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Efficacy of dihydroartemisinin/piperaquine and artesunate monotherapy for the treatment of uncomplicated Plasmodium falciparum malaria in Central Vietnam

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dc.contributor.author Rovira-Vallbona, E. en_US
dc.contributor.author Van Hong, N. en_US
dc.contributor.author Kattenberg, J. H. en_US
dc.contributor.author Huan, R. M. en_US
dc.contributor.author Hien, N. T. T. en_US
dc.contributor.author Ngoc, N. T. H. en_US
dc.contributor.author Guetens, P. en_US
dc.contributor.author Hieu, N. L. en_US
dc.contributor.author Mai, T. T. en_US
dc.contributor.author Duong, N. T. T. en_US
dc.contributor.author Duong, T. T. en_US
dc.contributor.author Phuc, B. Q. en_US
dc.contributor.author Xa, N. X. en_US
dc.contributor.author Erhart, A. en_US
dc.contributor.author Rosanas-Urgell, A. en_US
dc.date.accessioned 2020-08-25T09:38:09Z
dc.date.available 2020-08-25T09:38:09Z
dc.date.issued 2020 en_US
dc.identifier.issn 0305-7453 en_US
dc.identifier.doi http://dx.doi.org/10.1093/jac/dkaa172 en_US
dc.identifier.other ITG-B1A; ITG-B3A; ITG-B7A; ITG-BLA; DBM; U-MALAR; JIF; DOI; CPDF; PMC; Abstract; ITMPUB; DSPACE68 en_US
dc.identifier.uri http://hdl.handle.net/10390/10885
dc.description.abstract BACKGROUND: Artemisinin-based combination therapies (ACTs) have significantly contributed to reduce Plasmodium falciparum malaria burden in Vietnam, but their efficacy is challenged by treatment failure of dihydroartemisinin/piperaquine ACT in Southern provinces. OBJECTIVES: To assess the efficacy of dihydroartemisinin/piperaquine for uncomplicated P. falciparum malaria in Gia Lai, Central Vietnam, and determine parasite resistance to artemisinin (ClinicalTrials.gov identifier NCT02604966). METHODS: Sixty patients received either dihydroartemisinin/piperaquine (4 mg/kg/day, 3 days; n = 33) or artesunate monotherapy (4 mg/kg/day, 3 days; n = 27) followed by dihydroartemisinin/piperaquine (AS + DHA/PPQ). Clinical phenotypes were determined during a 42 day follow-up and analysed together with ex vivo susceptibility to antimalarials and molecular markers of drug resistance. RESULTS: Day 3 positivity rate was significantly higher in the AS + DHA/PPQ arm compared with dihydroartemisinin/piperaquine (70.4% versus 39.4%, P = 0.016). Parasite clearance time was 95.2 h (AS + DHA/PPQ) versus 71.9 h (dihydroartemisinin/piperaquine, P = 0.063) and parasite clearance half-life was 7.4 h (AS + DHA/PPQ) versus 7.0 h (dihydroartemisinin/piperaquine, P = 0.140). Adequate clinical and parasitological response at Day 42 was 100% in both arms. By RT-qPCR, 36% (19/53) patients remained positive until Day 7. No recurrences were detected. kelch13 artemisinin resistance mutations were found in 87% (39/45) of isolates and 50% (20/40) were KEL1/C580Y. The piperaquine resistance marker plasmepsin-2 was duplicated in 10.4% (5/48). Isolates from Day 3-positive patients (n = 18) had higher ex vivo survival rates to artemisinin compounds (P < 0.048) and prevalence of kelch13 mutations (P = 0.005) than Day 3-negative patients (n = 5). The WHO definition of artemisinin resistance was fulfilled in 60% (24/40) of cases. CONCLUSIONS: Although dihydroartemisinin/piperaquine remained effective to treat P. falciparum, the high Day 3 positivity rate and prevalence of KEL1 strains calls for continuous monitoring of dihydroartemisinin/piperaquine efficacy in Central Vietnam. en_US
dc.language English en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/32437557 en_US
dc.subject Malaria en_US
dc.subject Protozoal diseases en_US
dc.subject Treatment regimen en_US
dc.subject Dihydroartemisinin-piperaquine en_US
dc.subject Artesunate en_US
dc.subject Vietnam en_US
dc.subject Asia-Southeast en_US
dc.title Efficacy of dihydroartemisinin/piperaquine and artesunate monotherapy for the treatment of uncomplicated Plasmodium falciparum malaria in Central Vietnam en_US
dc.type Article en_US
dc.citation.issue 8 en_US
dc.citation.jtitle Journal of Antimicrobial Chemotherapy en_US
dc.citation.volume 75 en_US
dc.citation.pages 2272-2281 en_US
dc.citation.abbreviation J Antimicrob Chemother en_US


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