level should be verified, and its condition checked (for example, cold chain maintained, vaccine vial monitors). The team should ensure that any leftover vaccine in good condition can be allocated for use within routine immunization or mop-up vaccination activities. At the health facility level, supervisors and logisticians should ensure that transport arrangements are well defined to make sure that movements of teams are implemented as planned. Vaccine supply, cold chain logistics and waste management During the campaign Vaccines and immunization supplies The team should ensure daily review of stock balances, highlight any vaccination delivery points in need of more supplies, and re- stock accordingly. They should monitor for any excess and redistribute vaccines and supplies if necessary. They should check on cold chain and vaccine accountability on continual basis. Waste management Supervision of the campaign should be ensured. Regular visits to the field should be carried out as part of the routine monitoring of campaign performance, to ensure inclusion of monitoring in all types of implementation areas (urban, rural, hard-to-reach, special strategy areas). Daily waste management practices should be checked. Registration procedures should be verified. Vaccine supply, cold chain logistics and waste management After the campaign Vaccine and immunization supplies and waste management A final evaluation should be carried out The sustainability of the strategy used should be evaluated. An evaluation report should be written, with recommendations for the next campaign. Waste management The team should ensure safe completion of final disposal, and that final accountability reports for vaccines used are received from all vaccination delivery sites. EYE Strategy Country Toolkit 10 60 EYE Strategy Country Toolkit The new approaches needed to prevent the international spread of yellow fever Yellow fever (YF) has a long history of causing severe, fast-moving outbreaks and epidemics with international spread. Since 2016, there have been unprecedented outbreaks in areas not previously deemed to be at high risk (including Angola in 2016 and coastal areas of southern Brazil in 2017 and 2018). In the 21st century context, populations are more interconnected than ever before, with many people moving long distances for employment and leisure, or due to unfortunate circumstances like climate change and natural disaster or insecurity. The International Health Regulations (2005) (IHR) set out obligations and mechanisms for countries to prepare for and prevent the international spread of outbreaks. Implementation and operationalization are a challenge in many settings. The Eliminate Yellow fever Epidemics (EYE) Strategy recommends full IHR implementation with innovative approaches to reduce the risk of YF spreading through high-risk workers and by increasing the resilience of large urban centres. More guidance on these topics will be developed and shared by the EYE Strategy (2017– 2026). Applying the International Health Regulations (2005) Rationale Under the EYE Strategy, mass vaccination programmes are not recommended in countries at moderate risk of YF epidemics; nor are they recommended in countries with potential for YF transmission. In those countries, the risk is reduced through heightened readiness, surveillance and IHR adherence. Countries can reduce their risk of importation by checking the YF immunization status of travellers on arrival into the country and on departure from areas at risk of YF to prevent YF exportation to under-immunized populations where the potential for local transmission exists. The IHR are inconsistently applied in countries at risk of YF, in airports and at land-border crossings, where the YF immunization status of travellers needs to be confirmed on arrival into and departure from areas at risk of YF. Engagement with port and border-control authorities is suggested to help identify gaps and ensure that the vaccination status of all travellers entering and leaving endemic areas is known and appropriately managed. This is particularly important at points of entry in at-risk countries. All countries need to engage with transportation agencies such as the International Air Transport Association (IATA), airlines and border-control/customs agencies to strengthen control of YF immunization status, in line with the IHR, based on area of origin and destination, at entry and departure. 11 - Preventing the international spread of yellow fever 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 61 A particular problem is the production of falsified immunization cards or certificates, as well as non-official card selling points. In addition to specific country control measures, a solution needs to be proposed at the global level to move towards a unique registration system and creation of non-falsifiable cards. This could leverage the ongoing efforts triggered by the coronavirus disease (COVID-19) pandemic, and the rollout of secure paper and electronic vaccine certificates.40 How to strengthen IHR implementation at the country level The country capacity and support needs for implementation of the IHR should be assessed. Regular monitoring of IHR implementation with respect to YF should be established, and baseline figures reported by country. Priority geographical urban hubs for targeted interventions should be identified (using a risk index to identify high travel volume–high-risk urban hubs). Mechanisms for countries to strengthen IHR implementation should be implemented, including: • clearly communicating YF immunization requirements to the global community through WHO and IATA; • reinforcing control at points of entry and departure; • engaging transportation agencies (e.g. IATA), airlines and border-control/customs agencies to strengthen the control of YF immunization status at both entry and departure based on area of origin and destination aligned to the IHR; • proposing and developing solutions to control the production of falsified immunization cards or certificates, as well as non-official card selling points; • strengthening the national control plan based on lessons learned during regional outbreaks (e.g. Ebola outbreaks); • updating efforts to move towards a unique registration system and the creation of non-falsifiable cards, including electronic and paper options. EYE Strategy Country Toolkit Protecting high-risk workers Rationale Globalization means that workers in a wide range of extractive industries (such as the oil and mining industries) and other sectors (such as construction and forestry) regularly move into and out of YF endemic areas, and are at risk of both developing the disease and spreading it nationally and internationally in under-immunized populations. These workers are particularly exposed to sylvatic transmission when the activity is in forests or recently deforested areas. Living in poor sanitation settings in periurban or urban areas increases the risk of YF spread. 40 Smart Vaccination Certificate Working Group. In: World Health Organization [website]. Geneva: World Health Organization; 2023 (https://www.who.int/groups/smart-vaccination-certificate-working-group, accessed 27 July 2023). 11 62 EYE Strategy Country Toolkit Involvement of companies from the major sectors affected (e.g. the extractive, construction and forestry industries, and the transportation sector) and public health experts is needed to develop strategies ensuring that all at-risk workers, whether international or local, are protected. The private sector should be involved in this effort, and should ensure that staff and their families are protected. How to protect high-risk workers Public-private partnerships should be built to prepare and coordinate an outbreak response. Coordination should take place with global, regional and national partners. Mapping of industry stakeholders should be done with ministries of trade and industry. Identification of formal and informal at-risk workers and their communities should be undertaken, in partnership with a working group on vulnerable populations (consisting of public health experts) and the International Organization for Migration (IOM). A multisector expert group should be established and convened to: • create a shared list of focal points and contacts in each district; • define the immunization strategies per category of at-risk workers and families; and • describe roles and responsibilities for preparedness and rapid outbreak response. Industry guidance on YF vaccination for workers and their families should be delivered, regardless of the type of work, gender or social demographics in at-risk areas, in order to: • develop communication materials/strategy and organize sensitization sessions with at-risk workers and their communities in formal industries on vaccine uptake and disease surveillance and treatment (to limit mobility to urban settings in case of YF symptoms); • organize disease surveillance and treatment between health-care facilities and places of employment (such as by identifying a focal point for workers); • negotiate vaccine access for workers and their communities via industry employers, and explore how to mitigate barriers to accessing vaccination; and • agree on monitoring and evaluation with key industry employers, to evaluate the offer and uptake of the YF vaccine among workers. Industry uptake of guidance should be monitored, evaluated and reviewed regularly. 