ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2016
Declining Efficacy of Artemisinin Combination Therapy Against P. Falciparum Malaria on the Thai-Myanmar Border (2003-2013): The Role of Parasite Genetic Factors.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 5 of them syntheses that pooled it.
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Who cites it
149 citing papers in PubMed, 5 syntheses or guidelines pooled it, 239 citations in OpenAlex.
- The effect of mefloquine dose on outcome of uncomplicated falciparum malaria treated with artesunate-mefloquine: a WWARN systematic review and individual patient data meta-analysis.Malaria journal · 2026Pooled it
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- Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria.The Cochrane database of systematic reviews · 2025Pooled it
- Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review ofInternational journal of molecular sciences · 2024Pooled it
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- Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021.Malaria journal · 2024Trial
- Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial.The Lancet. Infectious diseases · 2021Trial
- Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial.The Lancet. Infectious diseases · 2021Trial
- Trial
- Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.Lancet (London, England) · 2020Trial
- Pharmacokinetics andAntimicrobial agents and chemotherapy · 2020Trial
- Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study.The Lancet. Infectious diseases · 2019Trial
- Sequential Open-Label Study of the Safety, Tolerability, and Pharmacokinetic Interactions between Dihydroartemisinin-Piperaquine and Mefloquine in Healthy Thai Adults.Antimicrobial agents and chemotherapy · 2019Trial
- Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children.Infectious diseases of poverty · 2018Trial
- Trial
- Effectiveness and safety of 3 and 5 day courses of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar.Malaria journal · 2018Trial
- Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar.Malaria journal · 2018Trial
- Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.Malaria journal · 2016Trial
- Hydroxamic Acids as HDAC Inhibitor Drug Leads for Malaria.Medicinal research reviews · 2026Review
- Article
89 more citing papers are in PubMed but not listed here.
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20 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundDeployment of mefloquine-artesunate (MAS3) on the Thailand-Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of Plasmodium falciparum K13 mutations (a marker of artemisinin resistance) in reducing treatment efficacy remains controversial.
methodsBetween 2003 and 2013, we studied the efficacy of MAS3 in 1005 patients with uncomplicated P. falciparum malaria in relation to molecular markers of resistance.
resultsPolymerase chain reaction (PCR)-adjusted cure rates declined from 100% in 2003 to 81.1% in 2013 as the proportions of isolates with multiple Pfmdr1 copies doubled from 32.4% to 64.7% and those with K13 mutations increased from 6.7% to 83.4%. K13 mutations conferring moderate artemisinin resistance (notably E252Q) predominated initially but were later overtaken by propeller mutations associated with slower parasite clearance (notably C580Y). Those infected with both multiple Pfmdr1 copy number and a K13 propeller mutation were 14 times more likely to fail treatment. The PCR-adjusted cure rate was 57.8% (95% confidence interval [CI], 45.4, 68.3) compared with 97.8% (95% CI, 93.3, 99.3) in patients with K13 wild type and Pfmdr1 single copy. K13 propeller mutation alone was a strong risk factor for recrudescence (P = .009). The combined population attributable fraction of recrudescence associated with K13 mutation and Pfmdr1 amplification was 82%.
conclusionsThe increasing prevalence of K13 mutations was the decisive factor for the recent and rapid decline in efficacy of artemisinin-based combination (MAS3) on the Thailand-Myanmar border.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.