Catch up on the latest guidelines and insights on tuberculosis with help from infectious diseases doc & TB expert Dr. Laila Woc-Colburn, @docwoc71 (Baylor)! We cover new recommendations for screening health care workers, treatment of both latent and active TB, and best practices for counseling patients throughout the process. Listen to find out more… And say goodbye to the annual PPD?
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Written and Produced by: Hannah R. Abrams
Cover Art and Infographic by: Hannah R. Abrams
Hosts: Hannah R. Abrams; Matthew Watto MD, FACP
Editors: Matthew Watto MD, FACP; Emi Okamoto MD
Guest: Laila Woc-Colburn, MD, FACP
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Latent tuberculosis infection (LTBI) occurs when macrophages wall off the mycobacterium and prevent it from spreading. Dr. Woc-Colburn recommends thinking of host defenses here as a real wall: if something occurs to prevent the body from doing regular maintenance on the wall (immunosuppression or age-related immunosenescence), LTBI can become active TB.
Goodbye to the annual PPD? The 2019 CDC guidelines for health care personnel screening include big changes to annual screening and strengthen recommendations for TB occupational hazard education.
Previous guidelines recommended all new health care personnel be screened with a PPD or IGRA. The new guidelines recommend a baseline risk assessment asking about TB exposure, travel to endemic regions, and history of immunosuppression to inform test interpretation. Greater emphasis is also placed on annual education for all providers on occupational exposures to TB. (Sosa 2019)
Serial screening is no longer routinely recommended for health care providers without LTBI, but can be considered for groups at high risk such as pulmonologists and respiratory therapists who may have ongoing exposure. (Sosa 2019)
Symptom evaluation is recommended for all health care providers with a suspected exposure. For providers with no history of LTBI or TB disease, testing should be done immediately and, if negative, repeated after 8-10 weeks. (Sosa 2019)
Dr. Woc-Colburn walks us through interpretation of the PPD (purified protein derivative) or TST (Tuberculin Skin Test) and IGRA (Interferon-Gamma Release Assay.)
PPDs should be read 48-72 hours after placement (don’t place them on Thursday!) by induration. Guidelines for diagnosing LTBI based on PPD induration remain unchanged, with the following cutoffs for various patient groups:
5mm: Patients with HIV, immunosuppression, nodular or fibrotic changes on chest X-ray, or recent contact with known active TB infection. (CDC 2016) Immunosuppression includes organ or stem cell transplant recipients, stem cell transplant recipients, patients on TNF-alpha antagonists, or on long-term prednisone > 15 mg/day. (CDC 2016)
10mm: Patients who have recently immigrated (< 5 years) from a high prevalence country, patients with active IV drug use, health care workers, and children < 4 years old. (CDC 2016) Per Dr. Woc-Colburn, patients with diabetes mellitus or cirrhosis are considered a “gray area” in which diagnostic utility of PPD is uncertain. (Dhiman 2012, Lee 2017)
15mm: All patients. (CDC 2016)
BCG at a young age should not affect interpretation of PPD after 5 years post-vaccination, and therefore PPDs in BCG-vaccinated individuals should be interpreted using standard diagnostic cutoffs. (CDC 2005)
Dr. Woc-Colburn points out two key clinical scenarios that can cause a false negative PPD: inadequate inoculation and anergy. To check for inadequate inoculation, or in older patients, consider giving a booster PPD. (CDC Core Curriculum 2013) Consider anergy in patients who are immunosuppressed; Dr. Woc-Colburn mentions that Candida antigen may serve as a positive control, though reliability may be low. (Stein 2007). She recommends considering IGRA instead in these patients. (CDC Core Curriculum 2013)
Indeterminate IGRA can be caused by inadequate response to the positive control or excessive response to the negative control. (CDC 2005) Laboratory error or sample handling issues may cause either type of indeterminate result, and inadequate response may indicate underlying immunosuppression. (CDC 2005) Dr. Woc-Colburn recommends repeating the test using a different assay if possible. Neutropenic patients may not make enough IFN-gamma to respond to the positive control.
First Dr. Woc-Colburn discusses the difference between latent and active tuberculosis, and reassure the patient they are not contagious. She discusses the regimen options with patients. She orders baseline liver function tests and counsels that they abstain from drinking and heavily fatty foods to reduce stress on the liver. Patients on isoniazid can also experience severe histamine- or tyramine- induced adverse effects (Bhise 2017, Miki 2005) and Dr. Woc-Colburn recommends her patients avoid tyramine- or histamine- containing foods such as cheeses and fish for the full 12 weeks of therapy.
Latent tuberculosis often is treated in the United States as it reduces the risk of progression to active tuberculosis for the individual and is a public health measure. According to the new 2019 CDC guidelines, all healthcare personnel with LTBI should be treated.
