Probiotics in Pediatric Diarrhea in Peru

秘鲁益生菌治疗小儿腹泻

• 批准号: 7691768
• 负责人: RICHARD A OBERHELMAN
• 金额: $ 53.64万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691768
• 关键词: 5 year old; Acute; Address; Adverse event; Age; Antibiotic Therapy; Area; Bacteria; Bifidobacterium bifidum; Breast Feeding; Campylobacter; Cause of Death; Cessation of life; Child; Child health care; Childhood; China; Chronic; Clinical; Clinical Management; Clinical Treatment; Clinical Trials; Communities; Developed Countries; Developing Countries; Development; Diarrhea; Disease; Double-Blind Method; Environment; Etiology; Europe; Evaluation; Feces; Food Supplements; Frequencies; Giardia; Guidelines; Incidence; Intestines; Lactobacillus; Life; Malnutrition; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Nutritional status; Oral Rehydration Therapy; Organism; Outcome; Participant; Pathology; Patients; Peer Review; Peru; Pharmacologic Substance; Placebos; Population; Probiotics; Protocols documentation; Public Health; Randomized; Relative (related person); Research; Role; Rotavirus; Rural Community; Safety; Shigella; Specimen; Testing; Time; Treatment Efficacy; United States; Viral; Virus; age group; base; burden of illness; cohort; community setting; double-blind placebo controlled trial; efficacy evaluation; enterotoxigenic Escherichia coli; gastrointestinal system; improved; microbial community; microorganism; mortality; pathogen; programs; randomized placebo controlled trial; resistant strain; treatment strategy

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.

描述（由申请人提供）：在发展中国家和中国，腹泻每年导致 5 岁以下儿童 10 亿次患病和 250 万人死亡，使其成为该年龄段第二大常见死因。尽管存在这种疾病负担，但自三十多年前口服补液疗法的发展以来，腹泻的临床治疗在很大程度上仍然停滞不前。多项小型研究已经证明了益生菌制剂或用于在肠道定殖的有益细菌对于改善儿童腹泻疾病的临床病程的功效。然而，这些小型研究是在营养良好的儿童腹泻主要由病毒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。我们建议在一项随机双盲安慰剂对照试验中评估乳杆菌 GG (LGG) 和两歧双歧杆菌 (Bb) 这两种有前景的益生菌制剂在圣克拉拉社区一级治疗腹泻的相对功效。圣克拉拉是秘鲁亚马逊地区的一个小镇，那里慢性营养不良和儿童腹泻非常流行。将 650 名 6 个月至 6 岁的儿童随机分为 3 组，在监测期间每次腹泻发作时分别接受 LGG、Bb 或安慰剂 5 天。将检查腹泻粪便标本中的细菌、病毒和寄生虫病原体。我们的多年研究将评估这些益生菌制剂对所有腹泻原因以及儿科腹泻的特定常见原因（如轮状病毒、产肠毒素大肠杆菌、志贺氏菌、贾第鞭毛虫和弯曲杆菌）的治疗效果。将在治疗组之间比较特定事件的结果，例如最后一次不成形大便的时间，以及特定受试者的结果，包括疾病的总体负担、不良事件的频率以及营养状况随时间的变化。对纵向队列进行深入研究并严格监测不良事件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。拟议的项目将对发展中国家益生菌的功效、实用性和安全性进行严格和彻底的评估，这些国家的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。