Transcript Etiology

Mohammad Tohidi M.D.
Professor of Internal Medicine
Department of Pulmonary Diseases
Ghaem Hospital MUMS Mashhad IRAN
Tuberculosis
Transmission and
Pathogenesis
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21Y O woman referred with the CC of cough
for 2 months.She has had small amount of
yellow sputum,no fever &night sweat
&hemoptysis, but she had 2 kg weight
loss.Past medical HX was unremarkable.On
PE she was slightly pale,but otherwise
normal.She received antibiotics & antitussive
with no significant effect.
 Chest radiography may be
particularly helpful in
suggesting or confirming the
cause of the cough
What we should do
next?
Evaluate based on likely clinical
possibilities:
Sputum for AFB Stain &culture
 PFT
 HRCT
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Sputum for AFB: ++++
Pulmonary
Tuberculosis
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Tuberculosis (TB) remains the leading cause of
death worldwide from a single infectious disease
agent. Indeed up to 1/2 of the world's
population(3.1 billion) is infected with TB. The
registered number of new cases of TB worldwide
roughly correlates with economic conditions: the
highest incidences are seen in those countries of
Africa, Asia, and Latin America with the lowest
gross national products. WHO estimates that eight
million people get TB every year, of whom 95% live
in developing countries. An estimated 2 million
people die from TB every year.
M. tuberculosis
M. bovis
M. africanum
M. microti
M. canettii
M. caprae
M. pinnipedii
Source: CDC Public Health Image Library/Dr. George P. Kubica
With the exception of M. pinnipedii,
all of the species in the
Mycobacterium tuberculosis complex
have been shown to cause disease in
humans; however, M. tuberculosis is
by far the most prevalent
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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)
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Thick lipid cell wall
Can remain dormant
for decades
Aerobic
Non-motile
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
Source: CDC, 2000
Less frequently transmitted by:
Ingestion of Mycobacterium bovis found in
unpasteurized milk products
Laboratory accident
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
When a person with TB disease of the lungs or larynx
coughs, sneezes or sings, droplet nuclei containing
the TB bacilli are expelled into the air
These droplets or particles, called droplet nuclei, are
about 1 to 5 microns in diameter - less than 1/5000 of
an inch
Droplet nuclei can remain suspended in the air for
several hours, depending on the environment
The average TB patient generates
75,000 droplets per day before
therapy
This falls to 25 infectious droplets
per day within two weeks of
effective therapy
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Large droplets settle
to the ground
quickly
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Smaller droplets
form “droplet nuclei”
of 1–5 µ in diameter
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Droplet nuclei can
remain airborne
When a person inhales air that contains
droplets, most of the larger droplets
become lodged in the upper respiratory
tract (the nose and throat), where
infection is unlikely to develop.
However, the droplet nuclei may reach
the small air sacs of the lung (the
alveoli), where infection begins
The alveoli contain a type of white blood cell,
called a macrophage, that eats up any foreign
objects in the air sac. When the TB bacteria
reaches the air sac it gets eaten up by the
macrophage
Once the TB bacteria is inside of the
macrophage it begins to multiply
No infection (70%)
Adequate
Exposure
Non-specific
immunity
Inadequate
Infection (30%)
 Not everyone who is exposed to TB will
become infected
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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 greater the time spent with the
infectious person or breathing in air with
infectious particles
CASE
Site of TB
Cough
Bacillary load
Treatment
CONTACT
Ventilation
Filtration
U.V. light
Closeness and
duration of contact
Immune status
Previous infection
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Sharing dishes and utensils
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Using towels and linens
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Handling food
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Sharing cell phones
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Touching computer keyboard
This next section describes the pathogenesis of TB (the
way TB infection and disease develop in the body)
At first, the tubercle bacilli multiply in the alveoli and a
small number enter the bloodstream and spread
throughout the body (dissemination)
Bacilli may reach any part of the body, including areas
where TB disease is more likely to develop. These
areas include the upper portions of the lungs, as well
as the kidneys, the brain, and bone
Disseminated TB refers to TB that
simultaneously involves multiple organs.
While “miliary” is given as an example of
disseminated TB, it really refers to a
radiographic manifestation of
disseminated TB. It’s important to note
that not all patients with disseminated TB
have a miliary pattern on CXR
Lungs (85% all cases)
2. Pleura
3. Central nervous system
1.
