The document summarizes the history and characteristics of tuberculosis (TB). It traces TB infections back to Egyptian mummies from 5000 BC and discusses how the disease migrated to Europe in the 1600-1800s. It then covers the early 1900s epidemic in Europe and a slight increase in rates in the 1980s. The document details the causative agent of TB, symptoms, methods of transmission and diagnosis, pathogenesis within the body, and historical and current treatment methods. It concludes with current global and national statistics on TB incidence and mortality.
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
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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
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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
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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
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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
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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
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10. Cough
Usually accompanied by blood or mucus
Difficulty Breathing
Chest Pain
Excessive sweating
Fatigue
Fever
Chills
Decreased Appetite
Uncontrollable Weight Loss
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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)
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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
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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
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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
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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
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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
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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
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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
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Editor's Notes
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
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
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
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
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.
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.
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.
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
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
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
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.
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
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
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