22 September 2010

Researchers suggest human malignant malaria originated in gorillas

Genetic match between human-infecting and wild gorilla-infecting malaria organisms found

Researchers have shown that the most common form of human malaria originated from infected gorillas. The new study has found a nearly perfect genetic match between malaria organisms that infect humans - known as Plasmodium falciparum - and those infecting wild gorillas. The discovery contradicts earlier studies that reported the origin of malignant malaria in chimpanzees and bonobo apes. The new study is published on 23 September 2010 in the prestigious science journal, Nature.

The team used novel non-invasive genetic methods to screen thousands of wild-living apes throughout central Africa for Plasmodium infections.

Silverback gorilla (Gorilla gorilla) foraging on herbs in a swampy clearing in northern Republic of Congo. Non-invasive studies of these elusive apes identified three new gorilla-specific Plasmodium species, one of which is nearly identical to human P. falciparum.

Silverback gorilla (Gorilla gorilla) foraging on herbs in a swampy clearing in northern Republic of Congo. Non-invasive studies of these elusive apes identified three new gorilla-specific Plasmodium species, one of which is nearly identical to human P. falciparum. [Ian Nichols and the National Geographic Society]

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Malaria afflicts 250 to 500 million people each year - killing more than one million of them, most frequently young children. Malaria is passed by mosquitoes from one person to the next. According to the World Health Organisation, P. falciparum is the most important of five different malarial parasites that infect humans.

The researchers, led by Dr Beatrice Hahn from the University of Alabama at Birmingham (UAB), suggest that understanding the origin of P. falciparum is critical to understanding its virulence in humans and could eventually help with malaria eradication efforts.

"Understanding where a human pathogen like Plasmodium falciparum originated can be an important step in learning how to prevent and treat the disease that it causes," says Dr Beatrice Hahn. "Like AIDS, malaria is of primate origin. Studies of the primate precursors of HIV have unravelled many aspects of AIDS pathogenesis. I expect the same to happen when the biology of the gorilla precursor of P. falciparum is compared to that of its human counterpart."

Previous studies had reported other primates as the likely source of P. falciparum.

"Two studies implicated chimpanzees and a third study suggested bonobo apes as the source," said Weimin Liu, who helped develop the experimental methods that ultimately solved this puzzle. "These prior studies had analysed only a few apes, most of them in captivity. This is why we did a comprehensive search of all African ape species, making sure to include only samples that were collected in the wild."

The researchers analysed more than 2,700 ape fecal samples collected from 57 field sites throughout central Africa. Fecal samples were screened because they can be collected without any direct interaction with the apes, which are a protected species. The researchers found that Plasmodium infection was widespread, with up to half of the apes in some communities being infected. It is not currently known whether Plasmodium infection causes a disease like malaria in apes, and this is an active area of ongoing work.

It was when the researchers compared ape and human Plasmodium sequences that they made their discovery, but also realised the need for an important technical innovation.

" Understanding where a human pathogen like Plasmodium falciparum originated can be an important step in learning how to prevent and treat the disease that it causes. "

Dr Beatrice Hahn

"When we used conventional genetic methods to characterise the Plasmodium sequences, we realised that most samples contained complex mixtures of genetically divergent parasites," says Dr Julian Rayner at the Wellcome Trust Sanger Institute who, together with Hahn, initiated the study. "At this point we knew that conventional polymerase chain reaction (PCR) methods would not do the trick."

Instead, the team used a highly accurate technique called single genome amplification (SGA) that Hahn and her UAB colleague George Shaw had pioneered to identify and characterise the transmitted forms of HIV type 1, the virus that causes AIDS in humans. This experimental strategy precluded PCR artefacts that had confounded earlier studies and had obscured the true nature of the malaria parasites infecting apes.

The new findings show that wild-living western gorillas were the source of human P. falciparum, but they do not answer the question as to when this jump from gorillas to humans occurred.

"Current estimates place the emergence of P. falciparum anywhere between 5,000 and 300,000 years ago; this is because we do not know exactly how fast, or slow, Plasmodium parasites evolve," says Paul Sharp, a longtime collaborator of Hahn's team and a specialist in evolutionary biology, from the Institute of Evolutionary Biology at the University of Edinburgh.

Similarly uncertain is whether present-day ape populations represent a source for ongoing human infection.

"Thus far, we have evidence for only a single gorilla-to-human jump," says Martine Peeters, from the Institut de Recherche pour le Développement (IRD) and University of Montpellier, whose team collected many of the ape fecal samples analysed in this study. "The notion that P. falciparum could have been transmitted only once from gorillas to humans spawning what we now recognise as a global epidemic is remarkable. However, we cannot exclude the possibility that transmissions between gorillas and humans occur at a local level but have not spread further around the world. To address this question we are working hard to screen humans who live in close proximity to wild apes and are thus at risk of being bitten by mosquitoes carrying ape parasites."

Hahn adds, "We will also need to study the biology and full genetic content of P. falciparum in gorillas."

Such studies, the Hahn team believes, can inform current malaria eradication efforts of potential zoonotic Plasmodium reservoirs and provide novel insight into what adaptive changes malarial parasites in apes might require in order to infect and cause disease in humans.

Notes to Editors

Publication details

  • Origin of the human malaria parasite Plasmodium falciparum in gorillas.

    Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD, Keele BF, Ndjango JB, Sanz CM, Morgan DB, Locatelli S, Gonder MK, Kranzusch PJ, Walsh PD, Delaporte E, Mpoudi-Ngole E, Georgiev AV, Muller MN, Shaw GM, Peeters M, Sharp PM, Rayner JC and Hahn BH

    Nature 2010;467;7314;420-5

Funding

This work was supported by grants from the National Institutes of Health, the National Science Foundation, the Agence Nationale de Recherche sur le Sida, the Great Ape Conservation Fund of the U.S. Fish and Wildlife Service, the Arthur L. Greene Fund, the Wallace Global Fund, the Bristol Myers Freedom to Discover Program, and the Wellcome Trust.

Participating Centres

  • Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  • Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  • Department of Ecology and Management of Plant and Animal Resources, Faculty of Sciences, University of Kisangani, Democratic Republic of the Congo
  • Department of Anthropology, Washington University, Saint Louis, Missouri, USA
  • Congo Program, Wildlife Conservation Society, Brazzaville, Republic of Congo
  • Lester E. Fisher Center for the Study and Conservation of Apes, Lincoln Park Zoo, Chicago, Illinois, USA
  • Department of Biological Sciences, University at Albany, State University of New York, Albany, New York, USA
  • Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA
  • VaccinApe, Bethesda, Maryland, USA
  • Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France
  • Institut de Recherches Médicales et d'études des Plantes Médicinales Prévention du Sida ou Cameroun, Centre de Recherche Médicale, Yaoundé, Cameroun
  • Department of Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA
  • Department of Anthropology, University of New Mexico, Albuquerque, New Mexico, USA
  • Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom
  • Sanger Institute Malaria Programme, The Wellcome Trust Sanger Institute, Cambridge, United Kingdom.

University of Alabama at Birmingham (UAB)

Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham (UAB) is the state of Alabama's largest employer and an internationally renowned research university and academic health center whose professional schools and specialty patient care programs are consistently ranked as among the nation's top 50; find more information at www.uab.edu and www.uabmedicine.org.

The University of Alabama at Birmingham (UAB) is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on all consecutive references.

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