Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial
Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial
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DOI：
10.1016/s0140-6736(04)16350-2
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发表时间：
2004-06-05
期刊：
影响因子：
168.9
通讯作者：
Winstanley, PA
中科院分区：
文献类型：
--
作者：
Alloueche, A;Bailey, W;Winstanley, PA
背景对磺胺嘧啶-乙胺嘧啶的耐药性增加导致其有效性下降。我们的目的是评估氯丙胍，氨苯砜（CD）的安全性，并比较这种药物的安全性和有效性与磺胺嘧啶乙胺嘧啶（SP）作为治疗简单的恶性疟Methods我们进行了一项双盲，随机试验，在1850年连续招募的儿童与简单的恶性疟，汇集来自五个非洲国家的数据。结果CD比SP显著更有效（比值比3.1 [95%CI 2.0-4.8]）; 1313例（96%）给予CD的患者和306例（89%）给予SP的患者在第14天达到了可接受的临床和寄生虫学应答。随机分配至CD组和SP组的患者中分别有46%和50%报告了不良事件（治疗差异-4.4%，95% CI -10.1至1.3）。在第7天，CD组的血红蛋白显著低于SP组，差异为-4 g/L（95% CI -6至-2）。CD和SP后第14天平均血红蛋白（仅对少数第7天数据引起关注的患者进行测量）分别为94 g/L（92-96）和97 g/L（92-102）。当基线体温高时，CD组葡萄糖-6-磷酸脱氢酶缺乏患者的血红蛋白下降20 g/dL或更多的几率大于SP组。CD组治疗前高铁血红蛋白血症发生率为（n=320，平均0.4% [95%CI 0.4-0.4]），第3天为4.2%（95%CI 3.8-4.6）（n=301），第7天为0.6%（0.6-0.7）（n=300）。CD组的血液学不良反应比SP组更常见，并且是可逆的。CD是一个有用的替代品，其中SP是失败的，由于阻力。
Background Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria.Methods We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data.Findings CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7( (n=300) at day 7).Interpretation CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.