Botulism

Overview

Organism
History
Epidemiology
Transmission
Disease in Humans
Disease in Animals
Prevention and Control

Organism

Clostridium botulinum
Gram

positive
Obligate anaerobic bacillus
Spores

Ubiquitous
Resistant to heat, light, drying and radiation
Specific conditions for germination

Anaerobic conditions
Warmth (10-50oC)
Mild alkalinity

Neurotoxins

Seven different types: A through G

Different

types affect different species

All cause flaccid paralysis
Only a few nanograms can cause illness
Binds neuromuscular junctions

Toxin: Destroyed by heat and cooking

food at 80oC for 30 minutes
Spores: Higher temperatures to be
inactivated

Neurotoxins
Neurotoxin

Human

Horses
Cattle

X
X

Sheep
Dogs

X
X

Avian

Mink & Ferret

X
X

Structure of a BoNT

Singh, B.R. (2000). Intimate details of the most

poisonous poison. Nature Structural Biology. 7 617-619

Light (L) Chain

Zinc-endopeptidase

activity
specific for different protein
components of vesicle fusion.
50 kDa

Binds to nerve cells

Translocates L chain

Heavy (H) Chain: 3 domains

100 kDa total

Amino-terminal (HN)
Carboxy-terminal (HC)

Responsible

for binding and

penetration of specific cells

Disulfide bond links two

polypeptide chains

3D Representation

Hanson, M. Cocrystal structure of synaptobreven-II bound to BoNT/B. Nature. 7, 687-692

(2000).

History

History

1793, Justinius Kerner

Wurstgift

Botulus = Latin for sausage

1895, Emile von Ermengem
Isolated

organism during Belgium

outbreak

U.S. outbreaks led to improved

industry processing

Transmission

Transmission

Ingestion
Organism
Spores
Neurotoxin

Wound contamination
Inhalation
Person-to-person not documented

Epidemiology

Epidemiology

In U.S., average 110 cases each year

Approximately

25% food-borne
Approximately 72% infant form
Remainder wound form

Case-fatality rate
5-10%

Infective dose- few nanograms

Epidemiology

1977, Largest botulism outbreak

Michigan

- 59 people
Poorly preserved jalapeno peppers

Alaska
27%

of U.S. foodborne botulism cases

1950-2000

226 cases from 114 outbreaks

Disease in Humans

Human Disease

Three forms
Foodborne
Wound
Infant

All forms fatal and a medical

emergency
Incubation period: can range from 6
hours to 2 weeks, typically 12-36 hours

Foodborne Botulism

Preformed toxin ingested from

contaminated food
Most common from home-canned
foods
Asparagus,

green beans, beets, corn,

baked potatoes, garlic, chile peppers,
tomatoes; type A
Improperly fermented fish (Alaska);
type E

110
100
90

Reported Cases

80
70
60
50
40
30
20

10
0

1982

1987

1992
Year

MMWR

1997

2002

Infant Botulism

Most common form in U.S.

Spore ingestion
Germinate

then toxin released

and colonize large intestine

Infants < 1 year old

94% < 6 months old

Spores from varied sources

Honey,

food, dust, corn syrup

110
100
90

Reported Cases

80
70
60
50
40
30
20
10
0

1982

1987

1992

Year
MMWR

1997

2002

Wound Botulism

Organism enters wound

Develops

under anaerobic conditions

From ground-in dirt or gravel
It does not penetrate intact skin
Associated with addicts of black-tar
heroin

Center for Food Security

Adult Clinical Signs

Nausea, vomiting, diarrhea

Double vision
Difficulty speaking or swallowing
Descending weakness or paralysis
Shoulders

to arms to thighs to calves

Symmetrical flaccid paralysis

Respiratory muscle paralysis

Infant Clinical Signs

Constipation
Lethargy
Poor feeding
Weak cry
Bulbar palsies
Failure to thrive

Diagnosis

Clinical signs
Toxin in serum, stool, gastric
aspirate, suspected food
Culture of stool or gastric aspirate
Takes

5-7 days

Electromyography also diagnostic

Mouse neutralization test
Results

in 48 hours

Treatment

Intensive care immediately

Ventilator

for respiratory failure

Botulinum antitoxin
Derived

from equine source

CDC distributes
Used on a case-by-case basis

Botulism immune globulin

Infant

cases of types A and G

Prevention and
Control

Human: Prevention
Do not feed honey to children <1 yr of age
Proper food preservation methods

Proper time, temperature and pressure

80oC for 30 min or 100oC for 10 min

Thus re-heating foods properly can be a controlling
factor.

Prompt refrigeration of foods

Keep susceptible foods out of the
temperature danger zone (4.4 60C).
Boil foods for > 10 minutes
Decontamination

Boil suspected food before discarding

Boil or chlorine disinfect utensils used

Potential Bioterrorism Threat

Aum Shinriky cult

Extremely potent and lethal
Easily produced and transported
Signs of deliberate aerosol or
foodborne release of toxin
No

common source
Large number of acute cases clustered
Uncommon toxin type (C, D, F, G)

Potential Bioterrorism Threat

Point source aerosol release

Incapacitate

or kill 10% of persons

within 0.5 km downwind

CDC surveillance system

Prompt

events

detection of botulism related

Additional Resources

CDC Division of Bacterial and

Mycotic Diseases

http://www.cdc.gov/ncidod/dbmd/
diseaseinfo/botulism_g.htm

Center for Civilian Biodefense

Strategies

http://www.hopkinsbiodefense.org/pages/agents/agentbotox.html

Acknowledgments
Development of this
presentation was funded
by a grant from the
Centers for Disease Control
and Prevention to the
Center for Food Security
and Public Health at Iowa
State University.

Acknowledgments
Author:

Glenda Dvorak, DVM, MS, MPH

Co-author:

Radford Davis, DVM, MPH

Reviewers:

Danelle Bickett-Weddle, DVM, MPH

Jean Gladon, BS

Mode of action of BoNT?

Botulinum toxin is a nerve poison. It

blocks acetylcholine release in
motor neurons, and thereby causes
muscle paralysis.

Affected persons die from

respiratory failure.

Mechanism