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Brittany Morgan
     BIO 204
   Section 103
  Dr. Lisa Davis
  19 April 2011
 5000 B.C. - Tuberculosis (TB) infections exist
      in Egyptian mummies

 1600’s to 1800’s – TB migrates to Europe and
      renders romantic appeal from the masses
            “I look pale. I should like to die of
            consumption… because ladies would say…
            ‘how interesting he looks in dying’”
              English poet George Gordon Byron


                      Early 1900’s – Epidemic TB infections envelop
                       Europe catalyzing the development of treatment

                      1980’s – TB disease rate slightly increases due
                       many factors
4/19/2011                                                                2
 Ralph Waldo Emerson, American Poet


 Edgar Alan Poe, American Writer/Poet


 Eleanor Roosevelt, American Humanitarian and First
      Lady

 Adolf Hitler, German Dictator


 Nelson Mandela, Anti-apartheid activist & former
      president of South Africa
4/19/2011                                              3
 Scientific Name: Mycobacterium tuberculosis
            Additional causative agents
              Mycobacterium avium complex (MAC)
              Mycobacterium bovis (transmitted from cattle)


 Common Name: Tuberculosis or TB
            Historically called “Consumption”

 Other Names
            White Plague
            Wasting Disease
            Koch’s Disease

4/19/2011                                                      4
 Mycobacterium tuberculosis Characteristics
   Nonmotile and rod-shaped
   Rods exhibit length of 2-4 micrometers
   Obligate aerobe
   Slow generation time:~15-20 hours
   Not Classified as Gram Positive or Negative
   An Acid Fast Stain Method provides the best method for
   identification
              E.g. Ziehl-Neelsen method
            High Virulence ID of Ten (10)
              Ten (10) represents the minimum number of bacteria
              required to cause the disease

4/19/2011                                                           5
Mycobacterium tuberculosis - Magnification: 1000x

4/19/2011                                                       6
Mycobacterium tuberculosis - Magnification: 15549x

4/19/2011                                                        7
 Methods of acquisition
            Inhalation of droplet nuclei from respiratory secretions
              80 to 85% of occurrences reveal primary infection of the lungs
            Inhalation of particles of dry sputum containing tubercle
            bacilli

 The elderly, infants, and individuals with weakened or
      compromised immune systems exhibit an increased risk of
      disease contraction

 Individuals infected with the latent or “Reactivation” form
      of tuberculosis will not show symptoms and cannot spread
      the disease to others
4/19/2011                                                                       8
 Two (2) to twelve (12) weeks for primary infection
      within the body

 Risk for development remains high for the first two (2)
      years after infection

 Incubation period for laboratory culture typically
      requires six (6) weeks

 Due to the highly resistant nature of tuberculosis, the
      infection’s duration can span weeks to years
4/19/2011                                                   9
 Cough
            Usually accompanied by blood or mucus
 Difficulty Breathing
 Chest Pain
 Excessive sweating
 Fatigue
 Fever
 Chills
 Decreased Appetite
 Uncontrollable Weight Loss
4/19/2011                                           10
4/19/2011   11
 Mantoux Tuberculin Skin Test
            Tuberculin, or Purified Protein Derivative (PPD), is injected in the skin
            to observe an inflammatory response within 48 to 72 hours
            Indicates only exposure to the disease and not infection

 Chest CT scan or X-ray
            Examine for the existence of tubercles

 Blood Test
            Interferon-gamma blood test such as the QFT-Gold test to test for TB
            infection

 Sputum examination and cultures

 Biopsy of the affected tissue (rarely performed)

4/19/2011                                                                           12
 Culturing
            Requires agar and egg based media
            that incorporate green malachite
            Incubation temperature of 37°C
            Colony growth becomes visible
            between six (6) to thirty (30) days

 Isolation
            Koch approached with four(4)
            postulates
              Identify, Obtain, Reproduce, and
              Recover

4/19/2011                                         13
 After inhalation and phagocytosis, the bacteria slowly multiply
      inside the consuming macrophages

