Aponte John J, Schellenberg David, Egan Andrea, Breckenridge Alasdair, Carneiro Ilona, Critchley Julia, Danquah Ina, Dodoo Alexander, Kobbe Robin, Lell Bertrand, May Jürgen, Premji Zul, Sanz Sergi, Sevene Esperanza, Soulaymani-Becheikh Rachida, Winstanley Peter, Adjei Samuel, Anemana Sylvester, Chandramohan Daniel, Issifou Saadou, Mockenhaupt Frank, Owusu-Agyei Seth, Greenwood Brian, Grobusch Martin P, Kremsner Peter G, Macete Eusebio, Mshinda Hassan, Newman Robert D, Slutsker Laurence, Tanner Marcel, Alonso Pedro, Menendez Clara
Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Lancet. 2009 Oct 31;374(9700):1533-42. doi: 10.1016/S0140-6736(09)61258-7. Epub 2009 Sep 16.
Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa.
We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo.
The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001) against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia, 38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group.
IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control.
Bill & Melinda Gates Foundation.
间歇性预防治疗（IPT）是控制婴儿疟疾的一种有前景的策略。我们对非洲使用磺胺多辛-乙胺嘧啶进行婴儿间歇性预防治疗（IPTi）的安全性和疗效进行了汇总分析。
我们汇总了六项双盲、随机、安慰剂对照试验（分别在坦桑尼亚、莫桑比克和加蓬各进行一项，在加纳进行三项）的数据，这些试验评估了使用磺胺多辛-乙胺嘧啶进行IPTi的疗效。在所有试验中，在世界卫生组织扩大免疫规划提供的常规疫苗接种时，给婴儿服用IPTi或安慰剂。通过使用标准结局定义和时间段，重新分析了这些试验中12个月龄以下婴儿的临床疟疾发病率、贫血风险（红细胞压积<25%或血红蛋白<80 g/L）以及住院率和不良事件发生率的数据。分析采用改良意向性治疗，包括所有接受至少一剂IPTi或安慰剂的婴儿。
这六项试验为7930名婴儿提供了数据（IPTi组，n = 3958；安慰剂组，n = 3972）。IPTi对临床疟疾的保护效力为30.3%（95%CI 19.8 - 39.4，p<0.0001），对贫血风险的保护效力为21.3%（8.2 - 32.5，p = 0.002），对与疟原虫血症相关的住院的保护效力为38.1%（12.5 - 56.2，p = 0.007），对全因住院的保护效力为22.9%（10.0 - 34.0，p = 0.001）。IPTi组有56例死亡，安慰剂组有53例死亡（率比1.05，95%CI 0.72 - 1.54，p = 0.79）。有1例死亡被判定可能与IPTi有关，因为它发生在一剂治疗后19天，随后被归因于可能的败血症。IPTi组676例非致命住院中有4例被认为与研究治疗有关，而安慰剂组860例中有5例。IPTi组3例严重皮肤不良事件均未被判定与研究治疗有关，而安慰剂组13例中有1例。
使用磺胺多辛-乙胺嘧啶的IPTi在一系列疟疾传播环境中是安全有效的，表明这种干预措施对疟疾控制有很大帮助。
比尔及梅琳达·盖茨基金会。
