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Mycobacterium tuberculosis
• Tuberculosis is a slow growing infection that is caused by
mycobacterium tuberculosis, multiplying once every 15-24 hours
• Most commonly found in the lungs (pulmonary TB), but may also
affect bone tissue, the central nervous system and other organs
• 2 types: Dormant TB and Active TB (90% patients)
http://www.youtube.com/watch?v=BTIiE2DFsiA
• Robert Koch discovered that
Mycobacterium tuberculosis causes TB in
1882
• Thought to be around for up to 4,000
years.
• Pulmonary tuberculosis was described by
Hippocrates, and the disease was known in
India from at least 500 B.C.
• In Europe during the 17th and 18th
centuries, one quarter of all adult deaths
resulted from tuberculosis
• In the late 18th century, they thought TB
was contracted from living in crowded,
unsanitary environments created by the
growth of cities during the Industrial
Revolution
• Incubation period is 4-12 weeks
• It is an acid fast bacterium (waxy cell walls rich in lipids &
polysaccharides)
• The waxy cell walls contribute to virulence by protecting the
mycobacterium from being destroyed by lysosomes or macrophages
• Tubercle Bacillus- long thin rod (Koch)
• Slow growing rod that grows optimally in environments rich in oxygen
• Obligate aerobe
• Airborne disease, spread by coughing and sneezing
• HIGHLY CONTAGIOUS
• Infected air droplets are breathed into the lung, where it
is contained or spread to other parts of the body, and then
the bacteria multiplies.
• Macrophages in the lung tissue begin to engulf and
contain the bacteria.
• Aerosol droplets infect the lung alveolar surfaces
• It was thought that TB came from the domestication of
cattle and through the ingestion of milk.
• Dormant TB is not contagious to others
• Consumption (weight loss)
• Fatigue
• Fever
• Night Sweats
• Chills
• Loss of appetite
• Coughing up blood
• Chest Pains
• Difficulty Breathing
• Failure of bone marrow to
produce replacement RBCs
First stage:
•3-8 weeks after TB is contained in the lungs, the bacteria implants into the alveoli;
the bacteria are disseminated by the lymphatic system to regional lymph nodes in
the lung tissue, forming the Ghon complex.
Second stage:
•Approximately 3 months. Circulation of bacteria to other organs via bloodstream.
At this time fatal disease can occur in the form of Active TB or Miliary TB.
Third stage:
•Pleurisy occurs. Lasting 3-7 months causing severe chest pain, but can be delayed
for up to 2 years. Pleurisy occurs with the release of bacteria into the pleural space
from sub-pleural concentrations of bacteria in the lung. The free bacteria are
thought to sensitize lymphocytes that are attracted and release inflammatory
cytokines.
Fourth stage:
•May take up to 3 years. Slowly developing extra pulmonary lesions. Also chronic
back pain can appear in some people.
How M. tuberculosis Affects the Body
-After inhalation of mycobacteria, it reaches the alveoli of the lung
-Macrophages engulf bacteria, initiating infection and bacilli can then be
transported to other parts of the body via lymph channels
-Within the first few weeks, the bacilli multiply very slowly
-Multiplication becomes more destructive after several weeks resulting in an
inflammatory response
-Fluid leaks into region of inflammation
-Site becomes saturated with lymphocytes in response to the inflammation
resulting in a fluid-filled lesion, known as a tubercle.
-The tubercle grows in size & pushes aside normal tissue, producing a large TB
lesion
Sickness Appears As A Cold
- little or no apparent impairment to
lung function
- if protective immune response is
effective, disease may not progress
-5% becomes latent & may become
active within 2 years after exposure
- another 5% the active disease may
return at a later time
Don’t Go Untreated!
