Core IM: 5 Pearls on Latent Tuberculosis Infection

March 28, 2018

CORE IM Podcast podcast 3 min read

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By Raphael Rabinowitz MD, Viren Kaul MD, Marty Fried MD, Shreya Trivedi MD; Illustration by Ramon Thompson. Quiz yourself on the 5 Pearls we will be covering:

  1. Who should be screened for latent tuberculosis infection (LTBI)? (1:45)
  2. What screening tests are available and how do they differ? (6:30)
  3. What are the LTBI treatment options available? (10:24)
  4. What are the major adverse drug effects to consider? (13:28)
  5. How frequently should you check liver function tests in a patient being treated for LTBI? What do you do with the results? 17:43
  6. Dr. Caplan-Shaw Recap (21:29)

A special thank you to Dr. Caralee E. Caplan-Shaw for peer-reviewing this podcast!

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Show notes

Pearl #1: Screening for TB

  1. In 2016 the USPSTF updated their latent tuberculosis screening recommendation to include screen all asymptomatic adults at increased risk of TB for LTBI.  This includes 3 main groups:
    1. Close contacts of a person with active tuberculosis
    2. Those at high risk for exposure including individuals with:
      1. Contact with prisons (employees and prisoners)
      2. Hospital and residential rehabilitation center employees
      3. Homeless shelter residents or employees
      4. Mycobacterial lab personnel
    3. Current or previous residents in highly endemic areas, regardless of length of stay in non-endemic country such as U.S.
  2. Not included in this guideline are immunocompromised groups such as HIV-infected patients, those receiving chemotherapy,  immunotherapy and post-transplant patients. Don’t forget about diabetic patients as immunocompromised!


Pearl #2: Latent Tuberculosis Screening Tests

  1. There are two categories of screening test: tuberculin skin tests (TSTs) and interferon gamma release assays (IGRAs).
  2. TST, for example the purified protein derivative (PPD) test, are inexpensive.
    1. Because of antigen cross-reactivity, the TST may be falsely positive in patients who have received the BCG vaccine.  
    2. If the BCG vaccine was given within the 1st year of life, the effects wane over time, especially if the TST is done greater than 10 years post vaccination.
    3. Also limiting utility is the need for test evaluation 48-36 hours post-injection.
  3. Interferon Gamma Release Assays or IGRAs (for example, QuantiFERON-TB in-tube test) are preferred as it requires only a single visit and has higher specificity in BCG-vaccinated patients.


Pearl #3: Treatment for Latent Tuberculosis

  1. There are several regimens currently approved by CDC:
    1. Isoniazid i.e INH daily for 9 months
    2. Rifampin (RMP)  daily for 4 months
    3. Combined INH / rifapentine (RPT) weekly for 12 weeks under directly observed therapy (DOT)
  2. Rifamycin-containing regimens have the advantage of shorter treatment periods, improved adherence, and fewer adverse drug events.


Pearl #4: Adverse effects of Latent Tuberculosis Therapies

  1. Hepatotoxicity is the major adverse drug event of LTBI treatments.
    1. Rifamycin-based regimens have lower risk than INH.
  2. Rifamycins are potent cytochrome P450 inducers. Many important medication classes will have decreased efficacy and need dose adjustment when on rifamycins.   
    1. These include warfarin, methadone, many antiepileptics and oral contraceptive pills.

Pearl #5: Liver Function Test Follow-up for Patients on Latent Tuberculosis Treatment

  1. 2007 ATS guidelines recommend NOT checking LFTs in asymptomatic patients.
  2. Baseline and follow-up LFTs should be checked in patients with chronic liver disease, chronic alcohol use, co-treatment with HAART, pregnant patients and any other risk for hepatotoxicity.
    1. Follow-up interval is generally every 2-4 weeks depending on co-morbid condition.
    2. Remember that ALT is the preferred test for detecting hepatocellular injury.
  3. Treatment should be held if ALT is more than 3x upper limit of normal in patients with symptoms (abdominal pain, jaundice, nausea/vomiting) or more than 5x upper limit of normal in asymptomatic patients.

References

  1. Bibbins-Domingo, K., Grossman, D. C., Curry, S. J., Bauman, L., Davidson, K. W., Epling, J. W., … & Kurth, A. E. (2016). Screening for latent tuberculosis infection in adults: US Preventive Services Task Force recommendation statement. Jama, 316(9), 962-969.
  2. Patel, S. et al.Risk of Progression to Active Tuberculosis Among Foreign-Born Persons With Latent Tuberculosis. Chest131,1811–1816 (2007).
  3. Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. American Journal of Respiratory and Critical Care Medicine161,(2000).
  4. Getahun, H., Matteelli, A., Chaisson, R. E. & Raviglione, M. Latent Mycobacterium tuberculosis Infection. New England Journal of Medicine 372,2127–2135 (2015).
  5. Lewinsohn, D. M. et al.Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clinical Infectious Diseases 64,111–115 (2017).
  6. Smieja, M., Marchetti, C., Cook, D. & Smaill, F. M. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database of Systematic Reviews(1999). doi:10.1002/14651858.cd001363
  7. Sterling, T. R. et al.Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection. New England Journal of Medicine365,2155–2166 (2011).
  8. Stagg, H. R. et al.Treatment of Latent Tuberculosis Infection. Annals of Internal Medicine161,419 (2014).
  9. Menzies, D. et al.Adverse Events with 4 Months of Rifampin Therapy or 9 Months of Isoniazid Therapy for Latent Tuberculosis Infection. Annals of Internal Medicine149,689 (2008).
  10. Saukkonen, J. J. et al.An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy. American Journal of Respiratory and Critical Care Medicine174,935–952 (2006).