Two Strategies for the Delivery of IPTc in an Area of Seasonal Malaria Transmission in The Gambia: A Randomised Controlled Trial

BackgroundThe Expanded Programme on Immunisation (EPI) provides an effective way of delivering intermittent preventive treatment for malaria (IPT) to infants. However, it is uncertain how IPT can be delivered most effectively to older children. Therefore, we have compared two approaches to the delivery of IPT to Gambian children: distribution by village health workers (VHWs) or through reproductive and child health (RCH) trekking teams. In rural areas, RCH trekking teams provide most of the health care to children under the age of 5 years in the Infant Welfare Clinic, and provide antenatal care for pregnant women. Methods and FindingsDuring the 2006 malaria transmission season, the catchment populations of 26 RCH trekking clinics in The Gambia, each with 400–500 children 6 years of age and under, were randomly allocated to receive IPT from an RCH trekking team or from a VHW. Treatment with a single dose of sulfadoxine pyrimethamine (SP) plus three doses of amodiaquine (AQ) were given at monthly intervals during the malaria transmission season. Morbidity from malaria was monitored passively throughout the malaria transmission season in all children, and a random sample of study children from each cluster was examined at the end of the malaria transmission season. The primary study endpoint was the incidence of malaria. Secondary endpoints included coverage of IPTc, mean haemoglobin (Hb) concentration, and the prevalence of asexual malaria parasitaemia at the end of malaria transmission period. Financial and economic costs associated with the two delivery strategies were collected and incremental cost and effects were compared. A nested case-control study was used to estimate efficacy of IPT treatment courses. Treatment with SP plus AQ was safe and well tolerated. There were 49 cases of malaria with parasitaemia above 5,000/µl in the areas where IPT was delivered through RCH clinics and 21 cases in the areas where IPT was delivered by VHWs, (incidence rates 2.8 and 1.2 per 1,000 child months, respectively, rate difference 1.6 [95% confidence interval (CI) −0.24 to 3.5]). Delivery through VHWs achieved a substantially higher coverage level of three courses of IPT than delivery by RCH trekking teams (74% versus 48%, a difference of 27% [95% CI 16%–38%]). For both methods of delivery, coverage was unrelated to indices of wealth, with similar coverage being achieved in the poorest and wealthiest groups. The prevalence of anaemia was low in both arms of the trial at the end of the transmission season. Efficacy of IPTc against malaria during the month after each treatment course was 87% (95% CI 54%–96%). Delivery of IPTc by VHWs was less costly in both economic and financial terms than delivery through RCH trekking teams, resulting in incremental savings of US$872 and US$1,244 respectively. The annual economic cost of delivering at least the first dose of each course of IPTc was US$3.47 and US$1.63 per child using trekking team and VHWs respectively. ConclusionsIn this setting in The Gambia, delivery of IPTc to children 6 years of age and under by VHWs is more effective and less costly than delivery through RCH trekking clinics. Trial RegistrationClinicalTrials.gov NCT00376155 Please see later in the article for the Editors' Summary

背景 扩大免疫规划（Expanded Programme on Immunisation, EPI）为婴儿提供了疟疾间歇预防治疗（intermittent preventive treatment for malaria, IPT）的有效途径。然而，目前尚不明确如何为大龄儿童最有效地开展IPT服务。为此，本研究对比了冈比亚儿童疟疾间歇预防治疗的两种递送方案：由村医（village health workers, VHWs）分发，或通过生殖与儿童健康（reproductive and child health, RCH）巡回服务团队实施。在农村地区，RCH巡回服务团队主要通过婴儿福利诊所为5岁以下儿童提供多数医疗服务，并为孕妇提供产前保健。

方法与结果 在2006年疟疾传播季期间，冈比亚境内26家RCH巡回诊所的服务辖区人群（每家服务400~500名6岁及以下儿童）被随机分配，分别接受RCH巡回团队或村医提供的IPT服务。在疟疾传播季期间，每月为受试者提供单剂量磺胺多辛-乙胺嘧啶（sulfadoxine pyrimethamine, SP）联合三剂量阿莫地喹（amodiaquine, AQ）的治疗方案。整个疟疾传播季期间，对所有儿童的疟疾发病情况进行被动监测；并在传播季结束时，对每个研究群组的随机抽样儿童进行检查。本研究的主要研究终点为疟疾发病率；次要终点指标包括儿童疟疾间歇预防治疗（IPTc）覆盖率、平均血红蛋白（haemoglobin, Hb）浓度，以及疟疾传播季结束时的无性体疟疾原虫血症患病率。同时收集两种递送方案相关的财务与经济成本，并对比增量成本与效应。本研究采用巢式病例对照研究来评估IPT疗程的有效性。SP联合AQ治疗安全性良好，耐受性佳。在通过RCH诊所递送IPT的区域，共记录49例疟原虫密度超过5000/µl的疟疾病例；而在村医递送IPT的区域，该病例数为21例（发病率分别为每1000儿童月2.8例和1.2例，率差为1.6 [95%置信区间（confidence interval, CI）：-0.24~3.5]）。村医递送方案的IPT三疗程覆盖率显著高于RCH巡回团队方案（74% vs 48%，差值为27% [95%CI：16%~38%]）。两种递送方案的覆盖率均与财富指数无关联，最贫困与最富裕群体的覆盖率均相近。传播季结束时，两组试验人群的贫血患病率均较低。每疗程IPT给药后1个月内，IPT针对疟疾的保护效力为87%（95%CI：54%~96%）。从经济与财务成本来看，村医递送IPTc均低于RCH巡回团队方案，分别可节省增量成本872美元与1244美元。按每名儿童计算，采用巡回团队方案与村医方案的IPTc至少首剂疗程的年度经济成本分别为3.47美元与1.63美元。

结论 在冈比亚的该研究场景中，为6岁及以下儿童提供IPTc时，由村医递送的方案相较于RCH巡回诊所方案，效果更优且成本更低。

试验注册 ClinicalTrials.gov NCT00376155 详见本文后文的编辑总结。