Module 2 – March 2010
Tuberculosis
Transmission and
Pathogenesis
Project Partners
Funded by the Health Resources and Services Administration (HRSA)
Module Overview
 Etiology
 Transmission
and
pathogenesis
 Risk assessment
 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
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
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
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
M.tb
of 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
 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 Pathogenesis
No infection (70%)
E
X
P
O
S
U
R
E
Adequate Immunity
Non-specific immunity
Inadequate Immunity
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
Brain
Pleura
Lymph Node
Spine
Cell-mediated Immune Response
Special immune
cells form a hard
shell (in this
example, bacilli
are in the lungs)
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)
E
X
P
O
S
U
R
E
No infection (70%)
Adequate Immunity
Containment
(95%)
Non-specific immunity
Adequate Defenses
Inadequate Immunity
Infection (30%)
Immunologic
defenses
Inadequate Defenses
Early Progression
(5%)
Reactivation
Hard shell
breaks down and
tubercle bacilli
escape and
multiply
(in this example,
TB disease
develops in the
lungs)
Source: CDC, 2001
Active TB Disease
TB
Germs:
 Awake and multiplying
 Cause damage to the lungs
Granuloma breaks
down and tubercle
escape and multiply
Person:
 Most often feels sick
 Contagious (before TB
treatment started)
 Usually have a positive
tuberculin skin test
 Chest X-ray is often abnormal
(with pulmonary TB)
TB Transmission and Pathogenesis (3)
E
X
P
O
S
U
R
E
No infection (70%)
Adequate Immunity
Containment
(95%)
Non-specific immunity
Adequate Defenses
Inadequate Immunity
Infection (30%)
Immunologic
defenses
Continued
containment
(90%)
Adequate Defenses
Inadequate Defenses
Early Progression
(5%)
Immunologic
defenses
Inadequate Defenses
Late progression (5%)
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 and others whose immune
system is compromised
 Persons with a history of prior, untreated TB or
fibrotic lesions on chest X-ray
 Recent TB infection (within past 2 years)
 Substance abuse (injection drug users, alcohol
abuse)
 Age (very young or very old)
 Tobacco use
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
 Anti-rejection drugs for organ transplant.
(e.g., Cyclosporine, Prograf, Steroids)
Persons taking blocking agents against
Tumor Necrosis Factor-Alpha including:
 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