Reducing Parasite Transmission Across a Varied Lanscape: Ecological and Social Contexts of a Malaria Intervention

Michigan State University, East Lansing MI

Investigators

Abstract

Intellectual merit: In this proposal, Dr. Walker and colleagues address ecological resiliency and stability of the malaria disease system in a holoendemic area of sub-Saharan Africa (lowland, western Kenya) when it is manipulated intentionally by intensive implementation of insecticide treated bed nets (ITNs) to reduce transmission. Research activities consist of 3 integrated components. First, the effects of ITN implementation on the population dynamics and population genetics of the main malaria vector, Anopheles gambiae will be quantitated, with attention to population equilibrium density, spatial relationships to landscape factors and transmission intensity, population genetic effective population size, and gene flow. Target site insecticide resistance factors (so-called knockdown resistance or kdr) will be used as a marker for empirical analysis of gene flow. The magnitude of the ratio of Anopheles gambiae to its sister species Anopheles arabiensis is postulated to be a valid measure of the intensity of the ITN effect. Anopheles gambiae populations are postulated not to respond to density reductions with compensating reductions in density-dependent mortality. The magnitude and underlying mechanism of the so-called ?community effect? of ITNs is postulated to be related to a change from aggregated to random distribution of vectors combined with a reduced density owing to mortality. ITN implementation is further postulated to deepen the normally shallow population structure of this species, will restrict gene flow, will reduce populations to levels below density equilibrium, increase the value of the arabiensis:gambiae ratio, and will shift adult female distribution from highly aggregated to more random relative to quantified landscape structure. Secondly, the effects of ITN implementation on population genetic structure of the primary malaria parasite, Plasmodium falciparum will be measured, using a combination of microsatellite markers, and frequencies of alleles operating at dihydrofolate antibiotic resistance and virulence (MSP-1) gene loci. It is hypothesized that a parasite population structure will deepen into a highly clonal one, such that gene flow of alleles conferring drug resistance and related to virulence will be restricted. Parasites will be sampled from the mosquito population at the diploid oocyst stage, to obtain clones for study. The generalized hypothesis that reduction in transmission rate confers selection pressure for more virulent parasite strains will be tested by examining whether those alleles at MSP-1 associated with higher virulence indeed increase in frequency with intensive ITN use. Male gametocytes are postulated to be favored, owing to limits on parasite population sexual reproduction as densities of parasites decline. Thirdly, the acceptability and utilization patterns by the human population of ITNs will be examined in the social science context under conditions where that population has extensive experience and knowledge of ITN use, compared to human populations that do not have this experience. Whether spatial patterns of ITN use conform to risk maps of malaria based upon spatial variations in transmission intensity will be examined. Broader impacts: Diseases as ecological systems show strong resiliency and stability to system perturbations, in particular those imposed on them by humans as an intentional attempt to control transmission. Human malaria represents a supreme example, where despite its apparent simplicity it has resisted rigorous attempts to control it, until very recently when insecticide treated bed nets (ITNs) have emerged as a powerful and simple control tool. The pressing question is, will this disease system resiliently resist this perturbation, and what are the sources of the resiliency and stability? Dr. Walker''s research team has a strong history of collaboration and of focused efforts on ecology and behavior of malaria vectors in lowland, western Kenya, where an on-going intervention against malaria transmission has been imposed since 1998 in a human population of 125,000. The research program takes advantage of this unique opportunity to evaluate the long term efficacy of this intervention and how malaria might resist and overcome it; or how it might be made sustainable. The project involves a graduate student from Michigan State University who will work with a diverse staff in Kenya.