VITAMIN A AND MUCOSAL RESPONSE TO VIRAL DIARRHEA

描述（改编自研究者摘要）： 最近的流行病学数据表明，提供维生素A补充剂 维生素A缺乏症风险的儿童 传染病的死亡率。 临床试验也 最近表明，提供高剂量的维生素A补充剂， 儿童麻疹死亡率降低。 现场和临床 研究表明，维生素A补充剂特别影响 从慢性病中恢复过来。虽然维生素A已经有充分的证据证明 对血清抗体应答和上皮细胞的影响 在小肠的分化，维生素的机制， 一个防止死亡或严重疾病的发展是不知道的。 阐明这些机制将对临床和公共卫生 影响 以人口为基础的补充方案是有效的 但代价高昂 有可能补充儿童参加 急性感染的治疗中心可以改善临床过程， 避免了同样数量的死亡， 通过一个社区范围的项目。 这一办法尚未尝试。 的 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 临床上有明显的改善。 具体目标为 如下：在一项双盲、安慰剂对照的临床试验中， 在秘鲁利马的儿科住院患者中进行轮状病毒腹泻研究 将确定维生素A补充剂是否影响（1）免疫 通过测量粘膜（唾液和粪便）对轮状病毒感染的反应 伊加和IgM）和血清（伊加，IgG，IgM）浓度的轮状病毒- 入院后第1、3、10、20天血清特异性抗体水平 通过测量轮状病毒脱落的持续时间， 粪便、腹泻持续时间（考虑粪便稠度、数量和 体重）和腹泻的严重程度（通过粪便重量测量）;（3） 恢复期间正常肠上皮功能的再生 通过测量乳糖酶的患病率来预防轮状病毒感染 使用呼吸氢试验（BHT）2、10和20天的功能不全 入院后 此外，安慰剂组的维生素A状态和 感染恢复后的对照组（入院后10天） 使用相对剂量反应（RDR）检验确定患病率 将测量该临床人群中维生素A缺乏症的发生率。

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.