Literature DB >> 1730079

Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.

V R Gordeuk1, P E Thuma, G M Brittenham, S Zulu, G Simwanza, A Mhangu, G Flesch, D Parry.   

Abstract

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.

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Year:  1992        PMID: 1730079

Source DB:  PubMed          Journal:  Blood        ISSN: 0006-4971            Impact factor:   22.113


  14 in total

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2.  Suppressed cytokine production in whole blood cultures may be related to iron status and hepcidin and is partially corrected following weight reduction in morbidly obese pre-menopausal women.

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4.  Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity.

Authors:  E E Voest; J P Neijt; J E Keunen; A W Dekker; B S van Asbeck; J W Nortier; F E Ros; J J Marx
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7.  Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu).

Authors:  S R Meshnick; Y Z Yang; V Lima; F Kuypers; S Kamchonwongpaisan; Y Yuthavong
Journal:  Antimicrob Agents Chemother       Date:  1993-05       Impact factor: 5.191

Review 8.  Superinfection in malaria: Plasmodium shows its iron will.

Authors:  Sílvia Portugal; Hal Drakesmith; Maria M Mota
Journal:  EMBO Rep       Date:  2011-12-01       Impact factor: 8.807

9.  Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

Authors:  Patricia Ferrer; Abhai K Tripathi; Martha A Clark; Carla Cerami Hand; Hugh Young Rienhoff; David J Sullivan
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Review 10.  Evolutionary biology and the concept of disease.

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