New Strategies for Assessment of the Persistence of Viable Bacilli in Latent and Active Tuberculosis (TB-LIVE)

Region Skane

Status: Enrolling

Conditions: Persistent Infection; Latent Tuberculosis; Mycobacterium Tuberculosis

Study type: Observational

Funder types: Other

Identifiers

NCT05621343

2021-04885

Details and patient eligibility

About

Current diagnostic tools such as interferon gamma release assay (IGRA) and purified protein derivative (PPD) can not distinguish patients with latent tuberculosis infection (LTBI) and persistence of live mycobacteria. This inability to rule out living mycobacteria in patients investigated for LTBI leads to unnecessary and potentially harmful treatment regimes all around the globe.

The goal of this observational study is to identify candidate biomarkers for viable bacilli in latent tuberculosis in order to decrease the use of unnecessary and ineffective antibiotic treatment.

Full description

Tuberculosis (TB) is the second leading cause of death due to a single infectious agent, with the main burden in resource-limited settings and in vulnerable populations. It is estimated that approximately 25% of the global population is infected with TB. LTBI is a condition where the mycobacteria rests within the body instead of creating active disease. About half of the active TB cases develop within 2 years of exposure and the other half reactivates as distant as several decades post exposure. Persistence of viable bacilli is a prerequisite for the reactivation of TB.

Through sampling of peripheral blood the investigators will investigate how selected cytokines, enzyme activity and gene expression changes during course of treatment, 4-6 months, and during follow up, 1 year. These patterns will be compared to the patterns of patients with: latent TB without treatment, active TB with treatment as well as healthy controls. Samples will be drawn at 0, 1, 6 and 12 months, after treatment initialization when applicable. Healthy controls will only be sampled once. Most of the analysis will be performed on TB-antigen stimulated blood.

The investigators hypothesize that there is a substantial fraction of latent TB patients who do not harbor live mycobacteria and that this is reflected in study outcome measures when given treatment. Furthermore, the investigators hypothesize that this fraction of latent TB patients will resemble healthy controls in terms of outcome measures whereas their counterpart, latent TB patients harboring living bacteria, will not.

Enrollment: 130 estimated patients

Sex: All

Ages: 15 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

LTBI (2 groups)

Inclusion Criteria:

• latent tuberculosis: Interferon gamma (IFN-γ) >0.70 IU/ml in the Quantiferon-TB Plus assay
• age 15-25 years OR high likelihood of recent TB transmission
• informed consent

Exclusion Criteria:

• active tuberculosis
• chronic illness
• immunosuppressive treatment
• pregnancy (including 6 months post-partum)
• previous treatment for either active or latent TB infection

Controls

Inclusion Criteria:

• age 15-25 years
• informed consent

Exclusion Criteria:

• latent- OR active tuberculosis
• chronic illness
• immunosuppressive treatment
• pregnancy (including 6 months post-partum)
• previous treatment for either active or latent TB infection

Active TB

Inclusion Criteria:

• diagnosed with active TB
• informed consent

Exclusion Criteria:

age < 15 years

Trial design

130 participants in 4 patient groups

Latent TB on treatment

Description:

Treatment according to existing Swedish guidelines with: Oral rifampicin 10 mg/kg (max 600mg) once daily during 4 months OR Oral isoniazide 5 mg/kg (max 300mg) once daily in combination with 40mg vitamin B6 (pyridoxin) during 6 months

Latent TB not on treatment

Description:

Latent TB without indication for treatment OR patient who do not want to receive treatment

Active TB with treatment

Description:

Treatment according to existing Swedish guidelines. Duration and choice of antibiotic therapy depending on the condition.

Healthy control

Description:

Healthy