International Health Unit, Department of Epidemiology and Social Medicine, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, BE-2610, Antwerpen, Belgium.
Trials. 2013 Sep 24;14:311. doi: 10.1186/1745-6215-14-311.
In malaria endemic areas, schoolchildren usually have asymptomatic malaria infections and consequently remain untreated. Therefore, intermittent preventive treatment with sulfadoxine-pyrimethamine in schoolchildren would be a plausible strategy in malaria stable transmission areas to prevent anaemia and malnutrition. However, in contrast to infancy and pregnancy, antimalaria intermittent preventive treatment in children has been barely investigated. As the implementation of intermittent preventive treatment may be challenged by sulfadoxine-pyrimethamine resistance, sulfadoxine-pyrimethamine combined with piperaquine may be a better alternative than sulfadoxine-pyrimethamine monotherapy. A clinical trial is being conducted to assess the efficacy and safety of intermittent preventive treatments versus controls in Democratic Republic of Congo (DRCongo) schoolchildren and their impact on sulfadoxine-pyrimethamine resistance.
METHODS/DESIGN: A phase IIIb, randomised, controlled trial will enroll asymptomatic schoolchildren. For interventions, sulfadoxine-pyrimethamine is compared to sulfadoxine-pyrimethamine plus piperaquine and to a control group. The two treatments are given four-monthly from baseline for a year as a single dose for sulfadoxine-pyrimethamine and two doses at 24-hour intervals for piperaquine. All participants receive praziquantel and albendazole as mass-treatment for helminthiasis at enrolment. The primary endpoint is haemoglobin concentration change at 12 months follow-up. Secondary endpoints are malaria parasite load and malaria prevalence, at baseline and at month 12. Malaria and helminthiasis incidence will be monitored throughout the study. Statistical analysis will use multilevel modelling due to repeated measurements and clustering effect of participants.
The very few studies on intermittent preventive treatment in schoolchildren in malaria stable transmission areas have contradictory results. This randomised controlled trial is unique in comparing efficacy and safety of a prophylactic combination therapy to monotherapy or a control group after 12 months follow-up. Resistance markers for sulfadoxine-pyrimethamine (including break through parasitaemias) will also be recorded. Its uniqueness lies also in the fact that we use piperaquine, a long acting antimalarial, in combination with sulfadoxine-pyrimethamine. Artemisinin derivatives have been excluded as it is part of the treatment policies in virtually all malaria endemic countries. Our findings may, therefore, contribute to the public health of youngsters who fail to thrive and grow due to multiple morbidities.
NCT01722539; PACTR201211000449323.
在疟疾流行地区，学龄儿童通常患有无症状疟疾感染，因此未得到治疗。因此，在疟疾稳定传播地区，对学龄儿童进行磺胺多辛-乙胺嘧啶间歇性预防治疗可能是一种合理的策略，以预防贫血和营养不良。然而，与婴儿期和妊娠期不同，儿童的抗疟疾间歇性预防治疗几乎没有得到研究。由于磺胺多辛-乙胺嘧啶耐药性的影响，磺胺多辛-乙胺嘧啶联合哌喹可能是磺胺多辛-乙胺嘧啶单药治疗的更好选择。目前正在开展一项临床试验，以评估在刚果民主共和国（DRCongo）学龄儿童中磺胺多辛-乙胺嘧啶间歇性预防治疗与对照治疗的疗效和安全性及其对磺胺多辛-乙胺嘧啶耐药性的影响。
方法/设计：这是一项 IIIb 期、随机、对照试验，将招募无症状学龄儿童。干预措施包括磺胺多辛-乙胺嘧啶与磺胺多辛-乙胺嘧啶加哌喹以及对照组进行比较。从基线开始，每年进行四次为期一年的单一剂量磺胺多辛-乙胺嘧啶治疗和两次间隔 24 小时的哌喹治疗。所有参与者在入组时接受驱虫治疗（吡喹酮和阿苯达唑）以治疗寄生虫感染。主要终点是 12 个月随访时血红蛋白浓度的变化。次要终点是基线和第 12 个月时的疟原虫载量和疟疾患病率。整个研究期间将监测疟疾和寄生虫感染的发病率。由于参与者的重复测量和聚类效应，统计分析将使用多层次模型进行。
在疟疾稳定传播地区，关于儿童间歇性预防治疗的研究很少，结果相互矛盾。这项随机对照试验的独特之处在于，它比较了在 12 个月随访后预防性联合治疗与单药治疗或对照组的疗效和安全性。还将记录磺胺多辛-乙胺嘧啶的耐药标志物（包括突破性寄生虫血症）。它的独特之处还在于，我们使用了哌喹，一种长效抗疟药物，与磺胺多辛-乙胺嘧啶联合使用。由于青蒿素衍生物是几乎所有疟疾流行国家治疗政策的一部分，因此将其排除在外。我们的研究结果可能有助于因多种疾病而发育不良和生长不良的年轻人的公共卫生。
NCT01722539；PACTR201211000449323。
