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Treatment of Latent Tuberculosis Infection

Treatment of Latent Tuberculosis Infection. 索任 醫師 社團法人中華民國防癆協會 第一胸腔病防治所. http://www.tb.org.tw. Latent infection vs. disease. 感染. 發病. Class I. contact. Infectious. Class III. Disease. Infected. Class II. 傳染. 傳染 transmission. 化學治療. Chemotherapy.

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Treatment of Latent Tuberculosis Infection

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  1. Treatment of Latent Tuberculosis Infection 索任 醫師 社團法人中華民國防癆協會 第一胸腔病防治所 http://www.tb.org.tw

  2. Latent infection vs. disease 感染 發病

  3. Class I contact Infectious Class III Disease Infected Class II 傳染

  4. 傳染 transmission 化學治療 Chemotherapy 結核病的傳染期= 病人延遲 +醫師延遲 +病人治療管理不當 Doctor’s delay 醫師延誤 Patient’s delay 預防性 Prophylactic 病人延誤 Preventive therapy 治療 treatment 傳染性 結核病 Infectious TB 結核潛伏 接觸 死亡 Exposure 感染 Subclinical infection Death 非傳染性 結核病 Non-Infectious TB BCG vaccination Source: Interventions for Tuberculosis Control and Elimination, IUATLD 2002 卡介苗 接種 結核病防治

  5. Treatment of LTBI – Milestones (1) • For more than 3 decades, an essential component of TB prevention and control in the U.S. has been the treatment of persons with LTBI to prevent TB disease.

  6. Treatment of LTBI – Milestones (2) • 1965: American Thoracic Society (ATS) recommends treatment of LTBI for those with previously untreated TB, tuberculin skin test (TST) converters, and young children. • 1967: Recommendations expanded to include all TST positive reactors (10 mm).

  7. Treatment of LTBI – Milestones (3) • 1974: CDC and ATS guidelines established for pretreatment screening to decrease risk of hepatitis associated with treatment • Treatment recommended for persons ≤ 35 years of age

  8. Treatment of LTBI – Milestones (4) • 1983: CDC recommends clinical and laboratory monitoring of persons  35 who require treatment for LTBI • 1998: CDC recommends 2 months of rifampin (RIF) plus pyrazinamide (PZA) as an option for HIV-infected patients (later changed)

  9. Treatment of LTBI – Milestones (5) • 2000: CDC and ATS issue updated guidelines for targeted testing and LTBI treatment * • 9-month regimen of isoniazid (INH) is preferred • 2-month regimen of RIF and PZA and a 4-month regimen of RIF recommended as options (later changed) * MMWR June 9, 2000; 49(No. RR-6)

  10. Treatment of LTBI – Milestones (6) • 2001: Owing to liver injury and death associated with 2-month regimen of RIF and PZA, use of this option de-emphasized in favor of other regimens ** • 2003: 2-month regimen of RIZ and PZA generally not recommended — to be used only if the potential benefits outweigh the risk of severe liver injury and death *** ** MMWR August 31, 2001; 50(34): 733-735 *** MMWR August 8, 2003; 52(31): 735-739

  11. Risk Factors for Tuberculosis Following Infection Reider HL. Epidemiol Rev 1989;11:79-98.

  12. Persons at Risk for DevelopingTB Disease • Persons at high risk for developing TB disease fall into 2 categories • Those who have been recently infected • Those with clinical conditions that increase their risk of progressing from LTBI to TB disease • HIV-infected persons • Those with a history of prior, untreated TB or fibrotic lesions on chest radiograph • Persons with certain medical conditions

  13. Alaska Village INH Preventive Therapy Comstock GW. Am Rev Respir Dis 1970;101:780-2

  14. IUAT Trial of INH Preventive Therapy Bull. WHO. 1982;60:555-64

  15. Risk of Tuberculosis in Close Contacts: Percentage Reduction with Isoniazid (USPHS Trial) Ferebee SH. Adv Tuberc Res 1970;17:28-106.

