BotulismBotulism

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

EpidemiologyEpidemiology

– Food-borne botulismFood-borne botulism

– Intestinal botulismIntestinal botulism – Wound botulism Wound botulism

Food-borne botulismFood-borne botulism

– Caused by eating foods that Caused by eating foods that contain botulism toxincontain botulism toxin

– Outbreaks have been associated Outbreaks have been associated with a variety of foods such as with a variety of foods such as garlic packed in oil, baked garlic packed in oil, baked potatoes wrapped in aluminum potatoes wrapped in aluminum foil, home-canned vegetables, foil, home-canned vegetables, jerky, and fermented fish.jerky, and fermented fish.

Food-borne botulismFood-borne botulism

Food-born botulism can occur when: Food-born botulism can occur when:

1. Food to be preserved is contaminated 1. Food to be preserved is contaminated with spores; with spores;

2. Preservation does not inactivate the 2. Preservation does not inactivate the spores but kills other putrefactive bacteria spores but kills other putrefactive bacteria that might inhibit growth of C. botulinum and that might inhibit growth of C. botulinum and provides anaerobic conditions, that allows provides anaerobic conditions, that allows germination and toxin production; germination and toxin production;

3. Food is not heated to a temperature 3. Food is not heated to a temperature that destroys toxin before being eaten. that destroys toxin before being eaten.

Intestinal botulism Intestinal botulism (infant (infant and child/adult)and child/adult)

Caused by ingesting spores of Caused by ingesting spores of the bacteria which germinate the bacteria which germinate and produce toxin in the and produce toxin in the intestines.intestines.

Intestinal botulism Intestinal botulism (infant (infant and child/adult)and child/adult)

Infants <12 months of age are particularly Infants <12 months of age are particularly susceptible to susceptible to C. botulinumC. botulinum spores spores because their digestive tracts are not fully because their digestive tracts are not fully developed and therefore not able to developed and therefore not able to prevent the germination and subsequent prevent the germination and subsequent toxin production in the intestines. toxin production in the intestines.

Adults or children >12 months rarely Adults or children >12 months rarely develop intestinal botulism, but may be develop intestinal botulism, but may be more susceptible if they have pre-existing more susceptible if they have pre-existing intestinal conditions.intestinal conditions.

Wound botulism Wound botulism

– Wound botulism occurs when Wound botulism occurs when C. botulinumC. botulinum spores infect and spores infect and

germinate in the wound, germinate in the wound, producing toxin which is absorbed producing toxin which is absorbed into the bloodstream.into the bloodstream.

– Typically, there are very few Typically, there are very few

cases of wound botulism reported cases of wound botulism reported each year.each year.

EpidemiologyEpidemiology

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

Number of botulism cases and cases per 100,000 persons in Georgia, 1980–2002.

EpidemiologyEpidemiology

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

Since the early 1990s, cases in the Since the early 1990s, cases in the United States have occurred almost United States have occurred almost exclusively in injection drug users.exclusively in 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)

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 When present, fever is probably

attributable to concurrent infection attributable to concurrent infection with other bacteria.with other bacteria.

Intestinal (infant) Intestinal (infant) botulismbotulism May be one cause of sudden infant May be one cause of sudden infant

death.death.

Honey can contain Honey can contain C. botulinumC. botulinum sporesspores– not recommended for infants not recommended for infants

<12 months old<12 months old

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

The decision to administer botulinum The decision to administer botulinum Antitoxin must be based on a clinical Antitoxin must be based on a clinical diagnosis and cannot be postponed while diagnosis and cannot be postponed while laboratory confirmation is awaited. laboratory confirmation is awaited.

Botulinum antitoxin neutralizes only Botulinum antitoxin neutralizes only toxin molecules that have not yet bound toxin molecules that have not yet bound to nerve endings; it cannot reverse to nerve endings; it cannot reverse existing paralysis. Thus antitoxin should existing paralysis. Thus antitoxin should be given early in the course of illness, be given early in the course of illness, ideally <24 h after symptom onset.ideally <24 h after symptom onset.

TreatmentTreatment

Infant botulism is treated with a licensed human-Infant botulism is treated with a licensed human-origin antitoxin; origin antitoxin; Botulism immune globulin was Botulism immune globulin was approved for use on October 23, 2003 for the treatment approved for use on October 23, 2003 for the treatment of infant botulism caused by types A and G. of infant botulism caused by types A and G.

Other forms of botulism are treated with equine-Other forms of botulism are treated with equine-source antitoxin. source antitoxin.

Treatment with equine-origin antitoxins long Treatment with equine-origin antitoxins long used in the United States is associated with used in the United States is associated with anaphylaxis, other hypersensitivity reactions and anaphylaxis, other hypersensitivity reactions and serum sickness.serum sickness.

Equine antitoxinEquine antitoxin

A new heptavalent despeciated equine A new heptavalent despeciated equine antitoxin has replaced the previously used non-antitoxin has replaced the previously used non-despeciated equine antitoxin in the United despeciated equine antitoxin in the United States.States.

Effective in the treatment of foodborne, Effective in the treatment of foodborne, intestinal, and wound botulismintestinal, and wound botulism

Effectiveness for inhalation botulism has not Effectiveness for inhalation botulism has not been proven.been proven.

PreventionPrevention No prophylaxis or licensed vaccine for No prophylaxis or licensed vaccine for

botulism is available. botulism is available.

An experimental vaccine for An experimental vaccine for administration to laboratory workers administration to laboratory workers is available from the CDC.is available from the CDC.