title: Diagnostic features associated with culture of Mycobacterium tuberculosis among young children in a vaccine trial setting.
abstract: OBJECTIVE
  To identify diagnostic features associated with culture of Mycobacterium tuberculosis (MTB), the standard for tuberculosis (TB) diagnosis, to inform clinical end point definitions for new TB vaccine trials.
  
  
  METHODS
  Children <2 years of age (n = 1445) were screened and investigated for TB during a Bacille Calmette Guerin vaccine trial in South Africa. Standardized clinical, radiologic, and microbiologic data were collected, including paired gastric lavage and induced sputum for MTB liquid culture. Adjusted odds ratios (AORs) were calculated using a multivariate logistic regression model.
  
  
  RESULTS
  Adjusted odds of positive MTB culture increased by 90% with history of wheezing (AOR, 1.9) and by 4% with each 1-mm increase in Mantoux diameter (AOR, 1.04). Odds of positive MTB culture doubled if the chest radiograph was suggestive of pulmonary TB (AOR, 2.16) and more than tripled if lower chest retraction was observed clinically (AOR, 3.37). Fever, night sweats, and presence of lymphadenopathy were negatively associated with MTB culture (AOR: 0.5, 0.62, and 0.2, respectively). Persistent cough, weight loss, and failure to thrive were not significantly associated with MTB culture in this study population.
  
  
  CONCLUSIONS
  Wheezing and lower chest retraction, consistent with intrathoracic airway obstruction; chest radiography suggestive of pulmonary tuberculosis; and Mantoux diameter were predictive of positive MTB culture. These variables should be considered for inclusion in composite clinical end point definitions for infant TB vaccine trials. Several clinical features, commonly used for TB diagnosis in older children, were not associated with positive MTB culture among children younger than 2 years.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Angelique.luabeya@uct.ac.za.
authors.forename: Kany Kany A
authors.initials: KK
authors.lastname: Luabeya
authors.forename: Humphrey
authors.initials: H
authors.lastname: Mulenga
authors.forename: Sizulu
authors.initials: S
authors.lastname: Moyo
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.forename: Welile
authors.initials: W
authors.lastname: Sikhondze
authors.forename: Hennie
authors.initials: H
authors.lastname: Geldenhuys
authors.forename: Hassan
authors.initials: H
authors.lastname: Mohamed
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.forename: Gregory
authors.initials: G
authors.lastname: Hussey
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
mesh_terms: D003470:Culture Media; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D013902:Radiography, Thoracic; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000382:microbiology / Q000517:prevention & control
chemical_list: D003470:Culture Media; D032581:Tuberculosis Vaccines