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ORIGINS AND PERSISTANCE OF HUMAN MALARIAS: CONTEXT MATTERS

Posted by leendertzf on 23 Apr 2010 at 07:10 GMT

ORIGINS AND PERSISTANCE OF HUMAN MALARIAS: CONTEXT MATTERS

Fabian H. Leendertz (1,2) and Thomas R. Gillespie (3,4)

1 Research Group ‘‘Emerging Zoonoses’’, Robert Koch-Institut, Berlin, Germany

2 Department of Primatology, Max-Planck-Institute for Evolutionary Anthropology, Leipzig,
Germany

3 Department of Environmental Studies and Program in Population Biology, Ecology and
Evolution, Emory University, Atlanta, Georgia USA

4Department of Environmental and Occupational Health, Rollins School of Public Health,
Emory University, Atlanta, Georgia USA


Examination of the role of our closest phylogenetic relatives, the great apes, in the evolution and persistence of human malarias has been limited by a lack of data from wild ape populations where opportunities for human-mosquito-ape malaria exchange are minimal. Interpretation of patterns of malaria infection in captive ape populations, such as sanctuaries, must consider the ample opportunities for human to ape transmission of such parasites as has been clearly demonstrated in cases of far lower overlap for respiratory and gastrointestinal viruses and bacteria (1,2).
The recent study by Krief et al. (2010) (3) highlights the importance of context when interpreting the potential for zoonotic transmission of Plasmodium. This study examined great apes living in three distinct contexts: 1) captive bonobos living in a small sanctuary (500m x 500 m forested enclosure) far from natural bonobo habitat and surrounded by human settlements in the suburban area of Kinshasa, an urban center of more than 10 million people where malaria is common (Fig 1a, Lola ya Bonobo Sanctuary); 2) chimpanzees living on an isolated island in Lake Victoria with no permanent human settlements that chimpanzees have never naturally inhabited (Fig 1b, Ngamba Island Sanctuary); 3) semi-wild chimpanzees living at a forest / village interface with high human overlap due to chimpanzee crop raiding and chimpanzees ranging at most times within 0-2 km of a village (Fig 1c, Kibale Forest). These are clearly not “natural settings”. With the exception of the Plasmodium strains of the reichenowi group (which is most likely a great ape group), it is far more likely that the apes examined in these contexts were infected with Plasmodium via mosquitoes carrying infected human blood. Human to ape Plasmodium transfer is further supported in these contexts, considering that chimpanzees living on Ngamba Island, a sanctuary situated on an isolated island with no permanent human settlements in Lake Victoria (Fig1b), demonstrate no Plasmodium infection3. Imagine confirming H1N1 in chimpanzees at the St Louis Zoo. Would we assume the chimpanzees are the reservoir?
Founder individuals in sanctuaries are removed from the wild at the age of 2-4 and live for long periods in close proximity to humans before being confiscated and introduced to a sanctuary. Thus, Plasmodium parasites would have to be maintained chronically since youth in these animals or human variants of the parasite infect the apes while living in sanctuaries. Consider the case of the “Lola ya” bonobos who display high prevalence of human malarias, they are surrounded by infected vectors for human malaria for most of their life (human malaria prevalence in Kinshasa is 34%(4)) and are well separated from any natural bonobo populations. Conversely, Ngamba Island chimpanzees, who lack all human malarias, live in an environment where vectors are rare and the probability of infected vectors is also low due to the small temporary human presence. Human to ape malaria transmission is the most parsimonious explanation for the pattern of infection observed.
The existence of human Plasmodium species in wild great apes inhabiting pristine contiguous forest with limited exposure to humans would be required to demonstrate the natural existence of these parasites in wild great apes. Recent detection of Plasmodium from non-invasively collected fecal samples from wild chimpanzees and gorillas provide important insights regarding the existence of human malarias in apes living in their natural habitat5 (M. Peeters pers. comm.). Systematic study of the ecological and epidemiological aspects of Plasmodium evolution and persistence using non-invasively collected samples of great apes living in remote regions, coupled with more detailed analyses of parasite strains detected in captive and wild great apes have great potential to shed light on the origin and zoonotic potential of these parasites (6).

