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Latent Tuberculosis: Identification and Treatment


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A presentation for primary care providers interested in recognizing and treating latent tuberculosis

Published in: Health & Medicine
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Latent Tuberculosis: Identification and Treatment

  1. 1. Tuberculin Testing and Treatment of Latent Tuberculosis Infection Andrew Catanzaro, MD
  2. 2. Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection <ul><li>Identifying Latent Cases of TB decreases morbidity, mortality, and spread of TB through our community </li></ul><ul><li>“ Unity has become the Health Department” </li></ul><ul><li>Louis Padilla, MD 2007 </li></ul>
  3. 3. Outline <ul><li>Latent TB: Screening and Treatment </li></ul><ul><li>Active TB: Screening </li></ul><ul><li>Cases </li></ul>
  4. 4. Latent TB: Screening and Treatment <ul><li>Define LTBI </li></ul><ul><li>TB pathogenesis </li></ul><ul><li>TB epidemiology </li></ul><ul><li>TST Testing </li></ul><ul><li>INH: Risk, Benefit, Alternatives </li></ul>
  5. 5. What is Latent TB Infection (LTBI)? Subclinical Disease <ul><li>LTBI is the presence of </li></ul><ul><li>M. tuberculosis organisms (tubercle bacilli) </li></ul><ul><li>without symptoms or radiographic evidence of TB disease. </li></ul>
  6. 6. TB Pathogenesis <ul><li>Transmission via inhalation of “Red Snappers” </li></ul><ul><ul><li>Cough, sneeze, talking release AFB droplets </li></ul></ul><ul><ul><li>1 cough = 3,000 AFB </li></ul></ul><ul><ul><li>Talking for 5 minutes = 3,000 AFB </li></ul></ul><ul><ul><li>1 AFB is infectious in the middle and upper respiratory tract </li></ul></ul>
  7. 7. TB Pathogenesis (2) <ul><li>Infection results in the respiratory tract </li></ul><ul><li>Identified by macrophages in the lung </li></ul><ul><li>Incomplete control at the lymph nodes </li></ul><ul><li>Development of immunity (3-8 weeks) </li></ul><ul><li>Caseation, cavitation, fibrosis OR </li></ul><ul><li>Latent TB infection </li></ul><ul><li>Lifetime Reactivation: 10% of non-immunosuppressed </li></ul>
  8. 8. LTBI vs. Pulmonary TB Disease <ul><li>Latent TB Infection </li></ul><ul><li>TST* positive </li></ul><ul><li>Negative chest radiograph </li></ul><ul><li>No symptoms or physical findings suggestive of TB disease </li></ul><ul><li>Pulmonary TB Disease </li></ul><ul><li>TST usually positive </li></ul><ul><li>Chest radiograph may be abnormal </li></ul><ul><li>Symptoms may include one or more of the following: fever, cough, night sweats, weight loss, fatigue, hemoptysis, decreased appetite </li></ul><ul><li>Respiratory specimens may be smear or culture positive </li></ul>
  9. 9. TB Epidemiology <ul><li>US 5.2 cases/100,000 </li></ul><ul><li>DC 10/100,000 cases per year </li></ul><ul><li>About 50 cases per year </li></ul><ul><li>Unity takes care of 20% of DC residents </li></ul>
  10. 10. Tuberculosis Epidemiology (2) <ul><li>50% cases foreign born </li></ul><ul><li>Worldwide 12 countries give 70% infection </li></ul><ul><ul><li>India </li></ul></ul><ul><ul><li>China </li></ul></ul><ul><ul><li>Indonesia </li></ul></ul><ul><ul><li>Bangladesh </li></ul></ul><ul><ul><li>Pakistan </li></ul></ul><ul><ul><li>Nigeria </li></ul></ul><ul><ul><li>Philippines </li></ul></ul><ul><ul><li>South Africa </li></ul></ul><ul><ul><li>Russian Federation </li></ul></ul><ul><ul><li>Ethiopia </li></ul></ul><ul><ul><li>Viet Nam </li></ul></ul><ul><ul><li>Democratic Republic of Congo </li></ul></ul>
