Clostridium botulinum

1. Botulism-
Clostridium
botulinum
Agnima Anne Varghese
119i5a
Infectious Diseases

2. Pathogen
• Clostridium botulinum is a bacterium that produces dangerous
toxins (botulinum toxins) under low-oxygen conditions.
Botulinum toxins are one of the most lethal substances known.
Botulinum toxins block nerve functions and can lead to
respiratory and muscular paralysis.
• Order – Eubacterium. Gram Positive. Spore forming.
• Strictly anaerobic bacillus that forms a subterminal spore.
• Produces seven distinct toxins, designated types A-G.
• Can produce toxin within 3 weeks. In addition prestorage at
3°C for up to 2-4 weeks stimulates the toxinogenesis of
nonproteolytic C. Botulinum type B at a subsequent storage at
8°C.

5. Epidemology
• Foodborne botulism occurs in outbreaks, whereas other
forms are sporadic.
• Foodborne botulism is associated with home-canned or
fermented foods.
• Infant botulism historically is associated with honey
ingestion.
• Wound botulism is associated with injection drug use of
“black-tar” heroin.
• Botulinum toxins A and B are used for therapeutic and
cosmetic purposes and may cause iatrogenic botulism.
• Botulism is a potential bioterrorism agent deployed by
aerosol or ingestion.

9. Miracle Poison
• The toxins exert their toxic effect primarily by binding and
entering peripheral cholinergic neurons and blocking
acetylcholine release at neuromuscular junctions, leading to
long-lasting descending paralysis.
• It got 7 serotypes (A-G). Has light and heavy chain each.
• Different serotypes bind to different protein and ganglioside
receptors on neuronal cell surfaces and have different cell entry
kinetics. For example, A, D,E and F. bind to SV2 receptors
whereas B and G bind to synaptotagmin I and II. In addition, B,
and C bind to gangliosides with greater affinity than A .E and A2
have been shown to enter cells faster than Al.
Parenteral human lethal dose 0.1–1ng/kg.
Oral lethal dose 1μg/kg

10. BoNT/A
BoNT/A is amphoteric toxin.
Catalytic domain/Light chain- enters
endocytic memberane and reach cytosol.
Cleaves SNARE.
Translocation domain- stabilizes former.
Binding domain- binds neuronal cells
The later 2 are parts of Heavy Chain
This toxin is also
made by
Cl. butyricum and
Cl. baratii

12. Botulism
Route- contaminated food, water, soil and open wounds.
Signs and symptoms
More than 90% of patients with botulism have 3-5 of the following
• Nausea
• Vomiting
• Dysphagia
• Diplopia
• Dilated/fixed pupils
• Extremely dry mouth unrelieved by drinking fluids
Mortality rates vary based on the age and the
type of botulism.
Foodborne botulism mortality rate of 5-10%.
Wound botulism mortality rate 15-17%.
mortalitydue to infant botulism less than 1%

13. •Following the onset of paralysis are nonspecific findings such as
nausea, vomiting, abdominal pain, malaise, dizziness, dry mouth,
dry throat, and, occasionally, sore throat
•Cranial nerve paralysis manifests as blurred vision, diplopia,
ptosis, extraocular muscle weakness or paresis, fixed/dilated
pupils, dysarthria, dysphagia, and/or suppressed gag reflex.
•Additional neurologic manifestations include symmetrical
descending paralysis or weakness of motor and autonomic nerves
•Respiratory muscle weakness may be subtle or progressive,
advancing rapidly to respiratory failure
The autonomic nervous system:
•Paralytic ileus advancing to severe constipation
•Gastric dilatation
•Bladder distention to urinary retention
•Orthostatic hypotension
•Reduced salivation and lacrimation.

14. Ophthalmic manifestations
1. Anticholinergic effects
• Accommodation paresis, with blurred vision
• Mydriasis and poorly reactive pupils
• Dry eye
2. Deficit at the neuromuscular junction
• Ophthalmoplegia manifests as diplopia.
• Blepharoptosis is common.
• Nystagmus may be notedmay be noted
Neurotoxin A may have no specific ophthalmic manifestations.
Low dose is used in BOTOX. 100u of Botox 0.44 ng of BoNT/A

16. BoNT ingestion results in hypotoniabotulinum toxin ingestion
results in hypotonia that manifests as descending symmetric
flaccid paralysis and is usually associated with gastrointestinal
symptoms of nausea, vomiting, and diarrhea. Cranial nerves are
affected early in the disease course. Later complications include
paralytic ileus, severe constipation, and urinary retention. that
manifests as descending symmetric flaccid paralysis and is
usually associated with gastrointestinal symptoms of nausea,
vomiting, and diarrhea. Cranial nerves are affected early in the
disease course. Later complications include paralytic ileus,
severe constipation, and urinary retention.
It cant cross BBB.
Iatrogenic botulism due to accidental overdose of botulinum toxin
(Botox)
Cases of botulism due to Botox overdosage have been reported.
Symptoms vary and can include dysphagia, ptosis, and diplopia,
as well as more severe presentations of systemic weakness or
muscle paralysis.

17. Wound botulism results when wounds are contaminated with C
botulinum spores. Wound botulism has developed following
traumatic injury that involved soil contamination, among injection
drug and after cesarean delivery. The wound may appear
deceptively benign. Traumatized and devitalized tissue provides
an anaerobic medium for the spores to germinate into vegetative
organisms and to produce neurotoxin, which then disseminates
hematogenously.
The nervous, endocrine, and metabolic systems are
predominantly affected.
Symptoms develop after an incubation period of 4-14 days, with a
mean of 10 days.
The clinical symptoms of wound botulism are similar to those of
foodborne botulism except that gastrointestinal symptoms
(including nausea, vomiting, diarrhea) are uncommon.

19. Lab diagnostic
• Presumptive diagnosis based on clinical presentation: acute,
bilateral cranial neuropathies with symmetrical descending
weakness.
• Mouse bioassay is the gold standard.
• Culture of serum, stool, and environmental samples requires
strict anaerobic conditions and is low yield.
• Characteristic electrophysiologic study findings are suggestive
of botulism.

21. Treatment
• Supportive care remains the mainstay of botulism treatment.
• Heptavalent botulinum antitoxin is available for noninfant
botulism in the United States.
• Human botulinum immune globulin (BabyBIG) is available for
the treatment of infant (younger than 1 year) botulism.
.
• Wound botulism requires incision and thorough debridement
of the infected wound, antitoxin therapy, and high-dose
intravenous penicillin therapy.
• Antibiotics are useful in wound botulism, but they have no role
in foodborne botulism.

22. Spirometry, pulse oximetry, vital capacity, and arterial blood gases
should be evaluated sequentially.
Respiratory failure can occur with unexpected rapidity.
Intubation and mechanical ventilation should be strongly
considered when the vital capacity is less than 30% of predicted,
especially when paralysis is progressing
DOC for wound botulism is Pencillin. Alternative is
Chloramphenicol and Clindamycin
Antitoxin indicated for naturally occurring non-infant botulism.
Equine-derived antitoxin that elicits passive antibody against A,
B, C, D, E, F, and G -- Botulinum antitoxin, heptavalent (HBAT)

23. Prevention
• Proper food preparation prevents foodborne botulism.
• There is no currently available vaccine

24. Thank You