ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2024
Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial.The Lancet. Infectious diseases · 2026Trial
- Emergence and spread of Plasmodium falciparum PX1 polymorphisms associated with decreased susceptibility to antimalarials in Uganda.Nature medicine · 2026Article
- Experimental evolution and functional genetics identify KIC1 as a determinant of reduced artemisinin susceptibility in BangladeshibioRxiv : the preprint server for biology · 2026Article
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- Rapid whole-genome sequencing of Plasmodium DNA from cryptic malaria cases in UK travellers provides insights into infection origins, transmission and antimalarial resistance.Journal of travel medicine · 2026Article
- Identification of an Orally Efficacious Imidazo[4,5-Journal of medicinal chemistry · 2026Article
- Physiological febrile heat stress increases cytoadhesion through increased protein trafficking ofeLife · 2026Article
- AbioRxiv : the preprint server for biology · 2026Article
- Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.Nature communications · 2026Article
- NovelmBio · 2026Article
- Artemisinin Partial Resistance Mutations in Zanzibar and Tanzania Suggest Regional Spread and African Origins, 2023.The Journal of infectious diseases · 2026Article
- Temporal trends in artemisinin partial resistance and other antimalarial drug mutations inFrontiers in genetics · 2026Article
- Temporal Trends in Artemisinin Partial Resistance and Other Antimalarial Drug Mutations inmedRxiv : the preprint server for health sciences · 2025Article
- Making the most of existing antimalarial medicines: a single dose cure with sulfadoxine-pyrimethamine plus artesunate-pyronaridine.Malaria journal · 2025Review
- Changes in susceptibility of Plasmodium falciparum to antimalarial drugs in Uganda over time: 2019-2024.Nature communications · 2025Article
- Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infections.The Journal of infectious diseases · 2025Article
- Artemisinin resistantmedRxiv : the preprint server for health sciences · 2025Article
- Genetic surveillance reveals low but sustained malaria transmission with clonal replacement in Sao Tome and Principe.Communications medicine · 2025Article
- Ex Vivo Drug Susceptibility ofPathogens (Basel, Switzerland) · 2025Article
- Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study.The Lancet. Microbe · 2025Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRecent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide.
methodsParasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor.
resultsA traveler, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival, 17.3% [95% confidence interval {CI}, 13.6%-21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6-388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 parasite lines.
conclusionsWe confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda.
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