Tuberculosis outbreak in a long-term care facility.

Khalil, Nashira J. ; Kryzanowski, Julie A. ; Mercer, Nicola J. 等

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is spread through airborne, aerosolized droplet nuclei produced by persons with pulmonary TB during forceful expiration (e.g., coughing, sneezing). (1) TB disease most commonly affects the lungs but can involve almost any organ of the body and was a major cause of morbidity and mortality in Canada throughout the first half of the 20th century.

Since then, the Canadian incidence rate of new cases has steadily declined to approximately 4.7 per 100,000 population per year. (2) The highest rates of TB disease occur in three groups: Aboriginal (28/100,000), (2) foreign-born (13/100,000) (2) and the elderly. In the elderly, incidence rates increase with age, from 5.4 (65-74 years) to 8.5 ([greater than or equal to] 75 years) per 100,000. (2) Classic symptoms of active pulmonary disease are cough, fatigue, weight loss, fever and night sweats. However, elderly patients may present atypically (unexplained weight loss, anorexia, weakness, or change in cognitive status), such that many active cases may be undiagnosed. (3)

In 1956, 75% of persons living in large cities in Ontario had latent TB infection (LTBI) by the age of 60. (4) In 2007, 20-30% of those aged 65 or older in long-term care (LTC) facilities may be infected. (5) Because persons with LTBI remain at risk for reactivation and post-primary TB disease, health care professionals caring for institutionalized elderly must be aware of the risks of TB in the elderly in order to manage this diagnosis.

A 1992 survey of 29 nursing homes and 26 homes for the aged in metropolitan Toronto found that 20% of respondent institutions reported at least one case of active TB in the previous five years. (6) Outbreaks reported in nursing homes in the United States demonstrate that TB transmission is very efficient within closed environments. (7-9) In Arkansas, unrecognized TB in a resident led to infection of 49 other residents, including 8 cases of active TB disease and 1 death. (7) A second outbreak in the state led to infection of 52 employees, 23 residents and 1 visitor. (9) Spread from a nursing home into the community was also reported in a Washington outbreak involving 6 residents, 1 employee and 1 visitor. (8)

To our knowledge, there have been no published reports of TB outbreaks in long-term care facilities in Canada. We present an outbreak of TB that occurred in a Residential and Long-Term Care (LTC) facility in Ontario among staff members and residents from May 2010 to January 2011.

METHODS

Following diagnosis of the index case, case finding was carried out by the local public health unit through the conventional concentric circle approach described in the Canadian Tuberculosis Standards (i.e., casual and community contacts are tested only if close contacts have a high rate of infection). (10) For the purpose of this investigation, all facility staff, volunteers and residents were considered close household contacts (shared airspace on a daily basis and/or >4 hours/week), and visitors and family members were considered close non-household contacts if they shared airspace 2-4 hours/week. Tuberculin skin testing (TST) was conducted for identified contacts at 8-12 week intervals, based on experimental and epidemiologic evidence indicating that TST conversion occurs within 8 weeks of exposure and infection. (10) Induration of 5 mm or greater was considered a positive result. Persons found to have a positive TST received a chest x-ray and a physician assessment to rule out active disease. All suspicious chest x-rays were followed by a chest computerized tomography (CT) scan and sputum samples for culture. One resident was referred for bronchoscopy after attempts to collect sputum were unsuccessful and sputum induction was not available.

Cases defined as confirmed active cases had a positive culture for M. tuberculosis complex with or without symptoms of TB disease, a positive TST or findings indicative of TB infection on x-ray or CT. Cases defined as new latent TB infection (LTBI) had a positive TST preceded by a documented negative TST prior to January 1, 2010 and no symptoms or findings suggestive of active TB disease.

Laboratory analysis of sputum and other samples was conducted at the Public Health Laboratories, Public Health Ontario (PHOL). Standard protocols for restriction fragment-length-polymorphism (RFLP), (6) spoligotyping, (11,12) and mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR) (13,14) methods were used.

