TB-> Mycobacteria!!! Microm442 Deck 18 Flashcards

1
Q

the sole genus of the family mycobacteriaceae (red snappers)

A

mycobacterium

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2
Q

Includes many environmental organisms

A

Often found in water, soil, foodstuffs

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3
Q

Nontuberculous mycobacteria

A
  • Pulmonary disease similar to TB
  • Lymphadenitis
  • Skin and soft tissue diseases
  • Disseminated diseases
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4
Q

important determinant of disease presence
and severity for all of these.

A

Host susceptibility

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5
Q

Acid fastness

A

Neither gram-negative nor –positive, but staining is often weakly positive.
* Results from the unique cell wall structure, with 60% mycolic acids (waxy coats) and lipoarabinomannan
(LAM in your book, or arabinogalactan below)
* Resists destaining by acid or ethanol
* Renders mycobacterial cells very resistant to drying (likely aids transmission in droplets)

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6
Q

Acid fast staining
(Ziehl-Neelsen or Kinyoun Stain)

A
  • Stain with carbol fuchsin
  • Decolorize with acid
    alcohol
  • Counterstain with
    methylene blue
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7
Q

Slow-growing and difficult to culture (fastidious) Divided into:

A

Slow-growing (um, particularly slow-growing?)
* M. tuberculosis, M. leprae are examples
* Generation times often 40x E. coli
* Forms visible colonies >7 day

Fast-growing (um, relatively fast-growing?)
* M. abscessus spp., chelonae are examples
* Forms visible colonies or growth ≤ 7 days

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8
Q
  • Carotenoids of various structures
  • May be used to speciate clinical isolates (can also use PCR and
    biochemical tests)
A

distinctive pigments

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9
Q

aerobic or not?

A

aerobic

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10
Q

nonmotile except

A

m. marinum

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11
Q

host genetics

A

thought to play important role in
susceptibility/manifestations -> Defects in innate immune receptor signaling, IFN-g pathways

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12
Q
  • Difficult to culture in vitro
  • Difficult to manipulate genetically
A
  • Renders laboratory
    study difficult
  • Hinders diagnosis
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13
Q

Slow mycobacterial growth make them difficult to treat

A
  • May be less likely to respond to standard antibiotics
  • Often grow to high densities before immunity develops
  • Can develop resistance to single agents easily
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14
Q

Recent(ish) resurgence

A
  • Poverty
  • Crowding
  • Malnutrition
  • Africa, Asia
    hardest-hit
  • Multidrug
    resistance
  • HIV/AIDS
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15
Q

TB: Impact of HIV

A

TB disease burden is highest in areas with endemic
HIV
* HIV increases susceptibility to TB infection
* HIV thought to worsen TB outcomes by impacting T-
cell-mediated immunity
* AIDS also increases susceptibility to nontuberculous
mycobacteria (NTM), especially M. avium complex

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16
Q

TB: Clinical features
* Primary: Period soon after initial infection

A
  • Often clinically quiescent
  • In the immunocompromised, disseminated disease can occur and be
    dramatic
  • In normal hosts, usually leads to latency (control)
17
Q

TB: Clinical features
Secondary: Reactivation disease

A
  • Night sweats, fever, weight loss (immune response)
  • Cough
  • Can infect spinal column (vertebrae) and meninges (central nervous
    system)
  • Much of clinical impact can be attributed to host response
  • But host response is necessary for control of infection, so…
18
Q

TB: Transmission

A
  • Nearly always thought to be from inhaling infectious particles
    (droplet nuclei)
  • Produced by infected person via cough, talking, sneezing
  • Can remain suspended in the air for hours
  • Small, airborne droplet nuclei can
    penetrate to lung airspaces (alveoli),
    where infection likely happens
  • Usually require prolonged, recurrent
    exposure for infection
19
Q
  • Bacteria ingested by macrophages
  • M. tb can replicate in macrophages, destroying them
  • Blood-borne inflammatory cells migrate to infection, ingest bacilli and
    continue the process (granuloma)
  • Effective cellular immunity can take weeks to
    develop
  • Enables rampant early replication
  • Infected macrophages can disseminate via
    lymphatics to lymph nodes and beyond
  • Immune response usually contains the infection
A

parthenogenesis after primary infection

20
Q

Primary infection, continued:

A

Immunocompetent hosts:
* Once hypersensitivity/cellular immunity develop, infection usually controlled
* Skin/blood test positivity develop concurrently
* Infection is latently persistent in most
* Usually can’t be reinfected after this stage
* Reactivation can occur later
* Immunocompromised hosts:
* Can get progressive, often disseminated disease
* Manifestations of primary infection varies with age:
* Often progressive in infants, elderly
* More variable in-between (see readings)

21
Q

Secondary tuberculosis: Reactivation

A
  • Most often occurs within 2 years
  • Usually in the apices (tops) of the lungs
  • Not clear why- maybe diminished lymphatic drainage
  • HIV is a common reason
  • Can be due to immunosuppression, subtle or overt
  • Necrosis of granulomas, cavitation
  • VERY infectious at this point
22
Q

most people dont develop past latency or so because

A

most exposed people are treated

23
Q
  • Cellular immunity is critical
A
  • No clear role for humoral (antibody) immunity
  • Little to no immune response in early infection
24
Q

Macrophages have multiple MTb receptors

A
  • Complement receptors (all mycobacteria)
  • MTb can resist acid phagolysosome
25
Q

CD4+ T-lymphocytes critical for

A

activating
immune cascade

26
Q
  • Increased macrophage killing and control
    (normal host)
  • Formulation of granulomas- contain infection
    and either heal or necrose and “caseate”
A

Hypersensitivity within 3-8 weeks of exposure

27
Q

Dx

A

TB: Diagnosis
* Microscopy
* Culture:
* Takes a long time (often 3-6 weeks), but
* PCR or other molecular: Increasingly used
* Skin test (PPD): Hypersensitivity to TB
antigens
* Old school now!
* IFN-g release tests (“QuantiFERON Gold”, “T-
Spot”, etc)
* Much more common now
* Not as impacted by vaccine as PPDTB: Diagnosis

28
Q

Treatment

A
  • ≥ 3 agents for disease (high bacterial burden):
  • To address high rates of resistance development to single
    agents
  • First line therapy includes 3 of these:
  • Isoniazid (INH), pyrazinamide, ethambutol (cell wall inhibitors)
  • Rifampin (polymerase inhibitor)
  • Aminoglycosides (ribosome inhibitor) still helpful (streptomycin)
  • Fluoroquinolones (moxifloxacin)- DNA gyrase inhibitor
  • Single agent for known exposure, no disease (low
    bacterial burden):
  • INH only for chemoprophylaxis
29
Q

prevention

A
  • BCG: Bacillus-Calmette-Guérin vaccine
  • Made from an attenuated version of M. bovis
  • Used in much of the world (not US)
  • Variable efficacy against TB for various
    hypothesized reasons
  • Gives false-positive skin test (PPD)- not IFN-g
    release tests