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Tuberculosis. Mycobacterium tuberculosis. What is it?. Tuberculosis is a slow growing infection that is caused by mycobacterium tuberculosis , multiplying once every 15-24 hours

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    1. Tuberculosis Mycobacterium tuberculosis

    2. What is it? • 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)

    3. History • 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

    4. Biology of Bacteria Organism • 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

    5. Transmission of bacteria • 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

    6. Symptoms • 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

    7. Stages of TB • 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.

    8. How M. tuberculosisAffects 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

    9. -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

    10. 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%

    11. 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

    12. 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

    13. 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

    14. 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”

    15. 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

    16. 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.

    17. 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

    18. 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

    19. Picture Sources • • • • • • • • • • • • • • •