eMedicine Specialties > Ophthalmology > Infectious Disease

Botulism

Bhupendra Patel, MD, FRCS, Professor of Ophthalmic Plastic and Facial Cosmetic Surgery, Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine
Simon F Taylor, MB, BS, FRANZCO, FRACS, Clinical Senior Lecturer, Oculoplastic Surgery, Save Sight Institute, University of Sydney

Updated: May 11, 2009

Introduction

Background

Botulism is a disease caused by the neurotoxins of Clostridium botulinum. This microorganism is a spore-forming, gram-positive, anaerobic bacillus, which may exist in soil or marine sediments throughout the world. The neurotoxin causes a paralytic disease with blockade of neuromuscular conduction.

Botulism generally is seen in 3 clinical scenarios, as follows: (1) the ingestion of preformed toxins in food contaminated with C botulinum, (2) contamination of wounds by C botulinum, and (3) colonization of the intestine by C botulinum in infants younger than 1 year.

Despite the uncommon nature of the disease, patients with botulism may present to an ophthalmologist with visual symptoms.

Purified botulinum toxin type A, in the form of BOTOX® purified neurotoxin complex, has been used therapeutically in the treatment of certain forms of strabismus and in blepharospasm associated with facial dystonia, including benign essential blepharospasm.^{[1 ]}

Pathophysiology

C botulinum is a heterogeneous group of spore-forming, anaerobic, gram-positive microorganisms. Organisms of types A to G are distinguished by the antigenic specificities of their toxins. Eight distinct toxins have been described (ie, A, B, C1, C2, D, E, F, G).^{[2 ]}In rare instances, a single strain of organism may produce more than one toxin. All toxins except C2 are neurotoxins; C2 is a cytotoxin of uncertain clinical significance. Toxin types A, B, E, and, in rare cases, F cause human disease; types C and D cause avian and nonhuman mammalian disease.^{[3 ]}

Rarely, clostridial species other than C botulinum have been reported to cause disease, including rare toxin-forming strains of Clostridium butyricum and Clostridium baratii.

Clostridial spores are highly heat resistant, with inactivation requiring exposure to a temperature of 120°C. However, the toxin may be inactivated by exposure to a temperature of 100°C for 10 minutes.

Botulinum neurotoxins, whether directly ingested, produced in a C botulinum contaminated wound, or produced by C botulinum colonization within the intestines, enter the vascular system and are transported to peripheral cholinergic nerve terminals. The peripheral cholinergic nerve terminals involved include neuromuscular junctions, cholinergic parasympathetic nerve endings, and some peripheral ganglia. The toxin causes blockade of neuromuscular conduction by binding to receptor sites on presynaptic motor nerve terminals, entering the nerve terminal, and inhibiting the release of acetylcholine by proteolysis of components of the neurotransmitter exocytosis apparatus.

Blockade of neurotransmitter release at the nerve terminal is considered permanent. Evidence exists that the axon may sprout new terminals and allow recovery of neurotransmission.

Botulism is generally seen in 3 clinical scenarios, based on the mode of acquisition.

• Food poisoning: This follows the ingestion of preformed toxins in food contaminated with C botulinum.
• Wound infection: Infection of wounds by C botulinum most commonly occurs where wounds are contaminated heavily with soil or water. Spores may germinate into toxin-producing vegetative microorganisms.
• Infant botulism: This results from intestinal colonization of organisms in infants younger than 1 year.^{[4,5 ]}The immature intestine system allows abnormal colonization. Toxin is produced in and absorbed from the gut, following ingestion of ingested spores. More recently, adult intestinal colonization botulism has been described in association with intestinal disease causing disturbance in normal intestinal flora.

Frequency

United States

Food-borne botulism is responsible for an average of 30 reported cases per year in the United States.^{[6 ]}Since 1950, the average number of outbreaks per year is 9.4. In the United States, the geographic distribution of cases by toxin type generally coincides with the organism type found in the local environment. Toxin type A is the most predominant type west of the Rocky Mountains; type B generally is distributed but is more common in the eastern United States; while type E is found in the Great Lakes region and Alaska. In the United States, type A accounts for 60% of cases, type B 18%, and type E 22%. Home-processed foods are responsible for most outbreaks. Type E outbreaks are associated with fish products.

Infant botulism was first recognized as a disease in 1976. Infant botulism is responsible for about 60 cases each year; hence, it is now the most frequent form of the disease in the United States in recent years. Average annual incidence is approximately 1.9 per 100,000 live births. Mean age at onset is about 13 weeks but ranges from 1-63 weeks. Infant botulism is underrecognized and underreported.

Wound botulism is rare, with only several reports annually in the United States.

International

Human botulism occurs worldwide.

Food-borne botulism is responsible for almost 1000 cases worldwide each year.

Mortality/Morbidity

• For food-borne disease with current medical supportive care, the US case-fatality rate for the period 1976-1984 was about 7.5%.^{[6 ]}Type A disease is generally more severe than type B, with greater need for ventilatory support and longer disease course. The case-fatality rate for type A is about 10% and for type B is about 5%. Mortality from botulism is higher amongst patients older than 60 years compared to younger patients. The case-fatality rate for those older than 60 years was 30%. The average duration of pulmonary support for those requiring mechanical ventilation is 6-8 weeks. Some patients experience residual weakness and autonomic dysfunction for as long as 1 year.
• The case-fatality rate for wound botulism is 10%. Survivors experience significant long-term morbidity.
• Infant botulism has a case-fatality rate of 1.3%. Generally, symptoms progress for 2 weeks and then stabilize for 3 weeks, before recovery begins. The average length of infant inpatient hospital is about 4 weeks, although excretion of organisms may continue for several months after discharge, and a 5% relapse rate exists.

Race

While no racial predilection exists, geographic distribution toxin type coincides with the organism type found in the local environment.

Sex

No sexual predilection exists.

Clinical

History

The diagnosis of botulism requires a high degree of clinical suspicion. Although laboratory confirmation is required, the diagnosis should be suspected on clinical findings, in those patients with an appropriate history and physical (particularly neurologic) examination.

• Food poisoning
  • The severity of illness varies from a mild condition to a very serious disease with death within 24 hours. The incubation period is generally 18-36 hours; however, it may vary from several hours to several days.
  • The initial symptoms are usually those of motor cranial nerve involvement with onset of diplopia, dysphonia, and dysphagia. A generally symmetric descending paralysis follows. Abdominal pain, with nausea and vomiting may precede or follow paralysis. A dry mouth and throat reflect cholinergic parasympathetic disturbance. Patients generally remain alert and responsive. Sensory deficits, besides blurred vision, have been reported only in rare cases.
• Wound infection^{[7 ]}
  • The incubation period averages about 7 days. Wound botulism may occur in any wound contaminated by soil or water.
  • Symptoms are generally the same as those seen in food-borne botulism, except gastrointestinal symptoms are absent. The source wound may appear relatively benign. Wound infections associated with intravenous drug needle puncture sites are becoming an important cause.
• Infant botulism^{[8 ]}
  • The incubation period varies from 3-30 days. In this form of botulism, the severity ranges from mild illness with failure to thrive to severe paralysis with respiratory failure.
  • Infant botulism causes acute bulbar dysfunction. The first sign of the disease may be constipation. Other features include lethargy, hypotonia with poor head control, poor feeding, with difficulty in sucking and swallowing, and pooled oral secretions. Respiratory failure occurs in up to one half of diagnosed infants.
  • The identification of contaminated honey as a source of spores has lead to the recommendation that honey should not be given to infants younger than 1 year. Susceptibility decreases with age as the normal intestinal flora develops.

Physical

The major systemic features of botulism involve motor weakness or paralysis. Paralysis begins with cranial nerve involvement and progresses caudally to involve extremities.

