Botulism is a paralytic disease caused by potent protein neurotoxins elaborated by clostridium botulinum. Botulism is characterized by symmetrical, descending, flaccid paralysis of motor and autonomic nerves usually beginning with cranial nerves

1. BotulismBotulism
Infectious Diseases, AIDS & ClinicalInfectious Diseases, AIDS & Clinical
Immunology Research Center TbilisiImmunology Research Center Tbilisi

2. DefinitionDefinition
 Botulism is a paralytic disease
caused by potent protein neurotoxins
elaborated by clostridium botulinum.
 Botulism is characterized by
symmetrical, descending, flaccid
paralysis of motor and autonomic
nerves usually beginning with cranial
nerves

3. Etiologic AgentEtiologic Agent
 C. botulinum is an anaerobic gram-
positive organism that form spors;
 C. botulinumC. botulinum is in soil and marine
environments throughout the world.
 C. botulinumC. botulinum elaborates the most
potent bacterial toxin.

4. – SporesSpores
 UbiquitousUbiquitous
 Resistant to heat, light, drying and radiationResistant to heat, light, drying and radiation
 Spores may survive boiling for several hoursSpores may survive boiling for several hours
at 100at 100 oo
CC
 Specific conditions for germinationSpecific conditions for germination
– Anaerobic conditionsAnaerobic conditions
– Warmth (10-50Warmth (10-50oo
C)C)
– Mild alkalinityMild alkalinity

5. NeurotoxinsNeurotoxins
 Seven different types: A through GSeven different types: A through G
– Different types affect different speciesDifferent types affect different species
– All cause flaccid paralysisAll cause flaccid paralysis
– Only a few nanograms can cause illnessOnly a few nanograms can cause illness
– Binds neuromuscular junctionsBinds neuromuscular junctions
 Toxin: Destroyed by boilingToxin: Destroyed by boiling
 Spores: Higher temperatures to beSpores: Higher temperatures to be
inactivatedinactivated

6. NeurotoxinsNeurotoxins
– toxins A, B, E and F cause illness in humanstoxins A, B, E and F cause illness in humans
– toxins C and D cause illness in birds andtoxins C and D cause illness in birds and
mammalsmammals
– toxin G has been associated with sudden death,toxin G has been associated with sudden death,
but not with neuroparalytic illness, in a fewbut not with neuroparalytic illness, in a few
patients in Switzerland.patients in Switzerland.
– Toxin type A produces the most severeToxin type A produces the most severe
syndrome, with the greatest proportion ofsyndrome, with the greatest proportion of
patients requiring mechanical ventilation. Toxinpatients requiring mechanical ventilation. Toxin
type B appears to cause milder disease thantype B appears to cause milder disease than
type A.type A.

7. NeurotoxinsNeurotoxins
Neurotoxin A B C D E F G
Human X X X X
Horses X X
Cattle X X X
Sheep X
Dogs X X
Avian X X
Mink & Ferret X X X

8. EpidemiologyEpidemiology
 IngestionIngestion
– OrganismOrganism
– SporesSpores
– NeurotoxinNeurotoxin
 Wound contaminationWound contamination
 InhalationInhalation

9. EpidemiologyEpidemiology
 Foodborne botulismFoodborne botulism
– caused by eating foods that containcaused by eating foods that contain
botulism toxinbotulism toxin
 Intestinal botulismIntestinal botulism (infant and child/adult)(infant and child/adult)
– caused by ingesting spores of the bacteriacaused by ingesting spores of the bacteria
which germinate and produce toxin in thewhich germinate and produce toxin in the
intestines.intestines.
 Wound botulismWound botulism
– C. botulinum spores germinate in theC. botulinum spores germinate in the
wound.wound.

10. EpidemiologyEpidemiology
 The highest incidence rate is reported from theThe highest incidence rate is reported from the
Republic of Georgia and Armenia, where illness isRepublic of Georgia and Armenia, where illness is
associated with risky home-canning practices.associated with risky home-canning practices.
 In the United States during 1990–2000, the medianIn the United States during 1990–2000, the median
number of foodborne cases of botulism per yearnumber of foodborne cases of botulism per year
was 23 (range, 17–43).was 23 (range, 17–43).
 Since the early1990s, cases in the United StatesSince the early1990s, cases in the United States
have occurred almost exclusively in injection drughave occurred almost exclusively in injection drug
users.users.