11 63 EYE Strategy Country Toolkit Building resilient urban centres Rationale Large cities are vulnerable to epidemics: viruses are more likely to be introduced, and dense populations enable rapid amplification of transmission. Epidemics in urban settings are particularly disruptive. Building resilience to epidemic risks in large cities is essential for global health security. In urban outbreaks, population density; crowding; low levels of population immunity; daily population movements in, out of, and around the city; and conditions conducive to high-vector density such as plentiful breeding sites in and around houses increase transmissibility, raising the risk of large-scale outbreaks. Inequalities and inequities may exacerbate risks, with particular subpopulations facing the greatest vulnerability in the event of a YF outbreak (e.g. urban poor, disadvantaged or discriminated groups and genders). Vector control is particularly difficult in crowded settings close to mining, oil extraction and forestry working areas, and in cities close to frontiers with intense cross-border movement for commerce or due to civil unrest or other issues. Creating plans for transportation hubs is crucial. Mass vaccination campaigns have proved to be particularly challenging in urban settings due to the size and logistical challenges of the operation, as well as the mobility of the population. Specific preparedness efforts are needed to ensure timely and rapid vaccination during urban outbreaks. How to build resilient urban centres Reducing the risk of epidemics in urban centres can be achieved through increased readiness by the development and piloting of urban readiness plans. To develop specific readiness plans: • plans should be linked to national contingency plans for YF and outbreak management, and based on risk assessment in urban areas (see the list of partners in the next section); • intervention plans should be linked to national contingency plans and should establish: • strategies for rapid implementation of an emergency vaccination campaign; • emergency management in health-care centres; and • increased control of transmission in transportation hubs (bus and railway stations, airports, ports). In addition, Aedes aegypti indices should be calculated regularly in cities at risk or with potential for YF. This monitoring should be integrated into urban emergency planning, and should trigger activities based on the estimated level of risk. These measures should be part of broader arbovirus surveillance and readiness in countries that are also at risk of the chikungunya, dengue and Zika viruses. Vector control of adults and larvae requires sustained efforts to maintain low mosquito density, particularly Aedes spp. vectors, which are well adapted to humans. Qualitative research should be used to understand what does and does not work for Aedes spp. control. Practical and effective strategies involving all parties need to be developed. These plans should identify key resources and a highly trained core team of health-care professionals (public health officers, laboratory experts, patient care and vector control specialists), who will be prepared to manage the outbreak response. An urban readiness plan should also identify key leaders and population representatives in different settings who will facilitate implementation and guide identification and engagement with all at-risk communities. The detailed list of contacts for each district should be shared with all partners. 11 64 EYE Strategy Country Toolkit Plans should detail coordination between agencies (roles and responsibilities and communication channels) in the preparedness phase (e.g. maintaining an appropriate pool of trained health-care workers) as well as during the epidemic (such as leadership roles, decision-making responsibilities and engagement with partners). Plans should be reviewed and adjusted based on: • pilot monitoring and evaluation and lessons learned; • new environmental or human risks (YF outbreak, population movement, deforestation and so on); and • analysis of how best to provide YF control services equitably, including vaccination to the groups at highest risk. The key people to contact and data sources to support these activities The global EYE focal point of the technical Risk Analysis Working Group can provide technical documents and assistance. The regional EYE focal point for the urban readiness plan can provide further assistance, including guidance and identifying key partners at the national level. Other country focal points with experience in developing and implementing urban readiness plans can provide advice. The national Rockefeller Foundation representative for the Resilient Cities programme can provide existing documents about risk assessment. The Index For Risk Management (INFORM) and the Global Facility for Disaster Reduction and Recovery (GFDRR) can be used.41 The IOM and United Nations High Commissioner for Refugees can provide data and lead the plan implementation for transportation surveillance and control. Key national stakeholders for vector-borne disease surveillance and activities (particularly for diseases involving Aedes spp. such as chikungunya, dengue and Zika viruses, and possibly West Nile virus) can provide key inputs, data and assistance for risk assessment and pilot implementation (including the ministry of health, the Global Fund to Fight AIDS, Tuberculosis and Malaria and nongovernmental organizations) and can also help with identification of national experts. National experts in disease control, vector-borne epidemiology, immunization, environmental risk and human risk can be contacted to establish an urban resilience expert group (with links to existing global resilience forums). Community leaders and communication experts can be engaged to help assess and ensure inclusion of all at- risk subpopulations and genders, with an equitable approach to planning and implementation. Private sector partners (in the oil extraction, mining and forestry sectors) should be involved. 41 DRMKC – INFORM. In: European Commission. Brussels: European Commission; 2023 (http://www.inform-index.org/, accessed 27 July 2023); GFDRR. Washington DC: World Bank; 2022 (https://www.gfdrr.org/en/, accessed 27 July 2023). 11 65 EYE Strategy Country Toolkit Further reading 42 Brent SE, Watts A, Cetron M, German M, Kraemer MU, Bogoch II et al. International travel between global and urban centres vulnerable to yellow fever transmission. Bulletin of the World Health Organization. 2018;96(5):343–54. doi:10.2471/BLT.17.205658. Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Weekly Epidemiological Record. 2017;92(16):193–204 (https://apps. who.int/iris/handle/10665/255374). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Kraemer MUG, Faria NR, Reiner RC Jr, Golding N, Nikolay B, Stasse S et al. Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015–16: a modelling study. Lancet Infectious Disease. 2017(3):330–8. doi:10.1016/S1473- 3099(16)30513-8. Schönenberger S, Hatz C, Bühler S. Unpredictable checks of yellow fever vaccination certificates upon arrival in the United Republic of Tanzania. J Travel Med. 2016;23(5). doi:10.1093/jtm/taw035. Service availability and readiness assessment (SARA): an annual monitoring system for service delivery: reference manual. Geneva: World Health Organization; 2014 (WHO/HIS/HSI/2014.5Rev1; https://iris.who.int/handle/10665/149025). Wilder-Smith A, Monath T. Responding to the threat of urban yellow fever outbreaks. Lancet Infectious Disease. 2016;17(3)248–50 doi:10.1016/S1473-3099(16)30588-6. 42 All references accessed 24–27 July 2023. 