期刊
MALARIA JOURNAL
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12936-018-2193-9
关键词
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资金
- Skills Development Fellowship [MR/N01507X/1]
- UK Medical Research Council (MRC)
- UK Department for International Development (DFID) under the MRC/DFID Concordat
- European Union
- National Institute of Health (NIH) [R01AI121558, R21AI121465]
- NIH [5R01AI107949, R56 AI106129 01A1, 5 R01 AI099473]
- Wellcome Trust [109312/Z/15/Z]
- MRC [MR/N01507X/1] Funding Source: UKRI
- Medical Research Council [MR/K010174/1B, MR/N01507X/1] Funding Source: researchfish
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI121558, R56AI106129, R21AI121465, R01AI099473, R01AI107949] Funding Source: NIH RePORTER
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.
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