Mycobacterium tuberculosis

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) http://www.youtube.com/watch?v=BTIiE2DFsiA

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

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

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

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

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.

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

Sickness Appears As A Cold -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 Chest X-Rays Tuberculin skin test - 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 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

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 “Little Red” 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 Mode of Action 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 Problem: 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

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