2763

Botulism (Clostridium botulinum)

247  Aimee Hodowanec and Thomas P. Bleck

SHORT VIEW SUMMARY

Definition • Botulism is a potential bioterrorism • Characteristic electrophysiologic study findings
• Botulism is a toxin-mediated paralytic illness agent deployed by aerosol or are suggestive of botulism.
caused by Clostridium botulinum. It is ingestion.
Therapy
classified as foodborne botulism, infant
Microbiology • Supportive care remains the mainstay of
botulism, wound botulism, iatrogenic botulism,
• C. botulinum is a gram-positive, strictly botulism treatment.
botulism of undetermined etiology, or
anaerobic bacillus that forms a subterminal • Heptavalent botulinum antitoxin is available
inhalational botulism.
spore. for noninfant botulism in the United States.
• C. botulinum produces eight distinct toxins, • Human botulinum immune globulin (BabyBIG)
Epidemiology
designated types A through H. is available for the treatment of infant
• Foodborne botulism occurs in outbreaks,
(younger than 1 year) botulism. To obtain,
whereas other forms are sporadic. Diagnosis
contact the California Department of Health
• Foodborne botulism is associated with • Presumptive diagnosis based on clinical
Services, Infant Botulism Treatment and
home-canned or fermented foods. presentation: acute, bilateral cranial
Prevention Program (510-540-2646;
• Infant botulism historically is associated neuropathies with symmetrical descending
www.infantbotulism.org).
with honey ingestion. weakness.
• Wound botulism is associated with injection • Mouse bioassay is the gold standard for Prevention
drug use of “black-tar” heroin. botulinum toxin. • Proper food preparation prevents foodborne
• Botulinum toxins A and B are used for • Culture of serum, stool, and environmental botulism.
therapeutic and cosmetic purposes and samples requires strict anaerobic conditions • There is no currently available vaccine.
may cause iatrogenic botulism. and is low yield.

Botulism and tetanus result from intoxication with the protein neuro- the first description of C. botulinum and showed that the organism
toxins elaborated by two related species of Clostridium. The toxins are elaborated a toxin that could induce weakness in animals.5 This was
very similar in structure and function but differ dramatically in their subsequently shown to be type A toxin; type B was discovered in 1904.6
clinical effects because they target different cells in the nervous system. Wound botulism was described in 1943,7 and infant botulism in 1976.8
Botulinum neurotoxins predominantly affect the peripheral neuro- The occurrence of sporadic cases without an apparent etiology, many
muscular junction and autonomic synapses and primarily manifest as related to gastrointestinal colonization, was first reported in 1986.9
weakness. In contrast, although tetanus toxin can affect the same Type A toxin was isolated and purified in 1946.10
systems, its effects reflect tropism for inhibitory cells of the central
nervous system (CNS) and primarily manifest as rigidity and spasm. EPIDEMIOLOGY
Both conditions have potentially high fatality rates, and both are pre- Foodborne botulism is most frequently recognized in outbreaks,
ventable through education and public health measures. whereas the other forms are sporadic. Although commercially canned
Clostridium botulinum produces most cases of botulism, with a few foods were commonly the source of toxin in the early part of this
other clostridial strains accounting for the remainder. Botulinum century, home-canned vegetables, fruits, and fish products are now the
toxins are designated types A through H based on antigenic differ- most common sources. In some cultures, such as among Alaskan
ences.1 Types A, B, E, F and H produce human disease, whereas types Natives, preferred food preparation practices involving fish fermenta-
C and D are almost exclusively confined to animals.2 Type G toxin has tion commonly lead to botulism.11 In China, homemade fermented
not been associated with naturally acquired disease. The clinical forms beans are the leading cause.12 Commercial foods and restaurants are
of botulism include foodborne botulism, infant botulism, wound botu- still occasional sources.13,14 Consumption of peyote for religious
lism, and botulism of undetermined etiology. Botulinum A toxin has reasons has resulted in botulism.15 In the United States, 263 cases
achieved prominence as a therapeutic modality in conditions that occurred from 1990 to 2000 because of 163 foodborne botulism events
result from excessive muscle activity (e.g., torticollis), leading to rare (17 to 43 cases per year).16 Rates of foodborne botulism appear to be
cases of iatrogenic botulism. Botulinum toxin has also been developed declining, with only 11 cases reported to the Centers for Disease
as a weapon, which could be used to contaminate food or beverage Control and Prevention (CDC) in 2010.17
supplies, or be aerosolized. Infant botulism primarily occurs with toxin types A, B, or F.
However, in 2014 a new toxin was discovered in association with a case
HISTORY OF BOTULISM of infant botulism. Toxin type H was identified following a case of
The term botulism derives from the Latin word botulus, or sausage. infant botulism in which the toxin produced was unable to be neutral-
Outbreaks of poisoning related to sausages and other prepared foods ized by any of the existing anti-A through anti-G antitoxins in mouse
occurred in Europe in the 19th century. Justinus Kerner, a district bioassay.18 In the past, infections were attributed to honey ingestion,19
health officer in southern Germany, recognized the connection but other sources have emerged as feeding honey to infants has been
between sausage and the paralytic illnesses of 230 patients in 1820 and discouraged.20 In the absence of competing flora found in children and
made sausage poisoning a reportable disease.3 At about the same time, adults, C. botulinum colonizes the intestine of infants (ages 6 days to
physicians in Russia recognized a disease with similar symptoms, 12 months). Infection occurs as a consequence of absorption of toxin
which they termed fish poisoning.4 In 1897, van Ermengen published produced by C. botulinum in situ.21 From 1992 to 2006, 2419 cases of
2763
 2763.e1
KEYWORDS
anaerobic infection; bioterrorism; botulism; clostridial infections;
foodborne illness; heptavalent botulinum antitoxin; human

