TuberculosisTHWART-TBNCT06221488
Testing Health Workers At Risk to Advance Our Understanding of TB Infection
An observational study of Tuberculosis and Tuberculosis Infection, run by Beth Israel Deaconess Medical Center at 1 site in South Africa.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Tuberculosis, Tuberculosis Infection
- What is being tested?
- TB infection testing
- How many people
- 300 participants
- Where
- 1 siteSouth Africa
- Study dates
- 15 Jan 2024to 31 Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population will be health workers (primarily clinical but may include support staff) who are >18 years of age.
Who may be able to join
- ≥18 years old
- Health worker
- Able to provide informed consent
Who cannot join
- Prior history of TB or known prior positive IGRA
- Current or prior history of taking anti-TB treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa1 site, 1 recruiting
- Recruiting
Stellenbosch University
Cape Town
Grant Theron, PhD, +27 21 9389693, gtheron@sun.ac.za
Ananja Van der Westhuizen, +27 76 173 7478, ananjavdw@gmail.com
About this study
Official title: THWART-TB: Testing Health Workers At Risk to Advance Our Understanding of TB Infection
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.
Read the detailed description
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.
- Conditions
- Tuberculosis, Tuberculosis Infection
- Being tested
- TB infection testing
- Keywords
- Tuberculosis, TB, TB infection, Health worker
- Medical subject headings
- Tuberculosis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TB infection testingDiagnostic test
Diagnostic testing with existing and novel tests to evaluate for TB infection and disease
| Study group | Role | What they receive |
|---|---|---|
| Health workers | Health workers with baseline negative interferon gamma release assays Receives: Diagnostic Test: TB infection testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interferon gamma release assay conversion
IGRA conversion using Quantiferon-Plus
Measured: Tested at months 0, 3, 6, 9, 12, 24
Secondary outcomes (1)
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.
Measured: Assessed at months 0, 3, 6, 9, 12, 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2024
- Study start15 Jan 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Stellenbosch
- Responsible party
- Principal investigator, Ruvandhi Nathavitharana, Beth Israel Deaconess Medical Center
- Investigators
- Ruvandhi Nathavitharana, MBBS MPH, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06221488
- Sponsor's protocol ID
- DP2AI176896
- Acronym
- THWART-TB
- Status last verified
- Jul 2026
- First submitted
- 15 Jan 2024
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nathavitharana RR, Mishra H, Sullivan A, Hurwitz S, Lederer P, Meintjes J, Nardell E, Theron G. Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers. Clin Infect Dis. 2022 Oct 12;75(8):1297-1306. doi: 10.1093/cid/ciac183.
PubMed 35348657
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- THWART-TB: Testing Health Workers At Risk to Advance Our Understanding of TB Infection
- ClinicalTrials.gov ID
- NCT06221488
- Acronym / sponsor ID
- THWART-TB / DP2AI176896
- Conditions
- Tuberculosis, Tuberculosis Infection
- Keywords
- Tuberculosis, TB, TB infection, Health worker
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- University of Stellenbosch
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 24 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Health workers | – | Diagnostic Test: TB infection testingHealth workers with baseline negative interferon gamma release assays |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will be health workers (primarily clinical but may include support staff) who are >18 years of age.
Key inclusion criteria (3 listed)
- ≥18 years old
- Health worker
- Able to provide informed consent
Key exclusion criteria (2 listed)
- Prior history of TB or known prior positive IGRA
- Current or prior history of taking anti-TB treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TB infection testingDiagnostic testing with existing and novel tests to evaluate for TB infection and disease | Diagnostic test | Health workers |
Primary outcome
Interferon gamma release assay conversion
Time frame: Tested at months 0, 3, 6, 9, 12, 24
IGRA conversion using Quantiferon-Plus
1 secondary outcome
TB disease
Time frame: Assessed at months 0, 3, 6, 9, 12, 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Background: PubMed 35348657Nathavitharana RR, Mishra H, Sullivan A, Hurwitz S, Lederer P, Meintjes J, Nardell E, Theron G. Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers. Clin Infect Dis. 2022 Oct 12;75(8):1297-1306. doi: 10.1093/cid/ciac183.
- Individual participant dataSharing planned: Undecided
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ruvandhi Nathavitharana, MBBS MPH principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Tuberculosis Infection, run by Beth Israel Deaconess Medical Center at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruvandhi Nathavitharana, MBBS MPH (+16467152601, rnathavi@bidmc.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interferon gamma release assay conversion (time frame: Tested at months 0, 3, 6, 9, 12, 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06221488, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.