2. INTRODUCTION
Botulism is an acute neurologic disorder that causes
potentially life-threatening neuroparalysis due to a
neurotoxin produced by Clostridium botulinum. The toxin
binds irreversibly to the presynaptic membranes of
peripheral neuromuscular and autonomic nerve
junctions. Toxin binding blocks acetylcholine release,
resulting in weakness, flaccid paralysis, and, often,
respiratory arrest. Cure occurs following sprouting of new
nerve terminals.
The 3 main clinical presentations of botulism include
infant botulism (IB), foodborne botulism (FBB), and
wound botulism (WB). Additionally, because of the
potency of the toxin, the possibility of botulism as a
bioterrorism agent or biological weapon is a great
3. Infant botulism is caused by ingested C botulinum spores that
germinate in the intestine and produce toxin. These spores
typically come from bee honey or the environment. Most
infants fully recover with supportive treatment; the attributed
infant mortality rate is less than 1%. Improperly canned or
home-prepared foods are common sources of the toxin that
can result in foodborne botulism. Wound botulism results
from contamination of a wound with toxin-producing C
botulinum. Foodborne botulism and wound botulism occur
predominantly in adults and are the focus of this article.
C botulinum is an anaerobic gram-positive rod that survives in
soil and marine sediment by forming spores. Under anaerobic
conditions that permit germination, it synthesizes and releases
a potent exotoxin. Microbiologically, the organism stains
gram-positive in cultures less than 18 hours old. The organism
may stain gram-negative after 18 hours of incubation,
potentially complicating attempts at diagnosis. On a molecular
weight basis, botulinum toxins are the most potent toxins
known.
4. Eight antigenically distinct C botulinum toxins are
known, including A, B, C (alpha), C (beta), D, E, F, and
G. Each strain of C botulinum can produce only a single
toxin type. Types A, B, E, and, rarely, F cause human
disease. Toxins A and B are the most potent, and the
consumption of small amounts of food contaminated
with these types has resulted in full-blown disease.
During the last 20 years, toxin A has been the most
common cause of foodborne outbreaks; toxins B and E
follow in frequency. In 15% of C botulinum infection
outbreaks, the toxin type is not determined. Toxins C
and D cause disease in various animals. Type G toxin has
been associated with sudden death but not with
neuroparalytic illness. It was isolated from autopsy
material from 5 patients in Switzerland in 1977.
5. ETIOLOGY
Causes of wound botulism have been associated with
traumatic injury involving contamination with soil, chronic
abuse of intravenous drugs (e.g, black-tar heroin), and
cesarean delivery. Wound botulism illness can occur even
after antibiotics are administered to prevent wound infection.
Foodborne botulism results from the ingestion of preformed
neurotoxins; A, B, and E are the most common. On average,
24 cases of foodborne botulism are reported annually.
High-risk foods include home-canned or home-processed
low-acid fruits and vegetables; fish and fish products; and
condiments, such as relish and chili peppers.
Commercially processed foods and improperly handled fresh
foods are occasionally associated with botulism outbreaks.
Outbreaks of foodborne botulism in restaurants, schools, and
private homes have been traced to uncommon sources, such
as commercial pot-pies, baked potatoes, beef stew, turkey
loaf, sautéed onions, chopped garlic in oil, and cheese sauce.
6. EPIDEMIOLOGY
Between 1990 and 2000, the Centers for Disease Control reported 263 individual
'cases' from 160 foodborne botulism 'events' in the United States with a case-fatality
rate of 4%. Thirty-nine percent (103 cases and 58 events) occurred in Alaska, all of
which were attributable to traditional Alaska aboriginal foods. In the lower 49 states,
home-canned food was implicated in 70 (91%) events with canned asparagus being
the most numerous cause. Two restaurant-associated outbreaks affected 25 persons.
The median number of cases per year was 23 (range 17–43), the median number of
events per year was 14 (range 9–24). The highest incidence rates occurred in Alaska,
Idaho, Washington, and Oregon. All other states had an incidence rate of 1 case per
ten million people or less.[20]
The number of cases of food borne and infant botulism has changed little in recent
years, but wound botulism has increased because of the use of black tar heroin,
especially in California.
