Botulism

Definition, Etiology, PathogenesisTop

Botulism is a group of systemic signs and symptoms associated with flaccid muscle paralysis caused by botulinum toxin, a bacterial neurotoxin.

1. Etiologic agent: A Clostridium spp bacillus (most frequently C botulinum) that is an obligate anaerobe producing spores and releasing botulinum toxin, a neurotropic exotoxin and one of the most toxic known substances; more rarely, botulism has also been associated with C baratii and C butryricum. After being absorbed into the bloodstream, botulinum toxin blocks the release of acetylcholine from motor nerve endings, causing flaccid muscle paralysis and autonomic dysfunction. Botulinum toxin affects only the peripheral nerves, does not enter the central nervous system (CNS), and does not penetrate intact skin.

To date, 7 serotypes of botulinum toxin have been identified (A-G). The majority of cases of botulism in humans are caused by serotype A or B, less frequently by serotype E. Serotype F is very rare. However, serotype E is the leading cause of food-borne botulism in North America and is primarily associated with food practices in northern aboriginal communities.

Dissolved botulinum toxin is colorless, odorless, and tasteless. It is inactivated by exposure to a temperature of 100 degrees Celsius for 10 minutes. Spores are destroyed at temperatures of 116 to 121 degrees Celsius (pressure cooking).

2. Reservoir and transmission: Spores are ubiquitous and survive in soil for years. The most frequent source of infection is food contaminated with spores, which contains replicating bacteria that produce high amounts of botulinum toxin. The most common route of transmission is via the gastrointestinal (GI) tract (food-borne botulism). Preserved foods (most commonly homemade) become an anaerobic environment of low acidity and low content of salt, nitrites, and sugar that may promote growth of Clostridium spp (eg, canned meat or vegetables, foil-wrapped vegetables and potatoes, garlic in oil, onions, meat, fish, sauces/dressings). Exceptionally rare forms of botulism are wound botulism, infant botulism, and inhalation botulism (the latter may be caused by the aerosolized toxin released into the air during a bioterrorist attack).

3. Incubation and contagious period: The rate of development and severity of the clinical manifestations depend on the rate of absorption and amount of ingested botulinum toxin. After contaminated food is consumed, the onset of symptoms occurs within 2 hours to 8 days (usually 12-72 hours). The shorter the incubation period, the more severe the course of disease. The patient is not contagious.

Clinical FeaturesTop

Clinical features are similar in all types of botulism. The principal manifestation is flaccid muscle paralysis, which has an acute onset and symmetric progression. It always starts and is most pronounced in the muscles with bulbar innervation (affecting cranial nerve motor nuclei, usually multiple), with subsequent descending progression. Characteristic features of bulbar palsy (the 4 D’s) are diplopia, dysarthria, dysphonia, and dysphagia (including impaired gag reflex on physical examination). Infants with botulism often present with generalized hypotonia. The clinical manifestations may vary from relatively mild to severe, including respiratory failure and coma-like state (with preserved consciousness). No sensory disturbances, fever, or altered mental status are observed. Other signs and symptoms:

1) Very frequent (≥90% of patients): Xerostomia (dry mouth).

2) Frequent (>60%-89%): Fatigue, constipation, weakness of the arms and lower extremities, blurred vision, nausea, ptosis, oculomotor nerve palsy, facial nerve palsy.

3) Moderately frequent and rare (≤60%): Dyspnea, vomiting, sore throat, vertigo/dizziness, abdominal cramps, paresthesias, tongue weakness, mydriasis or rigid pupils, hyporeflexia or areflexia, diarrhea, nystagmus, ataxia.

DiagnosisTop

Diagnosis is based on the patient’s medical history and clinical features. Neurologic examination may be necessary to exclude other CNS disorders (Table 1). In every case of suspected botulism, attempt to confirm or exclude the diagnosis on the basis of laboratory tests; consultation with a reference laboratory is usually required. Public health authorities generally require immediate notification of all cases of botulism (a 24-hour service is usually available).

Diagnostic Tests

Detection of botulinum toxin in blood samples or culture of toxigenic strains from other samples is the primary method of laboratory confirmation of botulism. Testing should be performed in every case. Samples may include serum (collected before antitoxin administration), feces, gastric contents, enema fluid, and potentially the food product of interest. For infant botulism, the key sample is feces; if not available (infants with botulism are often constipated), enema samples or rectal swabs may be acceptable.

Differential Diagnosis

Differential diagnosis: Table 1.

The diagnosis of botulism is highly improbable in patients without paralysis affecting multiple cranial nerves. Electromyography (EMG) is useful in differential diagnosis.