11 66 Why surveillance and laboratory capacities matter Strong yellow fever (YF) surveillance 43 and laboratory capacities are critical in endemic areas to define the risk, strategies and priorities for intervention and monitoring impact, and to inform the optimal allocation of limited vaccine supply. Key messages Case-based surveillance is the surveillance standard for YF disease in humans. As YF is a vector-borne disease, a multifaceted “One Health” approach is promoted. Surveillance of mosquito vectors and disease in neotropical non-human primates can provide valuable insight into YF virus circulation. YF surveillance is greatly enriched by comprehensive investigations of suspect and probable cases, with inclusion of active case-searching for any additional suspect cases in the family and local community. An investigation should ensure that the best available information is available on vaccination status, local community vaccination coverage, clinical course of the case, travel and employment history, and should consider factors relevant to accessing health services (e.g. whether an individual is from a marginalized group, and barriers due to distance, violence, discrimination or other reasons). A detailed clinical and epidemiological investigation is necessary to interpret laboratory results. When YF is suspected, the team should always enquire and report whether there is a history of YF vaccination (carefully documenting the date of YF vaccination if so). The details of clinical presentation (e.g. acute febrile jaundice and/or unexplained bleeding), appropriate laboratory tests and epidemiologic history of the location where the presumed infection occurred will facilitate final case classification. A history of YF vaccination administered more than 30 days before the onset of symptoms makes YF diagnosis very unlikely. The YF vaccine is perfectly safe and provides lifelong immunity (vaccine failure is very rare). Initial symptoms of YF are nonspecific, and many people will have only mild symptoms. There is a delay of approximately 10–14 days between the onset of symptoms (nonspecific general signs of viral infection, including fever) and the appearance of jaundice and end-organ failure symptoms in severe cases of YF disease (Fig. 14). Blood samples (at least 4 ml) should be taken from all suspected cases and transported in a timely manner and in appropriate temperature conditions (see WHO YF laboratory guidelines).44 Accompanying 12 - Strengthening surveillance and laboratory capacities 43 This section refers to surveillance for human cases. In the Americas, YF surveillance also incorporates epizootic surveillance of non-human primates. 44 Yellow fever laboratory diagnostic testing in Africa: interim guidance. Geneva: World Health Organization; 2016 (WHO/OHE/ YF/LAB/16.1; https://extranet.who.int/iris/restricted/handle/10665/246226, accessed 27 July 2023). EYE Strategy Country Toolkit 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 67 information (such as patient identification, date of sample, date of symptom onset and vaccination status) is equally important. As serum is the principal diagnostic sample for serology and molecular testing, use of techniques to prevent blood haemolysis before serum separation is critical. Countries can access support to ensure streamlined international transport of samples to a regional reference laboratory for confirmatory testing by contacting: EYE.Strategy@who.int. Fig. 14. The three phases of YF infection: infection, remission, intoxication Incubation 3 to 6 days Mosquito bite 3 Phases 3 to 6 days 1 to 2 days Jaundice Liver and kidney failure Possible haemorrhage Fever Non-specific general signs of viral infection including fever Vira em ia Anti bod ies Potential transmission Leading to protection >day 7 Infection Remission Intoxication Recovery (or death) Time Reports of YF cases must be assessed, as they could require declaration of a public health emergency by countries, according to the International Health Regulation (2005) (IHR). Testing can take the following forms. Molecular assay: polymerase chain reaction (PCR) • A PCR test is positive in the early stages of the disease (within 10 days of onset of symptoms). • A PCR test can be negative when samples are collected immediately after exposure (within three days of infection from a mosquito). • A PCR test can be positive owing to the vaccination in those who have received the YF vaccine within 14 days before the onset of symptoms. Immunological testing: enzyme-linked immunosorbent assay (ELISA) serologic test to detect YF virus immunoglobulin M (IgM) • IgM antibodies generally start to appear three days after the onset of initial symptoms (fever), but can also be positive for years after YF vaccination. • An individual who develops jaundice due to severe YF infection is very likely to have a positive IgM for YF; however, it can also be positive in people with milder forms of infection or who recently received the YF vaccine. EYE Strategy Country Toolkit 12 Adapted from: Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Staples JE. Incubation periods of Yellow fever virus. Am J Trop Med Hyg. 2010 Jul;83(1):183-8. doi: 10.4269/ajtmh.2010.09-0782. PMID: 20595499; PMCID: PMC2912597. 68 • IgM antibodies often persist for a fairly long period of time (several years), making it challenging to interpret acute infection from prior vaccination.45 • Immunization history is very important for the interpretation of serology results, because the ELISA IgM test cannot distinguish between IgM response induced by recent YF vaccination (IgM may persist for a prolonged period of time after vaccination – years, in some instances) or wild-type virus infection. • Other flaviviruses such as dengue, West Nile and Zika viruses may give a false-positive YF ELISA result due to cross-reactivity of the test. Detection of neutralizing antibodies using the plaque reduction neutralization test (PRNT) • PRNT is more specific than the ELISA test. • A positive PRNT test can indicate whether YF vaccination and cross-reactivity among flaviviruses has been documented. Table 3 overleaf lists the case definitions recommended for public health surveillance of yellow fever. 45 Gibney KB, Edupuganti S, Panella AJ, Kosoy OI, Delorey MJ, Lanciotti RS et al. Detection of anti-yellow fever virus immunoglobulin M antibodies at 3–4 years following yellow fever vaccination. Am J Trop Med Hyg. 2012;87(6):1112–5. doi:10.4269/ajtmh.2012.12-0182. EYE Strategy Country Toolkit 12 69 Table 3. Case definitions for public health surveillance for YF, 2018 Type of case Definition Suspected Any person with acute onset of fever, with jaundice appearing within 14 days of onset of symptoms Probable A suspected case AND one of the following: • presence of YF-specific IgM antibody in the absence of YF immunization within 30 days before onset of illness;a or • positive postmortem liver histopathology; or • epidemiological link to a confirmed case or an outbreak. Confirmed 1. A probable case with an absence of YF immunization within 30 days before onset of illness AND one of the following: • detection of fourfold increase in YF IgM or immunoglobulin G (IgG) antibody titres between acute and convalescent serum samples, or both; or • detection of YF-specific IgM and neutralizing antibodies in the absence of differential neutralizing antibodies; or • detection of YF-specific IgM and neutralizing antibodies in a neutralizing titre at least fourfold higher than any other positive differential neutralizing antibodies. OR 2. A suspected case with an absence of YF immunization within 14 days before onset of illness AND one of the following: • detection of YF virus genome in blood or other organs by real-time reverse transcriptase PCR; or • detection of YF antigen in blood, liver or other organs by immunoassay; or • isolation of YF virus. a For further detail, please review case definition detail on required testing for flavivirus differential. Source: Yellow fever outbreak toolbox. In: World Health Organization [website]. Geneva: World Health Organization; 2022 (https://www.who.int/emergencies/outbreak-toolkit/disease-outbreak-toolboxes/yellow-fever-outbreak-toolbox, accessed 27 July 2023). EYE Strategy Country Toolkit 12 70 The difference between a presumptive positive sample and a probable case Presumptive positive sample is a term that refers to interim country laboratory IgM serology results, often with incomplete details of the clinical and epidemiological investigation. These presumptive specimens are conventionally still in process for confirmatory testing (e.g. on their way to regional reference laboratory for PRNT and differential testing). Probable YF case refers to a final case classification, based on the best available interpretation of all laboratory results (national and regional reference laboratory, including differential testing results), and in conjunction with interpretation of detailed investigation of clinical, immunization history and epidemiological context. How to interpret complex laboratory diagnostics results Interpretation of laboratory results and final classification of cases is dependent on detailed case investigation, including the clinical history, vaccination status and epidemiology. YF diagnostics use both serological (IgM, PRNT) and molecular (PCR) methods. Each laboratory method has