Flashcards in Micro: Tetanus & Botulism Deck (24):
What are the different mechanisms of action of bacterial toxins?
type 1: bind to host cell surface and incite response but not internalized, superantigens
type 2: injure cytoplasmic membrane
type 3: AB toxins, B binds, A internalized
What are the different mechanisms of A of an AB toxin once it is internalized?
ADP-ribosylation of host cell protiens
cleavage of host cell rRNA
cleavage of synaptobrevins
What is the microbiology of c. tetani?
obligate anaerobe, spore forming (spores in soil), Gram+ rod, sluggish motility in fresh culture
What is the pathogenesis of c. tetani?
infects dirty or soiled wound - spores germinate in wound and give off neurotoxin which is cleaved to heavy chain (cell receptor specificity) and light chain (toxic moiety) linked by disulfide
What does the tetanus toxin do once given off?
bind to PERIPHERAL nerves, transported retrograde to cell bodies and diffuses to terminals of inhibitory GABA neurons and glycinergic interneurons - light chain cleaved and binds to target
What does the light chain of the tetanus toxin do?
zinc dependent endopeptidase that cleaves synaptobrevin - leaves LMNs uninhibited --> continuous contraction of antagonistic muscles and eventually rigidity, works at alpha motor neuron not NMJ
also get hypersympathetic state (HTN, sweating, tachy)
Why does possible recovery from tetanus take so long?
requires regrowth of inhibitory neurons and motor end plate
What are the clinical syndromes caused by tetanus?
generalized: lockjaw, sardonic smile, ab rigidity, opisthotonus (flexed arms, extended back and legs), severe pain, respiratory compromise - pt is mentally alert (not a central nerve dz)
localized: site of inoculation, can progress to generalized
cephalic: head or neck wound, facial paralysis followed by generalized
neonatal: generalized, follows umbilical stump inoculation
What is the course of generalized tetanus?
autonomic dysfunction several days after muscular symptoms
worsens for 2 wks then slow recovery
How is tetanus diagnosed?
spatula test: does gently examining tongue and throat promote pharyngeal muscle spasm
EMG, eliminate alternatives
What are the principles of treatment of tetanus?
halt toxin production: wound debridement, antibiotics (metronidazole, NOT penicillin)
neutralize unbound toxin: HTIG PLUS active immunization at different site
manage airway (tracheostomy), control spasms (environment, benzodiazepenes, baclofen), manage dysautonomia (IV Mg, labetalol to block alpha AND beta, avoid diuretics)
supportive care, NUTRITION
What is the available prevention for tetanus?
full series (3 inj) tetanus toxoid = adult Td booster/10 yrs (esp elderly), child DTaP once, Tdap booster for pregnant women
if tetanus prone wound in pt >5 yrs since booster - give human TIG and tetanus toxoid booster at different site
case of tetanus does NOT give immunity
What is the microbiology of c. botulinum?
obligate anaerobe, spore forming gram + rod (spores in soil, lake sediment, plants,bees, honey)
growth on egg yolk agar, lipase positive --> clear halo around colonies
What are the four main clinical forms of c. botulinum?
food borne illness - products w pH >4.6
infant botulism - most common, ingestion of honey or dust borne spores?
wound botulism - only one w fever!
adult enteric botulism - toxin produced in gut and engulfed there, not ingested
iatrogenic from botox, biological warfare agent
What is the pathogenesis of botulism?
spores heat stable, toxin heat labile - similar to tetanus toxin - most potent toxin known for mammals!
How many different serotypes of c. botulinum are there?
A-G - A,B,E, F in food-borne
A and B in wound
What does botulism toxin do in the body?
attaches to cholinergic ganglionic and PS synpases and NMJs, internalized
light chain is zinc containing that cleaves SNAP, synaptobrevin or syntaxin - prevents release of Ach at NMJ
What are the clinical manifestations of botulism?
4-36 h after exposure: nausea, diarrhea, dry mouth, slurred speech, blurred vision, difficulty chewing and swallowing, then descending symmetrical weakness of CNs, upper extremities, trunk, and lower extremities
no fever, no sensory deficits, pt remains alert
wound has no GI prodrome and can have fever
infant - constipation, hypotonia, drooling
How is botulism diagnosed?
EMG (low amp APs, tetanic and post-tetanic facilitation, absent post-tetanic exhaustion)
What are predispositions to adult enteric botulism?
recent surgery, antibiotics, achlorhydria, intestinal dysmotility
What is the course of infant botulism/adult enteric botulism?
symptoms plateau at 1-3 wks, recovery begins at 6
relapses and remissions over month
may have permanent damage
What different assays are used for different forms of botulism?
infant/enteric: stool for culture and toxin assay
food borne: serum, stool, vomitus, food for toxin assay
wound: anaerobic culture of wound, no toxin assays
What is the treatment for botulism?
immediate antitoxin - does not reverse paralysis, but prevents more - watch for serum sickness and anaphylaxis if used equine, human only for infant
hospitalize and ventilate
purgatives to expel retained food + small volume enteral feeding
antibiotics for wound (pen, metro) - *NOT aminoglycosides or clinda b/c aggravate neuromuscular blockade, don't give nonreabsorbable (oral vanc,etc) for infant or enteric