Executive Summary
The resurgence in cases of active pulmonary tuberculosis (TB) and the emergence of drug-resistant strains of TB have increased the risk that health care workers (HCWs) may acquire serious TB infections which may not respond to usual therapy. Multiple steps are needed to reduce this risk. These include updated periodic training of HCWs to maintain awareness of potential risks of TB; optimizing the design, ventilation, and patient flow in clinical spaces; periodic TB surveillance testing of HCWs; appropriate use of effective respiratory protection; active infection control procedures; and periodic updating of written TB control plans.¹

ACOEM Position
The American College of Occupational and Environmental Medicine (ACOEM) fully supports implementation of the Centers for Disease Control and Prevention (CDC) Guidelines for Preventing the Transmission of Mycobacterium Tuberculosis in Health-Care Facilities, 2005.^2,3 In particular, the College endorses the use of individual risk assessments for each clinical facility and its specific components, with review of the institution’s TB control program at appropriate intervals, in accordance with its case experience. The use of two-step tuberculosis skin testing (TST) of newly hired HCWs who have no documentation of a negative TST result in the previous 12 months can avoid pseudo-conversions (positive TST reactions due to anamnestic responses rather than to recent workplace infections). According to the latest CDC Guidelines, blood assay for Mycobacterium tuberculosis (BAMT) provides an alternative to two-step and periodic TSTs, but cost and lack of a transportable sampling medium may limit its usefulness in most facilities at this time.^2,4

The use of NIOSH-approved powered air purifying respirators (PAPRs) or particulate filter respirators (N-95) will enhance protection for HCWs engaged in high-risk procedures such as bronchoscopy and other airway instrumentation, endoscopy, dental procedures, and sputum induction.³ At least one comparative quantitative study has demonstrated that PAPRs, when appropriately worn, can increase the safety factor over an appropriate N-95 respirator by a factor of ten.⁵ Other studies have also demonstrated that the quality of the N-95 respirator may be more important relative to a good fit than the fitting technique of the user, prompting our recommendation for national standards for N-95 mask quality.^6,7 

In addition, health care facilities should implement appropriate fit testing and medical-certification procedures consistent with the Occupational Safety and Health Administration (OSHA) Standard 1910.139 requirements.³ HCWs who are HIV-positive are at particular risk of infection with TB and should be afforded the highest level of protection, which may include exclusion from activities at high risk of exposure to TB. The employer should make every attempt to honor requests for voluntary reassignment. All HCWs who could potentially care for or have airborne exposure from patients with active TB should have TSTs every 3 to 12 months, depending on the risk assessment and previous TST results. HCWs with unprotected close contact to a patient with active TB should be retested as soon as possible (new “baseline”) and, if negative, again 8 to 10 weeks later to determine if an infection (conversion) has occurred due to that exposure. 

Background

Tuberculosis is a highly communicable disease. Its spread is enhanced by the way TB organisms destroy lung tissue that they infect, often giving rise to cavities containing infected secretions. These secretions stimulate cough, which can help transmit the infection to other parts of the lung, as well as to other persons. Infective droplet nuclei may also be produced by sneezing, singing, or talking. Laryngeal TB is highly infectious and may be more difficult to diagnose and present without coughing. TB organisms tend to remain airborne after being coughed or exhaled into the surrounding air, often creating clusters of infection among exposed individuals in the patient’s dwelling, workplace, aircraft or other transport vehicles, and social settings. 

The risk of spread of TB from a given source case is related to the organism load in expectorated sputum or exhaled air and to how well those organisms are cleared from the air thus contaminated. This baseline risk level can be modified by the following measures:

• Prompt masking of persons suspected of having active TB and their isolation into a room under negative pressure.
• Appropriate and approved respiratory protection worn by potentially exposed HCWs.
• Prompt diagnosis and treatment of patients with active TB with regimens appropriate to community patterns of microbial resistance.

A high index of suspicion for TB can limit its spread to HCWs. Thus, all health care and clerical workers with initial patient contact should be periodically trained to recognize the symptoms and signs of TB and to initiate protection protocols. 

