Probiotics in Pediatric Diarrhea in Peru

描述（由申请人提供）：在发展中国家和中国，腹泻每年导致10亿次疾病发作和250万例5岁以下儿童死亡，使其成为该年龄组第二常见的死亡原因。尽管有这种疾病负担，但自30多年前口服补液疗法发展以来，腹泻的临床管理在很大程度上仍然停滞不前。多个小型研究已经证明了益生菌制剂或用于定植肠道的有益细菌对改善儿童腹泻疾病的临床病程的功效。然而，这些小型研究是在腹泻主要由营养良好的儿童的病毒性病原体引起的地区进行的，其局限性限制了这些研究在腹泻仍然严重威胁儿童健康的地区的相关性。我们提议在一项随机双盲安慰剂对照试验中评估两种有前景的益生菌制剂乳酸杆菌GG （LGG）和两歧双歧杆菌（Bb）治疗腹泻的相对疗效，该试验在秘鲁亚马逊地区的圣克拉拉镇进行，该城镇是慢性营养不良和儿童腹泻高度流行的地方。650名6个月至6岁的儿童将被随机分为3组，在监测期间每次腹泻发作时分别接受LGG、Bb或安慰剂治疗5天。将对腹泻粪便标本进行细菌、病毒和寄生虫病原体检查。我们的多年研究将评估这些益生菌制剂对所有腹泻原因的治疗效果，以及儿童腹泻的特定流行原因，如轮状病毒、产肠毒素的大肠杆菌、志贺氏菌、贾第鞭毛虫和弯曲杆菌。将比较治疗组之间的特定疾病结局（如持续未形成大便的时间）和特定受试者结局（包括总体疾病负担、不良事件发生频率和营养状况随时间变化）。对不良事件进行严格监测的纵向队列深入研究将使我们能够解决许多悬而未决的问题，例如母乳喂养和营养不良对治疗效果的影响以及接受新疗法的策略。拟议的项目将允许在发展中国家对益生菌有机体的功效、实用性和安全性进行关键和彻底的评估，在这些国家，儿童继续遭受腹泻疾病的沉重负担，需要新的和改进的治疗方法。

DESCRIPTION (provided by applicant): Diarrhea causes a billion illness episodes and 2.5 million deaths/year in children under the age of 5 years in the developing world and China, making it the second most frequent cause of death in this age group. Despite this burden of disease, the clinical management of diarrhea has remained largely stagnant since the development of oral rehydration therapy over thirty years ago. Multiple small studies have demonstrated the efficacy of probiotic agents, or beneficial bacteria used to colonize the gut, for improving the clinical course of diarrheal illness in children. However limitations of these small studies, done in areas where diarrhea is caused predominantly by viral pathogens in well nourished children, limit the relevance of these studies in areas where diarrhea remains a serious threat to child health. We propose to evaluate the relative efficacy of Lactobacillus GG (LGG) and Bifidobacterium bifidum (Bb), two promising probiotic agents, in a randomized double-blinded placebo-controlled trial for the treatment of diarrhea at the community level in Santa Clara, a town in the Peruvian Amazon where chronic malnutrition and childhood diarrhea are highly endemic. Six hundred and fifty children ages 6 months to 6 years will be randomized to 3 groups, which will receive LGG, Bb, or placebo respectively for 5 days with each episode of diarrhea during the surveillance period. Diarrhea stool specimens will be examined for bacterial, viral, and parasitic pathogens. Our multiyear study will allow for the evaluation of treatment with these probiotic agents for all causes of diarrhea and on specific prevalent causes of pediatric diarrhea such as rota virus, enterotoxigenic E. coli, Shigella, Giardia and Campylobacter. Episode-specific outcomes such as time to last unformed stool, and subject-specific outcomes, including overall burden of disease, frequency of adverse events, and changes in nutritional status overtime, will be compared between treatment groups. Intensive study of a longitudinal cohort with stringent monitoring of adverse events will allow us to address many unanswered questions, such as the impact of breastfeeding and malnutrition on therapeutic efficacy and strategies for acceptance of the new therapies. The proposed project will allow for a critical and thorough evaluation of the efficacy, practicality, and safety of probiotic organisms in a developing country, where children continue to suffer high burdens of diarrheal diseases and are in need of new and improved approaches to treatment.