Journal article
Efficacy of artesunate-mefloquine for chloroquine-resistant Plasmodium vivax malaria in Malaysia: An open-label, randomized, controlled trial
- Abstract:
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Background. Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown.
Methods. A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan–Meier analysis.
Results. From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8–75.6) after CQ and 0% (95% CI, 0–.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5–9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P = .001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5–9.3; P = .005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60–.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment.
Conclusions. High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected.
Clinical Trials Registration. NCT01708876.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 448.6KB, Terms of use)
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- Publisher copy:
- 10.1093/cid/ciw121
Authors
- Funder identifier:
- https://ror.org/011kf5r70
- Grant:
- 1074795
- Publisher:
- Oxford University Press
- Journal:
- Clinical Infectious Diseases More from this journal
- Volume:
- 62
- Issue:
- 11
- Pages:
- 1403–1411
- Publication date:
- 2016-05-12
- Acceptance date:
- 2016-02-10
- DOI:
- EISSN:
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1537-6591
- ISSN:
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1058-4838
- Language:
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English
- Keywords:
- Pubs id:
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pubs:619916
- UUID:
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uuid:1b72d3ef-9452-4b27-a46f-eee49cc5f62e
- Local pid:
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pubs:619916
- Source identifiers:
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619916
- Deposit date:
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2016-05-15
Terms of use
- Copyright holder:
- Grigg et al
- Copyright date:
- 2016
- Rights statement:
- © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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