limitations. Adherence to the testing algorithm is important. Final interpretation occurs after all testing is complete (e.g. differential IgM and PRNT for other flavivirus). All suspected YF cases should be tested by an accredited laboratory with expertise in YF. In all instances, the clinical, vaccination and epidemiology data are necessary to interpret YF diagnostics results accurately. Refer to the 2022 updated Global Yellow Fever Laboratory Network (GYFLaN) testing algorithm for additional support.46 Performance indicators for surveillance quality and YF lab diagnostics All levels of laboratories are expected to report their performance to the national and regional level on a routine basis.47 Indicators are set by region, and include monitoring of timeliness of sample transport, processing and results. All laboratories are also recommended to participate regularly in external quality assurance and quality control (EQA/QC) activities, aligned with regional requirements. Regions will regularly communicate outputs and indicators to the global focal point. Current indicators – informed by the requirements for the WHO African Region– include: • yearly rates of suspect cases of YF reported relative to estimated national population (e.g. cases/100 000 total population per year); • the proportion of suspect cases that are confirmed for YF; • the duration of any stock-outs or periods of time where supplies are not available to run YF molecular and/or serologic tests according to recommended protocols; • any interruptions to a network YF laboratory’s ability to test YF specimens (e.g. gaps in human resources or funds, laboratory shutdowns, lack of skilled technicians); • the proportion of national laboratories that have undergone EQA/QC activities or other external assessments each year; 46 Eliminate Yellow Fever Strategy – laboratory information (EYE LABS) Geneva: TechNet-21; 2022 (https://www.technet-21. org/en/eye-labs-home-page, accessed 27 July 2023). 47 Surveillance standards for vaccine-preventable diseases, second edition. Geneva: World Health Organization; 2018 (https:// extranet.who.int/iris/restricted/handle/10665/275754, accessed 27 July 2023). EYE Strategy Country Toolkit 12 71 • the percentage of districts reporting and collecting blood samples from at least one suspected case of YF per year (target >80%); • completeness of monthly reporting (target ≥90%); • timeliness of monthly reporting (target ≥80%); • the percentage of cases investigated within 48 hours of notification (target ≥80%); • the proportion of cases investigated that require follow-up to complete critical details (e.g. immunization history, dates of symptom onset); • the percentage of all suspect cases for which specimens were collected (target ≥50%); 48 • the percentage of samples sent to the laboratory within three days of investigation (target ≥ 80%); • the percentage of samples reaching the laboratory in adequate 49 condition (target ≥80%); • for IgM tests: the percentage of laboratory results reported within seven days after receipt of blood specimen (target ≥80%); • for virus detection: the percentage of laboratory results reported within 21 days after receipt of acute blood specimen (target ≥80%); • for IgG tests: the percentage of laboratory results reported within seven days after receipt of convalescent blood specimen (target ≥80%); • the time between suspect cases symptom onset and the following activities: • case investigation; • sample obtained; • sample received in national laboratory; • initial laboratory result (usually IgM); • shipment from national to regional reference laboratory (where required); • receipt of regional reference laboratory results at country and regional levels. 48 This is the target during non-outbreak periods. Once an outbreak has been confirmed, the priority is to detect outbreaks in neighbouring areas and confirm them in the laboratory. 49 An adequate specimen is a blood specimen collected within seven weeks of the onset of symptoms and where the reverse cold chain was effectively maintained. EYE Strategy Country Toolkit 12 72 EYE Strategy Country Toolkit Further reading 50 Control of yellow fever: field guide. Washington DC: Pan American Health Organization; 2005 (Scientific and Technical Publication No. 603; https://iris.paho.org/handle/10665.2/47057). Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Weekly Epidemiological Record. 2017;92(16):193–204 (https://iris. who.int/handle/10665/275754). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Surveillance standards for vaccine-preventable diseases, second edition. Geneva: World Health Organization; 2018 (https://extranet.who. int/iris/restricted/handle/10665/275754). 50 All references accessed 24–27 July 2023. 12 73 The importance of timely and detailed investigation of yellow fever outbreaks The risk of large urban yellow fever (YF) outbreaks has increased due to changes in outbreak drivers, including human migration and travel patterns, vector distribution and density, low population immunity, and rampant informal urbanization. Rapid and thorough investigation can facilitate confirmation of YF and provide better understanding of disease transmission dynamics (urban or intermediate transmission versus isolated sylvatic transmission case). It also supports risk analysis of ongoing transmission. Comprehensive investigations are a critical source of information to inform an appropriate response plan, including preparation of an application to access the global YF vaccine stockpile coordinated by the International Coordinating Group (ICG) on Vaccine Provision. Comprehensive investigation also provides information about critical risks, needs or barriers to access the affected communities. It can describe the characteristics of the groups that will support planning and implementation of an effective response tailored to the local context, including equitably reaching all at-risk subpopulations, according to need.and barriers due to distance, violence, discrimination or other reasons). How to conduct an efficient and effective YF outbreak investigation When evaluating a possible YF outbreak it is important to characterize clearly whether there is evidence of amplification and rapid spread from a sporadic case due to sylvatic transmission. 13 - Yellow fever outbreak investigation The key questions the investigation must answer include: • Is there an epidemic of YF or are cases sporadic (e.g. characteristic of sylvatic, intermediate or urban transmission)? • What is the setting where case(s) are reported (zone affected, climate and seasonal factors, urban or rural, number of cases, presence of vulnerable populations and so on)? • What is the risk of epidemic spreading (factors affecting disease transmission and propagation such as dense urban slums, vector density and low population immunity)? • What is the best strategy to control the epidemic? EYE Strategy Country Toolkit 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 74 EYE Strategy Country Toolkit An efficient and effective YF outbreak investigation can be broken down into four steps:51 Pre-investigation phase; Field investigation; Confirmation and description of the YF outbreak; and Development of the investigation report and notification of authorities. Step 1 – Pre-investigation phase This phase includes the following activities: • An outbreak coordination committee should be set up that oversees all phases, from investigation to response. It is recommended that the committee includes decision-makers from the national Essential Programme on Immunization and communicable disease programme. Regional focal points and the Eliminate Yellow fever Epidemics (EYE) Secretariat can support technical questions on investigations and response, and can help to ensure streamlined transport of samples to regional reference laboratories. • A rapid response team should be deployed that will conduct the field investigation. It is recommended that the rapid response team includes an entomologist familiar with common YF vectors, an epidemiologist, a laboratory specialist (where applicable), a clinician and a logistician with a direct link to the laboratory coordinator to ensure proper sampling and efficient transport. A coordinator should be designated early, and all team members should be vaccinated for YF at least 10 days before the field investigation. Step 1 Step 2 Step 3 Step 4 51 Investigation of yellow fever epidemics in Africa: field guide. Geneva: World Health Organization; 2008 (https://extranet. who.int/iris/restricted/handle/10665/69874, accessed 24 July 2023). The field investigation should be prepared. This includes: • preparing the logistics and the necessary equipment, determining the procedures for communication and informing the national laboratory; • estimating the budget required for