Tuberculosis testing: Which patients, which test?

,; ,

Applied Evidence

Tuberculosis testing: Which patients, which test?

J Fam Pract. 2015 September;64(9):553-557,563-565

Curt Elliott, MD

Jeff Hall, MD

The most appropriate test to identify latent TB depends on the patient’s risk for developing active TB and other factors. This review provides practical guidance on who to test, how, and when.

PDF Download

References

1. World Health Organization. Tuberculosis. World Health Organization Web site. Available at: http://www.who.int/mediacentre/factsheets/fs104/en/. Accessed July 7, 2015.

2. Zumla A, Raviglione M, Hafner R, et al. Current concepts: tuberculosis. N Engl J Med. 2013;368:745-755.

3. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. 2000;49:1-51.

4. Hauck FR, Neese BH, Panchal AS, et al. Identification and management of latent tuberculosis infection. Am Fam Physician. 2009;79:879-886.

5. Getahun H, Matteelli A, Chaisson RE, et al. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372:2127-2135.

6. Arshad S, Bavan L, Gajari K, et al. Active screening at entry for tuberculosis among new immigrants: a systematic review and meta-analysis. Eur Respir J. 2010;35:1336-1345.

7. Greenaway C, Sandoe A, Vissandjee B, et al; Canadian Collaboration for Immigrant and Refugee Health. Tuberculosis: evidence review for newly arriving immigrants and refugees. CMAJ. 2011;183:E939-E951.

8. Jensen PA, Lambert LA, Iademarco MF, et al; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54:1-141.

9. Taylor Z, Nolan CM, Blumberg HM; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2005;54:1-81.

10. Pai M, Menzies D. Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-negative adults. UpToDate Web site. Available at: http://www.uptodate.com/contents/diagnosisof-latent-tuberculosis-infection-tuberculosis-screening-in-hivnegative-adults. Accessed July 7, 2015.

11. Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics. 2004;114:1175-1201.

12. Centers for Disease Control and Prevention. Anergy skin testing and tuberculosis [corrected] preventive therapy for HIV-infected persons: revised recommendations. MMWR Recomm Rep. 1997;46:1-10.

13. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 1996;45:1-18.

14. Farhat M, Greenaway C, Pai M, et al. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis. 2006;10:1192-1204.

15. Wang L, Turner MO, Elwood RK, et al. A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements. Thorax. 2002;57:804-809.

16. Centers for Disease Control and Prevention (CDC). Fact sheets: BCG vaccine. CDC Web site. Available at: http://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm. Accessed July 16, 2015.

17. Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med. 1999;159:15-21.

18. van Zyl-Smit RN, Zwerling A, Dheda K, et al. Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. PLoS One. 2009;4:e8517.

19. Mazurek GH, Jereb J, Lobue P, et al; Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC). Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep. 2005;54:49-55.

20. Mazurek GH, Jereb J, Vernon A, et al; IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010;59:1-25.

21. Muñoz L, Santin M. Interferon- release assays versus tuberculin skin test for targeting people for tuberculosis preventive treatment: an evidence-based review. J Infect. 2013;66:381-387.

22. Zwerling A, Behr MA, Verma A, et al. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011;8:e1001012.

23. Mandalakas AM, Detjen AK, Hesseling AC, et al. Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2011;15:1018-1032.

24. American Academy of Pediatrics Committee on Infectious Diseases, Pickering L, ed. Red Book. Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:741.

25. Zwerling A, van den Hof S, Scholten J, et al. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax. 2012;67:62-70. 26. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149:177-184.

27. Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon- release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest. 2012;142:63-75.

28. Dorman SE, Belknap R, Graviss EA, et al; Tuberculosis Epidemiologic Studies Consortium. Interferon-release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. Am J Respir Crit Care Med. 2014;189:77-87.

29. Scott C, Kirking HL, Jeffries C, et al; Centers for Disease Control and Prevention (CDC). Tuberculosis trends—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:265-269.

30. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician. 2005;72:1761-1768.

31. Rangaka MX, Wilkinson KA, Glynn JR, et al. Predictive value of interferon-release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:45-55.

32. Metcalfe JZ, Everett CK, Steingart KR, et al. Interferon-release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and metaanalysis. J Infect Dis. 2011;204:S1120-S1129.

33. Keshavjee S, Farmer PE. Tuberculosis, drug resistance, and the history of modern medicine. N Engl J Med. 2012;367:931-936.

34. Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009;58:7-10.

