Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy.
BACKGROUND
The ability to detect tuberculosis-specific lymphocytes by enzyme-linked immunospot (ELISPOT) assay may have important implications for the diagnosis and monitoring of tuberculosis in children, for which routine methods lack sensitivity. We conducted a study to determine the presence and time course of ELISPOT responses in children with tuberculosis.


METHODS
Blood samples were obtained from children with a clinical diagnosis of tuberculosis, and interferon-gamma ELISPOT assays were performed using purified protein derivative (PPD), early secretory antigenic target 6 (ESAT-6), and culture filtrate protein 10 (CFP10) as stimulants. A subset of children were retested after 1, 3, and 6 months of therapy.


RESULTS
Detectable responses to ESAT-6 or CFP10 were found in 49 of 70 children with clinical tuberculosis but were more frequently found in those with culture-proven disease (P = .05). The number of subjects with responses to PPD increased after 1 month of therapy (P = .0004) and decreased at 3 and 6 months.


CONCLUSIONS
Tuberculosis-specific ELISPOT testing is a promising tool that should be evaluated as a potential diagnostic test for childhood tuberculosis. We caution against the use of an early decrease in response as a marker of successful antituberculous chemotherapy.
Nicol
M P
MP
School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa. mnicol@curie.uct.ac.za
Pienaar
D
D
Wood
K
K
Eley
B
B
Wilkinson
R J
RJ
Henderson
H
H
Smith
L
L
Samodien
S
S
Beatty
D
D
D000942:Antigens, Bacterial / Q000276:immunology*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D012680:Sensitivity and Specificity; D014373:Tuberculin / Q000276:immunology*; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy*
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D014373:Tuberculin