Immunologic and Microbiologic Predictors

Pilot Study to Assess Immunologic and Microbiologic Predictors of Response to Short Course Anti-TB Treatment in HIV-non-infected Adults with Initial Episodes of Smear Positive and Smear-Negative Pulmonary Tuberculosis

Information:

Goal of Study:

This is a prospective observational study assessing immunologic and microbiologic parameters during standard short course combination anti-TB chemotherapy. The study used investigational methods to assess the regulation and temporal sequence of changes in host immunological responses and microbiologic markers during standard short course anti-TB chemotherapy in smear (+) and smear (-) culture-confirmed pulmonary TB, non-HIV infected subjects. Immunologic parameters were correlated with clinical and microbiologic changes during treatment.

Objectives of Study:

Immunological Parameters

1. Serum/plasma TNF-α, IFN-γ, IL-6 and chemokine levels
2. Baseline expression of RNA for cytokines
3. TNF-α, IFN-γ, IL-6 and chemokine immunoreactivity in supernatants from MTB culture filtrate-stimulated whole blood cultures, expectorated and inducted sputum samples, and bronchoalveolar lavage (BAL) fluid (smear-negative patients only)
4. Phenotypic analysis of cells in peripheral blood, sputum and BAL fluid (smear-negative patients only) samples by flow cytometry

Microbiologic Parameters

1. Expression of α-antigen, α-crystallin and other relevant MTB genes in sputum and BAL (smear-negative patients only) collected at baseline, and in sputum from smear-positive patients throughout anti-TB therapy

Parameters Associated with MTB Replication

1. Immunoreactivities of MTB α-antigen, α-crystallin, and other defined mycobacterial antigens in serum, sputum, and BAL fluid (smear-negative patients only), including ELISA
2. Killing of MTB in whole blood cultures as a means of simultaneously evaluating the effect of anti-TB chemotherapy and of host immune effector mechanisms on tubercle bacilli

The results of this completed study can be found in:

Palaci M, Dietze R, Hadad DJ, Ribeiro FK, Peres RL, Vinhas SA, Maciel EL, do Valle Dettoni V, Horter L, Boom WH, Johnson JL, Eisenach KD. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007; 45:4064-4066. PMCID: PMC2168542.

Wallis RS, Vinhas SA, Johnson JL, Ribeiro FC, Palaci M, Peres RL, Sá RT, Dietze R, Chiunda A, Eisenach K, Ellner JJ. Whole blood bactericidal activity during treatment of pulmonary tuberculosis. J Infect Dis 2003; 187:270-278.

Ribeiro-Rodrigues R, Resende Co T, Johnson JL, Ribeiro F, Palaci M, Sá RT, Maciel EL, Lima FEP, Dettoni V, Toossi Z, Boom WH, Dietze R, Ellner JJ, Hirsch CS. Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. Clin Diagn Lab Immunol 2002; 9:818-823. PMCID: PMC120011.