[Effects of prophylaxis on QuantiFERON TB-2G responses among children].
OBJECTIVE
To study the effect of treatment of latent tuberculosis infection (LTBI) on QuantiFERON TB-2G (QFT-2G) test results.


METHODS
QFT-2G was used for a contact investigation in a junior high school and those positive or doubtful positive (TB Antigen-Nil response > or = 0.1 and < 0.35 IU/ml) were indicated for treatment of LTBI with INH. All subjects who completed treatment of LTBI were re-tested with QFT-2G approximately 1 month after completion of treatment and a subset were again re-tested 8 to 11 months after the completion of treatment. The levels of IFN-gamma response in each QFT-2G test were compared.


RESULTS
Initially, 43 subjects (28 QFT-2G positive and 15 doubtful positive) were indicated treatment of LTBI, and 41 (95%) completed 6-months treatment. These 41 subjects were re-tested with QFT-2G approximately 1 month after the completion of treatment. Among 28 pre-treatment positives, 19 remained positive, 6 became doubtful positive, and 3 reverted to negative. Among 13 pre-treatment doubtful positives, 1 converted to positive, 5 remained doubtful positive, and 7 reverted to negative. The QFT-2G responses after the completion of treatment significantly declined compared with the pre-treatment level (geometric means; before treatment ESAT-6: 0.30 IU/ml, CFP-10: 0.09 IU/ml, after treatment ESAT-6:0.18 IU/ml, CFP-10: 0.05 IU/ml, dependent t-test; ESAT-6: p = 0.020, CFP-10: p = 0.005). At 8 to 11 months after the completion of treatment, 30 randomly selected subjects received the third QFT-2G test. Among 19 positives at the completion of treatment, 14 remained positive, 4 become doubtful positive, and 1 reverted to negative. Among 8 doubtful positives at completion of treatment, 4 converted to positive, 3 remained doubtful positive, and 1 reverted to negative. A further decline of QFT-2G responses was not observed. Three subjects negative at the completion of treatment were re-tested and remained negative at the third test.


CONCLUSIONS
QFT-2G responses significantly declined after the treatment of LTBI, despite the rate of reversion in QFT-2G being low. This low reversion rate suggests QFT-2G would not be useful as a marker to evaluate the success of treatment for LTBI. However, the finding that QFT-2G responses significantly decline after the treatment of LTBI suggests the possibility that this decline could be used as a marker of the susceptibility of the infective M. tuberculosis strain to the prophylactic drug used. The outbreak investigation has been carried out for over two years, and none of 229 students who were TST positive, but QFT-2G negative and because of this result not indicated treatment of LTBI, have developed TB, suggesting that QFT-2G reflects TB infection more accurately than the TST, even in school children.
Higuchi
Kazue
K
Immunology Division, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (JATA) Matsuyama, Tokyo, Japan. higuchi@jata.or.jp
Okada
Kenji
K
Harada
Nobuyuki
N
Mori
Toru
T
D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D002648:Child; D016358:Contact Tracing; D004196:Disease Outbreaks; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007538:Isoniazid / Q000008:administration & dosage; D007564:Japan / Q000453:epidemiology; D008297:Male; D011933:Reagent Kits, Diagnostic; D012574:Schools / Q000706:statistics & numerical data; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission
D000995:Antitubercular Agents; D015415:Biomarkers; D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma; D007538:Isoniazid