Prevalence of antimalarial drug resistance molecular markers in Makenene, central Cameroon

Antimalarial drug resistance remains a significant challenge in the fight against malaria in Cameroon. Given the high prevalence of malaria in Makenene in central Cameroon and the limited knowledge of drug resistance profiles in the area, the prevalence of Plasmodium falciparum drug resistance genetic markers was assessed.

185 samples from asymptomatic individuals with P. falciparum parasitaemia collected between September and October 2021 were sequenced for the Pfdhfr, Pfdhps, Pfcrt, Pfmdr1, and PfK13 genes.

One hundred percent of the samples harboured parasites with triple mutant PfdhfrI₅₁R₅₉N₁₀₈I₁₆₄ (IRNI), associated with high level of resistance to pyrimethamine. The septuple mutant PfdhfrIRNI and PfdhpsA₄₃₆G₄₃₇K₅₄₀G₅₈₁S₆₁₃ (AGKGS), associated with resistance to sulfadoxine-pyrimethamine, was detected in 62.0 % of the isolates. The new Pfdhps I431V mutation was observed in 18.8 %. The octuple mutant IRNI + VAGKGS haplotype, overrepresented in pregnant women taking intermittent preventive treatment with sulfadoxine-pyrimethamine, was found in 17.4 %. The Pfdhps K540E mutation, linked to "super" resistance to sulfadoxine, was only detected in 1.9 %. The Pfcrt C₇₂V₇₃I₇₄E₇₅T₇₆ haplotype, implicated in chloroquine resistance, was absent in Makenene. The Pfmdr1 N₈₆F₁₈₄ haplotype, selected in parasites with a recrudescence in patients treated with artemether-lumefantrine, was found in 73.2 %. No isolate harboured the Y₈₆Y₁₈₄ haplotype, selected in parasites with recrudescence in patient treated with dihydroartemisinin-piperaquine. Moreover, no mutation associated with artemisinin partial resistance was detected in PfK13.

The in-depth analysis of genetic mutations associated with antimalarials resistance in this study, notably those with a high prevalence of mutations on the Pfdhfr and Pfdhps genes, highlights the immediate need for proactive strategies to combat resistance in Makenene. Continuous monitoring, including molecular and in vivo surveillance is crucial to uphold the effectiveness of current treatments and, more particularly, artemisinin-based combination therapies, and to enable better decision-making on effective treatment policy in Cameroon and in Africa as a whole.