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VR Gordeuk, PE Thuma, GM Brittenham, S Zulu, G Simwanza, A Mhangu, G Flesch and D Parry
Department of Medicine, MetroHealth Medical Center, Cleveland, OH 44109.
To determine if iron chelation therapy has activity against human malaria,
we administered desferrioxamine B in amounts of 100 mg/kg per day by
continuous 72-hour subcutaneous infusions to 28 volunteers with
asymptomatic Plasmodium falciparum infection in a randomized, double-
blind, placebo-controlled crossover trial. Peripheral blood concentrations
of P falciparum ring forms were determined at 12-hour intervals in all
subjects and serum concentrations of desferrioxamine B + ferrioxamine (the
iron complex of desferrioxamine B) were measured in 26 subjects. Geometric
mean concentrations of asexual intraerythrocytic parasites decreased with
both chelator and placebo treatment, but the decrement with desferrioxamine
B was significantly greater than that with placebo (P less than .006)
during both the initial and crossover periods. Compared with placebo,
desferrioxamine B treatment was associated with an almost 10-fold
enhancement of the rate of parasite clearance during both phases of the
trial (P less than .007). Mean +/- SEM steady state concentrations of
desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and
7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to
be approximately 4 to 20 mumol/L. No drug toxicity was detected.
Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6
months. We conclude that desferrioxamine B enhances the clearance of P
falciparum parasitemia and that iron chelation may provide a new strategy
to be developed for the treatment of malaria.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
