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102 Cards in this Set

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What are mycobacteria?
Acid-fast, long, slender, nonmotile, nonspore-forming, filamentous rods.
What are the oxygen requirements of mycobacteria?
Obligate aerobes.
What test distinguishes mycobacteria from the majority of other bacteria?
Ziehl-Neelsen stain
Why is the Ziehl-Neelsen stain used on mycobacteria?
Mycobacterium spp. contain a complex lipid coat, they are difficult to stain with Gram stain.

Furthermore, once stained, mycobacterium retain the dye and do not decolorize easily, even with acid, hence they are "acid-fast".
How do mycobacteria appear?
As red rods growing in a cord-like fashion.
What property accounts for the appearance of mycobacteria?
High (60%) lipid content of mycobacterial cell walls.
What is the name of the branched, long-chain fatty acids of the mycobacteria cell wall?
Mycolic acids
What are two major Mycobacterium species that cause disease in humans?
M. tuberculosis
M. leprae
What are four minor species of mycobacterium?
M. avium-intracellulare (MAC)
M. bovis
M. kansasii
M. scrofulaceum
What type of organism is M. tuberculosis?
Strictly aerobic, acid-fast, intracellular, filamentous rod.
Which cells do M. tuberculosis show tropism for?
Macrophages (cells of the reticuloendothelial system)
What are two mechanisms employed by M. tuberculosis to evade host cell defenses?
1) Pathogen resides within intracellular vesicles called phagosomes
2) Encodes proteins that prevent fusion of phagosomes wiht lysosomes.
What form of immunity is important in fending off M. tuberculosis?
Cellular immunity
Why is cellular immunity important in regards to m. tuberculosis?
Because M. tuberculosis is an intracellular organism.
Is there an antibody response to M. tuberculosis?
YES
Is the antobody response to M. tuberculosis protective?
NO
Why isn't the antibody response to M. tuberculosis protective?
M. tuberculosis are intracellular pathogens that are protected from antibody activity.
What are five complex lipids and factors that contribute to the hardiness and virulence M. tuberculosis?
1) Mycolic acids, which enable acid-fastness
2) Wax D, which enhances immunogenicity
3) Phosphatides, which result in caseous necrosis
4) Cord factor, which correlates with virulence
5) Arabinogalactan, which is a cell wall component
(M. tuberculosis produces neither exotoxins or endotoxins).
How long must M. tuberculosis be cultured for growth to occur?
6-8 weeks on solid media because it is an extremely slow-growing organism.

There is a new, faster liquid media in which growth occurs in 2-4 weeks.
Which is the special culture medium for M. tuberculosis?
Lowenstein-Jensen agar
how is M. tuberculosis transmitted?
Respiratory aerosol
Why is person-to-person transmission common with M. tuberculosis?
It can persist in the environment for prolonged periods, partly because the organism is resistant to desiccation.
What is the reservoir for M. tuberculosis?
Humans
What percentage of the world's population is infected with M. tuberculosis?
33%
What is the overall percentage of developing reactivation disease after M. tuberculosis infection?
10%
When is the risk for reactivation of M. tuberculosis the greatest?
In the first 2 years after primary infection?
What is the overall percentage of developing reactivation disease after M. tuberculosis infection in patients with acquired immune deficiency syndrome (AIDS)?
33-50%
How does the yearly percentage of M. tuberculosis correlate to developing reactivation disease?
Increases 10% annually
What are the possible clinical manifestations of tuberculosis?
1) Primary disease or initial host infection
2) Secondary disease or reactivation tuberculosis
3) Granuloma formation
4) Granuloma rupture with dissemination.
What is the primary infection of M. tuberculosis?
An infection, usually asymptomatic, often confined to the lungs and occurring after the first exposure to M. tuberculosis.
Where is the site of primary tuberculosis infection?
Usually the lower lobes of the lung.
What is the reactivation tuberculosis?
A secondary infection resulting from reactivation of dormant M. tuberculosis that persisted in inactive primary lesions.
What causes reactivation of tuberculosis?
Age
Malnutrition
Other causes of decreased cell-mediated immunity.
Where is the site of secondary tuberculosis infection?
Usually the upper lobes of the lung.
Why does tuberculosis secondarily infect the upper lobes of the lung?
It prefers the higher oxygen tension found there.
What is a granuloma?
A central area of multinucleated giant cells (macrophages that eventually necrose and fibrose, surrounded by a rim of epithelioid cells
What is another name for granuloma?
Tubercle
Why does the body form granulomas?
To attempt to sequester teh infectious process.
What type of necrosis is seen inside a granuloma?
Caseous necrosis
What is caseous necrosis?
A combination of liquefaction and coagulation necrosis resembling cottage cheese
What is a fibrosed granuloma called?
A Ghon complex, visualized as a solitary nodule on chest x-ray.
What are the clinical manifestations of a ruptured granuloma?
Localized pulmonary involvement (chronic pneumonitis)

