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. 2025 Mar 3;80(3):828-839.
doi: 10.1093/jac/dkaf006.

Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023

Alioune Wade  1   2 , Seynabou D Sene  1   2 , Emanuelle Caspar  3 , Fatoumata Diallo  1   2 , Lucien Platon  3 , Lucas Thiebaut  3 , Mariama N Pouye  1   2 , Aboubacar Ba  1   2 , Laty Gaye Thiam  1   2 , Magal Fall  1   2 , Bacary Djilocalisse Sadio  4 , Ife Desamours  5 , Noemi Guerra  5 , Kelly Hagadorn  5 , Alfred Amambua-Ngwa  6 , Amy K Bei  1   2   5 , Ines Vigan-Womas  2   7 , Didier Ménard  3   8   9   10 , Alassane Mbengue  1   2   11
Affiliations

Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023

Alioune Wade et al. J Antimicrob Chemother. .

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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Figures

Figure 1.
Figure 1.
Study sites in the Kédougou region from 2021 to 2023. The study was conducted at four different sites over the years: in 2021 (Bandafassi, Camp-Militaire and Dalaba), Dalaba and Bandafassi in 2022, and finally in 2023 between Dalaba and Ndiormi.
Figure 2.
Figure 2.
Demographic characteristics of our study population. (a) Represents the male–female ratio. (b) Shows the distribution of patients recruited at the different sites over the 3 years. (c) Shows the age distribution of the study population. (d) Shows the number of patients recruited in each year.
Figure 3.
Figure 3.
Mutational frequency of molecular markers resistance over the 3 years. (a). The ‘Non-Synonymous’ category indicates the frequency of SNPs detected for each marker. ‘Synonymous’ represents synonymous mutations detected on the Pfkelch13 gene, while ‘WT’ designates the normal or unmutated form of one of the markers. (b). Shows the frequency distribution of mutations detected for each gene in different years.
Figure 4.
Figure 4.
Haplotypes frequency of molecular markers resistance over the 3 years. Representation of the different haplotypes for each marker according to the 3 different years.
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References

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