#178 Tuberculosis Updates with Laila Woc-Colburn MD

October 21, 2019 | By Matthew Watto, MD

Managing the ‘White Plague’ in the Modern Age

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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Credits

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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We’ll be doing two live interviews on stage, plus recording two recap episodes to bring you high yield clinical pearls from the conference. Look out for us in our red Curbsiders shirts and say hello. Take a picture with Stuart! Give Paul a hug! Recap episodes will release the week starting Monday 10/28/19.

Time Stamps

• 00:00 Sponsor: ACP’s National Internal Medicine Day I.M. Proud Story Contest
• 00:24 Disclaimer, Intro, Guest bio, Pun
• 03:51 Guest one-liner, Career Advice; Picks of the Week*: Leonardo Da Vinci by Walter Isaacson; Aditya Shah (@IDdocAdi) antibiotic stewardship on Twitter; @EpicEMRParody on Twitter; Zima is a presumably delicious beverage (we’ve never tried it…ha)
• 09:52 Sponsor: ACP’s National Internal Medicine Day I.M. Proud Story Contest
• 11:30 Case of latent TB; Interpretation of PPD (Tuberculin Skin Test)
• 17:05 PPD and BCG vaccine; Who needs an IGRA?
• 19:20 LTBI treatment threshold; IGRA explained including what to do with “indeterminate results”
• 25:22 LTBI natural history; Why endemic countries don’t treat LTBI
• 30:08 TB infection, immunity and reinfection
• 33:33 How to counsel patients about latent tuberculosis treatment
• 38:25 Dietary and alcohol restrictions during LTBI therapy
• 44:18 Screening of healthcare workers
• 48:02 Case of active TB; AFB smears and nucleic acid amplification tests
• 56:05 Initiation of antibiotics for tuberculosis and how to handle TB resistance
• 58:13 Airborne precautions; Who needs them and how to isolate patients
• 61:24 Direct observed therapy and why adherence to tuberculosis therapy is challenging
• 68:11 Tuberculosis UV light and sanatoriums
• 71:00 Take home points
• 72:25 Outro

Tuberculosis Pearls

1. 2019 CDC guidelines no longer recommend annual PPD or IGRA for all health care workers. Instead, there is an increased emphasis on occupational exposure education.
2. Isoniazid/Rifapentine is a new once-weekly treatment option for latent TB infection that can reduce overall treatment time to 12 weeks. Key adverse effects are hepatotoxicity and drug-drug interactions.
3. Consider HIV testing in all patients suspected of having active TB disease.
4. If you are unsure if your patient may have TB disease, Dr. Woc-Colburn recommends: err on the side of caution and isolate.

Tuberculosis Show Notes

Latent Tuberculosis

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. 

Screening for Health Care Workers

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.

Baseline Screening

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)

Annual Screening

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)

Post-Exposure Testing

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)

Diagnostics

Dr. Woc-Colburn walks us through interpretation of the PPD (purified protein derivative) or TST (Tuberculin Skin Test) and IGRA (Interferon-Gamma Release Assay.)

Interpreting the PPD: Induration

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)

Finding a False Negative PPD

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) 

Interpreting an Indeterminate IGRA

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.

Pre-treatment counseling

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.

Treatment

Should we treat LTBI?

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. 

LTBI Regimen Options

New Regimen: Isoniazid/Rifapentine

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

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

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.

Active Tuberculosis (TB Disease)

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.

Step One: Move the Patient Into Isolation

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.

Step Two: Initiate Diagnostics

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.

Acid-Fast Bacilli (AFB) Smear  vs. Nucleic Acid Amplification Tests (NAAT)

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.

Step Three: Initiate Therapy

Empiric Therapy

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)

Hospital Discharge

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)

Transitioning to Home Therapy

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.

Goals

Listeners will learn the current standard of care for diagnosis, treatment, and surveillance of tuberculosis.

Learning objectives

After listening to this episode listeners will…  

1. Recognize updates in tuberculosis screening and treatment guidelines
2. Identify best diagnostic modalities for latent and active tuberculosis
3. Identify best practices for the management of tuberculosis during the diagnostic period
4. Employ treatment algorithms and best practices for latent and active tuberculosis

Links*

1. Leonardo Da Vinci by Walter Isaacson
2. Aditya Shah (@IDdocAdi) antibiotic stewardship on Twitter
3. @EpicEMRParody on Twitter

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on my Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

References

1. Sosa L et al. Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019. MMWR 2019. [https://www.cdc.gov/mmwr/volumes/68/wr/mm6819a3.htm#B1_down]
2. Centers for Disease Control and Prevention. Tuberculin Skin Testing Fact Sheet. Updated 2016. [https://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm]
3. Dhiman R et al. A Guide to the Management of Tuberculosis in Patients with Chronic Liver Disease. J Clin Exp Hepatol. 2012. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940527/]
4. Lee M et al. Diabetes Mellitus and Latent Tuberculosis Infection: A Systemic Review and Metaanalysis. Clin Infect Dis. 2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399944/]
5. Centers for Disease Control and Prevention. Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. MMWR 2005. [https://www.cdc.gov/mmwr/pdf/rr/rr5417.pdf]
6. Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis: What the Clinician Should Know, Sixth Edition 2013. [https://www.cdc.gov/tb/education/corecurr/pdf/corecurr_all.pdf]
7. Stein M et al. Reliability of control skin tests with common antigens in children undergoing tuberculin skin test. Ann N Y Acad Sci. 2007. [https://www.ncbi.nlm.nih.gov/pubmed/17785311/]
8. Borisov A et al. Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection. MMWR 2018. [https://www.cdc.gov/mmwr/volumes/67/wr/mm6725a5.htm]
9. Bhise S. Isoniazid toxicity. J Drug Design and Research, 2017. [https://pdfs.semanticscholar.org/10be/e11efbe5adf5aa32c27cb2964352184e81cd.pdf]
10. Miki M et al. An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward. Intern Med. 2005. [https://www.ncbi.nlm.nih.gov/pubmed/16357449]
11. Centers for Disease Control and Prevention. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Updated 2019. [https://www.cdc.gov/tb/publications/ltbi/treatment.htm]

Disclosures

Dr. Woc-Colburn reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

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.