the investigation and mobilizing resources; and • obtaining administrative permits for the investigation. Existing information should be gathered and reviewed, and the context analysed for risk of spread. This includes: • reviewing existing YF surveillance data and vaccine coverage in the finest detail possible; • collecting information on suspected cases (including clinical signs, date of onset, YF vaccination status); • assessing the local risk for amplification and spread, population movements, vulnerable groups and population immunity profile; and • assessing local capacity for control and response, mapping of actors and partners, means of communication in the affected area, security and so on. 13 75 52 Yellow fever: rapid field entomological assessment during yellow fever outbreaks in Africa: handbook: methodological field approaches for scientists with a basic background in entomology. Geneva: World Health Organization; 2014 (https:// extranet.who.int/iris/restricted/handle/10665/112785, accessed 27 July 2023). EYE Strategy Country Toolkit Step 2 – Field investigation This phase includes several core activities to be conducted simultaneously. • Data and specimens from cases should be collected, including data on: • age, gender and area of residence; • clinical signs and symptoms, date of onset, course of disease; • YF vaccination status, date of vaccination and source of information; • movements and travel history, epidemiological linkage with suspected cases (such as same area of residence or shared travel); • any relevant factors of vulnerability (e.g. marginalized subpopulation, barriers to accessing care); and • date of specimen collection and testing results. • Case-finding should be conducted. It is important to detect as many cases as possible to draw proper conclusions and orient the recommendations. This step helps to inform the team about whether the outbreak is spreading and amplifying; it also describes the populations who are most affected, including any particular barriers or vulnerabilities of these groups. Special care should be given if vulnerable or hard-to- reach populations are affected. Active case-finding can support this by: • drawing up a list of suspected cases received from the health facilities; • verifying the accuracy of the list of cases from health facilities (interviewing staff, performing retrospective searches from the admission and consultation registers and so on); • making home visits to every suspected case, and taking specimens from individuals and family members; • in the place visited, looking for other suspected cases in the community (including interviewing local authorities, village chiefs, religious authorities, teachers); and • ensuring that the sociodemographic nature of the affected communities is documented, including accessibility, gender, cultural and economic characteristics, and highlighting any barriers to health services and care. • Rapid entomological investigation should be conducted. The main objectives are to identify the likely species of mosquito vector(s) implicated in transmission and to assess vector density. The details used to collect specimens for investigation purposes depend on the vector’s stage of development, and can be found in other WHO guidelines.52 These include the capture of active and resting adult vectors, the collection 13 76 EYE Strategy Country Toolkit of immature forms (larvae and pupae) and the calculation of Stegomyia indices for the density assessment (Breteau, Container and House Indices for Aedes spp). A brief summary of key indices and thresholds is set out below. Key indices are: • the Breteau Index: the number of containers found positive for larvae and pupae per 100 houses surveyed; • the Container Index: the percentage of containers that are found positive; and • the House Index: the percentage of houses found positive for larvae or pupae. There is an epidemic risk when the results are: • >5% for the Breteau Index; • >3% for the Container Index; • >4% for the House Index. • The entomological investigation should be interpreted, from which three scenarios are possible. • all indices have values above the risk threshold, so the epidemic risk is established; • one index has a value over the risk threshold, while others are below the threshold – the risk is thus established in the area(s) based on the values over the risk threshold; or • none of the indices has a value over the risk threshold, in which case the area is considered safe or without risk of YF epidemic. It is not required or routinely recommended to test for YF virus presence in vectors through polymerase chain reaction (PCR) or other techniques. Step 3 – Confirmation and description of the YF outbreak The description should cover time, place and person. • An epidemic curve should be drawn to depict the evolution of the epidemic over time (with date of case onset on the horizontal axis, and number of cases (or deaths) on the vertical axis). The curve will help to determine the stage of the outbreak, the possible origin of the virus, the scale of the epidemic and the speed at which the epidemic is spreading. • Maps should be developed to indicate the geographical distribution of cases and visualize the spread of the outbreak and the areas at risk. These may be electronic/geographical information system (GIS) or hand- drawn maps, depending on the context and resources available. • Case characteristics should be analysed (including age and gender distribution) that can influence mortality and morbidity. This is particularly useful in defining the vaccination strategy (defining how many people need to be vaccinated and the target population). This helps in identifying high-risk groups. 13 77 • The level of severity should be assessed. Data collected should be analysed to gain a better understanding of the outbreak and guide outbreak response activities. It is important to calculate key indicators such as weekly incidence, attack and case fatality rates to assess the outbreak severity for each geographical level and specific groups. • The risks of the disease spreading should be evaluated. It is important to analyse the data carefully to assess whether there is evidence of urban, intermediate or sylvatic transmission. The response should be informed by the investigation assessment of the risk of further amplification of the outbreak, as well as the risk of future epidemics if appropriate control strategies are not implemented. Key factors include: • human migration: migration by nomads, travel by traders, religious gatherings, forced population displacements and so on; • vector density: evaluated from the entomological investigation; • population immunity: the proportion of population already immunized (the risk of spread is considerably reduced when at least 60–80% of the population is immunized); and • other factors including the surveillance quality, seasonality (e.g. rainy season), population density, presence of vulnerable groups (e.g. children living in poor urban areas), hard-to-reach communities, a fragile or conflict context or other access barriers. • A root-cause analysis should be conducted to assess the potential causes of the outbreak (generally failure to administer or receive the vaccine, or low performance of the surveillance system), which will allow corrective measures to be taken. Step 4 – Development of the investigation report and notification of authorities A preliminary outbreak investigation report summarizing the main features of the epidemic (together with an analysis of risk of spread, explanation of causes and recommendation for the response) must be submitted to the ministry of health within a few days of completion of the investigation. The occurrence of YF cases may constitute a public health emergency of international concern, and should be assessed and notified under the International Health Regulations (2005) (IHR). EYE Strategy Country Toolkit 13 78 Further reading 53 Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Weekly Epidemiological Record. 2017;92(16):193–204 (https://apps. who.int/iris/handle/10665/255374). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Surveillance standards for vaccine-preventable diseases, second edition. Geneva: World Health Organization; 2018 (https://iris.who.int/ handle/10665/275754). 