  11. 11. TB Epidemiology (3) TB Cases in Immigrants, 2006 <ul><li>Total Cases 7,700 </li></ul><ul><li>Mexico 25% </li></ul><ul><li>Philippines 10% </li></ul><ul><li>Viet Nam 8% </li></ul><ul><li>India 7% </li></ul><ul><li>China 5% </li></ul>
  12. 12. Latent TB: Screening and Treatment <ul><li>Define LTBI </li></ul><ul><li>TB pathogenesis </li></ul><ul><li>TB epidemiology </li></ul><ul><li>TST Testing </li></ul><ul><li>INH: Risk, Benefit, Alternatives </li></ul>
  13. 13. TST Testing Goals <ul><li>Detects persons with LTBI who would benefit from treatment </li></ul>
  14. 14. TST New Features <ul><li>Tuberculin skin testing </li></ul><ul><li>Emphasis on targeting persons at high risk </li></ul><ul><li>5-mm induration cutoff level for immunosuppressed (e.g. HIV positive) patients </li></ul><ul><li>Skin-test conversion defined as increase of  10 mm of induration within a 2-year period, regardless of age </li></ul><ul><li>____________________________________________________ </li></ul><ul><li>4 MMWR August 61, 2004; 53(33): 683-686 </li></ul>
  15. 15. Before you test: Identify Risk Factors That Lead to Development of TB Disease
  16. 16. Persons at Risk for Developing TB Disease <ul><li>Those who have been recently infected </li></ul><ul><li>Those with clinical conditions that increase their risk of progressing from LTBI to TB disease </li></ul>Persons at high risk for developing TB disease fall into 2 categories
  17. 17. Recent Infection as a Risk Factor (1) <ul><li>Close contacts to person with infectious TB </li></ul><ul><li>Skin test converters (within past 2 years) </li></ul><ul><li>Recent immigrants from TB-endemic regions of the world (within 5 years of arrival to the U.S.) </li></ul>Persons more likely to have been recently infected include
  18. 18. Recent Infection as a Risk Factor (2) <ul><li>Residents and employees of high-risk congregate settings (e.g., correctional facilities, homeless shelters, health care facilities) </li></ul>
  19. 19. Increased Risk for Progression to TB Disease (1) <ul><li>HIV-infected persons </li></ul><ul><li>Those with a history of prior, untreated TB or fibrotic lesions on chest radiograph </li></ul>Persons more likely to progress from LTBI to TB disease include
  20. 20. Increased Risk for Progression to TB Disease (2) <ul><li>Underweight or malnourished persons </li></ul><ul><li>Injection drug users </li></ul>
  21. 21. Increased Risk for Progression to TB Disease (3) <ul><li>Persons with certain medical conditions such as </li></ul><ul><ul><li>Silicosis </li></ul></ul><ul><ul><li>Diabetes mellitus </li></ul></ul><ul><ul><li>Chronic renal failure or on hemodialysis </li></ul></ul><ul><ul><li>Gastrectomy or jejunoilial bypass </li></ul></ul>
  22. 22. Tuberculin Testing
  23. 23. Mantoux Tuberculin Skin Test <ul><li>Preferred method of skin testing for M. tuberculosis infection </li></ul><ul><li>TST is useful for </li></ul><ul><ul><li>Determining how many people in a group are infected (e.g., contact investigation) </li></ul></ul><ul><ul><li>Examining persons who have symptoms of TB </li></ul></ul>
  24. 24. Reading the TST (1) <ul><li>Measure reaction in 48 to 72 hours </li></ul><ul><li>Measure induration, not erythema </li></ul><ul><li>Record reaction in millimeters, not “negative” or “positive” </li></ul><ul><li>Ensure trained health care professional measures and interprets the TST </li></ul>
  25. 25. Pretesting (2) <ul><li>Educate regarding significance of a positive TST result </li></ul><ul><li>Positive TST reactions can be measured accurately for up to 7 days </li></ul><ul><li>Negative reactions can be read accurately for only 72 hours </li></ul>
