ICL 2.4: Legionella & non-TB Mycobacteria Flashcards
what is the basic microbiology of legionella?
aerobic gram (-) bacilli
stains poorly
intracellular bacterium
short summary of the epidemiology of legionella
Water-borne infections such as Legionellosis (Legionnaire’s disease; serious) and Pontiac fever (high disease rate but self-limiting)
what is the short summary of the pathogenesis, clinical presentation, diagnosis and treatment of legionella infections
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
in what medium is legionella grown?
requires special culture media
buffered charcoal yeast extract AND cystein and iron
it has a “cut-glass” appearance on BYCE
how do we stain legionella?
it stains poorly with gram stain
instead we have to use silver stain
what time of the year is legionella most common?
summer and fall
what age group is most succeptible to legionella infections?
> 50 years old
where is legionella found?
naturally found in lakes and streams, A/C systems, water systems
- commercial A/C systems like hotels, resorts, health care
- fountains
- shower heads/humidifiers
- produce sprayers at kroger
- hot tubs
- hospital devices used for inhalation therapy
what is legionella resistant to?
- high temperature
- chlorine
it forms biofilms in pipes of all kinds of water systems, yikes
is the number of outbreaks associated with drinking water caused by legionella increasing or decreasing?
incidence of legionella outbreaks associated with drinking water is increasing
what types of people are most at risk for legionella infections?
- smokers
- chronic lung disease patients
- immunosuppressed individuals (transplants, cancer, AIDS)
- > 50 years old
how is legionella spread?
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
what is the main legionella species we’re going to talk about?
there’s over 50 legionella species
but L. pneumophilia is what causes 90% of infections
what is the shape of legionella?
it’s pleomorphic
so it’s coccobaccilli in tissue but long rods in lab media
what’s the pathogenesis of legionella?
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
what type of organism does l. pneumophilia infect?
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
what is legionellosis?
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
how long is the incubation period of legionellosis?
2-10 days
who is more susceptible to legionellosis?
it preferentially affects those with underlying pulmonary disease
what are the symptoms of legionellosis?
- fever
- chills
- dry cough
- headache
- CXR pneumonia
what is Pontiac fever?
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!
what are the symptoms of Pontiac fever?
- fever
- chills
- myalgia
- malaise
- headache
- dizziness
what are the two diseases that can be caused by L. pneumophilia?
- Legionellosis
2. Pontiac fever
what is the pathology of legionella?
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
what would a lung tissue sample from a legionella infection show?
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!
what are the 2 tests that you can do to diagnose legionella?
- urine antigen immunoassay
2. culturing of sputum
how does a urine antigen immunoassay work?
used to diagnose legionella infection quickly, only takes 15 minutes!
ELISA detects Legionella LPS in patient’s urine
but it only detects serogroup 1
how does culturing sputum for legionella diagnosis work?
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
what are the clues for diagnosing legionnaire’s disease?
- pneumonia; rales with signs of consolidation
- CXR abnormalities by the third day of illness; patchy unilobar infiltrate that progresses to consolidation
- fever (> 39∘C) is almost always present
- hyponatremia = low serum sodium levels <130 mg/L; due to lung damage
- GI symptoms, especialyl diarrhea
- neurological findings; especialyl confusion
- gram stain of respiratory secretions shows many neutrophils but few, if any, microorganisms
which drugs do legionella infections not respond to?
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
how do you treat legionella?
- macrolides
- fluoroqinolones
legionella are naturally β-lactam resistant because β- lactams don’t penetrate macrophages
antiobiotics will need to reach the interior of macropahges!!
which drugs are macrolides?
- azithromycin
2. clarithromycin
which drugs are fluoroquinolones?
- ciprofloxacin
2. levofloxacin
how can we prevent legionella?
reduce Legionella numbers in water supplies!
we can do this by:
- high heat
- higher chlorine concentration
- copper-silver ionization
- surveillance of A/C and water systems
FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of legionella
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)
what is the basic microbiology of non-TB mycobacteria?
obligate aerobes
gram (+) rod, bacilli intracellular bacterium
thick PG layer with no outer membrane
high G-C genome content
what are the 4 species of mycobacterium?
- M. avium complex (MAC)
- M. intracellulare
- M. leprae
- M. tuberculosis complex
- M. marinum
- ulcerans
what are the subspecies of M. avium complex (MAC)?
- M. avium subsp. hominissuis**
- M. avium subcsp. avium
- M. acium subsp. silvaticum
- M. avium subsp. paratuberculosis
are mycobacterium motile?
non-motile
no flagella
what stain do you use for mycobacterium?
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
what disease does M. leprae cause?
leprosy aka Hansen’s disease
where are M. leprae infections most common?
most cases (90%) in Angola, Brazil, D.R. Congo, India, Madagascar, Mozambique, Tanzania, Nepal
how is M. leprae transmitted?
person-to-person transmission
it’s by droplets/secretions from nose and mouth
natural reservoir is not known (probably humans)
what are most causes of M. leprae caused by?
armadillos!
in the US most cases in California, Texas, Hawaii, Louisiana
what is the pathology of m. leprae?
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
how do you diagnose M. leprae?
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
how can M. leprae be classified?
- paucibacillary = negative smear from lesion because low bacterial numbers; strong CMI response
1-5 hypopigmented patches
- multibacillary = positive smear from lesion because abundance of bacteria; strong humoral response; highly infectious
more than 5 hypopigmented patches
how do you treat M. leprae infections?
- Paucibacillary (PB; tuberculoid) or early stages of infection:
6 months: rifampicin and dapsone
- Multibacillary (MB; lepromatous) or severe forms of disease:
12 months: clofazimine, rifampicin, and dapsone
where is MAC usually found?
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
how is MAC transmitted?
infection by ingestion (mainly water) or inhalation
what diseases can MAC cause in immunocompetent persons?
- 45-60 yr old, white men, heavy smokers, often alcoholics
TB-like nodules in lungs; present with persistent cough, fatigue, weight loss
- Lady Windermere Syndrome
- solitary pulmonary nodule
cough, fever, shortness of breath
what is Lady windermere Syndrome?
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
what do MAC infections in HIV/AIDS patients cause?
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
how do you treat MAC infection in HIV/AIDS patients?
clarithromycin or azithromycin
sometimes add ethambutol + rifampicin
what are the two rare mycobacerial diseases?
- M. ulcerans
2. M. marinum
what is M. ulcerans
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
what is M. marinum?
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
FLASHCARD: microbiology, epidemiology, clinical symptoms, diagnosis and treatment of mycobacterium leprae
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;
FLASHCARD: MAC
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)
how do you treat M. ulcerans or M. marinum?
you can treat both ulcers with rifampicin and ethambutol!
