The African continent is emblematic of tuberculosis as a global health emergency with little known about the long-term sequelae. There is cumulative evidence for prolonged pulmonary morbidity and loss of longevity in former TB patients, which is caused by post-TB lung disease (PTLD), the result of the interplay between the infective agent and the host immune response. It is likely that TB patients from resource-constrained settings, who usually present with more extensive TB disease and are exposed to multiple co-risk factors of lung health, are left with substantial and chronic post-TB lung impairment.

TB Sequel Project consists of two phases: 2017-2022 and 2023-2027. The core of the project is a cohort of TB patients and survivors followed up from diagnosis to up to 8-10 years.

Phase one (TB Sequel I)
Since its inception, the TB Sequel Network has worked to advance knowledge and foster collaboration on PTLD, a problem faced by more than half of TB patients despite microbiologic cure. During the first funding period, the TB Sequel Network performed cutting edge research to address this problem. The TB Sequel cohort of 1560 newly diagnosed TB patients was worldwide the first prospective research project of this size and length, thereby creating a uniquely relevant scientific platform to comprehensively explore the development of pulmonary TB sequelae (now called PTLD), its clinical phenotypes and underlying risk factors. Further, TB Sequel investigators studied the role of specific inflammatory pathways and oxidative stress in PTLD pathogenesis; this work served as the immediate basis for currently ongoing marker analyses and the development of new therapeutic concepts. The TB Sequel research data contributed to several conference abstracts and the resulting manuscripts are expected to lead to an increase of relevant publications in this field in the coming 1-2 years. TB Sequel investigators co-organized the “1st International Post-Tuberculosis Symposium” and were lead authors of multiple publications summarizing PTLD epidemiology and developing standards for diagnosis and clinical management.

Phase two (TB Sequel II)
The proposed research activities will directly link with the existent research platform infrastructure at all partner sites and address new and eminent research questions. We will make use of the existent TB Sequel cohort to provide a unique prospective analysis of long-term PTLD-related morbidity burden and health outcomes for a time period of up to 8-10 years after TB treatment cessation. We will further expand on the findings of the established trials infrastructure within the network and perform host-directed therapy trials which go beyond prevention of PTLD and also addresses strategies of PTLD-treatment. Finally, we will together with National TB Programs (NTPs), local health/non-communicable diseases (NCDs) clinics and other health system stakeholders develop and implement first clinical activities towards a local pathway of care for PTLD. The newly collected clinical samples and data as well as the wealth of existing repositories from the first funding period will be the basis of a comprehensive host-pathogen research programme and several PTLD-related socio-economic impacts and costs-analyses. Both cross-sectional themes will, in addition to classical methods, deploy modelling and machine learning approaches to identify new markers and signatures which can support a future personalized therapy- and socio-economic intervention approach to patients with TB and/or PTLD.

The project is organized into 3 work packages: