Elsevier

Pediatric Neurology

Volume 32, Issue 3, March 2005, Pages 149-154
Pediatric Neurology

Review article
Recent advances in infant botulism

https://doi.org/10.1016/j.pediatrneurol.2004.10.001Get rights and content

Since infant botulism was first identified three decades ago, our understanding of botulinum toxins and the organisms that produce them has grown. A newer classification system now recognizes Clostridium baratii and Clostridium butyricum along with Clostridium botulinum as causative agents. Recently, increasing therapeutic use of botulinum toxins has sparked substantial new research into their mechanisms of action. This research, and some case reports from infants sickened by unusual botulinum toxins suggest that disease caused by different toxin types may result in varying clinical presentations. Perhaps most significantly for pediatricians and child neurologists, a specific treatment for infant botulism has just been approved. This article reviews the clinical presentation, diagnosis, and treatment of infant botulism, including human botulism immune globulin, and discusses the various organisms and toxins that cause this disease.

Introduction

Since infant botulism was first recognized and described in 1976 [1], [2], it has become the most commonly reported syndrome caused by botulinum toxin. Over 60% of newly reported botulism cases are infantile, accounting for approximately 75 cases per year in the United States. Botulism typically results from toxins produced by the anaerobic, spore forming gram-positive bacilli Clostridium botulinum. The toxins, which block cholinergic synapses, cause four recognized types of distinct human disease, including food-borne botulism, wound botulism, adult intestinal colonization, and infant botulism. Food-borne botulism occurs through ingestion of preformed toxin, whereas in the other three types, disease occurs through the infection and growth of clostridial organisms that germinate in a wound or in the gastrointestinal tract and then produce the toxins, which are absorbed into the body.

Section snippets

Clinical syndrome

Infant botulism usually occurs between 2 weeks and 1 year of age, with a median age of 10 weeks. Although botulism in infants younger than 2 weeks rarely is reported, the youngest patient in the literature was 6 days of age [3] when he became ill, and one infant with confirmed botulism in California was only 54 hours old at the onset of symptoms [4]. While the hypothesized incubation period for botulism is 3–30 days [5], the California infant with symptoms after 54 hours of life suggests that

Epidemiology

In older children and adults with intestinal botulinal colonization, host susceptibility factors are thought to play a role in allowing colonization and growth of clostridia. Infant susceptibility to gut colonization is thought to be due to age-associated perturbations in the normal gut flora caused by immaturity or dietary changes. Because the syndrome has been associated with weaning from breast milk, changes in gut flora with the introduction of new foods have been implicated in allowing

Pathophysiology—organisms

Although the clostridia that cause botulism are a heterogeneous group, historically all clostridia that produce botulinum toxins were classified as the single species Clostridium botulinum because of their ability to produce neurotoxin with similar pharmacologic properties. However, this began to change in the 1980s after Clostridium baratii and Clostridium butyricum were isolated and identified as causative agents in a few infants diagnosed with botulism [24]. Currently, the genetically and

Pathophysiology—toxins

The seven botulinum serotypes along with tetanus neurotoxin comprise the clostridial neurotoxin family, which cause the neuroparalytic syndromes of tetanus and botulism by a shared mechanism of blocking neurotransmitter release. It is this presynaptic blockade that leads to the incremental response on high-frequency repetitive nerve stimulation due to post-tetanic facilitation. Tetanus neurotoxin acts mainly at the central nervous system synapse, whereas the seven botulinum neurotoxins act

Diagnosis

Electrophysiology is usually the quickest way to make a diagnosis of botulism. The electrodiagnostic findings usually include normal nerve conduction studies. Electromyography commonly reveals increased insertional activity along with polyphasic motor units of small amplitude and short duration, consistent with acute denervation, although these finding are not specific for botulism and can be seen in axonal neuropathies or certain myopathies. Typically, M-wave amplitude is small, and paired

Treatment

Until recently, the treatment for infantile botulism was largely supportive, consisting of respiratory Figure 1 and nutritional care. However, a significant advancement in treatment came in October 2003, when human botulism immune globulin (Baby-BIG) was approved by the Food and Drug Administration for use in infant botulism. Baby-BIG is derived from pooled plasma of adults immunized with pentavalent botulinum toxoid and selected for high titers of neutralizing antibodies against type A and B