 The host’s body responds with neutrophil infiltration and fluid
      accumulation within the lung’s alveoli
            Eventually the organism ruptures and destroys the neutrophil

 Alveolar macrophages appear and phagocytize the bacteria again
      permitting multiplication and subsequent destruction
            Phagocytes rupture releases infective organisms without the
            production of toxins

 With additional cell infection, an inflammatory response begins
      releasing significant amount of fluid into the lungs
4/19/2011                                                                  14
 Tissue necrosis or solidification of chronic granulomas, called
      tubercles, form with increased infection
            Granulomas can encapsulate living bacteria for extended periods
            permitting secondary or “Reactivation” infection when the immune
            system weakens

 Three (3) to four (4) weeks into development, delayed
      hypersensitivity and cell-mediated immunity begin

 Spread of bacteria through the circulatory or lymphatic systems
      results in miliary or extrapulmonary tuberculosis creating
      further complications

 Patient experiences severe symptoms (violent coughing, weight
      loss, and extreme fatigue) until the body eventually “wastes”
      away
4/19/2011                                                                  15
4/19/2011   16
 Initial treatment utilized cold, clean air
      to aid in recovery as causative agents
      stemmed from “bad” air

                                                             “Little Red”
 Streptomyocin provided the bacteria’s first treatment
            Discovered by Selman Waksman in 1919 from the throat
            of a sick chicken

 Isoniazid appeared after Streptomyocin resistant TB
      strains evolved
            Synthesized from coal tar and employed in 1952
4/19/2011                                                                   17
 Multiple Drug Therapy
            Employs three drug treatments to attack different
            genetic types of tuberculosis
            Includes isoniazid plus rifampin along with additional
            drug combinations

 Bacillus Calmette-Guerin vaccine exists to treat
      tuberculosis
            Not used in the United States as the vaccination
            includes benign bacilli that may became virulent and
            fatal
            The vaccine also renders the skin test negative limiting
            diagnosis
4/19/2011                                                              18
 One-third of the global
      population hosts the TB
      bacterium
            9+ million individuals become
            sick from TB in one year
            Nearly two (2) million deaths
            occur due to TB in a year

 11,545 cases of TB were
      reported in the US in 2009
            Morbidity rate dropped to       CDC 2009 Age Cross-Section of TB
            3.8% in 2009 from 4.2% in
            2008

4/19/2011                                                                 19
 Colorado mortality rate is less than 3.5%




4/19/2011                                     20
4/19/2011   21
 Progression of tuberculosis stemmed from the
      colonization of cities and close-quartered work space
      in industry

 Methods to prevent infection include:
            Limiting exposure to airborne particles
            Adequate nutrition
            Maintaining a healthy immune system




4/19/2011                                                     22

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Final Tuberculosis Presentation BIO 204

