Title | Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Verity R, Hathaway NJ, Waltmann A, Doctor SM, Watson OJ, Patel JC, Mwandagalirwa K, Tshefu AK, Bailey JA, Ghani AC, Juliano JJ, Meshnick SR |
Journal | Malar J |
Volume | 17 |
Issue | 1 |
Pagination | 46 |
Date Published | 2018 Jan 24 |
ISSN | 1475-2875 |
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. |
DOI | 10.1186/s12936-018-2193-9 |
Alternate Journal | Malar. J. |
PubMed ID | 29361940 |
PubMed Central ID | PMC5782373 |
Grant List | R01 AI099473 / AI / NIAID NIH HHS / United States R01 AI121558 / AI / NIAID NIH HHS / United States R21 AI121465 / AI / NIAID NIH HHS / United States 5 R01 AI099473 / / National Institutes of Health / United States R56 AI106129 01A1 / / National Institutes of Health / United States 109312/Z/15/Z / / Wellcome Trust / United Kingdom R01 AI107949 / AI / NIAID NIH HHS / United States 5R01AI107949 / / National Institutes of Health / United States MR/N01507X/1 / / UK Medical Research Council / United States / / Wellcome Trust / United Kingdom R21AI121465 / / National Institutes of Health / United States R56 AI106129 / AI / NIAID NIH HHS / United States R01AI121558 / / National Institutes of Health / United States |
Submitted by kej2006 on June 6, 2018 - 4:13pm