• Clinical physical findings involve the following:
  • Symptoms of motor cranial nerve involvement with onset of dysarthria, dysphonia, and dysphagia may be present.
  • A generally symmetric descending paralysis occurs, with involvement of neck, arms, thorax, and legs.
  • Respiratory difficulties occur with intercostal and diaphragmatic weakness.
  • Autonomic features are to be expected, reflecting cholinergic neurotransmission disruption, with impairment of salivary secretion, paralytic ileus, constipation, and urinary retention.
  • Postural hypotension may be present.
  • The gag reflex may be suppressed.
  • Typically, patients are afebrile.
• 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
• Ophthalmic manifestations may reflect a deficit at the neuromuscular junction.^{[9,10 ]}
  • Oculoparesis or ophthalmoplegia manifests as diplopia.
  • Blepharoptosis is common.
  • Nystagmus may be noted.
• Ocular manifestations may be the manifesting features of botulism. However, their absence does not exclude this disease, since the various toxins appear to involve the ocular system to various degrees. Neurotoxin A may have no specific ophthalmic manifestations.
• In wound botulism, the symptoms are generally the same as those seen in food-borne botulism, except gastrointestinal symptoms are lacking.
• In the infant, the clinical examination may note neurologic features of ptosis, ophthalmoplegia, weak gag reflex, and poorly reactive pupils, in addition to systemic features of generalized muscle weakness with hypotonia and a weak cry.

Causes

Botulism is a disease caused by the neurotoxins of C botulinum.

Differential Diagnoses

Myasthenia Gravis

Other Problems to Be Considered

Guillain-Barré syndrome
Lambert-Eaton syndrome
Poliomyelitis
Hypermagnesemia
Mushroom poisoning

Workup

Laboratory Studies

• The diagnosis of botulism requires a high degree of clinical suspicion. The diagnosis must be considered in an afebrile patient with progressive descending paralysis, especially in the presence of gastrointestinal symptoms.
• Serum toxin bioassay: The demonstration of toxin in serum involves a bioassay in mice. The identification of the toxin type is performed by a mouse toxin neutralization test.
• Isolation of organism by culture
  • Food-borne: The demonstration of organism (or its toxin) in vomitus, gastric aspirate, or feces is highly suggestive of the diagnosis of botulism, because intestinal carriage is rare. Anaerobic cultures are required. Early cases of botulism are more likely to involve diagnosis by toxin assay, whereas later cases are more likely to yield a positive specimen culture.
  • Wound culture: In wound botulism, wound cultures yielding the organism are highly suggestive of botulism.
  • Source culture: Isolation of the organism from food without toxin is not sufficient for a diagnosis.

Other Tests

• Electrophysiology: Nerve conduction velocity is normal. Action potentials on electromyography are decreased with supramaximal stimulus. Single fiber electromyography may be helpful.

Treatment

Medical Care

• Supportive care for the duration of the paralytic illness, with extensive nursing support, is the mainstay of treatment.
  • Ventilatory support: In adults, ventilatory support will be needed in as many as one third of cases. Pulse oximetry, arterial blood gas analysis, and spirometry should be monitored. Mechanical ventilation is considered when vital capacity is less than 30% of predicted.
  • Parenteral nutrition may be required in view of gastrointestinal disturbance.
  • Urinary catheterization may be required for urinary retention.
• Antitoxin: In food-borne illness, trivalent (types A, B, and E) equine antitoxin should be administered, with antitoxin neutralizing botulinum toxin not yet bound to nerve terminals. Therefore, the antitoxin should be given as soon as possible, prior to receiving laboratory confirmation of diagnosis. Antitoxin has not been shown to be beneficial in infant botulism. Human botulism immune globulin is being evaluated for infant botulism.
• Antibiotics may be helpful in the eradication of C botulinum in wound botulism, but they appear to have no role in infant botulism or in botulism of food poisoning. Remember that aminoglycoside antibiotics and tetracyclines may increase neuromuscular blockade by impairment of neuronal calcium entry.

Surgical Care

• In wound botulism, exploration and extensive surgical debridement of infected wounds is required.

Medication

Antitoxin appears to be the only effective medication. Guanethidine has been used and shown to be not effective, despite reports of improvement in accommodative paresis.

In infant botulism, intravenous therapy with botulism immune globulin (BIG), which was approved by the US Food and Drug Administration (FDA) in 2003, is recommended to shorten the duration and to diminish the potential complications.

Antitoxins

Trivalent (types A, B, and E) equine botulism antitoxin should be used in the presence of food-borne botulism.

Botulism antitoxin

Intravenous administration of one vial of botulism antitoxin results in serum levels of type A, B, and E antibodies capable of neutralizing serum toxin concentrations in excess of those reported for botulism patients. Circulating antitoxins have a half-life of 5-8 days.

