Publication: Levamisole inhibits sequestration of infected red blood cells in patients with falciparum malaria
Issued Date
2007-08-01
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ISSN
00221899
DOI
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2-s2.0-34447646485
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.196, No.3 (2007), 460-466
Suggested Citation
Arjen M. Dondorp, Kamolrat Silamut, Prakaykaew Charunwatthana, Sunee Chuasuwanchai, Ronnatrai Ruangveerayut, Somyot Krintratun, Nicholas J. White, May Ho, Nicholas P J Day Levamisole inhibits sequestration of infected red blood cells in patients with falciparum malaria. Journal of Infectious Diseases. Vol.196, No.3 (2007), 460-466. doi:10.1086/519287 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24528
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Title
Levamisole inhibits sequestration of infected red blood cells in patients with falciparum malaria
Abstract
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 (n = 21; P = .006). 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. © 2007 by the Infectious Diseases Society of America. All rights reserved.