Abstracts (first author)
Erythrocyte polymorphisms associated with protection against P. vivax malaria in Papua New Guinea children
Malaria parasites have long coexisted with hominid ancestors: P. falciparum might had infected humans before the out-of-Africa migration and followed the human expansion throughout the tropics. This long-term interaction may have driven the co-evolution of the host-parasite and left evolutionary foot-prints in both human and parasite genomes. According to the “malaria hypothesis”, the high frequencies of deleterious mutations of some human populations are probably due to the strong selective pressure of malaria A remarkable range of polymorphisms have been associated with protection against malaria.Populations of the South West Pacific, a co-endemic region for all four human malaria parasite species, are highly diverse and exhibit a range of unique red blood cell polymorphisms, with geographical patterns paralleling malaria endemicity. We conducted three independent studies in the Madang area of Papua New Guinea to analyse the association of South East Asian Ovalocytosis (SAO) (caused by band 3 deletion SLC4A1∆27) and Gerbich negative blood group (caused by a deletion in exon3 of the glycophorin C gene (GYPC)), with protection against P. vivax malaria, testing the hypothesis that P. vivax malaria contributed to the selection of those polymorphisms. Our results showed that SAO was associated with a 46% reduction in risk of clinical P. vivax episodes in a cohort of infants 3-21 months and a 52-55% reduction in P. vivax reinfection in children 5-14 yrs. A case-control study of children 0.5–14 yrs revealed the potential for a strong protection against severe P. vivax malaria. Analysis of Gerbich blood group variants in a cohort of children 1-3 yrs showed that GYPC homozygote is associated with strong protection against P. vivax malaria and that the strength of protection increases with parasitemia. This strongly suggest that P. vivax malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Pacific populations.