1. Pulmonary Board Review Tuberculosis Curtis M. Grenoble, MHS, PA-C Lock Haven University PA Program Fall 2008

2. Historical Perspective During the 1800’s 1 in 5 persons in the US had active TB! “captain of all men of death” – leading killer 1985 there were 9.3 cases per 100,000 Resurgence in early 1990’s – HIV, and public policy as well in the late 80’s Now 7.4 cases per 100,000

3. Reported TB Cases* United States, 1982–2007 Year No. of Cases *Updated as of April 23, 2008.

4. Number of TB Cases in U.S.-born vs. Foreign-born Persons United States, 1993–2007* No. of Cases *Updated as of April 23, 2008.

5. Transmission of Tuberculosis Causative organism: Mycobacterium tuberculosis Aerosolized droplets containing MTB

6. Persons at Risk HIV Homeless Live or work in crowded conditions Immigrants IVDA Prison Immunosuppresion for any reason DM Debilitation – ETOH HCW

7. Purpose of Targeted Testing Find persons with TB disease / LTBI that would benefit from treatment Groups that are not high risk should not be tested DECISION TO TEST IS A DECISION TO TREAT! High Risk Groups: Close contacts of a person known or suspected to have TB Foreign-born persons of high incidence countries Residents and employees of high-risk congregate settings Health care workers (HCW) serving high-risk clients Medically underserved, low income populations Children exposed to adults in high-risk categories Persons who inject illicit drugs Persons with HIV / certain medical conditions

8. How is the skin test read? Test is read by a trained health worker 48 - 72 hours after the tuberculin injection Diameter of the indurated area is measured transversely across the forearm Erythema (redness) is not measured Test result is measured in millimeters (mm) –≥ 5mm: HIV+, recent TB exposure, x-ray evidence, immunosuppressed –≥ 10mm: recent immigrants from high risk country, illicit drug users, HCW, correctional facilities, LTC facilities, DM CRF –≥ 15mm: Persons with no known risk, HCW otherwise at low risk and received baseline testing at start of employment

9. False Positive PPD Skin Tests Error in administering the test Cross-reaction with nontuberculous mycobacterial antigens Any previous bacille Calmette-Guérin vaccination Delayed Positive Reaction Booster phenomenon

10. Person: Not acutely ill Not contagious Germs: “Sleeping” but still alive Surrounded (walled off ) by body’s immune system Latent Tuberculosis Infection LTBI

11. In LTBI TB germs are “sleeping” and body defenses are keeping them from growing The TB skin test is usually positive Chest x-ray = normal Sputum culture = negative

12. Isoniazid Regimens INH daily for 9 months (270 doses within 12 months) INH twice/week for 9 months (76 doses within 12 months) INH daily for 6 months (180 doses within 9 months) INH twice/week for 6 months (52 doses within 9 months)

13. Isoniazid Regimens 9-month regimen of INH - Preferred 6-month regimen - less effective but is an alternative Daily vs. intermittent (twice weekly) –Use directly observed therapy (DOT) for intermittent regimen Completion of Therapy –Determined by total number of doses administered –Not on duration alone.

14. Alternative Regimens: Rifampin Rifampin (RIF) - daily for 4 months is an acceptable alternative when treatment with INH is not feasible. –Side effect Rifabutin - alternative to Rifampin (e.g. - HIV-infected persons receiving protease inhibitors)

15. Hepatitis Risk in LTBI Treatment Incidence of hepatitis in persons taking INH is lower than previously thought (0.1 to 0.15%) Hepatitis risk increases with age –Uncommon in persons < 20 years old –Nearly 2% in persons 50 to 64 years old Risk increased with underlying liver disease or heavy alcohol consumption

16. Laboratory Monitoring INH Patients Baseline LFT’s HCG, HIV, Hepatitis Panel, Etoh Obtain repeat LFT’s during treatment only if patient becomes symptomatic, or if high risk for toxicity Discontinue INH if transaminase levels are 3 times the upper limit of normal if symptoms of hepatotoxicity (rash, anorexia, N/V, RUQ pain, fatigue, weakness, dark urine, numb hands/feet) 5 times the upper limit of normal if patient is asymptomatic

17. What causes TB infection to become TB disease? Wall breaks down due to a weakened immune system ~10% of those infected with develop disease over their lifetime

18. Germs: Awake and multiply Cause damage Person: May feel sick May be contagious TB disease

19. Symptoms of TB Cough –Productive, lots of sputum –Persistent 3 weeks or longer –Coughing up blood or bloody sputum –Does not respond to other antibiotics

20. Symptoms of TB Fatigue Weight loss (unexplained) Loss of appetite Night Sweats Chest pain (Constitutional symptoms)

21. TB Disease in the Body BrainEye Lymph nodeThroat Lung * (Most Common) Bone SpineKidney Up to 40% of TB in children involves extrapulmonary sites (bones, LN, kidneys)

23. Sputum Collection Sputum specimens essential to confirm TB Sputum: mucus from within the lung, not saliva 3 specimens on 3 different days Spontaneous morning sputum Positive (Acid-fast bacilli) –Need at least 10,000 bacilli per ml –Positive in about half those with TB disease –Signal a very infectious person –Others (mycobacterium avium) may produce “false positive” –Sputum culture (“Gold standard”)

24. General Principles of TB Treatment Always treat with multiple drugs Never add a single drug to a failing regimen Treatment course depends on drugs selected Non-adherence The single most important reason for tuberculosis treatment failure

25. Anti TB Medications First-Line Second-Line Isoniazide INH Rifampin RIF Ethambutal EMB Rifabutin Pyrazinamide PZA Streptomycin Capreomycin Kanamycin Amikacin Ethionamide Para-aminosalicyclic Cycloserine Cipro Levofloxacin

27. Resources for Health Care Providers Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30333 Telephone: 800-311-3435; 404-639-3311 Web site: http://www.cdc.govhttp://www.cdc.gov National Jewish Medical and Research Center 1400 Jackson St. Denver, CO 80206 Telephone: 303-388-4461 Physician Consult Line (Monday - Friday, 8 a.m. to 5 p.m. MT): 800-652-9555 Web site: http://www.njc.orghttp://www.njc.org American Thoracic Society 1740 Broadway New York, NY 10019 Telephone: 212-315-8700 Fax: 212-315-6498 Web site: http://www.thoracic.orghttp://www.thoracic.org