Air Pollution Effects on Transmission of Mycobacterium tuberculosis in Urban Slum Community in Uganda

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Air pollution and tuberculosis (TB) represent two of the most devastating and life-threatening global public health problems. With hundreds of million persons living in urban slums worldwide, vulnerable, marginalized and hard- to-reach populations are most affected by indoor and outdoor air pollution and Mycobacterium tuberculosis (Mtb) transmission. This project explores if and how air pollution fine particulate matter (PM2.5) exposure increases the transmission of Mtb from TB index cases to their household contacts (HC) in a high TB incidence urban slum area (Namuwongo) in Kampala/Uganda. We have previously shown that air pollution PM2.5 exposures suppress essential, protective, Mtb-specific, human innate and adaptive host immune responses. A key unanswered question of great significance to global TB control efforts is whether air pollution exposure increases the risk for transmission of Mtb in vulnerable communities, both through increased infectiousness (of the TB index cases) and susceptibility to Mtb infection (of their contacts). We hypothesize that inhalational exposure to PM2.5 increases the infectiousness of TB index cases by increasing their source strength i.e. the Mtb content in their respiratory aerosols, and by triggering cough. We further hypothesize that PM2.5 exposure suppresses protective immune responses leading to increased susceptibility to Mtb infection in the HC of the TB index cases. Both would be expected to increase transmission of Mtb in the community. To address our hypotheses, we will evaluate (1) the source strength of TB index cases and new Mtb infection in their HC (Mtb transmission) (SA1), (2) personal air pollution (PM2.5) exposures (SA2) and (3) how personal air pollution (PM2.5) exposure is associated with PM load in airway macrophages, source strength, and Mtb transmission to HC (SA3). To assess the source strength of the TB index cases, we will quantify the Mtb load in their respiratory aerosols using a novel face mask sampling approach. We will also determine TB index case cough frequencies with the Leicester Cough Monitor, assess chest radiographs and time to culture positivity (MGIT culture). Transmission of Mtb from TB index cases to HC will be ascertained by tuberculin skin test and QFN-Plus blood test between weeks 0 and 8. All measures combined reflect infectiousness of TB index cases. Exposure to PM2.5 of TB index cases and a random sample of HC will be studied using multiple approaches: `gold standard' gravimetric (UPAS) and real- time air monitoring between weeks 0 and 8, assessment of PM load in airway macrophages obtained by sputum induction of TB index cases and in randomly selected as well as newly Mtb-infected HC, stationary household PM2.5 and outdoor PM2.5 monitoring, and household study with questionnaires. Associations between TB index case source strength, Mtb transmission and PM2.5 exposure will be sought using linear modeling, to identify both main effects and modifying factors. Deciphering environmental factors that contribute to transmission of Mtb in vulnerable urban populations will provide much needed data for mandated public health actions and improved TB control approaches worldwide.