Evaluation of a Novel Microbiological Diagnostic Test for Latent Mycobacterium Tuberculosis Infection
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Enrollment
- 250
- Locations
- 1
- Primary Endpoint
- Prevalence of Mtb DNA in blood
Study Overview
Brief Summary
Tuberculosis (TB) is an infectious disease that is caused by bacteria (bugs). The infection is passed on when a patient with active lung TB coughs bugs into the air, which are then breathed in by an uninfected person. In 90% of people who get infected, the TB infection remains dormant and the person never falls ill with active TB disease. However, 10% of people with dormant TB infection will eventually go on to develop active TB disease at some time in the future, with symptoms such as cough and weight loss. Dormant TB infection can be treated with a 3-month course of antibiotics, which prevent the infection from becoming active and causing problems in the future. However, existing tests for dormant TB rely on detecting the body's immune response to infection, rather than detecting the TB bugs themselves. Because the immune response doesn't go away when dormant TB is treated, existing tests for dormant TB do not change from positive to negative after antibiotic treatment.
Thus, clinicians can't know if antibiotic treatment of dormant TB infection was successful or not.
Moreover, existing tests can't distinguish the 90% of people with dormant TB infection who will never develop active TB (and who don't need antibiotics) from the 10% who will go on to fall ill with active TB at some point in the future (who do need antibiotics). So the investigators end up giving antibiotics to many more people than we need to. Recently, a group of scientists in Germany have developed a sensitive new blood test that was able to detect very small numbers of TB bugs in the blood of just seven people with dormant TB infection. This finding has created a lot of excitement in the TB field, as nobody has been able to find TB bugs in people with dormant infection before. Our research study will evaluate this new blood test in a larger group of 100 people, with and without dormant TB infection, to see if the findings from Germany are really true. If they are, then this could lead to the development of a more accurate test for dormant TB infection in the future.
Detailed Description
Objectives:
i) To determine whether M. tuberculosis (Mtb) DNA can be detected in CD34+ peripheral blood mononuclear cells (PBMC) isolated from
- asymptomatic adults being screened for LTBI (LTBI screenees)
- adults with newly-diagnosed active tuberculosis (active cases) ii) To determine whether strains of Mtb isolated from CD34+ PBMC of recent household TB contacts are genetically identical to those isolated from the sputum of index cases with pulmonary TB to whom they have been exposed iii) To characterise immunological, clinical and epidemiological correlates of ability to detect Mtb in CD34+ PBMC in a heterogeneous population of IGRA-positive and -negative LTBI screenees.
iv) To determine whether presence of Mtb DNA in CD34+ PBMC of IGRA-positive LTBI screenees associates with the presence of a peripheral blood transcriptional signature recently reported to predict risk of progression to active TB v) To assess longitudinal change in CD34+ PCR assay results in
- LTBI screenees completing chemoprophylaxis for LTBI
Study Design
- Study Type
- Observational
- Observational Model
- Other
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •i) For LTBI screenees
- •Inclusion Criteria:
- •Age ≥16 years
- •Undergoing screening for LTBI
- •Gives written informed consent to participate
Exclusion Criteria
- •Known HIV infection
- •Declines HIV testing
- •Previous antimicrobial treatment for active TB or latent TB infection
- •Clinical suspicion of active TB
- •Already initiated chemoprophylaxis
- •ii) For adults with active TB Inclusion criteria
- •Age ≥16 years
- •Newly-diagnosed active TB about to initiate treatment
- •Gives written informed consent to participate
- •Exclusion criteria
- •Known HIV infection
- •Declines HIV testing
- •Already initiated anti-TB treatment
- •Haemoglobin concentration <10 g/dl at screening
Arms & Interventions
Latent TB screenees
Patients attending TB clinic who are being screened for latent TB. Includes recent migrants from a country with high TB prevalence, occupational health referrals with a positive IGRA, household contacts of TB cases and patients who are about to start biological therapy (eg. anti-TNF)
Active TB patients
Patients with active TB who are not already on anti-tuberculous treatment
Outcomes
Primary Outcomes
Prevalence of Mtb DNA in blood
Time Frame: 3 years
Prevalence of Mtb DNA in blood of latent screenees and active TB participants
Secondary Outcomes
No secondary outcomes reported