Chapter 247  Botulism (Clostridium botulinum)

botulinum antitoxin; infant botulism; paralysis; toxin; wound
botulism
 2764
infant botulism were identified in the United States (average, 2.1 cases anaerobic, it may actually favor the growth of C. botulinum.45 Proper
per 100,000 live births).22 Two infants without other exposures are preparation of food in a pressure cooker will render spores inert.
believed to have contracted botulism through soil contamination.23
Rare cases of infant botulism have been associated with Clostridium PATHOGENESIS
Part III  Infectious Diseases and Their Etiologic Agents

baratii24 or Clostridium butyricum.25 In foodborne botulism, toxin is ingested with the food in which it was
Wound botulism may be caused by either type A or type B organ- produced. It is absorbed primarily in the duodenum and jejunum and
isms. In such cases, C. botulinum spores contaminate the wound, passes into the bloodstream, by which it reaches peripheral cholinergic
leading to subsequent germination and toxin production. Almost synapses (including the neuromuscular junction). Infant botulism and
exclusively associated with injection drug use of “black-tar” heroin, probably adult botulism of unknown etiology have a somewhat differ-
wound botulism was first reported in the United States in the 1990s. ent pathogenesis in that they are acquired through the ingestion of
Spore contamination of heroin during preparation can lead to infec- spores rather than preformed toxin. The infant’s intestinal flora is
tion, particularly in patients who inject by “skin-popping” (i.e., drug thought to be particularly permissive for the germination of spores,
injection into tissue rather than the vein).26,27 The majority of wound which leads to the production of toxin. The spores are acquired from
botulism cases have been reported in California. However, black-tar environmental sources contaminated with soil in which botulinum
heroin-related cases have also been described in Europe, including 12 spore counts are high.46 In adults, achlorhydria and antibiotic use may
cases in Germany in 2005.28-30 predispose to gastrointestinal colonization with C. botulinum. In cases
Adult botulism of unknown etiology usually involves type A toxin, of wound botulism, spores are introduced into a wound, where they
but types B and F have also been implicated.31 Affected adults become germinate and produce toxin. Lastly, in inhalational botulism, the
colonized with and subsequently infected by toxin-producing clos- toxin crosses through the pulmonary alveolar epithelium to gain access
tridia. Adults at risk include those with loss of bowel flora because of to the bloodstream.47 The clinical manifestations of botulism depend
anatomic abnormalities, functional disorders, or antibiotic use.32-35 on the type of toxin produced, rather than the site of its production.
Adult botulism of unknown etiology has also been attributed to types Botulinum toxin is synthesized as a single polypeptide chain of low
B and F31; in this setting, type F botulism was caused by C. baratii.35 potency; the molecular weight varies from 150 to 165 kDa, depending
Botulinum toxin types A and B are approved by the U.S. Food and on the toxin type. The botulinum toxins are zinc-dependent metallo-
Drug Administration (FDA) for cosmetic and therapeutic purposes proteinases,48 as is tetanospasmin (the neurotoxin associated with C.
(e.g., blepharospasm, strabismus, cervical dystonia). Iatrogenic botu- tetani). The toxin is then nicked by a bacterial protease to produce two
lism cases are uncommon, but have been reported with the therapeu- chains, with the light chain constituting about one third of the total
tic36 and unlicensed cosmetic use of botulinum toxin A.37,38 mass. As with tetanospasmin, the chains remain connected by a disul-
Rare cases of inhalational botulism have been associated with the fide bond. The nicked toxin type A becomes, on a molecular weight
intranasal use of contaminated cocaine.39 Inhalation is also one of the basis, the most potent toxin found in nature. In contrast to the spores,
potential routes of a bioterrorist attack with botulinum toxin. C. botu- the toxin is heat labile. Different toxin types may undergo different
linum has been considered a high enough probability for use in bioter- postsynthetic processing.49
rorism that it has been targeted by a blue ribbon panel for special In the laboratory, the clostridial toxins have provided a major tool
research emphasis. A bioterrorist attack with this toxin could cause for understanding the mechanisms of neurotransmitter release. Once
intoxication via ingestion or as an aerosol. In the event of intentional present at the synapse, the toxins prevent the release of acetylcholine
contamination of food with botulinum toxin, the signs and symptoms (ACh). This appears to result from a three-stage process.50 The heavy
of the victims of such an attack would be indistinguishable from a chain of the toxin mediates binding to presynaptic receptors. The
natural outbreak of botulism, except that epidemiologic investigation nature of these receptors is uncertain; different toxin types bind to
might reveal that the common food ingested was not typically associ- different receptors, with type B receptors outnumbering type A recep-
ated with botulism or that different foods in the same area were all tors by a factor of four.51 The toxin enters the cell by receptor-mediated
contaminated. Introduction of toxin into milk trucks or other large, endocytosis.52 Once inside the neuron, the toxin types differ in the
closed food or beverage transports would produce sporadic cases. In mechanisms by which they inhibit ACh release.53 The release of syn-
such a circumstance, individual clinicians would be unlikely to recog- aptic vesicles by an action potential is initiated by an abrupt rise in the
nize an attack early in its development. Automated systems for the intracellular free Ca2+ concentration, mediated by voltage-dependent
collection of epidemiologic data are required for this purpose.40 calcium channels (Fig. 247-1).54 This increase in free calcium triggers
Predicting the consequences of dissemination into the environment an interaction between synaptotagmin (in the vesicle membrane) and
is more problematic because there are no data regarding the stability syntaxin (on the presynaptic cell membrane), clamping the vesicle to
of the toxin in water or sunlight. One CDC expert estimated that an
aerosol release of toxin could affect 10% of people within 500 meters.41
Once in the atmosphere, the decay rate of the toxin is estimated to be
1% to 4% per minute. Modeling an aerosol exposure suggests that Botulinum
substantial inactivation may take up to 2 days, but would be accelerated toxins
by extremes of temperature and humidity.41 A and E

