Effects of sanitation on pathogen transmission and child health in Bangladesh

说明(申请人提供)：腹泻疾病在低收入国家的儿童中造成大量和持续的疾病负担；死亡率估计将全球儿童死亡的10%归因于腹泻。粪便-口腔病原体(被认为是腹泻的最重要原因)通过各种复杂的、环境中介的途径从粪便传播到新宿主，这些途径相互作用，也受到人类行为的影响。防止病原体从粪便传播到环境中的卫生干预措施(例如，提供厕所)可以阻断这些传播途径，减轻腹泻疾病的负担。尽管卫生设施在减少腹泻方面具有潜在的重要性，但迄今为止关于农村地区儿童胃肠道感染卫生干预措施的所有研究都使用了非随机设计。此外，很少有研究包括对卫生相关行为的详细监测，以及对从粪便到儿童疾病的复杂病原体传播途径的微生物学评估。目的：这项研究的主要目的是评估卫生基础设施和家庭卫生做法的改善对孟加拉国农村地区病原体传播途径上的粪便污染的影响，并评估这些途径如何调节卫生设施改善对24个月大儿童腹泻和寄生虫感染的影响。我们假设，卫生条件的改善将减少饮用水、家庭土壤和儿童手的污染；我们还假设，这些途径将调解干预导致的腹泻流行率和寄生虫感染的任何减少。方法：我们将通过在WASH Benefits中嵌套微生物学和行为测量来验证我们的假设，这是一项由盖茨基金会资助并由我们的团队领导的随机对照试验，目前正在孟加拉国农村进行。我们将从干预后12个月开始，每季度访问试验中的卫生和控制武器共720户家庭，为期2年。每次巡视时，我们都会从管井、池塘、储水、儿童游乐区的泥土、管井附近的泥土和儿童手中收集样本，以进行粪便指示细菌分析。在最后两轮采样中，我们将分析主要粪便病原体的样本，并进行来源追踪，以区分人类和动物的粪便污染。我们将通过抽查和被动红外传感器测量来监测卫生做法。这些数据将利用现有试验方案中衡量的健康结果(腹泻、蠕虫和粪便原虫感染)。我们将比较使用意向治疗和编制者平均因果效应估计器的研究组之间的粪便污染。我们将通过分析直接和间接影响来估计污染通过个别途径对健康结果的贡献。我们的团队(加州大学伯克利分校、斯坦福大学、ICDDR，B)在由NIH、CDC、DFID、美国环保局和盖茨基金会资助的项目中，在孟加拉国和其他低收入国家的水、卫生和个人卫生研究方面拥有丰富的合作经验。

DESCRIPTION (provided by applicant): Diarrheal illness creates a large and persistent disease burden among children in low-income countries; mortality estimates attribute 10% of global deaths among children < 5 to diarrhea. Fecal-oral pathogens (believed to be the most important causes of diarrhea) are transmitted from feces to new hosts through a variety of complex, environmentally mediated pathways that interact with each other and are also influenced by human behavior. Sanitation interventions that prevent the spread of pathogens from feces into the environment (e.g. provision of latrines) could block these transmission pathways and reduce the burden of diarrheal disease. Despite the potential importance of sanitation in reducing diarrhea, all studies to date of sanitation interventions on child gastrointestinal infections in rural settings have used non-randomized designs. Additionally, few studies have included detailed monitoring of sanitation-related behaviors and microbiological assessment of the complex pathogen transmission pathways that lead from feces to child illness. Aims: The principal aims of this study are to assess the impact of improvements in sanitation infrastructure and household sanitation practices on fecal contamination along pathogen transmission pathways in rural Bangladesh, and to assess how these pathways mediate the impact of sanitation improvements on diarrhea and parasitic infections in children < 24 months old. We hypothesize that improved sanitation will reduce contamination of drinking water, household soil, and children's hands; we also posit that these pathways will mediate any reductions in diarrhea prevalence and parasitic infections caused by the intervention. Methods: We will test our hypotheses by nesting microbiological and behavioral measurements within WASH Benefits, a randomized controlled trial currently underway in rural Bangladesh funded by the Gates Foundation and led by our team. We will visit a total of 720 households from the trial's sanitation and control arms quarterly for 2 years, starting 12 months after intervention. At each visit, we will collect samples from tubewells, ponds, stored water, soil from the child play area, soil near tubewells and from children's hands for analysis of fecal indicator bacteria. During the last two sampling rounds, we will analyze samples for prominent fecal pathogens and perform source tracking to distinguish fecal contamination from humans versus animals. We will monitor sanitation practices through spot checks and passive infrared sensor measurements. These data will leverage the health outcomes measured in the existing trial protocol (diarrhea and helminth and protozoan infections in stool). We will compare fecal contamination between the study arms using intention to treat and complier average causal effect estimators. We will estimate the contribution of contamination to health outcomes through individual pathways by analysis of direct and indirect effects. Our team (UC Berkeley, Stanford, ICDDR,B) has extensive experience collaborating on studies of water, sanitation and hygiene in Bangladesh and other low-income countries on projects funded by the NIH, CDC, DFID, USEPA and the Gates Foundation.