An external contractor completed an assessment of the heating, ventilation and air conditioning (HVAC) airflow in December 2010. Air flow measurements were taken in 15 locations within the Facility using an Accubalance 8371. Data-logging measurements of carbon monoxide (CO), carbon dioxide (C[O.sub.2]), temperature and relative humidity were collected in six locations using a TSI QTrak Monitor. Measurements of CO, C[O.sub.2], temperature and relative humidity were recorded at five-minute intervals for three days in duration at each location. The number of air changes per hour (ACH) was calculated: ACH = [Air Supply (cfm) x 60 minutes/hour] / [Volume of the Room (cf)]

RESULTS

A case of active pulmonary TB was diagnosed in May 2010 in a staff member at a 121-bed combined retirement residence and LTC facility that includes private and shared accommodations (two beds per room). The building is separated into two distinct sides: Long-Term Care and Residential. The LTC side has only one floor whereas the Residential side has two floors. Residents typically eat in separate dining rooms; however crossover between facility sides may occur for social activities. The index case presented with classic symptoms of TB disease, including cough, fever, night sweats and pleuritic chest pain in April 2010. Individual risk factors included immigration to Canada in 2004 from a high TB incidence country (Philippines). A 1-step baseline TST was documented as negative in 2007. A chart review did not identify a past history of TB disease or conditions that might have led to a false-negative TST reaction.

Following identification of the index case, primary care physicians attending to facility residents were alert to subtle changes in patient condition and identified additional cases (one in July and two in October 2010). The LTC residents diagnosed with active disease primarily presented with weight loss and worsening chronic cough. By January 2011, a total of 3 laboratory-confirmed active cases and 24 newly identified LTBI among residents and staff had been identified (see Table 1).

The attack rate among staff members was 0.8% (1/121) for active cases and 7.4% (9/121) for new LTBI. For residents (LTC and Residential), attack rates were 2% (3/146) for active cases and 10.3% (15/146) for new LTBI. By January 2011, 24% (10/42) of the identified family members and visitors of active cases had received a TST. None were positive.

In this outbreak, 96.5% (54/56) of LTC residents had a documented 2-step TST at the time of admission to the facility. Although the Canadian Tuberculosis Standards recommend that all employees have a 2-step TST at the time of hiring, documented baseline TST results were available for only 40% (48/121) of staff members.

Laboratory testing

All three genotyping methods confirmed that the four active cases were infected by an identical strain that was unique in the TB genotype database in Ontario and in Canada (Public Health Ontario Laboratory, Toronto, ON and National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB). The outbreak spoligotyping pattern was spoligo-international type (SIT) #167 belonging to the T1-lineage of TB strains, a EuroAmerican strain. At least 42 SIT #167 isolates from several countries worldwide have been reported to the international spoligotyping database curated at L'Institut Pasteur de la Guadeloupe. (15)

Environmental testing

Nine of the 15 locations tested had air exchange rates below the American Society of Heating, Ventilating and Air-Conditioning Engineers (ASHRAE) guidelines, which set a range between 2 (e.g., in corridors) and 10 (e.g., in washrooms, sterilizing, diagnostic and treatment areas) total air exchanges per hour (ACH). (16) Resident rooms, dining rooms and common areas require 4 ACH. Carbon dioxide levels (a surrogate measure of fresh air addition) exceeded the 1000 ppm guideline in the staff meeting area and common area E (although ACH was adequate), indicating that occupancy within the affected rooms was higher than that for which the rooms were designed (see Table 2).

Figure 1 shows the room locations of the active TB and LTBI cases, as well as air flow measurement results within the facility.

Treatment and outcomes

The strain was sensitive to all first-line drugs used to treat TB in Canada: isoniazid (INH), rifampin, ethambutol and pyrazinamide. The index case completed a six-month course of treatment including all four medications without incident. The three residents with active TB disease initiated treatment with isoniazid, rifampin and ethambutol. One also received pyrazinamide. One resident died due to treatment complications (INH hepatitis). The two other residents died during treatment, with TB identified as a contributing factor. The primary causes of death were pulmonary embolism and renal carcinoma.

