Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The parasite that escaped out of Africa

21.02.2014
Origin of deadly human malaria parasite linked to primates in Africa, not Asia, as once thought, according to Penn-led study

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.


This is a photo of Lewis, an adult chimpanzee from Goualougo Triangle in the Republic of Congo.

Credit: David Morgan and Crickette Sanz

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

Members of the labs of Beatrice Hahn, MD, and George Shaw, MD, PhD, both professors of Medicine and Microbiology at Penn, in collaboration with Paul Sharp, PhD, an evolutionary biologist from the University of Edinburgh, and Martine Peeters, PhD, a microbiologist from the Institut de Recherche pour le Développement and the University of Montpellier, tested over 5,000 ape fecal samples from dozens of field stations and sanctuaries in Africa for P. vivax DNA. They found P. vivax-like sequences in chimpanzees, in western and eastern gorillas, but not in bonobos. Ape P. vivax was highly prevalent in wild communities, exhibiting infection rates consistent with stable transmission of the parasite within the wild apes.

Ape P. vivax infects both gorillas and chimpanzees, unlike the ape precursor of P. falciparum, the deadliest human malaria parasite, which only infects gorillas. The origin of P. falciparum in gorillas was discovered several years ago by the same international group of investigators. The team continued its widespread screen of malaria parasite DNA in wild-living primates, and noted that P. vivax was also endemic in gorillas and chimpanzees in central Africa.

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.

Solving a Paradox

Of the five Plasmodium species known to cause malaria in humans, P. vivax is the most widespread. Although highly prevalent in Asia and Latin America, P. vivax was thought to be absent from west and central Africa due to a mutation that causes the Duffy-negative phenotype in most indigenous African people. P. vivax parasites enter human red blood cells via the Duffy protein receptor. Because the absence of the receptor on the surface of these cells confers protection against P. vivax malaria, this parasite has long been suspected to be the agent that selected for this mutation. However, this hypothesis had been difficult to reconcile with the belief that P. vivax originated in Asia.

"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 in humans," says Hahn.

"One interpretation of the relationships that we observed is that a single host switch from apes gave rise to human P. vivax, analogous to the origin of human P. falciparum," Sharp adds. "However, this seems unlikely in this case since ape P. vivax does not divide into gorilla- and chimpanzee-specific lineages. "

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 Duffy negative 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.

Forest Reservoirs

"The existence of a P. vivax reservoir within the forests of central Africa has public health implications," notes Peeters. "First, it solves the mystery of P. vivax infections in travelers returning from regions where 99 percent of the human population is Duffy negative. It also raises the possibility that Duffy positive humans whose work may bring them in close proximity to chimpanzees and gorillas may become infected by ape P. vivax. This has already happened once and may happen again, with unknown consequences."

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.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>