Cough aerosols of Mycobacterium tuberculosis predict new infection: a household contact study

Abstract

Rationale: Airborne transmission of Mycobacterium tuberculosis results from incompletely characterized host, bacterial, and environmental factors. Sputum smear microscopy is associated with considerable variability in transmission.

Objectives: To evaluate the use of cough-generated aerosols of M. tuberculosis to predict recent transmission.

Methods: Patients with pulmonary tuberculosis (TB) underwent a standard evaluation and collection of cough aerosol cultures of M. tuberculosis. We assessed household contacts for new M. tuberculosis infection. We used multivariable logistic regression analysis with cluster adjustment to analyze predictors of new infection.

Measurements and main results: From May 2009 to January 2011, we enrolled 96 sputum culture-positive index TB cases and their 442 contacts. Only 43 (45%) patients with TB yielded M. tuberculosis in aerosols. Contacts of patients with TB who produced high aerosols (≥10 CFU) were more likely to have a new infection compared with contacts from low-aerosol (1-9 CFU) and aerosol-negative cases (69%, 25%, and 30%, respectively; P = 0.009). A high-aerosol patient with TB was the only predictor of new M. tuberculosis infection in unadjusted (odds ratio, 5.18; 95% confidence interval, 1.52-17.61) and adjusted analyses (odds ratio, 4.81; 95% confidence interval, 1.20-19.23). Contacts of patients with TB with no aerosols versus low and high aerosols had differential tuberculin skin test and interferon-γ release assay responses.

Conclusions: Cough aerosols of M. tuberculosis are produced by a minority of patients with TB but predict transmission better than sputum smear microscopy or culture. Cough aerosols may help identify the most infectious patients with TB and thus improve the cost-effectiveness of TB control programs.

Figure 1.

Study profile. AFB = acid-fast bacilli; CASS = cough aerosol sampling system; HHC = household contacts; IC = index tuberculosis cases; IGRA = interferon-γ release assay; TB = tuberculosis; TST = tuberculin skin test.

Figure 2.

Distribution of CFU of Mycobacterium tuberculosis in aerosols from 96 patients with pulmonary tuberculosis. (A) Distribution of cough aerosol results according to sputum acid-fast bacilli (AFB) smear microscopy grade. Patients with 0 CFU M. tuberculosis in aerosols (white circles). Patients with 1–9 CFU of M. tuberculosis in (low) aerosol (gray circles). Patients with greater than or equal to 10 CFU of M. tuberculosis in (high) aerosol (black circles). Dashed horizontal lines indicate the median for subjects who produced aerosol (CFU ≥1). Below the graph, the median CFU and range are given for subjects who produced aerosol (CFU ≥1). Because aerosol CFU data are presented on a log scale, 1 was added to all CFU for plotting purposes. (B) Distribution of CFU counts in cough aerosols. TB = tuberculosis.

Figure 3.

Tuberculin skin test (TST) and interferon-γ release assay (IGRA) results in household contacts uninfected at baseline, according to aerosol or sputum results in index tuberculosis (TB) cases. (A) Proportion of contacts with TST, IGRA, or TST and IGRA (both together) conversion at 6 weeks. We present data using two different criteria to define TST conversion. Criterion 1: first TST less than 10 mm, second TST greater than or equal to 10 mm, and difference between first and second TST greater than or equal to 10 mm. Criterion 2: first TST less than 5 mm, second TST greater than or equal to 10 mm, and difference between first and second TST greater than or equal to 6 mm. Comparisons (odds ratios adjusted for clustering and 95% confidence intervals) are based on Criterion 1. The n under each column denotes the number of contacts fulfilling each outcome criterion. The N under each column denotes the number of household contacts “at risk” of conversion in each exposure category. We highlight the N to emphasize a change in exposure categories when using aerosol versus sputum. (B) Quantitative IGRA analysis. Standard box plots of interferon-γ values for each group of contacts. Values are normalized interferon-γ (TB antigen − Nil) results after calculating a delta for each individual from paired blood samples (6-wk level − baseline level).