Fifteen residents were offered treatment for LTBI. Three completed the standard regime (5 mg/kg of INH daily for nine months). One died of unrelated causes while on treatment, two were discontinued secondary to treatment complications and nine residents either refused or had an underlying medical condition that precluded treatment.

Nine staff members with new LTBI were offered treatment. Six completed the standard regime, two refused and one deferred treatment until after pregnancy.

Control measures

Control measures implemented by the facility with assistance of the local public health unit included contact tracing and case follow-up as described above and closing the facility to admissions and resident transfers unless authorized by the public health unit.

DISCUSSION

The facility and local public health unit were concerned with identifying the source of the outbreak and transmission links between the cases. A chart review provided some evidence that one of the residents diagnosed in October 2010 may have been symptomatic as far back as December 2009. The molecular genotyping showed that the four active cases were infected by an identical strain unique in Canada. Since all cases were linked by person, place and time, this outbreak was identified to be an isolated cluster. Close living conditions and prolonged exposure due to delayed diagnosis of active disease were potential factors in the transmission of TB among residents and staff. (17)

In particular, barriers to access of diagnostic services may have delayed diagnosis of some active cases. Many residents were unable to expectorate sufficient amounts of sputum on demand; therefore, samples for microscopic and microbiologic testing were collected opportunistically or via invasive bronchoscopy. Had sputum induction facilities been available in the public health unit, it is possible that suspected cases of active TB might have been identified earlier.

Virtually all patients will produce sputum samples using induction techniques, and a single induced sputum sample has better sensitivity than bronchoscopy for the diagnosis of TB. (2) Sputum induction requires a small, negative pressure room with at least 12 ACH. Air should be exhausted through a dedicated exhaust or HEPA filtered (reference TB guidelines). While a separate sputum induction room may not be practical in all hospitals, complete or partially enclosed booths could be used as an alternative. Complete enclosed booths range in cost from approximately $3000 for a fully enclosed portable tent to $7500 or greater for a booth. (18)

Other factors related to the outbreak setting and population presented challenges to this investigation. The TST "booster effect" was first described in elderly persons in whom it was thought to demonstrate LTBI acquired remotely, with subsequent waning of immunity. However, research suggests that the recommended 2-step test may be insufficient to fully elicit the booster phenomenon in the elderly. (17) Among the LTC residents, most had a documented 2-step TST at the time of admission to the facility. Given that only 7.3% of residents had a positive baseline TST when the true prevalence of LTBI for residents [greater than or equal to] 65 years of age in long-term care facilities in Canada may approach 20-30%, (2) it is possible that some of the LTBI cases identified among residents were not new infections.

The TST booster effect has also been described in persons with sensitivity to non-tuberculous mycobacterial antigens or prior BCG vaccination. In this investigation, most (7 of 10) staff members who were identified with active TB or new LTBI were born outside of Canada. Depending on TB epidemiology and vaccination recommendations in their country of origin, these persons may have been previously infected with TB or other mycobacteria in their country of origin and/or vaccinated with BCG. Documented baseline TST results were available for only 40% of staff members, although the Canadian Tuberculosis Standards recommend that all employees have a 2-step TST at the time of hiring.

Following primary infection, the estimated lifetime risk for the development of TB disease is 10%, although certain factors increase personal risk. For example, HIV infection increases risk to 10% annually, 50-110 times higher than persons without known risk factors. (10) Frail elderly adults residing in long-term care settings have been reported to have 5-50 times greater risk of active disease compared with community-dwelling elderly of a similar age. (17)

Poor adherence has been cited as the most important reason for the failure of treatment to prevent TB disease, (2) but treatment in the elderly is associated with significant morbidity. Of the 18 residents offered treatment for active TB disease or LTBI, 9 initiated treatment and only 3 completed treatment successfully. The mortality rate for residents with active TB disease was 100%.

