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.
Highlights
The earliest models of malaria transmission assumed a completely mixed and homogenous parasite population[1,2]
There are several epidemiological studies describing spatial heterogeneity of malaria on varying geographical scales[8,9,10,11,12,13,14,15,16,17,18,19]. This heterogeneity is characterized by infection hotspots which usually persist even after transmission has been reduced in surrounding areas[9,11,20,21,22,23,24,25], and act as reservoirs of infection[21,26]
Study populations 5199 P. falciparum parasite isolates were collected from the Kombo coastal districts in The Gambia, and Kilifi County and Rachuonyo South district in Kenya (Figure 1) between 1998 and 2011. 107, 177 and 82 single nucleotide polymorphisms (SNPs) were successfully genotyped in 133, 1602, and 1034 parasite isolates from The Gambia, Kilifi and Rachuonyo South district, respectively (Table 1). 26, 57 and 49 SNPs were present at frequencies of 5% and above in The Gambia, Kilifi and Rachuonyo, respectively
Summary
The earliest models of malaria transmission assumed a completely mixed and homogenous parasite population[1,2]. Achieving any meaningful reduction in transmission in regions containing malaria hotspots will require a scale up of control activities, including repeated mass administration of Artemisinin Combination Therapy (ACT) drugs, increased coverage of long lasting insecticide treated nets (LLINs) and intensive indoor residual spraying (IRS). These measures are very costly and may not be realistic for universal coverage in most of the resource-poor endemic countries. There are few empiric estimates of parasite mixing with which to parametize such models
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