Chest ACCP Career Connection
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shukla, S. J.
Right arrow Articles by Fraser, V. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shukla, S. J.
Right arrow Articles by Fraser, V. J.
(Chest. 2002;122:1609-1614.)
© 2002 American College of Chest Physicians

Factors Associated With the Treatment of Latent Tuberculosis Infection Among Health-Care Workers at a Midwestern Teaching Hospital*

Sunita J. Shukla, MPH; David K. Warren, MD; Keith F. Woeltje, MD, PhD; Carol A. Gruber, RN and Victoria J. Fraser, MD

* From the Division of Infectious Diseases (Ms. Shukla, and Drs. Warren and Fraser), Washington University School of Medicine, St. Louis, MO; Division of Infectious Diseases (Dr. Woeltje), Medical College of Georgia, Augusta, GA; and Department of Occupational Health and Safety (Ms. Gruber), Barnes-Jewish Hospital, St. Louis, MO.

Correspondence to: David K. Warren, MD, Division of Infectious Diseases, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Ave, St. Louis, MO 63110; e-mail: dwarren{at}im.wustl.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: To assess factors associated with initiating therapy and compliance with treatment for latent tuberculosis infection among health-care workers with positive tuberculin skin test results.

Design: Prospective cohort study.

Setting: An urban midwestern teaching hospital in St. Louis, MO.

Study population: Health-care workers with positive tuberculin skin test results.

Measurements: (1) Rates of initiating therapy for latent tuberculosis infection among all health-care workers with positive tuberculin skin test results, and (2) compliance rates with therapy for latent tuberculosis infection among health-care workers with recent tuberculin skin test conversion.

Results: A total of 440 tuberculin skin test-positive health-care workers were evaluated from January 1, 1994, to May 1, 2000. Of those evaluated, 1 health-care worker had presumed active tuberculosis, 1 had no record of being evaluated, 1 had missing records, and 33 were not recommended isoniazid therapy, leaving 404 workers for analysis. Overall, 396 of 404 health-care workers (98%) with positive tuberculin skin test results initiated isoniazid therapy. In univariate analysis, bacille Calmette-Guérin (BCG) vaccination (p = 0.02) and foreign birth (p = 0.03) were significantly associated with not initiating isoniazid therapy. Compliance data were available for 388 of 404 health-care workers (96%). Of these, 318 of 388 health-care workers (82%) were compliant with 6 months of therapy. BCG vaccination (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8 to 7.1) and symptoms while receiving therapy (OR, 4.5; 95% CI, 2.0 to 10.1) were significantly associated with noncompliance in multivariate analysis. Among new converters, Asian race (p = 0.006), foreign birth (p = 0.01), BCG vaccination (p = 0.006), and symptoms while receiving therapy (p < 0.001) were significantly associated with noncompliance in univariate analysis.

Conclusion: This hospital had a high rate of initiating isoniazid therapy for tuberculosis infection among their health-care workers, and a high rate of compliance with therapy. These rates of initiation and completion of isoniazid therapy were much higher than those previously reported in the literature. This may be largely due to a focused program, which includes active follow-up of health-care workers with positive tuberculin skin test results, consisting of physician counseling and monthly phone consultations by nurses, along with free services and medications provided on-site.

Key Words: compliance • health-care workers • isoniazid • latent infection • tuberculosis


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Health -care workers are at risk for tuberculosis exposure and infection when they care for patients.1 A comprehensive tuberculosis control program for health-care facilities reduces the risk of nosocomial tuberculosis and is mandated by the Occupational Health and Safety Administration.2 Although effective infection-control measures can greatly decrease the risk of nosocomial tuberculosis infection, the risk of tuberculosis exposure and infection among health-care workers will always be present to some extent.3 Therefore, screening workers for latent tuberculosis infection, using the Mantoux test, remains an integral part of tuberculosis control programs for health-care facilities. Tuberculin skin testing programs serve two important purposes: to monitor tuberculosis acquisition among health-care workers, and to identify workers with latent tuberculosis infection who need treatment.1 3 Rapid identification of employees with positive tuberculin skin test results should be followed by an evaluation for active tuberculosis disease and appropriate therapy of latent infection.4