53 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 13 79 The importance of responding appropriately to yellow fever outbreaks Rapid containment of an outbreak is essential to prevent large amplification into epidemics with international spread: yellow fever (YF) is a serious disease with demonstrated ability to cause a serious public health impact and to spread rapidly internationally. All YF cases must be assessed, as they may constitute a public health emergency of international concern, which should be notified under the International Health Regulations (2005) (IHR).54 14 - Response to yellow fever outbreaks EYE Strategy Country Toolkit An active YF outbreak response revolves around five core activities: 1 appropriate case management; 2 vector surveillance and control activities (when appropriate); 3 active surveillance for new cases; 4 a high-quality reactive vaccination campaign (where warranted); and 5 proper social mobilization and risk communication. What is included in each core activity of a comprehensive outbreak response 1 Appropriate case management Appropriate case management is essential to reduce the morbidity and mortality of YF outbreaks. There is no specific treatment for YF. Rest, and symptomatic and supportive treatment of symptoms (including fever, dehydration, possible bacterial superinfection) are the only possible strategies. Intensive care may be required in the most severe cases. Patients with suspected or confirmed YF should stay under mosquito nets during the day to prevent mosquito bites and limit the risk of propagation of the virus among the mosquito population, leading to potential onward spread. 54 See Annex 2. In: International Health Regulations (2005), third edition. Geneva: World Health Organization; 2016 (https:// apps.who.int/iris/handle/10665/246107, accessed 27 July 2023) for further detail. 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 80 2 Vector surveillance and control activities (when appropriate) Vector surveillance and control can reduce the risk of YF virus transmission among populations until vaccination takes effect, particularly in urban settings. Basic surveillance of vectors using mosquito traps will provide valuable information on the density of the mosquitoes, and help with targeting control interventions in hotspots. Vector control will not interrupt the sylvatic cycle of YF, but it may provide local benefits in adjoining rural areas. These interventions will benefit greatly from active engagement with communities and adaptation to the local context. In urban settings, the plan for immediate intervention relies on the following: • Adult vectors need to be destroyed by spraying insecticides in towns and villages. Fogging – using special truck-mounted devices or portable backpack sprayers – is most effective when conducted when mosquito activity is most intense, close to dawn and dusk. Two successive treatments at two-week intervals are recommended to eliminate the high density of mosquitoes that hatch after the first treatment. • All breeding sites around health facilities, patients’ households and worksites should be eliminated. Cleaning campaigns (such as removal of tyres, empty cans), covering of reservoirs, administration of larvicides should be organized. Additional efforts should focus on cleaning water storage containers (found to breed mosquitoes) in and around houses. Such measures should be done every week, with community involvement. Scrubbing the containers after use will further eliminate eggs of the mosquitoes. • The eggs of survivors should be captured. Ovitraps – which are simple cylindrical or flowerpot- shaped plastic containers with low levels of water and 10% hay infusion – can be placed in sentinel areas to attract gravid mosquitoes to lay their eggs in them. These traps can then be emptied periodically to destroy the immature stages of the mosquitoes. • Advice should be sought from local experts. An entomologist can support the programme and help with surveillance, placing the traps and monitoring them periodically, and can assess the impact of all control interventions. Community leaders can help to guide how to engage with populations, determine areas that are disadvantaged or vulnerable, and liaise with civil society groups that can support vector control activities. 3 Active surveillance for new cases Epidemiological surveillance should be reinforced to keep track of the scale of the epidemic and the transmission dynamics of the outbreak, and to answer to the following questions: • Are there any new cases? • If so, where are they? Raising awareness among health-care workers regarding the presentation and reporting requirements for suspected YF cases can help to improve the sensitivity of the surveillance system. Focused efforts should be made to reduce barriers and improved access for communities or subpopulations identified to be at particularly high risk, and to build trust to encourage early health-seeking behaviours. If needed, the case definition should be adapted (to make it more sensitive) and rapid transmission of the information ensured. Surveillance activities need to be linked to the response, to adapt control measures continually to the epidemiological situation. Regular epidemiologic updates should be provided at district and national levels to communicate the evolution of the outbreak and document the impact of response activities. EYE Strategy Country Toolkit 14 81 4 A high-quality reactive vaccination campaign (where warranted) Reactive vaccination campaigns (RVCs) are instrumental in controlling the spread of YF epidemics in areas with low underlying population immunity (especially if it is <80%). However, it takes from 5 to 10 days for vaccinated people to become immune. RVCs require strong coordination, careful planning and rapid mobilization of resources. The International Coordinating Group (ICG) on vaccine provision manages the global stockpile of YF vaccine funded by Gavi, the Vaccine Alliance. This is provided to countries within 14 days of an approved campaign. Funds are also available to support operational costs in Gavi-eligible countries (see Section 8 for details on the process to access these). The following YF outbreak vaccination responses are suggested to follow a phased approach for implementation: • First, a limited reactive campaign can be mounted rapidly, with the possibility of using in-country doses of the YF vaccine, where feasible. If this is not possible, then the activity may be achieved with the next stage of response and should not delay ICG application. • Second, a broader RVC should be mounted, comprehensively targeting the affected area, which may be supported by application to the ICG where helpful to the country. Preparation for the RVC requires planning tailored to communities and districts, with inclusion of all high-risk subpopulations and particular care for groups that may have barriers to access vaccination or be in hard-to-reach communities (e.g. gender, sociocultural reasons, geographical locations) (see Section 4 for more details). • Third, analysis should be undertaken of underlying population immunity and potential needs for a pre-emptive vaccination campaign targeting at-risk populations in anticipation of imminent epidemic threat in areas that do not have a current YF outbreak (i.e. where YF cases have not been confirmed) but that face heightened risk and vulnerability, and where population immunity is low. A conservative approach should be taken to ensure that adequate doses of YF vaccine are available to cover the target population in the affected area. For example, if the RVC occurs during a period with seasonal influx of visitors, more doses and vaccination teams or sessions may be required, and should be incorporated into the response microplans. RVCs require the development of macro- and detailed microplanning that will include the following activities: • selecting the target areas and immunization sites; • defining the target group and estimating the size of the target population (primary target group of 9 months to 60 years of age); • defining a tailored approached where necessary to ensure high uptake among all subpopulations, ages and genders in the target population; • estimating the number of vaccines required for the emergency activities; • arranging for RVC cards to be printed and distributed; • estimating the quantity of cold chain supplies; • developing a waste management plan; EYE Strategy Country Toolkit 14 82 • setting up a surveillance system for adverse event following immunization (AEFI) monitoring; • defining the scope and preparing monitoring and evaluation activities; • requesting vaccine and immunization supplies (see Section 15); • selecting vaccination teams and providing training; • arranging transportation to vaccination sites; and • conducting social mobilization, with attention to any particular subpopulations with specific 5 Proper social mobilization and risk communication Information about YF prevention should be part of primary health-care programmes during outbreaks. Specific messages about prevention of YF are recommended to include: • promotion of YF vaccination through campaign activities; • prevention of mosquito breeding areas by: • placing covers or screens over containers of daily water supplies; • ensuring