Adjusting for Heterogeneity of Malaria Transmission in Longitudinal Studies

Abstract

(See the article by Bejon et al, on pages 9–18.) Although the heterogeneity of malaria transmission has been known for many years, it has only recently become recognized as having importance in the analysis of longitudinal studies [1]. Assumptions of homogenous transmission (ie, that every participant in a given study is exposed to the same number of infectious bites) can lead to incorrect conclusions (eg, that placental malaria is a risk factor for childhood malaria or that parasitemia is protective against clinical malaria) [2–3]. In both these cases, associations have been confused with a causal pathway, and the outcomes have been confounded by the heterogeneity of risk in malaria transmission. Persons living in an area of higher transmission are more likely to develop malaria again than are persons living outside that locality. In turn, after repeated attacks, these persons will develop immunity against clinical disease and become asymptomatic carriers of infection. Infection itself is not the cause of the observed association, but rather exposure to repeated infections in the area of residence. In this issue of the Journal, 2 original articles have examined the effects of heterogeneity in malaria transmission in great depth, using cohort studies to determine how best to consider variation in risk when analyzing studies. One, an observational cohort [4], and the other, a cohort in a vaccine study [5], use measurements of antibodies as their outcome measures.