11. PathogenesisPathogenesis
 Toxin enters bloodstream from mucosal surface orToxin enters bloodstream from mucosal surface or
woundwound
 Binds to peripheral cholinergic nerve endingsBinds to peripheral cholinergic nerve endings
 Inhibits release of acetylcholine, preventingInhibits release of acetylcholine, preventing
muscles from contractingmuscles from contracting
 Symmetrical, descending paralysis occursSymmetrical, descending paralysis occurs
beginning with cranial nerves and progressingbeginning with cranial nerves and progressing
downwarddownward
 Can result from airway obstruction or paralysis ofCan result from airway obstruction or paralysis of
respiratory musclesrespiratory muscles
 Secondary complications related to prolongedSecondary complications related to prolonged
ventilatory support and intensive careventilatory support and intensive care

12. Clinical ManifestationsClinical Manifestations

13. Food-borne botulismFood-borne botulism
 Incubation periodIncubation period -- 18-36 h (depending18-36 h (depending
on toxin dose can range from a few hours toon toxin dose can range from a few hours to
several days).several days).
 Home-canned goods (foodborne)Home-canned goods (foodborne)
– particularly low-acid foods such asparticularly low-acid foods such as
asparagus, beets, and cornasparagus, beets, and corn

14.  Nausea, vomiting, diarrheaNausea, vomiting, diarrhea
 Diplopia, dysarthria, dysphonia,Diplopia, dysarthria, dysphonia,
dysphagiadysphagia
 Descending weakness or paralysisDescending weakness or paralysis
– Shoulders to arms to thighs to calvesShoulders to arms to thighs to calves
 Symmetrical flaccid paralysisSymmetrical flaccid paralysis
 No feverNo fever
 Respiratory muscle paralysisRespiratory muscle paralysis

15. Wound botulismWound botulism
 Incubation period –Incubation period – 10 days.10 days.
 Gastrointestinal symptoms are lackingGastrointestinal symptoms are lacking
 Wound botulism has been documented:Wound botulism has been documented:
 After traumatic injury involving contamination withAfter traumatic injury involving contamination with
soil;soil;
 After cesarean deliveryAfter cesarean delivery
 After antibiotics have been given to prevent woundAfter antibiotics have been given to prevent wound
infection.infection.
 (When present, fever is probably attributable to(When present, fever is probably attributable to
concurrent infection with other bacteria).concurrent infection with other bacteria).

16. Intestinal (infant)Intestinal (infant)
botulismbotulism
 May be one cause of sudden infant death.May be one cause of sudden infant death.
 Honey can containHoney can contain C. botulinumC. botulinum sporesspores
– not recommended for infants <12 months oldnot recommended for infants <12 months old

17.  ConstipationConstipation
 LethargyLethargy
 Poor feedingPoor feeding
 Weak cryWeak cry
 Bulbar palsiesBulbar palsies
 Failure to thriveFailure to thrive

18. DiagnosisDiagnosis
 A diagnosis of botulism must beA diagnosis of botulism must be
considered in patients with symmetricconsidered in patients with symmetric
descending paralysis who are afebriledescending paralysis who are afebrile
and mentally intact.and mentally intact.

19. A 14-year-old with botulism. Note the weakness of hisA 14-year-old with botulism. Note the weakness of his
eye muscles and the drooping eyelids in the image toeye muscles and the drooping eyelids in the image to
the left, and the large and non moving pupils in thethe left, and the large and non moving pupils in the
right image.right image.

