Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023
- PMID: 39846779
- PMCID: PMC11879165
- DOI: 10.1093/jac/dkaf006
Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023
Abstract
Background: Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.
Objective: To assess the proportion of P. falciparum parasites carrying molecular signatures associated with antimalarial resistance (PfKelch13, Pfmdr1, Pfcrt, dhfr and dhps) in isolates collected at Kédougou using multiplex amplicon deep sequencing.
Methods: Venous blood samples were collected from patients diagnosed with P. falciparum infection over a 3-year period (2021, 2022 and 2023). Parasite DNA was extracted, and multiplex amplicon sequencing was used to investigate gene polymorphisms.
Results: Analysis of PfKelch13 did not reveal any non-synonymous mutations. Pfcrt mutations were present in 45% of the samples, mainly K76T (44%) and I356T (36%). The dominant Pfmdr-1 allele was Y184F (62%). The sextuple mutant 51I/59R/108N + 436A/437G/613S dhfr/dhps was observed in 10% of the samples.
Conclusion: The absence of PfKelch13 mutants suggests that ACT efficacy remains uncompromised, although clinical outcome studies are required to confirm this. Analysis of Pfcrt and Pfmdr-1 shows that CQ-R alleles, probably from previous CQ use, are slowly decreasing. Likewise, the detection of the dhfr/dhps sextuple mutant highlights the need to monitor sulfadoxine-pyrimethamine resistance and the emergence of 581G. There is therefore a need for continued antimalarial resistance surveillance in Senegal.
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References
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- World Health Organization. World Malaria Report 2024: Addressing Inequity in the Global Malaria Response. World Health Organization, 2024. Licence: CC BY-NC-SA 3.0 IGO.
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Grants and funding
- K01 TW010496/TW/FIC NIH HHS/United States
- C1001647/Institut Pasteur de Paris, the Agence Universitaire de la Francophonie (AUF
- EDTCP fund Emerging Genomic Selection and Antimalarial Tolerance in African
- R01 AI168238/AI/NIAID NIH HHS/United States
- Crick African Network (CAN
- R01 AI168238/TW/FIC NIH HHS/United States
- National Institute of Allergy and Infectious Diseases, of the National Institutes of Health
- Crick African Network
- Suez Foundation
- UL1 TR001863/TR/NCATS NIH HHS/United States
- EQU202403018026/FRM
- G45267/G4 group funding
- FC1001647/Welcome Trust
- FC1001647/Cancer Research UK, the UK Medical Research Council
- MR/P028071/1/UK's Global Challenges Research Fund
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