Disseminated systemic involvement
Why does a ruptured granuloma cause these diseases?
Spread of infectious, caseous material
What is miliary tuberculosis?
Disseminated tuberculosis in which multiple organs are seeded with small M. tuberculosis tubercles that resemble millet seeds.
What are four extrapulmonary manifestations of miliary tubercuosis?
1) Osteomyelitis
2) Meningitis
3) Intestinal infection
4) Erythema nodosum
What virus predisposes individuals to reactivating tuberculosis?
HIV
When are HIV patients most susceptible to reactivating tuberculosis?
When their CD4 count drops below 500.
Why are HIV patients susceptible to developing tuberculosis?
Defective cell-mediated immunity.
What test is uesd to screen for exposure to M. tuberculosis?
Purified protein derivative (PPD) test
Does a positive PPD test indicate active disease?
NO
PPD tests detect prior infection or exposure to M. tuberculosis, NOT active disease
What are exampes of a positive PPD test not caused by active disease?
History of vaccination, as well as for patients born in certain other countries.
What is measured when evaluating a PPD test?
Diameter of induration, or skin elevation, at the injection site.
What should not be measured?
Diameter of erythema
What type of reaction is responsible for induration?
Delayed (type IV) hypersensitivity
Under what conditions can a PPD test be positive?
1) Exposure to M. tuberculosis
2) Atypical mycobacteria present
What criteria are used for determinig a positive PPD?
1) >15mm of induratin is considered positive in those without risk factors
2) >10 mm is positive for those with risk factors (homeless, immigrants from high-risk countries, health care workers)
3) >5mm is positive in those with defective cell-mediated immunity (AIDS patients, or close contacts of those with active TB)
Under what conditions can a PPD test be negative?
1) No previous exposure to M. tuberculosis.
2) Exposure withing 4-6 weeks of PPD test (it takes this long to mount an immune response)
3) Anergy (defective cell-mediated immunity)
How can a negative PPD be distinguished from anergy?
By placing a common allergen on the other arm when admistering a PPD.
What are the most common symptoms of tuberculosis?
Fatigue
Night Sweats
Weight loss
Cough
Hemoptysis
(90% of M. tuberculosis infections are asymptomatic).
What three laboratory tests are used to diagnose M. tuberculosis infection?
1) Acid-fast staining of sputum
2) PCR amplification of m. tuberculosis RNA/DNA
3) DNA probes
What are two major obstacles in the treatment of M. tuberculosis?
1) Emergence of multiple-drug-resistant strains of M. tuberculosis.
2) Need for long therapy, which decreases compliance and selects for resistant strains.
What are five drugs used to treat M. tuberculosis infection?
RIPE
1) Rifampin
2) Isoniazid (INH) and Vitamin B6
3) Pyrazinamide
4) Ethambutol
What is the time course for M. tuberculosis treatment?
6-9 months, depending on the drug regimen and local resistance rates to the drugs used
Note: treatment time course is in constant flux.
How long does it take for an infected patient to be rendered noninfectious with treatment?
2-3 weeks
What drug regimen is used for active M. tuberculosis prophylaxis?
INH for 6-9 months with supplemental vitamin B6
Who gets prophylaxis for M. tuberculosis?
1) Asymptomatic persons with a positive PPD