Despite the known benefit of treatment of latent tuberculosis infection, compliance with therapy for latent tuberculosis infection in hospital employees has not always been optimal.2 3 5 6 7 8 Barrett-Connor5 found only 41.3% of physicians with positive tuberculin skin test results initiated therapy for latent infection, while LoBue and Catanzaro9 noted an 84% rate of initiating therapy among all health-care workers. Camins et al3 and LoBue and Catanzaro9 reported compliance rates with isoniazid therapy among health-care workers of 55% and 48.4%, respectively. Other studies5 6 10 11 have revealed compliance rates with therapy for latent tuberculosis infection to range from 8 to 60% in health-care workers. However, these studies are limited by small sample sizes,5 6 10 11 retrospective study designs,9 and lack of multivariate analysis to assess factors associated with noncompliance. In addition, previous studies5 6 10 11 have not addressed rates of initiation or compliance with therapy among new converters, a group that has been noted to be at increased risk of active tuberculosis.

The low reported rate of initiating and completing isoniazid therapy among health-care workers is in stark contrast to our current understanding of the effectiveness of therapy for latent tuberculosis infection. American Thoracic Society guidelines suggest that the maximum beneficial effect of isoniazid therapy is likely obtained after 9 months of therapy.12 In healthy persons, latent tuberculosis infection can be cured with 93 to 98% certainty by administration of isoniazid for 6 to 12 months with sufficient compliance with therapy.13 The effectiveness of isoniazid therapy has been known for > 40 years. A community-wide controlled trial14 conducted in Alaska showed a 60% decrease in the incidence of active tuberculosis, even with a population consisting of partially and fully compliant patients. In addition, this study found that the difference in case rates of tuberculosis between the placebo-treated and isoniazid-treated groups was greatest for those who were most compliant with their medication.14 The 5-year follow-up by the International Union Against Tuberculosis Committee on Prophylaxis15 also showed that the relative risks of acquiring active tuberculosis decreased as the duration of isoniazid therapy increased; these interregimen differences were found to be statistically significant.

The purpose of this study was to assess rates of initiating therapy for latent tuberculosis infection among employees at a midwestern teaching hospital with positive tuberculin skin test results. In addition, this study sought to identify factors associated with noncompliance with therapy of latent tuberculosis infection among all health-care workers and, in particular, health-care workers with recent tuberculin skin test conversions.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Barnes-Jewish Hospital (BJH) is a 1,200-bed tertiary-care hospital affiliated with Washington University School of Medicine, located in St. Louis, MO. From January 1, 1994, to May 1, 2000, 13 to 28 patients per year with active, culture-positive tuberculosis were admitted to this hospital, for an average incidence of 4.4 cases per 10,000 hospital admissions per year. In comparison, the incidence of active tuberculosis in the United States in 1999 was 6.4 cases per 100,000 population, 3.8 cases per 100,000 population in Missouri,16 3.5 cases per 100,000 population in St. Louis County, and 12.3 cases per 100,000 population in St. Louis City.17

The BJH Occupational Health Department provides tuberculin skin testing for all employees at the time of hire and annually, as well as after exposure to a case of active tuberculosis. Two-step initial skin testing of all new employees began in 1998; one-step testing was performed prior to that time. The first tuberculin skin test is administered on the initial visit to the occupational health department and read 2 to 3 days later. The second test is performed within 3 weeks of the initial skin test and read within 2 to 3 days. House-staff and some fellows in training at BJH are considered employees, with baseline testing and postexposure testing handled through the BJH Occupational Health Department. All hospital employees with positive tuberculin skin test results are examined and evaluated for isoniazid therapy by a physician. Medications for the treatment of latent tuberculosis infection, laboratory testing, and medical evaluations are provided at no cost to health-care workers through the Occupational Health Department. Employees receiving therapy are called by occupational health nurses monthly to assess for side effects and compliance with the medication. An occupational health database is maintained, which includes information on the test dates, the type of medications received, dates received, and the number of months the medication(s) are received.

A prospective cohort study was performed on all employees with a positive tuberculin skin test result between January 1, 1994, and May 1, 2000. All employees with positive tuberculin skin test results were evaluated by occupational health nurses and physicians. Data concerning the employees’ current and prior tuberculin skin test results, medication(s) received, history of active tuberculosis, previous chest radiographs, and compliance rates were obtained from employee records located in the BJH Occupational Health Department. Phone interviews of employees were conducted where demographic information was incomplete.

