The whole iceberg: Estimating the incidence of yellow fever virus infection from the number of severe cases

Abstract

Background: Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission. Methods: We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome. Results: For YF virus infections, the probability of being asymptomatic was 0.55 (95% credible interval [CI] 0.37-0.74), mild disease 0.33 (95% CI 0.13-0.52) and severe disease 0.12 (95% CI 0.05-0.26). The probability of death for people experiencing severe disease was 0.47 (95% CI 0.31-0.62). Conclusions: In outbreak situations where only severe cases may initially be detected, we estimated that there may be between one and seventy infections that are either asymptomatic or cause mild disease for every severe case identified. As it is generally only the most severe cases that are recognized and reported, these estimates will help improve the understanding of the burden of disease and the estimation of the potential risk of spread during YF outbreaks.