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

Abstract

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.

Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax

“…3C). These findings are consistent with results from epidemiological surveys in Cameroon and Gabon, which demonstrated that humans living in the immediate vicinity of wild-living chimpanzees and gorillas do not harbor ape Laverania parasites (Sundararaman et al, 2013; Delicat-Loembet et al, 2015). Thus, P. praefalciparum parasites appear incapable of infecting humans, suggesting that the particular gorilla parasite strain that was able to cross the host species barrier must have carried one or more highly unusual mutations that conferred an ability to colonize humans.…”

Molecular interactions governing host-specificity of blood stage malaria parasites

“…The Laverania cluster into host species-specific clades with little or no evidence of cross-species transmission, despite geographical overlap in host distributions [5,24,25]. Mosquito vectors of the ape Laverania readily bite humans, indicating that human exposure to these parasites occurs with regularity in parts of equatorial Africa [26].…”

Wild African great apes as natural hosts of malaria parasites: current knowledge and research perspectives

“…However, recent broad-scale investigations based on the detection of malaria parasite DNA (mitochondrial, nuclear and apicoplast sequences) in faecal samples of wild AGA populations resulted in the genetic characterisation of a wide array of other Plasmodium species. This showed that the entire diversity of human-derived P. falciparum sequences is encompassed by the gorilla P. praefalciparum clade (Liu et al, 2010;Sundararaman et al, 2013) and led to the substantial indication that P. falciparum originated from a relatively recent zoonotic transmission of P. praefalciparum from gorillas to humans (Liu et al, 2010).…”

“…They could thus, in theory, act as vectors for interspecies transmissions. Studies led in Cameroon (Sundararaman et al, 2013) and Gabon (Délicat-Loembet et al, 2015) searched for evidence of zoonotic transfers of ape Laverania species by testing large numbers of human blood samples (N = 1402 and N = 4281) from people living in the vicinity of chimpanzee and gorilla populations with high Laverania prevalence rates. No ape parasites (Laverania or non-Laverania) were detected in these samples, implying that zoonotic transfers might be rare events.…”

“…Given the close resemblance to their human counterparts and past experimental findings, it is likely that, similarly to P. vivax, zoonotic transfers of P. ovale-and malariaelike parasites from chimpanzees also take place. It would be useful to characterise more of these parasites in order to search for evidence of such transmissions (Sundararaman et al, 2013).…”