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ID Week 3 > ICL 2.4: Legionella & non-TB Mycobacteria > Flashcards

ICL 2.4: Legionella & non-TB Mycobacteria Flashcards

1
Q

what is the basic microbiology of legionella?

A

aerobic gram (-) bacilli

stains poorly

intracellular bacterium

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2
Q

short summary of the epidemiology of legionella

A

Water-borne infections such as Legionellosis (Legionnaire’s disease; serious) and Pontiac fever (high disease rate but self-limiting)

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3
Q

what is the short summary of the pathogenesis, clinical presentation, diagnosis and treatment of legionella infections

A

80% of cases in people > 40 yrs old

Compromised pulmonary f(x) and low CMI response are risk factors

Nonspecific “flu-like” symptoms: fever, chills, headache, dry cough

diagnosis: urine antigen (LPS) immunoassay
treatment: macrolides (azithromycin) or fluoroquinolones (cipro): must penetrate infected cells

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4
Q

in what medium is legionella grown?

A

requires special culture media

buffered charcoal yeast extract AND cystein and iron

it has a “cut-glass” appearance on BYCE

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5
Q

how do we stain legionella?

A

it stains poorly with gram stain

instead we have to use silver stain

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6
Q

what time of the year is legionella most common?

A

summer and fall

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7
Q

what age group is most succeptible to legionella infections?

A

> 50 years old

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8
Q

where is legionella found?

A

naturally found in lakes and streams, A/C systems, water systems

  1. commercial A/C systems like hotels, resorts, health care
  2. fountains
  3. shower heads/humidifiers
  4. produce sprayers at kroger
  5. hot tubs
  6. hospital devices used for inhalation therapy
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9
Q

what is legionella resistant to?

A
  1. high temperature
  2. chlorine

it forms biofilms in pipes of all kinds of water systems, yikes

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10
Q

is the number of outbreaks associated with drinking water caused by legionella increasing or decreasing?

A

incidence of legionella outbreaks associated with drinking water is increasing

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11
Q

what types of people are most at risk for legionella infections?

A
  1. smokers
  2. chronic lung disease patients
  3. immunosuppressed individuals (transplants, cancer, AIDS)
  4. > 50 years old
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12
Q

how is legionella spread?

A

legionella is found in soil and water – especially iron rich tap water

no person-person spread known to occur!

there’s also no animal reservoir known

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13
Q

what is the main legionella species we’re going to talk about?

A

there’s over 50 legionella species

but L. pneumophilia is what causes 90% of infections

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14
Q

what is the shape of legionella?

A

it’s pleomorphic

so it’s coccobaccilli in tissue but long rods in lab media

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15
Q

what’s the pathogenesis of legionella?

A

macrophages in the lung normally engulf bacteria everyday in an endosome that then fuses with a lysosome and degrades the bacteria

however, with legionella it inhibits fusion with lysosome

Dot/Icm secretion system secretes hundreds of proteins into the inside of the macrophage to disable it so that antigen processing and lysosome fusion is all turned off

this allows the legionella to replicate to super high numbers in the macrophage in legionella-containing vacuole (LCV)

in the meantime, it’s allowing the macrophage to present antigen which recruits new inflammatory cells to the region which cause a strong inflammatory response and is what gives you pneumonia and inflammation in the lungs

ultimately the macrophage is killed

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16
Q

what type of organism does l. pneumophilia infect?

A

L. pneumophilia infects amoebae in the environment then replicates

by infecting amoeba and replicating inside them, it’s protected from chlorine and other inactivating agents

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17
Q

what is legionellosis?

A

aka Legionnaires disease; caused by L. pneumophilia

lots of people are infected but very few show disease

preferentially affects those with underlying pulmonary disease

it’s a pneumonia that causes serious, permanent damage

mortality is 15-20% in healthy people but 7% in immunocompromised people

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18
Q

how long is the incubation period of legionellosis?

A

2-10 days

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19
Q

who is more susceptible to legionellosis?

A

it preferentially affects those with underlying pulmonary disease

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20
Q

what are the symptoms of legionellosis?

A
  1. fever
  2. chills
  3. dry cough
  4. headache
  5. CXR pneumonia
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21
Q

what is Pontiac fever?

A

cause by L. pneumophilia

affects healthy and high-risk individuals

high disease rate, >90%

it’s self-limiting (2-5 days) and there’s no pneumonia

it’s never fatal!

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22
Q

what are the symptoms of Pontiac fever?

A
  1. fever
  2. chills
  3. myalgia
  4. malaise
  5. headache
  6. dizziness
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23
Q

what are the two diseases that can be caused by L. pneumophilia?

A
  1. Legionellosis

2. Pontiac fever

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24
Q

what is the pathology of legionella?

