Mustafa Bakir, MD; Kerry A. Millington, DPhil; Ahmet Soysal, MD; Jonathan J. Deeks, PhD; Serpil Efee; Yasemin Aslan, SRN; Davinder P.S. Dosanjh, DPhil; Ajit Lalvani, DM
Enzyme-linked immunospot (ELISpot) assay is an increasingly widely used, T-cellâ€“based, interferon-Î³â€“release assay for diagnosing tuberculosis infection, but whether positive results are prognostic of active tuberculosis is not known.
To determine whether ELISpot results predict the development of active tuberculosis among persons with recent tuberculosis exposure.
Longitudinal cohort study of children and adolescents with tuberculosis contact recruited from October 2002 to April 2004.
Community-based contact investigations in Turkey.
908 children and adolescents with recent household tuberculosis exposure.
Enzyme-linked immunospot assay, incorporating early secretory antigenic target-6 and culture filtrate protein-10, and tuberculin skin test were done at baseline.
Incidence 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.
Isoniazid 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]).
Only 3 of the 15 incident cases were confirmed by culture.
Positive 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.
Interferon-γ–release assays, such as enzyme-linked immunospot (ELISpot), are increasingly used to help diagnose latent tuberculosis infection, but information about the ability of these tests to predict development of tuberculosis among exposed persons is scant.
This longitudinal study followed 908 children and adolescents with recent household exposure to tuberculosis, most of whom received preventive therapy. Of 381 children with positive ELISpot results, 11 subsequently developed active tuberculosis compared with 12 of 550 children with positive tuberculin skin test results.
Household contacts with positive ELISpot results have about a 3- to 4-fold increased risk for progression to active tuberculosis compared with contacts with negative ELISpot results. Compared with the tuberculin skin test, ELISpot could allow more focused targeting of preventive therapy to fewer contacts.
Study flow diagram detailing the follow-up of 908 children with complete baseline results for enzyme-linked immunospot (ELISpot) and tuberculin skin test (TST). IPT = isoniazid preventive therapy; IR = incidence rate.
* Index patients and child contacts were recruited at the 7 government-run tuberculosis clinics in the Anatolian side of Istanbul.
† Pediatric Infectious Disease Clinic at Marmara University Hospital, Istanbul.
‡ When sputum microscopy and culture reports for all 443 index cases were obtained and checked, 4 contacts had index cases who did not have sputum smear–positive results and 2 contacts had index cases whose sputum grew nontuberculosis atypical mycobacteria.
§ Two contacts were removed because of loss of ELISpot plates, and 33 contacts were removed because of an episode of bacterial contamination of peptide pool reagents.
∥ Twenty (5%) contacts had positive ELISpot results and 37 (7%) contacts had negative ELISpot results at recruitment.
¶ Isoniazid preventive therapy was administered on the basis of age and TST result and was interpreted in accordance with Turkish Ministry of Health guidelines. Eighteen contacts who had positive ELISpot and negative TST results at recruitment and 49 contacts who had negative ELISpot and TST results at recruitment were given IPT because their TST converted. In total, 688 contacts received IPT, of whom 41 were exposed to index cases with multidrug-resistant tuberculosis. Thirteen incident cases received IPT: 6 had positive ELISpot and TST results, 4 had positive ELISpot and negative TST results (2 of whom had converted TST results), and 3 had negative ELISpot and negative TST results (2 of whom had converted TST results). None of the incident cases had negative ELISpot and positive TST results.
** Per 1000 person-years of follow-up.
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Bakir M, Millington KA, Soysal A, Deeks JJ, Efee S, Aslan Y, et al. Prognostic Value of a T-Cell–Based, Interferon-γ Biomarker in Children with Tuberculosis Contact. Ann Intern Med. 2008;149:777–786. doi: 10.7326/0003-4819-149-11-200812020-00248
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Published: Ann Intern Med. 2008;149(11):777-786.
Infectious Disease, Mycobacterial Infections, Prevention/Screening.
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