1 / 57

Tuberculosis Today

Tuberculosis Today. James S. Seebass, D.O. Oklahoma State University Center for Health Sciences • College of Osteopathic Medicine. Global Burden of Tuberculosis. ~ 8 million new cases of active TB/year 2-3 million deaths worldwide/year 1 in 3 persons with Mycobacterium tb infection

merlin
Download Presentation

Tuberculosis Today

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Tuberculosis Today James S. Seebass, D.O. Oklahoma State University Center for Health Sciences • College of Osteopathic Medicine

  2. Global Burden of Tuberculosis • ~ 8 million new cases of active TB/year • 2-3 million deaths worldwide/year • 1 in 3 persons with Mycobacterium tb infection • 22 high TB burden countries; hot spots for MDR with drug resistance as high as 14%*

  3. Transmission and Pathogenesis of Tuberculosis

  4. Transmission of Tuberculosis “In approaching the consumptive one breathes pernicious air. One takes the disease because there is in this air something disease-producing” Aristotle

  5. Transmission of Tuberculosis Generation of Droplet Nuclei • One cough produces 500 droplets • The average tuberculosis (TB) patient generates 75,000 droplets per day before therapy • This drops to 25 infectious droplets per day within 2 weeks of effective therapy

  6. Transmission of Tuberculosis CASE CONTACT Site of TB Cough Bacillary load Treatment Ventilation Filtration U.V. light Closeness and duration of contact Immune status Previous infection

  7. Tuberculin Reactivity Among Contacts by Index Status Contact status Index Status Household Casual (n=858) (n=4207) Sm +, Cx + 20.2% 3.7% Sm –, Cx + 1.1% 0.2% Van Geuns, et al. BIUAT 1975;50:107

  8. Likelihood of Developing TB In Contacts by Index Status TB Among Contacts Index Status Close Casual Close Casual (Ages: 0 -14 yrs) (Ages: 15 - 29 yrs) Sm +, Cx + 38% 24% 11% 6% Sm –, Cx + 18% 18% 1% 3% Grzybowski S, et al. BIUAT. 1975;60:90

  9. Effects of Therapy on M. tuberculosis

  10. General Issues: Clinical Suspicion • To diagnose TB you must first think of TB • Knowing when to consider TB in the differential diagnosis = knowing who is at risk • risk for infection • risk for disease

  11. General Issues: Clinical Suspicion (2) • Risk for infection • Homeless or unstably housed • Foreign-born from high prevalence country • Residence in institution • Healthcare worker • Contact with pulmonary TB patient

  12. General Issues: Clinical Suspicion (3) • Risk for disease • HIV infection • CXR with fibrotic lesions consistent with old TB • Substance abuse • Diabetes mellitus • Chronic renal failure • Immunosuppressive therapy (equivalent to 15 mg prednisone/day for at least 1 month)

  13. General Issues: Clinical Suspicion (4) • Risk for disease (continued) • Solid organ transplant recipients • Silicosis • Hematologic malignancies • Head and neck cancers • Malnutrition • Gastrectomy or jejunoileal bypass • Prior TB disease

  14. Risk Factor How many times higher is the risk of TB disease HIV/AIDS 113-170 Diabetes 4.1 “old TB” on CXR 13.6 Chronic renal failure 25 Other conditions 3-16 Risk for Development of TB Disease

  15. Who Should Be Screened:“TARGETED TESTING” Screening should be targeted to those at higher risk of TB • Populations with increased rates of TB infection • Persons with increased risk of progression to active TB if infected • NOT the general population

  16. New Tuberculosis Guidelines: Tuberculin Testing Criteria for Tuberculin Positivity >5 mm>10 mm>15 mm HIV infection Recent immigrants No risk Contact to Injection drug users active TB case Children Abnormal CXR High risk medical 15 mg/day prednisone conditions for 1 month Residents and employees homes, hospitals of jails/nursing

  17. Risk of Infection Recent contacts of infectious TB cases: • 4-5% risk of developing active disease within the first 1-2 years • Risk may double if contact is < 4 years old • Nationwide about 20% of TB contacts are infected

