Trial reportPloS one2014
Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01280162 (An Active Malaria Epidemiology Cohort Study With Evaluation of a 2 Day Versus 3 Day Treatment Regimen of Dihydroartemisinin), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Active Malaria Epidemiology Cohort Study With Evaluation of a 2 Day Versus 3 Day Treatment Regimen of Dihydroartemisinin (DHA)-Piperaquine for Patients With Uncomplicated Malaria
Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Risk of sudden unexplained death after use of dihydroartemisinin-piperaquine for malaria: a systematic review and Bayesian meta-analysis.The Lancet. Infectious diseases · 2018Pooled it
- Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review.Malaria journal · 2014Pooled it
- Evaluating malaria elimination strategies among military forces in Cambodia: a multi-arm clinical trial comparing monthly prophylaxis and focused screening and treatment.BMC infectious diseases · 2025Trial
- Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.The New England journal of medicine · 2019Trial
- Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia.Antimicrobial agents and chemotherapy · 2017Trial
- Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand.Malaria journal · 2016Trial
- Antibody profiles to plasmodium merozoite surface protein-1 in Cambodian adults during an active surveillance cohort with nested treatment study.Malaria journal · 2016Trial
- Randomized, double-blind, placebo-controlled clinical trial of a two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted for concern over prolonged corrected QT interval.Antimicrobial agents and chemotherapy · 2014Trial
- Pharmacokinetics and Pharmacodynamics of Antimalarial Agents: Optimizing Combination Therapies to Overcome Resistance Mechanisms.Journal of clinical pharmacology · 2026Review
- A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine.Current drug metabolism · 2025Review
- Artemisinin-resistant malaria.Clinical microbiology reviews · 2024Review
- Article
- Classification of disease recurrence using transition likelihoods with expectation-maximization algorithm.Statistics in medicine · 2022Article
- Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009-2011: a randomized controlled trial and brief review.Malaria journal · 2022Review
- Dynamic Classification ofJournal of data science : JDS · 2022Article
- Time to scale up molecular surveillance for anti-malarial drug resistance in sub-saharan Africa.Malaria journal · 2021Article
- Malaria in Cambodia: A Retrospective Analysis of a Changing Epidemiology 2006-2019.International journal of environmental research and public health · 2021Article
- Relapse or reinfection: Classification of malaria infection using transition likelihoods.Biometrics · 2020Article
- Prevalence of CYP2D6 Genotypes and Predicted Phenotypes in a Cohort of Cambodians at High Risk for Infections withThe American journal of tropical medicine and hygiene · 2020Article
- Unsymmetrical Bisquinolines with High Potency againstMolecules (Basel, Switzerland) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 7 institutions in 3 countries.
Funding
Abstract
introductionEmerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.
methodsEfficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline). The first 80 volunteers with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1 to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg piperaquine) and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with vivax infection received primaquine at study discharge with six months follow-up.
resultsEighty patients (60 vivax, 15 falciparum, and 5 mixed) were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69-94) and 90% for the three-day regimen (95% CI 75-97). PCR-adjusted falciparum efficacy was 75% in both groups with nearly half (45%) still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable in vitro piperaquine IC50 levels in all falciparum treatment failures.
conclusionsIn the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC50 levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.
trial registrationClinicalTrials.gov NCT01280162.
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Registered trials
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.