• (e.g., brain, meninges)
Lymph nodes
5. Genitourinary system
6. Bones and joints
7. Disseminated
4.
 (e.g., miliary)
Brain
Pleura
Lymph Node
Spine
Within 2 to 10 weeks, however, the body's
immune system usually intervenes,
halting multiplication and preventing
further spread
The immune system is the system of cells
and tissues in the body that protect the
body from foreign substances
Person:
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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
If the immune system is compromised, then the
bacilli multiply and spread to other sites in the
body. People who have TB infection but not TB
disease are NOT infectious - in other words, they
cannot spread the infection to other people
Persons with LTBI have a low bacillary load (e.g.,
≤~103)
It is very important to remember that TB infection
is not considered a case of TB
No infection (70%)
Adequate
Exposure
Non-specific
immunity
Early progression (5%)
Inadequate
Inadequate
Infection (30%)
Immunologic
defenses
Adequate
Containment (95%)
If a person has a healthy immune system, the body will wall off
the bacteria and keep it asleep (latent). In areas where the
prevalence of HIV is low, the majority of people exposed and
infected with TB are able to contain the infection
A small proportion, however, will progress to primary, active TB
disease. This generally will be individuals with a weakened
immune system or, as with infant, sbecause their immune
system is not fully developed
The highest risk period for early progression to disease is within
the first year or two following infection
•This typically occurs when the immune system
becomes weak allowing the TB bacteria to
multiply out of the control of the immune
system
•The TB bacteria can then escape from the
granuloma and enter the airway
•This is the usual mechanism of development
of active TB among adults
TB
Germs:
Awake and multiplying
 Cause damage to the lungs
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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)
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Granuloma breaks down and
tubercle escape and multiply
No infection (70%)
Adequate
Exposure Non-immunologic
defense
Early progression (5%)
Inadequate
Inadequate
Infection (30%)
Immunologic
defenses
Late progression(5%)
Inadequate
Adequate
Containment (95%)
Immunologic
defenses
Adequate
Continued containment (90%)
 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)
To diagnose TB you must first think of
TB
 Knowing when to consider TB in the
differential diagnosis = knowing who
is
at risk
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 risk for infection
 risk for disease
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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
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Overcrowded habitation (housing)
Persons born in countries with high
prevalence of TB
Persons more likely to progress from LTBI
to TB disease include:
 HIV-infected persons
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Persons with a history of prior, untreated TB
or fibrotic lesions on chest X-ray
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Recent TB infection (within past 2 years)
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Injection drug users
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Age (very young or very old)
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)
Risk Factor
HIV/AIDS
How many times higher is
the risk of TB disease
113-170
Diabetes
4.1
“old TB” on CXR
13.6
Chronic renal failure
Other conditions
25
3-16
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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 reinfection)
Source: TB/HIV: A Clinical Manual. Second Edition. WHO, 2004
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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
Reported TB Cases by Form of Disease United States, 2001
Both (7.4%)
Extrapulmonary (20.1%)
Pleural (18.3%)
Lymphatic (42.5%)
PulPulPlnary (72.5%)
oary (72.5%)
mona (2.5%)‫حححح‬
Other (12.3%)
Bone/joint (10.2%)
Genitourinary (5.9%)
Peritoneal (4.6%)
Meningeal (6.0%)
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Pulmonary manifestations of tuberculosis
(TB) include primary,
Reactivation,
Endobronchial,
Lower lung field infection,
Tuberculoma.
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Fever was the most common symptom
Chest pain and pleuritic chest pain(25%)
One-half of patients with pleuritic chest pain
had evidence of a pleural effusion
fatigue, cough, arthralgias and
pharyngitis(rare).
The physical examination was usually normal;
pulmonary signs included pain to palpation
and signs of an effusion.
hilar adenopathy, occurring in 65 percent
Approximately one-third :pleural effusions,
typically within the first three to four months
after infection
 Lower and upper lobe infiltrates were observed
in 33 and 13 percent of adults, respectively. Most
infiltrates resolved over months to years.
 the infiltrates progressed within the first year
after skin test conversion, so-called progressive
primary TB.
 Right middle lobe collapse may complicate the
adenopathy.
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Multiple terms have been used to describe
this stage of TB: chronic TB, postprimary
disease, recrudescent TB, endogenous
reinfection, and adult type progressive TB.
