Browsing by Author "Marinho, Claudio R. F."

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    Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development
    (Nature Publishing Group, 2018-10-18) Diez Benavente, Ernest; Oresegun, Damilola R.; Florez de Sessions, Paola; Walker, Eloise M.; Roper, Cally; Dombrowski, Jamille G.; de Souza, Rodrigo M.; Marinho, Claudio R. F.; Sutherland, Colin J.; Hibberd, Martin L.; Mohareb, Fady R.; Baker, David A.; Clark, Taane G.; Campino, Susana
    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.