Background: The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia.
Methods: P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently.
Results: The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas.
Conclusions: K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar.
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http://dx.doi.org/10.1093/infdis/jiu491 | DOI Listing |
Lancet Infect Dis
December 2024
MMV Medicines for Malaria Venture, Geneva, Switzerland.
Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.
Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).
Lancet Microbe
December 2024
Malaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
Background: Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We therefore aimed to determine the safety and efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Praziquantel alone is insufficient for the control of schistosomiasis due to poor efficacy against juvenile worms and increasing concerns about the risk of drug resistance. We compared the efficacy and safety of praziquantel combined with four different artemisinin-based combinations to praziquantel alone in treating infection in Kenyan children. In this randomized, open-label, five-arm, head-to-head, non-inferiority trial, children (aged 9-15 years) with infection according to duplicate Kato Katz thick smears from a stool sample in the Mwea irrigation scheme of central Kenya, were enrolled.
View Article and Find Full Text PDFMalar J
December 2024
Malaria Research and Training Center, Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
Background: Malaria remains a significant public health concern, despite global efforts to combat the disease with highest burden in Africa. Reports of emerging artemisinin partial- resistance in East Africa emphasize the importance of molecular data to guide policy decisions. Hence the need for researchers to collaborate with National control programmes to conduct genomics surveillance of malaria to inform malaria control and elimination policies.
View Article and Find Full Text PDFFront Genet
December 2024
Biomedical Sciences Department, Institute of Tropical Medicine, Antwerp, Belgium.
Introduction: Vietnam's goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).
Methods: The custom targeted NGS amplicon sequencing assay, AmpliSeq Pf Vietnam v2, targeting drug resistance, population genetic- and other markers, was applied to detect genetic diversity and resistance profiles in samples from 8 provinces in Vietnam (n = 354), in a period of steep decline of incidence (2018-2020). Variants in 14 putative resistance genes, including and , were analyzed and within-country parasite diversity was evaluated.
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