Description

• An acute illness caused by neurotoxins produced by Clostridium botulinum or related neurotoxigenic species, which results in cranial nerve palsies and a symmetric, descending, flaccid paralysis
• The neurotoxin may be elaborated either in the large intestine of individuals temporarily colonized with the bacterium, or ingested, or absorbed from infected wounds.
• There are three main forms of the disease:
  • Infant botulism (IB) is the intestinal toxemia form in which swallowed spores germinate and colonize the infant's colon and elaborate toxin in situ.
  • Foodborne botulism in children and adults occurs when preformed toxin is ingested with improperly prepared or stored foods.
  • Wound botulism occurs when spores of the bacterium contaminate the wound, germinate, and produce toxin that is then absorbed.

Epidemiology

• IB is the most common form of human botulism in the United States.
• IB occurs in the 1st year of life, with ~90% of cases reported in the first 6 months of life.
• IB affects infants of all racial backgrounds and socioeconomic groups.
• Male to female ratio is 1:1.
• Toxin types A and B represent 98.5% of cases in United States (1976 to 2015), with dual toxin types (e.g., Ba, Bf) and more rare type E and type F comprising the remaining 1.5%.
• IB has been recognized in all 50 states, with a greater proportion of toxin type B cases east of the Mississippi River and toxin type A cases west of the Mississippi.
• Recognized on five of the six inhabited continents, Africa being the exception.
• Often, a history of a recent change in feeding practice is found.
• Honey is an identified food reservoir of C. botulinum spores. Honey consumption in U.S. IB patients from 1976 to 2015 was only approximately 4.8%.
• For the majority of IB cases, spore acquisition likely occurs from the natural environment, that is, infants inhale and then swallow spores attached to airborne microscopic dust particles. Nearby soil disruption may play a role.
• Breastfed infants who acquire IB tend to be older at onset than are formula-fed infants.
• Foodborne cases are usually associated with home-processed, low acid foods-especially vegetables, fruits, and condiments. Restaurant-associated outbreaks have occurred. Recent outbreaks in U.S. prisons have been associated with fermented alcoholic beverage commonly referred to as pruno.
• Wound botulism has been associated with "black tar" heroin injection drug use and traumatic injuries in teenagers.

Risk Factors

• Infants who have <1 bowel movement per day may be at increased risk of developing IB.
• Honey is an identified, avoidable food source of C. botulinum spores.
• Ingestion of improperly canned or preserved low-acid foods may result in foodborne botulism.

General Prevention

• Do not feed honey or raw honey-containing products to infants.
• Botulinum toxin is heat-labile; 5 minutes of boiling will destroy the toxin.
• Spores are heat-resistant.
• Proper food preservation, storage, and preparation will prevent foodborne botulism.

Pathophysiology

• Neurotoxin is endocytosed at peripheral cholinergic nerve endings; it blocks release of acetylcholine at the neuromuscular junction.
• Cranial nerves are usually affected first and most severely, leading to ptosis, ophthalmoplegia, decreased facial expression, difficulty swallowing, and loss of airway-protective reflexes. Respiratory failure may ensue.
• Sensation and sensorium remain intact.
• Recovery occurs through regeneration of motor neuron axon terminals and the formation of new motor end plates.
• Infants are particularly prone to temporary colonic colonization by C. botulinum. When foods other than breast milk are introduced to breastfed infants, perturbation of the intestinal microbiome may predispose to illness.

Etiology

C. botulinum, the etiologic agent, is a gram-positive, spore-forming, obligate anaerobic bacterium that is found in dust, soil, and marine sediments worldwide. Rarely, neurotoxigenic Clostridium butyricum and Clostridium baratii may cause disease due to toxin type E and type F, respectively.

History

• IB
  • Symptoms include constipation, poor feeding/poor latch, diminished facial expression, droopy eyelids, difficulty swallowing, and generalized weakness.
  • Fever is typically absent (barring concomitant infections).
  • Infants may appear lethargic (from ptosis and decreased facial expression).
  • Occasionally, rapid progression of symptoms may result in respiratory arrest or an apparent life-threatening event (ALTE).
• Foodborne botulism
  • ~50% of patients report emesis.
  • There may initially be complaints of diarrhea followed by constipation.
  • The incubation period from ingestion to the onset of symptoms is usually 18 to 36 hours (range, a few hours to several days).
  • Patients complain of weakness and dry mouth.
  • Visual complaints include blurry vision, loss of accommodation, and diplopia.
  • Patients may complain of difficulty swallowing or slurred speech.
  • Patients may have urinary retention.
  • Occasionally, progression may be quite rapid, and the abrupt onset of lethargy and weakness may suggest bacterial sepsis or meningitis.
• Wound botulism
  • Often history of IV drug use
  • Incubation period ranges from 4 to 14 days.
  • Fever may be present from wound infection not botulism.
  • Patients often report constipation but rarely nausea or vomiting.
  • Patients may complain of purulent discharge from the wound.

