What is Infant Botulism?

Infant botulism is a paralytic disease caused by ingestion of Clostridium botulinum, an organism found in soil that releases a neurotoxin after colonizing the gastrointestinal tract.1 In a global study by Koepke et al, the United States was found to have the highest number of infant botulism cases with a total of 2419 from 1976-2006, resulting in an incidence of 2.1 cases per 100,000 live births.2 Approximately 98% of cases of infant botulism occur in patients between 1 and 6 months of age.3 While foodborne botulism occurs after ingestion of toxin, infant botulism differs in that the organisms in the intestines are continually making toxin.3 As botulinum spores can be widely found in the environment, ingestion of the organisms may be a relatively common occurrence in humans; however, normal flora in intestines of adults are able to compete against the botulinum organisms. Babies are more susceptible to the disease, as their intestinal flora may not be able to clear the organism from their body.4 Once the toxin travels through the bloodstream, it binds to the neuromuscular junction, blocking acetylcholine.1,5 Without acetylcholine in the presynaptic junction, muscle excitation cannot occur, causing “symmetric, descending motor weakness and flaccid paralysis with autonomic dysfunction progressing over the course of hours to a few days, proceeding from cranial nerves to the trunk, extremities, and finally the diaphragm.”6

The main risk factor that has been implicated in infant botulism is honey exposure in children younger than one year of age, as honey has been found to contain botulinum spores. Therefore, honey consumption among infants younger than one year of age is not recommended.1 Although this is the most well-known risk factor, 85% of patients with infant botulism have no known honey exposure. Honey consumption among infants has declined, yet the incidence of the disease has remained at approximately the same rate in the United States.3 Living in rural areas near construction sites is another risk factor for the disease, as microscopic spores can be ingested from dirt and dust from the environment.2,7 Additionally, constipation is a risk factor because “with fewer bowel movements per day, the gut flora may be disrupted, which could encourage spore growth and colonization.”7

Typical clinical findings of infant botulism include progressive hypotonia, flaccid paralysis extending from the cranial nerves to the extremities, and constipation. Parents of infants with the condition often note that their babies have a weak latch while trying to breastfeed or are unable to feed at all. Other signs are a weak “sheep-like” cry, drooling, decreased head control, loss of facial expression, and diminished deep tendon reflexes. Ptosis, fixed pupils, mydriasis, impaired extraocular movements, and inability to follow may be ophthalmic physical examination findings. Apnea can occur, as well.1,8

There are several clinical mimics of infant botulism that all present as “floppy baby syndrome”: spinal muscular atrophy, metabolic diseases like mitochondrial disease, Guillain-Barré syndrome, and other neurologic infections. Therefore, it is important to know the appropriate diagnostic studies to perform to lead to an accurate diagnosis.8 Botulinum toxin can be found in stool, gastric aspirate, vomit, and blood; however, these tests have a low sensitivity. The confirmatory and most sensitive diagnostic test for botulism is toxin neutralization mouse bioassay of stool samples, conducted at either the CDC or state health departments.6

Electrophysiology studies can be helpful for diagnosis, as well. The typical triad of electromyographic findings for infant botulism are low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and absence of post-tetanic exhaustion.9 To rule out other causes of paralysis, muscle and nerve biopsies can be performed.10 Other testing that can be performed to rule out other differentials includes cerebrospinal fluid analysis and culture, metabolic panels, and hepatic panels. However, the results of these studies are typically unremarkable.6,7

Since symptoms may progress before confirmatory diagnostic results are returned, all treatment should start as soon as a clinical diagnosis is made. Infants should be hospitalized so they can receive respiratory support and parenteral nutrition, if necessary.

Treatment for infant botulism approved by the US Food and Drug Administration is intravenous human botulism immune globulin, referred to as BabyBIG. A 5-year, double-blind, randomized control trial performed in California found that infants treated with BabyBIG had a reduced mean duration of hospital stay from 5.7 weeks to 2.6 weeks. Additionally, duration of time spent in the intensive care unit was reduced by a mean of 3.2 weeks, mechanical ventilation was reduced by 2.6 weeks, and tube feeding was reduced by 6.4 weeks. Although the immune globulin is an expensive treatment, the study also found that its use results in an $88,600 reduction in mean hospital charges per patient.5 Acquiring the drug as soon as possible after clinical diagnosis is crucial to decrease the morbidity of the disease.7

Although infant botulism causes severe symptoms, the prognosis for the disease has greatly improved and the mortality rate has declined to 3% to 6%.1,6 As regeneration of motor end plates occurs, patients progressively improve. Peripheral muscles typically take longer than the diaphragm to recover.7

The most worrisome complication of the disease is respiratory failure, and studies have found that “approximately half of all infants with infantile botulism require mechanical ventilation at some point during the course of infection.”7 Fortunately, “neurologic sequelae are rarely seen as a result of infantile botulism,” and no permanent deficits occur.7 Speech, occupational, and physical therapy may be needed during the recovery process to ensure that the infants are able to catch up to milestones they have missed and get back on track developmentally.

Summary

The etiology of Grace’s case of infant botulism cannot be attributed to honey, as she had no exposure. Although there is no way to definitively determine what caused her disease, a possible etiology is ingestion of spores from a local park, where another infant acquired infant botulism after exposure there, as well. Additionally, Grace had a history of constipation, which could have put her at increased risk for the disease.

This case demonstrates the significance of maintaining a broad differential diagnosis, which should include consideration of diseases that are less prevalent. Lack of clinical awareness of rare conditions can lead practitioners down the wrong path. As a primary care provider, it is crucial to consider infant botulism in infants presenting with “floppy baby syndrome,” even if they do not have a history of honey consumption.  Early recognition prevents delays in diagnosis so that the highly effective immune globulin treatment can be started as soon as possible.

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Victoria Hauff, PA-C, currently works in dermatology in Woodstock, Georgia.  Judith Stallings, EdD, MHE, PA-C, is PA program director at Augusta University.

References

  1. Hay WW, Deterding RR, Levin MJ, Azbug MJ. Current Diagnosis and Treatment: Pediatrics. 22nd Edition. New York: McGraw-Hill Education; 2014.
  2. Koepke R, Sobel J, Arnon SS. Global occurrence of infant botulism, 1976-2006. Pediatrics. 2008;122(1):e73-e82.
  3. Tseng-Ong L, Mitchell WG. Infant botulism: 20 years’ experience at a single institution. J Child Neurol. 2007;22(12):1333-1337.
  4. Grant KA, McLauchlin J, Amar C. Infant botulism: advice on avoiding feeding honey to babies and other possible risk factors. Community Pract. 2013;86(7):44-46.
  5. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354(5):462-471.
  6. Fox CK, Keet CA, Strober JB. Recent advances in infant botulism. Pediatr Neurol. 2005;32(3):149-154.
  7. Brown N, Desai S. Infantile botulism: a case report and review. J Emerg Med. 2013;45(6):842-845.
  8. Francisco AM, Arnon SS. Clinical mimics of infant botulism. Pediatrics. 2007;119(4):826-828.
  9. Smith JK, Burns S, Cunningham S, Freeman J, McLellan A, McWilliam K. The hazards of honey: infantile botulism. BMJ Case Rep. 2010. doi: 10.1136/bcr.05.2010.3038,2010
  10. Keet CA, Fox CK, Margeta M, et al. Infant botulism, type F, presenting at 54 hours of life. Pediatr Neurol. 2005;32(3):193-196.