Botulism: Practice Essentials, Background, Pathophysiology (original) (raw)

Practice Essentials

Botulism is an acute neurologic disorder that causes potentially life-threatening paralysis due to a neurotoxin produced by Clostridium botulinum or related species (C baratii and C. butyricum). Exposure may occur via 4 routes [1] :

• Ingestion (foodborne botulism)
• Colonization of a wound (wound botulism) or intestines (infant botulism) by Clostridium botulinum
• Cosmetic or therapeutic injection (iatrogenic botulism)
• Bioterrorism (inhalational or ingestion-related botulism)

Signs and symptoms

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
• 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 symmetrical descending paralysis or weakness of motor and autonomic nerves
• Respiratory muscle weakness may be subtle or progressive, advancing rapidly to respiratory failure

The autonomic nervous system is also involved in botulism (typically in cases caused by toxin type B), with manifestations that include the following [2] :

• Paralytic ileus advancing to severe constipation
• Gastric dilatation
• Bladder distention advancing to urinary retention
• Orthostatic hypotension
• Reduced salivation
• Reduced lacrimation

Other neurologic findings include the following [3, 4] :

• 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

Ophthalmic manifestations may reflect the anticholinergic effects of the neurotoxins.

• Accommodation paresis, with blurred vision
• Pupil dysfunction with mydriasis and poorly reactive pupils
• Dry eye symptoms with impairment of lacrimation

Ocular manifestations may be the manifesting features of botulism. However, their absence does not exclude this disease, since the seven different toxins appear to involve the ocular system to various degrees.

As reported by physicians caring for 332 different botulism patients [5] :

• 99% had no fever
• 93% experienced descending paralysis
• 91% had no mental status change
• 84% had at least one ocular weakness finding
• 82% had no acute neuroimaging changes
• 80% had blurry vision
• 78% had difficulty speaking
• 75% had diplopia
• 69% had a change in their voice
• 65% had shortness of breath
• 63% had a dry mouth
• 62% experienced sensation of a thick tongue
• 58% had impaired gag reflex
• 55% had dizziness
• 54% had palatal weakness

Diagnosis

The diagnosis must initially be made clinically, as waiting for laboratory confirmation would harmfully delay therapy. [6]

The standard for laboratory diagnosis is a mouse neutralization bioassay confirming botulism by isolation of the toxin. Toxin may be identified in the following:

• Serum
• Stool
• Vomitus
• Gastric aspirate
• 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. Wound cultures that grow C botulinum suggest the presence of wound botulism.

Electromyography [7, 8]

Characteristic electromyographic findings in patients with botulism include the following:

• Brief, low-voltage compound motor-units
• Small M-wave amplitudes
• 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.

See Workup for more detail.

Management

Rigorous and supportive care, including use of the following, is essential in patients with botulism:

• Meticulous airway management - Of paramount importance, since respiratory failure is the most important threat to survival in patients with botulism
• Cathartics and enemas - Administered to patients with bowel sounds to remove unabsorbed botulinum toxin from the intestine
• Stress ulcer prophylaxis - A standard component of intensive care management
• Nasogastric suction and intravenous hyperalimentation - Helpful if an ileus is present; if no ileus is present, tube feeding can be used for nutritional supplementation
• Foley catheter - Often used to treat bladder incontinence; the catheter must be monitored conscientiously and changed regularly
• Antibiotic therapy - Useful in wound botulism, but has no role in foodborne botulism

Magnesium salts, citrate, and sulfate should not be administered, because magnesium can potentiate the toxin-induced neuromuscular blockade.

Wound botulism requires the following:

• Incision and thorough debridement of the infected wound
• Antitoxin therapy
• Penicillin G IV (metronidazole if penicillin-allergic)
• Tetanus toxoid booster

Prevention of nosocomial infections

Measures to reduce the risk of nosocomial infections include the following:

• Close observation for hospital-acquired infections - Especially pneumonia (particularly aspiration pneumonia); precaution against aspiration is also necessary
• Close observation for urinary tract infection
• Meticulous skin care - 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 patient’s supportive care.

See Treatment and Medication for more detail.

Background

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 or intestinal botulism, foodborne botulism, and wound botulism. Iatrogenic botulism may also occurr via cosmetic or therapeutic injection of any commercially made botulinum toxin (e.g. Botox, Dysport, Xeomin, Myobloc). Additionally, because of the potency of the toxin and ease of aerosolization, the possibility of inhalational botulism as a bioterrorism agent or biological weapon is of great concern [9] . For more information, see CBRNE – Botulism.

Infant botulism is caused by ingested C botulinum spores that germinate in the intestine and produce toxin. These spores typically come from the environment. [10] Natural honey and corn syrup have been theorized as sources, however, most infants with botulism have not been exposed to honey. Most infants fully recover with supportive treatment; the attributed infant mortality rate is less than 1%. [11] 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. [1] Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin. On a molecular weight basis, botulinum toxins are the most potent toxins known.

