Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published December 8, 2021


What are the recommended treatment regimens for latent tuberculosis infection?

Latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis and with bacillary replication absent or below some undefined threshold as a result of immunologic control. Most persons with LTBI never become sick with tuberculosis; however, approximately 5 to 15% have progression to tuberculosis disease. Read the NEJM Clinical Practice Article here.

Clinical Pearls

Q: Who should be screened for LTBI?

A: In 2020, the United States had a tuberculosis incidence of 2.2 per 100,000 persons, but most countries in Africa, Asia, Eastern Europe, Latin America, and the Pacific Islands have substantially higher incidence. Persons who were born, lived, or had prolonged travel (>1 month) in these higher-incidence settings should undergo testing for LTBI regardless of duration of residence in the United States. Within lower-incidence countries, there are specific settings (e.g., correctional facilities and homeless shelters) with higher tuberculosis incidence that warrant testing for LTBI. Close contact with a person with infectious tuberculosis disease is a risk factor for M. tuberculosis infection, with the risk of progression to tuberculosis disease being highest in the first 2 years after infection. Persons with immunosuppressive conditions, including human immunodeficiency virus (HIV) infection and iatrogenic immunosuppression, typically have substantially increased risk of progression from LTBI to tuberculosis disease, such that routine testing for LTBI is indicated.

Q: Is there a preferred test for the diagnosis of LTBI?

A: There are no direct microbiologic tests for diagnosis of LTBI. Instead, interferon-γ release assays (IGRAs) and tuberculin skin testing provide indirect assessment of infection through detection of cell-mediated immune responses to stimulation by M. tuberculosis antigens. These tests cannot discriminate LTBI from tuberculosis disease, and they cannot be used to monitor treatment efficacy because immunologic responses that are detected by the tests are long-lasting even after effective treatment. Current U.S. guidelines give preference to the use of IGRAs in adults and older children, but tuberculin skin tests are considered to be acceptable.

Morning Report Questions

Q: How does prior vaccination against bacille Calmette–Guérin (BCG) affect tests for LTBI?

A: Vaccination against BCG can cause a positive tuberculin skin test owing to shared antigenic components with purified protein derivative, although the effect on the tuberculin skin test of BCG received in infancy is minimal, especially 10 years or more after vaccination. IGRA results are unaffected by previous BCG vaccination, because stimulatory antigens that are used in these assays are absent from BCG vaccines. In settings of low tuberculosis prevalence, the specificity of IGRAs is more than 95%; the specificity of tuberculin skin tests is also more than 95% in populations without BCG vaccination but is lower in populations in which BCG vaccines are administered. Nevertheless, IGRAs can yield false positive results, particularly when used in low-risk populations. 

Q: What are the recommended treatment regimens for LTBI?

A: Decisions about whether to recommend LTBI treatment are based on risks of adverse effects from treatment weighed against the risk of development of tuberculosis disease. All persons with LTBI should undergo testing for HIV infection. Isoniazid monotherapy has long been used for LTBI treatment. However, given its longer treatment duration, lower completion rates, and higher rates of hepatotoxic effects as compared with rifamycin-based regimens, isoniazid monotherapy is no longer considered in U.S. guidelines to be a preferred LTBI treatment. Preferred LTBI treatment regimens include 3 months of once-weekly rifapentine plus isoniazid, 4 months of once-daily rifampin, or 3 months of once-daily isoniazid plus rifampin.

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