Strategies for mitigating emerging artemisinin-based antimalarial drug resistance in Rwanda: a promising approach for managing therapies in malaria-endemic countries

Abstract

Malaria treatment failures associated with reduced efficacy of chloroquine (CQ) and amodiaquine (AQ) antimalarial drugs emerged in Rwanda during the 1980s, prompting the policy shift towards adopting artemisinin-based combination therapies in 2006 as an alternative. However, recent findings from malaria surveillance and therapeutic efficacy studies have revealed a countrywide increase in antimalarial drug resistance. Particularly, artemether-lumefantrine (AL) efficacy has significantly decreased, probably due to the emergence of Plasmodium falciparum (Pf) genomic mutations. To mitigate the current drug resistance, Rwanda has adopted targeted multiple first-line therapies. Through the national malaria control program, antimalarial drugs were deployed in accordance with the reported resistance profile. A significant rise in Pfkelch13 mutations, particularly A675V associated with AL resistance, was mainly reported in the western region; therefore, artesunate-pyronaridine was recommended. Dihydroartemisinin-piperaquine was considered in eastern and central regions, where R561H mutations were predominant. On the contrary, AL was maintained in the southern region, where the prevalence of the R561H mutation was low. Insights from this data-driven model will inform its extension to other malaria-endemic countries facing emerging Pf genetic diversity.

Keywords: Health policy; Malaria; Parasitology; Treatment.

Figure 1. Distribution of Plasmodium falciparum. 13 mutations in Rwanda (2014–2024). The size of each point and intensity of its colour correlate with the frequency of mutations.

Figure 2. Frequency of Plasmodium falciparum mutations in various regions of Rwanda.

Figure 3. Deployment plan of multifirst-line therapy in Rwanda March 2025. Blue point: dihydroartemisinin-piperaquine (DHA-PPQ), red triangle: artesunate-pyronaridine (AS-PY), green square: artemether-lumefantrine (AL).