botulism

BotulismBotulismInfectious Diseases, AIDS & Clinical Infectious Diseases, AIDS & Clinical Immunology Research Center TbilisiImmunology Research Center Tbilisi

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

Etiologic AgentEtiologic Agent C. botulinum is an anaerobic

gram-positive organism that form spors;

C. botulinum C. botulinum is in soil and marine environments throughout the world.

C. botulinum C. botulinum elaborates the most potent bacterial toxin.

– SporesSpores UbiquitousUbiquitous Resistant to heat, light, drying and Resistant to heat, light, drying and

radiationradiation Spores may survive boiling for several hours Spores may survive boiling for several hours

at 100 at 100 ooCC Specific conditions for germinationSpecific conditions for germination

– Anaerobic conditionsAnaerobic conditions– Warmth (10-50Warmth (10-50ooC)C)– Mild alkalinityMild alkalinity

NeurotoxinsNeurotoxins Seven different types: A through GSeven different types: A through G

– Different types affect different speciesDifferent types affect different species– All cause flaccid paralysis All 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 be Spores: Higher temperatures to be

inactivatedinactivated

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 and toxins C and D cause illness in birds and

mammalsmammals– toxin G has been associated with sudden toxin G has been associated with sudden

death, but not with neuroparalytic illness, death, but not with neuroparalytic illness, in a few patients in Switzerland. in a few patients in Switzerland.

– Toxin type A produces the most severe Toxin type A produces the most severe syndrome, with the greatest proportion of syndrome, with the greatest proportion of patients requiring mechanical ventilation. patients requiring mechanical ventilation. Toxin type B appears to cause milder Toxin type B appears to cause milder disease than type A.disease than type A.

NeurotoxinsNeurotoxinsNeurotoxin A B C D E F GHuman X X X XHorses X XCattle X X XSheep XDogs X XAvian X XMink & Ferret X X X

EpidemiologyEpidemiology

IngestionIngestion– OrganismOrganism– SporesSpores– NeurotoxinNeurotoxin

Wound contaminationWound contamination InhalationInhalation


Foodborne botulismFoodborne botulism– caused by eating foods that contain caused by eating foods that contain

botulism toxinbotulism toxin Intestinal botulism Intestinal botulism (infant and (infant and

child/adult)child/adult)– caused by ingesting spores of the caused by ingesting spores of the

bacteria which germinate and produce bacteria which germinate and produce toxin in the intestines.toxin in the intestines.

Wound botulism Wound botulism – C. botulinum spores germinate in the C. botulinum spores germinate in the

wound.wound.


The highest incidence rate is reported from The highest incidence rate is reported from the Republic of Georgia and Armenia, where the Republic of Georgia and Armenia, where illness is associated with risky home-canning illness is associated with risky home-canning practices.practices.

In the United States during 1990–2000, the In the United States during 1990–2000, the median number of foodborne cases of median number of foodborne cases of botulism per year was 23 (range, 17–43). botulism per year was 23 (range, 17–43).

Since the early1990s, cases in the United Since the early1990s, cases in the United States have occurred almost exclusively in States have occurred almost exclusively in injection drug users.injection drug users.

PathogenesisPathogenesis Toxin enters bloodstream from mucosal surface or Toxin enters bloodstream from mucosal surface or

wound wound Binds to peripheral cholinergic nerve endingsBinds to peripheral cholinergic nerve endings Inhibits release of acetylcholine, preventing Inhibits release of acetylcholine, preventing

muscles from contractingmuscles from contracting Symmetrical, descending paralysis occurs Symmetrical, descending paralysis occurs

beginning with cranial nerves and progressing beginning with cranial nerves and progressing downwarddownward

Can result from airway obstruction or paralysis of Can result from airway obstruction or paralysis of respiratory muscles respiratory muscles

Secondary complications related to prolonged Secondary complications related to prolonged ventilatory support and intensive careventilatory support and intensive care

Clinical ManifestationsClinical Manifestations

Food-borne botulismFood-borne botulism Incubation period Incubation period -- 18-36 h 18-36 h

(depending on toxin dose can range (depending on toxin dose can range from a few hours to several days).from a few hours to several days).