Skin testing consisted of 0.1 mL (five tuberculin units) of purified protein derivative (Tubersol; Connaught; Swiftwater, PA) injected intradermally on the volar surface of the forearm and read 48 to 72 h later by one of the occupational health nurses. A positive test result was defined as >= 10 mm of induration. A new converter was defined as an individual having a >= 10 mm increase in induration within 2 years of a previously documented negative test result at BJH. Employees were defined as nurses, physicians, clinical, and nonclinical personnel. Baseline chest radiographs were obtained from any employee who had a skin test result >= 10 mm of induration. Annual chest radiographs of tuberculin skin test-positive employees were discontinued in the early 1980s at this facility. Known tuberculin skin test-positive employees are administered an annual questionnaire regarding symptoms suggestive of active tuberculosis, and a chest radiograph is performed in symptomatic employees. No baseline laboratory testing was performed unless the employee was older (approximately >= 65 years), was at an increased risk of hepatoxicity due to underlying liver disease, or acquired symptoms while receiving therapy. Two health-care workers were reported to have abnormal liver function test results. Because normal results were not consistently documented, it is unclear exactly how many total liver function tests were performed.

Clinical health-care workers included those with direct patient contact, such as patient-care technicians, orderlies, physical, respiratory and occupational therapists, translators, and phlebotomists. Nonclinical health-care workers included those who did not have direct patient contact, such as custodial, clerical, and laboratory staff. Noncompliance was defined as receiving < 6 months of therapy or refusal of therapy. Compliance data were cross-checked with outpatient pharmacy records. This study was approved by the Washington University Institutional Review Board.

Statistical analysis was performed using SPSS version 8.0 (SPSS; Chicago, IL). Comparison of ages between compliant and noncompliant health-care workers, as well as new converters and health-care workers with long-standing tuberculosis infections, was conducted using the Student’s t test. Nonnormally distributed variables were compared using Wilcoxon rank-sum test. Statistical analysis of new converter demographics, initiation, and compliance with therapy were done using the {chi}2 test or Fisher exact test. Multivariate analysis was performed by logistic regression. Inclusion of variables in the final regression model was based on variables having a significance of <= 0.05 in univariate analysis and those that added to the overall predictive power of the model. However, variables that were closely correlated with one another, such as race and place of birth, could not both be included in a final model. A p value <= 0.05 was considered significant on two-tailed testing.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
A total of 440 health-care workers with positive tuberculin skin test results were evaluated during the study period. Of these, one health-care worker had presumed active tuberculosis (an individual with night sweats and a right upper lobe pulmonary infiltrate on chest radiograph, who had multiple sputum specimens that were smear-negative and culture-negative for Mycobacterium tuberculosis; however, she responded clinically to four-drug antituberculosis therapy for 6 months). One health-care worker was never evaluated by the Occupational Health Department. One health-care worker had missing medical records, and 33 health-care workers were not recommended for isoniazid therapy, leaving 404 health-care workers for analysis (Table 1 ). The median age for those who were not recommended isoniazid therapy was 38 years (range, 29 to 62 years). There were 11 nonclinical workers, 9 clinical workers, 9 physicians, and 4 nurses among those who were not recommended isoniazid therapy (Table 2 ).


View this table:
[in this window]
[in a new window]

  		Table 1.. Demographics of 404 Health-Care Workers With Positive Tuberculin Skin Test Results*

 

View this table:
[in this window]
[in a new window]

  		Table 2.. Demographics of 33 Health-Care Workers for Whom Therapy for Latent Tuberculosis Infection Was Not Recommended*

 
There were no known skin test conversions due to documented nosocomial exposure during the study period. One hundred eighty-nine of 404 health-care workers (47%) had a positive tuberculin skin test result at the time of hire. Of the 215 of 404 health-care workers (53%) who had negative tuberculin skin test results at hire, 173 health-care workers (80%) had subsequent skin test conversions within 2 years of a prior negative test result, and 42 health-care workers (20%) had documented positive tuberculin skin test results >= 2 years after a documented negative test result. (Annual skin testing was not consistently enforced prior to 1994.) One hundred seventy of 173 new converters (98%) initiated therapy for latent tuberculosis infection.