A

it replicates inside alveolar macrophages

lung damage is actually due to cytokine/chemokine responses, not the bacteria itself!

cell-mediated immunity is important for protection though

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25
Q

what would a lung tissue sample from a legionella infection show?

A

there’s no white space…it just looks like “moth-eaten” lungs with fluid-filled patches

the tissue is all filled with neutrophils and macrophages from the huge immune response that is being mounted on the legionella

so it’s the cytokine storm thats causing damage and ultimately causing the disease!

26
Q

what are the 2 tests that you can do to diagnose legionella?

A
  1. urine antigen immunoassay

2. culturing of sputum

27
Q

how does a urine antigen immunoassay work?

A

used to diagnose legionella infection quickly, only takes 15 minutes!

ELISA detects Legionella LPS in patient’s urine

but it only detects serogroup 1

28
Q

how does culturing sputum for legionella diagnosis work?

A

you get sputum and put it on BYCE

getting the sputum might be hard though….

it’ll be 3-5 days before the colonies are visible (“cut glass” appearance)

you need to confirm with direct fluorescent anitbodies

29
Q

what are the clues for diagnosing legionnaire’s disease?

A
  1. pneumonia; rales with signs of consolidation
  2. CXR abnormalities by the third day of illness; patchy unilobar infiltrate that progresses to consolidation
  3. fever (> 39∘C) is almost always present
  4. hyponatremia = low serum sodium levels <130 mg/L; due to lung damage
  5. GI symptoms, especialyl diarrhea
  6. neurological findings; especialyl confusion
  7. gram stain of respiratory secretions shows many neutrophils but few, if any, microorganisms
30
Q

which drugs do legionella infections not respond to?

A

legionella doesn’t respond to beta-lactam and/or aminoglycoside antibiotics

that’s because legionella hides out in the macrophages which B-lactam and aminoglycosides can’t penetrate

31
Q

how do you treat legionella?

A
  1. macrolides
  2. fluoroqinolones

legionella are naturally β-lactam resistant because β- lactams don’t penetrate macrophages

antiobiotics will need to reach the interior of macropahges!!

32
Q

which drugs are macrolides?

A
  1. azithromycin

2. clarithromycin

33
Q

which drugs are fluoroquinolones?

A
  1. ciprofloxacin

2. levofloxacin

34
Q

how can we prevent legionella?

A

reduce Legionella numbers in water supplies!

we can do this by:

  1. high heat
  2. higher chlorine concentration
  3. copper-silver ionization
  4. surveillance of A/C and water systems
35
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of legionella

A

MICROBIOLOGY: Aerobic, Gram − rods; BCYE plates

PATHOLOGY: Invade and grow in both human alveolar macrophages and free-living amoebae; Prevent lysosome fusion and replicate in special vacuole; Secretes proteins into host cell and triggers strong inflammatory response

EPIDEMIOLOGY: Affects only a minority of those exposed (risk factors such as > 50 yrs old and smokers); Causes waterborne infections such as Legionellosis (Legionnaires’ disease) and Pontiac fever (self-limiting)

CLINICAL: Early nonspecific“flu-like” symptoms; CXR; Cleared by cell-mediated immune response

DIAGNOSIS: Urine LPS immunoassay + culture (fluor Ab)

TREATMENT: Antibiotics that penetrate infected cells (eryth, azith, cipro)

36
Q

what is the basic microbiology of non-TB mycobacteria?

A

obligate aerobes

gram (+) rod, bacilli intracellular bacterium

thick PG layer with no outer membrane

high G-C genome content

37
Q

what are the 4 species of mycobacterium?

A
  1. M. avium complex (MAC)
  2. M. intracellulare
  3. M. leprae
  4. M. tuberculosis complex
  5. M. marinum
  6. ulcerans
38
Q

what are the subspecies of M. avium complex (MAC)?

A
  1. M. avium subsp. hominissuis**
  2. M. avium subcsp. avium
  3. M. acium subsp. silvaticum
  4. M. avium subsp. paratuberculosis
39
Q

are mycobacterium motile?

A

non-motile

no flagella

40
Q

what stain do you use for mycobacterium?

A

yes they’re gram (+) but you can’t use the gram stain to stain them because they have a really waxy coat

instead you use an acid-fast test

41
Q

what disease does M. leprae cause?

A

leprosy aka Hansen’s disease

42
Q

where are M. leprae infections most common?

A

most cases (90%) in Angola, Brazil, D.R. Congo, India, Madagascar, Mozambique, Tanzania, Nepal

43
Q

how is M. leprae transmitted?

A

person-to-person transmission

it’s by droplets/secretions from nose and mouth

natural reservoir is not known (probably humans)

44
Q

what are most causes of M. leprae caused by?

