Research Task 1: The TB-Cohort
Research Task 2: The Host
Research Task 3: The Pathogen
Research Task 4: Socio-economics
Research Task 5: Therapeutic Interventions

The core of the current project is a prospective cohort of up to 1600 patients across four countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB diagnosis, and followed up for at least 2 years. The overall goal of the cohort is to describe the evolution of pulmonary symptoms and functional lung impairment as well as risk factors (clinical, immunological, microbiological, etc.) contributing to the lung outcome.
The TB cohort facilitates the conduct of the other Research Tasks by providing the required data and samples. Data and information derived from the cohort will be analyzed and refurbished to inform a broader research community as well as local, national and supranational authorities about the relevant findings and new insights.

The majority of TB studies to date have focussed on diagnosis and treatment responses without considering the implications of sustained loss of lung function and subsequent long-term sequelae. The aims of this research task are to understand the pathophysiology and identify confounders for exacerbated lung damage leading to long-term clinical sequelae within the TB core cohorts and to define pre- or early-treatment biomarkers in blood/sputum that may predict treatment response and pulmonary outcome.
This state of the art project will bring together a leading team of researchers to elucidate inflammatory pathways that could be targeted for host-adjunctive therapies to potentially limit lung pathology and avoid long-term damage.

Host factors and environmental factors are widely accepted as major determinants driving the course of infection and outcome of treatment. The potential influence of pathogen diversity is less well understood. The overall objective of this research task is to describe the genetic characteristics, metabolic state, dynamic of bacterial load before and during treatment, and to assess the impact of these factors on transmission, treatment outcome and long term sequelae of TB disease, for all patients enrolled into the TB cohort.

There is growing consensus that progress in tuberculosis (TB) control in the low- and middle-income countries will require not only investment in strengthening diagnostics and treatment but also actions on the socio-economic determinants and consequences of TB, as well as measures to improve patients’ quality of life and well-being after suffering TB disease.
The published literature contains surprisingly little evidence about the costs to the health systems of treating TB and the impact of TB and TB treatment on patients’ quality of life, economic well-being, and productivity. The main goal of the Socio-Economic Research Task is to evaluate the health-related quality of life impacts of TB and TB treatment and assess the economic cost to patients and to the health system of pulmonary TB and the treatment in four countries in Africa. The information generated by the study will help policy makers budget for TB care and treatment and provide evidence for investment in new drug regimens, TB control, and household interventions.

Delayed eradication of infection and resolution of inflammation are common in tuberculosis despite eventual microbiologic cure. Prolonged and intense inflammation in the lung in TB results in depletion of glutathione (GSH), leaving the lung susceptible to damage by reactive oxygen species (ROS). This study will conduct a randomized, controlled phase 2 trial of adjunctive N-acetylcysteine (NAC) in TB patients.