Levamisole inhibits sequestration of infected red blood cells in patients with falciparum malaria
| Autor: | May Ho, Nicholas J. White, Ronnatrai Ruangveerayut, Arjen M. Dondorp, Somyot Krintratun, Nicholas P. J. Day, Kamolrat Silamut, Sunee Chuasuwanchai, Prakaykaew Charunwatthana |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Erythrocytes Parasitemia Biology Antimalarials Adjuvants Immunologic parasitic diseases medicine Immunology and Allergy Humans Malaria Falciparum Doxycycline Quinine Plasmodium falciparum Levamisole medicine.disease biology.organism_classification Red blood cell Infectious Diseases medicine.anatomical_structure Immunology Adjunctive treatment Female Malaria medicine.drug |
| Zdroj: | The Journal of infectious diseases. 196(3) |
| ISSN: | 0022-1899 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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