title: 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.
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sesh A
authors.initials: SA
authors.lastname: Sundararaman
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: Kyle
authors.initials: K
authors.lastname: Bittinger
authors.forename: Fatima
authors.initials: F
authors.lastname: Mouacha
authors.forename: Steve
authors.initials: S
authors.lastname: Ahuka-Mundeke
authors.forename: Magnus
authors.initials: M
authors.lastname: Manske
authors.forename: Scott
authors.initials: S
authors.lastname: Sherrill-Mix
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Malenke
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
authors.forename: Christian
authors.initials: C
authors.lastname: Laurent
authors.forename: Eitel
authors.initials: E
authors.lastname: Mpoudi Ngole
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sharp
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
mesh_terms: D000818:Animals; D018420:Ape Diseases / Q000453:epidemiology* / Q000469:parasitology* / Q000635:transmission; D001483:Base Sequence; D001499:Bayes Theorem; D002163:Cameroon / Q000453:epidemiology; D004272:DNA, Mitochondrial / Q000235:genetics; D004197:Disease Reservoirs / Q000469:parasitology*; D006071:Gorilla gorilla; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016013:Likelihood Functions; D008288:Malaria / Q000453:epidemiology / Q000635:transmission / Q000662:veterinary*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D002679:Pan troglodytes; D010802:Phylogeny; D010961:Plasmodium / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary; D013045:Species Specificity
chemical_list: D004272:DNA, Mitochondrial