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Efficacy of Two versus Three-Day Regimens of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Military Personnel in Northern Cambodia: An Open-Label Randomized Trial
- Source :
- PLoS ONE, Vol 9, Iss 3, p e93138 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Introduction Emerging 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. Methods Efficacy 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 360mg dihydroartemisinin and 2880mg 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. Results Eighty 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. Conclusions In 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 Registration ClinicalTrials.gov NCT01280162
- Subjects :
- Male
Primaquine
medicine.medical_treatment
lcsh:Medicine
law.invention
Randomized controlled trial
Dihydroartemisinin/piperaquine
Recurrence
law
Medicine and Health Sciences
Clinical endpoint
Medicine
Plasmodium Vivax
Malaria, Falciparum
lcsh:Science
Protozoans
Multidisciplinary
Clinical Pharmacology
Malarial Parasites
Artemisinins
Drug Resistance, Multiple
Plasmodium Falciparum
Infectious Diseases
Military Personnel
Research Design
Quinolines
Cambodia
geographic locations
Research Article
medicine.drug
Adult
medicine.medical_specialty
Clinical Research Design
Cardiology
Dihydroartemisinin
Research and Analysis Methods
Models, Biological
Cardiovascular Pharmacology
Drug Administration Schedule
Antimalarials
Piperaquine
Internal medicine
parasitic diseases
Parasitic Diseases
Malaria, Vivax
Humans
Plasmodium Malariae
Clinical Trials
Pharmacology
business.industry
lcsh:R
Organisms
Biology and Life Sciences
Tropical Diseases
medicine.disease
Parasitic Protozoans
Malaria
Surgery
Regimen
Pharmacodynamics
lcsh:Q
Clinical Medicine
business
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....544c902a5ac63798144832d01f9072d6