Compliance data were available for 388 of 404 health-care workers (96%). Three hundred eighteen of 388 health-care workers (82%) studied were compliant with therapy. Eight health-care workers (2%) refused therapy, and 62 health-care workers (16%) completed < 6 months of therapy. Of the eight health-care workers who refused therapy, 50% were white, 38% were clinical workers, 50% were < 35 years old, and 63% were foreign-born individuals who had prior bacille Calmette-Guérin (BCG) vaccinations. Thirty-five of 70 noncompliant individuals (50%) were nonclinical health-care workers, which was not statistically different than clinical health-care workers. In multivariate analysis, BCG vaccination and symptoms on therapy were associated with noncompliance among all health-care workers with positive tuberculin skin test results (Table 3 ). Among new converters, significant risk factors for noncompliance with therapy in univariate analysis were Asian race, foreign birth, BCG vaccination, and symptoms while receiving therapy (Table 4 ).


View this table:
[in this window]
[in a new window]

  		Table 3.. Analysis of Compliance With Therapy for Latent Tuberculosis Infection Among Health-Care Workers*

 

View this table:
[in this window]
[in a new window]

  		Table 4.. Analysis of Compliance With Therapy for Latent Tuberculosis Infection Among New Tuberculin Skin Test Converters*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This prospective cohort study of 404 health-care workers with positive tuberculin skin test results noted a high rate of initiating isoniazid therapy and a high rate of compliance with therapy. This is likely due to active follow-up, consisting of physician counseling and monthly phone consultations by nurses in the BJH Occupational Health Department, along with free services and medication. Foreign-born health-care workers, the majority of whom received BCG vaccination, continue to be a group that is less likely to initiate therapy of latent tuberculosis infection. This may be largely due to the preconceived notion that BCG vaccination provides lifelong immunity against tuberculosis, along with the inability of the current skin testing method to distinguish between positive results from true infection or vaccination with absolute certainty. Hence, measures should be taken in order to overcome cultural barriers, which may lead to refusing therapy and noncompliance with therapy.

Our study noted a high rate of initiation (98%) and compliance (82%) with isoniazid therapy, in contrast to the 84% initiation rate3 and the 48 to 66% compliance rates seen in prior studies.3 9 This observation may be due to health-care workers being seen by a physician after their skin test conversion, and our ability to prescribe isoniazid therapy with minimal inconvenience to the health-care worker, plus encouragement to receive therapy. Health-care workers with positive tuberculosis skin test results are seen by a physician who counsels them on the risks, benefits, and possible side effects of receiving preventive therapy. Health-care workers experiencing symptoms while receiving therapy who are not experiencing drug toxicity may need to be more closely monitored and counseled further about the efficacy of remaining compliant with therapy. In our study, there were only two health-care workers with elevated liver transaminase levels, and these individuals were able to complete therapy with continued close monitoring.

One major limitation of the study was that patient information, such as past tuberculin skin test dates and test results prior to hire at BJH, along with tuberculosis risk factors, were based on self-reporting. Thus, information regarding prior tuberculosis test dates could have been subject to recall bias (since BJH did not start routine annual skin testing until 1994), which could have affected the number of new converters in the study. There were seven health-care workers under the age of 35 years who were not recommended isoniazid therapy. They were mostly foreign-born individuals who had prior BCG vaccinations. In addition, other factors that could have resulted in no recommendation of therapy included heavy alcohol use, pregnancy, or underlying liver disease. Even if these seven health-care workers were included among those who did not initiate therapy, BJH would still have a 96% (395 of 411 health-care workers) initiation rate, which is still higher than what is reported in the literature. Another limitation in this study was the inability to truly decipher between some health-care workers who were not recommended therapy and those who actually refused it. In addition, insufficient self-reporting led to the inability to analyze certain factors (IV drug use, alcohol use, homeless, etc) associated with tuberculosis exposure and infection.