CHARACTERISTICS OF Synaptotagmin Calcium channel

SNAP-25
CLOSTRIDIUM BOTULINUM Syntaxin
C. botulinum is a large, gram-positive, strictly anaerobic bacillus that Synaptobrevin
forms a subterminal spore.42 The species is divided into four physio- Synaptic
logic groups. Group I organisms are proteolytic in culture and can vesicle
Synaptobrevin
produce toxin types A, B, and F. Group II organisms are nonproteo- Botulinum
Syntaxin
lytic and can produce toxin types B, E, and F. Group III organisms toxin C1
produce toxin types C and D, and group IV produces type G. A single
strain almost always produces only one toxin type. Group II organisms Tetanus toxin
Botulinum Synaptic
grow optimally between 25° and 30° C, and the other groups grow toxins B, D, F, G cleft
best between 30° and 37° C. Although each strain of the organism typi-
cally contains several plasmids, only type G toxin is encoded on a
plasmid (unlike C. tetani, in which the toxin apparently is always Presynaptic membrane
encoded on a plasmid).43 FIGURE 247-1  Components of the transmitter release mechanism.
C. botulinum spores are found throughout the world in soil samples SNAP-25, synaptosomal-associated protein-25. (From Bleck TP, Brauner JS.
and marine sediments.44 These spores are able to tolerate 100° C Tetanus. In: Scheid WM, Whitley RJ, Durack DT, eds. Infections of the
at 1 atm for several hours; because boiling renders solutions more Central Nervous System. 2nd ed. New York: Raven Press; 1997:629-653.)
 2765
the presynaptic membrane. Synaptobrevin (also referred to as vesicle- TABLE 247-1  Symptoms and Signs in Patients
associated membrane protein55) also binds to syntaxin and appears to with the Common Types of Human Botulism
dock the vesicle to the membrane at the proper location for fusion.
There are different isoforms of synaptobrevin within neurons; a protein TYPE A (%) TYPE B (%) TYPE E (%)

Chapter 247  Botulism (Clostridium botulinum)

