Probiotics in Pediatric Diarrhea in Peru

描述（由申请人提供）：腹泻在发展中国家和中国每年导致10亿例5岁以下儿童发病和250万例死亡，使其成为该年龄组的第二大最常见死因。尽管存在这种疾病负担，但自三十多年前口服补液疗法发展以来，腹泻的临床管理基本上仍然停滞不前。多项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在改善儿童腹泻疾病的临床过程中的功效。然而，这些小型研究的局限性，在腹泻主要由病毒病原体引起的营养良好的儿童中进行，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。我们建议评估乳酸杆菌GG（LGG）和两歧双歧杆菌（Bb），两个有前途的益生菌制剂的相对疗效，在一个随机双盲安慰剂对照试验中治疗腹泻在社区一级的圣克拉拉，在秘鲁亚马逊的一个城镇，慢性营养不良和儿童腹泻是高度流行的。将650名6个月至6岁的儿童随机分为3组，分别接受LGG、Bb或安慰剂治疗5天，在监测期间每次发生腹泻。将检查腹泻粪便标本中的细菌、病毒和寄生虫病原体。我们的多年研究将允许评价这些益生菌制剂对所有腹泻原因和儿科腹泻的特定流行原因（如轮状病毒、肠致病性大肠杆菌）的治疗。大肠杆菌、志贺氏菌、贾第虫和弯曲杆菌。将比较治疗组之间的特定事件结局（如至末次不成形便的时间）和特定受试者结局（包括总体疾病负担、不良事件频率和营养状态随时间的变化）。通过对不良事件进行严格监测的纵向队列的深入研究，将使我们能够解决许多未回答的问题，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的有效性、实用性和安全性进行严格和彻底的评估，因为发展中国家的儿童仍然遭受着巨大的肠道疾病负担，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.