Review articleRecent advances in infant botulism
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
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