Infant botulism, the most common form of botulism encountered in the United States, has a unique pathogenesis. Unlike food-borne botulism, which results from the ingestion of preformed toxin, infant botulism occurs following the ingestion of Clostridium botulinum spores that germinate and colonize the infant gut. Botulinum neurotoxin is produced in vivo and absorbed, producing clinical disease. This form of botulism occurs almost exclusively in children younger than 1 year¹. The first clear association of in vivo production of botulinum neurotoxin and a syndrome of weakness in infants was described in 1976.² Subsequently, the pathophysiology, epidemiology, clinical manifestations, and specific therapy have been elucidated.

PATHOPHYSIOLOGY

C. botulinum is a gram-positive, spore-forming, obligate anaerobe that is found worldwide in soil and dust. Approximately 90% of U.S. cases of infant botulism are caused by toxin types A and B. However, cases due to toxin type E from C. butyricum and toxin type F from C. baratii have been reported.³ The spores can be found on fresh fruits and vegetables and in honey. The infant intestinal microflora plays a critical role in the pathophysiology of infant botulism. Experiments in mice show that adult mouse microflora completely inhibits gut colonization with C. botulinum or that significantly higher numbers of spores are required for successful colonization than in infant mice.⁴ Honey is the only food that has been unequivocally linked to specific cases of infant botulism.⁵ Corn syrup was implicated as a source of infection in the past, but changes in the production process have largely eliminated the risk of infection from corn syrup.⁶ With the decrease in the ingestion of honey by infants, the exact source of the spores is rarely found in individual cases.³ Once the spores are ingested botulinum toxin is produced in the gut. Then it is absorbed into the bloodstream and carried to peripheral cholinergic synapses, where it blocks the release of acetylcholine. Autonomic effects occur, as well as the classic somatic muscle weakness or paralysis. Botulinum toxin does not penetrate the central nervous system.¹

EPIDEMIOLOGY

Although C. botulinum spores are ubiquitous, there is a clear geographic clustering of cases. The majority of reported cases are from California and the eastern Pennsylvania, New Jersey, and Delaware region, apparently mirroring the geographic distribution of spores. Toxin serotype also varies geographically. Type B toxin causes about 90% of cases in Pennsylvania, whereas the majority of California cases are due to type A toxin.⁵ All reported cases of infant botulism have occurred in patients under one year of age, and 95% of cases occurred in the first 6 months of life. C. baratii toxin-type F causes disease in younger infants.³ The youngest reported case was 38 hours old.⁷ No sex, race, or seasonal risk factors have been identified. Arnon and colleagues showed that the age distribution of infant botulism is almost identical to that of sudden infant death syndrome (SIDS).⁸ However, others have not found definite evidence to support a link between SIDS and infant botulism.^9,10

The clinical severity of infant botulism varies widely. The onset of symptoms may be gradual (days) or abrupt (hours). Catastrophic presentations have been reported leading to delay in diagnosis.¹¹ Additionally, with rapid viral testing, cases of concomitant viral infections with infant botulism have been reported where diagnosis of botulism was delayed.^12,13 Some infants, regardless of treatment, never require airway intervention, whereas others need prolonged endotracheal intubation.¹ If the patient is evaluated early in the course of disease or has a slowly progressive course, the initial abnormal physical findings may be limited to weakness of the muscles innervated by the cranial nerves. Clinical assessment should include careful and repeated examination of pupillary constriction, extraocular movement, and gag, suck, and swallow reflexes. Repeated stimulation of a muscle is the most sensitive way to induce a clinically evident paralysis.¹⁴ The paralysis of infant botulism is symmetrical, flaccid, and descending. Weakness is detectable in all affected infants on presentation. Initial deep tendon reflexes may be normal, only to diminish later. The majority of patients are afebrile on presentation. Constipation, present in approximately 95% of patients at the time of presentation, is frequently overlooked.¹

Other diagnostic considerations such as myasthenia gravis, Guillain-Barré syndrome, and spinal muscular atrophy (SMA), can usually be eliminated by history and physical examination. In reviewing 618 cases of infants treated with botulism immunoglobulin for intravenous use (BIG-IV), Francisco and Arnon found that of the cases that were not laboratory confirmed, SMA type 1 and metabolic disorders were the most common “mimics” of infant botulism.¹⁵ Other “mimics” were Miller Fisher variant of Guillain-Barré syndrome, neuroblastoma, and viral infections.¹⁵ The initial working diagnosis of infant botulism is based exclusively on clinical findings and suspicion. Constipation and abnormal cranial nerve function are key features in distinguishing infant botulism from the other entities.¹ Sepsis is the most common clinical diagnosis at the time of hospital admission in patients later found to have infant botulism.¹

Laboratory confirmation of the diagnosis requires the isolation of C. botulinum or the demonstration of botulinum toxin from the patient’s stool. The mouse neutralization test is the preferred confirmatory method and is available from state health laboratories and from the Centers for Disease Control and Prevention (CDC) in Atlanta. Because of severe constipation, an enema with sterile, nonbacteriostatic water is often required to obtain a sample. The stool sample should be kept at 4°C during transport.⁵ Polymerase chain reaction testing though promising is not being used clinically.^16,17 Other laboratory tests are typically normal. Electromyography (EMG) demonstrates brief, small, abundant motor unit potentials, and repetitive stimulation of peripheral nerves shows facilitation of neuromuscular transmission, though this is not found in all cases. Additionally, EMG testing is unpleasant and technically challenging and is rarely needed for the initial diagnosis.⁵