  18. Risk of Infection (2) Foreign born persons: • High and intermediate incidence (Asia and Pacific Islands, Africa, Central and South America, Eastern Europe, Middle East) • Emphasis on newcomers to the U.S. (<5 years)

  19. Risk of Infection (3) Medically underserved/low-income groups: • Homeless • Migrant workers • Low-cost hotel dwellers or crowded impoverished living conditions • Street drug users • Racial and ethnic minorities • Children with parents that have TB risk factors

  20. Risk of Infection (4) • Pregnant women belonging to any risk groups or if the local TB epidemiologic situation warrants it • Correctional facilities (inmates and staff) • Healthcare workers • Nursing home • Long-term care facilities • Renal dialysis units

  21. Risk of Progression HIV infection: • Screen as early as possible (anergy increases as HIV disease advances) • Screen every 6-12 months; thereafter depends on lifestyle and environment • Exceptionally high rate of reactivation (7-10% per year) • Rapid development to active disease from new infection

  22. Risk of Progression (2) Individuals with abnormal chest x-ray compatible with past TB regardlessof age • Risk of active disease is 10 times that of a person with a normal x-ray and no other risk factors • Annual reactivation rate: 0.3  1.5% versus .05  0.1% • PPD and sputum part of screening in spite of stability of chest x-ray and history of treatment

  23. Risk of Progression (3) Recent infection: • 4-5% risk of developing active disease within the first 1-2 years Infants and children < 4 years of age • 40% progression to disease in infants younger than 12 months

  24. Risk of Progression (4) Medical conditions: • Immunosuppressive therapy (including anti-TNF-alpha, e.g. infliximab) • Lymphoma, leukemia • Injection drug use • Diabetes • Malnutrition • Renal failure • Silicosis • Alcoholism

  25. Frequency of Screening • Retesting: dependent on ongoing risk of TB exposure • Frequency: dependent on degree of chronic TB exposure (use local epidemiology) • Annual testing*: healthcare workers, long-term care residents, shelter or homeless program or substance recovery program staff • Q 6 month testing*: TB clinic frontline staff, ER workers, pulmonologists performing bronchoscopy *Need to correlate with local epidemiologic data

  26. Tuberculin Skin Test Interpretation: False-Negative Results • Host factors • HIV • Recent TB infection (<3 months) • Infections (viral, fungal, bacterial) • Other illness affecting lymphoid organs • Live virus vaccination • Immunosuppressive drugs • Overwhelming TB • Age (newborn, elderly)

  27. Tuberculin Skin Test Interpretation: False-Negative Results (2) • Technical factors • The tuberculin used (i.e., improper storage, contamination) • Improper method of administration, reading and/or recording of results

  28. Tuberculin Skin Test Interpretation: False-Positive Results (3) Causes • Cross-reactions from atypical mycobacterial infections • Recent or multiple BCG vaccination • Misinterpretation of immediate hypersensitivity to tuberculin • Switching tuberculin products (tubersol with applisol)

  29. Tuberculin Skin Test Interpretation Absence of PPD reaction DOES NOT EXCLUDE DISEASE

  30. TST Interpretation: Boosted Reaction • Delayed hypersensitivity to tuberculin in some individuals may gradually wane over time • Initial PPD may be “falsely negative” • A booster response may incorrectly be interpreted as a “conversion”

  31. BCG Vaccination and Interpretation of the Tuberculin Skin Test • CDC recommendation: • Ignore history of BCG when interpreting the skin test • Consult TB experts if confused (my recommendation)

  32. Tuberculosis Screening Flowchart At-risk person Tuberculin test + symptom review Negative Positive Chest x-ray Normal Abnormal Candidate for Rx of latent TB Treatment not indicated Evaluate for active TB

  33. “A Rose by Any Other Name” Terms no longer in use: • prophylaxis • chemoprophylaxis • preventive therapy • preventive treatment Rose du jour: Treatment of latent tuberculosis infection LTBI

  34. New Guidelines for TB Prevention: Changes From the Past • DECISION TO TEST IS DECISION TO TREAT! • No 35-year-old cut-off • 9 months of INH preferred over 6 months • New alternatives to INH (rifampin-based regimens) • Baseline laboratory monitoring not routinely indicated

