Contrasting Epidemiology and Genetic Variation of Duffy Negative Plasmodium vivax across Africa

Abstract

Plasmodium vivax uses the Duffy antigen/chemokine receptor for entry into human erythrocytes. However, several recent studies have showed that P. vivax can infect Duffynegative Africans and that they are no longer completely resistant to P. vivax. While the reports of P. vivax cases in different parts of Africa raise serious public health concerns of a potential spread across the continent, the epidemiology and biology of P. vivax malaria in Africa remain largely unclear. Here, we compare the prevalence, parasitemia, and microsatellite-based variation of P. vivax in Duffy negative individuals from WestCentral, Southern, and East Africa, as well as with Duffy positive P. vivax infections collected in the same areas. The proportion of Duffy negativity ranges widely from 99% in West African to 30-40% in East African countries. Considerable differences were observed in Duffy-negative P. vivax prevalence among Cameroon, Botswana, and Ethiopia. Plasmodium vivax parasite density in Duffy-negative infections is significantly lower than in Duffy-positive infections, regardless of geographical or ethic group differences. Maximum likelihood analyses of the Duffy binding protein (DBP) sequences indicated that Duffy-negative P. vivax isolates were not monophyletic and did not share from a single source origin. Instead, they were found in multiple well-supported clades without clear geographical boundary. By contrast, analyses of five microsatellite loci showed clear genetic structure among the African isolates. The Duffy-negative P. vivax from Cameroon, Botswana, and Ethiopia each constituted distinct genetic clusters, different from the Duffy-positive P. vivax. P. vivax from Ethiopia displays the greatest diversity that constituted admixed clusters resembling both the Duffy-positive and Duffynegative isolates from Botswana. P. vivax from Cameroon forms distinct lineages. These findings help clarify the genetic origin and spreading pathways of P. vivax in Africa. This information will contribute to our limited knowledge of P. vivax epidemiology and biology in Africa.