The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Daniel W. Ulrich. This current second edition chapter is a revision and update of the original authorís work.
A 1 month-old baby boy presents to the pediatrician's office with a chief complaint of decreased activity, poor feeding, and constipation. Pertinent past medical history reveals that the infant was born at 39 weeks gestation, with no complications during the pregnancy or birth. The infant is exclusively breast fed, up to date on immunizations and has not suffered from any previous illness. On further questioning, his mother reports her baby has not been himself for the past week. He has had no fever and there are no sick contacts. He has been less active and with a weak cry during this time. His mother also notes her baby has not been as interested in feeding and has recently become constipated. His urine output is decreased with only four wet diapers in the last 24 hours. Typically, he has 3 to 4 soft stools per day, usually after feeds, but has had no bowel movement in the past 5 days.
Exam: VS T37.0, P 144, R 42, BP 75/50, Weight 4.5 kg (50%), Height 55 cm (50%), HC 37 cm (50%). He is awake, lethargic appearing, with expressionless facies, and a weak cry. His anterior fontanel is flat and soft. He has poor head control. He has diminished pupillary reflexes, absent corneal reflexes, bilateral ptosis, and decreased tearing. He has a weak suck and gag reflexes with increased oral secretions. His neck is supple without adenopathy. Heart and lungs are normal. Aeration is good. His abdomen is soft, non-tender, with decreased bowel sounds throughout. No hepatosplenomegaly. His extremities are slightly cool with capillary refill time of 3 seconds. His skin shows no rash or petechiae. He has decreased muscle tone throughout and diminished deep tendon reflexes.
He is hospitalized for possible sepsis. A sepsis work up is done and he is started on IV fluids and empiric antibiotics of ampicillin and gentamicin for sepsis. After 8 hours in the hospital, his overall condition deteriorates, and a code blue is called for apnea. His blood gas is significant for marked acute respiratory acidosis, and he is intubated and placed on mechanical ventilatory support.
His neurological clinical condition worsens such that he becomes completely flaccid. His cultures remain negative for bacterial growth. Viral studies are negative. An electromyography study is done which shows brief, small, abundant, motor unit potentials, known by the acronym BSAP, a characteristic pattern associated with infant botulism (1). Botulinum immunoglobulin (BIG) is administered. He gradually improves, and he is weaned off the ventilator after 14 days. His stool assay returns positive for botulism toxin. He continues to gradually improve over the next three weeks such that he is able to feed on his own, and he is then discharged from the hospital.
Clostridium botulinum is a gram negative, spore forming obligate anaerobe that can be normally found in the soil worldwide. It is found in a wide variety of fresh and cooked agricultural products including fruits, vegetables, and honey (2). Historically, a significant number of cases were linked to ingestion of honey in infants. Since then it has been recommended that no infant be given honey under 1 year of age (2,3,4). Could the honey have caused the infant botulism, or could the honey be merely associated with botulism since it was a common "treatment" for infant constipation which is a feature of infant botulism? Honey is longer given to infants, yet cases of infant botulism still occur.
The usual incubation period is estimated to be between 3 to 30 days from time of exposure to spores (2). Infant botulism has been reported from all inhabited continents except Africa. Areas with the highest incidence in the United States include Hawaii, Utah, California and Pennsylvania (3). The most striking epidemiological feature of infant botulism is its age distribution, in which 95% of cases are found between the ages of 3 weeks to 6 months of age, with a peak between 2 to 4 months of age (2). Once ingested, the bacteria produces neurotoxin within the GI tract. The toxin is subsequently absorbed and carried by the blood stream to peripheral cholinergic synapses, in particular the neuromuscular junction, where it binds irreversibly (3). This reaction results in flaccid paralysis and hypotonia while relatively sparing the autonomic nervous system. Muscle tone and strength returns only when new motor endplates are regenerated, which can take weeks to months (1).
