Abstract
BackgroundThe Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM.MethodsSamples were taken from the 2013–14 Demographic and Health Survey conducted in the DRC, focusing on children under 5 years of age. A short subregion of the var2csa gene was sequenced in 115 spatial clusters, giving country-wide estimates of sequence polymorphism and spatial population structure.ResultsResults indicate that var2csa is highly polymorphic, and that diversity is being maintained through balancing selection, however, there is no clear signal of phylogenetic or geographic structure to this diversity. Linear modelling demonstrates that the number of var2csa variants in a cluster correlates directly with cluster prevalence, but not with other epidemiological factors such as urbanicity.ConclusionsResults suggest that the DRC fits within the global pattern of high var2csa diversity and little genetic differentiation between regions. A broad multivalent VAR2CSA vaccine candidate could benefit from targeting stable regions and common variants to address the substantial genetic diversity.
Highlights
The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women
The adverse effects of pregnancy-associated malaria (PAM) are mediated by the sequestration of infected erythrocytes in the placental microvasculature through binding of VAR2CSA—a large and genetically diverse parasite protein expressed during pregnancy-to human chondroitin sulfate A (CSA) [4, 5]
This study focused on quantifying genetic variation at the var2csa locus in samples obtained from the 2013–14 Demographic and Health Survey (DHS); a large, crosssectional study separated into spatial clusters spanning the DRC
Summary
The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM. The adverse effects of PAM are mediated by the sequestration of infected erythrocytes in the placental microvasculature through binding of VAR2CSA—a large and genetically diverse parasite protein expressed during pregnancy-to human chondroitin sulfate A (CSA) [4, 5]. Occurring anti-VAR2CSA antibodies provide partial protection against future episodes of PAM, such that primigravid women are most susceptible and risk of severe infection and LBW decreases in subsequent pregnancies [4, 6, 7]. Vaccines against VAR2CSA are currently undergoing initial trials [8,9,10]
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