termed cellubrevin performs a similar function in non-neuronal secre- Neurologic Signs and Symptoms
tory cells.56 Synaptophysin, the third major component of this mecha- Dysphagia 96 97 82
nism, probably forms the fusion pore that allows release of the vesicle Dry mouth 83 100 93
contents into the synaptic cleft.57 Diplopia 90 92 39
Clostridial neurotoxins inhibit vesicle release by cleaving peptide Dysarthria 100 69 50
bonds in these proteins.58 Each toxin has a specific locus of activity. Upper extremity weakness 86 64 NA
Tetanospasmin, along with botulinum neurotoxins B, D, F, and G,
Lower extremity weakness 76 64 NA
cleaves synaptobrevin.59,60 Tetanospasmin and botulinum neurotoxin
Blurred vision 100 42 91
B appear to share the same cleavage site on synaptobrevin.61 In con-
trast, botulinum toxins A62 and E act on the 25-kDa synaptosomal- Dyspnea 91 34 88
associated protein-25 (SNAP-25),63 and botulinum toxin C1 affects Paresthesias 20 12 NA
syntaxin. The pathogenesis of toxin H has not yet been characterized. Gastrointestinal Signs and Symptoms
The toxins only affect the free proteins; once they have complexed to Constipation 73 73 52
cause transmitter release, they are not subject to attack.64 Synapto- Nausea 73 57 84
brevin and synaptotagmin cleavage also occurs normally, as an effect Vomiting 70 50 96
of an endogenous protease, and these proteins are probably involved Abdominal cramps 33 46 NA
in organelle recycling.65 The endogenous protease does not appear
Diarrhea 35 8 39
homologous to the clostridial toxins. However, the result is that stimu-
lation of the presynaptic cell (e.g., the alpha motor neuron) fails to Miscellaneous Symptoms
produce transmitter release, thus producing paralysis in the motor Fatigue 92 69 84
system or autonomic dysfunction when parasympathetic nerve termi- Sore throat 75 39 38
nals or autonomic ganglia are involved. Dizziness 86 30 63
Once damaged, the synapse was originally thought to be rendered Neurologic Findings
useless. Because of the widespread interest in the therapeutic use of Ptosis 96 55 46
botulinum toxin, substantial research into the mechanisms of recovery Diminished gag reflex 81 54 NA
is underway. The initial recovery of function in type A botulism Ophthalmoparesis 87 46 NA
requires sprouting of the presynaptic axon and the subsequent forma-
Facial paresis 84 48 NA
tion of a new synapse. Later, the original synapse recovers, and the
Tongue weakness 91 31 66
newer ones are pruned away.66 With type F botulism, recovery is sub-
stantially faster, suggesting that the original synapse regains function Pupils fixed or dilatated 33 56 75
more rapidly.67 Nystagmus 44 4 NA
Botulinum toxin is transported within nerves in a manner analo- Upper extremity weakness 91 62 NA
gous to tetanospasmin and can thereby gain access to the CNS. Lower extremity weakness 82 59 NA
However, symptomatic CNS involvement is rare.68 Ataxia 24 13 NA
DTRs diminished or absent 54 29 NA
CLINICAL MANIFESTATIONS DTRs hyperactive 12 0 NA
The classic presentation of botulism is that of a patient who develops
Initial Mental Status
acute, bilateral cranial neuropathies associated with symmetrical
Alert 88 93 27
descending weakness. The CDC suggests attention to these cardinal
features: (1) fever is absent (unless a complicating infection occurs), Lethargic 4 4 73
(2) the neurologic manifestations are symmetrical, (3) the patient Obtunded 8 4 0
remains responsive, (4) the heart rate is normal or slow in the absence DTRs, deep tendon reflexes; NA, not available.