safe disposal of discarded items that could become containers for standing water (such as discarded tyres, tins and jars); • community mobilization to clean up the discarded items or bury them; • awareness of YF disease symptoms and how to access care quickly and at early stages of infection. At the district level, communication focal points should be involved in identifying and training social mobilizers (see Section 4, Section 6 and the WHO guide 55 for more details). Checking whether a single case of YF is an outbreak requiring a response 55 Communication and social mobilization in yellow fever mass vaccination campaigns: 10 points from field experience. Geneva: World Health Organization; 2015 (https://extranet.who.int/iris/restricted/handle/10665/156053, accessed 24 July 2023). Immediate steps on new case confirmation include: • notifying the national ministry of health and WHO; • characterizing what is known so far (including number of cases – confirmed or suspected – and any available case details); • assessing the resources and technical expertise readily available, and asking the ministry of health and WHO for technical support, if required; • launching an in-depth investigation rapidly; • determining a best estimate of underlying population immunity surrounding the case(s) (Fig. 15; Table 4). EYE Strategy Country Toolkit 14 83 EYE Strategy Country Toolkit Vaccination response ISOLATED CASE: seek more information about spread Data suggests additional cases possible Consider targeted interventions (e.g. vaccinate missed persons, vector control) Consider targeted interventions (e.g. vaccinate missed persons) ANY warrants RCCE & enhanced surveillance High immunity OUTBREAK OUTBREAK or imminent risk of outbreak OUTBREAK Not an outbreak. Consider targeted interventions Enhance human and vector surveillance & investigation Risk communication & engagement with communities (RCCE) Vaccination response *Use LOW IMMUNITY pathway if content is complex, large-scale population movement, or security compromise. What is the context? Newly confirmed YF cases(s) Low immunity* Rural Urban Investigate for possible outbreak and spread Isolated case (e.g. remote) NO additional cases identified Additional cases / Cluster (confirmed or probable cases and deaths) Vaccination response and complementary interventions (eg. vector control, mapping of transportation hubs and further investigation along main routes) Assess if isolated case vs. signs of possible spread Fig. 15. Checking whether the case is an outbreak 14 84 Table 4. Determining the response strategy Area with low/no vaccination coverage Area with good vaccination coverage (e.g. >80% population immunity) • Initiate vaccination in the affected area, such as the village, district, town or city, or within 10–50 km of the affected area (scale to be determined by several factors, such as population density and vaccination coverage) • Offer targeted vaccination to susceptible individuals or unvaccinated groups in the immediate area • Large-scale emergency vaccination or re-vaccination is not justified • Review and ensure that additional core elements for comprehensive response are in place, including surveillance enhancement and case-finding, case management, vector surveillance and control, social mobilization and risk communication Source: Yellow fever surveillance and outbreak response: revision of case definitions, October 2010. Weekly Epidemiological Record. 2010;85(47):465–72 (https://extranet.who.int/iris/restricted/handle/10665/241676, accessed 24 July 2023). EYE Strategy Country Toolkit Documenting campaign progress and impact All RVCs should be documented and reported to stakeholders and partners. It is important to initiate planning, budgeting and protocol development for the post-campaign vaccination coverage survey during the initial stages of the response to ensure that the monitoring and reporting is completed in a timely manner. Elements for inclusion in summary reports are: • the number of people vaccinated and doses used during the campaign; • the administrative coverage obtained; • the results of the independent vaccination coverage survey; • the number of doses of vaccine remaining on completion of the campaign; • any reports of serious AEFIs; and • a summary of lessons learned, course-corrective actions and examples of best practice, as well as any key challenges encountered. 14 85 Further reading 56 A toolkit for integrated vector management in sub-Saharan Africa. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/ handle/10665/250267). Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017–2026. Wkly Epidemiol Record. 2017;92(16):193–204 (https://apps.who.int/ iris/handle/10665/255374). Entomological surveillance for Aedes spp. in the context of Zika virus: interim guidance for entomologists. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/204624). Global Strategy to Eliminate Yellow fever Epidemics (EYE). Document for SAGE – 26 September 2016. Geneva: World Health Organization; 2016. (https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/11_session_Yellow-fever/Oct2016_Session11_EYE_ strategy.pdf). Immunization supply chain interventions to enable coverage and equity in urban poor, remote rural and conflict settings. New York: United Nations Children’s Fund; 2020 (https://www.unicef.org/documents/immunization-supply-chain-interventions). Investigation of yellow fever epidemics in Africa: field guide. Geneva: World Health Organization; 2008 (https://iris.who.int/ handle/10665/69874). Vaccination in humanitarian emergencies: implementation guide. Geneva: World Health Organization; 2017 (https://iris.who.int/ handle/10665/258719). Vector control operations framework for Zika virus. Geneva: World Health Organization; 2016 (WHO/ZIKV/VC/16.4; https://apps.who.int/ iris/handle/10665/207481). 56 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 14 86 The International Coordinating Group (ICG) on Vaccine Provision for yellow fever A global reserve of 6 million of doses of yellow fever (YF) vaccine is always available to respond rapidly to YF outbreaks.57 The stockpile is managed by the International Coordinating Group (ICG) on Vaccine Provision Committee, which includes representatives from WHO, the United Nations Children’s Fund (UNICEF), Médecins Sans Frontières and the International Federation of Red Cross and Red Crescent Societies (IFRC), and is funded by Gavi, the Vaccine Alliance.58 The conditions required to access the YF vaccine stockpile All countries can submit an ICG request, regardless of their Gavi eligibility. Gavi-eligible countries may also apply for financial support of operational costs related to the emergency vaccination campaigns. A timely response is essential. The global stockpile is intended to be used to prevent outbreaks and large- scale epidemics. Countries should apply as quickly and completely as possible for emergency response if a confirmed YF outbreak occurs, and if in-country vaccine stocks are inadequate for response. Non-Gavi-eligible countries are eligible to receive YF vaccines from the emergency vaccine stockpile provided that the request is approved by the ICG Committee (based on the results of the assessment of the risk of amplification and spread of the disease); and that the ministry of health writes a letter committing to reimburse the costs of the vaccines and of the shipment, and submits it to the UNICEF Supply Division. 15 - Access to yellow fever vaccine stockpiles for emergency response EYE Strategy Country Toolkit 57 2023 Yellow Fever Emergency Stockpile. New York: United Nations Children’s Fund; 2023 (https://www.unicef.org/supply/ media/20091/file/EmergencyStockpileAvailabilityReportYFV27112023.pdf, accessed 29 November 2023). 58 ICG for yellow fever. In: World Health Organization [website]. Geneva: World Health Organization; 2023 (https://www.who. int/groups/icg/yellow-fever, accessed 29 November 2023). 