TB Comorbidities
Improving Childhood Tuberculosis Treatment Outcomes and Post-TB Lung Functioning and Quality of Life in Rural South Africa
- Investigator: Meredith Brooks
- Funding Source: Charles H. Hood Foundation
We will assess the TB care cascade in cihldren, expanding it to include a child-specific definition of post-TB lung disease (PTLD), among children in a high TB/HIV burden setting in Eastern Cape South Africa, and identify risk-factors for completing each step of the newly expanded TB care cascade. Additionally, we will collect rich data regarding nutritional status, air pollutant exposure, lung capacity, and quality of life to estimate their effect on TB disease and PTLD in children.
- Investigator: Pranay Singha
- Funding Source: NIH Fogarty International Center
- Investigator: Alana Brennan
- Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases
Evidence is needed on the growing epidemic of type 2 diabetes mellitus, gaps in the diabetes cascade-of-care and the impact of care and treatment on diabetes outcomes in HIV-positive and HIV-negative patients with diabetes in low- and middle-income countries. This research uses a probabilistic record linking algorithm to transform laboratory measurements used for monitoring and diagnosing diabetes (blood glucose and hemoglobin A1c) from South Africa’s National Health Laboratory Services database into a national prospective cohort of patients being screened for the condition and links to an existing national HIV cohort. The findings of this research will provide the necessary evidence for South Africa to understand the burden of the diabetes epidemic and begin to build effective policies, programs and interventions to improve management and clinical outcomes of patients in care and on treatment for diabetes.
Multiomic Signatures of Lung Injury in Tuberculosis
- Investigator: Akshay Gupte
- Funding Source: University of Pennsylvania Center for AIDS Research
Pulmonary tuberculosis (PTB) is associated with lung injury which can persist despite successful therapy. Lung sequelae of treated PTB are increasingly recognized as an independent risk factor for chronic obstructive pulmonary disease (COPD) and, an important contributor of excess morbidity and mortality. Furthermore, PTB is characterized by granuloma formation, necrosis, and cavitation in the lung tissue which can impair drug penetration in affected lung tissue leading to persistent foci of bacterial replication, drug resistance and poor treatment outcomes. The overall goal of this study is to explore host metabolomic and genetic signatures associated with lung injury in PTB patients with and without diabetes and HIV.
Phenotype, Progression and Immune Correlates of Post-Tuberculosis Lung Disease
- Investigator: Akshay Gupte
- Funding Source: National Institute of Allergy and Infectious Diseases
Pulmonary tuberculosis (PTB) is associated with lung injury which can persist despite successful therapy. Lung sequelae of treated PTB are increasingly recognized as an independent risk factor for chronic obstructive pulmonary disease (COPD) and, an important contributor of excess morbidity and mortality. This project aims to: 1) characterize the early natural history of post-TB lung disease (PTLD) and provide rationale for long-term monitoring and bronchodilator therapy in affected cases, 2) characterize the functional and morphological phenotype of PTLD by serial pulmonary function testing and multi-detector computed tomography, 3) identify immune profiles measured during early, late and post-therapy associated with PTLD.
Point-of-care Questionnaire and mHealth Assisted Diagnosis of Post-TB Lung Disease
- Investigator: Akshay Gupte
- Funding Source: National Institutes of Health
Pulmonary tuberculosis (PTB) is associated with lung injury which can persist despite successful therapy. Lung sequelae of treated PTB are increasingly recognized as an independent risk factor for chronic obstructive pulmonary disease (COPD) and, an important contributor of excess morbidity and mortality. Spirometry is the gold standard for diagnosing lung function defects, however it is technically challenging and expensive to perform, and may not be available at the point-of-care in many TB-endemic settings. The overall goal of this project is to develop and validate a questionnaire-based screening algorithm, assisted by machine learning analysis of cough sounds and lung auscultation data, to identify individuals with a high probability of having Post-TB Lung Disease for referral and confirmatory testing.
Providence/Boston Center for AIDS Research (CFAR): HIV-TB SWG
- Investigator: Karen Jacobson
- Funding Source: National Institute of Allergy and Infectious Diseases
RePORT-India Lung Health Study
- Investigator: Akshay Gupte
- Funding Source: CRDF Global
Pulmonary tuberculosis (PTB) is the most common form of TB disease and is characterized by granuloma formation, necrosis, and cavitation in the lung tissue. This lung injury in PTB may affect tuberculosis treatment outcomes. Granulomatous lesions, fibrosis, and cavitation impair drug penetration in affected lung tissue and may lead to persistent foci of bacterial replication and drug resistance. The overall goal of this project is to identify clinical and imaging markers of lung injury that are associated with unfavorable treatment outcomes in PTB.
The Impact of Alcohol Consumption on TB Treatment Outcomes
- Investigator: Karen Jacobson
- Funding Source: National Institute of Allergy and Infectious Diseases
- Investigator: Kaku So-Armah
- Funding Source: National Institute on Alcohol Abuse and Alcoholism
Tuberculosis (TB) is the leading cause of death from a single infectious agent and the leading cause of death in people with HIV (PWH). An estimated 8.5 million people with TB are cured every year but many do not return to full health. Up to half of those completing treatment for pulmonary TB have post-TB lung disease, a disabling under-diagnosed group of lung deficits. Alcohol and HIV are associated with lung immune dysfunction and alcohol use is associated with delayed TB diagnosis, increasing the risk of lung injury during active TB disease. However, it is not known whether alcohol use is associated with post-TB lung disease in PWH. We hypothesize that hazardous drinking increases susceptibility to and worsens post-TB lung disease in PWH. Our objective is to investigate hazardous drinking as a modifiable risk factor for post-TB lung disease in PWH. To achieve this, we propose an 18-month observational study of 200 PWH completing pulmonary TB treatment in Mbarara, Uganda. Our primary aim (Aim 1a) is to determine the relationship between past-year hazardous drinking and post-TB lung disease. In Aim 1b we assess the association of past-month heavy drinking and post-TB lung disease progression over time. In Aim 1c we explore whether smoking modifies the association of past- month heavy drinking and post-TB lung disease progression over time. In Aim 2, we will qualitatively evaluate factors that can improve tailoring of pharmaco-behavioral alcohol and smoking interventions in PWH receiving TB treatment. We will conduct in-depth interviews with 24 PWH during or after TB treatment and 12 TB healthcare providers. Our quantitative and qualitative data will lay the foundation for future work to tailor alcohol and smoking interventions to improve long-term health in HIV/TB co-infection.
Tuberculosis—Learning the Effect of Parasites and Reinforcing Diets (TB-LEOPARD)
- Investigator: Pranay Sinha
- Funding Source: Burroughs Wellcome Fund
Tuberculosis—Learning the Impact of Nutrition (TB LION)
- Investigator: Pranay Sinha
- Funding Source: Warren Alpert Foundation
Understanding HIV’s Impact on RR/MDR-TB Development and Transmission Through Genomics
- Investigator: Tara Bouton
- Funding Source: National Institute of Allergy and Infectious Diseases