References
1. Köndgen S, Kühl H, N’Goran PK, Walsh PD, Schenk S, Ernst N, Biek R, Formenty P, Matz-Rensing K, Schweiger B, Junglen S, Ellerbrok H, Nitsche A, Briese T, Lipkin WI, Pauli G, Boesch C, Leendertz FH. (2008). Pandemic human viruses cause decline of endangered great apes. Curr Biol 18: 260–264.
2. Rwego, I.B., G. Isabirye-Basuta, T.R. Gillespie, and T.L. Goldberg. (2008) Gastrointestinal bacterial transmission among humans, mountain gorillas, and domestic livestock in Bwindi Impenetrable National Park, Uganda. Conservation Biology. 22:1600-1607.
3. Krief S, Escalante AA, Pacheco MA, Mugisha L, André C, et al. (2010) On the Diversity of Malaria Parasites in African Apes and the Origin of Plasmodium falciparum from Bonobos. PLoS Pathog 6: e1000765.
4. Kazadi W, Sexton JD, Bigonsa M, W’Okanga W, Way W (2004) Malaria in primary school children and infants in Kinshasa, Democratic Republic of the Congo: surveys from the 1980s and 2000 Am. J. Trop. Med. Hyg., 71: 97–102
5. Prugnollea, F. et. al. African great apes are natural hosts of multiple related malaria species, including Plasmodium falciparum. PNAS 107,1458-63 (2010).
6. Gillespie TR, Nunn CL, Leendertz FH. (2008). Integrative approaches to the study of primate infectious disease: implications for biodiversity conservation and global health. Yrbk Phys Anth 51, 53-69.

Acknowledgements
This work was supported by the Robert Koch-Institute, the Max-Planck-Society, and Emory University.


Fig1 A-C: Please see the referenced figure here:

http://www.plospathogens....

Satellite image of territories and enclosures of great apes investigated (shaded areas). A: Bonobo sanctuary “Lola ya Bonobo” in the periphery of Kinshassa, DRC; B: Chimpanzee sanctuary “Ngamba Island” with no permanent human population; C: Complete territory of wild chimpanzees living in close contact to human settlements in Kibale Forest, Uganda. White bars represent 2500 meters.

No competing interests declared.

RE: ORIGINS AND PERSISTANCE OF HUMAN MALARIAS: CONTEXT MATTERS

AnaniasEscalante replied to leendertzf on 23 Apr 2010 at 17:33 GMT

Response to Leendertz and Gillespie

Ananias A. Escalante1, Sabrina Krief2, Georges Snounou3,4

1 School of Life Sciences, Arizona State University, Tempe, Arizona, USA

2 UMR 7206 Ecoanthropologie et ethnobiologie, Dpt Hommes Natures Sociétés, Muséum National d’Histoire Naturelle, Paris, France

3 INSERM UMR S 945, F-75013 Paris, France

4 Université Pierre & Marie Curie, Faculté de Médecine Pitié-Salpêtrière, F-75013 Paris, France

We thank Drs Leendertz and Gillespie for their comments, and wholeheartedly agree with the final sentence of their comment, which eloquently sums up and extends the concluding paragraph of our article on the diversity of malaria parasites in African Apes [1]. We are, however, puzzled by the objections they seem to raise concerning the origin of some of the parasite lineages we observed.

The contention of Leendertz and Gillespie is that the P. malariae and P. falciparum lineages we found in the bonobos and the P. vivax-like lineage we detected in chimpanzees, were most likely the results of human to ape transmissions. Whereas we do not exclude this possibility, we disagree that this is the most parsimonious explanation of the pattern of infection we observed.