of hypotension, and (5) sensory deficits do not occur (except for Data from Tacket CO, Rogawski MA. Botulism. In: Simpson LL, ed. Botulinum
Neurotoxin and Tetanus Toxin. San Diego, CA: Academic Press; 1989:351-378;
blurred vision).35 The first two features were important for the exclu- Hughes JM. Botulism. In: Scheld WM, Whitley RJ, Durack DT, ed. Infections of the
sion of poliomyelitis; rare exceptions have been noted to most of these Central Nervous System. New York: Raven Press; 1991:589-602; and Weber JT,
generalizations. Hibbs RG, Darwish A, et al. A massive outbreak of type E botulism associated with
Foodborne botulism usually develops between 12 and 36 hours traditional salted fish in Cairo. J Infect Dis. 1993;167:451-454.
after toxin ingestion. The patient initially complains of nausea and a
dry mouth, and diarrhea may occur at this stage. If diarrhea does
occur, it is due to other substances in the ingested material; botulinum
toxin itself will produce constipation when it affects parasympathetic Hughes summarized published reports to analyze differences in
autonomic ganglia. Evidence of cranial nerve dysfunction most com- the clinical findings of intoxication with different toxin types (Table
monly starts with the eyes, reflecting parasympathetic involvement 247-1).74 Type A is significantly more commonly associated with dys-
(blurred vision as a result of pupillary dilation) or involvement of arthria, blurred vision, dyspnea, diarrhea, sore throat, dizziness, ptosis,
cranial nerves III, IV, or VI.69 Pupillary reactions may remain abnormal ophthalmoplegia, facial paresis, and upper extremity weakness. Types
for months after motor recovery.70 Nystagmus is occasionally noted, B and E appear to produce more autonomic dysfunction. None of these
usually in type A disease. Lower cranial nerve dysfunction manifests differences is diagnostic of the toxin type, however. It is important to
as dysphagia, dysarthria, and hypoglossal weakness. Weakness then note that the pupils are either dilatated or unreactive in less than 50%
spreads to the upper extremities, the trunk, and the lower extremities. of patients; although these are useful signs when present, their absence
Respiratory dysfunction may result from either upper airway obstruc- in no way diminishes the likelihood of botulism.
tion (the weakened glottis tending to close during attempted inspira- Infants with botulism present with constipation, which may be fol-
tion) or diaphragmatic weakness. Patients who need mechanical lowed by feeding difficulties, hypotonia, increased drooling, and a
ventilation require mean periods of 58 days (type A) and 26 days (type weak cry.75 Upper airway obstruction may be the initial sign76 and is
B) for ventilatory weaning.71 Recovery may not begin for up to 100 the major indication for intubation.46 In severe cases, the condition
days.72 Autonomic problems may include gastrointestinal dysfunction, progresses to include cranial neuropathies and respiratory weakness,
alterations in resting heart rate, loss of responsiveness to hypotension with ventilatory failure occurring in about 50% of diagnosed patients.
or postural change, hypothermia, and urinary retention.73 The condition progresses for 1 to 2 weeks and then stabilizes for
 2766
another 2 to 3 weeks before recovery starts.78 Relapses of infant botu-
lism may occur.79
Wound botulism lacks the prodromal gastrointestinal disorder of
the foodborne form but is otherwise similar in presentation. Fever, if
Part III  Infectious Diseases and Their Etiologic Agents

