Thursday, November 21, 2024
11/21/2024
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.
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