Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/33031
Title: Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in Northern Cambodia: An open-label randomized trial
Authors: Chanthap Lon
Jessica E. Manning
Pattaraporn Vanachayangkul
Mary So
Darapiseth Sea
Youry Se
Panita Gosi
Charlotte Lanteri
Suwanna Chaorattanakawee
Sabaithip Sriwichai
Soklyda Chann
Worachet Kuntawunginn
Nillawan Buathong
Samon Nou
Douglas S. Walsh
Stuart D. Tyner
Jonathan J. Juliano
Jessica Lin
Michele Spring
Delia Bethell
Jaranit Kaewkungwal
Douglas Tang
Char Meng Chuor
Prom Satharath
David Saunders
Armed Forces Research Institute of Medical Sciences, Thailand
Brigham and Women's Hospital
Armed Forces Research Institute of Medical Sciences
Royal Cambodian Armed Forces
National Center for Parasitology, Entomology and Malaria Control
The University of North Carolina at Chapel Hill
Mahidol University
Fast Track Biologics
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 25-Mar-2014
Citation: PLoS ONE. Vol.9, No.3 (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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84899754743&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/33031
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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