1 EYE Strategy 2 YF risk 3 YF vaccine 4 Fragile populations 5 Vaccine coverage 6 Communication 7 Monitoring campaigns 8 RI 9 PMVC 10 Campaign logistics 11 International spread 12 Surveillance 13 Outbreak investigation 14 Outbreak response 15 Vaccine stockpiles 87 EYE Strategy Country Toolkit The following conditions need to be fulfilled to apply for the vaccine: • at least one of the YF notifications has been laboratory confirmed; • a careful assessment of the epidemic risk has been conducted to differentiate the start of an epidemic from sporadic cases due to sylvatic transmission; • a vaccination plan for the immunization campaign has been provided; • the request has been reviewed and approved by the national epidemic coordination committee or similar approval body; and • if implemented through an agency, that agency can demonstrate extensive experience in conducting a mass vaccination campaign. For more information For further information and assistance regarding those conditions, please review the guidelines for ICG requests for YF emergency stockpile and/or contact the YF focal point at WHO at: ICGsecretariat@who.int. How to apply for the YF vaccine in the ICG stockpile To apply for the YF vaccine in the stockpile, the country needs to submit a completed ICG YF vaccine request application form and supporting annexes, budget and vaccination plan to the ICG Secretariat. On receipt of the request, the ICG Secretariat will summon the ICG Committee, which will review the request. A decision will be taken, usually within two working days. When the ICG Committee accepts a request, the ICG Secretariat will authorize the UNICEF Supply Division to send the vaccines from the global emergency stockpile. The vaccine and associated supplies required for implementation will be sent by air and will arrive within 14 days, in accordance with ICG procedures. In order to expedite the process and avoid delays, countries are urged to use the support of their WHO country office to draft and submit YF vaccine requests to the ICG. The requirements for a successful ICG request Guidelines on access to the ICG YF stockpile and current request forms, annexes and budget template can be downloaded from the ICG website.59 59 Yellow fever vaccines stockpiles. Geneva: World Health Organization; 2023 (https://www.who.int/groups/icg/yellow-fever/ stockpiles, accessed 27 July 2023). 15 88 The request should be submitted to the ICG Secretariat by email and should include the following documents: • a completed ICG YF vaccine request application form (5 pages); • maps (one or more illustrating locations of cases and areas to be vaccinated/adjacent areas); • completed application annexes (annexes 1–4 on the ICG website); • a completed campaign budget (if operational funds are requested); • a vaccination plan by district; • an outbreak investigation report and spot map showing case locations in the affected areas; and • a copy of the original regional reference laboratory results. Information about the risk of spread is required, such as (but not limited to): • presence of subpopulations particularly vulnerable to YF spread (such as low-immunity, hard-to- reach, transient subpopulations); • characterization of population movements including volume, frequency and type of connectivity; and • existence of transportation hubs in the affected area and along the travel routes of cases as relevant). The application form will include an epidemiological summary and rationale for conducting a reactive campaign. The form requests completion of the following information. Epidemiological information, including a summary of available details on the current outbreak and a rationale for the response, is required. The country is asked to provide an overview of the number of cases, how they were confirmed and key risks for onward spread that have informed the area proposed for the response. A short summary of past outbreaks and background immunity to YF is required. This is supported by the annexes to the request form. Data allowing assessment of cases – including line-listing with clinical presentation, history of vaccination status, date of symptoms onset, date of sampling, laboratory results by test (immunoglobulin M (IgM) or polymerase chain reaction (PCR)) in a national reference laboratory and in a regional reference laboratory (IgM, plaque reduction neutralization test (PRNT) with titres, PCR on blood) – are needed. Details of the epidemiological investigation, including active case-finding, are needed. The WHO field guide on investigation of YF epidemics in Africa provides 60 a framework for investigation of YF epidemics. Maps of confirmed and suspected cases and deaths, preferably at the subdistrict level are to be included. Epidemiological curves of suspected and confirmed cases at the district level are recommended to support the application. 60 Investigation of yellow fever epidemics in Africa: field guide. Geneva: World Health Organization; 2008 (https://extranet. who.int/iris/restricted/handle/10665/69874, accessed 24 July 2023). EYE Strategy Country Toolkit 15 89 EYE Strategy Country Toolkit Environmental, seasonal and vector distribution data with reference to factors that could affect local transmission and risk of amplification are needed, such as (but not limited to): • setting and land-use patterns in affected area; • type of biome and whether non-human primates are present in the area; • seasonal factors – including occurrence and timing of rainy seasons; • basic entomological surveys, if available (e.g. species and density of Aedes spp. mosquitoes, environmental conditions), population immunity levels/vaccination coverage, urban/rural settings), although sampling and testing for virus circulation in vector populations is not expected; and • data on population immunity. A map of the areas proposed for reactive vaccination, preferably at subdistrict level, is needed. The needs of the requested area of response – including target population, number of doses and needs for additional support, including vaccination cards – should be outlined. Information on whether the country is also applying for financial support for operational costs (for Gavi-eligible countries) is also needed. The annexes to the request form also include the following information: • a line-list of cases and epidemiological information, history of YF outbreaks and history of vaccination campaigns; • country requirements regarding injection materials, and whether in-country stock is available that can be replenished at a later date by the ICG. The ICG prioritizes requests for vaccines on the basis of: • emergency situation criteria (the number of people at risk at a certain time and place and evidence of an epidemic situation); and • the risk of amplification and spread (risk of spread to other areas or bordering countries, vector densities, number of non-immune people). A successful ICG request should also present how the country plans to organize the reporting and to structure the monitoring and evaluation component, including a timely independent post-campaign coverage assessment. The criteria for release of YF vaccine by the ICG 15 90 The final number of vaccine doses delivered will depend on: • the number of doses available at the global level; • current epidemics in other countries; and • the country’s preparedness and readiness to conduct a mass vaccination campaign. The activity report should include: • a summary of how the campaign was organized, with a description of logistics and human resources required, target population, funds disbursed and so on; • the number of doses administered, reports of adverse events following immunization (AEFIs), independent evaluation of vaccination coverage, vaccine utilization and accounting for wastage and any leftover vaccine. The cost Any country facing a YF epidemic is eligible to receive vaccines from the emergency vaccine stockpile. Gavi- eligible countries may also apply for financial support for emergency vaccination campaign operational costs, provided they submit a vaccination plan with a detailed budget for operational costs along with the request. In order to ensure the sustainability of the YF emergency stockpile, all countries that receive vaccines and material from this stockpile should have their costs reimbursed, including the shipment expenses. The reporting requirements for reactive campaigns supplied by the ICG Any reactive campaign completed using YF vaccine provided by the ICG must submit a report on the campaign impact within three months of the campaign. The report serves as a justification document for donors that provide funds for the constitution of the vaccine and injection materials in emergency stockpiles. A summary of lessons learned, including local successes from any course-corrective actions should also be included, as well as any key challenges encountered. Further reading 61 Guidelines for ICG request for yellow fever emergency stockpile. Geneva: World Health Organization; 2020 (https://cdn.who.int/media/ docs/default-source/documents/emergencies/international-coordinating-group-icg-on-vaccine-provision/guidelines_icg-request_ yellow-fever_en.pdf?sfvrsn=789dda3c_13). International coordinating group for yellow fever control (ICG): ICG yellow fever vaccine FAQ request for yellow fever vaccine stockpile. Geneva: World Health Organization; 2020 (https://cdn.who.int/media/docs/default-source/documents/emergencies/international- coordinating-group-icg-on-vaccine-provision/faq_icg-request_yellow-fever_en.pdf?sfvrsn=13ba7f0e_12). 61 All references accessed 24–27 July 2023. EYE Strategy Country Toolkit 15 World Health Organization 20 Avenue Appia 1211 Geneva 27 Switzerland www.who.int