VITAMIN A AND MUCOSAL RESPONSE TO VIRAL DIARRHEA

描述(改编自调查员摘要)： 最近的流行病学数据表明，提供维生素A补充剂 对有患维生素A缺乏症风险的儿童减少 传染病的死亡率。临床试验也已经 最近表明，提供大剂量维生素A补充剂可以 患麻疹的儿童可降低死亡率。现场和临床都有 研究表明，维生素A补充剂对 从腹泻病中恢复。尽管维他命A有很好的记录 对血清抗体应答和上皮细胞的影响 小肠的分化，维生素的机制 对死亡或严重疾病的发展有保护作用尚不清楚。 阐明这些机制将对临床和公共卫生 这意味着什么。基于人口的补充方案是有效的 但代价不菲。儿童补充剂是可能的 有急性感染的治疗中心可以改善临床病程 减少疾病，并避免本应避免的死亡人数 通过一个社区范围的计划。还没有人尝试过这种方法。这个 本研究的目的是研究维生素A的作用机制 急性腹泻儿童的补充剂，并确定是否 在临床上有了明显的改善。具体目标是 以下是：在一项双盲、安慰剂对照的临床试验中 在秘鲁利马，轮状病毒腹泻的儿科住院患者中的研究 将决定补充维生素A是否影响(1)免疫力 通过检测粘膜(唾液和粪便)对轮状病毒感染的反应 Ig A和Ig M)和血清(Ig A、Ig G、Ig M)浓度。 入院后第1、3、10、20天特异性抗体；(2)病程 通过测量轮状病毒在人体内脱落的时间 大便、腹泻持续时间(考虑大便稠度、数量和 体重)和腹泻的严重程度(以粪便重量衡量)； 恢复期正常肠上皮功能的再生 通过测量乳糖酶的流行率来预防轮状病毒感染 呼气氢气试验(BHT)2天、10天和20天 入院后。此外，安慰剂和安慰剂的维生素A状况 对照组在感染恢复后(入院后10d) 使用相对剂量-反应(RDR)试验来确定患病率 将对这一临床人群中维生素A缺乏的程度进行测量。

DESCRIPTION (adapted from investigator's abstract): Recent epidemiologic data shown that provision of vitamin A supplements to children at risk of developing vitamin A deficiency decreases mortality rates from infectious disease. Clinical trials have also recently shown that provision of high-dose vitamin A supplements to children with measles decreases mortality. Both field and clinical studies suggest that vitamin A supplementation specifically affects recovery from diarrheal disease. Although vitamin A has well-documented effects on the serum antibody response and on epithelial cell differentiation in the small intestine, the mechanism by which vitamin A protects against death or development of severe disease is not know. Elucidating these mechanisms will have clinical and public health implications. Population-based supplementation programs are effective but costly. It is possible that supplementation of children attending treatment centers with acute infections can improve the clinical course of disease and avert the same number of deaths that would be prevented by a community-wide program. This approach has not been attempted. The goal of this study is to examine the mechanisms of action of vitamin A supplementation in children with acute diarrhea and to determine if there is a clinically demonstrable improvement. Specific Aims are as follows: In a double-blind, placebo- controlled clinical trial conducted in Lima, Peru among pediatric inpatients with rotavirus diarrhea studies will determine if vitamin A supplementation affects (1) the immune response to rotavirus infection by measuring mucosal (salivary and fecal IgA and IgM) and serum (IgA, IgG, IgM) concentrations of rotavirus- specific antibody 1, 3, 10 and 20 days after admission; (2) the course of rotavirus disease by measuring duration of rotavirus shedding in the stool, duration of diarrhea (considering stool consistency, number and weight), and severity of diarrhea (as measured by stool weight); (3) the regeneration of normal intestinal epithelial function during recovery from rotavirus infection by measuring the prevalence of lactase insufficiency using the breath hydrogen test (BHT) 2, 10 and 20 days after admission. In addition, the vitamin A status of placebo and control subjects after recovery from infection (10 d after admission) using the relative dose-response (RDR) test to determine the prevalence of vitamin A deficiency in this clinical population will be measured.