2) Children exposed to patients with active TB
3) Patients with a positive PPD who will become immunosuppressed (HIV patients).
What is one complication of INH prophylaxis?
Hepatitis
Who is at increased risk for this complication?
1) Persons >35 year of age
2) Persons with a history of alcohol abuse.
Is there a vaccine for M. tuberculosis?
YES
BCG vaccine
Is the vaccine for M. tuberculosis given in the US.
NO
What type of vaccine is M. turberculosis?
Live-attenuated vaccine containing M. bovis.
Should the TB vaccing be given to the immunocompromised?
NO
It's a live vaccine
What do atypical mycobacteria cause?
Tuberculosis, usually with disseminated rather than pulmonary manifestations
What are four atypical mycobacteria?
M. avium-intracellulare (MAC)
M. kansasii
M. scrofulaceum
M. bovis
Do M. avium-intracellulare (MAC)
M. kansasii
M. scrofulaceum
M. bovis cause a positive PPD?
YES
but not always
Which atypical mycobacterial opportunistic infection classically affects AIDS patients?
MAC
What CD4 counts are usually associated with MAC infection in AIDS patients?
CD4<50
What is a common complication of MAC in the immunocompromised?
Disseminated, or miliary disease.
What diseaseis associated with MAC infection in teh non-AIDS population?
COPD
What disease is M. scrofulaceum associated with?
Scrofula
What physical finding is seen in Scrofula?
Cervical lymphadenitis
What patient population is scrofula commonly seen in?
Children
What is the etiology of scrofula?
M. tuberculosis
M. scrofulaceum
What is the source of M. bovis?
Unpasteurized milk
What makes M. bovis useful?
Attenuated strains of M. bovis are used to make a vaccine against tuberculosis.
What are M. leprae?
Obligate, intracellular, acid-fast bacilli indistinguishable from other mycobacteria.
What is an animal reservoir for M. leprae?
Armadillos
What temperatures does M. leprae prefer?
Cool temperatures (30C)
What areas of the body does M. leprae infect?
Superficial areas that are cooler
(skin, superficial nerves)
What are two clinical manifestations of M. leprae?
Tuberculoid leprosy
Lepromatous leprosy
How is M. leprae transmitted?
Prolonged contact with patients infected with lepromatous leprosy.
What is the eponym for leprosy?
Hansen disease
What are the major differences between the two forms of leprosy?
Tuberculoid leprosy:
1) Cell-mediated immune response
2) Granuloma formation
3) Containment

Lepromatous leprosy:
1) Humoral response
2) NO granuloma formation
3) Dissemination
Clinically, what is the significance of the differences between the two forms of leprosy?
Tuberculoid leprosy has few lesions and little tissue destruction.

Lepromatous leprosy has many lesions with extensive destruction of bone and overlying soft tissues, resulting in the typical "leonine facies"
Which form of leprosy has the worse prognosis?
Lepromatous leprosy
What is a feared complication of lepromatous leprosy?
Erythema nodosum leprosum
What is the treatment for erythema nodosum leprosum?
Thalidomide
In which form of leprosy is the lepromin skin test positive?
Tuberculoid form
Can M. leprae be grown in culure?
NO
How is M. leprae diagnosed?
Acid-fast stain of infected tissue samples.
What is the treatment for leprosy?
Dapsone
Rifampin
Clofazimine
for approximately 2 years.
What are two complications of this prolonged coure of treatment for leprosy?
Hemolysis
Methemoglobinemia