TuberculosisMICRO-LTBI_UGNCT06751706
Detection of Mycobacterium Tuberculosis in Blood of TB Patients and Their Contacts in Uganda
An observational study of Tuberculosis and Latent Tuberculosis, run by Queen Mary University of London at 1 site in Uganda.
Trial summary
Mycobacterium tuberculosis (Mtb) is a major human pathogen, responsible for an estimated 10.6 million cases of active tuberculosis (TB) and 1.6 million deaths in 2021. Most adult cases of active TB arise from progression of latent tuberculosis infection (LTBI), whose global prevalence is estimated at 23%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Latent Tuberculosis
- How many people
- 60 participants
- Where
- 1 siteUganda
- Study dates
- 30 Sep 2024to 30 Sep 2026
- How long will I take part?
- 1 Day
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * 20 index cases of pulmonary TB (Group A) * 20 recent household contacts of Group A index cases * 20 historical TB contacts who previously participated in a TB household contact study
Who may be able to join
- Able and willing to give written informed consent to participate
- Age ≥18 years
- New diagnosis of smear-positive or Xpert-confirmed pulmonary TB
- At least one asymptomatic adult household contact likely to fulfil TB contact eligibility criteria below
- Able and willing to give written informed consent to participate
- Age ≥18 years
Show all 10Show fewer
- Household contact with an index case of smear-positive pulmonary TB in Group A above.
- Able and willing to give written informed consent to participate
- Age ≥18 years
- Participant in previous TB household contact study
Who cannot join
- More than 7 days of anti-TB treatment taken
- Confirmed or suspected pregnancy (female participants)
- Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study.
- Recent TB contacts (Group B):
- Clinical or radiological features of active TB
- Current or previous anti-TB treatment
Show all 13Show fewer
- Confirmed or suspected pregnancy (female participants)
- Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study.
- Historical TB contacts (Group C):
- Clinical or radiological features of active TB
- Current or previous anti-TB treatment
- Confirmed or suspected pregnancy (female participants)
- Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda1 site
Infectious diseases institute, Makarere University
Kampala, P.O. Box 22418
About this study
Mycobacterium tuberculosis (Mtb) is a major human pathogen, responsible for an estimated 10.6 million cases of active tuberculosis (TB) and 1.6 million deaths in 2021. Most adult cases of active TB arise from progression of latent tuberculosis infection (LTBI), whose global prevalence is estimated at 23%. Preventive therapy (e.g. a 6-month course of the anti-TB drug isoniazid) is effective in reducing risk of progression from LTBI to active TB. Global roll-out of preventive therapy will be required to achieve the World Health Organization target of TB elimination by 2050, but this will only be cost-effective and implementable if targeted at the 10-20% of latently infected individuals who are at highest risk of disease progression.
There is currently no gold standard test for LTBI. Existing diagnostic - the tuberculin skin test (TST) and Interferon-γ Release Assays (IGRA) - diagnose Mtb infection by detecting memory T cell responses to Mtb antigens. Their value is limited by very low positive predictive value (PPV) for progression to active TB (1.5% for TST, 2.7% for IGRA), inability to detect antimicrobial resistance in latently infected individuals and lack of response to administration of preventive therapy. Development of a nucleic acid amplification test (NAAT) for LTBI could overcome these limitations by allowing targeting of preventive therapy at latently infected individuals with the highest risk of progression to active TB, with antimicrobial selection guided by genetic antimicrobial resistance profiling and capacity for test of cure on treatment completion.
Read the detailed description
For many years, development of such a test was not considered realistic due to the paucibacillary nature of LTBI and uncertainty regarding the cellular location of Mtb bacilli in LTBI. However, the investigators and others have recently reported that Mtb DNA can be detected in the peripheral blood of latently infected TB contacts in both high- and low-burden settings. In our studies, which utilized digital polymerase chain reaction (dPCR) to detect Mtb DNA in peripheral blood mononuclear cell (PBMC) subsets of TB contacts in Ethiopia, signal was detected more frequently in extracts of CD34+ PBMC (hematopoietic stem cells [HSC] and their progenitors) vs. CD34- PBMC, but it was not restricted to them. Administration of isoniazid preventive therapy (IPT) reduced the proportion of participants in whom Mtb DNA could be detected in PBMC, showing that this signal is dynamic and suggesting that presence of Mtb DNA may reflect presence of viable bacilli. The investigatorsalso sequenced Mtb DNA in PBMC extracts using targeted next-generation sequencing (tNGS) to reveal mutations that confer antimicrobial drug resistance.