Botulism outbreaks and deaths from 1950-1997
7. PATHOPHYSIOLOGY
The mechanism of action involves toxin-mediated blockade of
neuromuscular transmission in cholinergic nerve fibers. This
is accomplished by either inhibiting acetylcholine release at
the presynaptic clefts of the myoneural junctions or by
binding acetylcholine itself. Toxins are absorbed from the
stomach and small intestine, where they are not denatured by
digestive enzymes. Subsequently, they are hematogenously
disseminated and block neuromuscular transmission in
cholinergic nerve fibers. The nervous, gastrointestinal,
endocrine, and metabolic systems are predominantly affected.
Because the motor end plate responds to acetylcholine,
botulinum 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
8. 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 users (particularly those
who use black-tar heroin), 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
9. CLINCAL SIGNS AND SYMPTOMS
Foodborne botulism
Foodborne botulism should be suspected in patients who present with an
acute gastrointestinal illness associated with neurologic symptoms.
Symptoms usually appear within 12-36 hours following consumption of
contaminated food products. The severity of the illness varies from mild to
severe, but death can occur within 24 hours.
The incubation period is usually 18-36 hours. Depending on toxin dose, the
incubation period ranges from 2 hours to 8 days. The onset of symptoms can
be abrupt or can evolve over several days.
10. Wound botulism
Patients with wound botulism typically have a history of
traumatic injury with wounds that are contaminated with soil.
Since 1994, the number of patients with wound botulism who
have a history of chronic intravenous drug abuse has increased
dramatically. In most cases, black-tar heroin has been the
implicated vehicle. A study by Yuan et al followed 17 heroin
users who had recurrent botulism after using black-tar heroin.
Physicians need to be alert to recognize botulism, especially in
patients who use black-tar heroin or in those with a history of
injection drug–associated botulism.[4]
Rare cases of wound botulism after cesarean delivery have been
documented.
Aside from a longer incubation period, wound botulism is
similar to foodborne botulism. The incubation period of wound
botulism ranges from 4-14 days, with a mean of 10 days. Unlike
foodborne botulism, wound botulism causes no gastrointestinal
symptoms. Patients may be febrile, but this is more likely due to
the wound infection rather than the wound botulism. In many
cases, the wound appears benign.
12. Generally, botulism progresses as follows:Preceding or
following the onset of paralysis are nonspecific findings
such as nausea, vomiting, abdominal pain, malaise,
dizziness, dry mouth, dry throat, and, occasionally, sore
throat. Except for nerves I and II, the cranial nerves are
affected first.
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 symmetric descending paralysis or
weakness of motor and autonomic nerves.
Respiratory muscle weakness may be subtle or
progressive, advancing rapidly to respiratory failure.
Progressive muscle weakness occurs and often involves
the muscles of the head and neck, as well as intercostal
diaphragmatic muscles and those of the extremities.
13. The autonomic nervous system is also involved.
Manifestations of this include the following:
1 Paralytic ileus advancing to severe constipation
2 Gastric dilatation
3 Bladder distention advancing to urinary retention
4 Orthostatic hypotension
5 Reduced salivation
6 Reduced lacrimation
14. Other neurologic findings include the following:
Changes in deep tendon reflexes, which may be either intact or diminished
Incoordination due to muscle weakness
Absence of pathologic reflexes and normal findings on sensory and gait
examinations
Normal results on mental status examination
Many patients with foodborne botulism and wound botulism are afebrile.
16. DIAGNOSIS
Laboratory Studies
Laboratory tests are not helpful in the routine diagnosis of botulism.
WBC counts and erythrocyte sedimentation rates are normal.
Cerebrospinal fluid is normal, except for occasional mild elevations in
protein concentration.
A mouse neutralization bioassay confirms botulism by isolating the
botulism toxin.
Toxin may be identified in serum, stool, vomitus, gastric aspirate, and
suspected foods. C botulinum may be grown on selective media from
samples of stool or foods. Note that the specimens for toxin analysis should
be refrigerated, but culture samples of C botulinum should not be
refrigerated.
Because intestinal carriage is rare, identifying the organism or its toxin in
vomitus, gastric fluid, or stool strongly suggests the diagnosis.Isolation of
the organism from food without toxin is insufficient grounds for the
diagnosis.
Only experienced personnel who have been immunized with botulinum
toxoid should handle the specimens.
Because the toxin may enter the blood stream through the eye or via small
breaks in the skin, precaution is warranted.
Wound cultures that grow C botulinum suggest of wound botulism.
17. Other Tests
Patients with botulism may have mild nonspecific
abnormalities on electrocardiography.
