title: Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics.
abstract: BACKGROUND
  The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10-20% of individuals, but the underlying mechanisms are poorly understood.
  
  
  METHODS
  We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.
  
  
  RESULTS
  We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02-1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99-1.98, p = 0.06).
  
  
  CONCLUSIONS
  We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America; Makerere University-Boston Medical Center Research Collaboration, Kampala, Uganda.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jones-López
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Laura F
authors.initials: LF
authors.lastname: White
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kirenga
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Francis
authors.initials: F
authors.lastname: Mumbowa
authors.affiliation: Makerere University-Boston Medical Center Research Collaboration, Kampala, Uganda.
authors.forename: Martin
authors.initials: M
authors.lastname: Ssebidandi
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moine
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Olive
authors.initials: O
authors.lastname: Mbabazi
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Gerald
authors.initials: G
authors.lastname: Mboowa
authors.affiliation: Makerere University-Boston Medical Center Research Collaboration, Kampala, Uganda.
authors.forename: Irene
authors.initials: I
authors.lastname: Ayakaka
authors.affiliation: Department of Preventive Medicine and Community Health, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Microbiology & Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Thornton
authors.affiliation: Mulago Hospital Tuberculosis Clinic, Mulago Hospital, Kampala, Uganda; Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Okwera
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Division of Infectious Diseases and Global Medicine, Department of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Fennelly
mesh_terms: D000328:Adult; D000336:Aerosols; D001500:BCG Vaccine / Q000276:immunology; D003371:Cough / Q000382:microbiology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000382:microbiology / Q000635:transmission; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D016017:Odds Ratio; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D014374:Tuberculin Test
chemical_list: D000336:Aerosols; D001500:BCG Vaccine; D007371:Interferon-gamma