These exciting results demonstrate the potential for development of a NAAT for detection and genomic drug-resistance testing of LTBI in peripheral blood. However, questions remain regarding whether detection of Mtb DNA in the blood of symptomatic individuals associates with the ability to visualize or culture bacilli in blood, which has been done in patients with active TB. Moreover, our existing method for detection of Mtb DNA in CD34+ PBMC using dPCR is not currently suitable for field use, as samples require lengthy laboratory processing. The GeneXpert platform, which can give results in less than 2 hours, has previously been used to detect Mtb DNA in whole blood of HIV-infected patients with active TB. Sensitivity of the Xpert® MTB/RIF Ultra assay (Xpert Ultra, which has a limit of detection [LOD] of 15.6 colony-forming units [CFU]/ml versus 112.6 CFU/ml for the original Xpert® MTB/RIF [assay) is sufficient to detect Mtb DNA in the range demonstrated in blood of latently infected TB contacts in Ethiopia and Uganda (20 to 1000 copies of rpoB in the majority of Mtb DNA-positive individuals). However, detection of Mtb in blood of latently infected individuals has not previously been attempted using this platform. Finally, the investigators wish to expand knowledge by comparing detection of Mtb DNA in recent vs. historical TB contacts, and by including patients with active TB as a positive control group.
The investigators therefore propose to conduct a study to compare the sensitivity of different methodologies for detection of Mtb and genomic drug resistance in peripheral blood of TB patients and recently vs. remotely exposed asymptomatic TB contacts in Kampala, Uganda.
Study objectives Primary objective
The primary objective of this study is to determine whether Mycobacterium tuberculosis (Mtb) can be detected in the blood of recent TB contacts, recruited in Kampala, Uganda, using any of the following methods:
- Digital PCR
- GeneXpert® MTB/RIF Ultra (Cepheid)
- Fluorescence microscopy
- Blood culture
- Targeted Next-Generation Sequencing
Secondary objectives
Secondary objectives of this study are:
- To determine whether Mtb persists in the blood of remotely exposed (historical) TB contacts, recruited in the same setting, and using the same methods.
- To determine whether Mtb can be detected in the blood of patients with newly-diagnosed active TB, recruited in the same setting, and using the same methods.
- To establish whether detection of Mtb in blood using the methods above associates with any of the following biomarkers of host immune response:
- QFT-Plus
- Blood RNA signatures for incipient tuberculosis
- Antibody profiles
- To determine whether Mtb strains isolated from the sputum/blood of index cases with pulmonary TB are genetically identical to those detected in the blood of their recent contacts.
Primary endpoint Proportion of TB patients and their contacts in whom Mtb DNA can be detected in peripheral blood using digital PCR.
Secondary endpoints
- Proportion of TB patients and their contacts in whom Mtb DNA can be detected in peripheral blood using the following methods:
- GeneXpert® MTB/RIF Ultra (Cepheid)
- Fluorescence microscopy
- Blood culture
- Targeted Next-Generation Sequencing
- Proportion of TB patients and their contacts with positive results for either of the following assays:
- QFT-Plus
- Blood RNA signatures for incipient tuberculosis
- Antibody profiles
- Genetic sequences of Mtb strains isolated from the sputum/blood of index cases with pulmonary TB and blood of these participants and their asymptomatic household contacts.
