Respiratory Flashcards
Encapsulated H. influenzae
Capsule = carbs -> necessary for virulence (adhesion, antiphago)
Serotypes - a-f (6) = different capsules, detect with antiserum assays
- serotype B = pentose (vs hexose) - most common, most virulent
Haemophilus influenzae overview
Gram (-)
Non-motile, non-spore
Small, pleimorphic (both bacillus and cocci)
Name - discovered during flu pandemic (1918) -> secondary infection?
Encapsulated/typable (ex HiB) -> meningitis
Unencapsulated -> ear aches, respiratory
75-80% are carriers, most unencapsulated
HiB pathogenesis
Aerosol -> colonization -> nasopharyngitis -> otitis media, sinusitis ->
- epiglottitis (life threat due to sudden airway!)
- bacteremia -> meningitis, cellulitis, arthritis (pyarthrosis), pneumonia
Virulence:
- IgA protease -> immune evasion
- LPS + host choline -> ciliary stasis
HiB treatment
Low mortality if treated early
Ampicillin - drug of choice but often resistant
Cephalosporin = initial regimen
Augmentin (ampicillin + beta-lactamase inhibitor)
Corticosteroids - decreases neuro damage from LPS inflammation
- previously 1/3 had neuro damage
Rifampin - prophylaxis for household contacts (short dose so no resistance!)
HiB epidemiology
3-5% carry HiB - decreasing with vaccine (dev’t world)
- was most common cause of child bacterial meningitis
- 60% got meningitis, 5-10% case fatality
Other strains increasing -> adult immune compromise
Immunity
- passive - from mom, few months
- active - 3-4 yo have had asymptomatic
- vaccine = capsule + diptheria toxoid (more immunogenic)
(new synthetic capsule fewer s/e than extract)
- requires complement system (-> disease if compromised)
Unencapsulated H influenzae
Restricted to respiratory tract (can’t survive outside)
- loves mucous, non-ciliated, damaged epithelium (secondary!)
- otitis media (second after Strep pneumoniae)
- conjunctivitis
- colonizes -immune compromise> URI, sinusitis (ex COPD, CF)
- meningitis if predisposed (neonate, CSF leak)
Different strains have different adhesins -> biofilms
Can persist extra or intracellularly (-> recurrent infections?)
Unencapsulated H influenzae tx
Amoxicillin for otitis media, sinusitis
- 25-30% resistance -> Augmentin (+lactamase inhibitor), ceftriaxone
- may have resistance to all due to biofilm
Immunity - specific to different strains (membrane, no capsule)
- no vaccine, limited passive immunity
- adults susceptible
H influenzae diagnosis
Hard to culture, susceptible to drying, disinfectants
Chocolate agar (blood + mild heat) - provides growth factors
- X = hemin (precursor), heat stable
- V = NADH precursor, heat labile
- facultative anaerobe - grow in CO2
-> encapsulated smooth -> spontaneous rough/unencapsulated
Satellite colonies - other colony (Staph) secretes V factor
Fermentation not useful
History! Age (young -> HiB, old -> unencapsulated)
Meningitis -> blood and CSF -> Gram, chocolate
- also immunofluorescence vs HiB capsule
- can test urease, indole, ornithine (HiB + for all)
Other Haemophilus
H ducreyi - STI -> chancre (ragged ulcer)
- common at seaports, Africa, Asia
-> sulfonamides, tetracycline, streptomycin
H aegypticus -> purulent conjunctivitis
- includes H influenzae subgroup aegypticus and Koch-Weeks
H parainfluenzae - respiratory colonizer -> pharyngitis, endocarditis
Bordatella overview
Bordatella pertussis -> whooping cough
Small, Gram (-)
Coccobacillus (sim to Haemophilus)
Obligate aerobe - can’t ferment
B parapertussis -> rare whooping cough
B bronchiseptica - respiratory in animals, sometimes humans
- similar virulence factors but not pertussis toxin
Bordatella epidemiology
Only humans (no reservoir) Major childhood killer pre-vaccine - high case fatality; more than measles, diptheria, polio, scarlet fever combined!
Vaccine - introduced 1937
- not lifelong - need boosters (also true for illness)
- original = heat killed -> encephalopathy, neuro damage
- now acellular virulence factors (pertussis toxin, FHA, pertactin, fimbrae) -> fewer side effects
- ie DTP = original, DTaP = acellular
Bordatella pathogenesis
Droplet -> adhere to ciliated cells ->
- multiplication and toxin release (-> ulceration, inflammation)
- organism does not disseminate (only toxins)
Adhesion:
- pilus
- filamentous hemagglutinin (FHA) - similar to pilus
- surface molecule pertactin -> bridges cilia
Exotoxins:
- pertussis toxin - targets G proteins (blocks G inhibitory)
-> AC -> cAMP, ion channels, phospholipase C -> insulin, histamine sensitization, innate immune fx
- calmodulin-stimulated adenylate cyclase -> high cAMP -> impairs WBCs
- dermonecrotic (aka mouse lethal, heat labile) -> actin polymerization -> vasoconstriction -> ischemia, necrosis of epithelium
- tracheal cytotoxin - outermembrane and released -> ciliostasis, kills tracheal cells
Endotoxin/LPS -> local inflammation
Bordatella clinical
Droplet -> 7-10 days -> catarrhal stage (mild URI) ->
paroxysmal stage = cough, whoop dt mucous, swollen glottis
Dx:
- usually PCR
- culture requires fresh medium (can’t store), grows very slowly
- rapid fluorescent antibodies
- history of contacts, cough, WBC’s
Tx: erythromycin (or tetracycline, chloramphenicol)
- NOT sensitive to penicillin, ampicillin
Legionella overview
Gram (-), pleiomorphic, intracellular growth
L pneumophila - discovered after Philly outbreak (old people at hotel, bacteria in cooling system -> 15% mortality)
Grows inside amoeba or biofilms -> spreads through air/water systems
8-18K cases/year
Legionella clinical
Atypical pneumonia (interstitial vs lobar) Can disseminate -> LPS shock (esp immune compromised) Milder = Pontiac fever (often not diagnosed)
Dx:
- test of choice = fluorescent antibody
- test serum pre and post (differentiate from earlier infection)
- fastidious - charcoal yeast + Fe + cysteine
- can detect antigens in urine
NOT susceptible to penicillins, sulfonamides
