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Title: Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia
Authors: Richard J. Maude
Kamolrat Silamut
Katherine Plewes
Prakaykaew Charunwatthana
May Ho
M. Abul Faiz
Ridwanur Rahman
Md Amir Hossain
Mahtab U. Hassan
Emran Bin Yunus
Gofranul Hoque
Faridul Islam
Aniruddha Ghose
Josh Hanson
Joel Schlatter
Rachel Lacey
Alison Eastaugh
Joel Tarning
Sue J. Lee
Nicholas J. White
Kesinee Chotivanich
Nicholas P.J. Day
Arjen M. Dondorp
Mahidol University
Nuffield Department of Clinical Medicine
University of Calgary
Centre for Specialized Care and Research
Dev Care Foundation
Shaheed Shwarwardhy Medical College
Chittagong Medical College Hospital
Hopital Jean-Verdier
Worcester Royal Infirmary
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: Journal of Infectious Diseases. Vol.209, No.1 (2014), 120-129
Abstract: Background. Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine.Methods. Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate.Results. Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0-28 025) parasites/L × hour in patients treated with levamisole and 5489 (IQR, 192-25 848) parasites/L × hour in controls (P =. 25). The "sequestration ratios" at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P >. 40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12-30) hours with levamisole vs 28 (IQR, 12-36) hours without levamisole (P =. 15).Conclusions. There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole. © 2013 The Author .
ISSN: 00221899
Appears in Collections:Scopus 2011-2015

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