TB Transmission Research – Uganda

Tuberculosis (TB) is a leading cause of death in HIV-infected persons in sub-Saharan Africa. Incomplete understanding of TB transmission dynamics in rural Africa and in settings with generalized HIV epidemics represents a major gap in knowledge and a significant obstacle to disrupting TB transmission.

Molecular Epidemiology and Geospatial Analysis of TB Transmission in Uganda (TRAP)

Principal Investigators: Gabe Chamie, UCSF and Moses Kamya, MU

Investigators: Diane Havlir, UCSF; Edwin Charlebois, UCSF; Phil Hopewell, UCSF; Bonnie Wandera, MU; Midori Kato-Maeda, UCSF

Coordinator: Olive Muggaga

Location Tororo

Funded By: National Institute of Health

This NIH-funded study seeks to characterize recent TB transmission networks, identify sites of ongoing TB transmission using molecular epidemiology, geographic information system (GIS) and social network analysis, and improve our understanding of how HIV influences TB transmission in rural East Africa. The objectives of the study, which began enrolling in 2012, are as follows:

Aim 1: Identify and characterize recent TB transmission networks in an East African rural setting. We are performing molecular epidemiologic analysis of all diagnosed, culture-positive TB cases initiating TB therapy in Tororo Municipality over 3 years in order to identify recent TB transmission networks defined by genotypic clustering of TB isolates.

Aim 2: Locate sites of frequent TB transmission through analysis of the geographic distribution and social networks of genotype-clustered incident TB cases. We will combine molecular epidemiologic, geospatial and social network data to identify TB transmission "hot spots", characterized by high levels of TB transmission. These "hot spots" may occur in commercial, social (e.g. markets, bars, churches), or health care settings. We will investigate how HIV influences where TB is transmitted at a community level.

Aim 3: Pilot test a place-based intensified TB case-finding strategy at two identified locations of high TB transmission risk.

This project will advance our understanding of how TB is spreading through a rural community with a generalized HIV epidemic in East Africa and serve as the foundation for developing novel ways to disrupt TB transmission and reduce TB mortality through early diagnosis and intensified case finding.

The Impact of Household Ventilation on Transmission of Tuberculosis Among Household Contacts of Active Tuberculosis Patients in Uganda (FreshAir)

Principal Investigators: Edwin Charlebois, UCSF; Gabriel Chamie, UCSF, and Roy Mugerwa, MU

Investigators: Diane Havlir, UCSF; Bonnie Wandera, MU; Annie Luetkemeyer, UCSF

Coordinator: Olive Muggaga

Location Kampala and Tororo

Funded By: UCSF-CFAR

This study’s objective is to better understand determinants of household transmission of TB in both urban (Kampala) and rural (Tororo) Uganda. The specific aims of the study are:

Aim 1: Describe the determinants of ventilation in homes of TB index patients in Uganda with a standardized household survey tool.

Aim 2: Correlate the determinants of ventilation to quantitative measures of household air exchange rate (AER) using an innovative carbon dioxide (CO2) tracer decay technique.

Aim 3: Compare air exchange rates in homes with and without demonstrated TB transmission to determine the impact of ventilation on household TB transmission.

Mycobacterium Tuberculosis Acquisition in Early Childhood in Uganda: The Influence of HIV-exposure and Malnutrition (LBTI)

Principal Investigators: Moses Kamya, Diane Havlir

Co-PI: Carina Marquez

Co-Investigators: Jane Achan, Edwin Charlebois, Gabriel Chamie, Annie Luetkemeyer

Coordinators: Mary Kyohere

Location Tororo

The primary aim of this study is to characterize TB acquisition and to assess the influence of HIV-exposure on latent TB infection (LTBI) in a birth cohort of HIV-exposed and un-exposed children under the age of 5 in Tororo, Uganda. We will test the hypotheses that (1) there is a significant increase in prevalence of LTBI across the 0-5 year age strata and (2) HIV-exposed, un-infected children have a higher prevalence of LTBI relative to HIV-unexposed children. We will also investigate the influence of nutritional status, socioeconomic status, and maternal LTBI on the childhood LTBI and interactions with HIV exposure. To measure LTBI we will use the tuberculin skin test and the Interferon Gamma Release Assay, and analyze concordance between the two tests.