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Tuberculosis
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  1. Tuberculosis

  2. Objectives • Know current epidemiologic trends in TB • Know indications for testing for TB exposure and the tests available • Be familiar with treatments for latent tuberculosis infections

  3. Background Epidemiology

  4. 9 million Cases Annually >1/3 in India and China 9 million Cases Annually>1/3 in India and China < 1 000 1 000 to 9 999 10 000 to 99 999 100 000 to 999 999 1 000 000 or more No Estimate

  5. Reported TB Cases* United States, 1982–2006 No. of Cases Year

  6. TB Case Rates,* United States, 2006 D.C. < 3.5 (year 2000 target) 3.6–4.6 > 4.6 (national average) *Cases per 100,000.

  7. TB Case Rates by Age Group and Sex, United States, 2006 Cases per 100,000

  8. Trends in TB Cases in Foreign-born Persons, United States, 1986–2006* No. of Cases Percentage *Updated as of April 6, 2007.

  9. Drug Resistant TB Counted Cases defined on Initial DST† by Year, 1993–2006* *Reported incident cases as of 7/18/07 †Drug Susceptibility Test Case Count Year of Diagnosis

  10. TB in Children • WHO estimate of TB in children • 1.3 million annual cases • 450,000 deaths • 15% of TB in low-income countries children vs. 6% in United States

  11. MAKING THE DECISION TO TEST FOR TB The Initial “Test” for TB Infection is the History

  12. Who Should be Tested? • Those at epidemiological increased risk of having TB infection • Those at increased individual risk of developing TB disease if infected • ONLY test if you are going to treat the patient – a decision to test is a decision to treat

  13. Questionnaire Risk Assessment for TB Infection in Children - NYCDOH Ozuah et al. JAMA;285:451 Risk factorSens.Spec.PPVNPVOR Contact to a case 26 99.6 38.9 99.3 92 Birth/travel to endemic area 63 89.7 5.4 99.6 15 Contact to HR adult 19 96.6 4.9 99.2 7 Age > 11 yr 67 71.0 2.1 99.6 5

  14. Epidemiologically-Defined Groups with HIGH Prevalence of Tuberculosis Infection • Immigrants from areas of world with a high incidence of TB • Homeless persons, and other low income groups with poor access to health care • Elderly persons • Residents and employees in congregate living facilities serving persons at high risk of TB (correctional institutions, homeless shelters, health care facilities, nursing homes, assisted living facilities, AIDS housing)

  15. Underlying Medical Conditions Which Increase Risk for Progression to Active TB Disease • HIV infection • Chronic renal failure • Immunosuppressive Rx • Diabetes mellitus • Malignancy • TNF Alpha blocker therapy • Transplant recipients • > 15 mg Prednisone/day • Silicosis

  16. Incidence of Tuberculosis by Selected Risk Factors in Persons with a Positive TST Risk Factor TB Cases/1000 person-years Recent TB Infection Infection < 1 year past Infection 1-7 years past HIV/AIDS Injection Drug Use HIV-positive HIV-negative or unknown Silicosis Radiographic findings consistent with old TB Weight Deviation from Standard (5% overweight  15% underweight) 12.9 1.6 35.0-162 76.0 10.0 68.0 2.0-13.6 0.7-2.6

  17. HOW TO TEST

  18. Tuberculin Skin Testing Tuberculin Skin Testing

  19. Induration of >5mm Considered a Positive TST • HIV positive persons • Recent contacts of TB cases • Fibrotic Changes on CXR c/w old (not treated) TB • Patients with organ transplants or other immunosuppression • Prednisone therapy 15 mg/day > 1 month

  20. Induration of >10mm Considered a Positive TST • Recent arrivals (<5 yrs) high prevalence countries • Intravenous Drug Users • Residents/employees - high-risk congregate facilities (health care, prisons, shelters, etc.)

  21. Induration of >15mm Considered a Positive TST • TB lab personnel • Persons with “high-risk” medical conditions • Children <4 yrs or exposed to adults at risk

  22. Interferon Gamma Release Assays • Quantiferon – measure of interferon gamma in supernatant, currently at third generation test – Quantiferon Gold In-tube • Elispot – measure of individual T-cells that produce interferon gamma.

  23. Positive Skin Test Now what?

  24. Before Treatment of LTBI: Exclude Active Tuberculosis • Absence of symptoms • Negative CXR • Negative medical evaluation • Order and wait for sputum culture if any question

  25. Hilar adenopathy with infiltrate and collapse

  26. Miliary TB in a child

  27. Chest Radiograph “Pearls” • Hilar nodes, pleural disease – extrapulmonary, few bacteria • Cavitary disease – many bacteria • Parenchymal scars – NOT active, only needs preventive therapy (LTBI) IF scar is > 2.5 cm • Calcified node is functionally like a normal chest radiograph (very very few live AFB)

  28. Childhood TB diagnosed by: • Combination of : • Contact with infectious adult case • Symptoms and signs • Positive tuberculin skin test • Suspicious CXR or CT/MRI • Bacteriological confirmation • Serology?

  29. Treatment

  30. Treatment of LTBI • Treatment regimens: • INH x 9 months • Alternative: Rifampin 600mg daily x 4 months for adults, 6 months for children and HIV+ • Possible: • INH & Rifampin x 3 to 4 months • INH, Rifampin, EMB & PZA x 2 months • No longer used: Rifampin/PZA x 2 months • New? Rifapentine & INH weekly x 12 weeks

  31. 19 controlled trials in 11 countries: United States Canada Greenland Mexico Japan Netherlands France Over 100,000 participants Household contacts (6), Entire communities (3), Inactive pulmonary lesions (5), Children with primary TB (2), School children (1) Railway workers (1), Mentally ill patients (1) 25-92% protection ISONIAZID PREVENTIVE THERAPYWorldwide Trials, 1955-1965 Tunisia Kenya India Philippines

  32. How Much Isoniazid Is Needed for the Prevention of Tuberculosis? • Longer durations of therapy corresponded to lower TB rates among those who took 0-9 mo • No extra increase in protection among those who took >9 months Community based study, Bethel Alaska Comstock GW, 1999. Int J Tuberc. Lung Dis 3:847-850

  33. IUATLD Study of INH Therapy for LTBI • Reduction in culture positive TB at 5 years all participants • 6 months therapy 65% • 12 months therapy 75% • Reduction in culture positive TB at 5 years in the group of completer-compliers (took > 80% of doses): • 6 months therapy 69% • 12 months therapy 93%

  34. Contacts Of INH Resistant TB • Four month regimen daily Rifampin for adults • Six month regimen daily Rifampin for HIV infected • Six month regimen daily Rifampin for children

  35. Treatment of Latent TB Infection in Special Situations • For children and adolescents (<18 years old): • Isoniazid for 9 months • For pregnant women: • Isoniazid for 9 or 6 months - may defer except for HIV- infected women and those recently infected with Mycobacterium tuberculosis • For persons exposed to isoniazid resistant TB: • Rifampin for 4 months • For persons likely infected with multidrug-resistant TB: • Pyrazinamide and ethambutol, or pyrazinamide and • quinolone for 6-12 months (i.e., at least 2 drugs to which the organism is susceptible)

  36. TB and BCG Vaccination • Efficacy for adult pulmonary TB 0-80% in randomized clinical trials • Best efficacy against serious childhood disease • 64% protection against TB meningitis • 78% protection effect against disseminated TB • BCG important for young children, inadequate as single strategy Colditz GA et al. JAMA 1994; 271: 698-702.