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Sci Rep. 2018 Oct 18;8(1):15429. doi: 10.1038/s41598-018-33767-3.

Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development.

Author information

1
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
2
School of Water, Energy and Environment, Applied Bioinformatics, Cranfield University, Cranfield, United Kingdom.
3
Genomics Institute of Singapore, Biopolis, Singapore.
4
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
5
Multidisciplinary Center, Federal University of Acre, Acre, Brazil.
6
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. taane.clark@lshtm.ac.uk.
7
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. taane.clark@lshtm.ac.uk.
8
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. Susana.campino@lshtm.ac.uk.

Abstract

Malaria infection during pregnancy, caused by the sequestering of Plasmodium falciparum parasites in the placenta, leads to high infant mortality and maternal morbidity. The parasite-placenta adherence mechanism is mediated by the VAR2CSA protein, a target for natural occurring immunity. Currently, vaccine development is based on its ID1-DBL2Xb domain however little is known about the global genetic diversity of the encoding var2csa gene, which could influence vaccine efficacy. In a comprehensive analysis of the var2csa gene in >2,000 P. falciparum field isolates across 23 countries, we found that var2csa is duplicated in high prevalence (>25%), African and Oceanian populations harbour a much higher diversity than other regions, and that insertions/deletions are abundant leading to an underestimation of the diversity of the locus. Further, ID1-DBL2Xb haplotypes associated with adverse birth outcomes are present globally, and African-specific haplotypes exist, which should be incorporated into vaccine design.

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