CONCLUSION

This outbreak investigation attempted to determine the source of the outbreak and transmission links among cases. All cases were linked via epidemiology and molecular diagnostics, but a source case could not be identified conclusively. Given the epidemiology of TB in elderly populations and the high mortality rate associated with treatment, outbreaks should remain an issue of concern for LTC facilities and physicians. With this in mind, some recommendations are provided:

* Baseline 2-step TST, or 1-step in select circumstances at hire or placement for staff and regular volunteers;

* Annual TST for staff and regular volunteers if the annual TST conversion rate in such facilities is 0.5% or higher;

* Baseline posterior-anterior and lateral chest X-ray for new residents;

* Baseline 2-step TST for new residents if required by public health authorities or if the past incidence of active TB in the population served by the institution is elevated;

* Consult as needed with a TB expert regarding management of positive TST results and treatment of active TB cases;

* Suspect active TB in any resident with fever, cough for more than 3 weeks, unexplained weight loss, hemoptysis, loss of appetite or night sweats;

* Proactively secure access to a diagnostic sputum induction service which can be used by residents with suspect disease. It is more sensitive and causes fewer adverse effects than bronchoscopy;

* Prepare written policies and procedures to facilitate the timely transportation of residents and/or laboratory specimens to diagnostic services;

* Check ventilation rates in all rooms regularly used by patients/residents and staff. To minimize the risk of transmission, modify (or upgrade) the system to meet ASHRAE guidelines for each room type. According to Canadian accreditation standards, facilities must be aware of and follow evidence-based international, federal, and provincial or territorial infection control guidelines.

[FIGURE 1 OMITTED]

Received: July 12, 2012 Accepted: November 22, 2012

Acknowledgements: The authors acknowledge the contributions of the following: Janice Walters; Lise Trotz-Williams; Wellington-Dufferin-Guelph Public Health staff; Marie-Line Gilbert; David C. Alexander and Jennifer L. Guthrie, Public Health Ontario Laboratories; Public Health Ontario Laboratories TB and Mycobacteriology laboratory staff.

Conflict of Interest: None to declare.

REFERENCES

(1.) Heymann D (Ed.). Control of Communicable Diseases Manual, 19th ed. Washington, DC: American Public Health Association, 2008.

(2.) Public Health Agency of Canada. Tuberculosis in Canada: 2009 and 2010 Pre Release. Ottawa, ON: PHAC, 2010.

(3.) Van den Brande P. Revised guidelines for the diagnosis and control of tuberculosis: Impact on management in the elderly. Drugs Aging2005;22(8):663-86.

(4.) Grzybowski S. Tuberculous infection in the population of the Province of Ontario. CMAJ1956;75(6):493-96.

(5.) Public Health Agency of Canada. Compendium of Latent Tuberculosis Infection (LTBI) Prevalence Rates in Canada. 2012. Available at: http://www.phacaspc.gc.ca/tbpc-latb/ltbi_compendium-eng.php (Accessed November 9, 2007).

(6.) Naglie G, McArthur M, Simor A, Naus M, Cheung A, McGeer A. Tuberculosis surveillance practices in long-term care institutions. Infect Control Hosp Epidemiol 1995;16(3):148-51.

(7.) Stead WW. Tuberculosis among elderly persons: An outbreak in a nursing home. Ann Intern Med 1981;94(5):606-10.

(8.) Munger R, Anderson K, Leahy R, Allard J, Kobayashi J. Tuberculosis in a nursing care facility--Washington. MMWR 1983;32:121.

(9.) Ijaz K, Dillaha JA, Yang Z, Cave MD, Bates JH. Unrecognized tuberculosis in a nursing home causing death with spread of tuberculosis to the community. J Am Geriatr Soc 2002;50(7):1213-18.

(10.) Long R, Ellis E (Eds.). Canadian Tuberculosis Standards, 6th ed. Ottawa: Public Health Agency of Canada and Canadian Lung Association, 2007.

(11.) van Embden JD, Cave MD, Crawford JT, Dale JW, Eisenach KD, Gicquel B, et al. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: Recommendations for a standardized methodology. J Clin Microbiol 1993;31(2):406-9.

