World Health Organization · 1st edition, 2026 · 70 pages
Standardised investigation tool for understanding immunity gaps and vaccination programme failures after yellow fever outbreaks in endemic countries
- Issuer
- World Health Organization
- Edition
- 1st edition, 2026
- Audience
- National health authorities, EPI focal points, outbreak investigation teams, WHO and UNICEF country offices in yellow fever endemic countries
- Evidence
- Expert consensus; methodology piloted in Guinea, Cameroon, and Central African Republic 2023–2024
- Reviewed
- 17 Oct 2026 · GMJ
What this guideline says
GMJ summary
This WHO user manual provides a systematic methodology for investigating the underlying causes of yellow fever outbreaks in endemic countries, particularly those with a history of mass vaccination campaigns where routine immunisation coverage has not sustained immunity gains. The tool aims to uncover both the epidemiological factors contributing to outbreaks and the specific reasons for immunity gaps in affected populations.
The assessment consists of two main components: Part A provides an in-depth outbreak analysis covering time, place, person, mode of transmission, surveillance indicators, and factors affecting disease transmission; Part B investigates root causes of immunity gaps, examining failure to vaccinate (policy-based, provider-based, and user-based reasons) and vaccine failure (poor vaccine quality, administration errors, host factors). The tool was piloted in Guinea, Cameroon, and the Central African Republic during 2023–2024.
The methodology employs document review, structured interviews with health personnel at central, district, and health facility levels, interviews with confirmed cases or their caregivers, and direct observation of vaccine storage and handling practices. The assessment is designed to be conducted after outbreak response measures (such as reactive vaccination campaigns) and should inform district-tailored recovery plans for vaccination services.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Assessment should be conducted after a reactive vaccination campaign in districts that recently experienced yellow fever outbreaks
- Investigation team must be multidisciplinary, led by an experienced international epidemiologist, including EPI and emergency programme representatives from district and central levels
- All team members must provide proof of yellow fever vaccination at least 10 days before field investigation starts
- Part A checklist systematically collects data on outbreak description (time, place, person, transmission mode), likelihood of case underestimation (surveillance completeness target ≥80%, specimen rate target ≥80%), and transmission factors (vector species, non-human primate presence, human exposure to sylvatic environments)
- Part B questionnaire investigates failure to vaccinate through examination of vaccination coverage accuracy, vaccination plan gaps for high-risk populations, missed sessions, vaccine stock-outs, lack of qualified vaccinators, knowledge gaps, and user hesitancy
- Vaccine failure investigation includes assessment of ice-lined refrigerator (ILR) function, vaccine storage at correct temperature (2–8°C), reconstituted vaccine discard after specified hours, subcutaneous injection technique, and use of diluent from same manufacturer
- Root cause analysis examines policy-based reasons (inaccurate coverage estimates, gaps in vaccination plans), provider-based reasons (missed sessions, stock-outs, lack of training, misconceptions about contraindications), and user-based reasons (vaccine hesitancy, access barriers, lack of campaign awareness)
- Assessment findings should inform a district-tailored recovery plan through a feedback workshop with national health authorities, WHO, UNICEF, and interviewed personnel to identify corrective measures and establish priorities
Immediate and underlying causes related to a yellow fever outbreak in a district
Table extracted from the guideline
| Category | Reasons | Immediate causes | Underlying causes |
|---|---|---|---|
| Failure to vaccinate | Policy-based | Inaccuracy of estimation of yellow fever vaccination coverage; Gap in vaccination plan for general population and populations at higher risk | |
| Failure to vaccinate | Provider-based (routine) | Missed routine vaccination sessions; Stock-out of yellow fever vaccines/equipment; Lack of qualified vaccinators; Lack of knowledge/misconceptions regarding yellow fever vaccination policy, co-administration, contraindications | Limitation in skills enhancement; Lack of supervision in vaccination activities |
| Failure to vaccinate | Provider-based (campaigns) | Stock-out of vaccines; District not fully covered by vaccination campaign; Lack of knowledge regarding co-administration and contraindications | Limitation in skills enhancement; Lack of supervision |
| Failure to vaccinate | User-based | Vaccine hesitancy/obstacles to vaccination; Yellow fever vaccine knowledge and misconceptions; Obstacles to routine vaccination; Lack of awareness of mass vaccination campaigns | |
| Vaccine failure | Provider-based | Poor quality of yellow fever vaccines due to: defective ice-lined refrigerator, poor storage of vaccine/diluents during and outside sessions; Staff practice failure in injection | Lack of trained staff; Misconceptions/lack of knowledge |
| Vaccine failure | User-based | Primary failure; Secondary failure; Host factors |
Source: World Health Organization, Root cause analysis of a yellow fever outbreak: user manual and questionnaire. Reproduced in summary form.
