Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis

Southeastern National Tuberculosis Center, Emerging Pathogens Institute, Room 257, University of Florida, Gainesville, FL 32610, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 07/2012; 186(5):450-7. DOI: 10.1164/rccm.201203-0444OC
Source: PubMed

ABSTRACT

Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission.
To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting.
We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures. A subset of 38 subjects was studied on 2 or 3 consecutive days to assess reproducibility.
M. tuberculosis was cultured from cough aerosols of 28 of 101 (27.7%; 95% confidence interval [CI], 19.9-37.1%) subjects with culture-confirmed TB, with a median 16 aerosol cfu (range, 1-701) in 10 minutes of coughing. Nearly all (96.4%) cultivable particles were 0.65 to 4.7 μm in size. Positive aerosol cultures were associated with higher Karnofsky performance scores (P = 0.016), higher sputum acid-fast bacilli smear microscopy grades (P = 0.007), lower days to positive in liquid culture (P = 0.004), stronger cough (P = 0.016), and fewer days on TB treatment (P = 0.047). In multivariable analyses, cough aerosol cultures were associated with a salivary/mucosalivary (compared with purulent/mucopurulent) appearance of sputum (odds ratio, 4.42; 95% CI, 1.23-21.43) and low days to positive (per 1-d decrease; odds ratio, 1.17; 95% CI, 1.07-1.33). The within-test (kappa, 0.81; 95% CI, 0.68-0.94) and interday test (kappa, 0.62; 95% CI, 0.43-0.82) reproducibility were high.
A minority of patients with TB (28%) produced culturable cough aerosols. Collection of cough aerosol cultures is feasible and reproducible in a resource-limited setting.

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Available from: Scott Dryden-Peterson, Dec 30, 2014
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    • "There are likely host factors, such as host genetics [9] and immune response [15] that explain why these individuals remain relatively resistant to Mtb infection. Alternatively, unmeasured components of shared environment, such as nutrition [29,30] or quantity of Mtb bacilli in the air [31-33], may potentially explain why some individuals remain PTST-. Further study is needed to examine the combined influences of genetics, immunology, and nutrition on resistance to Mtb infection, as well as explore additional epidemiological factors. "
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    ABSTRACT: Background Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment. Methods During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed. Results When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009). Conclusions Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
    Full-text · Article · Jun 2014 · BMC Infectious Diseases
    • "Sputum smear positivity should be considered a risk factor for infectiousness but there are both epidemiologic [22] and experimental studies [23] that have shown considerable variability of infectiousness among sputum smear-positive patients. Some studies suggested that the presence of a cough could generate potentially infectious aerosols that may increase the risk of disease transmission, regardless of the sputum smear status in the index case [24,25]. Our results showed that the positivity of both IGRA tests was associated with the presence of a cough. "
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    ABSTRACT: Background The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts. Methods We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case. Results 156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively. Conclusions Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough.
    No preview · Article · May 2014 · BMC Infectious Diseases
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    • "A fundamental difference between field efficacy trials and laboratory animal exposure is the number of exposures. It is highly likely that a human infection develops after multiple exposures, probably containing only a few organisms [27]. "
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    ABSTRACT: There is an urgent need for an improved TB vaccine. Vaccine development is hindered by the lack of immune correlates and uncertain predictive value of preclinical animal models. As data become available from human efficacy trials, there is an opportunity to evaluate the predictive value of the criteria used to select candidate vaccines. Here we review the efficacy in animal models of the MVA85A candidate vaccine in light of recent human efficacy data and propose refinements to the preclinical models with the aim of increasing their predictive value for human efficacy.
    Full-text · Article · Dec 2013 · Tuberculosis (Edinburgh, Scotland)
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