title: Cough Aerosols of Mycobacterium tuberculosis in the Prediction of Incident Tuberculosis Disease in Household Contacts.
abstract: Tuberculosis disease develops in only 5%-10% of humans infected with Mycobacterium tuberculosis The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts.
  
  
  
  We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status.
  
  
  
  During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1-59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4-25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89-41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena.
  
  
  
  We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine Makerere University-Boston Medical Center Research Collaboration.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jones-López
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine.
authors.forename: Carlos
authors.initials: C
authors.lastname: Acuña-Villaorduña
authors.affiliation: Makerere University-Boston Medical Center Research Collaboration.
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.
authors.forename: Mary
authors.initials: M
authors.lastname: Gaeddert
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Kubiak
authors.affiliation: Makerere University-Boston Medical Center Research Collaboration.
authors.forename: Irene
authors.initials: I
authors.lastname: Ayakaka
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Massachusetts.
authors.forename: Laura F
authors.initials: LF
authors.lastname: White
authors.affiliation: Department of Microbiology, Makerere University College of Health Sciences.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Makerere University-Boston Medical Center Research Collaboration Mulago Hospital Tuberculosis Clinic, Mulago Hospital, Kampala, Uganda.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Okwera
authors.affiliation: Pulmonary Clinical Medicine Section, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Fennelly
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols; D002648:Child; D003371:Cough / Q000382:microbiology*; D005191:Family Characteristics; D005260:Female; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis; D012189:Retrospective Studies; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000336:Aerosols
keywords: Mycobacterium tuberculosis; cough-generated aerosols; inoculum; predictors of disease progression; transmission