Results from nerve conduction studies are normal, and
electromyography (EMG) reveals reduced amplitude of
compound muscle action potentials.
EMG may be useful in establishing a diagnosis of botulism, but
the findings can be nonspecific and nondiagnostic, even in
severe cases. Characteristic findings in patients with botulism
include brief low-voltage compound motor-units, small M-
wave amplitudes, and overly abundant action potentials. An
incremental increase in M-wave amplitude with rapid
repetitive nerve stimulation may help to localize the disorder
to the neuromuscular junction.
Single-fiber EMG may be a more useful and sensitive method
for the rapid diagnosis of botulism intoxication, particularly in
the absence of signs of general muscular weakness.
The results of the edrophonium chloride, or Tensilon, test for
myasthenia gravis may be falsely positive in patients with
botulism. If positive, it is typically much less dramatically
positive than in patients with myasthenia gravis.
18. TREATMENT
Medical Care
Rigorous and supportive care is essential in patients with
botulism.
Meticulous airway management is paramount, as respiratory
failure is the most important threat to survival in patients with
botulism.Patients with symptoms of botulism or known
exposure should be hospitalized and closely observed.
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 rapidly and
hypoxemia with hypercarbia is present.
Many patients require intubation and ventilatory support for a
few days to months.
Tracheostomy may prove necessary to manage secretions.
19. Patients with bowel sounds are administered cathartics
and enemas to remove unabsorbed botulinum toxin from
the intestine.
Magnesium salts, citrate, and sulfate should not be
administered because magnesium can potentiate the
toxin-induced neuromuscular blockade.
Stress ulcer prophylaxis is also a standard component of
intensive care management.
If an ileus is present, nasogastric suction and intravenous
hyperalimentation are very helpful supportive measures.
If no ileus is present, tube feeding can be used for
nutritional supplementation.
A Foley catheter is often used to treat bladder
incontinence. This must be monitored conscientiously
and changed regularly.
20. Measures to reduce the risk of nosocomial infections include
the following:
Close observation for hospital-acquired infections, especially
pneumonia(particularly aspiration pneumonia), is necessary,
as is precaution to prevent aspiration. Aggressive pulmonary
toilet with clearance of secretions, ventilatory support, and
incentive spirometry are typically used.
Close observation for urinary tract infection is essential. Foley
catheters should be changed on a regular basis.
Meticulous skin care is required to prevent decubital ulcers
and skin breakdown.
Careful attention to peripheral and central intravenous
catheters with regular site rotation to reduce the risks of
thrombophlebitis, cellulitis, and line infections should be part
of the supportive care.
Deep venous thrombosis (DVT) prophylaxis is also a standard
component of intensive care management.
21. Surgical Care
Wound botulism requires incision and thorough
debridement of the infected wound, antitoxin therapy,
and high-dose intravenous penicillin therapy.
Diet
Nasogastric suction and intravenous hyperalimentation
are important when an ileus is present. If no ileus is
present or when the ileus resolves, tube feeding can be
used for nutritional supplementation.
Oral intake should be reinstituted gradually under the
following conditions:Respiratory status is stable without
mechanical ventilation.
Swallowing safety has been assessed and confirmed with
a swallowing study, as appropriate.
Ileus has resolved.
23. MEDICATIONS
Antibiotics are useful in wound botulism, but they have
no role in foodborne botulism.
1. Antibiotics:
- Penicillin G (Pfizerpen): Preferred drug of choice for
wound botulism. Interferes with synthesis of cell wall
mucopeptide during active multiplication, resulting in
bactericidal activity against susceptible microorganisms.
(Adjunctive to antitoxin: 20 million units/day IV divided
q4-6hr)
24. - Chloramphenicol (Chloromycetin): Alternate to
penicillin. Binds to 50S bacterial-ribosomal subunits and
inhibits bacterial growth by inhibiting protein synthesis.
Effective against gram-negative and gram-positive
bacteria. (50 mg/kg/day IV divided q6hr; in exceptional
cases, patients with moderately resistant organisms or
severe infections may require increased dosage up to 100
mg/kg/day; decrease these high doses as soon as possible)
- Clindamycin (Cleocin): Alternative to penicillin.