  26. 26. TST Interpretation (1) <ul><li>5-mm induration is interpreted as positive in </li></ul><ul><li>HIV-infected persons </li></ul><ul><li>Close contacts to an infectious TB case </li></ul><ul><li>Persons with chest radiographs consistent with prior untreated TB (e.g. fibrosis) </li></ul>
  27. 27. TST Interpretation (3) <ul><li>10-mm induration is interpreted as positive in </li></ul><ul><li>Recent immigrants </li></ul><ul><li>Injection drug users </li></ul><ul><li>Residents or employees of congregate settings </li></ul>
  28. 28. TST Interpretation (4) <ul><li>10-mm induration is interpreted as positive in (cont.) </li></ul><ul><li>Persons with clinical conditions that place them at high risk </li></ul><ul><li>Children < 4 years; infants, children, and adolescents exposed to adults at high-risk </li></ul>
  29. 29. TST Interpretation (5) <ul><li>Persons with no known risk factors for TB.* </li></ul>*Although skin testing programs should be conducted only among high-risk groups, certain individuals may require TST for employment or school attendance. Diagnosis and treatment of LTBI should always be tied to risk assessment. 15-mm induration is interpreted as positive in ____________________________________________________
  30. 30. BCG Vaccination <ul><li>BCG vaccination </li></ul><ul><ul><li>Reactivity in BCG vaccine recipients generally wanes over time; positive TST result is likely due to TB infection if risk factors are present </li></ul></ul><ul><ul><li>Thus a history of BCG vaccination is irrelevant to testing </li></ul></ul>
  31. 31. Factors That May Cause False-Negative TST Reactions (2) <ul><li>Recent TB infection </li></ul><ul><ul><li>Defined as 2 to 10 weeks after exposure </li></ul></ul><ul><li>Very young age </li></ul><ul><ul><li>Newborns </li></ul></ul>
  32. 32. LTBI Treatment Regimens
  33. 33. Treatment Guidelines <ul><li>Treatment of LTBI </li></ul><ul><li>HIV-negative persons – INH for 9 months preferred regimen </li></ul><ul><li>Rifampin for 4 months is an alternative </li></ul>
  34. 34. Treatment of LTBI <ul><li>Motivators: </li></ul><ul><li>5% TB Infection Rate at 1 year </li></ul><ul><li>15% Lifetime risk of TB </li></ul><ul><li>1 case of reactivation can result in 200-300 cases of TB </li></ul>
  35. 35. Initiating Treatment <ul><li>Before initiating treatment for LTBI </li></ul><ul><li>Rule out TB disease (i.e., wait for culture result if specimen obtained) </li></ul><ul><li>Determine prior history of treatment for LTBI or TB disease </li></ul><ul><li>Assess risks and benefits of treatment </li></ul><ul><li>Determine current and previous drug therapy </li></ul>
  36. 36. Rifampin Regimens (1) <ul><li>Rifampin (RIF) given daily for 4 months is an acceptable alternative when treatment with INH is not feasible. </li></ul><ul><li>In situations where RIF cannot be used (e.g., HIV-infected persons receiving protease inhibitors), rifabutin may be substituted. </li></ul>
  37. 37. Regimens (2) <ul><li>RIF daily for 4 months (120 doses within 6 months) </li></ul><ul><li>RIF and PZA for 2 months should generally not be offered due to risk of severe adverse events 6 </li></ul><ul><li>_____________________________________ </li></ul><ul><li>6 MMWR August 8, 2003; 52 (31): 735-739 </li></ul>
  38. 38. Completion of Therapy <ul><li>Completion of therapy is based on the total number of doses administered, not on duration alone. </li></ul>
  39. 39. Management of Patient Who Missed Doses <ul><li>Extend or re-start treatment if interruptions were frequent or prolonged enough to preclude completion </li></ul><ul><li>When treatment has been interrupted for more than 2 months, patient should be examined to rule out TB disease </li></ul><ul><li>Recommend and arrange for DOT as needed </li></ul>
