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1 August 2007

Volume 196, Number 3
The Journal of Infectious Diseases 2007;196:460–466
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19603-0017$15.00
DOI: 10.1086/519287
MAJOR ARTICLE

Levamisole Inhibits Sequestration of Infected Red Blood Cells in Patients with Falciparum Malaria

Arjen M. Dondorp,1,2

Kamolrat Silamut,1

Prakaykaew Charunwatthana,1

Sunee Chuasuwanchai,1

Ronnatrai Ruangveerayut,3

Somyot Krintratun,3

Nicholas J. White,1,2

May Ho,4 and

Nicholas P. J. Day1,2

1Faculty of Tropical Medicine, Mahidol University, Bangkok, and 2Mae Sot Hospital, Mae Sot, Tak Province, Thailand; 3Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; 4Department of Microbiology and Infectious Diseases, Health Sciences Centre, Calgary, Alberta, Canada

Background.Sequestration of infected red blood cells (iRBCs) in the microcirculation is central to the pathophysiology of falciparum malaria. It is caused by cytoadhesion of iRBCs to vascular endothelium, mediated through the binding of Plasmodium falciparum erythrocyte membrane protein–1 to several endothelial receptors. Binding to CD36, the major vascular receptor, is stabilized through dephosphorylation of CD36 by an alkaline phosphatase. This is inhibited by the alkaline phosphatase–inhibitor levamisole, resulting in decreased cytoadhesion.

Methods.Patients with uncomplicated falciparum malaria were randomized to receive either quinine treatment alone or treatment with a single 150‐mg dose of levamisole as an adjunct to quinine. Peripheral blood parasitemia and parasite stage distribution were monitored closely over time.

Results.Compared with those in control subjects, peripheral blood parasitemias of mature P. falciparum parasites increased during the 24 h after levamisole administration ( ; ). The sequestration ratio (between observed and expected peripheral blood parasitemia) of early trophozoite and midtrophozoite parasites increased after levamisole treatment, with near complete prevention of early trophozoite sequestration and >65% prevention of midtrophozoite sequestration.

Conclusion.These findings strongly suggest that levamisole decreases iRBC sequestration in falciparum malaria in vivo and should be considered as a potential adjunctive treatment for severe falciparum malaria.

Trial registration.Current Controlled Trials identifier: 15314870.

Received 11 January 2007; accepted 2 March 2007; electronically published 15 June 2007.

Reprints or correspondence: Dr. A. M. Dondorp, Deputy Director, Mahidol‐Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand ().

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  • Potential conflicts of interest: none reported.

    Presented in part: Joint International Tropical Medicine Meeting, Bangkok, 29 November–1 December 2006.

    Financial support: Wellcome Trust of Great Britain.

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