EPIDEMIOLOGY, PREDISPOSING FACTORS, ETIOLOGIES OF PROLONGED DIARRHEA

长期腹泻的流行病学、诱发因素、病因

基本信息

批准号：
6234773
负责人：
RICHARD L GUERRANT
金额：
$ 6.88万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-06-01 至 1998-05-31
项目状态：
已结题

项目摘要

With the improved understanding and control of acute diarrheal illnesses, prolonged diarrheal illnesses and now emerging as a leading cause of morbidity and mortality. However, the epidemiology, etiology and pathogenesis of prolonged diarrheal remain very poorly understood. Several investigators have described bacterial overgrowth in the upper small bowel of patients with prolonged diarrhea or malnutrition; however, their specific nature and role in causing disease remain unknown. Based on studies with colonizing, non-toxigenic E. coli in piglets (19) and in human volunteers (20), we have recently demonstrated that the non-toxigenic, human colonizing E. coli strain 1392+ (CFA/II) but not the CFA/II negative derivative, colonizes the small intestine in large numbers and causes prolonged diarrhea in a rabbit model (17), establishing that colonization per se can cause prolonged small intestinal net secretion and diarrhea. We postulate that prolonged diarrhea is more common than generally recognized, has significant predisposing risk factors, and that combinations of specific infections (such as C. pylori gastritis with achlorhydria, and small bowel colonization with specific colonizing bacteria) derange small bowel electrolyte and nutrient absorption in susceptible hosts to cause prolonged diarrhea. Our overall objective is to determine the epidemiology, predisposing factors, etiologies, and pathogenesis of prolonged diarrhea in a highly endemic area, the tropical, developing Northeast of Brazil. We shall follow a cohort of infants born in an urban favela (slum) in Fortaleza, Ceara for frequency, risk factors, potential etiologies and the sequence of events leading to prolonged diarrhea (>14d). We shall conduct detailed fecal studies of 500 cases of all diarrhea and 100 cases of prolonged illness (to include 50 cases of sequential sampling of cases that become prolonged), then conduct intubation and balance studies of 50 children and 30 adults with prolonged diarrhea (>14, <30 days) and controls to examine potential etiologies (including quantitative cultures of adherent flora), host differences, and functional derangements. We shall determine the role and mechanisms by which colonizing Enterobacteriaciae either alone or in concert with other agents such as C. pylori or rotaviruses may contribute to prolonged intestinal dysfunction and malnourishing diarrhea. These studies will define potential risk factors and the sequence of events that lead to prolonged diarrhea, its etiologies and the key host factors and functional derangements that must be considered in controlling this important problem.

随着对急性腹泻的认识和控制的提高疾病，长期腹泻疾病，现在正在成为一种发病率和死亡率的主要原因。然而，长期腹泻的流行病学、病因和发病机制人们仍然知之甚少。多名调查人员已描述了患者小肠上部的细菌过度生长长期腹泻或营养不良；然而，他们的具体性质和引起疾病的作用仍不清楚。基于对仔猪中定植的非产毒大肠杆菌的研究 (19) 和我们最近在人类志愿者 (20) 中证明非产毒、人类定植大肠杆菌菌株 1392+ (CFA/II)，但不是 CFA/II 负衍生物，定植于小肠大量出现并导致兔子模型长期腹泻 (17)，确定定植本身会导致长期小肠净分泌和腹泻。我们假设长期腹泻比人们普遍认识的更为常见显着的诱发危险因素，以及这些因素的组合特定感染（例如幽门螺杆菌胃炎伴胃酸缺乏，以及特定定植细菌的小肠定植）扰乱小肠电解质和营养吸收易感宿主引起长期腹泻。我们的整体目的是确定流行病学、诱发因素、长期腹泻的病因和发病机制流行区，巴西东北部热带、发展中地区。我们将跟踪出生在城市贫民窟（贫民窟）的一群婴儿福塔莱萨、塞阿拉的频率、危险因素、潜在病因以及导致长期腹泻（>14天）的事件顺序。我们将对所有 500 例病例进行详细的粪便研究腹泻和长期患病100例（其中50例对延长的病例进行连续采样），然后对 50 名儿童和 30 名成人进行插管和平衡研究长期腹泻（>14 天，<30 天）和对照进行检查潜在的病因（包括粘附的定量培养菌群）、宿主差异和功能紊乱。我们将确定殖民化的作用和机制肠杆菌单独或与其他制剂一起使用例如幽门螺杆菌或轮状病毒可能会导致长期肠道功能障碍和营养不良性腹泻。这些研究将定义潜在的风险因素和事件的顺序导致长期腹泻的病因及关键宿主因素以及控制时必须考虑的功能紊乱这个重要的问题。