Journal
CLINICAL INFECTIOUS DISEASES
Volume 63, Issue 1, Pages 10-20Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciw199
Keywords
Mycobacterium tuberculosis; cough-generated aerosols; inoculum; predictors of disease progression; transmission
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Funding
- Division of Global Medicine, Department of Medicine, University of Florida
- Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine
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Background. 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. Methods. 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. Results. 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. Conclusions. 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.
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