• Mustafa Bakir, Kerry A Millington, Ahmet Soysal, Jonathan J Deeks, Serpil Efee, Yasemin Aslan, Davinder P S Dosanjh, and Ajit Lalvani.
• Marmara University School of Medicine, Istanbul, Turkey.
• Ann. Intern. Med. 2008 Dec 2;149(11):777-87.

BackgroundEnzyme-linked immunospot (ELISpot) assay is an increasingly widely used, T-cell-based, interferon-gamma-release assay for diagnosing tuberculosis infection, but whether positive results are prognostic of active tuberculosis is not known.ObjectiveTo determine whether ELISpot results predict the development of active tuberculosis among persons with recent tuberculosis exposure.DesignLongitudinal cohort study of children and adolescents with tuberculosis contact recruited from October 2002 to April 2004.SettingCommunity-based contact investigations in Turkey.Patients908 children and adolescents with recent household tuberculosis exposure.InterventionEnzyme-linked immunospot assay, incorporating early secretory antigenic target-6 and culture filtrate protein-10, and tuberculin skin test were done at baseline.MeasurementsIncidence rates ratios of progression to active tuberculosis for contacts with positive tuberculin skin test and ELISpot results, and relative incidence rates comparing contacts with positive and negative test results.ResultsIsoniazid preventive therapy was given to 688 (76%) contacts according to local guidelines. Fifteen contacts developed active tuberculosis over 1201 person-years of follow-up. Of 381 contacts with positive ELISpot results, 11 developed active tuberculosis over 536 person-years of follow-up (incidence rate, 21 per 1000 person-years [95% CI, 10.2 to 36.7 per 1000 person-years]), a statistically significant 3- to 4-fold increased risk for progression relative to ELISpot-negative contacts. Of 550 contacts with positive tuberculin skin test results, 12 developed active tuberculosis over 722 person-years of follow-up (incidence rate, 17 per 1000 person-years [CI, 8.6 to 29.0 per 1000 person-years]).LimitationOnly 3 of the 15 incident cases were confirmed by culture.ConclusionPositive ELISpot results predict subsequent development of active tuberculosis in recent tuberculosis contacts. Although tuberculosis contacts with positive ELISpot results have an incidence rate of tuberculosis similar to that of contacts with positive tuberculin skin test results, ELISpot testing could allow more focused targeting of preventive therapy to fewer contacts.

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