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

TL;DR

This study found high levels of drug resistance in malaria parasites in Makenene, Cameroon, emphasizing the need for updated treatment strategies.

Contribution

The study reports the prevalence of specific genetic markers of antimalarial drug resistance in a previously understudied region of Cameroon.

Findings

100% of samples had parasites with triple mutant PfdhfrIRNI, linked to pyrimethamine resistance.

62% of isolates had the septuple mutant PfdhfrIRNI and PfdhpsAGKGS, associated with sulfadoxine-pyrimethamine resistance.

73.2% of samples had Pfmdr1NF haplotype, linked to artemether-lumefantrine resistance.

Abstract

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.

Image 1

•100 % triple mutant Pfdhfr
IRNI, associated with resistance to pyrimethamine.•62.0 % of septuple mutant IRNI and AGKGS (resistance to sulfadoxine-pyrimethamine).•The new Pfdhps I431V mutation was observed in 18.8 %.•73.2 % of Pfmdr1 NF haplotype, selected in artemether-lumefantrine resistance.•No mutation associated with artemisinin partial resistance.

100 % triple mutant Pfdhfr
IRNI, associated with resistance to pyrimethamine.

62.0 % of septuple mutant IRNI and AGKGS (resistance to sulfadoxine-pyrimethamine).

The new Pfdhps I431V mutation was observed in 18.8 %.

73.2 % of Pfmdr1 NF haplotype, selected in artemether-lumefantrine resistance.

No mutation associated with artemisinin partial resistance.

Figures