Micro J210 Atypical Bacteria

  1. What are three human diseases caused by atypical bacteria?
    • 1. Chronic pulmonary disease-Mycobacterium TB
    • 2. Borrelia Burgdorferi (lyme disease): vector born
    • 3. Helicbacter pylori (peptic ulcer)
  2. What do atypical bacteria have in common?
    • -Human pathogens only
    • -Cause chronic infections that can go unnoticed
    • - Important to diagnose quickly
    • -Curable with antibiotics if caught early
  3. What is mycobacterium tuberculosis?
    • -Gram positive
    • -Nonmotile, aerobic bacillus has a very lipid rich cell wall.
    • -They are not stained by normal grain stain but by acid-fast stain (acid-fast bacilli)
    • -Chronic pulmonary disease
  4. What are the virulence factors of M. Tuberculosis?
    • -Cell wall lipids withstand phagocytic killing and cause necrosis of tissue
    • -Able to stay alive in macrophages, intracellular growth
    • - Lipoarabinomanna (LAM) can induce inflammation
    • -Surface proteins are very immunogenic-Induce CMIR (Cell-meidated immune response)
    • -Highly infectious (5-200 organisms can start the disease).
  5. What is the cell wall structure of M. Tuberculosis?
    • -PG layer is bound to arabinogalactose-mycolic acid
    • -Cell wall is overlaid with lipids such cord factor, sulfatides, wax D, and surface proteins.
    • -Has a plasma membrane, PG layer, arabinogalactan, mannose-capped lipoarabinomannan, plasma-associated and cell wall associated protein, mycolic acid, glycolipid surface molecules
  6. What are the disease caused by M Tuberculosis?
    • -Granulomatous infection of the lung (TB)
    • Effectiveness of bacterial elimination is in part related to the size of infection
    • Localized collections of activated macrophages (granulomas) prevent further spread of the bacteria
    • -Macrophages can penetrate into small granulomas (less than 3 mm) and kill all the organisms contained in them. Larger necrotic/caseous granulomas become encapsulated with fibrin that effectively protects bacteria from macrophage killing
    • -Bacteria can remain dormant or reactivate later, when immunologic response wanes it.
    • -Pulmonary disease called Wasting disease (malaise, weight loss, bloody sputum)
  7. What are granulomas?
    • -Lesions in the lung.
    • -Form when an intracellular pathogen or its constituents cannot be totally eliminated.
    • -infected macrophages are gathered in the center of the lesion surrounded by T cells
  8. What is extra-pulmonary disease?
    • aka Military TB
    • -Hematogenous spread to multiple organs
    • -High mortality
    • -Caused by M. Tuberculosis
  9. What is the epidemiology of TB?
    • -Highly infectious (5-200 to start disease)
    • -Worldwide, 1/3 of population is infected with TB
    • -Fewer than 15,000 new cases in US in 2003 (mostly AIDS patients)
    • -Populations at risk: immunocompromised, HIV, drug/alcohol, homeless, exposed to disease
    • -Humans are the only natural reservoir, person to person spread by infectious aerosols.
  10. How do you diagnosis TB?
    • -Skin test, Mantoux test
    • -Reactivity of intradermal injection of mycobacterial antigen PPD
    • -PPD is purified-protein derivative of cell wall
    • -Reaction is measured in 48 hours
    • - Induration of more than 15 mm is considered a positive skin test
  11. What is the TB immunization?
    • -Live attenuated Mycobacterium bovis: Bacillus of Calmette Guerin (BCG)
    • -Not for immunocompromised patients
    • -Recipients become skin test positive for TB
    • -Effective
  12. What does a >5 mm of induration in a TB test?
    -HIV positive, patients receiving immunosuppressive therapy, recent contacts of patients with TB, patients with abnormal chest radiographs with prior TB
  13. What does a >10 mm of induration in a TB test?
    -Recent immigrants from high-prevalence countries, injection drug users, residents of high risk setting, elderly, patients with AIDS, homeless, health care/prison workers, high risk: chronic renal failure, diabetes, weight loss, children younger than 4 years or exposed to adults at high risk
  14. What does a >15 mm of induration in a TB test?
    -Persons at low risk for tuberculosis
  15. What is a mycobacterium bovis?
    • -Used for TB immunization
    • -A cattle pathogen
    • -Cause disease in zoo keepers/cattle farmers
    • -Can cause pulmonary disease by consumption of contaminated milk but is destroyed by milk pasteurization.
