Understanding Mechanisms of Sustained Malaria Transmission in Zambia Through Plasmodium falciparum Genetics
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Pringle, Julia C
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Malaria remains an enormous public health burden, particularly in sub-Saharan Africa where it is among the leading causes of childhood mortality. Recently, renewed global commitment to malaria elimination has laid the groundwork for 35 nations to declare elimination targets and implement elimination programs. Zambia, one such country, is located in southern Africa where malaria control efforts have been challenging. Although Zambia has achieved significant progress towards its targeted elimination deadline of 2021, much work remains. Zambia faces a heterogenous transmission landscape, with regions of low prevalence in the south and regions of high transmission in the northwest, along the international border with the Democratic Republic of the Congo (DRC). To eliminate malaria, Zambia must address the obstacles to malaria control in regions where interventions have been ineffective as well as the barriers to elimination in regions where unknown mechanisms continue to sustain transmission. We examine the barriers to malaria control and elimination in two epidemiologically distinct regions in Zambia. We focus on the utility of P. falciparum genetic methods to draw inferences regarding the mechanisms that continue to sustain malaria transmission in these settings. In southern Zambia, we use microsatellite genotyping to demonstrate that local malaria transmission contributes to the burden of malaria in spite of control measures including reactive case detection. We further identify a region in our study site as a local transmission hotspot, and suggest that this may be an area to prioritize for additional vector control measures. Along the border between Nchelenge District, Zambia and Haut-Katanga Province, DRC, we use amplicon deep sequencing at two diverse P. falciparum loci, Pfama1 and Pfcsp, to infer that cross-border malaria transmission may contribute to the high burden of malaria in this region. We characterize the extent to which this malaria-parasite population is genetically similar to the strain included in the vaccine, RTS,S/AS01. Our analysis indicates that only 5.2% of parasites in this region match the vaccine strain in the C-terminal Pfcsp locus, suggesting that the vaccine may have reduced efficacy in this region. This dissertation demonstrates the value of incorporating parasite genetic analyses into malaria control and elimination efforts.