Global Vaccine Safety

Yellow fever mass vaccination campaigns using fractional dose

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

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.


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