Recent Epidemiology of TB
By the early 1980s, hopes were high that TB would be eradicated in the United States by 2010.⁴ Even in high-prevalence areas such as East Africa, multi-drug, short-course treatment regimens had achieved tremendous success, both in far- advanced and less serious cases. For several reasons, however, the optimism was short-lived. A large number of immigrants with unrecognized TB arrived in the U.S. during the 1980s and continues to this day.^8,9 Cutbacks in funding for TB surveillance allowed such cases and domestic ones to give rise to many additional infections among close contacts because of crowding and other adverse socioeconomic conditions. The emerging prevalence of AIDS has added to the caseload, so that a total of over 52,000 unexpected U.S. cases of active TB occurred by 1992,¹⁰ a pattern that continued but only recently leveled off. Both the overall number of U.S. cases and the U.S. case rate fell by 2.3 and 3.2 percent, respectively, between 2005 and 2006, for example.¹¹ However, Alaska, California, the District of Columbia, New York, Texas, and Hawaii continued to report more than 6 new cases per 100,000 population, in contrast to the national average of 4.6. 

Emergence of Drug-Resistant TB Strains
To compound the problem and increase in its threat to HCWs, many of the new TB isolates were found to be resistant to isoniazid (INH) and/or other drugs, which are usually effective in treating this infection. Most ominous in this regard are the TB strains that are resistant to multiple combinations of such drugs, hence the term multi-drug resistant TB (MDR-TB). Such MDR-TB has infected at least 19 HCWs, eight of whom have died.¹¹ Of even greater concern are the extensive drug-resistant strains of TB (XDR-TB) which are resistant to not only INH and rifampin but also fluoro- quinolones and at least one of the three second-line injectable drugs. Unfortunately, the percentage of such strains in industrialized nations has increased from 3% in 2000 to 11% in 2004.¹² 

Action Steps to Reduce the Spread of TB
Recognition of the resurgence of TB, particularly the threat of XDR-TB, has led the CDC to issue guidance on an updated basis aimed at limiting TB transmission, especially in health care facilities.² Both the CDC guidelines and OSHA requirements call for a TB infection-control program in each such facility, with the program to include a written control plan. The written plan is based on careful risk assessment for the institution as a whole, as well as analyses for specific components such as those in which high-risk activities occur. 

Risk assessment will support implementation of many of the following action steps:¹³

• Periodic training of HCWs to enhance awareness and maintain an appropriate index of suspicion for new TB cases.
• Appropriate management of patients likely to have undiagnosed TB, in emergency, ambulatory, and inpatient settings.
• Engineering controls, including the use of negative-pressure rooms, adequate air exchanges in rooms of patients with suspected TB, careful handling of contaminated air, stand-alone high-efficiency particulate air (HEPA) filter units, and adjunctive use of ultraviolet germicidal irradiation. 
• Masking of patients with suspected TB prior to the initiation of effective therapy when patients are in uncontrolled areas of health care facilities. There should be a high index of suspicion of possible active TB in populations at high risk for TB, such as homeless or incarcerated people. In situations in which a patient with known or suspected active pulmonary TB refuses to wear a mask, questions as to available options should be directed to the institution’s legal counsel or to the state public health department’s legal counsel. 
• Mandatory respiratory protection of HCWs in contact with TB patients, particularly when engaged in high-risk procedures such as bronchoscopy, intubation, sputum induction, surgery, and autopsy. Periodic training must include respirator fit testing and the proper care and use of respirators. 

The effectiveness of a TB infection-control program is measurable by ongoing monitoring of tuberculin conversions among HCWs, scrutiny of clusters of such conversions, investigation of possible person-to-person transmission, and similar analyses. Local public health authorities may be able to provide assistance in investigating a cluster of positive protein derivative (PPD) conversions in the workplace. 

The use of the Bacille Calmette-Guérin (BCG) vaccine in childhood should not be used as an explanation for a positive reaction to the second TST in two-step testing but may explain 8- to 10-mm reactions in persons upon their initial tests. Similar reactions, sometimes larger in size, can occur because inhalation of atypical mycobacteria such as Mycobacterium avium-intracellulare or M. kansasii can cause such responses, but these effects will not usually confound serial TST readings in adults. 

