Abstract
Background. Malaria control, and finally malaria elimination, requires the identification and targeting of residual foci or hotspots of transmission. However, the level of parasite mixing within and between geographical locations is likely to impact the effectiveness and durability of control interventions and thus should be taken into consideration when developing control programs. Methods. In order to determine the geographic-genetic patterns of Plasmodium falciparum parasite populations at a sub-national level in Kenya, we used the Sequenom platform to genotype 111 genome-wide distributed single nucleotide polymorphic (SNP) positions in 2486 isolates collected from children in 95 primary schools in western Kenya. We analysed these parasite genotypes for genetic structure using principal component analysis and assessed local and global clustering using statistical measures of spatial autocorrelation. We further examined the region for spatial barriers to parasite movement as well as directionality in the patterns of parasite movement. Results. We found no evidence of population structure and little evidence of spatial autocorrelation of parasite genotypes (correlation coefficients <0.03 among parasite pairs in distance classes of 1km, 2km and 5km; p value<0.01). An analysis of the geographical distribution of allele frequencies showed weak evidence of variation in distribution of alleles, with clusters representing a higher than expected number of samples with the major allele being identified for 5 SNPs. Furthermore, we found no evidence of the existence of spatial barriers to parasite movement within the region, but observed directional movement of parasites among schools in two separate sections of the region studied. Conclusions. Our findings illustrate a pattern of high parasite mixing within the study region. If this mixing is due to rapid gene flow, then “one-off” targeted interventions may not be currently effective at the sub-national scale in Western Kenya, due to the high parasite movement that is likely to lead to re-introduction of infection from surrounding regions. However repeated targeted interventions may reduce transmission in the surrounding regions.
Highlights
Malaria incidence has markedly reduced in some parts of Africa[1,2,3]
We examined the parasite population structure based on principal component analysis (PCA), and used measures of local and global spatial autocorrelation to test for geographical relatedness among parasite genotypes
Sequenom assay performance We genotyped 111 genome-wide distributed exonic single nucleotide polymorphic (SNP) in 2486 P. falciparum positive samples collected from 95 primary schools in Western Kenya (Figure 1 and Figure 2). 83 of the 111 SNPs were successfully typed in 1809 samples from 88 schools in Western Kenya (1097 from Nyanza province and 712 from Western province)
Summary
Malaria incidence has markedly reduced in some parts of Africa[1,2,3]. In some instances, this has been associated with malaria control efforts[4], but has not been temporally associated with scaling-up malaria control in others[5]. In a recent randomized controlled trial of targeted integrated vector control in Rachuonyo south district in Western Kenya, an initial impact was seen within hotspot areas, but this did not reduce transmission outside the hotspot, and reductions within hotspots were not sustained[9] This may have been due to rapid mixing of parasites from areas outside the intervention zones. In order to determine the geographic-genetic patterns of Plasmodium falciparum parasite populations at a sub-national level in Kenya, we used the Sequenom platform to genotype 111 genome-wide distributed single nucleotide polymorphic (SNP) positions in 2486 isolates collected from children in 95 primary schools in western Kenya We analysed these parasite genotypes for genetic structure using principal component analysis and assessed local and global clustering using statistical measures of spatial autocorrelation. We found no evidence of the existence of spatial barriers to parasite movement within the region, but observed directional movement of parasites among schools in two separate sections of the region
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