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

Autor: 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
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Malaria Journal, Vol 17, Iss 1, Pp 1-8 (2018)
Druh dokumentu: article
ISSN: 1475-2875
DOI: 10.1186/s12936-018-2193-9
Popis: 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.
Databáze: Directory of Open Access Journals
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