  • 1. Brittany Morgan BIO 204 Section 103 Dr. Lisa Davis 19 April 2011
  • 2.  5000 B.C. - Tuberculosis (TB) infections exist in Egyptian mummies  1600’s to 1800’s – TB migrates to Europe and renders romantic appeal from the masses “I look pale. I should like to die of consumption… because ladies would say… ‘how interesting he looks in dying’”  English poet George Gordon Byron  Early 1900’s – Epidemic TB infections envelop Europe catalyzing the development of treatment  1980’s – TB disease rate slightly increases due many factors 4/19/2011 2
  • 3.  Ralph Waldo Emerson, American Poet  Edgar Alan Poe, American Writer/Poet  Eleanor Roosevelt, American Humanitarian and First Lady  Adolf Hitler, German Dictator  Nelson Mandela, Anti-apartheid activist & former president of South Africa 4/19/2011 3
  • 4.  Scientific Name: Mycobacterium tuberculosis Additional causative agents  Mycobacterium avium complex (MAC)  Mycobacterium bovis (transmitted from cattle)  Common Name: Tuberculosis or TB Historically called “Consumption”  Other Names White Plague Wasting Disease Koch’s Disease 4/19/2011 4
  • 5.  Mycobacterium tuberculosis Characteristics Nonmotile and rod-shaped Rods exhibit length of 2-4 micrometers Obligate aerobe Slow generation time:~15-20 hours Not Classified as Gram Positive or Negative An Acid Fast Stain Method provides the best method for identification  E.g. Ziehl-Neelsen method High Virulence ID of Ten (10)  Ten (10) represents the minimum number of bacteria required to cause the disease 4/19/2011 5
  • 6. Mycobacterium tuberculosis - Magnification: 1000x 4/19/2011 6
  • 7. Mycobacterium tuberculosis - Magnification: 15549x 4/19/2011 7
  • 8.  Methods of acquisition Inhalation of droplet nuclei from respiratory secretions  80 to 85% of occurrences reveal primary infection of the lungs Inhalation of particles of dry sputum containing tubercle bacilli  The elderly, infants, and individuals with weakened or compromised immune systems exhibit an increased risk of disease contraction  Individuals infected with the latent or “Reactivation” form of tuberculosis will not show symptoms and cannot spread the disease to others 4/19/2011 8
  • 9.  Two (2) to twelve (12) weeks for primary infection within the body  Risk for development remains high for the first two (2) years after infection  Incubation period for laboratory culture typically requires six (6) weeks  Due to the highly resistant nature of tuberculosis, the infection’s duration can span weeks to years 4/19/2011 9
  • 10.  Cough Usually accompanied by blood or mucus  Difficulty Breathing  Chest Pain  Excessive sweating  Fatigue  Fever  Chills  Decreased Appetite  Uncontrollable Weight Loss 4/19/2011 10
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  • 12.  Mantoux Tuberculin Skin Test Tuberculin, or Purified Protein Derivative (PPD), is injected in the skin to observe an inflammatory response within 48 to 72 hours Indicates only exposure to the disease and not infection  Chest CT scan or X-ray Examine for the existence of tubercles  Blood Test Interferon-gamma blood test such as the QFT-Gold test to test for TB infection  Sputum examination and cultures  Biopsy of the affected tissue (rarely performed) 4/19/2011 12
  • 13.  Culturing Requires agar and egg based media that incorporate green malachite Incubation temperature of 37°C Colony growth becomes visible between six (6) to thirty (30) days  Isolation Koch approached with four(4) postulates  Identify, Obtain, Reproduce, and Recover 4/19/2011 13
  • 14.  After inhalation and phagocytosis, the bacteria slowly multiply inside the consuming macrophages  The host’s body responds with neutrophil infiltration and fluid accumulation within the lung’s alveoli Eventually the organism ruptures and destroys the neutrophil  Alveolar macrophages appear and phagocytize the bacteria again permitting multiplication and subsequent destruction Phagocytes rupture releases infective organisms without the production of toxins  With additional cell infection, an inflammatory response begins releasing significant amount of fluid into the lungs 4/19/2011 14
  • 15.  Tissue necrosis or solidification of chronic granulomas, called tubercles, form with increased infection Granulomas can encapsulate living bacteria for extended periods permitting secondary or “Reactivation” infection when the immune system weakens  Three (3) to four (4) weeks into development, delayed hypersensitivity and cell-mediated immunity begin  Spread of bacteria through the circulatory or lymphatic systems results in miliary or extrapulmonary tuberculosis creating further complications  Patient experiences severe symptoms (violent coughing, weight loss, and extreme fatigue) until the body eventually “wastes” away 4/19/2011 15
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  • 17.  Initial treatment utilized cold, clean air to aid in recovery as causative agents stemmed from “bad” air “Little Red”  Streptomyocin provided the bacteria’s first treatment Discovered by Selman Waksman in 1919 from the throat of a sick chicken  Isoniazid appeared after Streptomyocin resistant TB strains evolved Synthesized from coal tar and employed in 1952 4/19/2011 17
  • 18.  Multiple Drug Therapy Employs three drug treatments to attack different genetic types of tuberculosis Includes isoniazid plus rifampin along with additional drug combinations  Bacillus Calmette-Guerin vaccine exists to treat tuberculosis Not used in the United States as the vaccination includes benign bacilli that may became virulent and fatal The vaccine also renders the skin test negative limiting diagnosis 4/19/2011 18
  • 19.  One-third of the global population hosts the TB bacterium 9+ million individuals become sick from TB in one year Nearly two (2) million deaths occur due to TB in a year  11,545 cases of TB were reported in the US in 2009 Morbidity rate dropped to CDC 2009 Age Cross-Section of TB 3.8% in 2009 from 4.2% in 2008 4/19/2011 19
  • 20.  Colorado mortality rate is less than 3.5% 4/19/2011 20
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  • 22.  Progression of tuberculosis stemmed from the colonization of cities and close-quartered work space in industry  Methods to prevent infection include: Limiting exposure to airborne particles Adequate nutrition Maintaining a healthy immune system 4/19/2011 22

