A Randomised Trial to Compare the Safety, Tolerability and Efficacy of Three Drug Combinations for Intermittent Preventive Treatment in Children
A Randomised Trial to Compare the Safety, Tolerability and Efficacy of Three Drug Combinations for Intermittent Preventive Treatment in Children
复制标题
DOI：
10.1371/journal.pone.0011225
复制
发表时间：
2010-06-21
期刊：
影响因子：
3.7
通讯作者：
Greenwood, Brian
中科院分区：
文献类型：
--
作者：
Bojang, Kalifa;Akor, Francis;Greenwood, Brian
背景：对婴儿和儿童进行间歇性预防治疗 (IPT) 的试验结果表明，IPT 对临床疟疾具有显着的预防作用。磺胺多辛-乙胺嘧啶 (SP) 单独给药或与其他药物联合给药已用于大多数 IPT 计划。然而，非洲许多地区对 SP 的抵抗力正在增加。因此，我们研究了在季节性传播地区的儿童中使用 SP 加 AQ、SP 加哌喹 (PQ) 和二氢青蒿素 (DHA) 加 PQ 是否同样安全有效。方法：在 2007 年疟疾传播季节期间，1008 名冈比亚儿童被单独随机分配接受 SP 加阿莫地喹 (AQ)、SP 加哌喹 (PQ) 或双氢青蒿素在疟疾传播高峰季节，每月三次 (DHA) 加 PQ。为了确定给药后副作用的风险，每轮给药开始三天后，对每个治疗组的参与者进行家访，并填写副作用问卷。为了帮助确定不良事件是否与药物相关，我们对从邻近村庄招募的 286 名年龄匹配的对照儿童进行了同样的调查问卷。在整个疟疾传播季节对发病率进行监测，并在疟疾传播季节结束时观察研究儿童。结果：所有三种治疗方案均显示出良好的安全性。没有报告与 IPT 相关的严重不良事件。最常见的不良事件是咳嗽、腹泻、呕吐、腹痛和食欲不振。接受 SP 加 AQ、DHA 加 PQ 或 SP 加 PQ 治疗的研究对象中分别有 15.2%、15.4% 和 18.7% 出现咳嗽，而对照组为 19.2%。 DHA加PQ、SP加AQ和SP加PQ组的疟疾发病率分别为每儿童年0.10例（95% CI：0.05，0.22）、0.06（95% CI：0.022，0.16）和0.06（95% CI：0.02，0.15）。对照组疟疾发病率为0.79例/儿童年（0.58，1.08）。结论：儿童IPT的三种方案均安全、高效。
Background: Results from trials of intermittent preventive treatment (IPT) in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP) given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ) and dihydroartemisinin (DHA) plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission.Methods: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ), SP plus piperaquine (PQ) or dihydroartemisinin (DHA) plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season.Results: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22), 0.06 (95% CI: 0.022, 0.16) and 0.06 (95% CI: 0.02, 0.15) respectively. The incidence of malaria in the control group was 0.79 cases per child year (0.58, 1.08).Conclusion: All the three regimens of IPT in children were safe and highly efficacious