The clinical spectrum of infant botulism ranges from mild disease to sudden infant death. The onset can be insidious or fulminant. The disease typically manifests as a descending flaccid paralysis of the cranial nerve musculature with ptosis, blurred vision, diplopia, dysphagia, dysarthria and decreased gag and corneal reflexes. In fact, it has been stated that it is not possible to have botulism without having multiple bulbar palsies (5). However, in infants, symptoms of poor feeding, weak suck, feeble cry and even obstructive apnea (from a floppy tongue) are not often initially recognized as bulbar in origin (5). The classic picture of infant botulism is an initial presentation of constipation (defined as 3 or more days without defecation in a previously regular infant), listlessness, and poor feeding together with maternal breast engorgement. The typical patient often has an expressionless face, feeble cry, ptosis, poor head control, generalized weakness, and hypotonia. Patients are most often afebrile unless a secondary infection is present and most initial laboratory tests are normal. The differential diagnosis includes sepsis (the most common admitting diagnosis), dehydration, constipation, hypothyroidism, other neurologic disease, inborn errors of metabolism or poisoning (5). The diagnosis is best confirmed with isolation of C. botulinum organism in the stool (often detectable only in the early stages of disease) or C. botulinum toxin in serum or stool. The toxin can be identified in the stool of infected infants for as long as 4 months (4), which explains why the clinical course can last for a few weeks to a few months. Although the electromyographic findings in infant botulism are unique, the procedure is painful and generally unnecessary unless the diagnosis is in question.
Treatment of infant botulism is fundamentally supportive and depends on the anticipation and avoidance of potentially fatal complications. Antibiotics should not be used routinely and should only be used to treat secondary infections (pneumonia, urinary tract infections, otitis media), because their use may result in the lysis of intraintestinal C. botulinum with liberation of additional neurotoxin (3). Of note, aminoglycoside antibiotics (e.g., gentamicin, tobramycin), which are weak pharmacologic neuromuscular blocking agents, should be particularly avoided since they will worsen paralysis acutely, often precipitating an acute respiratory arrest in unsuspected infant botulism patients initially being treated for sepsis (3,5). Note that this is what occurred in the case description above. Human botulinum immunoglobulin (BIG), which acts by interrupting the neuromuscular blockade, has been approved for the treatment of infant botulism. A single intravenous dose of BIG has been shown to reduce the typical course of hospitalization from 5.5 to 2.5 weeks with a two-thirds reduction in the rate of intubation/mechanical ventilation (4).
Most infants will show gradual improvement over a period of 10 days to 2 months with rare cases of relapse. Common complications including respiratory failure (requiring mechanical ventilation), secondary infections (e.g., pneumonia and UTI), and SIADH (syndrome of inappropriate anti-diuretic hormone) require appropriate management to optimize the infant's ultimate prognosis, which is potentially excellent with a full neurologic recovery.
"Infant botulism" differs from "botulism" in that food-borne botulism results from the ingestion of a food in which C. botulinum has produced pre-formed toxin so its onset is more rapid compared to infant botulism. It is most commonly seen in older children and adults and often occurs in outbreaks traced to spoiled, low acidity canned foods (2). While all forms of botulism produce disease through a similar pathway, food-borne botulism more often begins acutely with gastrointestinal symptoms such as nausea, vomiting, and diarrhea. A characteristic pattern of dysarthria, dysphagia, dry mouth, diplopia, and blurred vision with ptosis, evolves during the onset of disease. Fulminate and extensive paralysis, respiratory distress and apnea are more likely to be experienced with food-borne botulism. Wound botulism is an exceptionally rare disease, but is important in pediatrics because adolescents and children are disproportionately affected.
1. The mother of a 1 month old infant asks if it is okay to coat a pacifier with honey to soothe her baby. What is your response?
2. What is the basic mechanism of action of botulinum toxin?
3. Describe the typical clinical presentation of infant botulism. Why may the diagnosis be unclear initially? What is the classic age distribution?
