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(Facility) IHS Chest Clinic Guidelines

Latent Tuberculosis Infection (LTBI)

Who to test

  1. Birth or residence in a country with a high or medium incidence rate of TB (most countries in Asia, Africa, Latin America, the Pacific Islands and Eastern Europe)
  2. Close contact to a person with infectious tuberculosis (TB) disease
  3. Immunosuppressed: HIV (CD4 < 200 or not on antiretroviral therapy), biologic therapy, cancer chemotherapy, solid organ or bone marrow transplantation, steroid Rx > 15 mg prednisone/day for > 1 month)
  4. Certain medical conditions with a history of exposure to TB or residence in a community with high incidence of TB as seen many Indian Health Service Areas: DM, CKD, leukemia/lymphoma, head or neck cancer, BMI < 20, silicosis, gastrectomy, ALD, chronic malabsorption, current or former cigarette smoker (see reference 3 by Springer et al)
  5. Social: person experiencing homelessness or incarceration or worker employed in a facility where these persons reside
  6. Health care workers require
    1. TB Baseline screening and risk assessment at the time of hire
    2. Confirmation of positive result ( if there is no known exposure) with a second test (either a second IGRA or a TB skin test)
    3. No serial TB testing recommended unless in a high risk facility or performing aerosol generating procedures
    4. Treatment for LTBI is strongly encouraged unless contraindicated

How to test

  1. Interferon-Gamma Release Assay (IGRA) tests, such as Quantiferon or T-Spot, are generally preferred over tuberculosis skin testing (TST) if over 5 years old.
    1. IGRA tests are preferred for recipients of BCG vaccine
    2. Dual IGRA and TST testing increases sensitivity for infection in immunocompromised patients
    3. Low risk persons with no history of exposure to TB and a low risk for disease progression (such as healthy health care personnel) who test positive by IGRA should get a second confirmatory test (IGRA or TST). A person is considered positive only if both tests are positive.

How to evaluate the patient who tests positive

  1. Obtain a history:
    1. Review and document positive test results in EHR
    2. Take a history including immunosuppressive medications and conditions
    3. Review history of TB exposure and risk factors
    4. Evaluate risk for developing active TB disease and treat patients with
      1. Recent infection
      2. Medical conditions as above under who to test plus:
        1. Children
        2. Pregnant, breastfeeding or postpartum women
        3. Recent contacts to infectious dr
      3. Born in, resided or travelled for >1 month in countries of high or medium rates of TB
    5. History of prior treatment: document drug, duration, doses and mode of treatment (directly observed or self-administered) and only treat once for LTBI in a patient’s life
  2. Symptom Review: ask about cough > 2-3 weeks, hemoptysis, fever, chills, night sweats, weight loss, loss of appetite, fatigue, chest pain, back pain, hematuria
  3. Physical exam including lymph nodes
  4. Obtain a Chest X-Ray (CXR) for all patients
    1. PA and L preferred in general
    2. During pregnancy CXR can be deferred to the second trimester unless HIV positive, other immunosuppression, recent contact of a case, documented conversion of test from negative to positive in last 2 years
  5. Sputum culture testing is not done routinely unless the patient has pulmonary TB symptoms or an abnormal chest x ray. If so, obtain 3 sputa for AFB smear and culture including 1 early morning specimen and at least one Nucleic acid amplification test (such as PCR or Xpert assay). Do not start treatment until cultures are back and confirmed to be negative.

How to treat Latent TB

Preferred Adult Regimens:

  1. A twelve week course of INH 900 mg po weekly and Rifapentine 900 mg po weekly (750 mg weekly if <50 kg) is a preferred combination of choice for LTBI treatment in the IHS . This regimen can be used for HIV positive patients if drug interactions are taken into account in selecting the appropriate HIV regimen used during LTBI treatment. This is best if given as directly observed therapy by a tribal TB worker, Community Health Representative of Public Health Nurse.
  2. Rifampin 600 mg po daily for 4 months is a preferred regimen that is strongly recommended for HIV negative adults and children. It is especially preferred for person with underlying liver disease.
  3. INH 300 mg po daily plus Rifampin 600 mg po daily for 3 months is conditionally recommended as a preferred regimen. This is infrequently used in the IHS given the simpler options available above.
2) Alternate regimens:
  1. INH 300 mg po daily for 6-9 months is an alternate regimen
  2. Supplement INH therapy with pyridoxine 50 mg po daily

Monitoring for toxicity

  1. Monitor the patient for symptoms of toxicity and physical exam monthly
    1. INH: rash, neuropathy, N/V, anorexia, jaundice, lupus-like illness
    2. Rifampin/Rifapentine: rash, flu-like illness, jaundice, bleeding
  2. Monitor the LFT’s monthly on INH and the LFT’s and CBC monthly on Rifampin (do not rely on symptoms and signs alone due to the high prevalence of chronic liver disease in the TB patient population)
  3. Common adverse reactions:
    1. INH: transaminitis, neuropathy, rash
    2. Rifampin/Rifapentine: cholestasis, thrombocytopenia, leukopenia, interstitial nephritis, rash

