Botulism

Clinical Features

The onset of symptoms of inhalation botulism usually occurs from 12 to 36 hours after exposure, but can vary according to the amount of toxin absorbed, and could be reduced following a BW attack. Recent primate studies indicate that the signs and symptoms may not appear for several days when a low dose of the toxin is inhaled versus a shorter time period following ingestion of toxin or inhalation of higher doses.

Cranial nerve palsies are prominent early, with eye symptoms such as blurred vision due to mydriasis, diplopia, ptosis, and photophobia, in addition to other cranial nerve signs such as dysarthria, dysphonia, and dysphagia. Flaccid skeletal muscle paralysis follows, in a symmetrical, descending, and progressive manner. Collapse and obstruction of the upper airway may occur due to weakness of the oropharyngeal musculature. As the descending motor weakness involves the diaphragm and accessory muscles of respiration, respiratory failure may occur abruptly. Progression from onset of symptoms to respiratory failure has occurred in as little as 24 hours in cases of severe foodborne botulism.

The autonomic effects of botulism are manifested by typical anticholinergic signs and symptoms: dry mouth, ileus, constipation, and urinary retention. Nausea and vomiting may occur as nonspecific sequelae of an ileus. Dilated pupils (mydriasis) are seen in approximately 50 percent of cases.

Sensory symptoms usually do not occur. Botulinum toxins do not cross the blood/brain barrier and do not cause CNS disease. However, the psychological sequelae of botulism may be severe and require specific intervention.

Physical examination usually reveals an afebrile, alert, and oriented patient, although the paralysis may limit the patient's ability to respond. Postural hypotension may be present. Mucous membranes may be dry and crusted and the patient may complain of dry mouth or sore throat. There may be difficulty with speaking and swallowing. Gag reflex may be absent. Pupils may be dilated and even fixed. Ptosis and extraocular muscle palsies may also be present. Variable degrees of skeletal muscle weakness may be observed depending on the degree of progression in an individual patient. Deep tendon reflexes may be diminished or absent. With severe respiratory muscle paralysis, the patient may become cyanotic or exhibit narcosis from CO2 retention.

Clinical Features

  • Botulism is characterized by acute afebrile descending symmetric paralysis. Recovery occurs over weeks to months and often requires extensive supportive care.
  • Disease generally begins with evidence of cranial nerve dysfunction and then progresses to muscle weakness (proximal muscle groups are affected first and may be more severely involved).
  • Severity of disease ranges from mild cranial nerve dysfunction to complete flaccid paralysis. Paralysis of pharyngeal or respiratory muscles may result in the need for prolonged mechanical ventilation.
    • Severity of disease correlates with the amount of toxin absorbed into the circulation.
    • Several studies have shown that a shorter incubation period correlates with more severe disease (see References: MacDonald 1985: Type A botulism from sauteed onions; Tacket 1984). Similarly, a study of botulism cases in Japan revealed that patients who had shorter incubation periods had a significantly higher risk of death (see References: Nishiura 2007).
    • Disease caused by toxin type A tends to be more severe than disease caused by toxin type B or E (see References: Shapiro 1998).
    • Among more than 200 patients in an outbreak in Thailand, respiratory failure was less likely to develop in those who did not manifest nausea or vomiting and did not have urinary retention requiring catheterization. Nausea or vomiting and any cranial neuropathy with urinary retention or difficulty swallowing were symptoms most predictive of respiratory failure (see References: Wongtanate 2007).
  • Death can result from airway obstruction or paralysis of respiratory muscles. Death also can result from complications related to prolonged ventilatory support and intensive care, such as aspiration pneumonia and other infectious conditions.
    • Before mechanical ventilation was widely available, the case-fatality rate was about 60% (see References: Shapiro 1998).
    • The case-fatality rate currently is low owing to adequate supportive care; overall the rate is 5% to 10% for foodborne disease and somewhat higher for wound botulism (see References: Shapiro 1998, Werner 2000).
    • In the event of a mass exposure (such as a bioterrorism attack), clinical resources could be overwhelmed rapidly and the case-fatality rate could be much higher.
    • A recent retrospective study of hospitalized foodborne botulism cases in the Republic of Georgia, 1980-2002, found that patients with shortness of breath and impaired gag reflex and without diarrhea were 23 times more likely to die than were patients without this syndrome (see References: Varma 2004). In this case series, the incubation period was similar among those who died and those who survived, as was the likelihood of receiving antitoxin.
  • Clinical features are outlined in the table below.

