EFFECT OF IRON CHELATION-THERAPY ON RECOVERY FROM DEEP COMA IN CHILDREN WITH CEREBRAL MALARIA
EFFECT OF IRON CHELATION-THERAPY ON RECOVERY FROM DEEP COMA IN CHILDREN WITH CEREBRAL MALARIA
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DOI：
10.1056/nejm199211193272101
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发表时间：
1992-11-19
影响因子：
158.5
通讯作者：
POLTERA, AA
中科院分区：
文献类型：
--
作者：
GORDEUK, V;THUMA, P;POLTERA, AA
背景。脑型疟疾是儿童恶性疟原虫感染的一种严重并发症，尽管进行了抗疟治疗，但死亡率仍为15%至50%。为了确定铁螯合联合奎宁治疗是否能加速意识的恢复，我们对83名赞比亚脑型疟疾患儿进行了一项随机、双盲、安慰剂对照的铁螯合剂去铁胺试验。要入选，患者必须小于6岁，患有恶性疟原虫，脑脊液正常，无细菌感染的证据，并且处于昏迷状态，不能被唤醒。去铁胺（每天每公斤体重100毫克，静脉注射72小时）或安慰剂被添加到奎宁和磺胺多辛-乙胺嘧啶的标准治疗中。采用Cox比例风险回归分析，观察患者完全意识恢复时间、寄生虫清除时间和死亡率。42例给予去铁胺的患者的完全意识恢复率是41例给予安慰剂的患者的1.3倍（95%置信区间，0.7 ~ 2.3）；去铁胺组的中位恢复时间为20.2小时，安慰剂组为43.1小时（P = 0.38）。在50例深度昏迷患者中，去铁胺的全意识恢复率提高了2.2倍（95%可信区间1.1 ~ 4.7），中位恢复时间从68.2小时减少到24.1小时（P = 0.03）。在69名获得寄生虫清除率数据的患者中，去铁胺清除率是安慰剂的2.0倍（95%置信区间，1.2至3.6）。在所有83例患者中，去铁胺组死亡率为17%，安慰剂组死亡率为22% （P = 0.52）。铁螯合治疗可加速寄生虫血症的清除，促进脑型疟疾深度昏迷的恢复。
Background. Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy.Methods. To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis.Results. The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52).Conclusions. Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.