International Journal of Infectious Diseases (Jul 2023)

Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon

  • Peter Thelma Ngwa Niba,
  • Akindeh Mbuh Nji,
  • Jean Paul Kengne Chedjou,
  • Helle Hansson,
  • Emma Filtenborg Hocke,
  • Innocent Mbulli Ali,
  • Olivia Achonduh-Atijegbe,
  • Marie-Solange B. Evehe,
  • Marie Helene Munck Jørgensen,
  • Calvino Tah Fomboh,
  • Liwang Cui,
  • Gillian Stresman,
  • Jude D. Bigoga,
  • Michael Alifrangis,
  • Wilfred F. Mbacham

Journal volume & issue
Vol. 132
pp. 108 – 117

Abstract

Read online

Objectives: This study aimed to investigate the evolution of Plasmodium falciparum antimalarial drug resistance markers by comparing the pre- and post-adoption of artemisinin-based combination therapies (ACTs) in Yaounde, Cameroon. Methods: The molecular characterization of known antimalarial drug resistance markers (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and Pfk13) in P. falciparum-positive samples collected in 2014 and 2019-2020 was achieved using nested polymerase chain reaction, followed by targeted amplicon deep sequencing on the Illumina MiSeq platform. Data derived were compared with those published during the pre-ACT adoption period from 2004 to 2006. Results: A high prevalence of Pfmdr1 184F, Pfdhfr 51I/59R/108N, and Pfdhps 437G mutant alleles was observed during the post-ACT adoption period. The Pfcrt 76T and Pfmdr1 86Y mutant alleles significantly declined between 2004 and 2020 (P <0.0001). Conversely, the resistance markers to antifolates, Pfdhfr 51I/59R/108N and Pfdhps 437G, significantly increased during the same study period (P <0.0001). We identified nine mutations in the propeller domains of Pfk13; although they were all present in single parasite isolates, none of them are known to confer artemisinin resistance. Conclusion: This study documented a near-complete reversion to sensitive parasites for markers conferring resistance to the 4-aminoquinolines and arylamino alcohols in Yaounde. In contrast, the Pfdhfr mutations associated with pyrimethamine resistance are moving toward saturation.

Keywords