Pathophysiology

Seven antigenically distinct C botulinum toxins are known, including A, B, C, D, E, F, and G [4] . Each strain of C botulinum can produce only a single toxin type. Types A, B, E, and, rarely, F cause human disease. [1] 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.

The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions. Toxins are absorbed from the stomach and small intestine, where they are not denatured by digestive enzymes. Subsequently, they are hematogenously disseminated to peripheral cholinergic nerve terminals (neuromuscular junctions, postganglionic parasympathetic nerve terminals, peripheral ganglia). The toxin is endocytosed by the neuron and is then allowed to cleave proteins essential for neurotransmitter release. The toxin does not cross the blood-brain-barrier, likely secondary to its large size, however, it may be transported to the central nervous system axonally. [12]

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.

Humans commonly ingest C botulinum spores, but germination does not typically occur in the adult intestine since special conditions are required (ie, anaerobic environment, low acidity, specific amino acid, salt and sugar concentrations, and temperatures 37oF-99oF). [1, 11]

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 rarely after cesarean delivery. [13, 14] 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. Symptoms develop after an incubation period of 4-13 days, with a median 6.5 day. [15] The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.

Frequency

In the United States over 100 cases of botulism are reported annually to the Centers for Disease Control and Prevention (CDC). Infant botulism with mean age of 13 weeks accounts for 60-70% of all botulism cases. [16, 10]

The incidences of foodborne and wound botulism are similar as of 2017. [17, 18] Disease due to Toxin A is found predominantly west of the Mississippi River in wound botulism. Toxin B is found most commonly in the eastern United States associated with infant botulism. Toxin E is found in northern latitudes, such as the Pacific Northwest, the Great Lakes region, and Alaska. The frequency of botulism in native Alaskans is among the highest in the world, uniquely implicating fermented beaver tail as the source of foodborne botulism in recent history [19] . Toxin E outbreaks are also frequently associated with fish products. [20]

Mortality/Morbidity

Mortality rates vary based on the age of the patient and the type of botulism and have significantly declined over the last century due to improvements in supportive care. The modern mortality for foodborne botulism is 5% or less. [1, 21] Wound botulism carries a mortality rate of roughly 10%. [22] The risk of death due to infant botulism is usually less than 1%. [10]

The recovery period from botulism flaccid paralysis takes weeks to months. [4] Death that occurs early in the course of disease is usually secondary to acute respiratory failure, whereas death later in the course of illness is typically secondary to complications associated with prolonged intensive care (eg, venous thromboembolism or hospital-acquired infection). Some patients demonstrate residual weakness or autonomic dysfunction for 1 year after the onset of the illness. However, most patients achieve full neurologic recovery. Permanent deficits may occur in those who sustain significant hypoxic insults.

Sex

Wound botulism is more common in females. [16] Foodborne botulism has no sexual predilection.

Age

Foodborne botulism and wound botulism predominately occur in adults. The mean age of infant botulism is 3 months [10] .

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Author

William N Bennett, V, MD Staff Physician, Infectious Disease Service, Chair, Antimicrobial Stewardship, Department of Medicine, Wright-Patterson Medical Center; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences School of Medicine

William N Bennett, V, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Joseph M Yabes, Jr, MD, FACP Deputy Director, USAF HIV Medical Evaluation Unit, Associate Program Director, Infectious Disease Fellowhip, Brooke Army Medical Center; Core Faculty, Infectious Disease Fellowship, Chair, Virtual Health Subcommittee, San Antonio Uniformed Services Health Education Consortium (SAUSHEC); Assistant Professor, Department of Medicine, Uniformed Services University of the Health Sciences; Adjunct Assistant Professor, Department of Medicine, University of Texas Health Science Center at San Antonio

Joseph M Yabes, Jr, MD, FACP is a member of the following medical societies: American College of Physicians, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America

Disclosure: Received income in an amount equal to or greater than $250 from: MedPage Today LLC.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Kirk M Chan-Tack, MD Medical Officer, Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration

Disclosure: Nothing to disclose.

David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine

David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received salary from Gilead Sciences for management position.

John Bartlett, MD † Professor Emeritus, Johns Hopkins University School of Medicine

John Bartlett, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Pharmacology, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, American Thoracic Society, American Venereal Disease Association, Association of American Physicians, Infectious Diseases Society of America, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The views expressed herein are those of the author(s) and do not reflect the official policy or position of Wright Patterson Medical Center, Brooke Army Medical Center, the Defense Health Agency, Uniformed Services University of the Health Sciences, U.S. Army Medical Department, U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, the DoD, or the U.S. Government.