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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)
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
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
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).
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
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)
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
What is extra-pulmonary disease?
- aka Military TB
- -Hematogenous spread to multiple organs
- -High mortality
- -Caused by M. Tuberculosis
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.
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
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
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
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
What does a >15 mm of induration in a TB test?
-Persons at low risk for tuberculosis
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.
Other than a TB, what other ways can you diagnosis M. TB?
-Microscopy and culture are sensitive and specific
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
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.
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
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
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
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%
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
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
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
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
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
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
How do you treat H. Pylori?
- -Treatment with antibiotics (recurrence problem)
- -No vaccines
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