Effects of water, sanitation, handwashing and nutritional interventions on soil-transmitted helminth infections in young children: A cluster-randomized controlled trial in rural Bangladesh

BackgroundSoil transmitted helminths (STH) infect >1.5 billion people. Mass drug administration (MDA) effectively reduces infection; however, there is evidence for rapid reinfection and risk of potential drug resistance. We conducted a randomized controlled trial in Bangladesh (WASH Benefits, NCT01590095) to assess whether water, sanitation, hygiene and nutrition interventions, alone and combined, reduce STH in a setting with ongoing MDA.Methodology/Principal findingsIn 2012–2013, we randomized 720 clusters of 5551 pregnant women into water treatment, sanitation, handwashing, combined water+sanitation+handwashing (WSH), nutrition, nutrition+WSH (N+WSH) or control arms. In 2015–2016, we enrolled 7795 children, aged 2–12 years, of 4102 available women for STH follow-up and collected stool from 7187. We enumerated STH infections with Kato-Katz. We estimated intention-to-treat intervention effects on infection prevalence and intensity. Participants and field staff were not blinded; laboratory technicians and data analysts were blinded.Prevalence among controls was 36.8% for A. lumbricoides, 9.2% for hookworm and 7.5% for T. trichiura. Most infections were low-intensity. Compared to controls, the water intervention reduced hookworm by 31% (prevalence ratio [PR] = 0.69 (0.50,0.95), prevalence difference [PD] = -2.83 (-5.16,-0.50)) but did not affect other STH. Sanitation improvements reduced T. trichiura by 29% (PR = 0.71 (0.52,0.98), PD = -2.17 (-4.03,-0.38)), had a similar borderline effect on hookworm and no effect on A. lumbricoides. Handwashing and nutrition interventions did not reduce any STH. WSH and N+WSH reduced hookworm prevalence by 29–33% (WSH: PR = 0.71 (0.52,0.99), PD = -2.63 (-4.95,-0.31); N+WSH: PR = 0.67 (0.50,0.91), PD = -3.00 (-5.14,-0.85)) and marginally reduced A. lumbricoides. Effects on infection intensity were similar.Conclusions/SignificanceIn a low-intensity infection setting with MDA, we found modest but sustained hookworm reduction from water treatment and combined WSH interventions. Impacts were more pronounced on STH species with short vs. long-term environmental survival. Our findings suggest possible waterborne transmission for hookworm. Water treatment and sanitation improvements can augment MDA to interrupt STH transmission.Trial registrationNCT01590095.

研究背景
土壤传播的蠕虫（Soil-transmitted helminths, STH）感染人数超过15亿。群体药物大规模给药（Mass drug administration, MDA）可有效降低感染负荷，但现有证据表明其会导致快速再感染，且存在潜在的药物耐药性风险。本研究在孟加拉国开展一项随机对照试验（WASH Benefits，临床试验注册号NCT01590095），旨在评估水、环境卫生、个人卫生与营养干预措施单独或联合使用，在持续开展MDA的环境中是否能降低土壤传播蠕虫的感染率。

研究方法与主要结果
2012-2013年，我们将5551名孕妇所在的720个群组随机分配至水处理组、环境卫生组、洗手组、联合水-环境卫生-洗手组（WSH）、营养组、营养+WSH组（N+WSH）以及对照组。2015-2016年，我们招募了4102名符合条件的女性所生的7795名2~12岁儿童进行土壤传播蠕虫感染随访，并成功收集7187份粪便样本。采用Kato-Katz法对土壤传播蠕虫感染进行定量计数，估算意向治疗（intention-to-treat）干预对感染患病率与感染强度的影响。研究参与者与现场工作人员未设盲，而实验室技术人员与数据分析人员实施设盲。
对照组的感染患病率分别为：蛔虫（A. lumbricoides）36.8%、钩虫（hookworm）9.2%、鞭虫（T. trichiura）7.5%，且绝大多数感染为低强度感染。与对照组相比，水处理组钩虫感染率降低31%（患病率比[PR]=0.69，95%置信区间：0.50~0.95；患病率差[PD]=-2.83，95%置信区间：-5.16~-0.50），但未对其他土壤传播蠕虫感染产生显著影响。环境卫生改善措施使鞭虫感染率降低29%（PR=0.71，95%置信区间：0.52~0.98；PD=-2.17，95%置信区间：-4.03~-0.38），对钩虫感染呈现相似的临界显著性效果，而对蛔虫感染无显著影响。洗手与营养干预未降低任何一种土壤传播蠕虫的感染率。WSH组与N+WSH组的钩虫感染率分别降低29%~33%（WSH组：PR=0.71，95%置信区间：0.52~0.99；PD=-2.63，95%置信区间：-4.95~-0.31；N+WSH组：PR=0.67，95%置信区间：0.50~0.91；PD=-3.00，95%置信区间：-5.14~-0.85），并小幅降低了蛔虫感染率。感染强度的变化趋势与上述结果一致。

研究结论与意义
在持续开展MDA的低强度感染环境中，我们发现水处理与联合WSH干预可实现钩虫感染率的适度且持续降低。相较于环境存活周期较长的蠕虫物种，干预措施对环境存活周期较短的蠕虫物种的干预效果更为显著。本研究结果提示钩虫可能存在经水传播途径。水处理与环境卫生改善措施可作为群体药物大规模给药的辅助手段，以阻断土壤传播蠕虫的传播。

临床试验注册号：NCT01590095。