Relationships between the outcome of Plasmodium falciparum infection and the intensity of transmission in Africa

Establishing the relationship between transmission intensity and health outcomes is crucial for the planning of long-term malaria control programs. Unfortunately this is fraught with methodologic difficulties. In this report, we address some of these problems by considering some important parameters that have previously been ignored. One important consideration is that the incidence of infection for Plasmodium falciparum malaria is much lower than entomologic inoculation rates (EIRs), especially at higher transmission levels. Moreover, biting rates of malaria vectors per host depend on his or her biomass and thus age. We propose an algorithm for estimating human infection rates from the EIR with allowance for these two factors. We then re-analyzed 1) data on EIR and age-specific incidence of clinical malaria in two villages in Senegal and 2) a survey of infant and child mortality rates across Africa. In each case, we review analyses of incidence in relation to the EIR and carry out a new analysis of morbidity and mortality rates in relation to the estimated incidence of infection (h). Reduction in malaria transmission may result in a shift of acute malaria attacks to older ages, and thus have little impact on life-time risk of clinical attacks. However, our analysis of the Senegalese data indicates that the peak incidence rate of disease relative to infection rates is in the youngest age groups in both the villages of Dielmo (EIR = 200 infectious bites per year) and Ndiop (EIR = 20). This suggests that simple models of acquired clinical immunity can explain age-incidence profiles better when incidence is expressed in relation to h, than when expressed in relation to the EIR. Relationships of malaria transmission intensity (in endemic areas) with overall mortality are very different from those with acute morbidity. Infant mortality rates (IMRs) decrease substantially when the EIR is reduced, probably largely because of prevention of indirect mortality. However, we were are not yet able to draw strong conclusions about the shape of relationships between the IMR and h because many of the available data points have similar values of h. The effects of transmission reduction on mortality rates in older age groups are also uncertain. However, it is clear that reduction of exposure during infancy is not reflected in increased mortality at older ages.