Inhibits bacterial growth, possibly by blocking
dissociation of peptidyl tRNA from ribosomes, causing
RNA-dependent protein synthesis to arrest. (150-450 mg
PO q6-8hr; not to exceed 1.8 g/day
1.2-2.7 g/day IV/IM divided q6-12hr; not to exceed 4.8
g/day)
25. 2. Antitoxins:
-Botulinum antitoxin, heptavalent (HBAT): Investigational
antitoxin indicated for naturally occurring noninfant botulism. Equine-
derived antitoxin that elicits passive antibody (ie, immediate immunity)
against Clostridium botulinum toxins A, B, C, D, E, F, and G.
Each 20-mL vial contains equine-derived antibody to the 7 known
botulinum toxin types (A through G) with the following nominal
potency values: 7500 U anti-A, 5500 U anti-B, 5000 U anti-C, 1000 U
anti-D, 8500 U anti-E, 5000 U anti-F, and 1000 U anti-G.
Investigational antitoxin indicated for naturally occurring noninfant
botulism
20 mL (1 vial) IV infusion; dilute further with 0.9% NaCl to 1:10 ratio
before administering
Administer slowly by IV infusion via volumetric infusion pump;
minimize allergic reactions by starting at 0.5 mL/min for initial 30
minutes
If no infusion-related reaction, may increase to 1 mL/min IV for next 30
minutes, then if no reaction evident, may increase to 2 mL/min for
remainder of infusion
26. COMPLICATIONS
1. Nosocomial infectionsHospital-acquired pneumonia, especially
aspiration pneumonia, can occur.Atelectasis and poor secretion
clearance also increase the risk of hospital-acquired pneumonia.
Urinary tract infection can occur from in-dwelling Foley catheters.
Skin breakdown and decubitus formation can occur.
Thrombophlebitis, cellulitis, and line infections can occur. These
patients often have peripheral and central intravenous catheters for
prolonged periods.
Fungal infections can occur; the predisposing factors include
prolonged hospitalization, parenteral nutrition, and central venous
catheters. DVT prophylaxis is essential to reduce the risk of these
potential complications. DVT and pulmonary embolism (PE) are
potential complications because patients can be bedridden for
weeks to months.
Stress ulcers can occur and are common in the intensive care unit
setting. Stress ulcer prophylaxis is essential to reduce the risk of this
potential complication.
2. Hypoxic tissue damage can lead to permanent neurologic deficits.
3. Death
27. PROGNOSIS
Botulism due to type A toxin is generally more severe than
that caused by type B or E.
Mortality rates vary based on the age of the patient and the
type of botulism. Foodborne botulism carries an overall
mortality rate of 5-10%. Botulism carries a higher mortality
rate in patients older than 60 years than in younger patients.
Wound botulism carries a mortality rate that ranges from 15-
17%. The risk of death due to infant botulism is usually less
than 1%.
The recovery period ranges from 30-100 days. Artificial
respiratory support may be required for months in severe
cases. Full neurologic recovery usually occurs. Hypoxic insults,
although infrequent, can result in permanent deficits. Some
patients experience residual weakness and autonomic
dysfunction for as long as a year after disease onset.
Mortality is due to the following:
Delayed diagnosis and respiratory failure
Hospital complications such as nosocomial infections (usually
pneumonia)
28. PREVENTION
Prompt notification of public health authorities regarding a
suspected case of botulism may prevent further consumption of a
contaminated home-canned or commercial food product.
Foodborne botulism is best prevented by strict adherence to
recommended home-canning techniques. High-temperature
pressure cooking is essential to ensure spore elimination from low-
acid fruits and vegetables. Although boiling for 10 minutes kills
bacteria and destroys the heat labile botulism toxin, the spores are
resistant to heat and can survive boiling for 3-5 hours. Food
contaminated by botulism toxins usually has a putrefactive odor;
however, contaminated food may also look and taste normal. Hence,
terminal heating of toxin-containing food can prevent illness and is
an important preventive measure.
Wound botulism due to intravenous drug abuse can be prevented by
cessation of drug use.
Wound botulism is best prevented by prompt thorough
debridement of contaminated wounds. Prophylactic use of
antibiotics after trauma cannot be relied on to prevent wound
botulism.
29. When preserving food at home, kill C
botulinum spores by pressure cooking at 250°F (120°C)
for 30 minutes.The toxin can be destroyed by boiling
for 10 minutes or cooking at 175°F (80°C) for 30
minutes.
Do not eat or taste food from bulging cans. Discard
food that smells bad.
Cessation of intravenous drug use prevents wound
botulism due to this vehicle.
