Levamisole inhibits sequestration of infected red blood cells in patients with falciparum malaria.
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.


CONCLUSIONS
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.


BACKGROUND
Current Controlled Trials identifier: 15314870.
Dondorp
Arjen M
AM
Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. arjen@tropmedres.ac
Silamut
Kamolrat
K
Charunwatthana
Prakaykaew
P
Chuasuwanchai
Sunee
S
Ruangveerayut
Ronnatrai
R
Krintratun
Somyot
S
White
Nicholas J
NJ
Ho
May
M
Day
Nicholas P J
NP
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D004318:Doxycycline / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology*; D005260:Female; D006801:Humans; D007978:Levamisole / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy*; D008297:Male
D000276:Adjuvants, Immunologic; D000962:Antimalarials; D007978:Levamisole; D004318:Doxycycline