- Conditions
- Tuberculosis, Latent Tuberculosis
- Keywords
- Tuberculosis, Latent tuberculosis, TB, TB Infection, TB Biomarker, Blood test for TB
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Group A: TB patients | New diagnosis of smear-positive or Xpert-confirmed pulmonary TB | |
| Group B: Recent TB contacts | Household contact with an index case of smear-positive pulmonary TB recruited to Group A. | |
| Group C: Historical TB contacts | Participant in previous TB household contact study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mtb DNA prevalence
Prevalence of detectable Mtb in each group
Measured: 1 year
Secondary outcomes (3)
Mtb detection using alternative methods
Determine if Mtb can be detected in the blood of TB patients and their contacts, recruited in Kampala, Uganda, using any of the following methods:
- GeneXpert® MTB/RIF Ultra (Cepheid)
- Fluorescence microscopy
- Blood culture
- Targeted Next-Generation Sequencing
Measured: 1 year
Mtb DNA detection association with IGRA and RNA signatures for incipient TB
Mtb DNA detection in blood and association with any of the following biomarkers of host immune response:
- QFT-Plus
- Blood RNA signatures for incipient tuberculosis
Measured: 1 year
Strain correlation between index case and contact
To determine if Mtb strains isolated from the sputum of index cases with pulmonary TB are genetically identical to those detected in the blood of their contacts.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2024
- Study start30 Sep 2024
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 60 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University
- Responsible party
- Sponsor
- Investigators
- Adrian Martineau, PhD, Principal investigator, Queen Mary University London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06751706
- Sponsor's protocol ID
- IDI-REC-2023-80
- Acronym
- MICRO-LTBI_UG
- Status last verified
- Jul 2026
- First submitted
- 20 Dec 2024
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection of Mycobacterium Tuberculosis in Blood of TB Patients and Their Contacts in Uganda
- ClinicalTrials.gov ID
- NCT06751706
- Acronym / sponsor ID
- MICRO-LTBI_UG / IDI-REC-2023-80
- Conditions
- Tuberculosis, Latent Tuberculosis
- Keywords
- Tuberculosis, Latent tuberculosis, TB, TB Infection, TB Biomarker, Blood test for TB
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Makerere University
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 30 Dec 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.
Mycobacterium tuberculosis (Mtb) is a major human pathogen, responsible for an estimated 10.6 million cases of active tuberculosis (TB) and 1.6 million deaths in 2021. Most adult cases of active TB arise from progression of latent tuberculosis infection (LTBI), whose global prevalence is estimated at 23%. Preventive therapy (e.g. a 6-month course of the anti-TB drug isoniazid) is effective in reducing risk of progression from LTBI to active TB. Global roll-out of preventive therapy will be required to achieve the World Health Organization target of TB elimination by 2050, but this will only be cost-effective and implementable if targeted at the 10-20% of latently infected individuals who are at highest risk of disease progression.
There is currently no gold standard test for LTBI. Existing diagnostic - the tuberculin skin test (TST) and Interferon-γ Release Assays (IGRA) - diagnose Mtb infection by detecting memory T cell responses to Mtb antigens. Their value is limited by very low positive predictive value (PPV) for progression to active TB (1.5% for TST, 2.7% for IGRA), inability to detect antimicrobial resistance in latently infected individuals and lack of response to administration of preventive therapy. Development of a nucleic acid amplification test (NAAT) for LTBI could overcome these limitations by allowing targeting of preventive therapy at latently infected individuals with the highest risk of progression to active TB, with antimicrobial selection guided by genetic antimicrobial resistance profiling and capacity for test of cure on treatment completion.
Detailed description
For many years, development of such a test was not considered realistic due to the paucibacillary nature of LTBI and uncertainty regarding the cellular location of Mtb bacilli in LTBI. However, the investigators and others have recently reported that Mtb DNA can be detected in the peripheral blood of latently infected TB contacts in both high- and low-burden settings. In our studies, which utilized digital polymerase chain reaction (dPCR) to detect Mtb DNA in peripheral blood mononuclear cell (PBMC) subsets of TB contacts in Ethiopia, signal was detected more frequently in extracts of CD34+ PBMC (hematopoietic stem cells [HSC] and their progenitors) vs. CD34- PBMC, but it was not restricted to them. Administration of isoniazid preventive therapy (IPT) reduced the proportion of participants in whom Mtb DNA could be detected in PBMC, showing that this signal is dynamic and suggesting that presence of Mtb DNA may reflect presence of viable bacilli. The investigatorsalso sequenced Mtb DNA in PBMC extracts using targeted next-generation sequencing (tNGS) to reveal mutations that confer antimicrobial drug resistance.
These exciting results demonstrate the potential for development of a NAAT for detection and genomic drug-resistance testing of LTBI in peripheral blood. However, questions remain regarding whether detection of Mtb DNA in the blood of symptomatic individuals associates with the ability to visualize or culture bacilli in blood, which has been done in patients with active TB. Moreover, our existing method for detection of Mtb DNA in CD34+ PBMC using dPCR is not currently suitable for field use, as samples require lengthy laboratory processing. The GeneXpert platform, which can give results in less than 2 hours, has previously been used to detect Mtb DNA in whole blood of HIV-infected patients with active TB. Sensitivity of the Xpert® MTB/RIF Ultra assay (Xpert Ultra, which has a limit of detection [LOD] of 15.6 colony-forming units [CFU]/ml versus 112.6 CFU/ml for the original Xpert® MTB/RIF [assay) is sufficient to detect Mtb DNA in the range demonstrated in blood of latently infected TB contacts in Ethiopia and Uganda (20 to 1000 copies of rpoB in the majority of Mtb DNA-positive individuals). However, detection of Mtb in blood of latently infected individuals has not previously been attempted using this platform. Finally, the investigators wish to expand knowledge by comparing detection of Mtb DNA in recent vs. historical TB contacts, and by including patients with active TB as a positive control group.
