Latent tuberculosis infection: An overview.

Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB) disease. Individuals with LTBI represent a reservoir for active TB cases. The detection and management of LTBI is now a key component of the World Health Organization's End TB Strategy and the Government of Canada's federal framework for action on TB prevention and control. This is because people with LTBI can progress to active TB or undergo reactivation, a risk that is greatly increased in those with immunocompromising conditions. This overview provides a summary of LTBI and reactivation risk, as well as the recent advances in the diagnosis and treatment of LTBI.

Potential biomarkers associated with discrimination between latent and active pulmonary tuberculosis.

SETTING: A third of the world's population has latent tuberculous infection (LTBI). Current TB diagnostics used in developing countries are ineffective and are unable to distinguish LTBI from active TB. Identifying biomarkers that could aid in the early detection of TB and in distinguishing TB states could be a major breakthrough in global TB control. OBJECTIVE: To identify potential immune biomarkers to distinguish active TB from LTBI. DESIGN: A cross-sectional study was conducted among 19 active TB patients, 8 TB-negative individuals (controls) and 16 LTBI non-human immunodeficiency virus infected individuals in Nairobi, Kenya. Excess supernatants from the QuantiFERON®-TB Gold In-Tube test were used to measure immune analytes using a Th17-focused Milliplex® assay. RESULTS: Overall antigen-specific responses were higher in the LTBI group than in active TB patients and controls. Interleukin (IL) 17F, macrophage inflammatory protein 3 alpha (MIP-3α), IL-13, IL-17A, IL-5, interferon-gamma (IFN-γ), IL-9, IL-1ß and IL-2 were significantly differentially produced by individuals with LTBI and active TB patients. Receiver operator curve analysis revealed good discriminative abilities of these analytes. Co-expression analysis highlighted uniquely co-expressed cytokine pairs between TB groups. CONCLUSION: These findings suggest that IL-17F, MIP-3α, IL-13, IL-17A, IL-5, IL-9, IL-1ß and IL-2, in addition to IFN-γ, could identify and uniquely discriminate between TB states.

IFN-γ promoter polymorphisms do not affect QuantiFERON® TB Gold In-Tube test results in a Canadian population.

BACKGROUND: Several studies have shown polymorphisms within the interferon-gamma (IFN-γ) promoter influence cytokine expression. The interferon-gamma release assay (IGRA) relies on the ability to produce IFN-γ in response to tuberculosis (TB) specific antigens. This study determined the relationship between the IFN-γ +874 A/T promoter polymorphism and the performance of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in an ethnically diverse Canadian population. METHODS: A total of 190 participants were categorised into three groups based on history of and exposure to TB: active TB (n = 55), TB exposed (n = 55) and presumably TB unexposed controls (n = 80). All participants underwent QFT-GIT testing, and DNA was extracted from whole blood and probed for polymorphism at position +874 (T/A) of intron 1 of IFN-γ. Statistical relationships between the QFT-GIT results, polymorphisms and demographic data were evaluated. RESULTS: IFN-γ +874 genotype frequencies among the entire study population (n = 190) were A/A (45.8%), T/A (39.5%), and T/T (14.7%). Among the three study groups, there was no correlation between QFT-GIT results and the IFN-γ +874 A/T genotype, and no correlation of genotype with IFN-γ production in response to either Mycobacterium tuberculosis antigens or mitogenic stimulation. CONCLUSION: Our results indicate that the IFN-γ +874 promoter polymorphism does not influence QFT-GIT performance in this study population.