title: The Role of Clinical Symptoms in the Diagnosis of Intrathoracic Tuberculosis in Young Children.
abstract: BACKGROUND
  Childhood tuberculosis (TB) is usually Mycobacterium tuberculosis (MTB) culture negative. Furthermore, clinical presentation may be altered by active case finding, isoniazid prophylaxis and early treatment. We aimed to establish the value of presenting symptoms for intrathoracic TB case diagnosis among young children.
  
  
  METHODS
  Healthy, HIV-uninfected, South African infants in an efficacy trial of a novel TB vaccine (MVA85A) were followed for 2 years for suspected TB. When suspected, investigation followed a standardized algorithm comprising symptom history, QuantiFERON Gold-in-Tube, chest radiography (CXR), MTB culture and Xpert MTB/RIF from paired gastric lavage and induced sputa. Adjusted odds ratios and 95% confidence intervals describe the associations between symptoms and positive MTB culture or Xpert MTB/RIF, and CXR compatible with intrathoracic TB.
  
  
  RESULTS
  Persistent cough was present in 172/1017 (16.9%) of the children investigated for TB. MTB culture/Xpert MTB/RIF was positive in 38/1017 children (3.7%); and CXR was positive, that is, compatible with intrathoracic TB, in 131/1017 children (12.9%). Children with persistent cough had more than triple the odds of a positive MTB culture/Xpert MTB/RIF (adjusted odds ratios: 3.3, 95% confidence interval: 1.5-7.0) and positive CXR (adjusted odds ratios: 3.5, 95% confidence interval: 2.2-5.5). Persistent cough was the only symptom that differentiated children with severe (56.5%) from nonsevere intrathoracic TB disease (28.2%; P = 0.001).
  
  
  CONCLUSIONS
  Persistent cough was the cardinal diagnostic symptom associated with microbiologic and radiologic evidence, and disease severity, of intrathoracic TB. Symptom-based definitions of TB disease for diagnostic, preventive and therapeutic studies should prioritize persistent cough above other symptoms compatible with childhood TB.
authors.affiliation: From the *South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine (IDM), Department of Pediatrics & Child Health, University of Cape Town; †Vaccines for Africa (VACFA), Institute of Infectious Disease & Molecular Medicine, University of Cape Town; ‡Division of Community Health, Stellenbosch University and Western Cape Government: Health, Cape Town, South Africa; §Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; and ¶Aeras, Rockville, Maryland.
authors.forename: Humphrey
authors.initials: H
authors.lastname: Mulenga
authors.forename: Michele D
authors.initials: MD
authors.lastname: Tameris
authors.forename: Kany Kany A
authors.initials: KK
authors.lastname: Luabeya
authors.forename: Hennie
authors.initials: H
authors.lastname: Geldenhuys
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Landry
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis; D011237:Predictive Value of Tests; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology