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Principal Investigator: STEPHAN K SCHWANDER
Organization: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
Fiscal Year: 2024
Award: $519,900
Funding agency: National Institute of Environmental Health Sciences
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.
Terms: <Address><Affect><Air Pollution><Airborne Particulate Matter><Area><Attention><Behavior><Biological><Blood Tests><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cessation of life><Characteristics><Chest><Clinical><Communities><Coughing><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Data><Death><Development><Diabetes Mellitus><Disease><Disease Frequency Surveys><Disorder><Electricity><Environment><Environmental Factor><Environmental Risk Factor><Exposure to><Frequencies><Funding><Gases><Grant><Health Inequity><Hematologic Tests><Hematological Tests><Hematology Testing><Home><Household><Household Air Pollution><Human><Immune><Immune response><Immunes><Immunological response><Impoverished><In Vitro><Incidence><Individual><Indoor Air Pollution><Industrialization><Inequalities in Health><Inequities in Health><Infection><Inflammatory Response><Inhalation Exposure><Intervention><Intervention Strategies><Knowledge><Lab Findings><Laboratory Finding><Life><Linear Models><Lung TB><Lung Tuberculosis><M tb><M tuberculosis><M tuberculosis infection><M. tb><M. tb infection><M. tuberculosis><M. tuberculosis infection><M.tb infection><M.tuberculosis infection><MTB infection><Macrophage><Measures><Modern Man><Monitor><Mycobacterium tuberculosis><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis infection><Mφ><NIEHS><National Institute of Environmental Health Sciences><PM2.5><Particulate Matter><Passive Smoking><Pathway interactions><Pattern><Persons><Pollution><Population><Poverty><Predisposition><Prevention><Public Health><Pulmonary TB><Pulmonary Tuberculosis><Questionnaires><Random Allocation><Random Selection><Regulation><Research><Research Design><Risk><Risk Factors><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Side><Slum><Smoking><Source><Sputum><Structure><Study Type><Susceptibility><TB infection><Testing><Thorace><Thoracic><Thorax><Time><Transmission><Transportation><Tuberculin Test><Tuberculosis><Uganda><Urban Health><Urban Population><Urbanization><air monitoring><airborne particulate><airway aerosol><ambient air pollution><anti-microbial><antimicrobial><biologic><case finding><cohort><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><design><designing><developmental><diabetes><disseminated TB><disseminated tuberculosis><environmental justice><environmental risk><experiment><experimental research><experimental study><experiments><face mask><fine particles><fine particulate matter><health inequalities><homes><host response><immune system response><immunoresponse><improved><indexing><indoor air contamination><infection due to Mycobacterium tuberculosis><interventional strategy><involuntary smoking><marginalization><mtb><novel><outdoor air pollution><pandemic><pandemic disease><pathway><recruit><residential air pollution><respiratory aerosol><second hand smoking><secondhand smoking><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><social role><solid fuel><study design><transmission process><tuberculin skin test><tuberculosis infection><tuberculous spondyloarthropathy><urban area><urban group><urban individual><urban location><urban people><urban region><vulnerable community>