Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon
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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.
Originalsprog | Engelsk |
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Tidsskrift | International Journal of Infectious Diseases |
Vol/bind | 132 |
Sider (fra-til) | 108-117 |
Antal sider | 10 |
ISSN | 1201-9712 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The pharmacovigilance study on AQ, SP, and SP - AQ conducted from 2004-2006 in Yaounde was supported by a subgrant to WFM (ITDC VG 34), from the Gates Malaria Partnership at the London School of Hygiene and Tropical Medicine , which received support from the Bill and Melinda Gates Foundation , USA. Additional financial support for equipment was provided by the International Atomic Energy , Agency grant number RAF6/0/25 , Vienna. The IPP study conducted in 2014 in Yaounde was supported financially by the National Institutes of Health Research Training Grant #R25 TW009345 awarded to the Northern Pacific Global Health Fellows Program by the Fogarty International Center/National Institutes for Health , USA and GID Training Grant - D43TW009074 FIC/NIH. The pharmacovigilance study on artesunate-amodiaquine and AL carried out from 2019 to 2020 in Yaounde was funded in whole by the Wellcome Trust (grant # 107741/A/15/Z ) and the UK Foreign, Commonwealth and Development Office , with support from the Developing Excellence in Leadership, Training and Science in Africa (DELTAS Africa) program. This study was also funded by the National Institutes of Health (NIH), USA (grant # U19AI089672 ). For the purpose of open access, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission.
Publisher Copyright:
© 2023 The Authors
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