Clinical Features of Foodborne and Wound Botulism

Note: Information presented is for foodborne and wound botulism; infant botulism is not included, since that condition is distinct from what would be expected in a bioterrorism attack. The presenting features of inhalational botulism likely would be comparable to those of foodborne and wound botulism.

Characteristic

Features

Incubation perioda

—Dependent on level of toxin exposure
—For foodborne botulism, 2 hr–8 days
—For wound botulism, 4-14 days
—Unknown for inhalational botulism; estimated to be 24-36 hr; the only three reported cases in humans had an incubation period of 72 hr

Symptoms (compiled from reports of foodborne botulism outbreaks caused by toxin types A, B, and E)b

—Nausea (88%)c
—Dry mouth (82%)
—Blurred vision (78%)
—Dysphonia (76%)
—Dysphagia (75%)
—Weakness (72%)
—Fatigue (69%)
—Dyspnea (65%)
—Dysarthria (63%)
—Double vision (60%)
—Dizziness (56%)
—Vomiting (52%)c
—Constipation (related to autonomic dysfunction) (45%)
—Sore throat (40%)
—Abdominal cramps or abdominal pain (40%)d
—Diarrhea (35%)c
—Paresthesias (29%)

Signs (compiled from cases of types A and B botulism reported to CDC in 1973 and 1974)d

—Alert mental status (90%)
—Weakness of upper extremities (75%)
—Ptosis (73%)
—Weakness of lower extremities (69%)
—Extraocular muscle weakness (65%)
—Diminished gag reflex (65%)
—Facial nerve dysfunction (63%)
—Dilated or fixed pupils (44%)
—Diminished or absent deep tendon reflexes in affected groups (40%)
—Nystagmus (22%)
—Ataxia (17%)
—Other considerations:
  ~Patients generally afebrile
  ~Mental status generally intact, although patients may appear lethargic
   or have difficulty communicating because of bulbar dysfunction
  ~Sensory exam generally normal

Laboratory features

—Normal CSF glucose, protein, cell count
—Normal CBC
—Normal imaging of brain and spine (ie, CT scan or MRI)
—Characteristic EMG findingse:
  ~Incremental response (facilitation) to repetitive stimulation (not
   always present and often seen only at 50 Hz)
  ~Short duration of motor unit potentials (MUPs); polyphasic MUPs
  ~Decreased amplitude of compound muscle action potentials
   (CMAPs) after a single nerve stimulus (most prominent in proximal
   muscle groups)
  ~Normal sensory nerve function
  ~Normal nerve conduction velocity (motor and sensory)

Complications

—Respiratory failure (which may require prolonged ventilatory support); in some outbreak settings, up to 30%-40% of patients required mechanical ventilation
—Aspiration pneumonia (among patients with respiratory failure)f
—Residual fatigue, dry mouth or eyes, dyspnea on exertion up to several years after initial presentationg

Case-fatality rateh

—5%-10% for foodborne botulismi
—15%-44% for wound botulismj

Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; CBC, complete blood count.

aSee References: Arnon 2001, Franz 1997.
bThe percentages were derived from compiling information available from published reports of large foodborne outbreaks caused by toxin type A, B, or E. The number of cases in each denominator ranged from 30 to 180. See References: Angulo 1998;  from s 1985: Type A botulism; St Louis 1988; Wainwright 1988; Weber 1993.
cGastrointestinal symptoms are uncommon in patients with wound botulism (see References: Merson 1973) and likely would be uncommon in the setting of inhalational exposure.
dSee References: Hughes 1981.
eSee References: Cherington 1998, Maselli 2000.
fSee References: Schmidt-Nowara 1983.
gSee References: Mann 1981, Mann 1983, Wilcox 1989.
hBefore mechanical ventilation was widely available, the case-fatality rate was much higher (about 60%). In the setting of a mass exposure, where intensive-care resources could rapidly be overwhelmed, the case-fatality rate may be higher than that currently observed.
iSee References: Shapiro 1998.
jSee References: Merson 1973, Shapiro 1998, Werner 2000.

Pediatric Considerations

  • Most pediatric cases of botulism occur in infants (ie, infant botulism), although foodborne and wound botulism also can affect the pediatric population.
  • In the event of an aerosol release of botulinum toxin, children may be at an even greater level of risk than adults, since children have a higher number of respirations per minute and consequently could have an increased level of exposure to toxin (see References: AAP 2000).
  • Signs and symptoms of botulism in children following a bioterrorist attack (ie, aerosol or foodborne exposure) would be similar to those seen in adults.
  • Assuring adequate intensive care resources for the pediatric population in the event of a bioterrorism attack involving an agent such as botulinum toxin should be an important priority in bioterrorism preparedness planning.
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