  35. Completion of INH Treatment for LTBI • Based on total number of doses, not duration • Need to take 270 doses within 12 months for 9 month regimen • Need to take 180 doses within 9 months for 6 month regimen

  36. Clinical Trials of Isoniazid Preventive Therapy Number of Cases Year

  37. Isoniazid-Induced Hepatitis N=13,838 Hepatitis Age (yr) Cases/1000 < 20 0.0 20-34 3.0 35-49 12.0 50-64 23.0 > 64 8.0 N=11,141 Hepatitis Age (yr)Cases/1000 0-14 0.0 15-34 0.8 35-64 2.1 ≥65 2.8 Nolan CL et al. JAMA 1999;281:10140 Kopanoff et al. Am Rev Resp Dis 1976;117:991

  38. Clinical Presentation: Site of Disease Reported TB Cases by Form of Disease United States, 2001 Both (7.4%) Extrapulmonary (20.1%) Pleural (18.3%) Lymphatic (42.5%) Pulmonary (72.5%) Other (12.3%) Bone/joint (10.2%) Peritoneal (4.6%) Meningeal (6.0%) Genitourinary (5.9%)

  39. Clinical Presentation: Pulmonary Symptoms and Signs • Cough – 40-80% • Sputum production • Pleuritic chest pain • Hemoptysis – does not always indicate active disease

  40. Clinical Presentation: Systemic Symptoms and Signs (2) • Fever – 65-80% • Chills/sweats • Fatigue/malaise • Anorexia/weight loss • No symptoms – 10-20%

  41. Radiographic Presentation: Pulmonary Tuberculosis Primary Post-primary Location of infiltrates Upper: Lower 60:40 85% upper Usually upper in children Cavitation Rare Often present Adenopathy Adults ~30% Rare Children-common Effusion May be present May be present

  42. Laboratory Diagnosis: Predictive Value of a Positive Smear Smear positive for AFB Initiate treatment for TB Culture and Speciation M. tuberculosis Non-tuberculous 50-90% mycobacteria 10-50% Continue treatment Adjust treatment

  43. Approach to a Patient Suspected of Having TB: AFB Smear Negative Smear negative for AFB High Low Moderate Assess the following: No Rx, Initiate Rx clinical/immune status wait for • risk of transmission culture • side-effects of Rx result • Invasive diagnostic procedure; bronchoscopy, FNA

  44. Antituberculosis Drugs In the United States First-line Drugs Second-line Drugs Isoniazid Cycloserine Rifampin Ethionamide Rifapentine Levofloxacin* Rifabutin* Moxifloxacin* Ethambutol Gatifloxacin* Pyrazinamide p-Aminosalicylic acid Streptomycin Amikacin/kanamycin* Capreomycin * Not approved by the United States Food and Drug Administration for use in the treatment of tuberculosis.

  45. Treatment of TuberculosisRelative Activities of Drugs Agent Early bactericidal Preventing Sterilizing activity drug resistance activity Isoniazid ++++ +++ ++ Rifampin ++ +++ ++++ Pyrazinamide + + +++ Streptomycin ++ ++ ++ Ethambutol ++ – +++ ++ + Highest ++++, High +++, Intermediate ++, Low +

  46. Treatment of TuberculosisStandard Regimen Initial Phase Continuation Phase Isoniazid Rifampin Pyrazinamide Ethambutol 0 1 2 3 4 5 6 months

  47. Recommended Regimens Initial Continuation Rating Reg. Drugs Interval/Dose Reg. Drugs Interval/Doses HIV- HIV+ 1 INH 7 days/wk (56) 1a INH/RIF 7 days/wk (126) AI AII RIF or 5 days/wk (40) or 5 days/wk (90) EMB 1b INH/RIF 2X weekly (36) AI AII PZA 1c INH/RPT* once weekly (18) BI EI 2 INH 7 days/wk (14) 2a INH/RIF 2X weekly (36) AII BII RIF then 2X weekly (12) 2b INH/RPT* once weekly (18) BI EI EMB PZA *RPT - Only for HIV (–) persons without cavitation who are smear (– ) by 2 mos

More Related