  16. 新城鄉、秀林鄉及南澳鄉結核菌素反應陽性之學齡前兒童結核病發病情形新城鄉、秀林鄉及南澳鄉結核菌素反應陽性之學齡前兒童結核病發病情形 追蹤期間：4.750.54年 索任. 衛生行政學刊 1992;12:67-72.

  17. Limitations of Preventive Therapy for Tuberculosis • Toxicity • Compliance • Drug resistance • Reinfection • Feasibility • PPD • Burden • Cost

  18. Isoniazid-related Hepatitis • Probable isoniazid-related cases of hepatitis • SGOT  250 Karmen units, or SGOT < 250 Karmen units, but SGPT  SGOT, and • Negative HBsAg (if done), and • Other causes of hepatitis not apparent • Possible isoniazid-related cases of hepatitis • SGOT < 250 Karmen units, or • SGOT  250, in the presence of other causes of liver disease, or • SGOT  250, but lacking other biochemical tests Kopanoff DE et al. Am Rev Respir Dis 1978;117:991-1001.

  19. Isoniazid-related Hepatitis Kopanoff DE et al. Am Rev Respir Dis 1978;117:991-1001.

  20. Cumulative Percentage of Isoniazid-related Hepatitis Cases by Month of Occurrence Kopanoff DE et al. Am Rev Respir Dis 1978;117:991-1001.

  21. Death Rate by Year Among Persons Started on INH Preventive Therapy Snider DE et al. Am Rev Respir Dis 1992;145:494-7.

  22. Limitations of Preventive Therapy for Tuberculosis • Toxicity • Compliance • Drug resistance • Reinfection • Feasibility • PPD • Burden • Cost

  23. Percent of Available INH Doses Taken During the First 4 Monthly Medication Orders Alcabes P et al. Compliance with isoniazid prophylaxis in jail.Am Rev Respir Dis 1989;140:1194-97.

  24. Results of a Directly Observed Intermittent Isoniazid Preventive Therapy Program in a Shelter for Homeless Men • 47 (73%) of 64 men recommended to take preventive regimens began therapy. • 23/47 (49%) completed the 6- to 12-month regimen. • Men who failed to complete therapy received a median of 11 biweekly doses over a median of 9 weeks. • The most common reason for incomplete treatment was that the men no longer frequented the shelter. • Out-of-state location of personal contacts in case of emergency was strongly associated with noncompliance. Mazar-Stewart V et al. Am Rev Respir Dis 1992;146:57-60.

  25. Limitations of Preventive Therapy for Tuberculosis • Toxicity • Compliance • Drug resistance • Reinfection • Feasibility • PPD • Burden • Cost

  26. Summary of Studies on Primary Anti-TB Drug Resistance Among M. Tuberculosis in Asia Cohn DL et al. Clin Infect Dis 1997;24(suppl 1):s121-30.

  27. 歷年新病人結核菌抗藥性情形 台灣省慢性病防治局台北示範中心

  28. Limitations of Preventive Therapy for Tuberculosis • Toxicity • Compliance • Drug resistance • Reinfection • Feasibility • PPD • Burden • Cost

  29. Tuberculosis Results From Recent Transmission • The minimum percentage of cases due to primary tuberculosis in the urban homeless in central Los Angeles was estimated to be 53%. • Barnes PF et al. JAMA 1996;275:305-7. • Nearly 1/3 of new cases of tuberculosis in San Francisco are the result of recent infection. • Small PM et al. N Engl J Med 1994;330:1703-9. • In the inner-city of New York, recently transmitted tuberculosis accounts for 40% of the incident cases and almost 2/3 of drug-resistant cases. • Alland D et al. N Engl J Med 1994;330:1710-6.

