Suttons’s Law: Local Immunodiagnosis of Tuberculosis

Abstract

Recently, important advances have been made in the immunodiagnosis of tuberculosis. New T cell interferon-gamma release assays (TIGRA) are more specific and more sensitive than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis (MTB) infection. However, like the TST, TIGRA are unable to distinguish between active tuberculosis (TB), latent TB infection (LTBI) and treated TB if performed on blood mononuclear cells alone. In active TB, MTB-specific T cells are actively recruited to the site of infection and can rapidly be identified in extrasanguinous fluids, such as pleural effusions, ascites, cerebrospinal fluid, and in bronchoalveolar lavages. This review summarizes recent findings comparing systemic and local immune responses against MTB. Although bacteriological and histological methods have the highest specificity for TB in terms of diagnosing active TB and the number of TB patients in whom extrapulmonary TIGRAs have been evaluated is still limited, a comparison of local and systemic MTB-specific immune responses is a promising technique to rapidly distinguish active TB from latent MTB infection in routine clinical practice.

T-cell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB meningitis in non-HIV patients

“…There were no cases in which the CSF-MC ELISPOT result (numerator) was positive and the PBMC ELISPOT result (denominator) was 0. Administration of linezolid, within regimens designed to balance efficacy and tolerability, needs to be guided by clear scientific evidence focused on the ideal dosage (per kg body weight per day) and duration [1,[5][6][7][8][9].…”

“…Furthermore, the low specificity of PBMC ELISPOT in the current (58%) and previous studies (57-75%) also indicate the limited value of this assay to distinguish between patients with latent infection and those with active disease (table s3). In contrast to the PBMC ELISPOT assay, the CSF-MC ELISPOT assay may increase the sensitivity and specificity of diagnosis of active tuberculosis, because M. tuberculosis-specific T-cells are recruited to the sites of the active infection [5][6][7]. However, the current and previous studies showed that the sensitivity and specificity of CSF-MC ELISPOT with the manufacturer's recommend cut-off value (o6 spots per 2.5610 5 cells or o24 spots per 10 6 cells) were not high enough to use as a rapid rule-out or rulein test for diagnosing TBM (table s3).…”

Serodiagnosis Efficacy and Immunogenicity of the Fusion Protein of Mycobacterium tuberculosis Composed of the 10-Kilodalton Culture Filtrate Protein, ESAT-6, and the Extracellular Domain Fragment of PPE68

“…Our ELISA results clearly demonstrated that the purified fusion protein CFP-10 -ESAT-6 -PPE68= has both sensitivity and the specificity better than those of CFP-10 -ESAT-6 and PPD in active-TB patients and controls. Various articles (9,13,14,33) have reported the utility of an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay for the diagnosis of TB. The developed tests show good sensitivity and specificity and are promising for TB diagnosis.…”

Performance of an interferon-gamma release assay in the diagnosis of tuberculous meningitis in children / Performanţa testului bazat pe eliberarea interferonului gamma în diagnosticul meningitei tuberculoase la copil

“…A positive QFT-IT blood test cannot distinguish between latent and active TB, but a positive QFT-G of the CSF may explain the etiology of tuberculous meningitis. Jafari et al showed that IGRA response assayed in mononuclear cells from the site of infection can provide superior discrimination between active TB and latent TB [28]. In the remaining patients (28.6%), the diagnoses of TB meningitis were supported either by positive sputum cultures for M. tuberculosis (three cases) or clinical manifestations, exposure to TB, biochemical characteristics and the cytologies of the CSF, chest XR and CT scan results and favorable responses to antituberculous treatment.…”