哌喹与磺胺多辛-乙胺嘧啶或双氢青蒿素随机对照试验用于儿童疟疾间歇性预防治疗。
Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children.
机构信息
Department of Parasitology and Mycology, Universite Cheikh Anta Diop, Dakar, Senegal.
出版信息
PLoS One. 2009 Sep 28;4(9):e7164. doi: 10.1371/journal.pone.0007164.
BACKGROUND
The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal.
METHODS
Treatments were delivered to children 3-59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events.
RESULTS
1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/microL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI -2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI -1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season.
CONCLUSIONS
Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00529620.
背景
哌喹半衰期长，适合间歇性预防治疗疟疾，但在非洲尚未进行其用于预防的研究。我们进行了一项整群随机试验，以确定在塞内加尔农村地区，由社区卫生工作者为儿童提供的哌喹联合二氢青蒿素（DHA）或磺胺多辛-乙胺嘧啶（SP），与 SP 加阿莫地喹（AQ）相比，用于间歇性预防治疗时，是否同样有效且更能耐受。
方法
在传播季节，由社区卫生工作者每月一次将治疗药物送到家中 3-59 月龄的儿童。33 名卫生工作者，每人覆盖约 60 名儿童，随机分为 SP+AQ、DHA+PQ 或 SP+PQ 组。主要终点是临床疟疾发作的发生率和不良事件的发生率。
结果
共纳入 1893 名儿童。所有组的每月轮次覆盖率和每日剂量依从性相似；90%的儿童接受了至少 2 次每月剂量。哌喹联合用药比 SP+AQ 更能耐受，常见的轻度不良事件风险显著降低。在试验过程中记录了 103 例临床疟疾发作。68 名儿童有寄生虫血症>3000/μL 的疟疾，SP+AQ 组 671 名儿童中有 29 名（4.3%），DHA+PQ 组 604 名儿童中有 22 名（3.6%）（风险差 0.47%，95%CI-2.3%，+3.3%），SP+PQ 组 618 名儿童中有 17 名（2.8%）（风险差 1.2%，95%CI-1.3%，+3.6%）。在传播季节结束时，所有组的寄生虫血症患病率以及与 SP 耐药相关的 Pfdhfr 和 Pfdhps 突变的儿童比例均非常低。
结论
季节性 IPT 中用 SP+PQ 治疗儿童非常有效且耐受良好；两种长效药物的联合使用可能会阻碍耐药寄生虫的出现。
试验注册
ClinicalTrials.gov NCT00529620。
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