Prognosis

The prognosis for full recovery from infant botulism without residual weakness is generally good if no complications occur. However, aspiration from decreased gastric emptying and death from paralysis of the diaphragm can occur quickly. In hospitalized patients, mortality rates are reported to be from 3% to 5% [51], [52]. Complications may also result from prolonged intubation and mechanical ventilation [53]. Nutritional support with nasogastric enteral feeds should be started as soon as the

Conclusion

Botulism should be suspected in any infant who presents with feeding difficulties, paralysis, autonomic involvement, or fulminant respiratory failure. The clinical syndromes caused by distinct botulinum toxins may be varied, perhaps due to the distinct properties of different botulinum toxins. Early recognition of infant botulism and treatment with human botulism immune globulin can substantially decrease the length and cost of hospitalization, morbidity, and mortality. With timely diagnosis

References (60)

  • T.D. Anderson et al.

    Airway complications of infant botulismTen-year experience with 60 cases

    Otolaryngol Head Neck Surg

    (2002)
  • S.S. Arnon et al.

    Intestinal infection and toxin production by Clostridium botulinum as one cause of sudden infant death syndrome

    Lancet

    (1978)
  • O.A. Sonnabend et al.

    Continuous microbiological and pathological study of 70 sudden and unexpected infant deathsToxigenic intestinal Clostridium botulinum infection in 9 cases of sudden infant death syndrome

    Lancet

    (1985)
  • J. Pickett et al.

    Syndrome of botulism in infancyClinical and electrophysiologic study

    N Engl J Med

    (1976)
  • E.H. Thilo et al.

    Infant botulism at 1 week of ageReport of two cases

    Pediatrics

    (1993)
  • Keet LA, Fox CK, Margeta M, et al. Infant botulism type F, presenting at 54 hours of life. Pediatr Neurol 2004 [Epub...
  • T.F. Midura

    UpdateInfant botulism

    Clin Microbiol Rev

    (1996)
  • S.S. Long et al.

    Clinical, laboratory, and environmental features of infant botulism in Southeastern Pennsylvania

    Pediatrics

    (1985)
  • S.S. Long

    Epidemiologic study of infant botulism in PennsylvaniaReport of the Infant Botulism Study group

    Pediatrics

    (1985)
  • M.S. Schreiner et al.

    Infant botulismA review of 12 years’ experience at the Children’s Hospital of Philadelphia

    Pediatrics

    (1991)
  • S.S. Long

    Infant botulism

    Pediatr Infect Dis J

    (2001)
  • G. Vita et al.

    Cardiovascular-reflex testing and single-fiber electromyography in botulismA longitudinal study

    Arch Neurol

    (1987)
  • H. Sugiyama et al.

    Intraintestinal toxin in infant mice challenged intragastrically with Clostridium botulinum spores

    Infect Immun

    (1978)
  • L.J. Moberg et al.

    The rat as an animal model for infant botulism

    Infect Immun

    (1980)
  • D.H. Burr et al.

    Susceptibility to enteric botulinum colonization of antibiotic-treated adult mice

    Infect Immun

    (1982)
  • L.J. Moberg et al.

    Microbial ecological basis of infant botulism as studied with germfree mice

    Infect Immun

    (1979)
  • J.S. Spika et al.

    Risk factors for infant botulism in the United States

    Am J Dis Child

    (1989)
  • L.D. Smith

    Clostridium botulinumCharacteristics and occurrence

    Rev Infect Dis

    (1979)
  • P. Aureli et al.

    Infant botulism and honey in EuropeA commentary

    Pediatr Infect Dis J

    (2002)
  • H. Therre

    Botulism in the European Union

    Euro Surveill

    (1999)
  • Cited by (85)

    • Clostridium botulinum

      2021, Foodborne Infections and Intoxications
    • Diseases of the Nervous System

      2019, Large Animal Internal Medicine
    View all citing articles on Scopus
    View full text