Mosquitoes as Potential Bridge Vectors of Malaria Parasites from Non-Human Primates to Humans

Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, where wild apes live, at different heights under the canopy. More than 2,400 anopheline mosquitoes belonging to 18 species were collected. Among them, only three species of Anopheles were found infected with ape Plasmodium: Anopheles vinckei, Anopheles moucheti, and Anopheles marshallii. Their role in transmission was confirmed by the detection of the parasites in their salivary glands. Among these species, An. vinckei showed significantly the highest prevalence of infection and was shown to be able to transmit parasites of both chimpanzees and gorillas. Transmission was also shown to be conditioned by seasonal factors and by the heights of capture under the canopy. Moreover, human landing catches of sylvan Anopheles demonstrated the propensity of these three vector species to feed on humans when available. Our results suggest therefore that the strong host specificity observed in the Laveranias is not linked to a specific association between the vertebrate host and the vector species and highlight the potential role of these vectors as bridge between apes and humans.Plasmodium | Laverania | Anopheles | ape-to-human infection | African rainforest R ecent studies on great apes in Africa have revealed the existence of a large diversity of Plasmodium parasites infecting chimpanzees and gorillas, some being related to the most deadly human parasite Plasmodium falciparum (subgenus Laverania), others to the human parasites Plasmodium malariae, Plasmodium ovale, or Plasmodium vivax (subgenus Plasmodium) (1-4).Within the subgenus Laverania, eight species are currently recognized. Among them, four species (Plasmodium reichenowi, Plasmodium gaboni, Plasmodium billcollinsi, and Plasmodium billbrayi) were observed only in chimpanzees and three (Plasmodium praefalciparum, Plasmodium adleri, and Plasmodium blacklocki) only in gorillas (2,3,5). In this subgenus, only P. falciparum infects humans. In natura, although these different host species cooccur in the same habitat where their ranges overlap, no transfer of Laverania parasites was ever documented between humans and apes or between gorillas and chimpanzees despite large sampling efforts (2, 3, 6). Similarly, ancient reciprocal transplant experiments of Laverania parasites between humans and apes (mostly chimpanzees) failed to produce infections (5). On the contrary, for parasites of the subgenus Plasmodium, like P. vivax or P. malariae, transfers were documented in natural populations (2, 4, 7) or during experimental infections (5). All this suggests therefore a strong host specifici...

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ape malaria transmission and potential for ape-to-human transfers in Africa

Makanga

Yangari

Rahola

et al. 2016

“…Because of its anthropophilic nature and high density, An. gambiae is considered the most important vector of human malaria in Africa (32,33). A recent study comparing the epidemiology of R. felis infection and malaria in northern and sub-Saharan Africa found a significant linear trend of increasing risk for R. felis infection.…”

Section: Discussionmentioning

confidence: 99%

Transmission potential of Rickettsia felis infection by Anopheles gambiae mosquitoes

Dieme

Bechah

Socolovschi

et al. 2015

138

A growing number of recent reports have implicated Rickettsia felis as a human pathogen, paralleling the increasing detection of R. felis in arthropod hosts across the globe, primarily in fleas. Here Anopheles gambiae mosquitoes, the primary malarial vectors in subSaharan Africa, were fed with either blood meal infected with R. felis or infected cellular media administered in membrane feeding systems. In addition, a group of mosquitoes was fed on R. felisinfected BALB/c mice. The acquisition and persistence of R. felis in mosquitoes was demonstrated by quantitative PCR detection of the bacteria up to day 15 postinfection. R. felis was detected in mosquito feces up to day 14. Furthermore, R. felis was visualized by immunofluorescence in salivary glands, in and around the gut, and in the ovaries, although no vertical transmission was observed. R. felis was also found in the cotton used for sucrose feeding after the mosquitoes were fed infected blood. Natural bites from R. felisinfected An. gambiae were able to cause transient rickettsemias in mice, indicating that this mosquito species has the potential to be a vector of R. felis infection. This is particularly important given the recent report of high prevalence of R. felis infection in patients with "fever of unknown origin" in malaria-endemic areas.Rickettsia felis | spotted fever | Anopheles gambiae I n 2002, Rickettsia felis, an obligate intracellular bacterium that belongs to the spotted fever group of Rickettsia, was definitively described (1, 2). Over the past 2 decades, an increasing number of reports have implicated R. felis as a human pathogen, paralleling an increase in reports of the detection of R. felis in arthropod hosts throughout the world (1, 3).By 2011, more than 70 human cases of R. felis had been reported worldwide, including in Central and South America, Asia, northern Africa, and Europe (1). More cases have been published since then, including the first probable human cases in Australia (4). In sub-Saharan Africa, recent studies have challenged the importance of R. felis infection in patients with "fever of unknown origin," with this bacterium detected in up to 15% of such patients (5-7). In 2011, a potential R. felis primary infection, called "yaaf," was suspected in the case of an 8-mo-old girl in Senegal with polymorphous skin lesions similar to those seen in patients from Mexico (8). The epidemiologic and clinical picture of this emerging infection in Africa, including its potential vectors, is poorly understood, however.Various arthropods, but primarily fleas, have been associated with R. felis (1, 3). More specifically, the cat flea Ctenocephalides felis is the arthropod in which R. felis has been most frequently detected. To date, it is the sole confirmed biological vector of R. felis, with both horizontal and vertical transmission making this flea a potential reservoir for this bacterium (9-11). However, in some countries where R. felis appears to be highly prevalent, such as Senegal, neither cat fleas nor other arthropods have been...

“…The discovery of this previously unrecognized reservoir has prompted concerns that wild-living apes might constitute a source of recurrent human infection (4,5,9,(11)(12)(13). In this study, we set out to examine this possibility for several reasons.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, P. praefalciparum was shown to be the immediate precursor of human P. falciparum (4). Because candidate Anopheles vectors have been identified that may transmit both ape and human parasites (11), the fact that a large fraction of wild-living apes is endemically Plasmodium infected has raised concerns that they might represent a source of recurring human infections (4,5,9,12,13).…”

mentioning

confidence: 99%

Plasmodium falciparum -like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria

Sundararaman

Liu²,

Keele

et al. 2013

Wild-living chimpanzees and gorillas harbor a multitude of Plasmodium species, including six of the subgenus Laverania , one of which served as the progenitor of Plasmodium falciparum . Despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. Here, we used Plasmodium species-specific PCR, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern Cameroon for ape Laverania infections. Among 1,402 blood samples, we found 1,000 to be Plasmodium mitochondrial DNA (mtDNA) positive, all of which contained human parasites as determined by sequencing and/or restriction enzyme digestion. To exclude low-abundance infections, we subjected 514 of these samples to 454 sequencing, targeting a region of the mtDNA genome that distinguishes ape from human Laverania species. Using algorithms specifically developed to differentiate rare Plasmodium variants from 454-sequencing error, we identified single and mixed-species infections with P. falciparum , Plasmodium malariae , and/or Plasmodium ovale . However, none of the human samples contained ape Laverania parasites, including the gorilla precursor of P. falciparum . To characterize further the diversity of P. falciparum in Cameroon, we used single-genome amplification to amplify 3.4-kb mtDNA fragments from 229 infected humans. Phylogenetic analysis identified 62 new variants, all of which clustered with extant P. falciparum , providing further evidence that P. falciparum emerged following a single gorilla-to-human transmission. Thus, unlike Plasmodium knowlesi -infected macaques in southeast Asia, African apes harboring Laverania parasites do not seem to serve as a recurrent source of human malaria, a finding of import to ongoing control and eradication measures.