The investigators therefore propose to conduct a study to compare the sensitivity of different methodologies for detection of Mtb and genomic drug resistance in peripheral blood of TB patients and recently vs. remotely exposed asymptomatic TB contacts in Kampala, Uganda.
Study objectives Primary objective
The primary objective of this study is to determine whether Mycobacterium tuberculosis (Mtb) can be detected in the blood of recent TB contacts, recruited in Kampala, Uganda, using any of the following methods:
- Digital PCR
- GeneXpert® MTB/RIF Ultra (Cepheid)
- Fluorescence microscopy
- Blood culture
- Targeted Next-Generation Sequencing
Secondary objectives
Secondary objectives of this study are:
- To determine whether Mtb persists in the blood of remotely exposed (historical) TB contacts, recruited in the same setting, and using the same methods.
- To determine whether Mtb can be detected in the blood of patients with newly-diagnosed active TB, recruited in the same setting, and using the same methods.
- To establish whether detection of Mtb in blood using the methods above associates with any of the following biomarkers of host immune response:
- QFT-Plus
- Blood RNA signatures for incipient tuberculosis
- Antibody profiles
- To determine whether Mtb strains isolated from the sputum/blood of index cases with pulmonary TB are genetically identical to those detected in the blood of their recent contacts.
Primary endpoint Proportion of TB patients and their contacts in whom Mtb DNA can be detected in peripheral blood using digital PCR.
Secondary endpoints
- Proportion of TB patients and their contacts in whom Mtb DNA can be detected in peripheral blood using the following methods:
- GeneXpert® MTB/RIF Ultra (Cepheid)
- Fluorescence microscopy
- Blood culture
- Targeted Next-Generation Sequencing
- Proportion of TB patients and their contacts with positive results for either of the following assays:
- QFT-Plus
- Blood RNA signatures for incipient tuberculosis
- Antibody profiles
- Genetic sequences of Mtb strains isolated from the sputum/blood of index cases with pulmonary TB and blood of these participants and their asymptomatic household contacts.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A: TB patients | – | –New diagnosis of smear-positive or Xpert-confirmed pulmonary TB |
| Group B: Recent TB contacts | – | –Household contact with an index case of smear-positive pulmonary TB recruited to Group A. |
| Group C: Historical TB contacts | – | –Participant in previous TB household contact study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * 20 index cases of pulmonary TB (Group A) * 20 recent household contacts of Group A index cases * 20 historical TB contacts who previously participated in a TB household contact study
Key inclusion criteria (10 listed)
- Able and willing to give written informed consent to participate
- Age ≥18 years
- New diagnosis of smear-positive or Xpert-confirmed pulmonary TB
- At least one asymptomatic adult household contact likely to fulfil TB contact eligibility criteria below
- Able and willing to give written informed consent to participate
Key exclusion criteria (13 listed)
- More than 7 days of anti-TB treatment taken
- Confirmed or suspected pregnancy (female participants)
- Existing medical condition which in the opinion of the investigator may adversely affect the participant's safety or ability to participate in the study.
- Clinical or radiological features of active TB
- Current or previous 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.
Primary outcome
Mtb DNA prevalence
Time frame: 1 year
Prevalence of detectable Mtb in each group
3 secondary outcomes
Mtb detection using alternative methods
Time frame: 1 year
Mtb DNA detection association with IGRA and RNA signatures for incipient TB
Time frame: 1 year
Strain correlation between index case and contact
Time frame: 1 year
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 2 Jul 2026.
- Individual participant dataSharing planned: Undecided
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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.
Adrian Martineau, PhD principal investigator
Queen Mary University London
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 Latent Tuberculosis, run by Queen Mary University of London at 1 site in Uganda.
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 10 inclusion and 13 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: enrolling by invitation, as of the sponsor's last update on 2 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 Uganda. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mtb DNA prevalence (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jul 2026.