Tuberculosis Transmission and Pathogenesis Draft Module 3 - September 2008 Interim

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

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

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

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

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

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

Transmission of M.tb

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

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

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

TB Transmission and PathogenesisExposure No infection (70%) Adequate Non-specific immunity Inadequate Infection (30%) Not everyone who is exposed to TB will become infected

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)

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

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

Spread of TB to Other Parts of the Body 1.Lungs (85% all cases) 2.Pleura 3.Central nervous system (e.g., brain, meninges) 4.Lymph nodes 5.Genitourinary system 6.Bones and joints 7.Disseminated (e.g., miliary) © ITECH, 2006

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

Cell-mediated Immune Response Source: CDC, 2001

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 bodys immune system Latent TB Infection (LTBI)

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

Reactivation Source: CDC, 2001

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 TB

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

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

High Prevalence High Prevalence for 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

High Risk High Risk for Progression 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) Persons more likely to progress from LTBI to TB disease include:

High Risk 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

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) High Risk High Risk for Progression (3)

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

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

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

True or False 1.Tuberculosis can be spread person to person by sharing the same cup or bottle. 2.TB bacteria in the air can be killed. 3.TB bacilli survive only a few minutes once expelled into the air. 4.Persons with LTBI and HIV have a 10% lifetime risk of progressing to active TB disease. 5.Tuberculosis accelerates the progression of HIV by activating the cell-mediated immune response

True or False (2) 6.Approximately 25% (1/4) of close contacts to a sputum smear-positive case will have LTBI 7.Mothers with active pulmonary TB can protect their infant from becoming infected with TB by breastfeeding 8.Mycobacterium bovis is the cause of most cases of tuberculosis 9.Diabetics are at higher risk for progression of LTBI to active TB disease than non-diabetics