The team found that wild-living apes in central Africa are commonly infected with parasites that, genetically, are nearly identical to human P. vivax.
Until recently, the closest genetic relatives of human P. vivax were thought to be parasites that infect Asian monkeys, leading researchers originally to believe that P. vivax originated in Asia.
However, this was always difficult to reconcile with the fact that P. vivax is virtually non-existent in Central and West Africa because 99 per cent of people in these regions have a protective mutation, Duffy negativity, that prevents P. vivax from invading their red blood cells.
“The absence of the Duffy antigen on the red blood cell surface obviously arose in West Africa, became ubiquitous, and spread to protect people from P. vivax,” says Dr Julian Rayner, author from the Wellcome Trust Sanger Institute. “But this has always been difficult to reconcile with the fact that all previous data that suggests that P. vivax arose in South-East Asia”
“This new data solves vexing questions about P. vivax infection: how can a mutation conferring resistance to P. vivax occurs at high frequency in the very region where this parasite seems absent and how can travellers returning from regions where almost all humans lack the receptor for P. vivax can be infected with this parasite.”
This work forms part of a larger body of work from the same international group of investigators, which several years ago established that P. falciparum, the most deadly form of human malaria, crossed into humans from lowland gorillas. In that initial work, the team noticed one or two cases of P. vivax in gorillas and chimpanzees in central Africa. They have now completed a much more comprehensive screen of malaria parasite DNA from wild-living ape faecal samples, establishing P. vivax is more common in apes than previously thought.
To examine the evolutionary relationships between ape and human parasites, the team generated parasite DNA sequences from non-invasive samples from wild and sanctuary apes, as well as from a global sampling of human P. vivax infections. They constructed a family tree from the DNA sequences and found that ape and human parasites were very closely related. Despite the relatedness between ape and human P. vivax, ape parasites were more diverse than the human parasites and did not group according to their host species. In contrast, the human parasites formed a single lineage that fell within the branches of ape parasite sequences.
From these evolutionary relationships, the team concluded that P. vivax is of African -- not Asian -- origin, and that all existing human P. vivax parasites evolved from a single ancestor that spread out of Africa. The high prevalence of P. vivax in wild-living apes, along with the recent finding of ape P. vivax in a European traveller, indicates the existence of a substantial natural reservoir of P. vivax in Africa.
“Our finding that wild-living apes in central Africa show widespread infection with diverse strains of P. vivax provides new insight into the evolutionary history of human P. vivax and resolves the paradox that a mutation conferring resistance to P. vivax occurs with high frequency in the very region where this parasite is absent from humans,” says Professor Beatrice Hahn, lead author from University of Pennsylvania.
As a next step, the team will compare and contrast the molecular and biological properties of human and ape parasites to identify host-specific interactions and transmission requirements, thereby uncovering vulnerabilities that can be exploited to combat human malaria.
“It is pivotal that we continue to monitor other species for malaria, and understand the relationships between human and primate malaria. If we want to eradicate malaria, we need to understand the full extent of the malaria reservoirs that could potentially infect people,” adds Dr Rayner.
Publication Details
Liu W et al.(2014) African origin of the malaria parasite Plasmodium vivax. Nature Communications, published online on 21 February 2014
doi: 10.1038/ncomms4346
Funding
This work was supported by grants from the US National Institutes of Health, the Agence Nationale de Recherche sur le Sida and Agence Nationale de Recherche of France, Harvard University, the Arthur L. Greene Fund, the Jane Goodall Institute, the Wellcome Trust, Google.org, the Skoll Foundation and the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT.
Participating Centres
A full list of participating centres appears on the Nature website.
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