1. Continuity Clinic Tuberculosis

2. Continuity Clinic 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. Continuity Clinic Background Epidemiology

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

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

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

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

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

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

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

12. Continuity Clinic 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. Continuity Clinic Questionnaire Risk Assessment for TB Infection in Children - NYCDOH Risk factor Sens. Spec. PPV NPV OR 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 Ozuah et al. JAMA;285:451

14. Continuity Clinic 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) Epidemiologically-Defined Groups with HIGH Prevalence of Tuberculosis Infection

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

16. Continuity Clinic 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 Incidence of Tuberculosis by Selected Risk Factors in Persons with a Positive TST

17. Continuity Clinic HOW TO TEST

18. Continuity Clinic Tuberculin Skin Testing

19. Continuity Clinic 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 Induration of >5mm Considered a Positive TST

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

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

22. Continuity Clinic 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. Interferon Gamma Release Assays

23. Continuity Clinic Positive Skin Test Now what?

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

25. Continuity Clinic Hilar adenopathy with infiltrate and collapse

26. Continuity Clinic Miliary TB in a child

27. Continuity Clinic 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. Continuity Clinic 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. Continuity Clinic Treatment

30. Continuity Clinic 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 Treatment of LTBI

31. Continuity Clinic 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 Tunisia Kenya India Philippines ISONIAZID PREVENTIVE THERAPY Worldwide Trials, 1955-1965

32. Continuity Clinic 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 Comstock GW, 1999. Int J Tuberc. Lung Dis 3:847-850 Community based study, Bethel Alaska How Much Isoniazid Is Needed for the Prevention of Tuberculosis?

33. Continuity Clinic 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 therapy69% –12 months therapy 93% IUATLD Study of INH Therapy for LTBI

34. Continuity Clinic 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. Continuity Clinic 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) Treatment of Latent TB Infection in Special Situations

36. Continuity Clinic 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. TB and BCG Vaccination