Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF.

SETTING: In early studies, Xpert® MTB/RIF accurately detected culture-proven pulmonary tuberculosis (TB). Recent reports have, however, found a lower than expected specificity in previously treated TB patients. OBJECTIVE: To investigate the diagnostic accuracy of Xpert in presumptive pulmonary TB patients in Southwestern Uganda. DESIGN: We obtained demographic and clinical information and collected three sputum samples from each patient for smear microscopy, Xpert and culture. We estimated Xpert sensitivity and specificity against culture, and stratified the analysis by previous treatment and sputum quality status. RESULTS: We analyzed results from 860 presumptive TB patients, including 109 (13%) with a previous history of anti-tuberculosis treatment; 205 (24%) were culture-positive. Xpert specificity was lower (91.8%, 95%CI 84.9-96.2) in previously treated than in new TB patients (97.5%, 95%CI 96.1-98.5; P = 0.01). In an adjusted analysis, patients with culture-, Xpert+ results were more likely to have been previously treated for TB (OR 8.3, 95%CI 2.1-32.0; P = 0.002), and to have mucosalivary sputum (OR 4.1, 95%CI 1.1-14.6; P = 0.03), but were less likely to self-report fever (OR 0.23, 95%CI 0.1-0.7; P = 0.008) than patients with concordant positive results. CONCLUSION: Xpert specificity was lower in previously treated patients with suspected TB. The clinical and programmatic impact of culture-, Xpert+ results requires evaluation in future studies.

Role of mechanical ventilation in the airborne transmission of infectious agents in buildings.

Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses.

Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.

BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing. METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used. RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles

The relative efficacy of respirators and room ventilation in preventing occupational tuberculosis.

OBJECTIVES: To evaluate the relative efficacy of personal respiratory protection as the concentrations of infectious aerosols increase or as room ventilation rates decrease. METHODS: We modified the Wells-Riley mathematical model of airborne transmission of disease by adding a variable for respirator leakage. We modeled three categories of infectiousness using various room ventilation rates and classes of respirators over a 10-hour exposure period. RESULTS: The risk of infection decreases exponentially with increasing room ventilation or with increasing personal respiratory protection. The relative efficacy of personal respiratory protection decreases as room ventilation rates increase or as the concentrations of infectious aerosols decrease. CONCLUSIONS: These modeling data suggest that the risk of occupational tuberculosis probably can be lowered considerably by using relatively simple respirators combined with modest room ventilation rates for the infectious aerosols likely to be present in isolation rooms of newly diagnosed patients. However, more sophisticated respirators may be needed to achieve a comparable risk reduction for exposures to more highly concentrated aerosols, such as may be generated during cough-inducing procedures or autopsies involving infectious patients. There is probably minimal benefit to the use of respirators in well-ventilated isolation rooms with patients receiving appropriate therapy.

Irritant-associated vocal cord dysfunction.

Vocal cord dysfunction (VCD) is a poorly understood entity that is often misdiagnosed as asthma. We report eleven cases of VCD in which there was a temporal association between VCD onset and occupational or environmental exposure. We conducted a case-control study to determine if the characteristics of irritant-exposed VCD (IVCD) cases differed from non-exposed VCD controls. Chart review of VCD patients at the authors' institution produced 11 cases that met IVCD case criteria. Thirty-three control VCD subjects were selected by age matching. There were statistical differences between the groups in ethnicity and chest discomfort. There were no statistical differences between the groups for gender, tobacco, smoking habits, symptoms, or pulmonary function parameters. Varied irritant exposures were associated with IVCD. IVCD should be considered in patients presenting with respiratory symptoms occurring after irritant exposures.

Personal respiratory protection against Mycobacterium tuberculosis.

Although there are no data demonstrating the effectiveness of personal respiratory protection in the prevention of occupational tuberculosis, there are sound theoretical bases supporting the use of respirators to reduce the risk of inhalational exposure. The major factor that limits the effectiveness of most respirators is the leakage between the face and the mask. There are data suggesting that traditional fit testing of respirators does not adequately predict the degree of protection in actual use, and more research is needed in that area. There is a large range of infectiousness of aerosols of TB, and classes of respirators vary greatly in the degree of protection they offer. I have argued that respirator selection should be based on anticipated exposures. High-risk exposures to TB are often associated with cough-inducing procedures or with aerosolization of infected tissues during autopsies. In my opinion, the most reasonable type of respirator for such high-risk situations in health care settings is a PAPR hood. The concentration of infectious aerosols in well-ventilated respiratory isolation rooms is likely to be very low, and the new N95 respirators offer a reasonable balance of comfort, cost, practicality, and protection. Preliminary data from mathematical modeling studies suggest there may be little additional benefit from more sophisticated personal respiratory protection in such settings. Additional research is needed to more accurately assess exposures to TB, to determine the size and aerodynamic behavior of TB generated by infectious patients, and to more accurately define the role and effectiveness of personal respiratory protection against TB.