Clinical Features

The onset of symptoms of inhalation botulism usually occurs from 12 to 36 hours following exposure, but can vary according to the amount of toxin absorbed, and the onset of the disease could be accelerated following a bioterrorism attack. Symptoms may not appear for several days when a low dose of the toxin is inhaled. At higher dosage levels, signs and symptoms develop in a shorter time period.

Cranial nerve muscle tremors are prominent early, with eye symptoms such as blurred vision due to abnormal dilatation of the pupil and light sensitivity, in addition to other cranial nerve signs such as slurred speech. Skeletal muscle paralysis follows, in a symmetrical, descending, and progressive manner.

Collapse of the upper airway may occur. 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 food-borne botulism.

The autonomic effects of botulism are: dry mouth, painful distended abdomen, constipation, and urinary retention. Nausea and vomiting may occur. Dilated pupils are seen in approximately 50% of cases. Sensory symptoms usually do not occur. Botulinum toxins do not cross the blood/brain barrier and do not cause central nervous system (CNS) disease. However, the psychological consequences of botulism may be severe and require specific intervention.

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

Physical examination usually reveals an alert but disoriented patient. Abnormally low blood pressure 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. Drooping eyelids and paralysis of the ocular muscles 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 present or absent.

With severe respiratory muscle paralysis, the patient may become cyanotic (bluish discoloration of the skin and mucous membranes) or exhibit narcosis from CO2 retention.

Diagnosis

The occurrence of an epidemic in patients without indications of fever will manifest itself by loss of muscle tone and paralysis, which strongly suggests botulinum intoxication.

Food-borne outbreaks tend to occur in small clusters. Higher numbers of cases should raise at least the consideration of a biological warfare attack with aerosolized botulinum toxin. Individual cases might be confused clinically with other neuromuscular disorders such as Guillain-Barre syndrome, myasthenia gravis, or tick paralysis.

Distinguishing Nerve Agent From Botulinum Poisoning

It may become necessary to distinguish nerve agent and/or atropine poisoning from botulinum intoxication.

• Nerve agent poisoning produces copious respiratory secretions and constriction of the pupils, whereas a decrease in secretions is more likely in botulinum intoxication.
• Atropine overdose is distinguished from botulism by its central nervous system excitation (hallucinations and delirium) even though the mucous membranes are dry and abnormal dilatation of the pupil is present.

Mechanism of Toxicity

Botulinum toxin binds to receptors on the nerve fibers (axon) of motor neurons. The toxin is taken into the axon, where it produces its toxic effect on cells; it inactivates the nerve fibers, preventing and blocking neuromuscular transmission.

Recovery follows only after the neuron develops a new nerve fiber (axon), which can take months. The toxin affects both autonomic (involuntarily) and motor (nicotinic) receptors. This interruption of neurotransmission causes cranial nerve and skeletal muscle paralysis.

Medical Management

Supportive care, including prompt respiratory support, can be lifesaving. Respiratory failure due to paralysis of respiratory muscles is the most serious effect and, generally, the cause of death.

Reported cases of botulism prior to 1950 had a mortality rate of 60%. With tracheotomy or intubation and ventilatory assistance, fatalities are less than 5% today.

Prevention of infections is a primary concern, along with hydration, suctioning for ileus, bowel and bladder care, and prevention of bed sores and deep venous thromboses. Intensive and prolonged nursing care may be required for recovery, which may take up to three months for initial signs of improvement, and up to a year for complete resolution of symptoms.

Antitoxin - Early administration of botulinum antitoxin is critical, since the antitoxin can only neutralize the circulating toxin in patients with symptoms that continue to progress. When symptom progression ceases, no circulating toxin remains, and the antitoxin has no effect. Antitoxin may be particularly effective in food-borne cases, where presumably toxin continues to be absorbed through the gut wall.

Three different antitoxin preparations are available in the U.S. A licensed trivalent (types A, B, E) equine antitoxin is available from the Centers for Disease Control and Prevention for cases of food-borne botulism.