20. Laboratory diagnosisLaboratory diagnosis
 Toxin in serum, stool, gastric aspirate,Toxin in serum, stool, gastric aspirate,
suspected foodsuspected food
 Culture of stool or gastric aspirateCulture of stool or gastric aspirate
– Takes 5-7 daysTakes 5-7 days
 Electromyography also diagnosticElectromyography also diagnostic
 Mouse neutralization testMouse neutralization test
– Results in 48 hoursResults in 48 hours

21. Laboratory diagnosisLaboratory diagnosis
Botulinum toxin can be detected by aBotulinum toxin can be detected by a
variety of techniques, including: variety of techniques, including:
Enzyme-linked immunosorbent assaysEnzyme-linked immunosorbent assays
(ELISAs);(ELISAs);
Electrochemiluminescent (ECL) testsElectrochemiluminescent (ECL) tests

22. Botulism DifferentialBotulism Differential
DiagnosesDiagnoses
 Guillain-Barré syndromeGuillain-Barré syndrome
 Myasthenia gravisMyasthenia gravis
 StrokeStroke
 Tick paralysisTick paralysis
 Lambert-Eaton syndromeLambert-Eaton syndrome
 Psychiatric illnessPsychiatric illness
 PoliomyelitisPoliomyelitis
 Diabetic ComplicationsDiabetic Complications
 Drug intoxicationDrug intoxication
 CNS infectionCNS infection
 OverexertionOverexertion

23. TreatmentTreatment
 Persons of all ages (including infants) in whomPersons of all ages (including infants) in whom
botulism is suspected should be hospitalizedbotulism is suspected should be hospitalized
immediately in an intensive care setting, withimmediately in an intensive care setting, with
frequent monitoring of vital capacity andfrequent monitoring of vital capacity and
mechanical ventilation if required.mechanical ventilation if required.
 In adults, botulism can be treated by passiveIn adults, botulism can be treated by passive
immunization with a horse-derived antitoxin,immunization with a horse-derived antitoxin,
which blocks the action of the toxin circulatingwhich blocks the action of the toxin circulating
in the bloodin the blood

24. TreatmentTreatment
 Intensive care immediatelyIntensive care immediately
– Ventilator for respiratory failureVentilator for respiratory failure
 Botulinum antitoxinBotulinum antitoxin
– Derived from equine sourceDerived from equine source
– CDC distributesCDC distributes
– Used on a case-by-case basisUsed on a case-by-case basis
 Botulism immune globulinBotulism immune globulin
– Infant cases of types A and GInfant cases of types A and G

25.  Equine antitoxinEquine antitoxin
– Trivalent and bivalent antitoxins availableTrivalent and bivalent antitoxins available
through the CDCthrough the CDC
– Licensed trivalent antitoxin neutralizes type A,Licensed trivalent antitoxin neutralizes type A,
B, and E botulism toxinsB, and E botulism toxins
– Effective in the treatment of foodborne,Effective in the treatment of foodborne,
intestinal, and wound botulismintestinal, and wound botulism
– Effectiveness for inhalation botulism has notEffectiveness for inhalation botulism has not
been provenbeen proven
– Does not reverse current paralysis, but may limitDoes not reverse current paralysis, but may limit
progression and prevent nerve damage ifprogression and prevent nerve damage if
administered earlyadministered early

26.  Hypersensitivity to equine antitoxinHypersensitivity to equine antitoxin
– 9% of people experience some hypersensitivity9% of people experience some hypersensitivity

27. Botulism VaccineBotulism Vaccine
 A toxoid vaccine (antigen types A, B,A toxoid vaccine (antigen types A, B,
C, D, and E) is available for laboratoryC, D, and E) is available for laboratory
workers at high risk of exposureworkers at high risk of exposure
 Limited supplies of this vaccineLimited supplies of this vaccine
availableavailable

28. Therapeutic Uses ofTherapeutic Uses of
Botulism ToxinBotulism Toxin
 There is a vaccine for botulism thatThere is a vaccine for botulism that
protects against type A, B, C, D, and Eprotects against type A, B, C, D, and E
available for those at high risk ofavailable for those at high risk of
exposure. In the event of a bioterroristexposure. In the event of a bioterrorist
attack of botulism toxin, however,attack of botulism toxin, however,
reserves would quickly be depleted.reserves would quickly be depleted.