Dosing

Adult

One 10 mL vial IV once

Pediatric

Administer as in adults; however, equine antitoxin rarely has been used in infant botulism because of lack of evidence of benefit and risks of hypersensitivity

Interactions

None reported

Contraindications

Documented hypersensitivity to equine antitoxin

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prior to administration of the antitoxin, perform skin testing to test for sensitivity to serum or antitoxin; approximately 9% of persons treated experience hypersensitivity reactions

Follow-up

Further Inpatient Care

• Prolonged support, particularly respiratory support, may be required.

Deterrence/Prevention

• Botulism is a public health emergency.
• Rapid epidemiologic investigation is critical to prevent further cases if hazardous foodstuffs are still available for consumption.
• State health departments should be contacted.

Prognosis

• With early detection and appropriate support, long-term outlook is good. See Mortality/Morbidity for mortality figures.

Patient Education

• As many US outbreaks of food-borne botulism are due to improperly preserved home-canned foods, provide education about the appropriate cooking time, pressure, and temperature required to destroy spores. Refrigeration of incompletely processed foods is required. Emphasize education about the effectiveness of boiling home-canned vegetables to destroy toxins.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article BOTOX® Injections.

Miscellaneous

Medicolegal Pitfalls

• Diagnosis of botulism requires a high index of clinical suspicion.
• Remember that in wound botulism, the wound may not appear grossly infected.

References

1. Laskawi R. The use of botulinum toxin in head and face medicine: an interdisciplinary field. Head Face Med. Mar 10 2008;4:5. [Medline].

2. Fach P, Micheau P, Mazuet C, Perelle S, Popoff M. Development of real-time PCR tests for detecting botulinum neurotoxins A, B, E, F producing Clostridium botulinum, Clostridium baratii and Clostridium butyricum. J Appl Microbiol. Mar 9 2009;[Medline].

3. Hatheway CL. Botulism: the present status of the disease. Curr Top Microbiol Immunol. 1995;195:55-75. [Medline].

4. Domingo RM, Haller JS, Gruenthal M. Infant botulism: two recent cases and literature review. J Child Neurol. Nov 2008;23(11):1336-46. [Medline].

5. Mitchell WG, Tseng-Ong L. Reviews of infant botulism at childrens hospital los angeles. J Child Neurol. Aug 2008;23(8):968. [Medline].

6. Centers for Disease Control and Prevention. Botulism in the United States, 1899-1996. Handbook for epidemiologists, clinicians, and laboratory workers. Atlanta, Ga: 1998:1-43. [Full Text].

7. Teismann IK, Steinstraeter O, Warnecke T, et al. Cortical recovery of swallowing function in wound botulism. BMC Neurol. May 7 2008;8:13. [Medline].

8. Domingo RM, Haller JS, Gruenthal M. Infant botulism: two recent cases and literature review. J Child Neurol. Nov 2008;23(11):1336-46. [Medline].

9. König H, Gassman HB, Jenzer G. Ocular involvement in benign botulism B. Am J Ophthalmol. Sep 1975;80(3 Pt 1):430-2. [Medline].

10. Albert DM, Jakobiec FA. Systemic bacterial infections and the eye. In: Ryan ET, Sullivan BA, eds. Principles and Practice of Ophthalmology: Clinical Practice. WB Saunders Co; 1994:3006-10.

Keywords

botulism, botulinum toxin, BOTOX®, strabismus, blepharospasm, facial dystonia, Clostridium botulinum, C botulinum

Contributor Information and Disclosures

Author

Bhupendra Patel, MD, FRCS, Professor of Ophthalmic Plastic and Facial Cosmetic Surgery, Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine
Bhupendra Patel, MD, FRCS is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Simon F Taylor, MB, BS, FRANZCO, FRACS, Clinical Senior Lecturer, Oculoplastic Surgery, Save Sight Institute, University of Sydney
Simon F Taylor, MB, BS, FRANZCO, FRACS is a member of the following medical societies: Australian Medical Association and Royal Australasian College of Surgeons
Disclosure: Nothing to disclose.

Medical Editor

Andrew W Lawton, MD, Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center
Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Brian R Younge, MD, Professor of Ophthalmology, Mayo Clinic School of Medicine
Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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