Cough-aerosol cultures of Mycobacterium tuberculosis in the prediction of outcomes after exposure. A household contact study in Brazil

Abstract

BackgroundMycobacterium tuberculosis cultures of cough-generated aerosols from patients with pulmonary tuberculosis (TB) are a quantitative method to measure infectiousness and to predict secondary outcomes in exposed contacts. However, their reproducibility has not been established.ObjectiveTo evaluate the predictive value of colony-forming units (CFU) of M. tuberculosis in cough aerosols on secondary infection and disease in household contacts in Brazil.MethodsAdult sputum smear+ and culture+ pulmonary TB cases underwent a standard evaluation and were categorized according to aerosol CFU. We evaluated household contacts for infection at baseline and at 8 weeks with TST and IGRA, and secondary disease.ResultsWe enrolled 48 index TB cases; 40% had negative aerosols, 27% low aerosols (<10 CFU) and 33% high aerosols (≥10 CFU). Of their 230 contacts, the proportion with a TST ≥10 mm at 8 weeks was 59%, 65% and 75%, respectively (p = 0.34). Contacts of high aerosol cases had greater IGRA readouts (median 4.6 IU/mL, IQR 0.02–10) when compared to those with low (0.8, 0.2–10) or no aerosol (0.1, 0–3.7; p = 0.08). IGRA readouts in TST converters of high aerosol cases (median 20 IU/mL, IQR 10–24) were larger than those from aerosol-negative (0.13, 0.04–3; p = o.o2). 8/9 (89%) culture+ secondary TB cases occurred in contacts of aerosol+ cases.ConclusionAerosol CFU predicts quantitatively IGRA readouts among household contacts of smear positive TB cases. Our results strengthen the argument of using cough aerosols to guide targeted preventive treatment strategies, a necessary component of current TB elimination projections.

Particle sizes of infectious aerosols: implications for infection control

“… 34 A consistent finding in tuberculosis aerosol studies is the variability of infectious aerosol production from patients with pulmonary tuberculosis. 33 These data suggest that a few patients with tuberculosis are infectious via cough aerosols, and some are very infectious, 41 coherent with the epidemiological observation of super-spreading. 42 , 43

Figure 1 Particle size distributions of cough aerosols from (A) patients with tuberculosis 24 and (B) patients with cystic fibrosis infected with Pseudomonas aeruginosa 27 (A) Reproduced from Fennelly et al, 24 by permission of the American Thoracic Society.

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“…Studies of those that included methods to measure particle sizes have consistently found pathogens in small particles (ie, <5 μm; table 1 ). Other studies without particle size data focused on other outcomes, 16 , 33 , 34 or used methods that could not provide sizing data. 35 , 36 , 37 , 38 , 39 , 40 …”

Host Determinants of Infectiousness in Smear-Positive Patients With Pulmonary Tuberculosis

“…The present study included data from 3 cohorts of adult patients (aged ≥18 years) with pulmonary tuberculosis, cohorts with near-identical inclusion criteria. The studies were conducted in Uganda and Brazil over a 13-year period [11, 12, 14].…”

“…Since first demonstrating the feasibility of culturing M. tuberculosis directly from cough-generated aerosol samples in 2004 [10], our group has completed several studies showing that the number of colony-forming units (CFUs) of M. tuberculosis in aerosol samples is a quantitative and more precise marker of infectiousness than sputum AFB smear [11–13], and have demonstrated reproducibility [14]. In studies from Uganda and Brazil, household contacts of the minority of tuberculosis cases with high aerosol CFU counts (≥10 CFUs) were found to have both a higher risk of infection—as measured by qualitative and quantitative readouts of tuberculin skin test and interferon gamma release assay—and higher rates of secondary tuberculosis disease during follow-up [13, 14]. Therefore, elucidating which host, environmental and bacterial factors are associated with M. tuberculosis aerosolization will provide fundamental insights into the pathogen’s aerobiology and may lead to interventions to interrupt transmission.…”

Microbial Aerosols

“…6 Subsequent cohorts of smear-positive culture-proven TB patients from Uganda and Brazil found that 100/233 (43%) patients produced culturable aerosols and of these 57 (24%) were high aerosol producers defined as production of ≥ 10 colony forming units (CFU) of M. tuberculosis from aerosol sampling. [7][8][9] Two other studies from South Africa have been done, one using a minor modification of the CASS method 10 and the other a novel stationary respiratory air sampling chamber in which the whole patient sits. 11 Infectious aerosol production has been found to be only partially related to bacterial burden measured as AFB smear grade or time to positivity in liquid culture media, and it appears to decrease rapidly after commencement of TB therapy.…”