Published online May 1, 2006
PEDIATRICS Vol. 117 No. 5 May 2006, pp. 1542-1548 (doi:10.1542/peds.2005-2095)
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Tuberculosis

Comparison of Enzyme-Linked Immunospot Assay and Tuberculin Skin Test in Healthy Children Exposed to Mycobacterium tuberculosis

Philip C. Hill, MPH, FRACPa, Roger H. Brookes, PhDa, Ifedayo M.O. Adetifa, MB, BS, FWACPa, Annette Fox, PhDa, Dolly Jackson-Sillah, MB, BS, MSca, Moses D. Lugos, FIMLSa, Simon A. Donkor, BSca, Roger J. Marshall, PhDb, Stephen R.C. Howie, MBCHB, FRACPc, Tumani Corrah, PhD, FRCPa, David J. Jeffries, PhDa, Richard A. Adegbola, PhD, FRCPatha and Keith P.W.J. McAdam, FRCPd

a Tuberculosis Division
c Bacterial Diseases Programme
d Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda
b School of Population Health, University of Auckland, Auckland, New Zealand

OBJECTIVE. To compare the enzyme-linked immunospot (ELISPOT) assay with the tuberculin skin test (TST) in children for the diagnosis of Mycobacterium tuberculosis infection in the Gambia.

METHODS. We divided child contacts of sputum smear-positive tuberculosis cases into 3 age categories (<5, 5–9, and 10–14 years) and assessed agreement between the 2 tests plus their relationship to prior Bacille Calmette-Guerin (BCG) vaccination. We categorized a child's level of M tuberculosis exposure according to where he/she slept relative to a case: the same room, same house, or a different house. The relationship between exposure and test result was assessed by multiple logistic regression.

RESULTS. In child contacts of 287 cases, 225 (32.5%) of 693 were positive by TST and 232 (32.3%) of 718 by ELISPOT. The overall agreement between tests was 83% and the discordance was not significant. Both tests responded to the M tuberculosis exposure gradient in each age category. The percentage of those who were TST positive/ELISPOT negative increased with increasing exposure. At the lowest exposure level, the percentage of ELISPOT-positive children who were TST negative was increased compared with the highest exposure level. Neither test had evidence of false positive results because of BCG.

CONCLUSIONS. In Gambian children, the ELISPOT is slightly less sensitive than the TST in the diagnosis of M tuberculosis infection from recent exposure, and neither test is confounded by prior BCG vaccination. Evidence of reduced TST sensitivity in subjects with the lowest known recent M tuberculosis exposure suggests that, when maximal sensitivity is important, the 2 tests may be best used together.

Key Words: tuberculin skin test • ELISPOT • tuberculosis • Mycobacterium tuberculosis

Abbreviations: TST—tuberculin skin test • BCG—Bacille Calmette-Guerin • ESAT-6—early secretory antigenic target 6 • CFP-10—culture filterate protein 10 • ELISPOT—enzyme-linked immunospot • MRC—Medical Research Council • SFU—spot forming units • OR—odds ratio • CI—confidence interval

Accepted Nov 3, 2005.




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