Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.
Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.
Wallis
R S
RS
Case Western Reserve University, Cleveland, Ohio 44106-4984, USA. rsw2@po.cwru.edu
Perkins
M
M
Phillips
M
M
Joloba
M
M
Demchuk
B
B
Namale
A
A
Johnson
J L
JL
Williams
D
D
Wolski
K
K
Teixeira
L
L
Dietze
R
R
Mugerwa
R D
RD
Eisenach
K
K
Ellner
J J
JJ
D000328:Adult; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001938:Brazil; D002473:Cell Wall / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006801:Humans; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009171:Mycolic Acids / Q000378:metabolism; D011859:Radiography; D013183:Sputum / Q000382:microbiology*; D017211:Treatment Failure; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D014454:Uganda
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D009171:Mycolic Acids