In summary, rates of initiating (98%) and completing (82%) therapy for latent tuberculosis infection were high among health-care workers in this study. Among all health-care workers with a positive tuberculin skin test result, foreign birth, BCG vaccination, Asian race, and symptoms on therapy were significantly associated with noncompliance. If analysis is restricted to new converters, foreign birth, Asian race, BCG vaccination, and symptoms on therapy were significantly associated with noncompliance. These findings demonstrate that BJH has effective administrative controls and monitoring practices to promote use of therapy for latent tuberculosis infection and completion of the recommended duration of therapy. However, continual efforts should be directed toward improving and maintaining measures to maximize initiation of and compliance with therapy for latent tuberculosis infection in order to prevent nosocomial tuberculosis infection among health-care workers.


   Acknowledgements
 
We thank Cherie Hill for statistical support.


   Footnotes
 
Abbreviations: BCG = bacille Calmette-Guérin; BJH = Barnes-Jewish Hospital; CI = confidence interval; OR = odds ratio

Funding for this study was provided in part by the Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health (U50/ccu710076).

Received for publication December 3, 2001. Accepted for publication April 30, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Maloney, SA, Pearson, ML, Gordon, MT, et al (1995) Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers. Ann Intern Med 122,90-95[Abstract/Free Full Text]
  2. Occupational Safety and Health Administration, Office of Health Compliance, February 9, 1996. OSHA instruction CPL 2.106: enforcement procedures and scheduling for occupational exposure to tuberculosis. Available: http://www. osha.gov/. Accessed October 8, 2002
  3. Camins, BC, Bock, N, Watkins, DL, et al Acceptance of isoniazid preventive therapy by health care workers after tuberculin skin test conversion. JAMA 1996;275,1013-1015[Abstract]
  4. Hallak, KM, Schenk, M, Neale, AV Evaluation of the two-step tuberculin skin test in health care workers at an inner-city medical center. J Occup Environ Med 1999;41,393-396[CrossRef][ISI][Medline]
  5. Barrett-Connor, E The epidemiology of tuberculosis in physicians. JAMA 1979;241,33-38[Abstract]
  6. Geiseler, PJ, Nelson, KE, Crispen, RG Tuberculosis in physicians: compliance with preventive measures. Am Rev Respir Dis 1987;135,3-9[ISI][Medline]
  7. Raad, I, Cusick, J, Sherertz, RJ, et al Annual tuberculin skin testing of employees at a university hospital: a cost-benefit analysis. Infect Control Hosp Epidemiol 1989;10,465-469[ISI][Medline]
  8. Nettleman, MD, Geerdes, H, Roy, MC The cost-effectiveness of preventing tuberculosis in physicians using tuberculin skin testing or a hypothetical vaccine. Arch Intern Med 1997;157,1121-1127[Abstract]
  9. LoBue, PA, Catanzaro, A Effectiveness of a nosocomial tuberculosis control program at an urban teaching hospital. Chest 1998;113,1184-1189[Abstract/Free Full Text]
  10. Ruben, FL, Norden, CW, Schuster, N Analysis of a community hospital employee tuberculosis screening program 31 months after its inception. Am Rev Respir Dis 1997;115,23-28
  11. Vogeler Douglas, M, Burke, JP Tuberculosis screening for hospital employees: a five-year experience in a large community hospital. Am Rev Respir Dis 1978;117,227-232[ISI][Medline]
  12. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161(4 pt 2),S221-S247[Free Full Text]
  13. Stead, WW Management of health care workers after inadvertent exposure to tuberculosis: a guide for the use of preventive therapy. Ann Intern Med 1995;122,906-912[Abstract/Free Full Text]
  14. Comstock, GW, Ferebee, SH, Hammes, LM A controlled trial of community-wide isoniazid prophylaxis in Alaska. Am Rev Respir Dis 1967;95,935-943[ISI][Medline]
  15. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 1982;60,555-564[ISI][Medline]
  16. Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 1999. Available at: http://www.cdc.gov/nchstp/tb/surv2000/content/st2000.htm. Accessed April 4, 2001
  17. Tomlinson, V Tuberculosis annual report for 1999. Missouri Epidemiologist 2000;22



This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Controlling Tuberculosis in the United States
Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1169 - 1227.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shukla, S. J.
Right arrow Articles by Fraser, V. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shukla, S. J.
Right arrow Articles by Fraser, V. J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS