Publication: Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria
Issued Date
2013-02-18
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ISSN
15376591
10584838
10584838
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2-s2.0-84873656674
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Infectious Diseases. Vol.56, No.5 (2013)
Suggested Citation
Debashish Das, Rupam Tripura, Aung Pyae Phyo, Khin Maung Lwin, Joel Tarning, Sue J. Lee, Warunee Hanpithakpong, Kasia Stepniewska, Didier Menard, Pascal Ringwald, Kamolrat Silamut, Mallika Imwong, Kesinee Chotivanich, Poravuth Yi, Nicholas P.J. Day, Niklas Lindegardh, Duong Socheat, Chea Nguon, Nicholas J. White, François Nosten, Arjen M. Dondorp Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria. Clinical Infectious Diseases. Vol.56, No.5 (2013). doi:10.1093/cid/cis958 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32481
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Title
Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria
Author(s)
Debashish Das
Rupam Tripura
Aung Pyae Phyo
Khin Maung Lwin
Joel Tarning
Sue J. Lee
Warunee Hanpithakpong
Kasia Stepniewska
Didier Menard
Pascal Ringwald
Kamolrat Silamut
Mallika Imwong
Kesinee Chotivanich
Poravuth Yi
Nicholas P.J. Day
Niklas Lindegardh
Duong Socheat
Chea Nguon
Nicholas J. White
François Nosten
Arjen M. Dondorp
Rupam Tripura
Aung Pyae Phyo
Khin Maung Lwin
Joel Tarning
Sue J. Lee
Warunee Hanpithakpong
Kasia Stepniewska
Didier Menard
Pascal Ringwald
Kamolrat Silamut
Mallika Imwong
Kesinee Chotivanich
Poravuth Yi
Nicholas P.J. Day
Niklas Lindegardh
Duong Socheat
Chea Nguon
Nicholas J. White
François Nosten
Arjen M. Dondorp
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. © 2012 The Author.