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

非痢疾志贺氏菌相关性腹泻对儿童的影响

• 批准号: 10247203
• 负责人: Subhra Chakraborty
• 金额: $ 52.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-14 至 2021-03-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247203
• 关键词: 5 year old; Address; Adult; Age; Algorithms; Anthropometry; Antibiotic Therapy; Antibiotics; Area; Bangladesh; Birth; Blood; Blood specimen; Case-Control Studies; Child; Child Development; Child Health; Chronic; Cognitive; Cohort Studies; Collaborations; Country; Detection; Development; Diagnostic; Diagnostic tests; Diarrhea; Dysentery; Enrollment; Expression Profiling; Feces; Functional disorder; Future; Gene Expression; Guidelines; Health; Hospitalization; Hospitals; Hydration status; Impairment; Infection; Inflammation; Inflammatory; Invaded; Kinetics; Laboratories; Length; Life; Literature; Malnutrition; Morbidity - disease rate; Mucous Membrane; Nature; Nutritional status; Patients; Performance; Peru; Proxy; Publishing; Recommendation; Research; Resources; Risk; Rural; Rural Hospitals; Sampling; Savings; Shigella; Shigella Infections; Symptoms; Testing; Visit; World Health Organization; care seeking; cognitive development; cost; diagnostic assay; evidence base; improved; indexing; inflammatory disease of the intestine; intestinal epithelium; mortality; mortality risk; novel; nutrition; prospective; recruit; standard care; stool sample; treatment guidelines

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. Such a rapid test is currently unavailable. 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 under 5 years of age seeking care in the Kumudini hospital in rural Mirzapur, Bangladesh with diarrhea (both dysentery and NDSD), that is positive for Shigella will be enrolled and prospectively followed. A third group with Shigella negative watery diarrhea will also be enrolled to compare. 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 our novel, simple and rapid test S-RLDT capable of identifying NDSD cases. 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.

项目总结/摘要 志贺氏菌是世界贫困地区儿童中度至重度腹泻的主要原因。 志贺氏菌以引起痢疾（便血）而闻名。然而，大多数感染志贺氏菌的儿童 出现水样腹泻。目前世界卫生组织（WHO）的治疗指南 志贺氏菌病（在缺乏快速、敏感、简单和廉价的诊断测试的情况下） 当粪便中出现可见的血液时使用抗生素。因此，非痢疾志贺氏菌相关性腹泻 （NDSD）病例不会使用抗生素治疗。没有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。特别脆弱的年幼儿童或 营养不良，志贺氏菌感染的识别和治疗可能会挽救生命。可以假设， NDSD病例，如果迅速发现，应使用抗生素治疗，以提高生存率和长期 儿童的发展潜力。此类病例的识别将需要快速检测来记录这些 感染，以便能够及时启动治疗，并以证据为基础。目前，这种快速测试 不可用.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 了解NDSD的病理生理学以及NDSD与痢疾相比对儿童的影响 志贺氏菌病。在米尔扎布尔农村的库穆迪尼医院寻求治疗的5岁以下儿童， 孟加拉国腹泻（痢疾和NDSD），志贺氏菌阳性，将入组， 前瞻性地跟踪。还将招募第三组志贺氏菌阴性水样腹泻患者进行比较。我们 研究的具体目标如下： AIM 1.确定与NDSD病例相关的住院发病率和风险及其对营养的影响 儿童的地位和认知发展。 AIM 2.了解NDSD对儿童肠道屏障功能、全身和肠道炎症的影响。 AIM 3.评估我们的新型，简单，快速的测试S-RLDT能够识别NDSD病例。 总的来说，我们提出的研究将通过了解 NDSD和NDSD对儿童健康的影响。这项研究将有助于了解是否有必要改变 现行志贺氏菌病治疗指南，以促进儿童更好的生存和发展。本研究还将 验证一种能够识别将从抗生素中受益的患者的快速测试。