Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial

Setting: Standardized clinical case definitions represent the best option for pediatric tuberculosis (TB) disease diagnosis and classification. OBJECTIVE: To apply published guidelines for intrathoracic TB classification for use in reporting diagnostic studies with passive case finding to presumed TB patients from International Maternal Pediatric Adolescent AIDS Clinical Trials P1041, a trial of isoniazid prophylaxis in healthy human immunodeficiency virus exposed, bacille Calmette-Gúerin vaccinated infants which employed active surveillance to assess a novel application of these guidelines in this setting. METHODS: P1041 presumed TB patients were retrospectively cross-classified by protocol-defined and National Institutes of Health (NIH) classifications, and agreement was assessed. RESULT S: Of 219 TB suspects, 166 had signs/symptoms, with 158 considered TB (21 confirmed, 92 probable, 45 possible) and 8 not TB (6 TB unlikely, 2 alternative diagnoses). Weight loss and failure to thrive represented the majority of the observed signs/symptoms. Among those with signs/symptoms, agreement between definitions was poor. Furthermore, 53 TB presumptives were without signs/symptoms, including 33 classified by the P1041 protocol as TB. CONCLUS ION: Poor agreement between P1041 and NIH classifications reflects cases identified through active vs. passive surveillance, the latter reflecting the intended use of NIH definitions. Given the interest in standardized definitions for broader application, future efforts could focus on expanding TB disease classification to presumed TB patients identified through active surveillance.