Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.
Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.
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DOI：
10.1182/blood.v79.2.308.bloodjournal792308
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发表时间：
1992-01
期刊：
影响因子：
20.3
通讯作者：
V. Gordeuk;P. Thuma;G. Brittenham;S. Zulu;G. Simwanza;A. Mhangu;G. Flesch;D. Parry
中科院分区：
文献类型：
--
作者：
V. Gordeuk;P. Thuma;G. Brittenham;S. Zulu;G. Simwanza;A. Mhangu;G. Flesch;D. Parry
为了确定铁络合疗法是否对人类疟疾有效，我们在一项随机、双盲、安慰剂对照的交叉试验中，对28名患有无症状恶性疟原虫感染的志愿者连续72小时皮下注射去铁胺B，剂量为每天100毫克/公斤。所有受试者每隔12小时测定一次环型恶性疟原虫外周血浓度，26例受试者测定去铁胺B+铁胺(去铁胺B的铁复合体)的血清浓度。用螯合剂和安慰剂治疗后，无性红细胞内寄生虫的几何平均浓度均降低，但在初始和交叉期间，去铁胺B组的下降幅度明显大于安慰剂组(P<0.006)。与安慰剂相比，在试验的两个阶段，去铁胺B治疗的寄生虫清除率几乎提高了10倍(P<0.007)。扫描电子显微镜显示，去铁胺B+铁胺在36小时和72小时的稳态浓度分别为6.90+/-0.60mumol/L和7.72+/-0.68mumol/L，体外半数抑制浓度(ID_(50))约为4~20mumol/L，未检测到药物毒性。24名受试者中有19人在随访1至6个月后出现寄生虫血症复发。我们得出结论，去铁胺B可提高恶性疟原虫血症的清除率，铁络合物可能为疟疾的治疗提供一种新的策略。
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.