20: exotoxin producing clostridia - jonathan Flashcards
What are the two major mechanisms that cause illness with Clostridia?
What are examples of each?
Exotoxin-mediated disease: Botulism-toxin
Invasion and inflammation: tissue invasion and damage due to host’s immune system
As an exotoxin producing bacteria, do clostridia organisms need to be consumed to cause illness?
As an exotoxin, botulism can be secreted by clostridia into food.
Only the exotoxin needs to be consumed to cause illness.
No clostridia need to be consumed.
Aside from Clostridia botulism, what other bacteria is a common exotoxin food-borne diarrheal bacterial disease?
Staphylococcus aureus
What are 2 possible pathogenic steps in establishing bacterial infection by ingesting toxin?
1) Toxins are pre-formed in food and ingested. No organism necessary. (ex: Botulism and S. aureus)
2) Ingestion of microorganism with adherence, colonization, and toxin is then formed in the gut. (ex: Botulism and Vibrio cholerae aka cholera toxin)
What are the general characteristics of Clostridium? Aerobic or anaerobic? Gram status and shape? Spore status? Catalase status? Oxidase stauts?
Obligate anaerobe Gram positive rods Spore forming Catalase negative Oxidase negative
What is unique about the spore formation of clostridium for Dx purposes?
Location of the spore in the bacterium may aid in species identification (e.g. terminal spores = Clostridium tetani)
State invasive status and basic illness of the following: Clostridium botulism Clostridium tetani Clostridium difficile Clostridium perifringens Costridium septicum (don't need to know) Clostridium ramosum (don't need to know)
Clostridium botulism: noninvasive and causes botulism
Clostridium tetani: generally noninvasive and causes tetanus (small invasive potential)
Clostridium defficile: noninvasive and causes pseudomembranous enterocolitis
Clostridium perifringens: very invasive and causes gangrene
Costridium septicum: invasive in malignancy
Clostridium ramosum: implies invasive in notes. Does not say.
What symptoms do the following toxins cause…
1) Botulism toxin?
2) Tetanus toxin?
3) Exotoxin A and B (Clostridium difficile)?
4) Alpha toxin (Clostridium perfringens)?
1) flaccid paralysis
2) tetanus (locked jaw)
3) diarrhea in pseudomembranous colitis
4) lecithinase which hosts cell membrane in combination with other degradative enzymes as the cause for “Gas Gangrene”
How would you Dx Clostridium tetani due to its spore location?
C. tetani have only one “terminal spore” that looks like a tennis racket. See slide 6 and 9 on Clostridia I ppt.
All other species have subterminal spores.
What is the general epidemiology of C. tetanus…
Where is its natural habitat?
How common is it in the U.S. vs other countries?
How does infection occur?
Natural habitat is in the soil
Rare in the U.S. due to immunization and common in developing nations (eg infected umbilical stump)
Cases occur due to puncture wounds (a random nail with that contains soil bacteria) where spores germinate in the deep and dirty wound under anaerobic conditions
What is the general pathogenesis of C. tetanus…
Is C. tetanus an invasive and/or toxin-mediate disease?
How many serotypes?
What organ system does C. tetanus infect?
C. tetanus is a noninvasive, toxin-mediated disease with one serotype.
Tetanus toxin is a neurotoxin that affects the CNS and PNS
What are the subunits of the tetanus toxin?
What do each do?
Subunits A and B
B subunit binds to neuronal ganglioside
A subunit has neurotoxin activity
What neurotransmitters does tetanus toxin affect?
inhibits the release of glycine and GABA resulting in spastic paralysis and convulsive contractions aka locked jaw
What are the clinical syndromes associated with C. tetani... What is the incubation period? What is are the major muscle symptoms? Bonus question: which muscle groups? Is fever involved? Is sensory deficit involved? Note: we'll mention respiration next…
Incubation period is 4 days to several weeks
Main clinical feature is violent muscle spasm, predominently the FLEXOR muscles, plus clenched teeth, and neck and back arched (these are extensors)
Symmetrical paralysis is unique to tetanus (along with strycnine)
No fever
No sensory deficit
Respiratory complications…
What pharyngeal and respiratory complications can occur with C. tetani?
