Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons.
BACKGROUND
BCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection.


METHODS
We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany.


RESULTS
During a 6-month period, 309 contacts (mean age 28.5 +/- 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (kappa = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7-52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (kappa = 0.58, with 95% CI 0.4-0.68), increasing to 0.68 (95% CI 0.46-0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany.


CONCLUSIONS
The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.
Diel
R
R
School of Public Health, University of Düsseldorf, Germany. Roland.Diel@uni-duesseldorf.de
Nienhaus
A
A
Lange
C
C
Meywald-Walter
K
K
Forssbohm
M
M
Schaberg
T
T
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000627:therapeutic use*; D016358:Contact Tracing; D000939:Epitopes; D005858:Germany / Q000453:epidemiology; D006403:Hematologic Tests; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D000939:Epitopes; D007371:Interferon-gamma