A

armadillos!

in the US most cases in California, Texas, Hawaii, Louisiana

45
Q

what is the pathology of m. leprae?

A

granulomatous disease of skin and peripheral nerves

when the macrophage can’t contain the infection you get macrophages in the middle surrounded by T cells that secrete cytokines into the middle and you get a necrotic center; granulomatous disease is what causes the legions

bacteria infects dermal macrophages and Schwann cells

lesions are often *hypopigmented

*sensory loss is common because of thickened nerves

46
Q

how do you diagnose M. leprae?

A

they cannot be grown in lab mediums!!

instead they can be grown in armadillos or mouse foot pads because M. leprae like cold temperatures like found in the extremities

you can also identify M. leprae by acid-fast bacilli in skin lesion biopsy or skin smear

47
Q

how can M. leprae be classified?

A
  1. paucibacillary = negative smear from lesion because low bacterial numbers; strong CMI response

1-5 hypopigmented patches

  1. multibacillary = positive smear from lesion because abundance of bacteria; strong humoral response; highly infectious

more than 5 hypopigmented patches

48
Q

how do you treat M. leprae infections?

A
  1. Paucibacillary (PB; tuberculoid) or early stages of infection:

6 months: rifampicin and dapsone

  1. Multibacillary (MB; lepromatous) or severe forms of disease:

12 months: clofazimine, rifampicin, and dapsone

49
Q

where is MAC usually found?

A

M. avium complex is usually found in soil, water, plants, animals

it’s also uncommon to find low numbers of MAC in lungs of people without apparent disease

50
Q

how is MAC transmitted?

A

infection by ingestion (mainly water) or inhalation

51
Q

what diseases can MAC cause in immunocompetent persons?

A
  1. 45-60 yr old, white men, heavy smokers, often alcoholics

TB-like nodules in lungs; present with persistent cough, fatigue, weight loss

  1. Lady Windermere Syndrome
  2. solitary pulmonary nodule

cough, fever, shortness of breath

52
Q

what is Lady windermere Syndrome?

A

a disease caused by MAC

it happens in elderly women, otherwise healthy, non-smokers

present with persistent dry cough, low-grade fever

CXR right middle zone infiltrates

due to years of cough suppression which allows bacteria to build up in the lungs and cause granulomas

53
Q

what do MAC infections in HIV/AIDS patients cause?

A

with HIV epidemic, MAC has become most common non-tuberculosis mycobacterial human disease in U.S.

usually disseminated infection with bacteremia

may disseminated infection with bacteremia

all this usually happens when the CD4 count is below 50

can diagnose by acid-fast stain or PCR

54
Q

how do you treat MAC infection in HIV/AIDS patients?

A

clarithromycin or azithromycin

sometimes add ethambutol + rifampicin

55
Q

what are the two rare mycobacerial diseases?

A
  1. M. ulcerans

2. M. marinum

56
Q

what is M. ulcerans

A

Africa “Buruli ulcer”

Australia “Bairnsdale ulcer”

Tropical wetlands, mud beneath stagnant water

*trauma to skin followed by exposure to mud

painless lump –> shallow ulcer –
> limb deformities

57
Q

what is M. marinum?

A

swimmer’s ulcer or Fishtank granuloma

**trauma to skin followed by exposure to contaminated water (salt or fresh water)

common in southern coastal U.S.

papulonodular lesion on elbow, knee, foot, hand

58
Q

FLASHCARD: microbiology, epidemiology, clinical symptoms, diagnosis and treatment of mycobacterium leprae

A

MICROBIOLOGY: technically gram + but use acid-fast stain; cannot grow in lab

EPIDEMIOLOGY: < 250,000 cases worldwide; Africa, India, Brazil; Armadillos in southern U.S.; person-to-person transmission by nasal and oral secretions

CLINICAL: Skin and peripheral nerves; Hypopigmented macules –> papules –> nodules

Paucibacillary (PB; tuberculoid; few bacteria; few macules) and multibacillary (MB; lepromatous; many bacteria; > 5 macules)

DIAGNOSIS: Acid-fast stain of biopsy

TREATMENT: PB: rifampicin and dapsone;

MB: clofazimine, rifampicin and dapsone;

59
Q

FLASHCARD: MAC

A

M. avium subsp. hominissuis and M. intracellular

Age, smoking, Lady Windermere Syndrome

Persistent cough

Diagnosed by acid fast or PCR of BAL

Treat with clarithromycin or azithromycin (may add ethambutol + rifampicin)

60
Q

how do you treat M. ulcerans or M. marinum?

A

you can treat both ulcers with rifampicin and ethambutol!

ID Week 3 (25 decks)

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