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Evidence of plasmodium falciparum Malaria multidrug resistance to artemisinin and piperaquine in Western Cambodia : dihydroartemisinin-piperaquine open-label multicenter clinical assessment
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Leang, Rithea, Taylor, Walter R. J., Bouth, Denis Mey, Song, Lijiang, Tarning, Joel, Char, Meng Chuor, Kim, Saorin, Witkowski, Benoit, Duru, Valentine, Domergue, Anais, Khim, Nimol, Ringwald, Pascal and Menard, Didier (2015) Evidence of plasmodium falciparum Malaria multidrug resistance to artemisinin and piperaquine in Western Cambodia : dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrobial Agents and Chemotherapy, 59 (8). pp. 4719-4726. doi:10.1128/AAC.00835-15 ISSN 0066-4804.
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Official URL: http://dx.doi.org/10.1128/AAC.00835-15
Abstract
Western Cambodia is recognized as the epicentre of Plasmodium falciparum multidrug resistance. Recent reports of dihydroartemisinin-piperaquine efficacy, the latest generation of ACTs recommended by the WHO, prompted further investigations.
Clinical efficacy of dihydroartemisinin-piperaquine in uncomplicated falciparum malaria was assessed in western and eastern Cambodia over 42 days. Day 7 piperaquine plasma concentrations were measured and day 0 isolates tested for in vitro susceptibilities to piperaquine and mefloquine, polymorphisms in the K13 gene and copy number of the mdr-1 gene (ACTRN12614000344695). 425 patients were recruited in 2011-2013. The proportion of patients with recrudescent infections was significantly higher in western (15.4%) compared to eastern Cambodia (2.5%, p<10-3). Day 7 PP plasma concentrations and PP median IC50 were independent of treatment outcomes, contrarily to mefloquine median IC50 which was found lower in recrudescent patient isolates (18.7 vs. 39.7 nM, p=0.005). The most significant risk factor associated with DHA-PP treatment failure was patients infected by parasites carrying the K13 mutant allele (OR=17.5, 95% CI: 1-308, p=0.04).
Our data support evidence of falciparum PP resistance in western Cambodia, an area of widespread artemisinin resistance. New therapeutic strategies are needed urgently and must be tested such as the use of triple ACTs
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||
Journal or Publication Title: | Antimicrobial Agents and Chemotherapy | ||||||
Publisher: | American Society for Microbiology | ||||||
ISSN: | 0066-4804 | ||||||
Official Date: | 2015 | ||||||
Dates: |
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Volume: | 59 | ||||||
Number: | 8 | ||||||
Page Range: | pp. 4719-4726 | ||||||
DOI: | 10.1128/AAC.00835-15 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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