Accurate monitoring of actual TST conversions provides important information about the effectiveness of the overall TB control program. One must also be aware, however, that community exposures rather than job-related ones, could be responsible for some of these TST conversions.¹⁴ For a HCW, a conversion of a TST should be considered work- related unless there was a known exposure to an identified pulmonary TB case outside the work environment. For HCWs in facilities where TB patients receive care, TST reactions of 10-mm induration or more are considered positive. For HCW with recent close unprotected exposure to a patient with infectious TB, or HCW with HIV, an induration of 5mm or greater or an increase of induration of 5mm or greater is also considered a positive result.

When a true conversion does occur, the HCW is now considered to have Latent TB Infection (LTBI) and should have a symptom review and chest radiographs as soon as possible to exclude active disease. In the great majority of cases, radiographs do not show active disease and nine months of INH or 4 months of rifampin therapy is recommended. Recognizing that adherence to nine months of INH has been poor in some non-HCW persons with LTBI, Lardizabal et al., recently presented results favoring the shorter course of rifampin.¹⁵ Although the design of this study relied on historical controls given INH, its findings are encouraging and should lead to the randomized control trials needed in order to establish the role of short-course rifampin (or rifapentine) as alternatives to nine months of INH.¹⁶ Pyridoxine should also be considered for prevention of INH neurotoxicity, but there is no evidence that it is required when rifampin is given.¹⁷ Rifampin toxicity may be minimized by avoiding interruptions in its use. 

The College does not believe that directly observed therapy – now considered a standard of care in many parts of the world – is necessary for all HCWs being treated for LTBI. Though widely practiced in various forms,¹⁸ this therapy was not found to be supported by evidence for or against its efficacy in systematic reviews.¹⁹ No direct studies of directly observed therapy’s efficacy in HCWs have been found. 

For HCWs with a previously positive TST, yearly surveillance should continue, with questions directed at symptoms compatible with pulmonary TB (persistent cough, hemoptysis, night sweats, weight loss, and/or persistent fatigue). If there is clinical suspicion of TB, the HCW should be further evaluated by a physician. Annual chest radiographs are not recommended for asymptomatic HCWs with a previously positive TST. 

The HCW with active pulmonary disease requires immediate therapy with INH, plus three other antituberculosis medications, pending the results of sputum culture and sensitivity determination. HCWs who are found to have active disease may return to work, including patient care, after three consecutive daily sputum smears are negative for acid-fast organisms, provided they are responding clinically and radiographically to treatment. 

Occupational physicians should take a leadership role in promoting an active TB control program, not only in health care institutions,²⁰ but also in other settings where the workforce includes persons at special risk of acquiring and spreading this infection. Such persons include those listed in the ACOEM position statement described above and may include travel assistants (e.g., flight attendants) and clerical and reception staff who may have the initial contact with persons with active TB, who have not yet been so identified.   

