MICRONUTRIENTS AND ENTERIC INFECTION IN AFRICAN CHILDREN

非洲儿童的微量营养素和肠道感染

• 批准号: 7113524
• 负责人: Sherwood Gorbach
• 金额: $ 28.69万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113524
• 关键词: Africa; African; Cryptosporidium; Cyclospora; HIV infections; ascorbate; child (0-11); clinical research; communicable disease transmission; cooperative study; cryptosporidiosis; diarrhea; diet therapy; dietary supplements; enteric bacteria; gastrointestinal infection; human subject; human therapy evaluation; nutrition related tag; nutritional epidemiology; opportunistic infections; parasite infection mechanism; pediatric AIDS; retinoids; rural area; selenium; tocopherols; zinc

Enteric infections remain a leading cause of childhood mortality in developing countries. In regions where HIV infection is prevalent, enteric infections and persistent diarrhea have even greater public health importance. Little is known, however, about the pattern of enteric infection in children in regions where HIV infection is common, and how infection is related to HIV activity as measured by plasma HIV RNA, or host immunocompetence, as determined by CD4 counts. Although micronutrient supplementation, including provision of vitamin A and zinc, are being promoted as effective means of reducing infectious diarrhea morbidity and prevalence, little is know about their efficacy in achieving these goals in African children, or in children who are HIV infected. This study had the following specific aims: 1) To determine the pathogen-specific pattern of enteric infections in HIV-infected and uninfected children living in rural South Africa, with a particular focus on infection with Cryptosporidium parvum and other protozoan pathogens. 2) To determine if infection with specific pathogens is associated with the development of persistent diarrhea lasting greater than 14 days; 3) To determine the efficacy of two micronutrient supplements; a) a mixture containing Vitamins A, C, E, and selenium; and b) the same micronutrient supplement with the addition of zinc, on the prevalent days of diarrhea in both HIV-infected and HIV- uninfected children.; 4) To determine if micronutrient supplementation improves gut integrity as measured by the mannitol-lactulose permeability test. 5) Based upon these findings to develop recommendations for use of micronutrient supplements in Africa and other regions with a high HIV- seroprevalence. To answer these questions we propose enrolling and studying three cohorts of children living in a rural region of South Africa over a three-year period; 1) 78 HIV-infected children; 2) 120 HIV-uninfected children born to HIV-infected mothers; 3) 120 HIV-uninfected children born to mothers without HIV infection. Children will be ascertained at three months of age and followed until age 2 years. Micronutrient supplementation will be given from enrollment until age 12 months. Children will be visited weekly by field staff, and diarrhea and other morbidity recorded. Stool for detection of enteric pathogens, including Salmonella, Shigella, Campylobacter, diarrheagenic E. coli (determined using probes for virulence genes), rotavirus, enteric adenoviruses 40/41, astroviruses and Norwalk virus, and the protozoan pathogens C. parvum (including genotyping of strains), Cyclospora cayetanensis, and Enterocytozoon bieneusi will be obtained from children when they have diarrhea, and from a subset of well children. Anthropometry will be measured regularly, and bioimpedance will be performed to determine body composition. A non-invasive test of gut permeability (the lactulose-mannitol test) will be performed on all children while they are receiving micronutrient supplementation. The study sample size is calculated to allow a determination of a 20 percent difference in prevalent days of diarrhea between the placebo treated group and the two micronutrient supplemented groups. This study will also allow us to determine risk factors for persistent diarrhea, and to develop algorithms for the management of infectious diarrhea in a region where HIV infection is common.

肠道感染仍然是发展中国家儿童死亡的主要原因。 在艾滋病毒感染流行的地区，肠道感染和持续性腹泻对公共卫生的重要性更大。 然而，人们对 HIV 感染常见地区儿童肠道感染的模式以及感染与 HIV 活性（通过血浆 HIV RNA 测量）或宿主免疫能力（通过 CD4 计数确定）之间的关系知之甚少。 尽管微量营养素补充剂（包括提供维生素 A 和锌）被宣传为降低感染性腹泻发病率和患病率的有效手段，但人们对其在非洲儿童或感染艾滋病毒的儿童中实现这些目标的功效知之甚少。 本研究有以下具体目的：1）确定生活在南非农村地区的艾滋病毒感染和未感染儿童肠道感染的病原体特异性模式，特别关注小隐孢子虫和其他原生动物病原体的感染。 2) 确定特定病原体的感染是否与持续超过 14 天的持续性腹泻的发生有关； 3) 确定两种微量营养素补充剂的功效； a) 含有维生素 A、C、E 和硒的混合物； b) 在艾滋病毒感染者和未感染艾滋病毒儿童腹泻流行的日子里，补充相同的微量营养素并添加锌。 4) 通过甘露醇-乳果糖渗透性测试来确定微量营养素补充剂是否可以改善肠道完整性。 5) 根据这些发现，制定在非洲和其他艾滋病毒血清流行率高的地区使用微量营养素补充剂的建议。 为了回答这些问题，我们建议在三年内招募和研究三组生活在南非农村地区的儿童； 1）78名艾滋病毒感染儿童； 2) 感染艾滋病毒的母亲所生的 120 名未感染艾滋病毒的儿童； 3) 未感染艾滋病毒的母亲所生的 120 名未感染艾滋病毒的儿童。 儿童将在三个月大时进行确定，并进行随访直至 2 岁。 从入学起至 12 个月大时将补充微量营养素。现场工作人员每周都会拜访儿童，并记录腹泻和其他发病情况。 用于检测肠道病原体的粪便，包括沙门氏菌、志贺氏菌、弯曲杆菌、致泻性大肠杆菌（使用毒力基因探针测定）、轮状病毒、肠道腺病毒 40/41、星状病毒和诺瓦克病毒以及原生动物病原体微小棒状杆菌（包括基因分型）菌株）、Cyclospora cayetanensis 和 Enterocytozoon bieneusi 将是从腹泻儿童和健康儿童的子集获得。 将定期进行人体测量，并进行生物阻抗以确定身体成分。 所有接受微量营养素补充剂的儿童都将进行非侵入性肠道通透性测试（乳果糖-甘露醇测试）。 研究样本量经过计算，可以确定安慰剂治疗组和两个微量营养素补充组之间腹泻流行天数有 20% 的差异。 这项研究还将使我们能够确定持续性腹泻的危险因素，并开发在艾滋病毒感染常见的地区管理感染性腹泻的算法。