February 21, 2014
The Parasite that Escaped Out of Africa: Origin of Deadly Human Malaria Parasite Linked to Primates in Africa, not Asia, as Once Thought, according to Penn-led Study
PHILADELPHIA — An international team of scientists has traced the origin of Plasmodium vivax, the second-worst malaria parasite of humans, to Africa, according to a study published this week in Nature Communications. Until recently, the closest genetic relatives of human P. vivax were found only in Asian macaques, leading researchers to believe that P. vivax originated in Asia.
The study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania, found that wild-living apes in central Africa are widely infected with parasites that, genetically, are nearly identical to human P. vivax.
This finding overturns the dogma that P. vivax originated in Asia, despite being most prevalent in humans there now, and also solves other vexing questions about P. vivax infection: how a mutation conferring resistance to P. vivax occurs at high frequency in the very region where this parasite seems absent and how travelers returning from regions where almost all humans lack the receptor for P. vivax can be infected with this parasite.
Of Ape and Human Parasites
To examine the evolutionary relationships between ape and human parasites, the team generated parasite DNA sequences from wild and sanctuary apes, as well as from a global sampling of human P. vivax infections. They constructed a family tree of the sequences and found that ape and human parasites were very closely related. But 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 traveler, indicates the existence of a substantial natural reservoir of P. vivax in Africa.
A more plausible scenario, say the researchers, is that an ancestral P. vivax stock was able to infect humans, gorillas, and chimpanzees in Africa until the Duffynegative mutation started to spread -- around 30,000 years ago -- and eliminated P. vivax from humans there. Under this scenario, existing human-infecting P. vivax is a parasite that survived after spreading out of Africa.
The team is also concerned about the possibility that ape P. vivax may spread via international travel to countries where human P. vivax is actively transmitted. Since ape P. vivax is more diverse, genetically, than human P. vivax, it potentially has more versatility to escape treatment and prevention measures, especially if human and ape parasites were able to recombine.
Given what biologists know about P. vivax’s ability to switch hosts, the team suggests it is important to screen Duffy positive and negative humans in west central Africa, as well as transmitting mosquito vectors, for the presence of ape P. vivax. Such studies are now possible through the development of molecular tools that distinguish ape from human P. vivax. This information is necessary to inform malaria control and eradication efforts of the propensity of ape P. vivax to cross over to humans.
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.
This work was supported by grants from the National Institutes of Health (R01 AI091595, R37 AI050529, R01 AI58715, T32 AI007532), the Penn Center for AIDS Research (P30 AI045008), the Agence Nationale de Recherche sur le Sida (ANRS 12125/12182/12255), the Agence Nationale de Recherche (Programme Blanc, Sciences de la Vie, de la Santé et des Ecosystèmes and ANR 11 BSV3 021 01, Projet PRIMAL), Harvard University, the Arthur L. Greene Fund, the Jane Goodall Institute, the Wellcome Trust (098051), the Leakey Foundation, Google.org, the Skoll Foundation, the Aspinall Foundation, and the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT program.
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