Micro: Tetanus & Botulism

Question 1

What are the different mechanisms of action of bacterial toxins?

Answer 1

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

Question 2

What are the different mechanisms of A of an AB toxin once it is internalized?

Answer 2

ADP-ribosylation of host cell protiens
cleavage of host cell rRNA
cleavage of synaptobrevins

Question 3

What is the microbiology of c. tetani?

Answer 3

obligate anaerobe, spore forming (spores in soil), Gram+ rod, sluggish motility in fresh culture

Question 4

What is the pathogenesis of c. tetani?

Answer 4

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

Question 5

What does the tetanus toxin do once given off?

Answer 5

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

Question 6

What does the light chain of the tetanus toxin do?

Answer 6

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)

Question 7

Why does possible recovery from tetanus take so long?

Answer 7

requires regrowth of inhibitory neurons and motor end plate

Question 8

What are the clinical syndromes caused by tetanus?

Answer 8

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

Question 9

What is the course of generalized tetanus?

Answer 9

autonomic dysfunction several days after muscular symptoms

worsens for 2 wks then slow recovery

Question 10

How is tetanus diagnosed?

Answer 10

spatula test: does gently examining tongue and throat promote pharyngeal muscle spasm
EMG, eliminate alternatives

Question 11

What are the principles of treatment of tetanus?

Answer 11

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

Question 12

What is the available prevention for tetanus?

Answer 12

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

Question 13

What is the microbiology of c. botulinum?

Answer 13

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

Question 14

What are the four main clinical forms of c. botulinum?

Answer 14

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

Question 15

What is the pathogenesis of botulism?

Answer 15

spores heat stable, toxin heat labile - similar to tetanus toxin - most potent toxin known for mammals!

Question 16

How many different serotypes of c. botulinum are there?

Answer 16

A-G - A,B,E, F in food-borne

A and B in wound

Question 17

What does botulism toxin do in the body?

Answer 17

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

Question 18

What are the clinical manifestations of botulism?

Answer 18

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

Question 19

How is botulism diagnosed?

Answer 19

EMG (low amp APs, tetanic and post-tetanic facilitation, absent post-tetanic exhaustion)
toxin assays

Question 20

What are predispositions to adult enteric botulism?

Answer 20

recent surgery, antibiotics, achlorhydria, intestinal dysmotility

Question 21

What is the course of infant botulism/adult enteric botulism?

Answer 21

symptoms plateau at 1-3 wks, recovery begins at 6
relapses and remissions over month
may have permanent damage

Question 22

What different assays are used for different forms of botulism?

Answer 22

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

Question 23

What is the treatment for botulism?

Answer 23

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

Question 24

How can botulism be prevented?

Answer 24

proper food prep and storage, avoid skin popping and black tar heroin, don’t give infants honey
no vaccine yet