Medical Research Council Laboratories, Banjul, The Gambia.
PLoS One. 2011;6(6):e17371. doi: 10.1371/journal.pone.0017371. Epub 2011 Jun 7.
Chlorproguanil-dapsone (Lapdap), developed as a low-cost antimalarial, was withdrawn in 2008 after concerns about safety in G6PD deficient patients. This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine (AL) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia. We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure.
1238 children aged 6 months to 10 years with uncomplicated malaria were randomized to receive CD or artemether-lumefantrine (AL) and followed for 28 days. The first dose was supervised, subsequent doses given unsupervised at home. G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia. The main endpoints were clinical treatment failure by day 28, incidence of severe anaemia (Hb<5 g/dL), and haemoglobin concentration on day 3.
One third of patients treated with AL, and 6% of patients treated with CD, did not complete their course of medication. 18% (109/595) of children treated with CD and 6.1% (36/587) with AL required rescue medication within 4 weeks, risk difference 12% (95%CI 8.9%-16%). 23 children developed severe anaemia (17 (2.9%) treated with CD and 6 (1.0%) with AL, risk difference 1.8%, 95%CI 0.3%-3.4%, P = 0.02). Haemoglobin concentration on day 3 was lower among children treated with CD than AL (difference 0.43 g/dL, 95% CI 0.24 to 0.62), and within the CD group was lower among those children who had higher parasite density at enrollment. Only 17 out of 1069 children who were typed were G6PD A- deficient, of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia. 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3.
AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen. There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon.
Clinicaltrials.gov NCT00118794.
氯喹二氨嘧啶（Lapdap）作为一种廉价的抗疟药物，因其在 G6PD 缺乏症患者中的安全性问题，已于 2008 年被停用。本试验于 2004 年进行，旨在评估 CD 在 G6PD 正常和 G6PD 缺乏症疟疾患者中的安全性和有效性，并与青蒿琥酯-甲氟喹（AL）进行比较，条件是在常规使用下治疗无并发症的疟疾。我们还研究了一种常见的基因变异，该变异影响氯喹的代谢，对治疗失败风险的影响。
1238 名 6 个月至 10 岁患有单纯性疟疾的儿童被随机分配接受 CD 或青蒿琥酯-甲氟喹（AL）治疗，并随访 28 天。第一剂是在监督下服用，随后在家中自行服用。测定 G6PD 基因型，以评估治疗和 G6PD 状态在贫血效应中的相互作用。主要终点是第 28 天的临床治疗失败、严重贫血（Hb<5 g/dL）的发生率和第 3 天的血红蛋白浓度。
三分之一接受 AL 治疗的患者和 6%接受 CD 治疗的患者没有完成疗程。18%（109/595）接受 CD 治疗的儿童和 6.1%（36/587）接受 AL 治疗的儿童在 4 周内需要抢救药物，风险差异 12%（95%CI 8.9%-16%）。23 名儿童出现严重贫血（17 名（2.9%）接受 CD 治疗，6 名（1.0%）接受 AL 治疗，风险差异 1.8%，95%CI 0.3%-3.4%，P=0.02）。与接受 AL 治疗的儿童相比，接受 CD 治疗的儿童第 3 天的血红蛋白浓度较低（差异 0.43 g/dL，95%CI 0.24-0.62），在 CD 组中，在登记时寄生虫密度较高的儿童中，血红蛋白浓度较低。在 1069 名被分型的儿童中，仅有 17 名是 G6PD A- 缺乏症，其中 2/9 名接受 CD 治疗，1/8 名接受 AL 治疗的儿童出现严重贫血。5/9 名接受 CD 治疗的儿童第 3 天血红蛋白浓度下降 2 g/dL 或以上。
AL 耐受性良好，疗效显著，尽管对六剂方案的依从性较差，但在操作条件下使用时仍具有良好的疗效。虽然 G6PD 缺乏症并不常见，但 CD 治疗后出现严重疟疾和贫血的病例更多。
Clinicaltrials.gov NCT00118794。
