title: Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial.
abstract: METHODS
  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-Guérin 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Stony Brook School of Medicine, Stony Brook, New York, New York, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Beneri
authors.affiliation: Harvard School of Public Heath, Boston, Massachusetts, USA.
authors.forename: L
authors.initials: L
authors.lastname: Aaron
authors.affiliation: Rutgers New Jersey Medical School, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of AIDS, Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Jean-Philippe
authors.affiliation: Respiratory and Meningeal Pathogens Research Unit, Medical Research Council, Faculty of Health Sciences, USA; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Madhi
authors.affiliation: Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Violari
authors.affiliation: Department of Pediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
authors.forename: M F
authors.initials: MF
authors.lastname: Cotton
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: C
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Department of Pediatrics, Stony Brook School of Medicine, Stony Brook, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nachman
mesh_terms: D019985:Benchmarking; D002648:Child; D002662:Child Health Services; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009316:National Institutes of Health (U.S.); D017410:Practice Guidelines as Topic / Q000592:standards*; D012189:Retrospective Studies; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy; D014481:United States