Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa.

Abstract

Background: The first models of malaria transmission assumed a completely mixed and homogeneous population of parasites. Recent models include spatial heterogeneity and variably mixed populations. However, there are few empiric estimates of parasite mixing with which to parametize such models. Methods: Here we genotype 276 single nucleotide polymorphisms (SNPs) in 5199 P. falciparum isolates from two Kenyan sites and one Gambian site to determine the spatio-temporal extent of parasite mixing, and use Principal Component Analysis (PCA) and linear regression to examine the relationship between genetic relatedness and relatedness in space and time for parasite pairs. Results: We show that there are no discrete geographically restricted parasite sub-populations, but instead we see a diffuse spatio-temporal structure to parasite genotypes. Genetic relatedness of sample pairs is predicted by relatedness in space and time. Conclusions: Our findings suggest that targeted malaria control will benefit the surrounding community, but unfortunately also that emerging drug resistance will spread rapidly through the population.

Geographic-genetic analysis of Plasmodium falciparum parasite populations from surveys of primary school children in Western Kenya

“…In order to predict whether targeting hotspots is potentially an effective way of interrupting transmission, we need to understand the spatial and temporal scales over which parasite mixing can be observed. Limited genetic differentiation between malaria parasites has been shown to occur on a regional scale in sub-Saharan Africa 18– 20 , although we previously identified spatial structure at fine micro epidemiological scales within geographically defined regions in Kenya and The Gambia 21 .…”

“…<10km), despite a high level of parasite mixing 21 . In the present analysis, we examined the level of parasite mixing at a sub-national scale in Western Kenya, using parasitological data from primary school surveys to describe the patterns of parasite mixing at a larger geographical scale.…”

Malaria Epidemiology at the Clone Level

“…Such studies are usually conducted at countrywide spatial scales, aiming to identify provinces or districts where malaria control could be scaled up towards elimination [36]. On the other hand, assuming that parasites spread from transmission foci to surrounding areas, clusters of genetically similar parasites are identified (Figure 1B), expecting that control efforts targeting foci may also have beneficial effects on surrounding areas [37]. The spatial scale of such studies is usually smaller.…”

“…Owing to these requirements, relatively few studies have been conducted. In Ghana, Kenya, Solomon Islands, and the Peruvian Amazon, relatedness of parasites collected across a range of a few km was found, suggesting gene flow at small scales but limited parasite migrations at larger scales [37, 42, 43]. It remains to be shown under what conditions, and at what geographical scale, transmission foci can be identified that are stable over time and thus could be targeted for malaria control.…”

“…It remains to be shown under what conditions, and at what geographical scale, transmission foci can be identified that are stable over time and thus could be targeted for malaria control. In eastern Kenya, relatedness of parasites sampled within less than one kilometer suggested high levels of gene flow [37]. In the same site, transmission foci, characterized by high numbers of individuals carrying antibodies against P. falciparum , were identified as the most probable source of parasites in their near surroundings [44].…”