Hospital Ventilation and Risk for Tuberculous Infection in Canadian Health Care Workers

Tuberculosis in health care workers was considered of historic interest only (1) until the early 1990s, when the occurrence of more than a dozen nosocomial outbreaks in U.S. health care centers indicated that tuberculosis remained an important occupational hazard (2). Although the risk for tuberculosis that is attributable to ventilation could not be estimated, inadequate air exchange rates (3, 4), incorrect direction of air flow (5-7), and recirculation of air (5, 6, 8, 9) were identified as contributing factors. These outbreaks, in conjunction with experimental evidence (10, 11), resulted in recommendations for improved ventilation of patient care areas and other measures to prevent nosocomial transmission of tuberculosis (12, 13). Subsequently, several centers reported that implementation of many of these infection control measures resulted in reduced nosocomial tuberculosis transmission (14-18), but they were unable to identify the impact of improved ventilation specifically. In most health care facilities in industrialized countries, the risk for tuberculosis transmission is unknown, but it is probably lower than in the outbreaks cited above. In these facilities, the need for implementation of all recommended measures has been questioned because such a program would be costly (19) and may be neither feasible (20) nor cost-effective (21, 22). We conducted a cross-sectional survey to estimate the association between ventilation of patient care areas in acute-care hospitals and tuberculin skin test conversion among health care workers. Methods Participants Seventeen hospitals in four Canadian cities (Montreal, Toronto, Alberta, and Vancouver) were selected. Fifteen hospitals were classified as posing moderate to high risk for nosocomial tuberculosis transmission because they admitted at least six patients with active tuberculosis annually (12, 23). Two hospitals that admitted fewer than two patients with active tuberculosis annually were classified as low risk. At these hospitals, personnel were eligible for the study if they worked at least 2 days per week and were members of the respiratory therapy or physiotherapy departments or worked as nurses, aides, orderlies, clerks, or housekeepers on selected nursing units. These units included the emergency department, medical or medical/surgical intensive care unit, respiratory diseases unit, and a sample of other medical and surgical wards. Nonclinical workers from several hospitals who did not have contact with patients or clinical specimens were also included. Physicians were not included because of difficulties in exposure estimation. Participants gave written informed consent before completing questionnaires or undergoing tuberculin testing. The study was approved by research ethics committees (equivalent to institutional review boards) at all participating institutions. Measurements At each participating hospital, staff in the infection control department completed questionnaires about past and present tuberculin screening of personnel, isolation policies, use of respirators (masks), availability of negative-pressure rooms (those with inward directional air flow), and changes to the ventilation systems on the units studied. Ventilation was measured in all bronchoscopy rooms, in one to three respiratory isolation rooms, and in two to four nonisolation or general patient rooms on each nursing unit selected for the study. Patient rooms were selected in consultation with the department head or nurse manager to minimize patient discomfort (for example, to avoid studying rooms of very ill patients) and to ensure good representation of rooms on that unit. The direction of air flow was assessed by using smoke tubes at all doors, windows, and ventilation system openings. Air exchanges per hour were estimated by releasing pure CO2 at 13.5 L/min for 5 minutes while a 15-inch fan was operating to ensure thorough mixing. The resultant CO2 concentrations were measured every minute for the next 20 minutes by using an infrared direct reading monitor (limit of detection, 1 ppm) (Analytic Development Co., Hoddesdon, United Kingdom) (24). All doors and windows were kept closed, and the ventilation system (if any) operated normally. Air exchanges per hour were calculated by using the following formula (25): Air exchanges per hour=[(LnCPEAK) (LnCT)]/[T/60], where LnCPEAK is the natural log of the peak concentration of CO2, LnCT is the natural log of the concentration of CO2 at time T, and T is the time in minutes from when the CO2 concentration was at its peak until the end of the measurement period or the CO2 concentration returned to the baseline value. We also calculated the percentage of rooms on each unit and each hospital that met current North American ventilation standards (12, 13): 2 air exchanges per hour for general patient rooms, 6 air exchanges per hour plus