More than 47 countries worldwide are endemic for yellow fever (YF) and regularly experience outbreaks. Yellow fever remains endemic in South America, and East and Central Africa. Recent epidemics have occurred in southern and East Africa, particularly Angola, the southern region of the Democratic Republic of Congo (DRC) and Uganda. In 2016, over 3867 cases, with 369 deaths, were documented in Angola. Mass YF vaccination campaigns have been extensively implemented for disease control; from 2007 to 2012, 12 campaigns have occurred in Africa with over 64 million doses distributed.10 YF vaccine is highly effective, with a single dose providing life-long protection; the safety profile of YF vaccine is well established. Although serious adverse reactions have been documented (hypersensitivity reactions, viscerotrophic and neurotrophic disease), these are extremely rare and often occur within defined risk groups.

Transmission of YF in 2016 was explosive, particularly in Angola (4347 suspected cases, with 377 deaths, December 2015–October 2016) and in DRC (2987 cases with 16 deaths, January–October 2016). Mass vaccination campaigns were rapidly implemented in both countries in 2016, with 30 865 375 individuals being vaccinated. Because of a global YF vaccine shortage, SAGE recommended that fractional dosage (1/5th of a dose: 0.1ml) could be used via the subcutaneous or intramuscular route. Of those vaccinated in DRC, about 50% (7.5 million) received a fractional dose. In DRC individuals aged >24 months living in Kinshasa were given a fractional dose, while infants and children aged 9–23 months living in Kinshasa or in those areas bordering Angola received a full dose.

One purpose of the GACVS meeting was to discuss the surveillance on adverse events following immunization (AEFI) in DRC following the mass vaccination campaign, with a focus on those who received fractional dosing in Kinshasa. AEFI surveillance (of serious and non-serious cases) in DRC was based on spontaneous reporting (as promoted during the campaign), on community surveys in targeted health zones reporting AEFIs, and sentinel surveillance from sentinel health-care facilities (on alert for all suspected serious cases) and through YF surveillance. The duration of surveillance for serious AEFI cases was 42 days; the vaccination campaign duration was 10 days. Given the current shortage in vaccine and the eventual need to expand the use of fractionated doses, GACVS urged DRC to conduct a detailed analysis of its AEFI reports. Wherever possible, cases with clinical presentation compatible with YF shortly after vaccination should be investigated in order to verify which virus types are involved.

GACVS strongly recommends use of the standardized tools for data collection, and harmonized tools, such as the WHO causality assessment tool, for country-level analysis of the AEFI surveillance data. This method allows for surveillance data to be aggregated, thus enhancing the sensitivity of surveillance for rare events. A comparison should be examined between those individuals who received a full dose of vaccine and those who received a fractional dose, taking into consideration any compounding factors.

¹⁰Breugelmans JG et al. Reporting rates in mass campaigns. Vaccine, 2013, 31(14): 1819–1829.

Full report of GACVS meeting of 30 November-1 December 2016, published in the WHO Weekly Epidemiological Record on 13 January 2017

The introduction of the yellow fever 17D vaccine in the 1930s provided an effective preventive measure resulting in a significant decline of the disease. However, there has been a resurgence of yellow fever resulting from changes in population dynamics, urbanization, deforestation coupled with other agricultural and developmental activities, climate changes and a decline in population immunity. In 2006, the Yellow Fever Initiative led by the WHO in partnership with UNICEF and GAVI was launched to control this resurgence in order to reduce the risk of epidemics in sub-Saharan Africa. This entailed a mass preventive vaccination campaign against the backdrop of other WHO-UNICEF yellow fever control strategies.

The recent (2007–2010) preventive yellow fever (YF) vaccination campaigns in West and Central African countries provided an opportunity for surveillance of AEFIs, thus further characterizing the safety of the vaccine. Nine countries were involved – Benin, Burkina Faso, Cameroun, Guinea, Liberia, Mali, Senegal, Sierra Leone and Togo. GACVS reviewed the recently published findings of surveillance of AEFIs conducted during those campaigns. In all, 38 million doses of the vaccine were administered, and 3116 AEFIs were observed (2952 non-serious and 164 serious). Of the serious AEFIs, 22 were classified as related to the YF vaccine and 142 were not related; of the 22, 6 clinical cases resembled acute neurotropic disease (YEL-AND), 5 clinical cases resembled acute viscerotropic disease (YEL AVD) and a further 11 involved hypersensitivity reactions. The attack rates per 100 000 vaccinated people obtained from the study therefore were 0.016, 0.013 and 0.029 for YEL-AND, YEL-AVD and hypersensitivity reactions respectively. These rates were lower than those seen with recipients of a first dose of YF vaccine in more developed settings. The median time to onset (days) was observed as 8 (YEL-AND), 4 (YEL-AVD) and 1.8 (hypersensitivity reactions). Vaccine virus identification, however, was not successful for acute cases.

The authors noted the challenges and limitations of the study to account for a relatively low specificity and sensitivity of active case findings due to many coincidental cases, operational issues with inadequate collection, storage and transportation of specimens, poor laboratory and investigation facilities, cultural practices hindering post-mortem examination, misclassification of cases, and inadequate prioritization of pharmacovigilance, amongst others. Despite the limitations, the authors concluded that the study has had impact on the countries in ensuring a proactive surveillance system as well as reinforcing the safety profile of YF vaccine in this particular setting.

GACVS noted the enormous challenges of conducting a pharmacovigilance study in a resource-limited setting. The committee suggested that enhanced vaccine safety monitoring, including additional resources to provide adequate capacity and expertise, should be included in planning vaccination campaigns. It observed that the criteria for case definition were very strict and difficult to apply appropriately in such settings. It therefore suggested that more operational criteria could be proposed that would be adapted to local clinical practice or that additional dedicated efforts be conducted to meet existing criteria. There is also a need to put standard operating procedures or tiered instructions in place to strengthen pharmacovigilance and address technical and logistic issues. GACVS also recommended that clinical and laboratory findings even if limited be more systematically correlated with post-mortem examinations.

Full report of GACVS meeting of 12-13 June 2013, published in the WHO Weekly Epidemiological Record on 19 July 2013