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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. . 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. . 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. . Clin Diagn Lab Immunol 2002; 9:818-823. PMCID: PMC120011.