Bacteremia in HIV-infected children under 5 years old hospitalized in Mozambique

描述（由申请人提供）：在撒哈拉以南非洲，每年有460万5岁以下儿童死亡。对疟疾、急性呼吸道感染（ARI）、腹泻和人类免疫缺陷病毒（HIV）等传染病的发病率进行了描述。关于大多数致病性细菌感染的发病率、死亡率或医院负担的现有估计主要局限于城市地区，因此U5菌血症的影响在很大程度上是未知的，因为大多数人生活在农村地区。早期研究表明，非洲住院儿童的菌血症超过高收入国家，革兰氏阴性菌，特别是非伤寒沙门氏菌（NTS）是最常见的分离物，特别是在艾滋病毒和疟疾流行率高的地方。据估计，侵袭性NTS疾病在非洲的发病率为每10万名3-5岁儿童175-388例。5岁以下儿童死亡率在地理区域之间存在重大差异，北部省份的死亡率分别最高。莫桑比克的城市/农村在保健结果方面也存在重大差异。据估计，2009年城市地区5岁以下儿童死亡率为135/1000活产，而农村地区为162/1000活产，农村地区儿童的三种主要杀手死亡频率更高。我们将在具有代表性的农村和城市环境中对感染hiv的5岁以下发热住院儿童进行一项前瞻性的基于医院的观察性研究，以确定培养证实菌血症的发病率、病因和抗生素敏感性模式。这项研究将在马普托市的马瓦拉内医院和莫桑比克赞比西亚省的克利马内省医院进行。我们的具体目标包括：1)检验农村地区（赞比西亚省）儿童因发烧住院的感染艾滋病毒的5岁以下儿童中菌血症的发生率高于城市地区（马普托市）儿童的假设；2)验证非伤寒沙门氏菌（NTS）是莫桑比克马普托城市和Zambezia省农村因发烧住院的艾滋病毒感染儿童U5菌血症的主要原因的假设。此外，我们将进一步对血液和粪便中的NTS样本进行遗传表征，以确定是否存在侵袭性ST313菌株。为了实现这些目标，我们组建了一支强大的多学科团队，代表爱德华多蒙德兰大学（UEM）和范德比尔特大学，并得到这两所主要机构强大的研究和服务基础设施的支持。我们的研究有望阐明农村/城市的健康差距，从而有针对性地加以缓解。该项目的结果还将提供目前无法获得的关键信息，以确定微生物学能力资源分配的优先次序，并指导国家药物处方实践。

DESCRIPTION (provided by applicant): Every year 4.6 million children <5 years of age (U5) die in sub-Saharan Africa. Incidence of disease for infections such as malaria, acute respiratory infection (ARI), diarrhea and human immunodeficiency virus (HIV) have been described. Existing estimates as to the incidence, mortality, or hospital burden of most pathogenic bacterial infections is predominantly limited to urban areas, thus the impact of U5 bacteremia is largely unknown as most people live in rural areas. Early studies suggest bacteremia in hospitalized African children exceeds that of high income countries and that gram-negative organisms, in particular non-typhoidal salmonella (NTS) are among the most common isolates, especially where the prevalence of HIV and malaria is high. The incidence of invasive NTS disease in Africa has been estimated at between 175-388 cases per 100,000 children aged 3-5 years. There are important differences by geographic region in U5 mortality, with the northern provinces having the highest rates respectively. Mozambique also has important urban/rural differences in health outcomes. U5 mortality in 2009 was estimated at 135/1000 live births in urban areas compared to 162/1000 live births in rural areas with higher frequency of death occurring in rural areas for each of the three main killers in children. We will conduct a prospective hospital-based observational study of HIV-infected children <5 years old, hospitalized with fever to determine the incidence, etiology, and antibiotic sensitivity patterns o culture confirmed bacteremia in representative rural and urban settings. The study will take place at Hospital Mavalane in Maputo city and the Quelimane Provincial Hospital in the Province of Zambezia, Mozambique. Our specific aims include: 1) To test the hypothesis that the incidence of bacteremia in HIV-infected children U5, hospitalized with fever is higher in children living in rural areas (Zambezia Province) compared with those living in urban areas (Maputo City); and 2) To test the hypothesis that non-typhoidal salmonella (NTS) is a major cause of bacteremia in HIV-infected children U5, hospitalized with fever in both urban Maputo City and rural Zambezia Province, Mozambique. Additionally, we will further genetically characterize NTS samples in blood and stool for the presence of the invasive ST313 strain. To accomplish these aims we have assembled a strong multidisciplinary team representing University Eduardo Mondlane (UEM) and Vanderbilt University and supported by the strong research and service infrastructures of these two major institutions. Our study holds promise to illuminate rural/urban health disparities that can then be targeted for mitigation. The results of this project will also provide crucial but currently unavailable information needed to prioritize resource allocation for microbiology capacity and guide national drug formulary practices.