One-half to two-thirds of patients developed
cough, weight loss and fatigue. Fever and night
sweats or night sweats alone were present in
approximately one-half. Chest pain and dyspnea
each were reported in approximately one-third
of patients, and hemoptysis in approximately
one-quarter.
 Dyspnea can occur when patients have
extensive parenchymal involvement, pleural
effusions, or a pneumothorax.
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fever, sweats and hemoptysis were less
common in the elderly, and these patients
were less likely to have cavitary disease or a
positive (PPD) skin test.
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reactivation TB typically involves the apicalposterior segments of the upper lobes (80 to 90
percent of patients), followed in frequency by
the superior segment of the lower lobes and the
anterior segment of the upper lobes
In recent large series of TB in adults, 70 to 87
percent had the upper lobe infiltrates typical of
reactivation; 19 to 40 percent also had cavities,
with visible air-fluid levels in as many as 20
percent
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CT scan may show a cavity or centrilobular
lesions, nodules and branching linear
densities, sometimes called a "tree in bud"
appearance.
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Hilar adenopathy, sometimes associated with
right middle lobe collapse
Infiltrates or cavities in the middle or lower
lung zones (see lower lung field TB below)
Pleural effusions
Solitary nodules
the known increasing incidence of primary TB
in adults, rather than "atypical" forms of TB.
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A normal chest radiograph is also possible
even in active pulmonary TB. As an example,
in one Canadian study of 518 patients with
culture-proven pulmonary TB, 25 patients (5
percent) had normal chest x-rays; 23 of these
patients had pulmonary symptoms at the
time of the normal radiograph.
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15 percent of patients had lesions in the
tracheobronchial tree at rigid bronchoscopy
and 40 percent at autopsy.
At least two mechanisms of developing
endobronchial TB are possible:
Direct extension to the bronchi from an
adjacent parenchymal focus, usually a cavity,
Spread of organisms to the bronchi via
infected sputum from a distant site.
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Complications of endobronchial TB can
include: Obstruction,
Atelectasis (with or without secondary
infections),
Bronchiectasis,
Tracheal or Bronchial stenosis .
a barking cough, two-thirds of patients, often
accompanied by sputum production. Patients
rarely develop so-called bronchorrhea
 Lithoptysis
 Wheezing and hemoptysis
 Dyspnea, when present, may signal: obstruction
or atelectasis.
 The clinical manifestations can also be subacute
or chronic, resembling bronchogenic carcinoma
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The most common radiographic finding of
endobronchial TB in adults is an upper lobe
infiltrate and cavity with ipsilateral spread to
the lower lobe and possibly to the superior
segment of the contralateral lower lobe
Extensive endobronchial TB can also be
associated with bronchiectasis on CT scan.
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When endobronchial TB occurs in patients
with primary disease, segmental atelectasis
may be the only finding; atelectasis is more
frequent in the right middle lobe and the
anterior segment of the right upper lobe.
Because endobronchial lesions can exist
without extensive parenchymal
abnormalities, 10 to 20 percent of patients
may have normal chest radiographs
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While it would be natural to expect that rates
of AFB smear positivity would be high with
extensive endobronchial involvement, rates
of 15 to 20 percent have been reported. This
lower rate may be due to bronchial
inflammatory tissue which might prevent
expectoration of infected secretions
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— Lower lung field TB is defined as disease
located below a line traced across the hila,
including the perihilar regions, on a standard
PA and lateral chest x-ray
2 to 9 percent in incidence in adults,
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Typical reactivation TB rarely involves the
superior segments of the lower lobes.
Endobronchial TB can affect lower lung fields
in both primary infection, especially when
adjacent lymph nodes are involved, and
during reactivation, when spread from upper
lobe disease secondarily infects the lower
lung fields.
Typical primary tuberculosis.
A
non-specific tuberculous pneumonitis,
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Compared to upper lobe TB, consolidation in the
lower lobes tends to be more extensive and
homogeneous. Cavitation may be present, and
large cavities are reported.
Elderly patients and those with diabetes, renal
or hepatic disease, those receiving
corticosteroids, and those with underlying
silicosis appear most at risk for lower lobe TB.
However, many patients have no underlying
medical illnesses.
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Pulmonary complications of TB include
hemoptysis, pneumothorax, bronchiectasis
and extensive pulmonary destruction
(including pulmonary gangrene).