Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial
Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(09)60997-1
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发表时间：
2009-10-01
期刊：
影响因子：
168.9
通讯作者：
Chandramohan, Daniel
中科院分区：
文献类型：
--
作者：
Gosling, Roly D.;Gesase, Samwel;Chandramohan, Daniel
背景 在疫苗接种时给予磺胺多辛（乙胺嘧啶）——婴儿间歇性预防治疗（IPTi）——是预防疟疾的一种有前景的策略。然而，人们对这种组合的抵制不断增加令人担忧。我们研究了一种短效和长效抗疟药物作为 IPTi 的替代方案。 方法 我们在坦桑尼亚疟疾传播中度（n=1280 名婴儿）和低度（n=1139）疟疾传播强度较高的地区对磺胺多辛-乙胺嘧啶具有高耐药性的地区进行了一项双盲、安慰剂对照试验。 8-16 周龄婴儿被随机分为 16 组，分别接受磺胺多辛（250 mg）加乙胺嘧啶（12.5 mg；n=319 中度传播部位和 283 低度传播部位）、氯丙胍（15 mg）加氨苯砜（18.75 mg；n=317 和 285）、甲氟喹（125 mg；n=320 和284) 或安慰剂 (n=320 和 284)，在第二次和第三次白喉、百日咳、破伤风以及麻疹免疫接种时给予。研究小组和孩子没有接受治疗。由于疟疾发病率低，低传播地点的招募工作提前停止。主要终点是对 2-11 个月龄所有临床疟疾发作的保护功效。分析是按意向治疗进行的。本研究已在 ClinicalTrials.gov 注册，编号为 NCT00158574。 结果 对所有随机分配的婴儿进行了分析。在中度传播部位，甲氟喹对 2-11 个月婴儿临床疟疾的保护效力为 38.1%（95% Cl 11.8-56.5，p=0.008），但磺胺多辛-乙胺嘧啶（-6.7%，-45.9 至 22.0）和氯丙胍-氨苯砜（10.8%，-24.6 至 22.0）均无效。 36.1）有保护作用。没有任何治疗方案对贫血有任何保护作用。或入院。第 1 天服用的 1731 剂甲氟喹中有 141 剂 (8%) 引起呕吐（比值比与安慰剂 5.50，95% Cl 3.56-8.46）。氯丙胍-氨苯砜组和甲氟喹组的婴儿死亡人数（分别为 18 名和 15 名）多于磺胺多辛-乙胺嘧啶组或安慰剂组（每组 8 名死亡；氯丙胍-氨苯砜与安慰剂组之间的差异 p=0.05）。中等传输设置。 IPTi 与磺胺多辛-乙胺嘧啶在对该组合具有极高耐药性的区域没有任何益处。 IPTi 的适当性应根据疟疾的预期发病率以及药物的疗效、耐受性和安全性来衡量。
Background Administration of sulfadoxine-pyrimethamine at times of vaccination-intermittent preventive treatment in infants (IPTi)-is a promising strategy to prevent malaria. However, rising resistance to this combination is a concern. We investigated a shortacting and longacting antimalarial drug as alternative regimens for IPTi.Methods We undertook a double-blind, placebo-controlled trial of IPTi in an area of high resistance to sulfadoxine-pyrimethamine at sites of moderate (n=1280 infants enrolled) and low (n=1139) intensity of malaria transmission in Tanzania. Infants aged 8-16 weeks were randomly assigned in blocks of 16 to sulfadoxine (250 mg) plus pyrimethamine (12.5 mg; n=319 in moderate-transmission and 283 in low-transmission sites), chlorproguanil (15 mg) plus dapsone (18.75 mg; n=317 and 285), mefloquine (125 mg; n=320 and 284), or placebo (n=320 and 284), given at the second and third immunisations for diphtheria, pertussis, and tetanus, and for measles. Research team and child were masked to treatment. Recruitment was stopped early at the low-transmission site because of low malaria incidence. The primary endpoint was protective efficacy against all episodes of clinical malaria at 2-11 months of age. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00158574.Findings All randomly assigned infants were analysed. At the moderate-transmission site, mefloquine had a protective efficacy of 38.1% (95% Cl 11.8-56.5, p=0.008) against clinical malaria in infants aged 2-11 months, but neither sulfadoxine-pyrimethamine (-6.7%, -45.9 to 22.0) nor chlorproguanil-dapsone (10.8%, -24.6 to 36.1) had a protective effect. No regimen had any protective efficacy against anaemia. or hospital admission. Mefloquine caused vomiting in 141 of 1731 (8%) doses given on day 1 (odds ratio vs placebo 5.50, 95% Cl 3.56-8.46). More infants died in the chlorproguanil-dapsone and mefloquine groups (18 and 15, respectively) than in the sulfadoxine-pyrimethamine or placebo groups (eight deaths per group; p=0.05 for difference between chlorproguanil-dapsone and placebo).Interpretation IPTi with a longacting, efficacious drug such as mefloquine can reduce episodes of malaria in infants in a moderate-transmission setting. IPTi with sulfadoxine-pyrimethamine has no benefit in areas of very high resistance to this combination. The appropriateness of IPTi should be measured by the expected incidence of malaria and the efficacy, tolerability, and safety of the drug.