Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay

AIDS. 2009 May 15;23(8):961-969. doi: 10.1097/QAD.0b013e32832956ad.

Abstract

Objective: To evaluate an enzyme-linked immunospot assay (ELISPOT) for the diagnosis of tuberculosis (TB) in HIV-infected children with suspected TB and to compare the performance of ELISPOT with the tuberculin skin test (TST).

Methods: Interferon-gamma responses to Mycobacterium tuberculosis-specific antigens were measured by ELISPOT in HIV-infected children with suspected TB. HIV-infected and HIV-uninfected children without TB were taken for comparison.

Results: Results were available for 188 children, of whom 139 (74%) were HIV-infected. Of these, 22 were classified as having definite TB: 24 probable TB, 14 possible TB and 128 not having TB. The median (range) age of patients was 20 (10-54.1) months. Median interferon-gamma responses to early-secreted antigenic target-6 and culture filtrate protein-10 were higher in children with definite or probable TB compared with children without TB (P < 0.002). In HIV-infected children with an interpretable ELISPOT result, the ELISPOT was positive in 14/21 (66%) with definite TB. A significantly higher proportion of HIV-infected children with definite or probable TB had a positive ELISPOT compared with a positive TST [25/39 (64%) vs. 10/34 (29%), P = 0.005]. In contrast to TST, results from ELISPOT were not affected by young age or severe immunosuppression. In HIV-infected children without active TB disease, 27% had a positive ELISPOT, suggesting latent TB infection.

Conclusion: ELISPOT is more sensitive than TST for the detection of active TB in HIV-infected children. However, the sensitivity of current ELISPOT assays is not sufficiently high to be used as a rule out test for TB.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antigens, Bacterial
  • Bacterial Proteins
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Humans
  • Immunocompromised Host / immunology*
  • Infant
  • Interferon-gamma / blood
  • Latent Tuberculosis / complications
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / immunology
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Nutritional Status
  • Sensitivity and Specificity
  • South Africa
  • Tuberculin Test / methods
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / diagnosis*
  • Tuberculosis, Pulmonary / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 antigen, Mycobacterium leprae
  • Interferon-gamma