Global Vaccine Safety

Yellow fever vaccine safety

Extract from report of GACVS meeting of 3-4 December 2003, published in the WHO Weekly Epidemiological Record on 16 January 2004

Cases of viscerotropic disease following yellow fever vaccination were described in the United States and other countries, and current evidence suggests that these cases were a result of vaccine-type virus and not of reversion of the vaccine virus to wild type. Unlike the viscerotropic complications of yellow fever vaccination, reported neurotropic cases from the United States have not been fatal. The neurotropic cases presented as GBS (thought to be immune- mediated), encephalopathy (thought to be due to active invasion of the central nervous system by the virus) or acute demyelinating encephalomyelitis (thought to be caused either by direct invasion of the brain by the virus or by an immune-mediated response to the virus). All cases of viscerotropic disease to date have been reported in primary vaccinees, starting 2–5 days after vaccination. Whether this reflects the persistence of pre-existing immunity at the time of revaccination or lower rates of revaccination in the study populations cannot be determined. The rate of reported viscerotropic disease varies in different settings. In particular, a lower rate has been reported in Brazil than in the United States. GACVS considered that it would be important to examine the possibility that naturally circulating yellow fever virus in endemic regions may account for some of these differences in risk.

The risk of viscerotropic complications of yellow fever vaccine is age-related; individuals aged 65 years and over who are first recipients of the vaccine are at considerably higher risk than younger subjects (although the young are not excluded from the risk). Recent evidence from the United States also suggests a higher risk of neurotropic disease in older vaccinees. There needs to be a better estimate of the risk, and prediction of subjects at risk and of factors predisposing to risk of both types of serious complication of the yellow fever vaccine. In communicating such risks, consideration needs to be given to highlighting potential contributing factors, such as age or sensitivity of surveillance systems, to risk estimates based on currently available data. Particular care should be taken that the vaccine is received only by those travellers truly at risk for yellow fever exposure. Furthermore, care should be taken that routine yellow fever vaccination programmes are not jeopardized by risk–benefit ratios that may be inapplicable to the target populations in endemic countries.

A critical and unresolved issue is the safety and efficacy of yellow fever vaccine in human subjects infected with immunodeficiency virus (HIV). It remains to be determined whether HIV-positive status materially affects seroconversion, the risk of invasion of the nervous system and of encephalopathy, the stage of HIV disease at which yellow fever vaccination should be contraindicated, and whether there are differences in the incidence of minor and major adverse effects in HIV-positive subjects.