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Novel interferon-gamma assays for diagnosing tuberculosis in young children in India

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SETTING: The tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used as supportive evidence to diagnose active tuberculosis (TB). Novel IGRAs could improve diagnosis, but data are lacking in young children.

DESIGN: Children (age 5 years) with suspected TB were prospectively screened at a tertiary hospital in Pune, India; the children underwent TST, and standard (early secretory antigenic target 6 and culture filtrate protein 10) and enhanced (five additional novel antigens) enzyme-linked immunospot (ELISpot) assays.

RESULTS: Of 313 children (median age 30 months) enrolled, 92% had received bacille Calmette-Guérin vaccination, 53% were malnourished and 9% were coinfected with the human immunodeficiency virus (HIV); 48 (15%) had TB, 128 (41%) did not, and TB could not be ruled out in 137 (44%). The sensitivity of enhanced (45%) and standard (42%) ELISpot assays for diagnosing TB was better than that of TST (20%) (P  0.03); however, enhanced ELISpot was not more sensitive than the standard ELISpot assay (P = 0.50). The specificity of enhanced ELISpot, standard ELISpot and TST was respectively 82% (95%CI 74–89), 88% (95%CI 81–94) and 98% (95%CI 93–100). Rv3879c and Rv3615c, previously reported to be promising antigens, failed to improve the diagnostic performance of the ELISpot assay.

CONCLUSION: The TST and the standard and novel ELISpot assays performed poorly in diagnosing active TB among young children in India.

Keywords: ELISpot; IGRA; India; Rv3615c; Rv3879c; TB; TST; children

Document Type: Research Article

Affiliations: 1: National AIDS Research Institute, Pune, India 2: Johns Hopkins Bloomberg School of Public Health, Baltimore, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3: Byramjee Jeejeebhoy Government Medical College, Pune, India 4: Department of Pediatrics, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 5: Imperial College, London, UK 6: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Byramjee Jeejeebhoy Government Medical College, Pune, India 7: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Publication date: 01 April 2017

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