  30. Limitations of Preventive Therapy for Tuberculosis • Toxicity • Compliance • Drug resistance • Reinfection • Feasibility • PPD • Burden • Cost

  31. Factors Causing Decreased Ability to Respond to Tuberculin (1) • Factors related to the person being tested • Infections • Viral (measles, mumps, chicken pox) • Bacterial (typhoid fever, brucellosis, typhus, leprosy, pertussis, overwhelming tuberculosis, tuberculous pleurisy) • Fungal (South American blastomycosis) • Live virus vaccinations (measles, mumps, chicken pox) • Metabolic derangements (chronic renal failure) • Nutritional factors (severe protein depletion) • Diseases affecting lymphoid organs (Hodgkin’s disease, lymphoma, chronic lymphocytic leukemia, sarcoidosis) • Drugs (corticosteroids and other immunosuppressive agents) • Age (newborns, elderly patients with “waned” sensitivity) • Recent or overwhelming infection with M. tuberculosis • Stress (surgery, burns, mental illness, graft-versus-host reactions) ATS. Am Rev Respir dis 1990;142:725-35.

  32. Factors Causing Decreased Ability to Respond to Tuberculin (2) • Factors related to the tuberculin used • Improper storage (exposure to light and heat) • Improper dilution • Chemical denaturation • Adsorption (partially controlled by adding Tween 80) • Factors related to method of administration • Injection of too little antigen • Delayed administration after drawing into syringe • Injection too deep • Factors related to reading the test and recording results • Inexperienced reader • Conscious or unconscious bias • Error in recording ATS. Am Rev Respir dis 1990;142:725-35.

  33. Effect of BCG Vaccination on Tuberculin Reactivity Quebec, Canada Menzies R et al. Am Rev Respir Dis 1992;145:621-25.

  34. Effect of Age and BCG Status on Tuberculin Reactions Induration  10mm Menzies R et al. Am Rev Respir Dis 1992;145:621-25.

  35. Influence of BCG Vaccination on PPD Reaction Swedish schoolchildren, 8-9 years of age Larsson LO et al. Eur Respir J 1992;5:584-6.

  36. Distribution of Tuberculin Reactivityfor Children  14 Years of Age, Chile Sepulveda RL et al. Am J Respir Crit Care Med 1994;149:620-4.

  37. Comparison of Subjects Vaccinated at Birth With Non-vaccinated Subjects of the Same Age Tuberculin tested 20-25 years after BCG vaccination, Spain Miret-Cuadras P et al. Tuberc Lung Dis 1996;77:52-8.

  38. Comparison of Subjects Vaccinated at 6-14 Years With Non-vaccinated Subjects of the Same Age Tuberculin tested 20-25 years after BCG vaccination, Spain Miret-Cuadras P et al. Tuberc Lung Dis 1996;77:52-8.

  39. PPD skin test Boosting • Some people with LTBI may have a negative skin test reaction when tested years after infection because of a waning response. • An initial skin test may stimulate (boost) the ability to react to tuberculin. • Positive reactions to subsequent tests may be misinterpreted as new infections rather than “boosted” reactions.

  40. Results of Second Tuberculin Test 4.78 Years After Previous Negative Test Miret-Cuadras P et al. Tuberc Lung Dis 1996;77:52-8.

  41. PPD skin test Two-Step Testing (1) • A strategy to determine the difference between boosted reactions and reactions due to recent infection. • If first TST is positive, consider the person infected • If first TST is negative, give second TST 1–3 weeks later • If second TST is positive, consider the person infected • If second TST is negative, consider the person uninfected at baseline

  42. PPD skin test Two-Step Testing (2) • Use two-step tests for initial baseline skin testing of adults who will be retested periodically (e.g., health care workers).

  43. Tuberculin Reaction Size in Children Aged 6 in Taiwan, 1996-1997 PPD RT23 1tu/0.1ml BCG(+) 39680 tested; ≧ 10 mm: 5424 (13.7%); ≧ 15 mm: 894(2.3%) BCG(-) 8640 tested; ≧ 10 mm: 291 (3.37%)

  44. Summary of Costs and Health Benefits of INH Preventive Therapy or 12, 24 and 52 Weeks’ Duration* Snider DE. JAMA 1986;255:1579-83.

  45. Factors Determining Effectiveness of Preventive Chemotherapy • Risk of tuberculosis given infection • Efficacy of regimen • Adherence to treatment Interventions for Tuberculosis Control and Elimination, IUATLD 2002

  46. Interventions for Tuberculosis Control and Elimination, IUATLD 2002

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