Plasmodium vivax genomic analysis: identification of relapses and association with pregnancy adverse outcome in women from the Brazilian Amazon

Abstract

Malaria in pregnancy is a serious public health problem and is characterized by the presence of Plasmodium spp. in the peripheral blood or the placenta, impacting on maternal and foetal health. Although P. vivax burden in pregnancy is less described than P. falciparum, recent studies indicate that both species represent a threaten to mother and foetus. Nevertheless, several hypotheses have been raised to explain the differential pregnancy outcomes upon vivax infection, from the host to the parasite side. One of the hypothesis is related to Plasmodium genetic structure that has been implicated in the severity of the disease. Actually, whereas it is clear that placental parasites present a distinct phenotype from those in peripheral circulation, it is not yet known if they differ genetically. In fact, preliminary analysis of a prospective follow-up cohort with pregnant women conducted by us in the Amazon region revealed a clear distinct profile in placental pathology and the occurrence of a large number of infection recurrences with a pattern similar to vivax relapses, during pregnancy upon vivax infection. These provided the rationale to develop a project to evaluate the genetic structure and diversity of P. vivax among pregnant women from the Brazilian Amazon. Thus, we propose to study the P. vivax genomics on samples isolated from pregnant women, through whole-genome Illumina paired-end sequencing on the MiSeq Analyser. This will allow to identify vivax haplotypes associated with adverse pregnancy outcomes and assess the causes of a large number of infection recurrences in this population group, discriminating between reinfection, recrudescence, and relapse. Consequently, clarifying the P. vivax biological aspects associated with gestational malaria may contribute to outline new strategies to treat the disease in pregnant women. (AU)