TreatmentTop

Specific Treatment

1. Botulinum antitoxin is indicated in all cases with the exception of infant botulism. It should be administered as soon as possible in patients with a justified suspicion of botulism or with confirmed wound botulism and immediately after making the clinical diagnosis in patients with neurologic symptoms. There are various antitoxin preparations and the administered product generally depends on the available supplies, except for infant botulism. Do not delay treatment to perform microbiologic tests! Prior to administration, perform a hypersensitivity skin test to botulinum antitoxin (equine protein), following the manufacturer’s label. If the test result is positive or equivocal, administer antitoxin according to a desensitization protocol, following the manufacturer’s instructions. When performing the skin test and administering antitoxin, have all necessary equipment and drugs ready in case of anaphylaxis (hypersensitivity may occur in as many as 9% of patients but is rarely severe).

Botulinum antitoxin minimizes nerve damage and disease severity; however, it does not reverse paralysis that has already developed. Treatment may be discontinued if the intensity of paralysis has peaked and symptoms begin to resolve. Do not administer botulinum antitoxin in patients who are allergic to equine proteins or have received equine proteins in the past, unless botulism is severe and life-threatening; if administration of botulinum antitoxin is necessary in such individuals, use a desensitization protocol or administer parenteral glucocorticoids prior to antitoxin.

2. Human Botulism Immune Globulin Intravenous (BIG-IV) is recommended for most cases of infant botulism. Delay in BIG-IV administration is associated with worse outcomes (prolonged mechanical ventilation). The benefits of this product—primarily significant reductions in duration of mechanical ventilation, intensive care unit stay, and overall hospital stay—are most pronounced in infants who receive treatment within 7 days of the onset of symptoms. There is currently only a single product available (BabyBIG®), which is active against C botulinum type A or B and usually can be acquired in consultation with public health authorities.

3. Elimination of botulinum toxin from the GI tract (gastric lavage, deep enemas): see Prevention, below.

4. Antibiotic therapy is indicated only in cases of wound botulism (IV penicillin G [INN benzylpenicillin] 3 million IU every 4 hours or IV metronidazole 500 mg every 8 hours for several days). Do not use aminoglycosides and clindamycin, as these may increase the neuromuscular blockade.

General Measures and Symptomatic Treatment

1. Start mechanical ventilation in case of severe respiratory failure. In some patients it may need to be continued for several months.

2. Place the patient in a supine position with the bed rest elevated to 20 to 25 degrees while supporting the cervical spine, as this improves ventilation and reduces the risk of aspiration. Avoid placing the patient in a supine or semirecumbent position without head elevation, which may impair mobility of the diaphragm and airway clearance.

3. Provide appropriate patient care (including prophylaxis of pressure ulcers) and rehabilitation in case of severe paralysis.

4. Maintain adequate volume status and nutritional support. If necessary, use a nasogastric tube, percutaneous endoscopic gastrostomy (PEG), or parenteral nutrition.

Follow-UpTop

Monitor the patient’s respiratory function (blood gas analysis, pulse oximetry), positioning (prophylaxis of aspiration), and ability to swallow and eat.

ComplicationsTop

Complications include respiratory failure, death (rare, mostly due to complications related to mechanical ventilation; however, mortality in patients >60 years is ~30%), aspiration, and persistent paresis.

PrognosisTop

Recovery is complete in the majority of patients (in adults within several weeks to several months). Abnormalities in neuromuscular conduction may resolve as late as after 3 to 6 months, while fatigue and dyspnea may persist for years. In untreated patients with severe botulism, the disease leads to death due to airway obstruction (paresis of the pharyngeal and upper airway muscles) and low tidal volumes (paresis of the diaphragm and accessory muscles of respiration).

PreventionTop

Nonspecific Prevention

1. Avoidance of suspicious food. If food and water cannot be obtained from trusted sources, they should be boiled before consumption at 85 to 100 degrees Celsius for 10 minutes. Every food product that may contain soil (particularly homemade preserved food) is potentially contaminated. Products that are spoiled or expired should be discarded. Canned food should be inspected prior to opening: if the lid is bulging (this suggests an accumulation of gas produced by C botulinum), the cans should be boiled for a long time and discarded or destroyed. Gas bubbles that appear after opening a jar suggest contamination of the preserved food.

2. Prompt notification of authorities of a justified suspicion or confirmed cases of botulism facilitates a timely epidemiologic investigation.

Specific Prevention

Prophylactic postexposure administration of botulinum antitoxin is not recommended.

TablesTop