T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis infection

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.