Tuberculosis Transmission and Pathogenesis

1. Interim Draft Module 3 - September 2008 Tuberculosis Transmission and Pathogenesis

2. Project Partners • Collaborative project Funded by the United States Agency for International Development (USAID)

3. Module Overview • Etiology • Transmission • TB Infection • TB Disease • Co-pathogenesis • of TB and HIV

4. Learning Objectives At the end of this presentation, participants will be able to: • Describe the transmission and pathogenesis of tuberculosis (TB) • Identify populations: • More likely to have been recently infected with TB • More likely to progress from latent TB infection (LTBI) to active TB disease • Explain the association between TB and HIV as it relates to the disease progression of each

5. Etiology M. tuberculosis M. bovis M. africanum M. microti M. canettii M. caprae M. pinnipedii Source: CDC Public Health Image Library/Dr. George P. Kubica

6. Characteristics of M. tuberculosis • Thick lipid cell wall • Can remain dormant for decades • Aerobic • Non-motile • Slightly curved, rod shaped bacilli • 0.2 - 0.5 microns in diameter; 2 - 4 microns in length • Acid fast - resists decolorization with acid/alcohol • Multiplies slowly (every 18 - 24 hrs)

7. Etiology (2) • Mycobacteria commonly found in the environment rarely cause disease in humans and are not spread from person to person • Mycobacteria other than tuberculosis (MOTT) most often cause disease in individuals with weakened immune systems • Mycobacterium avium and M. intracellulare are the more common MOTT sometimes seen in patients co-infected with HIV

8. Transmission of M.tb Transmission of M.tb

9. How is TB Transmitted? • Person-to-person through the air by a person with TB disease of the lungs Source: CDC, 2000 • Less frequently transmitted by: • Ingestion of Mycobacterium bovis found in unpasteurized milk products • Laboratory accident

10. Transmission of M. tuberculosis • Millions of tubercle bacilli in lungs (mainly in cavities) • Coughing projects droplet nuclei into the air that contain tubercle bacilli • One cough can release 3,000 droplet nuclei • One sneeze can release tens of thousands of droplet nuclei

11. Fate of M. tb Aerosols Large droplets settle to the ground quickly Smaller droplets form “droplet nuclei” of 1–5 µ in diameter Droplet nuclei can remain airborne

12. TB Transmission and Pathogenesis No infection (70%) Adequate Non-specific immunity Exposure Inadequate Infection (30%) •  Not everyone who is exposed to TB will become infected

13. The Chance of Infection Increases… • When the concentration of TB bacteria circulating in the air is greater • Coughing; smear +; cavitary disease • Exposure occurs indoors • Poor air circulation and ventilation; small, enclosed space • Poor or no access to sunlight (UV light)

14. The Chance of Infection Increases…(2) • The greater the time spent with the infectious person or breathing in air with infectious particles

15. TB Germs Cannot be Spread By: • Sharing dishes and utensils • Using towels and linens • Handling food • Sharing cell phones • Touching computer keyboard

16. Spread of TB to Other Parts of the Body • Lungs (85% all cases) • Pleura • Central nervous system • (e.g., brain, meninges) • Lymph nodes • Genitourinary system • Bones and joints • Disseminated • (e.g., miliary) © ITECH, 2006

17. TB Can Affect Any Part of Your Body: Extrapulmonary TB Brain Pleura Lymph Node Spine

18. Cell-mediated Immune Response Source: CDC, 2001

19. Latent TB Infection (LTBI) • Person: • Not ill • Not contagious • Normal chest x-ray • Usually the tuberculin skin test is positive • Germs: • Sleeping but still alive • Surrounded (walled off) by body’s immune system

20. TB Transmission and Pathogenesis (2) Immunologic defenses No infection (70%) Adequate Non-specific immunity Early progression (5%) Exposure Inadequate Inadequate Infection (30%) Adequate Containment (95%)

21. Reactivation Source: CDC, 2001

22. TB Active TB Disease Germs: • Awake and multiplying • Cause damage to the lungs Person: • Most often feels sick • Contagious (before pills started) • Usually have a positive tuberculin skin test • Chest X-ray is often abnormal (with pulmonary TB) Granuloma breaks down and tubercle escape and multiply

23. TB Transmission and Pathogenesis (3) Immunologic defenses Immunologic defenses No infection (70%) Adequate Non-immunologic defense Early progression (5%) Exposure Inadequate Inadequate Late progression(5%) Infection (30%) Inadequate Adequate Containment (95%) Adequate Continued containment (90%)

24. Risk Assessment • Evaluate for risk factors that increase the likelihood: • that a person may have LTBI (high prevalence) • for progression of LTBI to active TB disease (high risk)

25. High Prevalencefor LTBI • Known contact to person with TB disease • Persons who live or spend time in certain congregate settings • facilities for the elderly • jails, prisons • shelters for the homeless • drug treatment centers • Overcrowded habitation (housing) • Persons born in countries with high prevalence of TB

26. High Risk for Progression Persons more likely to progress from LTBI to TB disease include: • HIV-infected persons • Persons with a history of prior, untreated TB or fibrotic lesions on chest X-ray • Recent TB infection (within past 2 years) • Injection drug users • Age (very young or very old)

27. High Risk for Progression (2) Persons with certain medical conditions such as: • Diabetes mellitus • Chronic renal failure or on hemodialysis • Solid organ transplantation • Certain types of cancer (e.g., leukemia) • Gastrectomy or jejunoileal bypass • Underweight or malnourished persons • Silicosis

28. High Risk for Progression (3) Persons taking immunosuppressive agents: • Prolonged corticosteroid therapy (>15mg daily for over 4 weeks) • Cancer chemotherapy • Cyclosporine Persons taking blocking agents against Tumor Necrosis Factor-Alpha: • Etanercept (Enbrel®) • Infliximab (Remicade®) • Adalimumab (HumiraTM)

29. The Effects of Immune Suppression from HIV on TB • Increased risk of reactivation of LTBI (10% annual risk among HIV+ vs. 10% lifetime risk among HIV-negative individuals) • More likely to have early progression to TB disease following infection • TB can occur at any point in the progression of HIV infection (any CD4 ct.) • High risk of recurrent TB (either relapse or re-infection) Source: TB/HIV: A Clinical Manual. Second Edition. WHO, 2004

30. The Effects of TB on HIV Progression • TB increases HIV replication by activating the immune system • Co-infected persons often have very high HIV viral loads • Immuno-suppression progresses more quickly, and survival may be shorter despite successful treatment of TB • Co-infected patients have a shorter survival period than persons with HIV who never had TB disease

31. Summary Activity • Write “True” on one side and “False” on the other side of the index card in front of you • As each question on the slides to follow is read, hold up your index card showing the answer to the statement • Be prepared to explain or defend your response

32. True or False • Tuberculosis can be spread person to person by sharing the same cup or bottle. • TB bacteria in the air can be killed. • TB bacilli survive only a few minutes once expelled into the air. • Persons with LTBI and HIV have a 10% lifetime risk of progressing to active TB disease. • Tuberculosis accelerates the progression of HIV by activating the cell-mediated immune response

33. True or False (2) • Approximately 25% (1/4) of close contacts to a sputum smear-positive case will have LTBI • Mothers with active pulmonary TB can protect their infant from becoming infected with TB by breastfeeding • Mycobacterium bovis is the cause of most cases of tuberculosis • Diabetics are at higher risk for progression of LTBI to active TB disease than non-diabetics