present, reflects wound infection rather than botulism. The wound

itself may rarely appear to be healing well while neurologic manifesta-
tions are occurring. Conversely, C. botulinum infection may produce
abscesses80; botulism has also been reported as a result of sinusitis with
this organism after cocaine inhalation.81 The reported incubation
period varies from 4 to 14 days.

0.2 mU
The signs and symptoms exhibited by victims of inhalational botu-
lism are the same as those seen with ingestion. The latency between
2 msec
exposure and clinical disease after inhalation appears to be between 12
hours and 3 days, with maximal disease by about 5 days.41 FIGURE 247-2  Repetitive nerve stimulation in infant botulism.
Botulinum toxin has been used to treat a variety of chronic pain Note the increment in response amplitude during the initial stimulations.
syndromes, achalasia, and anal fissures.82 It has also achieved wide- (Courtesy Vern Juel, MD, Department of Neurology and Laboratory of
Electromyography, University of Virginia, Charlottesville.)
spread notoriety for its use in cosmetic procedures. In 2004, four
patients suffered from clinical symptoms of botulism after the unli-
censed cosmetic use of botulinum toxin A.37
and canned vegetables.88-91 Techniques based on the polymerase chain
DIAGNOSIS reaction and on mass spectrometry are also being explored as potential
A history appropriate to the type of botulism suspected is the most diagnostic tools.92-94
important diagnostic test. If others are already affected, the condition Electrophysiologic studies reveal normal nerve conduction veloci-
is easily recognized. However, because the toxin may not be evenly ties; the amplitude of compound muscle action potentials is reduced
distributed in foodstuffs, the absence of other patients does not elimi- in 85% of cases, although not all motor units may demonstrate this
nate the diagnosis. abnormality.95 Repetitive nerve stimulation at high rates (20 Hz or
Botulism has a limited differential diagnosis. Myasthenia gravis and greater, compared with the 4-Hz rate used in the diagnosis of myas-
the Lambert-Eaton myasthenic syndrome (LEMS) each share some of thenia gravis) may reveal a small increment in the motor response (Fig.
the characteristics of botulism, but are rarely fulminant, and myasthe- 247-2), as opposed to the decrement expected in myasthenia. This test
nia lacks autonomic features. An edrophonium test may be considered, is very uncomfortable and should not be requested unless botulism or
but an improvement in strength is not pathognomonic of myasthenia LEMS is a serious consideration. Botulism can be distinguished elec-
gravis and has been reported in botulism.83 Tick paralysis is excluded trophysiologically from LEMS.96 In infant botulism, the increments
by a careful physical examination because the Dermacentor tick will may be very dramatic. In questionable cases, single-fiber electromyog-
still be attached. Classic acute inflammatory demyelinating polyneu- raphy studies may be useful. There is currently some debate regarding
ropathy (the Guillain-Barré syndrome) frequently begins with sensory the sensitivity of electrodiagnostic techniques in cases of infant botu-
complaints, rapidly produces areflexia, rarely begins with cranial nerve lism.97 The therapeutic use of botulinum A toxin for dystonic disorders
dysfunction, and does not alter pupillary reactivity. Patients with botu- can produce electrophysiologic evidence of toxin dissemination to
lism do not become areflexic until the affected muscle group is com- distant sites.98
pletely paralyzed. The Miller Fisher variant of the Guillain-Barré If botulinum toxin is used as a biological weapon, the diagnosis
syndrome presents with oculomotor dysfunction and may produce would depend on the route of exposure. Contaminated food or bever-
other cranial neuropathies but includes a prominent ataxia that is ages would result in an epidemic resembling that of a natural food-
lacking in botulism. Patients with polio are febrile on presentation and borne outbreak. A deliberate release of botulinum toxin should be