The new guidelines include the option of the “3HP” or isoniazid/rifapentine treatment for healthy individuals with LTBI who are >2 years old. A higher dose of isoniazid and rifapentine is administered weekly for 12 weeks. This is also recommended for patients with HIV and LTBI on antiretrovirals that will not be affected by rifapentine’s drug-drug interactions. (Borisov 2018). Patients considering this regimen should be counseled on risk of hepatotoxicity and hypersensitivity reaction.
Isoniazid monotherapy for LTBI is a 9 month course of daily isoniazid and vitamin B6 supplementation. The regimen is generally well tolerated, but carries some risk of hepatotoxicity and risk of peripheral neuropathy (CDC 2019). Pyridoxine (vitamin B6) should be given to those at high risk of neuropathy, including pregnant or breastfeeding women and patients with diabetes, cirrhosis, renal failure, or alcoholism. Dr. Woc-Colburn recommends counseling patients on abstinence from alcohol during the treatment period. She recommends isoniazid monotherapy for patients with liver disease who are not near transplantation because of its lower hepatotoxicity and fewer drug-drug interactions.
Rifampin monotherapy for LTBI is a 4 month course of daily or BID dosing. Side effects include orange bodily fluids, fever, rash, and hepatotoxicity, as well as significant drug-drug interactions for a wide variety of medications metabolized by CYP enzymes, including oral contraceptives. (CDC 2019) Dr. Woc-Colburn recommends rifampin monotherapy for patients with liver disease who are rapidly approaching transplant because of the shorter time course of therapy.
Patients with active tuberculosis have signs and symptoms including persistent cough, hemoptysis, fever, night sweats, weight loss, malaise, and abnormal chest imaging. Dr. Woc-Colburn outlines the key initial steps in management of suspected active TB.
For a patient with high clinical suspicion of active TB, move into isolation immediately. For more ‘intermediate-risk’ patients, Dr. Woc-Colburn suggests that when in doubt, you err on the side of caution and isolate. Other ways she suggests to risk-stratify these patients include HIV testing and asking your radiology colleagues to specifically review the X-ray for cavitary lesions or Ghon complexes.
Testing requirements to ‘clear’ respiratory isolation precautions will vary by hospital. However, the aim of initial diagnostic testing is to identify if the patient has an actively infectious TB infection. Sputum testing reflects what is in the patient’s respiratory droplets and is the basis of this initial testing.
AFB smear is less sensitive than newer nucleic-acid amplification tests for detecting TB in respiratory specimens, but an expert panel recommends that gene testing does not replace the need for AFB smear and culture in suspected TB disease. (CDC/APHL 2013) Per 2005 guidelines, Dr. Woc-Colburn recommends that every 8 hour sputum AFB testing include a morning sample to improve yield and considers 3 negative samples indicative of absence of infectious TB disease. (Jensen 2005)
NAAT includes newer assays that provide information on isoniazid or rifampin resistance within 24-48 hours. (CDC Assay Availability 2013) Depending on local hospital policy, Dr. Woc-Colburn considers removing airborne precautions after 2 consecutive negative samples.
For most of the US, antibiotic resistance rates are low and RIPE (a rifamycin like rifampin, isoniazid, pyrazinamide, and ethambutol) is an appropriate initial empiric therapy. (Jensen 2005) However, if you are in or your patient has recently emigrated from a TB-endemic area with high resistance rates (such as Russia, China, India or South Africa), Dr. Woc-Colburn recommends you reach out to your regional reference center to determine what empiric therapy to start based on regional patterns in the suspected place of exposure. (Dheda 2017)
Patients with suspected or confirmed TB disease may be discharged after 3 consecutive negative sputum AFB smears or after 14 days of therapy. (Jensen 2005)
Patients should not be discharged until a specific plan is in place for directly observed therapy. Key points Dr. Woc-Colburn emphasizes in counseling: it is critical that patients take all of the prescribed therapy because of the risk of mutation and drug resistance development. However, the pill burden is high and patients may experience nausea, malaise, fevers, arthralgias, gout, and hepatitis as a consequence of RIPE therapy. Dr. Woc-Colburn also counsels patients that they cannot travel outside their home for non health care-associated reasons until they have negative sputum cultures (Jensen 2005) and should not go to crowded places such as malls or movie theaters. When outside, she recommends her patients wear a surgical mask to block droplet transmission.
Listeners will learn the current standard of care for diagnosis, treatment, and surveillance of tuberculosis.
After listening to this episode listeners will…
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Dr. Woc-Colburn reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Woc-Colburn L, Abrams HR, Watto MF. “#178 Tuberculosis Updates with Laila Woc-Colburn MD”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list October 21, 2019.
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A few clarifications. Your guest said early on that we should consider someone immunosuppressed if on "15mg/kg" of prednisone a day ( if I heard her right. It is 15 mg a day total. - She talked about doing anergy testing. Just finished studying for the MOC. Specifically read that you NEVER do anergy testing and if it is a choice on the boards, don't pick it. - She also mentioned that ethambutol causes hyperuricemia. In a practice question I did, the correct answer is pyrazinamide. It causes this much more frequently and to a greater degree than ethambutol.
Is there a preference for screening with PPD or IGRA?