respiratory failure possible
aspiration, dysphagia, and oral pharyngeal involvement
complications may be pulmonary infections and respiratory problems
What is the Dx for C. tetani…
Clinical vs lab or both?
mainly clinical Dx and Hx
the organism is rarely still in the wound
the exotoxin causes symptoms
What is the Tx for C. tetani (list 5 treatments including 2 antibiotics)?
human tetanus Ig
penicillin plus wound debridement (penicillin is used for Gram +)
metronidazole is used if there is a penicillin allergy
respiratory support if necessary
immunization with tetanus toxiod to prevent recurrence
What are the two drugs used for C. tetani and why?
Penicillin is used for Gram +. It is a cell wall inhibitor.
Metronidazole is used if there is a penicillin allergy. It is a DNA replication inhibitor used for anaerobes.
What is the prognosis of C. tetani infection?
60% fatality rate due to pulmonary complications and secondary infections
This is why we get vaccinated
What is the immunization for C. tetani?
What is the immunization and booster schedule and what the vaccine is called.
DPT vaccine (diphtheria, pertussis, tetanus) Three doses in first 6 months. Booster at year 1, prior school entry, and every 10 years.
Inactivated toxiod vaccine
Due to the severity of C. tetanus, there is a prophylaxis protocol if a person has a possibly infected wound.
Wounds are either…
1) less than 6 hours old, clean, non-penetrating with neglible tissue damage
2) other wounds
In each circumstance, what prophylactic Tx is required for…
A) Pt with vaccine within 5 years?
B) Pt with vaccine between 5 and 10 years?
C) Pt with vaccine more than 10 years?
D) Pt with unknown vaccine status?
A) 1 and 2: no Tx required
B) 1 and 2: give one vaccine of inactivated toxiod
C) 1: give one vaccine of inactivated toxiod. 2: one vaccine plus human tetanus Ig
D) 1: three course vaccine. 2: three course vaccine plus human tetanus Ig
Slide 30 has flow chart.
What is the bacteria and spore shape of Clostridium botulism?
Gram + rod with subterminal oval spores
Spore location is not diagnostic
What is the general epidemiology of C. botulism…
Incidence level?
Natural habitat vs clinically-relevant habitat?
What is wound botulism?
What is the source of infant botulism?
(we discuss these latter two questions later in the deck)
Very low incidence
Soil organism that is often found in canned foods and smoked fish.
Botulism spores can germinate, grow, and produce botulism toxin in 2-3 days
Wound botulism is rare. Spores germinate in a wound.
Infant botulism is from honey. C. botulism grows anaerobically in the GI tract.
Are botulism spores heat labile?
Is botulism toxin heat labile?
Spores are resistant to heat
Toxin is heat labile
therefore cook all canned foods
Let's chat about botulism toxin… Is it resistant to heat? Is it resistant to stomach acid? How many types of toxins #? Which are the most common? How many subunits?
Heat labile
Resistant to stomach acid
7 types of toxin (A to G) with A, B, and E being the most common
two subunits to each toxin
Pathogenesis…
Is C. botulism invasive?
What tissue is ultimately affected?
How does the toxin travel to that tissue?
C. botulism is not invasive.
Affects nerves: flaccid paralysis (flaccid descending paralysis. Starts with the head and goes down. If hits respiratory muscles, you’re dead.)
The botulism toxin is absorbed in the intestine, carried through blood to nerves.
The toxin binds to a receptor on the nerve an is taken up by the nerve.
What does botulism toxin do to nerves?
blocks acetylcholine release from nerve at neuromuscular junction
details: the toxin is a protease that degrades the Ach vessicle docking proteins
What are the clinical symptoms of botolulism toxin… Main symptom? Fever? Mental status? Sensory system? Affects on pharynx? Affects on eyes? Respiration?
Flaccid paralysis with bilateral symmetry in peripheral and cranial nerves
No fever
Normal mental status
No sensory deficit
Dysphagia and dry throat
Diplopia (double vision) and diluted pupils
May affect respiratory muscles