-Some alveolar blood vessels become
eroded & rupture causing hemorrhaging
and the tubercles can break open
- Bacilli is released and carried through
the body via the bloodstream
- Bronchi become irritated
- Fluid fills the lungs and lung tissue is
being liquefied by the M. tuberculosis
bacilli
- Patient is infected and is highly
contagious because TB bacilli can be
found in the patient’s sputum
- There can be more than one billion
bacilli in each mL of fluid
- If untreated, fatality rate : 40-60%
Diagnosis of TB
•Tuberculin skin test
- small amount of tuberculin is
injected under the skin of the
forearm
-Within 48-72 hours, if the area is
inflamed then the patient is positive
for TB exposure
• Chest X-Rays
- Shows tubercular lesions in lung
tissue caused by the disease
- Can show lesions far before the
clinical symptoms are noticeable
- invented in 1895 by Wilhelm
Roentgen
- not fully reliable until 1920s
Early Treatment
• Administration of creosote,
carbolic acid, gold, iodoform,
arsenic, and menthol oil orally or
as a nasal spray
• Some physicians prescribed
sulfur gas enemas and urged
them to drink papaya juice
• Surgical procedures of removing
ribs to reduce the size of the
thoracic cavity and the removal
of infected lung tissue
• Prescribed and performed these
forms of treatment up to the
1940s
Tuberculosis Sanitaria
-
-
Quarantined establishments that
provided patients with much
sunshine and fresh air, as well as
rest and good nutrition
No TB meds administered
First sanitariums were established
in the Alps of Switzerland
Trudeau Institute
-
-
-
First sanitarium established in the
United States by Edward Livingston
Trudeau
Saranac Lake of the Adirondacks in
New York during the 1880s
Became a popular idea and many
were set up around the United
States to provide a home to isolate
the patients with Tuberculosis
Beneficial because the patients with
TB were isolated and the physicians
could maintain control of the
patients
“Little Red”
Streptomycin
-
Isolated in 1943 from a culture
comprised of bacteria obtained from
the throat of a sick chicken
Found that it inhibits the growth of
tubercle bacilli
By 1945 it was used clinically to treat TB
By 1947 it became widely available in
large amounts
Mode of Action
- Inhibits synthesis of waxy cell wall of
tubercle bacillus, leaving bacilli naked and
unprotected from the killing machinery of
macrophages
Drug Resistance & Other TB Drugs
• Some TB was becoming resistant
to streptomycin
• P-aminosalicylic acid was
supplemented for the resistant
bacteria
• Isoniazid also became a mainstay
for treatment against drug
resistant TB
Mode of Action: Isoniazid
- blocks synthesis of mycolic acids
that are a main constituent of the
waxy cell walls
• Rifampin is also used today in
treatment
Mode of Action : Rifampin
- Serves as an inhibitor of
synthesis of the tubercle bacillus
RNA
To minimize the
emergence of drug
resistance, multiple
drug therapy is
used most
Common today.
Most Common Treatment
• Today, multiple drug therapy is used with
two combinations of anti-TB meds
• First, Isoniazid, Rifampin, and
Pyrazinamide is administered daily for 8
weeks
• Then, Isoniazid is administered daily,
twice, or three times a week for 16 weeks
Problem:
- Many patients stop taking meds when symptoms
clear up
-This makes the drug resistance increase and
decreases the chances of the TB being cured
- TB bacteria die very slowly therefore patients must
be on anti-TB meds for 6-9 months
Interesting Facts:
• One person is infected with TB every second
• Someone in the world dies from TB every 18 seconds
• Causes more deaths worldwide than any other infectious
diseases
• Each year 8 million people develop TB and 3 million die
worldwide
Picture Sources
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http://www.futura-sciences.com/uploads/tx_oxcsfutura/img/mycobacterium_tuberculose.jpg
http://www.naturalypure.com/images/TuberculosisPhoto1.jpg
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http://www.flickr.com/photos/ashclements/54559142/
http://www.crazyabouttv.com/Images/housemd.jpg
http://www.voanews.com/korean/Archive/images/HK_gov_Tuberculosis_xray_150.jpg
http://www.nurse.net/clinical/tb/tb.shallow.jpg
http://www.flickr.com/photos/wearytraveler142/3006670423/
http://www.adirondackhistory.org/newtb/bigtb5.html
http://www.adirondackhistory.org/newtb/big28794.html
http://www.adirondackhistory.org/newtb/big24439.html
http://www.247-pharmacy.com/buy/img/prod-pics/streptomycin.gif
http://aminj.myweb.uga.edu/streptomycin.gif
http://www.jonbarron.org/images/pills_tb.jpg
http://www.flickr.com/photos/angelo-gr/2832551717/