inward direction of air flow for isolation rooms, and 15 air exchanges per hour plus inward direction of air flow for bronchoscopy rooms. The ventilation measurements for all rooms studied on each nursing unit were matched to all personnel working there; averages from all rooms studied in each hospital were assigned to physiotherapists and respiratory therapists. Ventilation measures in bronchoscopy suites were matched to respiratory therapists. Records of all patients with confirmed newly diagnosed active pulmonary tuberculosis who were admitted to the study hospitals between 1 July 1992 and 30 June 1995 were reviewed. Microbiologic results and dates of admission, initiation of respiratory isolation, treatment, and discharge were recorded. Occupational tuberculosis exposure was estimated as the total days during which patients with smear-positive tuberculosis were neither isolated nor treated on each unit. Workers completed self-administered questionnaires on demographic information, training, work history, and known occupational or nonoccupational exposure to tuberculosis. Information on previous tuberculin testing and bacille Calmette-Gurin vaccination was abstracted from personnel health records and from childhood vaccination records (if available). Previous bacille Calmette-Guerin vaccination was verified for Quebec-born participants by using the previously validated (26) central registry of the Institut Armand Frappier. To estimate workers' risk for community exposure, information on incidence of all forms of active tuberculosis in each city from 1985 to 1993 was matched to each participant at the level of the census tract (average size, 4000 to 5000 persons). Matching was done by using the postal code of workers' home addresses and the Statistics Canada postal code conversion file. Workers with documented previous positive results on tuberculin tests or a history of previous antituberculosis therapy were not tuberculin tested. Five tuberculin units of purified protein derivativetuberculin, which is bio-equivalent to purified protein derivativestandard (Tubersol, Connaught Laboratories, Toronto, Ontario, Canada), was administered intradermally in the volar aspect of the forearm by using the Mantoux technique. The transverse diameter of induration was demarcated 48 to 72 hours later by using the ballpoint pen technique (27), was measured by using machinists' calipers, and was recorded in mm. Participants with negative results on the initial test underwent a second test (using the same technique) 1 to 4 weeks later to elicit the booster phenomenon. All workers with positive reactions ( 10 mm [28]) to the first or second test were referred to nonstudy personnel for chest radiography and medical evaluation; results of these evaluations were unavailable. Statistical Analysis The primary outcome measure was tuberculin conversion, defined as induration of 10 mm or greater with an increase of at least 6 mm (28) more than 1 year after a negative result on tuberculin testing (<10 mm). Workers were included in the analysis of conversion if they had had at least two documented tuberculin tests more than 1 year apart at the same hospital and if the earlier test or tests were negative. Results in workers who were tuberculin positive ( 10 mm) at hiring were not included because these infections did not result from occupational exposure at the study hospitals. Workers who had never been tested before the survey were not included because positive results on tuberculin tests that might have been positive at the time of hiring (had the workers been tested) could not be distinguished from subsequent occupation-related tuberculosis infection. Bivariate associations were tested by using unpaired t-tests for continuous variables and chi-square tests for categorical variables (29). Survival analyses were done to make use of the variable interval between hiring and tuberculin conversion or last negative tuberculin test (30). Proportional hazards regression, adjusted for potentially confounding factors, was performed to estimate the effect of ventilation; adjustment for potential clustering (31) was then done because we used hospital unitbased measures of exposure. The resultant parameter estimates and standard errors were used to calculate hazard ratios and 95% CIs for tuberculin conversion (30). Proportional hazards regression adjusted for clustering was performed by using Stata software, version 6.0 (Stata Corp., College Station, Texas). All other data analyses were performed by using SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Sources The funding sources had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results Study Hospitals and Population The 15 moderate- to high-risk hospitals were of similar size, but the age and adequacy of ventilation of the facilities differed greatly (Table 1). Most hospitals had a current policy of performing tuberculin skin testing in workers at hiring, but fewer than ha