The impact of non-dysentery Shigella-associated diarrhea in children

项目摘要/摘要 志贺氏菌是世界贫困地区儿童中重度腹泻的主要原因。 志贺氏菌以引起痢疾(大便中有血)而闻名。然而，大多数感染志贺氏菌的儿童 出现水样腹泻。世界卫生组织(WHO)目前的治疗指南 志贺氏菌病(在缺乏快速、敏感、简单和廉价的诊断试验的情况下)推荐治疗。 当粪便中有可见的血迹时，使用抗生素。因此，非痢疾性志贺氏菌相关性腹泻 (NDSD)病例不会使用抗生素治疗。无痢疾可能并不意味着死亡风险低。 并且不排除志贺氏菌是腹泻的原因。在特别脆弱的年幼儿童或患有 营养不良、志贺氏菌感染的鉴定和治疗可能会挽救生命。可以假设 NDSD病例如迅速确诊，应使用抗生素治疗，以提高存活率和长期存活率。 儿童的发展潜力。识别此类病例将需要进行快速测试以记录这些情况 感染，以便能够迅速开始治疗，并以证据为基础。 为了解决这些问题，我们建议进行前瞻性纵向病例对照研究，以了解 儿童新城疫的病理生理学及与痢疾志贺氏菌病的比较。这个 孟加拉国患有腹泻(痢疾和NDSD)的儿童在医院寻求治疗，这是阳性的 志贺氏菌和第三组志贺氏菌阴性水样腹泻将被纳入并前瞻性跟踪。我们的 研究的具体目标如下： 目的1.确定与NDSD病例相关的发病率和住院风险及其对营养的影响 儿童的地位和认知发展。 目的2.了解NDSD对儿童肠道屏障功能、全身和肠道炎症的影响。 目的3.评价简便、快速的S-罗氏凝集试验是否适用于脑脊髓炎的发现和治疗 流行国家乡村医院临床环境中的志贺氏菌病。 总而言之，我们提议的研究将通过了解糖尿病的病理生理学，对该领域产生广泛影响。 NDSD和NDSD对儿童健康的影响。这项研究将有助于了解是否需要改变 目前志贺氏菌病的治疗指南，以更好地生存和发展的儿童。这项研究还将 验证一种能够识别哪些患者将受益于抗生素的快速测试。

PROJECT SUMMARY / ABSTRACT Shigella is a primary cause of moderate-to-severe diarrhea in children living in impoverished areas of the world. Shigella is known for causing dysentery (blood in stool). However, majority of the children infected with Shigella present with watery diarrhea. The current World Health Organization (WHO) guidelines for treatment of shigellosis (in the absence of a rapid, sensitive, simple and inexpensive diagnostic test) recommends treatment with antibiotics when presence of visible blood in stool. Thus, the non-dysentery Shigella associated diarrhea (NDSD) cases would not be treated with antibiotics. Absence of dysentery may not indicate a low risk of death and does not exclude Shigella as a cause of diarrhea. In particularly vulnerable younger children or with malnutrition, identification and treatment of Shigella infection might be life-saving. It may be hypothesized that NDSD cases, if identified quickly, should be treated with antibiotics to improve survival and long-term developmental potential in children. Identification of such cases will require a rapid test to document these infections so that treatment can be initiated promptly, and evidence based. To address these questions, we propose to conduct a prospective longitudinal case control study to understand the pathophysiology of NDSD and the impact of NDSD in children compared to dysentery shigellosis. The children seeking care in the hospital in Bangladesh with diarrhea (both dysentery and NDSD), that is positive for Shigella and a third group with Shigella negative watery diarrhea will be enrolled and prospectively followed. Our study has the following specific aims: AIM 1. Determine morbidity and risk of hospitalization associated with NDSD cases and its impact on nutritional status and cognitive development of the children. AIM 2. Understand the impact of NDSD on gut barrier function, systemic and gut inflammation in children. AIM 3. Evaluate if the simple and rapid test S-RLDT could be applicable for case detection and treatment of shigellosis in the clinical settings of the rural hospitals of the endemic countries. Collectively, our proposed research would broadly impact the field by understanding the pathophysiology of NDSD and the impact of NDSD in child health. This study will help to understand if there is a need to change the current guidelines of shigellosis treatment for better survival and development of the children. This study will also validate a rapid test capable of identifying the patients who will benefit from antibiotics.