Active TB Disease treatment

  1. Treat with 4 drugs: INH, Rifampin, Ethambutol and Pyrazinamide
    1. Treat 2 weeks in the hospital with daily therapy then
    2. Continue for more 6 weeks with 4 drugs always with home based daily DOT (daily is defined as every day, Monday through Friday)
    3. Stop EMB when the culture results show sensitivity to the other 3 drugs
    4. Stop PZA when 8 weeks of therapy are completed
    5. Continue therapy for 6 months total with INH and Rifampin three times weekly if cultures collected at 8 weeks are subsequently negative and there were no cavities on the CXR (always use DOT for the duration)
    6. Continue therapy with INH and Rifampin three times weekly for 9 months total if there were cavities on the first CXR and the week 8 culture is positive (always use DOT for the duration)
    7. Treat immunocompromised patients for 9 months with daily therapy
    8. Check an HIV serology for every case of active TB
    9. Monitor for treatment success by obtaining a monthly sputum for AFB smear and culture until negative
    10. Obtain a follow-up chest x-ray at 2 months and at the completion of therapy.
  2. Monitoring for toxicity
    1. Monitor for INH and Rifampin toxicity as above
    2. Monitor for EMB toxicity with a baseline color vision test and repeat as needed
    3. Monitor for PZA toxicity by following for hepatotoxicity and gout
  3. Managing hepatotoxicity
    1. Stop INH, RIF, PZA and EMB if the ALT and AST are 5 times greater than normal regardless of symptoms.
    2. Stop INH, RIF, PZA and EMB if the ALT and AST are 3 times greater than normal and the patient has symptoms
    3. If drugs are stopped wait until the LFTs are almost normal ( < 2 times the upper limit of normal) then re-challenge sequentially with the 3 drugs to determine which drug is the cause of toxicity:
      1. Inpatient Higher risk rechallenge: INH daily for 3 days then change to Rifampin daily for 3 days then change to PZA daily for 3 days. Check LFT’s daily. Ethambutol can be started with the initial INH challenge since it is rarely hepatotoxic and continued during the rechallenge with Rifampin and pyrazinamide as a second drug.
      2. Outpatient Lower Risk Rechallenge: Give Ethambutol and Rifampin daily for one week. If tolerated and LFTs are normal after one week add on INH for one week. If tolerated and LFTs normal after one more week consider adding PZA and checking labs in one week.
      3. Call for infectious disease consultation in the event of toxicity

Contact Investigations

  1. Test all family and social circle contacts with a TST (IGRA testing is often used for school, nursing home or hospital outbreak testing)
  2. Repeat PPD testing at 8-10 weeks on all contacts who are initially PPD negative
  3. Get CXR’s on the close home contacts to rule out active TB
  4. Offer LTBI therapy to the TST (greater than 5 mm) or IGRA positive adults and children who have not been treated for latent TB before
  5. Offer LTBI therapy to PPD negative children less than 5 years old with a clear CXR. Repeat the PPD at 8-10 weeks and if PPD negative stop INH.
  6. Offer LTBI treatment to HIV positive or other substantially immune-compromised contacts even if PPD tests are negative.
  7. Test all PPD positive contacts for HIV.

How to run an IHS Chest Clinic

  1. Schedule at least one TB clinic per month as the local Service Unit
  2. Run the TB clinic in conjunction with the Service Unit TB technician
  3. The TB technician should
    1. check that the appropriate blood work has been drawn
    2. perform a screening review of symptoms
    3. estimate the degree of adherence
    4. Make phone calls or home visits to all patients who miss appointments
    5. Give DOT to all cases of active TB and to high risk contacts such as dialysis patients or HIV positive patients.
  4. The Chest Clinic clinician should
    1. Monitor for signs and symptoms of toxicity
    2. Check the LFT’s and CBCs that are ordered
    3. Review the duration of therapy at each visit: “5 of 9 months of INH completed”
    4. Check an HIV serology on every active case of TB and every case of Latent TB if the patient gives verbal informed consent.
  5. Carefully document when treatment for TB is completed in the EHR or paper problem list to avoid confusion in the future.
  6. Participate in a local or national IHS monthly TB ECHO teleconference (contact for more information).

When to call Infectious Diseases consultant:

  1. HIV co-infection
  2. Transplant patient
  3. Drug-drug interactions (especially with Rifampin or Rifapentine)
  4. Possible drug resistance (not improving, cultures remain positive)
  5. Drug toxicity on treatment for TB
  6. Pregnancy
  1. Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep 2020;69(No. RR-1):1–11. DOI: external icon.
  2. Testing and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations; NSTC/NTCA Clinical Recommendations, February 2021;
  3. Springer YP, Kammerer JS, Silk BJ, Langer AJ. Tuberculosis in Indigenous Persons - United States, 2009-2019. J Racial Ethn Health Disparities. 2022 Oct;9(5):1750-1764. doi: 10.1007/s40615-021-01112-6. Epub 2021 Aug 26. PMID: 34448124; PMCID: PMC8881557.
  4. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis; Payam Nahid, Susan E. Dorman, Narges Alipanah, Pennan M. Barry, Jan L. Brozek, Adithya Cattamanchi, Lelia H. Chaisson, Richard E. Chaisson, Charles L. Daley, Malgosia Grzemska ; Clinical Infectious Diseases, Volume 63, Issue 7, 1 October 2016, Pages e147–e195,