An observational study in Tuberculosis and Tuberculosis Infection, sponsored by Beth Israel Deaconess Medical Center. Recruiting at 1 site in South Africa. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Beth Israel Deaconess Medical Center · Observational
It has been estimated that 1.7 billion people have tuberculosis (TB) infection; yet current tests are unable to predict which people are at highest risk of developing TB disease, which can be life-threatening. THWART-TB is a prospective longitudinal cohort study of health workers (HWs) in Cape Town, South Africa, where our preliminary data reveals HWs have a high annual TB infection risk (34%). This cohort, who will undergo frequent serial evaluation (every 3 months) with a combination of novel assays never previously evaluated together, presents a unique opportunity to evaluate immune responses at the time of initial infection and to characterize the dynamic profile of these immune responses over time in a high-risk population. The knowledge generated will improve our understanding of TB infection and help to identify which people exposed to TB may remain at risk, enabling us to better target preventive strategies.
Tuberculosis (TB) remains a leading infectious cause of death in South Africa and globally.1.7 billion people worldwide are estimated to have been infected with TB (LTBI). However, current LTBI tests cannot distinguish between current infection versus a persistent immune response to a cleared infection and have a low predictive value to identify which people are at future risk of developing active TB disease. Moreover, LTBI following exposure to Mycobacterium tuberculosis (Mtb) is not a steady state process. The dynamic host-pathogen interactions that lead to bacterial clearance, suppression, or disease are not understood. The investigators propose to establish a prospective longitudinal cohort study of health workers (HWs) in Cape Town, South Africa, where previous data demonstrated HWs have a high annual TB infection risk (34%). Our fundamentally innovative approach will characterize early TB infection using serial testing every 3 months for one year with a combination of established and novel assays never previously evaluated together. This presents a unique opportunity to evaluate host and pathogen responses at the time of initial infection and to characterize the dynamic profile of these responses over time in a high-risk population, establishing a longitudinal platform for future studies, including through biobanked specimens. This study will generate critical data of local relevance given the devastating ongoing impact of TB in South Africa.
The investigators hypothesize that Mtb persistence or clearance in the first year after incident infection (determined by follow up interferon gamma release assay (IGRA) after a new IGRA conversion) correlates with dynamic changes in host blood transcriptional markers of incipient and active TB, Mtb antibody responses and Mtb DNA detection.
Aim 1: To evaluate the temporal dynamics of established and novel interferon-gamma based tests for latent TB infection. The investigators hypothesize high-frequency serial IGRA testing will enable us to identify how often sustained conversions and reversions occur after early TB infection (based on initial IGRA conversion) over 1 year follow up. The investigators will compare the performance of established and novel IGRAs and new LTBI tests.
Aim 2: To evaluate the temporal dynamics of host responses to TB based on RNA biosignatures and Mtb antibodies. The investigators hypothesize that sustained IGRA conversion may predict seroconversion and a contemporary rise in host-response blood transcriptional biomarkers of TB and will evaluate how these profiles change over time
Aim 3: To evaluate the temporal dynamics of novel assays to detect pathogen-directed Mtb DNA markers of early infection. The investigators hypothesize IGRA conversion, seroconversion, or rise in host-response blood transcriptional biomarkers of TB will predict detection of Mtb DNA using a range of novel assays to identify a pathogen-derived marker of early infection that is complementary to evaluation of the host immune response.
The investigators will conduct a prospective cohort study recruiting HWs at Tygerberg Hospital in Cape Town, where our prior study demonstrated the feasibility of recruiting this population. The investigators will recruit equal numbers of men and women and ensure participant diversity reflective of the South African population. The investigators will conduct serial testing every 3 months (based on a systematic review suggesting this testing interval may be optimal while being pragmatically feasible) with a combination of established and novel assays chosen to evaluate host and pathogen-derived signatures never evaluated before in parallel to identify correlates of risk and protection: IGRAs, novel LTBI tests, blood RNA biosignatures, Mtb-specific antibody responses and Mtb DNA detection assays. HWs are a unique population to understand serial host and pathogen dynamics including whether tests revert to negative i.e. whether initial IGRA conversions are transient versus persistent, and whether re-conversions may potentially represent reinfection given high exposure risk.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 300 is above the median of 253 across 317 observational studies indexed under Tuberculosis.
Browse Tuberculosis studies →Beth Israel Deaconess Medical Center is the lead sponsor of 568 studies on the registry; 80 are open to participants now.
Of its 76 completed or terminated interventional studies of FDA-regulated products, 62 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
The study population will be health workers (primarily clinical but may include support staff) who are >18 years of age.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Health workers with baseline negative interferon gamma release assays
Diagnostic Test: TB infection testing
Diagnostic testing with existing and novel tests to evaluate for TB infection and disease
Interferon gamma release assay conversion
IGRA conversion using Quantiferon-Plus
Time frame: Tested at months 0, 3, 6, 9, 12, 24
TB disease
Development of active TB disease, defined by positive Xpert Ultra or defined clinically based on clinician starting treatment for active TB disease with combination of suggestive symptoms and/or abnormalities on chest x-ray in the absence of bacteriological confirmation.
Time frame: Assessed at months 0, 3, 6, 9, 12, 24
Plan to share: Undecided
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Beth Israel Deaconess Medical Center →