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

Sesh A. Sundararaman, Weimin Liu, Brandon F. Keele, Gerald H. Learn, Kyle Bittinger, Fatima Mouacha, Steve Ahuka-Mundeke, Magnus Manske, Scott Sherrill-Mix, Yingying Li, Jordan A. Malenke, Eric Delaporte, Christian Laurent, Eitel Mpoudi Ngole, Dominic P. Kwiatkowski, George M. Shaw, Julian C. Rayner, Martine Peeters, Paul M. Sharp, Frederic D. BushmanBeatrice H. Hahn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)7020-7025
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume110
Issue number17
DOIs
Publication statusPublished - 23 Apr 2013

Keywords

  • DIVERSIFICATION
  • great apes
  • Plasmodium coinfections
  • AMPLIFICATION
  • nextgen sequencing
  • ERYTHROCYTE INVASION
  • Plasmodium diversity
  • RESISTANCE
  • diagnostic Laverania PCR
  • KNOWLESI
  • TRANSMISSION
  • ORIGIN

Fingerprint

Dive into the research topics of 'Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria'. Together they form a unique fingerprint.

Cite this