From the guideline
Verbatim
“A yellow fever outbreak provides an opportunity to learn more about the local epidemiology of the disease by identifying its source and contributing factors. It also helps strengthen the immunization program by uncovering the causes of underlying immunity gaps.”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As someone who has worked extensively on immunisation programme strengthening in the South Caucasus, I recognise the value of this systematic root cause analysis methodology well beyond yellow fever. While Georgia is not endemic for yellow fever, the structured approach to investigating immunity gaps—examining policy failures, provider knowledge and capacity, user hesitancy, and cold chain integrity—is directly applicable to challenges we face with measles resurgence, suboptimal HPV vaccine uptake, and coverage inequities among internally displaced populations and ethnic minorities. The tool's emphasis on multi-level data collection (central, district, facility) and triangulation through document review, interviews, and direct observation mirrors best practices we have advocated through the Public Health Institute of Georgia. I would particularly stress to Georgian colleagues the sections on supervision gaps and missed opportunities during routine sessions, as our own programme reviews have identified these as persistent weaknesses. One implementation caveat: the resource requirements for this depth of investigation—international epidemiologist, field visits, extensive interviews—may exceed capacity during simultaneous outbreaks or in resource-constrained settings, requiring prioritisation of which outbreaks warrant full root cause analysis versus rapid assessment.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 17 Oct 2026
Applicability
Georgia and the South Caucasus
This manual is highly relevant for Georgia and the South Caucasus region, which lie adjacent to yellow fever endemic zones and face risks from imported cases among travellers, migrant workers, and refugees from endemic countries in Africa and South America. While Georgia is not endemic for yellow fever, the systematic root cause analysis methodology can be adapted for investigating immunity gaps and vaccination programme failures for other vaccine-preventable diseases within the national immunisation programme. Georgian public health authorities should consider this framework for strengthening outbreak investigation capacity, improving routine immunisation coverage monitoring (particularly for mobile and hard-to-reach populations), and ensuring robust cold chain management—challenges that are universal regardless of the specific pathogen. The emphasis on multi-level assessment (central, district, health facility) aligns well with Georgia’s decentralised health system structure established under the Universal Health Care programme.
Questions this guideline answers
Quick answers
When should this root cause analysis tool be used?
The assessment should be conducted in a district that recently experienced a yellow fever outbreak that triggered a reactive vaccination campaign and where there is a need for in-depth evaluation of root causes. It should be completed after implementation of outbreak response measures, not during the acute phase.
What qualifications are needed for the investigation team?
The team must be multidisciplinary with skills in outbreak investigation and vaccination activities (mass campaigns and routine vaccination). It must be led by an international, experienced epidemiologist and include representatives of both the EPI and emergency programmes and health personnel from district and central levels. All team members must have documented yellow fever vaccination at least 10 days before field work begins.
How long does reconstituted yellow fever vaccine remain usable?
The questionnaire assesses whether vaccinators know the correct discard time for reconstituted yellow fever vaccine, which varies by manufacturer. Investigators should compare responses against the specific manufacturer's instructions included with the vaccine being used. Improper timing of discard (too early or too late) constitutes a gap in vaccine handling practices.
What surveillance indicators suggest underestimation of outbreak scale?
Key indicators include: universal health coverage index score <80%, completeness of reporting from designated units <80%, specimen rate (percentage of suspected cases with specimens collected) <80%, scattered populations with poor access to care, lack of trained community health workers involved in yellow fever surveillance, and delays in care-seeking by confirmed cases. Any of these suggest the true outbreak size may be larger than reported.
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- Issuer
- World Health Organization
- Type
- Manual
- Edition
- 1st edition, 2026
- Status
- Current
- Published
- 2026-06-03
- Languages
- English
- Scope
- Investigation of yellow fever outbreaks in endemic countries to identify root causes of immunity gaps
- Audience
- National health authorities, EPI focal points, outbreak investigation teams, WHO and UNICEF country offices in yellow fever endemic countries
- Pages
- 70
- Licence
- CC BY-NC-SA 3.0 IGO
- ISBN
- 978-92-4-012138-6
- Evidence
- Expert consensus; methodology piloted in Guinea, Cameroon, and Central African Republic 2023–2024
- Record history
- Created 17 Oct 2026 · updated 17 Oct 2026 · next check Apr 2027
Root cause analysis of a yellow fever outbreak: user manual and questionnaire. Geneva: World Health Organization; 2026. Licence: CC BY-NC-SA 3.0 IGO.GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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