Effect of High-Dose or Split-Dose Artesunate on Parasite Clearance in Artemisinin-Resistant Falciparum Malaria
Open Access
- 21 November 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 56 (5), e48-e58
- https://doi.org/10.1093/cid/cis958
Abstract
Background. The emergence of Plasmodium falciparum resistance to artemisinins on the Cambodian and Myanmar-Thai borders poses severe threats to malaria control. We investigated whether increasing or splitting the dose of the short-half-life drug artesunate improves parasite clearance in falciparum malaria in the 2 regions. Methods. In Pailin, western Cambodia (from 2008 to 2010), and Wang Pha, northwestern Thailand (2009–2010), patients with uncomplicated falciparum malaria were randomized to oral artesunate 6 mg/kg/d as a once-daily or twice-daily dose for 7 days, or artesunate 8 mg/kg/d as a once-daily or twice-daily dose for 3 days, followed by mefloquine. Parasite clearance and recrudescence for up to 63 days of follow-up were assessed. Results. A total of 159 patients were enrolled. Overall median (interquartile range [IQR]) parasitemia half-life (half-life) was 6.03 (4.89–7.28) hours in Pailin versus 3.42 (2.20–4.85) hours in Wang Pha (P = .0001). Splitting or increasing the artesunate dose did not shorten half-life in either site. Pharmacokinetic profiles of artesunate and dihydroartemisinin were similar between sites and did not correlate with half-life. Recrudescent infections occurred in 4 of 79 patients in Pailin and 5 of 80 in Wang Pha and was not different between treatment arms (P = .68). Conclusions. Increasing the artesunate treatment dose up to 8 mg/kg/d or splitting the dose does not improve parasite clearance in either artemisinin resistant or more sensitive infections with P. falciparum. Clinical Trials Registration. ISRCTN15351875.Keywords
This publication has 22 references indexed in Scilit:
- Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal studyThe Lancet, 2012
- Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effectsBritish Journal of Clinical Pharmacology, 2012
- Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimatorMalaria Journal, 2011
- Intrahost modeling of artemisinin resistance in Plasmodium falciparumProceedings of the National Academy of Sciences of the United States of America, 2010
- Artemisinin Resistance inPlasmodium falciparumMalariaThe New England Journal of Medicine, 2009
- Evidence of Artemisinin-Resistant Malaria in Western CambodiaThe New England Journal of Medicine, 2008
- Qinghaosu (Artemisinin): The Price of SuccessScience, 2008
- Validation and application of a liquid chromatographic–mass spectrometric method for determination of artesunate in pharmaceutical samplesJournal of Pharmaceutical and Biomedical Analysis, 2007
- Deployment of Early Diagnosis and Mefloquine- Artesunate Treatment of Falciparum Malaria in Thailand: The Tak Malaria InitiativePLoS Medicine, 2006
- CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatmentSeminars in Radiation Oncology, 2003