(12.) Cowan LS, Diem L, Brake MC, Crawford JT. Transfer of a Mycobacterium tuberculosis genotyping method, Spoligotyping, from a reverse line-blot hybridization, membrane-based assay to the Luminex multianalyte profiling system. J Clin Microbiol 2004;42(1):474-77.

(13.) McWilliams T, Wells AU, Harrison AC, Lindstrom S, Cameron RJ, Foskin E. Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis. Thorax 2002;57(12):1010-14.

(14.) Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rusch-Gerdes S, Willery E, et al. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat of Mycobacterium tuberulosis. J Clin Microbiol 2006;44(12):4498.

(15.) Demay C, Liens B, Burguiere T, Hill V, Couvin D, Millet J, et al. SITVITWEB--a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. Infect GenetEvol 2012;12(4):755-66.

(16.) American Society of Heating, Refrigerating and Air-Conditioning Engineers. HVAC Design Manual for Hospitals and Clinics. 2003.

(17.) Thrupp L, Bradley S, Smith P, Simor A, Gantz N, Crossley K, et al. Tuberculosis prevention and control in long-term-care facilities for older adults. Infect Control Hosp Epidemiol 2004;25(12):1097-108.

(18.) Curry FJ. Conducting Sputum Induction Safely. National Tuberculosis Center, Institutional Consultation Services, 1999.

Nashira J. Khalil, MHSA, [1] Julie A. Kryzanowski, MD, MSc, [2] Nicola J. Mercer, MD, MPH, [3] Edward Ellis, MD, MPH, [4] Frances Jamieson, MD [5]

Author Affiliations

[1.] Public Health Agency of Canada, Ottawa, ON

[2.] Public Health Services, Saskatoon Health Region, Saskatoon, SK

[3.] Wellington-Dufferin-Guelph Public Health, Fergus, ON

[4.] Public Health Preventive Medicine Consultant, Ottawa, ON

[5.] Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON

Correspondence: Dr. Nicola Mercer, Wellington-Dufferin-Guelph Public Health, 474 Wellington Road 18, Suite 100, RR#1, Fergus, ON N1M 2W3, Tel: 519-846-2715, ext. 2500, E-mail: nicola.mercer@wdgpublichealth.ca

Table 1. Characteristics by Case Definition, May 1, 2010 to
January 31, 2011, Ontario (n=28)

Characteristic                       Case Definition

                               Confirmed
                               Active TB         New LTBI
                                 (n=4)            (n=24)
Number of persons                  4                24
Number of deaths                   3                0
Number of hospitalizations         3                0
Sex
  Female                           3                19
  Male                             1                5
Age
  Range                      40 to 92 years   22 to 94 years
  Mean                          76 years         65 years
  Median                        86 years         72 years
Designation
  LTC residents                    3                10
  Residential residents            0                5
  Staff members                    1                9

Characteristic               Case Definition

                                   All
                                 (n=28)
Number of persons              28 (100.0%)
Number of deaths                3 (10.7%)
Number of hospitalizations      3 (10.7%)
Sex
  Female                       22 (78.6%)
  Male                          6 (21.4%)
Age
  Range                      22 to 94 years
  Mean                          66 years
  Median                       77.5 years
Designation
  LTC residents                13 (46.4%)
  Residential residents         5 (17.9%)
  Staff members                10 (35.7%)

Table 2. Results From Environmental Testing

Location                     ASHRAE        Air        Meets
                           Total ACH     Changes      ASHRAE
                           Guideline    per Hour    Guideline

Dining Room A                  4           0.8          N
Dining Room C                  4            5           Y
Common Area B                  4           3.4          N
Common Area E                  4           4.4          Y
Staff Meeting (Mtg) Area       4           6.1          Y
Room 27                        4            4           Y
Room 31                        4           3.4          N
Room 30                        4           4.0          Y
Room 19                        4           3.3          N
Room 14                        4           3.3          N
Room 7                         4           3.8          N
Room 37                        4           3.2          N
Room 34                        4           3.1          N
Room 22                        4           2.4          N
Common Area D                  10          25           Y