Home-canned goods (foodborne)Home-canned goods (foodborne)– particularly low-acid foods such as particularly low-acid foods such as

asparagus, beets, and cornasparagus, beets, and corn

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

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 After traumatic injury involving contamination

with soil;with soil; After cesarean deliveryAfter cesarean delivery After antibiotics have been given to prevent After antibiotics have been given to prevent

wound infection.wound infection. (When present, fever is probably attributable (When present, fever is probably attributable

to concurrent infection with other bacteria).to concurrent infection with other bacteria).

Intestinal (infant) Intestinal (infant) botulismbotulism May be one cause of sudden infant death.May be one cause of sudden infant death. Honey can contain Honey can contain C. botulinumC. botulinum spores spores

– not recommended for infants <12 months not recommended for infants <12 months oldold

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

DiagnosisDiagnosis A diagnosis of botulism must be A diagnosis of botulism must be

considered in patients with considered in patients with symmetric descending paralysis symmetric descending paralysis who are afebrile and mentally who are afebrile and mentally intact.intact.

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

Laboratory diagnosisLaboratory diagnosis

Toxin in serum, stool, gastric Toxin in serum, stool, gastric aspirate, suspected foodaspirate, suspected 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

Laboratory diagnosisLaboratory diagnosis

Botulinum toxin can be detected by Botulinum toxin can be detected by a variety of techniques, including: a variety of techniques, including:

Enzyme-linked immunosorbent Enzyme-linked immunosorbent assays (ELISAs);assays (ELISAs);

Electrochemiluminescent (ECL) Electrochemiluminescent (ECL) teststests

Botulism Differential Botulism 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

TreatmentTreatment

Persons of all ages (including infants) in Persons of all ages (including infants) in whom botulism is suspected should be whom botulism is suspected should be hospitalized immediately in an intensive hospitalized immediately in an intensive care setting, with frequent monitoring of care setting, with frequent monitoring of vital capacity and mechanical ventilation if vital capacity and mechanical ventilation if required.required.

In adults, botulism can be treated by passive In 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 which blocks the action of the toxin circulating in the bloodcirculating in the blood

TreatmentTreatment Intensive care immediatelyIntensive care immediately

– Ventilator for respiratory failure Ventilator 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

Equine antitoxinEquine antitoxin– Trivalent and bivalent antitoxins available Trivalent and bivalent antitoxins available

through the CDCthrough the CDC– Licensed trivalent antitoxin neutralizes Licensed trivalent antitoxin neutralizes

type A, B, and E botulism toxinstype A, B, 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 Effectiveness for inhalation botulism has

not been provennot been proven– Does not reverse current paralysis, but Does not reverse current paralysis, but

may limit progression and prevent nerve may limit progression and prevent nerve damage if administered earlydamage if administered early

Hypersensitivity to equine antitoxinHypersensitivity to equine antitoxin– 9% of people experience some 9% of people experience some

hypersensitivityhypersensitivity

Botulism VaccineBotulism Vaccine A toxoid vaccine (antigen types A, A toxoid vaccine (antigen types A,

B, C, D, and E) is available for B, C, D, and E) is available for laboratory workers at high risk of laboratory workers at high risk of exposureexposure

Limited supplies of this vaccine Limited supplies of this vaccine availableavailable

Therapeutic Uses of Therapeutic Uses of Botulism ToxinBotulism Toxin There is a vaccine for botulism There is a vaccine for botulism

that protects against type A, B, C, that protects against type A, B, C, D, and E available for those at D, and E available for those at high risk of exposure. In the event high risk of exposure. In the event of a bioterrorist attack of botulism of a bioterrorist attack of botulism toxin, however, reserves would toxin, however, reserves would quickly be depleted. quickly be depleted.

botulism

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