References

1. American College of Occupational Medicine. Guidelines for employee health services in health care institutions. J Occup Med. 1986;28(7):518-23.
2. Centers for Disease Control and Prevention. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR. 2005;54(No. RR-17),1-141.
3. US Department of Labor, Occupational Safety and Health Administration. Directive Number CPL 2.106: Enforcement Procedures and Scheduling for Occupational Exposure to Tuberculosis. Washington, DC: OSHA; February 9, 1996.
4. Centers for Disease Control and Prevention. Guidelines for using the QuantiFERON®-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR. 2005;54(No. RR-15);49-55.
5. Nicas M. Respiratory protection and the risk of Mycobacterium tuberculosis infection. Am J Ind Med. 1995;27(3):317-33.
6. Lee K, Slavcev A, Nicas M. Respiratory protection against Mycobacterium tuberculosis: quantitative fit test outcomes for five type N95 filtering-facepiece respirators. J Occup Environ Hyg. 2004;1(1):22-8.
7. Coffey CC, Lawrence RB, Campbell DL, Zhuang Z, Calvert CA, Jensen PA. Fitting characteristics of eighteen N95 filtering-facepiece respirators. J Occup Environ Hyg. 2004;1(4):262-71.
8. American Lung Association. The American Lung Association Conference on Reestablishing Control of Tuberculosis in the United States. Am J Respir Crit Care Med. 1996;154:251-62.
9. McKenna MT, McCray E, Onorato I. The epidemiology of tuberculosis among foreign-born persons in the United States, 1986 to 1993. N Engl J Med. 1995;332(16):1071-6.
10. Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. N Engl J Med. 1992;326(4):231-5.
11. Pratt R, Robison V, Navin T, Hlavsa M, Pevzner E. Trends in tuberculosis incidence – United States, 2006. MMWR. 2007;56:245-50.
12. Menzies D, Fanning A, Yuan L, Fitzgerald M. Tuberculosis among health care workers. N Engl J Med. 1995;332(2):92-8.
13. Kenyon TA, Ridzon R, Luskin-Hawk R, et al. A nosocomial outbreak of multidrug-resistant tuberculosis. Ann Intern Med. 1997;127(1):32-6.
14. Bailey TC, Fraser VJ, Spitznagel EL, Dunagan WC. Risk factors for a positive tuberculin skin test among employees of an urban, midwestern teaching hospital. Ann Intern Med. 1995;122(8):580-5.
15. Lardizabal A, Passannante M, Kojakali F, Hayden C, Reichman LB. Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin. Chest. 2006;130(6):1712-7.
16. Ashkin D, Julien J, Lauzardo M, Hollender E. Consider rifampin but be cautious. Chest. 2006;130(6):1638-40.
17. Forget EJ, Menzies D. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf. 2006;5(2):231-49.
18. Noyes J, Popay J. Directly observed therapy and tuberculosis: How can a systematic review of qualitative research contribute to improving services? A qualitative meta synthesis. J Adv Nurs. 2007;57:(3)227-43.
19. Volmink J, Garner P. Directly observed therapy for treating tuberculosis. Cochrane Database Syst Rev. 2006;19(2):CD003343.
20. Davies YM, McCray E, Simone PM. Hospital infection control practices for tuberculosis. In: Iseman MD, Huitt GA, eds. Chest Medicine. Vol. 18 – Tuberculosis. Philadelphia: WB Saunders; 1997:19-33.

Additional References

American Thoracic Society, Centers for Disease Control and Infectious Diseases Society of America. Treatment of Tuberculosis, 2003. MMWR. 2003;52(RR11);1-77.

Beck-Sague C, Dooley SW, Hutton MD, et al. Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients. JAMA. 1992;268(10):1280-6.

Bowden KM, McDiarmid MA. Occupationally acquired tuberculosis: what’s known. J Occup Med. 1994;36(3):320-5.

Centers for Disease Control and Prevention, Department of Health and Human Services. Draft Guidelines for Infection Control in Health Care Personnel. Federal Register. 1997;62:47275-327 [September 8, 1997].

Cleveland JL, Kent J, Gooch BF, et al. Multidrug resistant Mycobacterium tuberculosis in an HIV dental clinic. Infect Control Hosp Epidemiol. 1995;16(1):7-11.

Dooley SW, Villarino ME, Lawrence M, et al. Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients. JAMA. 1992;267(19):2632-4.

Edlin BR, Tokars JI, Grieco MH, et al. An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992;326(23):1514-21.

Maloney SA, Pearson ML, Gordon MT, Del Castillo R, Boyle JF, Jarvis WR. Efficacy of control measures in preventing nosocomial transmission of multi-drug resistant tuberculosis to patients and health care workers. Ann Intern Med. 1995(2);122:90-5.

Pearson ML, Jereb JA, Frieden TR, et al. Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis: a risk to patients and health care workers. Ann Intern Med. 1992;117(3):191-6.

Stroud LA, Tokars JI, Grieco MH, et al. Evaluation of infection control measures in preventing the nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in a New York City hospital. Infect Control Hosp Epidemiol. 1995;16(3):141-7.

Wenger PN, Otten J, Breeden A, Orfas D, Beck-Sague CM, Jarvis WR. Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among healthcare workers and HIV-infected patients. Lancet. 1995;345(8944):235-40.

Wright A, Bai G, Barrera L, et al. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs worldwide, 2000-2004. MMWR. 55(11):301-5.

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These guidelines were updated by the American College of Occupational and Environmental Medicine (ACOEM) Medical Center Occupational Health Section and Occupational and Environmental Lung Disorders Committee. The authors were William G. Buchta, MD, MS, MPH; Melanie D. Swift, MD; Francesca K. Litow, MD, MPH; Lawrence W. Raymond, MD, ScM; and Lawrence D. Budnick, MD, MPH. These updated guidelines were approved by the ACOEM Board of Directors on February 2, 2008.