Resistance to artemisinin, the main component of current antimalarial treatments recommended by WHO, is widespread in South-East Asia, but has not been described in Africa. In a study published in 2020, scientists from the Institut Pasteur, in collaboration with the NMCP in Rwanda, the WHO and Columbia University provided for the first time evidence of the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda.
The emergence and spread of Plasmodium falciparum artemisinin-resistant Pfkelch13 mutants is a major and growing threat to malaria elimination in Southeast Asia. To date, artemisinin resistance has been reported in Southeast Asia, and has not been detected in Africa, the region of the brunt of the global burden of malaria
We conducted clinical drug efficacy studies in 2013-2015 at two health facilities in Rwanda and performed genomic investigations on blood samples collected from enrolled patients’ prior treatment. We identified 14 non-synonymous Pfkelch13 mutations in 35/505 samples (6.9%). The Pfkelch13 R561H allele was the most predominant (19/35) allele, observed exclusively in one site (Masaka). In vitro susceptibility testing confirmed the role of Pfkelch13 R561H mutation in conferring artemisinin resistance. Analyses of Pfkelch13 flanking regions and phylogenetic analysis of whole-genome sequences showed that Rwandan Pfkelch13 R561H mutants originate from Africa with no genetic relatedness with parasites harbouring the Pfkelch13 R561H mutation previously identified in Southeast Asia. The reduced genetic diversity around the Pfkelch13 R561H mutation indicates a recent selective sweep without any association with a particular Southeast Asian genetic backbone or with molecular signatures associated with resistance to antimalarial drugs.
Our findings clearly show early warning signs of emergence and clonal expansion of in vitro artemisinin-resistant indigenous Plasmodium falciparum kelch13 R561H mutant in Rwanda. Our findings call for increased surveillance of P. falciparum parasite populations in Rwanda and neighbouring countries, to contain the spread of artemisinin resistance and prolong the life span of Artemisinin-based Combined Treatments.
This study is part of the priority scientific area Antimicrobial Resistance of the Institut Pasteur's strategic plan for 2019-2023.