Journal article
Split dosing of artemisinins does not improve antimalarial therapeutic efficacy
- Abstract:
- It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates. To test these various hypotheses we performed a logistic meta-regression analysis of cure rates from all falciparum malaria treatment trials (n = 40) with monotherapy arms containing artemisinin or a derivative (76 arms). There was no evidence that split dosing enhanced cure rates.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-017-12483-4
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Scientific Reports More from this journal
- Volume:
- 7
- Issue:
- 12132
- Pages:
- 1-5
- Publication date:
- 2017-09-21
- Acceptance date:
- 2017-09-06
- DOI:
- ISSN:
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2045-2322
- Pmid:
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28935919
- Language:
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English
- Keywords:
- Pubs id:
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pubs:732944
- UUID:
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uuid:7ac5b4ff-fd19-4fd2-a664-c3c96045397f
- Local pid:
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pubs:732944
- Source identifiers:
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732944
- Deposit date:
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2017-10-10
Terms of use
- Copyright holder:
- © White, Watson, and Ashley 2017
- Copyright date:
- 2017
- Notes:
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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