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Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda
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Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda
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Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda
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Journal Article
Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda
2020
Overview
Artemisinin resistance (delayed
P. falciparum
clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa
1
–
4
. Here we genotyped the
P. falciparum K13
(
Pfkelch13
) propeller domain, mutations in which can mediate artemisinin resistance
5
,
6
, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda
7
. While cure rates were >95% in both treatment arms, the
Pfkelch13
R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of
Pfkelch13
-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.
Identification in Rwanda of mutations in
Plasmodium falciparum
capable of conferring in vitro resistance to artemisinin, an essential medicine for the treatment of malaria, underscore the crucial need for surveillance in Africa to safeguard efficacy of life-saving therapies.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Amino Acid Substitution - genetics
/ Animals
/ Antimalarials - therapeutic use
/ Artemisinins - therapeutic use
/ Biomedical and Life Sciences
/ Communicable Diseases, Emerging - drug therapy
/ Communicable Diseases, Emerging - epidemiology
/ Communicable Diseases, Emerging - parasitology
/ Genotype
/ Humans
/ Letter
/ Malaria
/ Malaria, Falciparum - drug therapy
/ Malaria, Falciparum - epidemiology
/ Malaria, Falciparum - parasitology
/ Microbiology and Parasitology
/ Mutation
/ Plasmodium falciparum - drug effects
/ Plasmodium falciparum - genetics
/ Protozoan Proteins - chemistry