Physical Exam

• IB
  • Patients are typically afebrile and appear lethargic.
  • Cranial nerve findings include ptosis, diminished facial expression, weak cry, poor latch/suck, drooling/dysphagia, weak gag, and poor head control.
  • Pupils
    • Often midposition initially; may be normal to sluggishly reactive but fatigue with repetitive stimulation
    • In some cases, pupils appear fixed and dilated for a period.
  • Frog-leg positioning due to weakness of hip girdle musculature
  • Generalized weakness and loss of motor milestones
  • Flaccid, descending paralysis, and hyporeflexia
  • The remainder of the physical examination is normal.
  • In infants, early in the course of the disease, pupillary and corneal reflexes may fatigue easily (refer to physical examination tools under "For Physicians-Clinical Diagnosis" tab at www.infantbotulism.org)
• Older children and adults
  • May appear alert and are afebrile
  • Ptosis, extraocular palsies, and dilated, sluggishly reactive pupils are often the first signs of descending paralysis.
  • Dysphagia, dysarthria, and hypoglossal weakness indicate lower cranial nerve involvement.
  • Respiratory failure may rapidly ensue from upper airway obstruction resulting from loss of pharyngeal tone, loss of airway-protective reflexes, and respiratory muscle weakness.
  • The triad of bulbar palsies, clear sensorium, and absence of fever should prompt immediate consideration of botulism.
  • Signs of autonomic instability may include unexpected fluctuations in skin color, BP and heart rate, and urinary retention.

Differential Diagnosis

• Top 2 clinical mimics of IB are spinal muscular atrophy (SMA) type I and metabolic disorders.
• Infections
  • In infants, sepsis, meningitis and polio-like enteroviruses may present in a similar way.
  • In older children and adults, bacterial sepsis, meningitis, poliomyelitis, tick paralysis, and diphtheric polyneuritis are considerations.
  • Postinfectious demyelinating processes may mimic botulism but generally have asymmetric findings.
  • Absence of fever and a clear sensorium make sepsis and meningitis less likely.
• Neurologic
  • Myasthenia gravis spares the pupillary constrictor response, which in botulism is either fatigable, sluggish, or absent.
  • In SMA type I (Werdnig-Hoffmann disease), extraocular and sphincter muscles are spared.
• Metabolic/genetic
  • Certain metabolic or genetic conditions may closely mimic IB.
• Toxins: Drug ingestions may lead to weakness and lethargy.

General Measures

• Patients with suspected botulism should be hospitalized and have continuous monitoring of heart rate, respiratory rate, and oxygenation, as well as frequent assessment of respiratory effort and airway-protective reflexes.
• The mainstay of therapy is meticulous supportive care.
  • Particular attention should be paid to respiratory and nutritional needs.
• Cases of suspected toxin ingestion should be treated early with induced emesis and/or gastric lavage in an attempt to decrease toxin exposure.
• All suspect cases should be immediately reported to the state health department and the CDC.

Medication

• Prompt recognition of IB and early treatment with intravenous human botulism immune globulin (BIG-IV; BabyBIG) significantly shortens hospital stay, time in intensive care, and duration of respiratory and nutritional support. BIG-IV is available through the California Department of Public Health's Infant Botulism Treatment and Prevention Program (IBTPP).
• Treatment with BIG-IV should be promptly initiated based on clinical findings and not delayed for laboratory diagnostic studies.
• Antibiotics are not helpful in IB:
  • In suspected IB, avoid aminoglycoside antibiotics (e.g., gentamicin); an abrupt worsening of weakness and respiratory failure may result from potentiating effects at the neuromuscular junction.
• Equine-derived antitoxin is not recommended for the treatment of IB but has been used to treat type-F IB cases.
• Antibiotics are indicated only for documented complications such as pneumonia or urinary tract infections.
• Cathartics are not beneficial.
• Foodborne or wound botulism
  • Should be treated with the licensed, equine-derived heptavalent botulinum antitoxin (BAT), available from the CDC
  • Antitoxin should not be administered to asymptomatic individuals who have only eaten suspect foods.
• Wound botulism should be treated with IV penicillin G 250,000 U/kg/24 h or equivalent and BAT antitoxin.

Admission, Inpatient, and Nursing Considerations

• Meticulous supportive care with particular emphasis on respiratory and nutritional needs is the most important consideration.
• Endotracheal intubation is necessary for patients with respiratory failure or loss of airway-protective reflexes.
• Wounds should be explored and debrided and anaerobic cultures obtained.

Prognosis

• IB has an estimated mortality rate of <1% in hospitalized patients. Complete recovery can be expected when the disease is recognized early and treated appropriately.
• The mortality rate of adult foodborne botulism is 20-25%. In patients <20 years old it is 10%.
• Foodborne botulism patients with a shorter incubation period usually have more severe involvement and a worse prognosis, probably related to an increased amount of toxin ingested.
  • Recovery can generally be expected, but fatigability may persist for up to 1 year.

Complications

• Fatal respiratory failure from paralysis of respiratory muscles is the most serious complication.
• Bulbar dysfunction in IB may lead to dehydration and starvation ketosis before presentation.
• Loss of airway-protective reflexes can lead to aspiration and pneumonia.
• Constipation and urinary retention may precede the onset of paralysis and may complicate later management. Cases of severe Clostridium difficile enterocolitis with hypovolemia, hypotension, and prolonged ICU stays have occurred in IB patients.
• Recurrent urinary tract infections and syndrome of inappropriate antidiuretic hormone secretion (SIADH) are rare complications of IB.

ICD9

• 005.1 Botulism food poisoning
• 040.41 Infant botulism
• 040.42 Wound botulism

ICD10

• A05.1 Botulism food poisoning
• A48.51 Infant botulism
• A48.52 Wound botulism

SNOMED

• 398565003 Infection due to clostridium botulinum (disorder)
• 414488002 Infantile botulism
• 398530003 Wound botulism (disorder)
• 398523009 Foodborne botulism (disorder)