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Published online January 2, 2007
PEDIATRICS Vol. 119 No. 1 January 2007, pp. e1-e5 (doi:10.1542/peds.2006-1057)
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EXPERIENCE & REASON

T-Cell–Based Diagnosis of Neonatal Multidrug-Resistant Latent Tuberculosis Infection

Luca Richeldi, MD, PhDa, Katie Ewer, PhDb, Monica Losi, PhDa, Barbara M. Bergamini, MDa, Kerry Millington, BScb,c, Leonardo M. Fabbri, MDa, Ajit Lalvani, FRCP, DMb,c

a Departments of Respiratory Disease and Pediatrics, University of Modena and Reggio Emilia, Modena, Italy
b Tuberculosis Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
c Tuberculosis Immunology Group, Department of Respiratory Medicine, National Heart and Lung Institute, Wright Fleming Institute of Infection and Immunity, Imperial College London, London, United Kingdom

ABSTRACT

Young children exposed to tuberculosis have a high risk of progression to severe tuberculosis disease, but diagnosis of recent infection is hindered by the poor sensitivity of the tuberculin skin test. Whether new blood tests can detect latent infection in this vulnerable group is unknown because there is no gold standard. We monitored a tuberculin skin test–negative infant whose mother had infectious multidrug-resistant tuberculosis with enzyme-linked immunospot, a blood test that enumerates Mycobacterium tuberculosis–specific T cells. The enzyme-linked immunospot test became persistently positive by 6 months, and 18 months later the child developed active tuberculosis despite appropriate chemoprophylaxis. At this point, the magnitude of the enzyme-linked immunospot response increased >10-fold. Our findings demonstrate that this blood test detected latent infection with dormant, yet viable, bacilli and illustrate how enzyme-linked immunospot could improve diagnosis of childhood tuberculosis infection.

Key Words: tuberculosis • neonate • diagnosis • ELISpot

Abbreviations: LTBI, latent tuberculosis infection • TST, tuberculin skin test • ELISpot, enzyme-linked immunospot • MDR, multidrug-resistant • PPD, purified protein derivative • ESAT-6, early secretory antigenic target 6 • CFP10, culture filtrate protein 10 • SKSD, streptokinase-streptodornase • SFC, spot-forming cell

Accepted Aug 2, 2006.


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