have asymmetrical weakness. Magnesium intoxication may mimic suspected if patients with acute flaccid paralysis and prominent bulbar
botulism.84 Rarely, botulism may be confused with diphtheria, organo- palsies present in large numbers. An unusual toxin type (such as C, D,
phosphate poisoning, or brainstem infarction.85 F, G, or H) or symptoms among patients with a common geographic
Conventional diagnosis of botulism relies on the demonstration of location may suggest an act of bioterrorism.41 The amount of inhaled
toxin in serum, gastric secretions, stool, or food samples. The most toxin–producing disease would probably not produce measurable
sensitive means of botulism toxin detection is the mouse bioassay.86 toxin in blood or other patient samples, except perhaps for nasopha-
After receiving an injection of sample, mice are followed for the devel- ryngeal secretions. Therefore, current approaches to the diagnosis of
opment of symptoms. Toxin type may be determined by injecting botulism and the detection of botulinum toxin would be of limited
infected mice with type-specific botulism antitoxin. Botulism symp- value during an attack. The diagnosis can be confirmed most rapidly
toms are absent from infected mice that receive the appropriate anti- with electromyography.
toxin. Confirmation and toxin typing are obtained in almost 75% of
cases.87 The mouse bioassay is labor and resource intensive, and there- THERAPY
fore, the testing is performed in a limited number of public health The importance of supportive therapy for botulism is underlined by
laboratories. A Biosafety Level 2 containment facility is a minimum the progressive improvement in mortality rates with advances in criti-
requirement for C. botulinum detection and evaluation, given its cal care, especially ventilatory support. The decision to intubate should
potency. Testing should be performed under the direction of local state be based on (1) bedside assessment of upper airway competency, and
or health departments. If after hours, the regional Poison Center (800- (2) changes in vital capacity (in general, an appropriately performed
222-1222) or the CDC’s Emergency Operations Center (770-488-7100) vital capacity measurement of <12 mL/kg frequently indicates intuba-
may be contacted. tion. However, the facial weakness of botulism may preclude a tight
Anaerobic cultures of serum, stool, and the implicated food, if seal on the spirometer mouthpiece, invalidating the test.). One should
available, may assist in making the diagnosis. However, samples rarely not wait for the partial pressure of arterial carbon dioxide (Paco2) to
yield C. botulinum because strict anaerobic conditions are required for rise or the oxygen saturation to fall before intubating the patient. In
growth, and competing fecal flora or nontoxigenic C. botulinum strains contrast to tetanus, the autonomic dysfunction of botulism is rarely life
can make isolation difficult. Toxin excretion may continue up to 1 threatening, and patients who receive appropriate airway and ventila-
month after the onset of illness, and stool cultures may remain positive tor management should recover unless complications supervene.
for a similar period. Patients intubated with high-volume, low-pressure endotracheal tubes
Enzyme-linked immunosorbent assay has been used to detect botu- should not automatically undergo tracheostomy, regardless of the
linum toxin in clinical specimens as well as contaminated food samples, duration of intubation, unless required for mechanical reasons.99 If
such as fish fillets, canned salmon and corned beef, pasta products, contaminated food may still reside in the gastrointestinal tract,
 2767
purgatives may be useful unless ileus has occurred. The detailed critical the only viable treatment options. To minimize additional exposures,
care management of botulism patients is beyond the scope of this text; exposed skin and clothing should be washed with soap and water,
Tacket and Rogawski have presented a useful approach.45 whereas contaminated surfaces should be cleaned with 0.1% hypochlo-
In March 2010, the CDC announced the availability of a new, hep- rite bleach solution if they cannot be avoided for the hours to days

