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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Malaria Journal 1/2018

Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo

Zeitschrift:
Malaria Journal > Ausgabe 1/2018
Autoren:
Robert Verity, Nicholas J. Hathaway, Andreea Waltmann, Stephanie M. Doctor, Oliver J. Watson, Jaymin C. Patel, Kashamuka Mwandagalirwa, Antoinette K. Tshefu, Jeffrey A. Bailey, Azra C. Ghani, Jonathan J. Juliano, Steven R. Meshnick
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12936-018-2193-9) contains supplementary material, which is available to authorized users.

Abstract

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 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.
Zusatzmaterial
Additional file 1. Details of systematic literature search in PubMed and Web of Science, including full search terms and details of all studies identified.
Additional file 2. Neighbour-joining tree of samples from DRC, Benin and Senegal, produced in Figtree ( https://​tree.​bio.​ed.​ac.​uk/​software/​figtree/​). Edges are coloured from red to blue according to their bootstrap percentage (black edges are terminal and so have no bootstrap value). Dotted lines leading away from the tree are coloured to indicate the origin of the sample.
Additional file 3. The number of clusters in which a variant was found plotted against percentage identity of top BLAST hit for that variant. Multiple variants have the same combination of BLAST percentage and cluster representation, so size of circles indicates the number of variants for a given combination.
Additional file 4. Regression of Nei’s (1972) genetic distance against great circle distance. The fitted relationship is non-significant ( ρ = −0.04, p = 0.217).
Additional file 5. Best-fitting GLM compared to data. Black circles represent the median model prediction for each of the 115 clusters, and vertical bars represent the 95% predictive interval. Predictions are presented relative to the observed allelic richness, meaning the model is a good fit wherever the interval crosses the dashed zero line.
Literatur
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