Background: 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 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.
Methods: Samples 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.
Results: Results 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.
Conclusions: Results suggest that the DRC fts within the global pattern of high var2csa diversity and little genetic
diferentiation between regions. A broad multivalent VAR2CSA vaccine candidate could beneft from targeting stable
regions and common variants to address the substantial genetic diversity.