In the case of the P. vivax-like lineage observed in chimpanzees a human origin is highly unlikely. If this lineage is indeed P. vivax, finding this species in 1/3 apes sampled in Uganda and 1/3 apes independently sampled in the Democratic Republic of Congo would be extraordinary as P. vivax is quite rare in Sub-Saharan African populations [2]; P. falciparum which dominates the epidemiological picture was not found in these six animals. Furthermore Leendertz and Gillespie characterize the Kanyawara chimpanzees as “semi-wild and living at a forest/village interface due to chimpanzee crop raiding and chimpanzees ranging at most times within 0-2 Km of a village”. This is not quite correct; chimpanzees' crop raiding activities are not frequent, do not exceed a few minutes, and when they occur only some individuals are present in the plantations. In fact the 45 members of the habituated Kanyawara chimpanzee community do not stay close to the villages and constantly travel within a 32 Km2 home range [3] because of their social fusion-fission system. For the bonobo that do live close to humans, our initial hypothesis was that the P. falciparum parasites infecting bonobos were of human origin; however, it was shaken when it became clear that the 4 mitochondrial haplotypes (based on ca. 98% of the 6kb genome) obtained from these parasites differed substantially from those derived from all the P. falciparum isolates collected from humans (see our Fig. 4). Indeed, the haplotype network analysis clearly indicates that the P. falciparum lineages in bonobos were substantially distinct and older that those found to date in humans (see our Table 2). Whereas the differentiation is not strong enough to separate them as independent species using phylogenetic analyses, such divergent haplotypes cannot be simply explained by a present day host switch from humans to bonobos. There is a remote possibility that the human P. falciparum lineages in the populations living close to the Lola ya Bonobo Sanctuary are ancient and unique to this location, but this remains to be demonstrated. The P. malariae lineages detected in two bonobos, could be of human origin, but it is equally likely that they represent a chronic infection acquired before the apes arrived to the sanctuary. In humans, infections by this parasite are notoriously long-lived. This is also the case in chimpanzees as recently demonstrated when two chimpanzees housed in Tokyo Zoo for 30 years were found infected with P. malariae [4]. It should be noted that malaria infections in their natural hosts (sometimes also in accidental or experimental hosts), including chimpanzees, often persist sub-patently for many years, where they are detectable only when the hosts are stressed or become ill. The negative results from the Ngamba Island chimpanzees might well reflect this; in fact the interesting observation for this site is that P. reichenowi-type parasites were not detected in these chimpanzees. It should also be noted that the apes on Ngamba Island have regular and frequent contact with humans: the team of 20 people who live on the island and care for them as well as groups of tourists who visit daily, often staying overnight.

Considering that apparently the same malaria parasite species were found in the bonobos and humans, we proposed that one can “justifiably explore whether African Apes could act as a reservoir” of human malaria parasites. Drs Leendertz and Gillespie have probably understood reservoir as "a natural host" from which humans can become infected [5]. However, we used it in an epidemiological sense, to denote host species where the infectious agent survives and can be transmitted to humans [6], irrespective of the fact that they might be domestic, synanthropic or wild animals. Ultimately, the detection of P. falciparum parasites in wild gorillas and chimpanzees [7] vindicates our conclusion that these hosts might be bona fide natural hosts and, therefore, reservoirs of parasites that infect humans.

Leendeertz and Gillespie are no doubt aware that African Apes living wild in pristine environment are dwindling in numbers. The remaining populations of these threatened species are increasingly in contact with humans, often with dire consequences. It might well be argued that it is the study of their pathogens in this context that is of primary importance to the challenge of preserving Great Apes.

1. Krief S, Escalante AA, Pacheco MA, Mugisha L, André C, et al. (2010) On the diversity of malaria parasites in African apes and the origin of Plasmodium falciparum from Bonobos. PLoS Pathog 6: e1000765.

2. Culleton RL, Mita T, Ndounga M, Unger H, Cravo PV, et al. (2008) Failure to detect Plasmodium vivax in West and Central Africa by PCR species typing. Malar J 7: 174.

3. Kahlenberg SM, Thompson ME, Muller MN, Wrangham RW (2008) Immigration costs for female chimpanzees and male protection as an immigrant counterstrategy to intrasexual aggression. Anim Behav 76: 1497-1509.

4. Hayakawa T, Arisue N, Udono T, Hirai H, Sattabongkot J, et al. (2009) Identification of Plasmodium malariae, a human malaria parasite, in imported chimpanzees. PLoS One 4: e7412.

5. Pavlovsky EN (1966) Natural nidality of transmissible diseases. Urbana, Illinois: University of Illinois Press.

6. Weber DJ, Rutala WA (2001) Biological basis of infections disease epidemiology. In: Thomas JC, Weber DJ, editors. Epidemiological methods for the study of infectious diseases. New York: Oxford University Press.

7. Prugnolle F, Durand P, Neel C, Ollomo B, Ayala FJ, et al. (2010) African great apes are natural hosts of multiple related malaria species, including Plasmodium falciparum. Proc Natl Acad Sci U S A 107: 1458-1463.

No competing interests declared.