Editor's Notes

  1. Tuberculosis (TB) infections trace back to 5000 B.C. as evidenced by bone deterioration in Egyptian mummiesIn the 1600’s, TB traveled to Europe and rendered a romantic state due to those inflicted by the 1800’sPoets, authors, musicians, and the wealthyObserved as a spiritual cleanser and a sign of extreme intelligenceReaching epidemic proportions in Europe in the 1900’s, treatment evaluation began to eliminate deathsIn the 1960’s, sanatoriums closed in light of drug treatment advancements that provided sufficient medical assistance to cause the disease to declineA slight increase in disease rate occurred in the 1980’s due to the prevalence of HIV, higher rates of immigration, and TB’s resistance to drug treatment“I look pale. I should like to die of consumption… because ladies would say… ‘how interesting he looks in dying’”English poet George Gordon Byron
  2. Additional causative agentsMycobacterium avium complex (MAC)Prevalent in AIDS patientsMycobacterium bovis(transmitted from cattle)Causes spinal and bone deterioration versus pulmonary tuberculosis effectsOther Names Consumption Because it seemed to consume people from withinWhite Plague Due to loss of skin colorWasting Disease Due to the lack of energy leading to less and less activityKoch’s Disease Due to Robert Koch identifying the instigating bacterium
  3. Obligate aerobe (requires oxygen to grow)Correlates with primary infection site of middle/upper lungsNot Classified as Gram Positive or NegativeBacterium lacks either characteristic yet the cell wall contains peptidoglycanA Gram stain test result would indicate a very weak Gram PositiveAn Acid Fast Stain Method provides the best method for identification due to the cell wall’s mycolic acid which does not stain easily because of decreased permeability
  4. TB is transmitted throughInhalation of respiratory secretions (including cough, sneeze or spit). In one of the sources I read, it stated that a single sneeze could release up to 40,000 droplets and if as few as ten of these infected bacterium make it into your respiratory tract, it’s likely you’ll become infected. 80 to 85% of occurrences reveal primary infection of the lungs. Microbe needs oxygen which is why it prefers the respiratory tract, but if the disease becomes advanced it can spread to the circulatory system and will eventually become a systemic infection. The elderly, infants, and individuals with weakened or compromised immune systems exhibit an increased risk of disease contractionIndividuals infected with the latent form of tuberculosis will not show symptoms and cannot spread the disease to others. This means that the bacteria are present in the body but are not active. Many people with latent TB will never have an active infection, however it can be somewhat of an opportunistic pathogen and if you become immuno compromised the bacterium will activate. Oral infection remains less efficient as the bacteria typically cannot survive the digestive acids
  5. Risk for development remains high for the first two (2) years after infection (this is primarily for those with a latent infection). Due to the highly resistant nature of tuberculosis, the infection’s duration can span weeks to years—I found this in several of my sources, however, the majority of my sources say it lasts somewhere from 12-18 months.
  6. The National Tuberculosis Association used proceeds from Christmas Seal campaigns to develop educational posters that emphasized prevention and control of the disease in the 1930s, and this is one of the posters used.
  7. Tuberculin Skin Test: The standard method of checking for exposure to the disease; but not entirely accurate for saying if someone is infected. If a person has been exposed to the bacterium even through the vaccination the test will yield a positive result. The purified protein derivative is injected under the top layer skin and the injection site should produce a little bump, which is known as a “wheal” and 48-72 hours later the injection site will be examined for the “flare” portion or the immune response to the protein derivative. A hard red bump is an indication if you have ever been exposed to the bacterium. Blood Test: Measures the immune system’s reaction to the bacteria. Can also be used to determine if the infection is active or latent. Sputum Culture: A culture of the mucus that is coughed up and they test it for the presence of the bacteria. Biopsy: Actually surgically take a portion of the lung to culture.