  16. Other than a TB, what other ways can you diagnosis M. TB?
    -Microscopy and culture are sensitive and specific
  17. What is the prevention of M. TB?
    • -Multiple drug regimens and prolonged treatment are required to prevent development of drug resistant strains
    • -Control of disease through active surveillance, prophylactic and therapeutic intervention, and careful case monitoring
    • -Some countries, TB vaccine
  18. What is vector-born disease Lyme Borelliosis?
    • -Lyme disease
    • -Genus borrelia are gram negative bacilli
    • -Spirochetes helps to penetrate tissue/cells
    • -Cause of lyme disease
    • -Borrelia burgdorfei: agent of lyme disease, leading cause of vector born disease in US
    • - Transmitted by hard-shelled (Ixodes) ticks that live on rodents, deer, domestic pets, more recently recognized in 49 states.
  19. What are the virulence factors of Borrelia burgdorferi?
    • -bacteria can escape from blood and penetrate tissues (similar to PMN)
    • -Outer surface protein (OSP) is very immunogenic and triggers inflammatory responses within tissues and causes damage right at the site
  20. What is the first stage of lyme disease?
    • Early manifestation stage:
    • -Easy to treat
    • -Incubation period of 3-30 days
    • -A rash at the site of tick bite, erythema migrans (migrates out, bullseye), occurs in 80% of cases
    • -Systemic symptoms of fatigue, headache, fever, chills, muscle pain, lymphadenopahty
    • -Resolves in 4 weeks due to humoral immunity
  21. What is the second stage of lyme disease?
    • Late manifestation
    • -Occurs in 80% of patients, hard to treat
    • -Occurs when bacteria escape from blood to tissues and survive there but stimulate immune system which causes the damage (protein induces inflammation)
    • -Occurs within few weeks to 2 years following onset of disease
    • -Late stage has two phases
  22. What are the two phases of the late stage of lyme disease?
    • -10-15% of patients and can last for days to months
    • 1. neurological and cardiac symptoms: meningitis, encephalitis, peripheral nerve neuropathy, heart block, myopericarditis, congestive heart failure.
    • 2. Arthalgias and arthritis: persist for months to years. Autoimmune arthritis which occurs in 89%
  23. What is the clinical case definition of lyme disease?
    • Either of the following
    • -Erythema migrans (5 in diameter)
    • -At least one late manifestation (Musculoskeletal, nervous system, cardiovascular) and lab confirmation of infection
  24. What is the lab criteria for diagnosis of lyme disease?
    • At least one of the following:
    • -Isolation of borrelia burgdorferi
    • -Demonstration of diagnostic levels of immunoglobulin (IgM or IgG antibodies to the spirochetes)
    • -significant increase in antibody titer between acute and convalescent serum samples
  25. What is helicobacter pylori?
    • -Discovered in 1993 as the cause of peptic ulcer
    • -Gram negative curved bacilli with polar flagella
    • -Present in stomach of many mammals including humans
    • -Bacteria are highly motile and have several virulence factors
    • -Can survive acid production
    • -No animal reservoir, transmission by fecal-oral route
  26. What are the virulence factors of H. pylori?
    • 1. Urease: is an enzyme that catalyzes the hydrolysis of urea into CO2 and ammonia which locally raises the ph from 2 to 6-7
    • 2. Adhesions: Mediate binding to host cells
    • 3. Tissue damaging toxins: cause damage and inflammation of the lining of stomach which leads to peptic ulcer
  27. What is the epidemiology of H. pylori?
    • -45% of adults in US are colonized
    • -Common, people in a low socioeconomic class or developing nations
    • -Ubiquitous and worldwide with no seasonal incidence of disease
    • -70-100% of patients with gastritis, gastric ulcers duodenal ulcers are infected
    • -Associated with gastritis, gastric ulcers, gastric adenocarcinoma and gastric MALT lymphoma (Cancer)
    • -Etiological agent of type B gastritis
  28. How do you diagnosis H. Pylori?
    • -Histological microscopic exam of gastric biopsy with upper endoscopy (Invasive)
    • -Urea breath test relatively sensitive- Easier to test. Noninvasive
    • -Antigen test is sensitive and specific, performed with stool specimens
    • -Urease production uncommon in intestinal helicobacters
  29. How do you treat H. Pylori?
    • -Treatment with antibiotics (recurrence problem)
    • -No vaccines
  30. What is the time course of H pylori?
    • infection-weeks/months-chronic superficial gastritis
    • years/decades: peptic ulcer, chronic superficial gastritis, lymphoproliterative disease, chronic atrophic gastritis- then adenocarcinoma
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Micro J210 Atypical Bacteria
Micro J210 Atypical Bacteria