Transcript Module 3_Pathogenesis TB DISEASE

Interim
Draft Module 3 - September 2008
Tuberculosis
Transmission and
Pathogenesis
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
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
Characteristics of M. tuberculosis
 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)
 Thick lipid cell wall
 Can remain dormant
for decades
 Aerobic
 Non-motile
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
Transmission
of
of M.tb
M.tb
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
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
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 Pathogenesis
No infection (70%)
Adequate
Exposure
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
© ITECH, 2006
6. Bones and joints
7. Disseminated
• (e.g., miliary)
TB Can Affect Any Part of Your Body:
Extrapulmonary TB
Brain
Pleura
Lymph Node
Spine
Cell-mediated Immune Response
Source: CDC, 2001
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
TB Transmission and Pathogenesis (2)
No infection (70%)
Adequate
Exposure
Non-specific
immunity
Early progression (5%)
Inadequate
Inadequate
Infection (30%)
Immunologic
defenses
Adequate
Containment (95%)
Reactivation
Source: CDC, 2001
Active TB Disease
TB
Germs:
 Awake and multiplying
 Cause damage to the lungs
Person:
 Most often feels sick
 Contagious (before pills started)
 Usually have a positive
Granuloma breaks
tuberculin skin test
down and tubercle
escape and multiply
 Chest X-ray is often abnormal
(with pulmonary TB)
TB Transmission and Pathogenesis (3)
No infection (70%)
Adequate
Exposure Non-immunologic
defense
Early progression (5%)
Inadequate
Inadequate
Infection (30%)
Immunologic
defenses
Adequate
Containment (95%)
Late progression(5%)
Inadequate
Immunologic
defenses
Adequate
Continued containment (90%)
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)
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 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)
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
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)
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