  8. CulturingRequires agar and egg based media that incorporate green malachiteRecently blood agar added as an acceptable culturing medium Incubation temperature of 37°C to obtain colony growth (which is to be expected as it can grow in humans)Colony growth becomes visible between six (6) to thirty (30) days with an average of ten (10) daysIsolationKoch approached with four(4) postulatesIdentify the causative organismObtain a pure culture of the causative organismReproduce the disease in experimental animalsRecover the organism from infected animalsIsolation first occurred in 1882 and provided means for diagnosis but no cure or treatment
  9. After inhalation and the bacteria are phagocitized, but they are unable to be broken down or destroyedand the bacteria slowly multiply inside the consuming macrophages.When the macrophages are not able to destroy the bacterium, the host’s immune response kicks in and neutrophil infiltration and fluid accumulate in the areas of infection (usually the lungs). Eventually the organism ruptures and the bacteria are released and destroys the neutrophils.Later macrophages and lymphocytes move into the area and alveolar macrophages appear and phagocytize the bacteria again permitting multiplication and subsequent destruction.Phagocytes rupture releases infective organismsMycolic acid in the cell wall prevents bacteria destruction and allows multiplicationWith additional cell infection, an inflammatory response begins releasing significant amount of fluid into the lungs
  10. If the infection continues eventually granulomas will form around the infected macrophages. Which is basically layers of T cells that surround the infected macrophage and seal off the area to immobilize the infection. This can cause tissue necrosis or solidification. Three (3) to four (4) weeks into development, delayed hypersensitivity and cell-mediated immunity begin (formation of granulomas)If the infection goes untreated for a long period of time, the bacteria can spread through the circulatory or lymphatic systems results in a systemic infection and further complicationPatient experiences severe symptoms (violent coughing, weight loss, and extreme fatigue) until the body eventually “wastes” away
  11. Picture of the pathology. This is a picture of a set of lungs from someone who was chronically infected with TB and you can see the necrosis due to the formation of granulomas and the walling off of the infected macrophages.
  12. Initial treatment utilized cold, clean air to aid in recovery as causative agents stemmed from “bad” airSanitariums incorporated wide open spaces and fresh air which only relieved symptoms and did not cure the disease“Little Red” provided the first sanatorium in 1884Streptomyocinwas the first drug used to treat TB which worked to reducing the synthesis of the “waxy” cell wall permitting destruction by macrophagesIsoniazid appeared after Streptomyocin resistant TB strains evolvedFirst used in the early1950’s and was made from coal tar It also targets the cell wall, by blocking creation of mycolic acids
  13. Multiple Drug TherapyEmploys three drug treatments to attack different genetic types of tuberculosis anIncludes rifmapin and two other drugs which are taken fora duration of at least nine (9) monthsBacillus Calmette-Guerin vaccine exists to treat tuberculosis Named after the French scientists that developed it. Not used in the United States as the vaccination includes benign bacteriathatmay became virulent and fatal, it does not always prevent the disease. The vaccine also renders the skin test negative limiting diagnosis
  14. One-third of the global population hosts the TB bacterium9+ million individuals become sick from TB in one yearNearly two (2) million deaths occur due to TB in a yearTB represents the largest killer of HIV infected patients11,545 cases of TB were reported in the US in 2009Represents a 10.5% decrease from 2008Morbidity rate dropped to 3.8% in 2009 from 4.2% in 2008