Journal article
Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study
- Abstract:
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Background Artemisinin resistance in Plasmodium falciparum extends across Southeast Asia where it is associated with worsening partner drug resistance and a decline in the efficacy of frontline artemisinin-based combination therapy. Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and curative treatment in the region, but its therapeutic efficacy has fallen in Cambodia.
Methods A prospective clinical and parasitological evaluation of DP was conducted at two sites in Upper Myanmar between August 2013 and December 2014, enrolling 116 patients with acute uncomplicated falciparum malaria. Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on admission. Parasite clearance half-lives based on 6 hourly blood smears, and day 42 therapeutic responses were assessed as well as parasite K13 genotypes.
Results Median parasite clearance half-life was prolonged, and clearance half-life was greater than 5 h in 21 % of patients. Delayed parasite clearance was significantly associated with mutations in the propeller region of the parasite k13 gene. The k13 F446I mutation was found in 25.4 % of infections and was associated with a median clearance half-life of 4.7 h compared with 2.7 h for infections without k13 mutations (p < 0.001). There were no failures after 42 days of follow-up, although 18 % of patients had persistent parasitaemia on day 3.
Conclusion The dominant k13 mutation observed in Upper Myanmar, F446I, appears to be associated with an intermediate rate of parasite clearance compared to other common mutations described elsewhere in the Greater Mekong Subregion. Discerning this phenotype requires relatively detailed clearance measurements, highlighting the importance of methodology in assessing artemisinin resistance.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.5MB, Terms of use)
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(Supplementary materials, zip, 58.1KB, Terms of use)
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- Publisher copy:
- 10.1186/s12936-016-1240-7
Authors
- Publisher:
- BioMed Central
- Journal:
- Malaria Journal More from this journal
- Volume:
- 15
- Issue:
- 1
- Article number:
- 185
- Publication date:
- 2016-03-31
- Acceptance date:
- 2016-03-16
- DOI:
- EISSN:
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1475-2875
- Language:
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English
- Keywords:
- Pubs id:
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pubs:627574
- UUID:
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uuid:06146bda-09cd-4477-9f70-fcf2e3a0fb31
- Local pid:
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pubs:627574
- Source identifiers:
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627574
- Deposit date:
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2016-06-23
Terms of use
- Copyright holder:
- Tun et al
- Copyright date:
- 2016
- Rights statement:
- © 2016 Tun et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
- Licence:
- CC Attribution (CC BY)
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