ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021
Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Pooled it
- Prevalence of Plasmodium falciparum plasmepsin2/3 gene duplication in Africa and Asia: a systematic review and meta-analysis.Malaria journal · 2025Pooled it
- Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.The Lancet. Infectious diseases · 2022Trial
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- Molecular mechanisms involved inFrontiers in microbiology · 2026Review
- Gametocyte production and transmission fitness of African and AsianAntimicrobial agents and chemotherapy · 2025Article
- Genetic surveillance of Plasmodium falciparum populations following treatment policy revisions in the Greater Mekong Subregion.Nature communications · 2025Article
- Gametocyte production and transmission fitness of African and AsianbioRxiv : the preprint server for biology · 2025Article
- The emergence of artemisinin partial resistance in Africa: how do we respond?The Lancet. Infectious diseases · 2024Review
- Indigenous emergence and spread ofAntimicrobial agents and chemotherapy · 2024Article
- AmBio · 2024Article
- Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa.Nature reviews. Microbiology · 2024Review
- Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: a descriptive epidemiological study.The Lancet. Infectious diseases · 2024Article
- Preventing antimalarial drug resistance with triple artemisinin-based combination therapies.Nature communications · 2023Article
- Clinical needs assessment to inform development of a new assay to detect antimalarial drugs in patient samples: A case study.PLOS global public health · 2023Article
- Plasmodium falciparum resistance to artemisinin-based combination therapies.Current opinion in microbiology · 2022Review
- Optimal control analysis of hepatocytic-erythrocytic dynamics ofInfectious Disease Modelling · 2022Article
- Antimalarial and antitumour activities of the steroidal quinone-methide celastrol and its combinations with artemiside, artemisone and methylene blue.Frontiers in pharmacology · 2022Article
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArtesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.
methodsBetween September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat, and Siem Reap Provinces, Cambodia. Adults and children with microscopically confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for 3 days plus single-dose primaquine, with follow-up on days 7, 14, 21, and 28. The primary outcome was day-28 polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR). An amodiaquine parasite survival assay (AQSA) was developed and applied to whole genome sequencing results to evaluate potential amodiaquine resistance molecular markers.
resultsIn 63 patients, day-28 PCR-adjusted ACPR was 81.0% (95% confidence interval [CI], 68.9-88.7). Day 3 parasite positivity rate was 44.4% (28/63; 95% CI, 31.9-57.5). All 63 isolates had the K13(C580Y) marker for artemisinin resistance; 79.4% (50/63) had Pfpm2 amplification. The AQSA resistance phenotype (≥45% parasite survival) was expressed in 36.5% (23/63) of isolates and was significantly associated with treatment failure (P = .0020). Pfmdr1 mutant haplotypes were N86/184F/D1246, and Pfcrt was CVIET or CVIDT at positions 72-76. Additional Pfcrt mutations were not associated with amodiaquine resistance, but the G353V mutant allele was associated with ACPR compared to Pfmdr1 haplotypes harboring F1068L or S784L/R945P mutations (P = .030 and P = .0004, respectively).
conclusionsFor uncomplicated falciparum malaria in Cambodia, artesunate-amodiaquine had inadequate efficacy owing to amodiaquine-resistant P. falciparum. Amodiaquine resistance was not associated with previously identified molecular markers.
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