35. World Health Organization. Global tuberculosis report 2014. World Health Organization Web site. Available at: http://www.who.int/tb/publications/global_report/en/. Accessed July 17, 2015.

36. Steingart KR, Schiller I, Horne DJ, et al. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014;1:CD009593.

37. Hall J, Elliott C. Tuberculosis: Which drug regimen and when. J Fam Practice. 2015;64:27-33.

PRACTICE RECOMMENDATIONS

› Test for latent tuberculosis (TB) infection by using a tuberculin skin test (TST) or interferon gamma release assay (IGRA) in all patients at risk for developing active TB. B
› Consider patient characteristics such as age, previous vaccination with bacille Calmette-Guérin (BCG), and whether the patient will need serial testing to decide whether TST or IGRA is most appropriate for a specific patient. C
› Don’t use TST or IGRA to make or exclude a diagnosis of active TB; use cultures instead. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE 1 › Judy C is a newly employed 40-year-old health care worker who was born in China and received the bacille Calmette-Guérin (BCG) vaccination as a child. Her new employer requires her to undergo testing for tuberculosis (TB). Her initial tuberculin skin test (TST) is 0 mm, but on a second TST 2 weeks later, it is 8 mm. She is otherwise healthy, negative for human immunodeficiency virus (HIV), and has no constitutional symptoms. Does she have latent tuberculosis infection (LTBI)?

CASE 2 › A mom brings in her 3-year-old son, Patrick. She reports that a staff member at his day care center traveled outside the country for 3 months and was diagnosed with LTBI upon her return. She wants to know if her son should be tested.

More than 2 billion people—nearly one-third of the world’s population—are infected with Mycobacterium tuberculosis.¹ Most harbor the bacilli as LTBI, which means that while they have living TB bacilli within their bodies, these mycobacteria are kept dormant by an intact immune system. These individuals are not contagious, nor are they likely to become ill from active TB unless something adversely affects their immune system and increases the likelihood that LTBI will progress to active TB.

Two tests are available for diagnosing LTBI: the TST and the newer interferon gamma release assay (IGRA). Each test has advantages and disadvantages, and the best test to use depends on various patient-specific factors. This article describes whom you should test for LTBI, which test to use, and how to diagnose active TB.

Why test for LTBI?

LTBI is an asymptomatic infection; patients with LTBI have a 5% to 10% lifetime risk of developing active TB.² The risk of developing active TB is approximately 5% within the first 18 months of infection, and the remaining risk is spread out over the rest of the patient’s life.² Screening for LTBI is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%,³ and treatment for LTBI is simpler, less costly, and less toxic than treatment for active TB.

Whom to test. Screening for LTBI should target patients for whom the benefits of treatment outweigh the cost and risks of treatment.⁴ A decision to screen for LTBI implies that the patient will be treated if he or she tests positive.³

The benefit of treatment increases in people who have a significant risk of progression to active TB—primarily those with recently acquired LTBI, or with co-existing conditions that increase their likelihood of progression (TABLE 1).⁵

Screening for latent TB infection is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%.

All household contacts of patients with active TB and recent immigrants from countries with a high TB prevalence should be tested for LTBI.⁶ Those with a negative test and recent exposure should be retested in 8 to 12 weeks to allow for the delay in conversion to a positive test after recent infection.⁷ Health care workers and others who are potentially exposed to active TB on an ongoing basis should be tested at the time of employment, with repeat testing done periodically based on their risk of infection.^8,9

Individuals with coexisting conditions should be tested for LTBI as long as the benefit of treatment outweighs the risk of drug-induced hepatitis. Because the risk of drug-induced hepatitis increases with age, the decision to test/treat is affected by age as well as the individual’s risk of progression. Patients with the highest risk conditions would benefit from testing/treating regardless of age, while treatment may not be justified in those with lower-risk conditions. A reasonable strategy is as follows:¹⁰
• high-risk conditions: test regardless of age
• moderate-risk conditions: test those <65 years
• low-risk conditions: test those <50 years.

Children with LTBI are at particularly high risk of progression to active TB.⁵ The American Academy of Pediatrics (AAP) recommends assessing a child’s risk for TB at first contact with the child and once every 6 months for the first year of life. After one year, annual assessment is recommended, but specific TB testing is not required for children who don’t have risk factors.¹¹ The AAP suggests using a TB risk assessment questionnaire that consists of 4 screening questions with follow-up questions if any of the screening questions are positive (TABLE 2).¹¹