Chapter 247  Botulism (Clostridium botulinum)

tavalent botulinum antitoxin (HBAT). HBAT contains equine-derived required for natural degradation.41
antibody to seven of the known botulinum toxin types (A-G).100 It Although the greatest improvement in muscle strength occurs in
replaced the trivalent (types A, B, and E) equine serum and is the only the first 3 months of recovery from botulism, patients still show
antitoxin available for noninfant botulism in the United States and was improvements in strength and endurance for up to 1 year after disease
FDA approved in 2013. Because of the risk of serious adverse reactions, onset.41,105 With prompt attention and supportive care, the mortality
as well as the potential for lifelong sensitization to equine proteins, rate for botulism ranges from less than 5% to 8%.105 The mortality rate
HBAT is not approved for administration in infants younger than 1 for infant botulism is less than 1%.21
year.101 Human botulinum immune globulin (BabyBIG) was approved Long-term consequences of botulism were detailed in an evaluation
by the FDA in 2003 for the treatment of infants (younger than 1 year) of 211 patients from the Republic of Georgia from 1998 to 2003.
botulism. Use of BabyBIG has resulted in decreased length of intensive Patients interviewed at least 6 months after illness reported higher rates
care unit stay, length of mechanical ventilation, and overall length of of fatigue, weakness, and dyspnea on exertion when compared with
hospital stay.102 The recommended dose is 50 mg/kg as an intravenous controls. Affected patients suffered from limitations in functional
infusion. For suspected cases of infant botulism in any state, the Cali- capacity and impaired psychosocial well-being.106
fornia Department of Health Services, Infant Botulism Treatment and
Prevention Program should be contacted (510-540-2646; PREVENTION
www.infantbotulism.org). In the event of intentional dissemination of The most important aspect of botulism prevention is proper food han-
botulinum toxin, heptavalent antitoxin (ABCDEFG) may be dispensed dling and preparation. It is impractical or undesirable to treat many
by the Department of Defense.41 Unfortunately, there is no anti-H foods in a manner to eliminate C. botulinum spores; hence, methods
botulinum antitoxin currently available. Treatment of botulism due to for the control of botulism focus on the inhibition of bacterial growth
type H botulinum toxin remains supportive. and toxin production.104 Because the toxin is heat labile, terminal
Patients with wound botulism should also undergo débridement, boiling or similarly intense heating of contaminated food will inacti-
even if the wound appears to be healing well. Anaerobic cultures vate it. Food containers that appear to bulge may contain gas produced
should be obtained at the time of surgery. The value of local instillation by C. botulinum and should not be opened. Other foods that appear to
of antitoxin is unknown. The role of antibiotic treatment is untested, be spoiled should not be tasted.
but penicillin G (10 to 20 million units daily) is frequently recom- In the event of an outbreak, foods suspected of being contaminated
mended. Metronidazole may be an effective alternative. Aminoglyco- should be refrigerated until retrieval by public health personnel. Labo-
sides and tetracyclines, which can impair neuron calcium entry, worsen ratory testing for botulism in the United States is only available at the
infant botulism.103 Lysis of C. botulinum in the gut by antibiotics may CDC and several state and city public health laboratories. According
also increase the toxin available in infant botulism.104 This effect has to the Working Group on Civilian Biodefense, persons with potential
not been reported in adult cases but should be considered when gas- exposure in a foodborne botulism outbreak should be monitored
trointestinal infection is suspected. closely for the development of signs and symptoms; antitoxin should
In the event of a bioterrorist attack, several logistical issues would be administered promptly at the first signs of illness.41
make treatment problematic. Based on the limited information avail- Immunity to botulinum toxin does not develop even with severe
able, a large-scale attack (either foodborne or by aerosol) would prob- disease, and the repeated occurrence of botulism has been reported.107
ably not begin to produce symptomatic victims for more than a day, An investigational pentavalent toxoid (ABCDE) vaccine was previ-
thereby delaying diagnosis and containment. Further, the supply of ously available for use among high-risk laboratory workers and mili-
antitoxins is small, reflecting the low incidence of the natural disease. tary personnel in the United States.108 However, in 2011, the CDC
With a large-scale attack, the available antitoxin would be quickly discontinued use of the vaccine because of data suggesting waning
exhausted. The recent discovery of a new botulinum toxin (type H), immunogenicity and frequent local reactions.109 New vaccine strate-
raises the possibility of a bioterrorist attack with an agent against which gies, including recombinant toxin A/B vaccines and inhalational vac-
we have no antitoxin. Thus, airway protection and ventilation may be cines, are currently being investigated.47,110

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