  40. 40. Monitoring During Treatment - Risk
  41. 41. Clinical Monitoring (1) <ul><li>Rash </li></ul><ul><li>Anorexia, nausea, vomiting, or abdominal pain in right upper quadrant*** </li></ul><ul><li>Fatigue or weakness </li></ul><ul><li>Dark urine*** </li></ul><ul><li>Persistent numbness in hands or feet*** </li></ul>Instruct patient to report signs or symptoms of adverse drug reactions
  42. 42. Clinical Monitoring (2) <ul><li>Review why on treatment </li></ul><ul><li>Discuss adherence to treatment </li></ul><ul><li>Adverse symptoms – rash, hepatitis </li></ul><ul><li>Plans to continue treatment </li></ul>Monthly visits should include a brief physical exam and a review of
  43. 43. Clinical Monitoring (3) <ul><li>Incidence of hepatitis* in persons taking INH is lower than previously thought (0.1 to 0.15%) </li></ul><ul><li>Hepatitis risk increases with age </li></ul><ul><ul><li>Uncommon in persons < 20 years old </li></ul></ul><ul><ul><li>Nearly 2% in persons 50 to 64 years old </li></ul></ul><ul><li>Risk increased with underlying liver disease or heavy alcohol consumption </li></ul><ul><li>*subclinical </li></ul>
  44. 44. Laboratory Monitoring (1) <ul><li>Baseline liver function tests (e.g., AST, ALT, and bilirubin) are not necessary except for patients with the following risk factors: </li></ul><ul><li>HIV infection </li></ul><ul><li>History of liver disease </li></ul><ul><li>Alcoholism </li></ul><ul><li>Pregnancy or in early postpartum period </li></ul>
  45. 45. Laboratory Monitoring (2) <ul><li>Repeat laboratory monitoring if patient has </li></ul><ul><li>Abnormal baseline results </li></ul><ul><li>Current or recent pregnancy </li></ul><ul><li>High risk for adverse reactions </li></ul><ul><li>Symptoms of adverse reaction </li></ul><ul><li>Liver enlargement or tenderness during examination </li></ul>
  46. 46. Clinical/Laboratory Monitoring <ul><li>Routine baseline and follow-up monitoring not required except for </li></ul><ul><ul><li>HIV-infected persons </li></ul></ul><ul><ul><li>Pregnant women or those in early postpartum period </li></ul></ul><ul><ul><li>Persons with chronic liver disease or who use alcohol regularly </li></ul></ul><ul><li>Monthly monitoring for signs or symptoms of possible adverse effects </li></ul>
  47. 47. Laboratory Monitoring (3) <ul><li>Asymptomatic elevation of hepatic enzymes seen in 10%-20% of people taking INH </li></ul><ul><ul><li>Levels usually return to normal after completion of treatment </li></ul></ul><ul><li>Some experts recommend withholding INH if transaminase level exceeds 3 times the upper limit of normal if patient has symptoms of hepatotoxicity, and 5 times the upper limit of normal if patient is asymptomatic 7 </li></ul>7 MMWR June 9, 2000; 49(No. RR-6): 39
  48. 48. Summary: TB Prevention <ul><li>For every patient </li></ul><ul><li>Assess TB risk factors – immigrant status, immunosuppressed </li></ul><ul><li>If risk is present, perform TST </li></ul><ul><li>If TST or QFT is positive, </li></ul><ul><ul><li>Rule out active TB disease </li></ul></ul><ul><ul><li>Discuss R/B/A </li></ul></ul><ul><ul><li>Consider baseline LFTs </li></ul></ul><ul><ul><li>Initiate treatment for LTBI </li></ul></ul><ul><ul><li>Monitor and reinforce need for treatment </li></ul></ul>
  49. 49. Guidelines Available Online <ul><li>CDC’s Morbidity and Mortality Weekly Report </li></ul><ul><li> </li></ul><ul><li>American Thoracic Society </li></ul><ul><li> </li></ul>