title: Culture is an imperfect and heterogeneous reference standard in pediatric tuberculosis.
abstract: In pediatric tuberculosis (pTB), culture is the accepted reference standard for assessing new diagnostic tests despite culture only confirming 10-50% of clinically diagnosed cases.
  
  
  
  Using the studies previously included in the systematic review of Gene Xpert, we evaluated the diagnostic yield of culture. Children with symptoms and signs suggestive of TB were considered to have a clinical diagnosis if they were 1) culture positive or 2) followed clinically for at least one month and started on Anti-Tuberculosis Therapy (ATT).
  
  
  
  Of 1989 children with presumptive pTB, 229 (11.5%) had culture-confirmation. Of the remaining 1760 culture negative children, 710 (24.4) were classified as culture-negative clinical TB and 821 were classified as "not TB". Diagnostic yield of culture was 24.4% (median 28.7% IQR 15.6%-42.4%; range 1.5%-65%).
  
  
  
  Culture, the accepted reference standard for pediatric TB diagnostics, has a low and variable yield that impacts how diagnostic studies should be reported as well as everyday clinical care.
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Global and Immigrant Health, Baylor College of Medicine, Houston, TX, USA. Electronic address: Andrew.DiNardo@bcm.eduu.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: DiNardo
authors.affiliation: The International Union Against Tuberculosis and Lung Disease (The Union), 61 Broadway, Suite 1720, New York, NY 10006, USA. Electronic address: adetjen@unicef.org.
authors.forename: Anne
authors.initials: A
authors.lastname: Detjen
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor College of Medicine Children's Foundation-Swaziland, Baylor College of Medicine, Mbabane, Swaziland. Electronic address: PAlonso@bcm.edu.
authors.forename: Pilar
authors.initials: P
authors.lastname: Ustero
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Global and Immigrant Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: Katherine.Ngo@bcm.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Ngo
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor International Pediatric AIDS Initiative, Baylor Tanzania Center of Excellence, Baylor College of Medicine, Mbeya, Tanzania. Electronic address: Bacha@bcm.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Bacha
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Global and Immigrant Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: Anna.Mandalakas@bcm.edu.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mandalakas
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000995:Antitubercular Agents / Q000627:therapeutic use; D001431:Bacteriological Techniques / Q000592:standards*; D002138:Calibration; D002648:Child; D002675:Child, Preschool; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000592:standards*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D011379:Prognosis; D012015:Reference Standards; D015203:Reproducibility of Results; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents
keywords: Culture; Diagnosis; Reference standard; Tuberculosis