4. What are the principle methods that can be used to confirm infection by C. botulinum?
5. What are the indications for antibiotic treatment in an infant with infant botulism? Why are aminoglycoside antibiotics contraindicated?
6. What is the role of human botulinum immunoglobulin in the treatment of infant botulism?
7. What is the prognosis for an infant infected with infant botulism?
8. Describe the basic difference between "botulism" and "infant botulism".
1. Wolfe GI, Barohn RJ. Chapter 73-Neuromuscular Junction Disorders of Childhood. In: Swaiman KF, Ashwal S (eds). Pediatric Neurology, Principles and Practice, third edition. 1999, St. Louis: Mosby, pp, 1231-1232.
2. Clostridial Infections: Botulism and Infant Botulism. In: Pickering LK, et al (eds). 2000 Red Book: Report of the Committee on Infectious Diseases, 25th edition. 2000, Elk Grove Village, IL: American Academy of Pediatrics, pp. 212-214.
3. Arnon SS. Chapter 146-Infant Botulism. In: Feigin RD, Cherry JD (eds.). Textbook of Pediatric Infectious Diseases, edition 7. 2014, Philadelphia: W.B. Saunders Company, pp. 1801-1809.
4. Long SS. Infant Botulism. Pediatr Infect Dis J 2001;20(7):707-709.
5. Schechter R, Arnon SS. Chapter 208-Botulism. In: Behrman RE, et al (eds). Nelson Textbook of Pediatrics, 16th Edition. 2000, Philadelphia, pp. 875-878.
Answers to questions
1. It is recommended to not give honey to any infant under 12 months of age.
2. Botulinum toxin is released by bacteria within the infant's GI tract. From here, the toxin is absorbed and carried by the blood stream to peripheral cholinergic receptors where it binds irreversibly. Clinically, the most important of the peripheral cholinergic receptors is the neuromuscular junction. Here the toxin's action results in flaccid paralysis and hypotonia, which are the classic clinical signs of infant botulism.
3. Initially, infected infants often present with a history of poor feeding, decreased activity and constipation. The diagnosis may not be considered initially because signs of an evolving bulbar palsy, flaccid paralysis, and hypotonia may be subtle. Additionally, the infant may be worked up for sepsis if he appears toxic or "lethargic", or for constipation until the "classic" manifestations of infant botulism become apparent. The classic age distribution for infant botulism is 3 weeks to 6 months of age.
4. Isolation of the clostridium botulinum organism in stool can be accomplished in the early stages of disease. It is rarely isolated in blood. The most common method for proving infection is to isolate botulinum toxin in blood or stool samples. Toxin can be detected in the stool of infected infants for up to 4 months. Electrophysiological testing, specifically electromyography, can aid in ruling out other neurologic disorders such as Guillain-Barre syndrome, congenital myopathies, and myasthenic conditions.
5. The use of antibiotics in infant botulism should be reserved only for proven secondary infections such as pneumonia, otitis media or urinary tract infections. Aminoglycosides should be avoided as they are weak pharmacologic neuromuscular blocking agents which may worsen paralysis acutely or cause respiratory failure in an unsuspected infant with botulism being treated for sepsis.
6. Human botulinum immunoglobulin (BIG), which acts by interrupting the blockade of nerve receptors by botulinum toxin, has been shown to reduce the need for mechanical ventilatory support and shorten overall duration of hospitalization.
7. If recognized early and given appropriate supportive care minimizing complications, full recovery and a normal neurologic function can be expected.
8. Classic "botulism" is a food borne disease in which high levels of toxin can be ingested in spoiled food. It often occurs in outbreaks linked to a particular source, and typically afflicts older children and adults. Wound botulism is rare, but is seen disproportionately in adolescents and children. Infant botulism has a more gradual onset. All types of botulism produce disease through a similar pathogenesis.