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Disease/ Disorder

Definition

Infantile Botulism is a neuromuscular junction disorder that is caused by exposure to the neurotoxin produced by Clostridium botulinum. The toxin works by blocking acetylcholine release at the synapse. This results in a descending muscle flaccid paralysis.1,2,3

Etiology

In infantile botulism, spores are absorbed by the intestinal tract of infants. The toxin is most commonly produced by Clostridium botulinum but can also be caused by Clostridium baratii and Clostridium butryicum.4 There are several toxins including A, B, C, D, E, F, G, but human cases are typically caused by A, B, E, and F.5 Each toxin type typically has a different pathophysiology. There are two other forms of botulism including foodborne botulism (through toxin contaminated foods) and botulism through wound contamination.3

Epidemiology including risk factors and primary prevention

In the United States, the most recent report from the CDC indicates 162 cases of infant botulism reported from 31 states.6

Spores can be found in dust and soil. Infants can then be exposed by this7 and honey, which is the only food proven to be associated with infant botulism.8,9 Age is a predisposing factor for infant botulism; most commonly it is seen in infants between 2 weeks and six months of age, and usually not seen in those greater than one year of age.1 Furthermore, decreased intestinal motility can assist spore growth and toxin production.10

Patho-anatomy/physiology

After absorption in the intestines, the botulinum toxin is released into circulation where it then reaches peripheral cholinergic nerve endings at the neuromuscular junction.11 At the neuromuscular junction, toxin proteins bind to the pre-synaptic end of the neuromuscular junction, preventing the release of acetylcholine. This can affect both striated and smooth muscles, and tears, salivary, and sweat glands.12-14 Incubation period is at least three days.15

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Infants typically present with constipation and progress to a pure motor symmetrical, descending, flaccid paralysis – especially affecting bulbar musculature early in the disease, and without effect on sensory nerves.1 Infantile botulism is also associated with weak cry, poor suck and swallow, and respiratory insufficiency.3

Of note, in foodborne or wound botulism, cranial nerve involvement is the most common finding.16

As the disease progresses, there is concern for hypoxemia, dehydration, and respiratory failure.1 It typically progresses over 1-2 weeks, stabilizes over 2-3 weeks, and most patients fully recover within weeks to months as the nerve terminals recover, allowing for improved acetylcholine transmission.  

Mortality usually occurs if there is respiratory failure. Hospitalization typically takes one to three months due to need for respiratory and nutritional support and physical deconditioning.13,17

Specific secondary or associated conditions and complications

Complications are usually related to respiratory distress including anoxic injury, cardiac arrest, syndrome of inappropriate antidiuretic hormone, nasogastric tube issues, urinary tract infections, and septicemia. There are several respiratory complications as well which is typical of intubated patients including pneumonia.18   

Essentials of Assessment

History

Families may notice constipation, urinary retention, sleepiness, poor feeding, expressionless fact, a weak cry, and drooling.1 Constipation is usually the first symptom but may not always be detected. The constellation of symptoms seen with infantile botulism may be confused with sepsis; however, it should be suspected in infants with acute flaccid paralysis, constipation, and cranial nerve deficits.19 In those with foodborne or wound botulism, acute gastrointestinal distress, vomiting, and subsequent onset of weakness occur within12 to 48 hours of ingestion or open wound.16

Physical exam

Infantile botulism may present with hypotonia and weakness, weak cry, poor suck, drooling, respiratory distress, cranial nerve dysfunction including ptosis, ophthalmoplegia, mydriasis, bulbar dysfunction, and poor gag reflex. There may also be decreased tearing, fluctuating blood pressure and heart rate. The hallmark of the condition is fatigability with repetitive muscle activity.1 Of note, there is an absence of fever. Symptoms are bilateral.13

Clinical functional assessment: mobility, self-care, cognition/behavior/affective state, laboratory studies

Diagnoses is made via presence of toxin in the stool, food, or wound.16 The toxin may be present for long periods of time (weeks to months), which can still produce toxin and spores.20 If stool cannot be collected, then an enema may be needed. The toxin can be detected within 24-48 hours and the organism may take 5 days for detection.1 Blood and cerebrospinal fluid tests will not be revealing for infantile botulism. Due to the prolonged length of time for collection and processing of sample, presumptive diagnosis may be made via history, exam, and electrodiagnostic studies. These studies can confirm infant botulism with brief-duration, small-amplitude, overly-abundant motor-unit action potentials.21 Repetitive nerve stimulation will show abnormalities including incremental response with high rate of stimulation and variable decremental response with low rate of stimulation. Single-fiber EMG can be considered as well to assess for botulism.22

Imaging

N/A

Supplemental assessment tools

N/A

Early prediction of outcomes

There is limited evidence for outcome predictors in infantile botulism. However, most patients fully recover.

Patient discharge should be based on nutritional status noted by improvements in suck, and swallow, and infant’s improved respiratory status and ability to be managed in the home setting.1 Providers should expect to see improvements in respiratory, swallow, and motor function.23,24

Environmental

N/A

Social role and social support system

N/A

Rehabilitation Management and Treatments

Available or current treatment guidelines

Prophylactic intubation for airway protection should be done if progressive respiratory insufficiency is noted.25 Respiratory function may not end up being impaired until more than 90-95% of receptors are blocked.1

Nasogastric tube feeds will also likely be required for nutritional support. Intravenous feeding is discouraged as are broad spectrum antibiotics (unless indicated for a secondary infection).25,26 Therapeutic enemas are unlikely to be effective for spore elimination.1

Current treatment involves the use of botulinum antitoxin (BIG-IV) which neutralizes the toxin immediately. As soon as botulism is clinically suspected, antitoxin should be immediately provided. BIG-IV should be used in infants less than one year old with toxin type A or B1 and for those older than one year old, a hepatvalent botulinum antitoxin (HBAT) should be used (as it blocks A through G).13 Recent data shows that outcomes such as mortality rate were reduced and the need for mechanical ventilation was lower if treated within 48 hours of onset of symptoms and tend to be better when patients are treated earlier.27,28

Those with wound botulism should undergo extensive debridement. Antibiotics can be considered as well.13

At different stages

N/A

Coordination of care

Vaccinations of live virus should be deferred for five months after BIG-IV.29

Public health officials should be contacted.13

Patient and family education

Measurement of treatment outcomes including those that are impairment-based, activity participation-based and environmentally-based:

Family and caregivers should monitor for recovery of weakness, respiratory issues, constipation, and cranial nerve deficits. They should be reassured that a majority of patients will recovery with supportive care, especially after treatment with antitoxin.27

Translation into practice: practice “pearls”/performance improvement in practice/changes in clinical practice behaviors and skills

Avoid raw honey in infants. In endemic areas, avoid exposure to significant amounts of soil and dust. Any infant with acute flaccid paralysis, constipation, cranial nerve deficits, and other anticholinergic signs should be suspected to have botulism. Due to its low incidence, it may not be as high on the differential – it is usually confused for sepsis.

Cutting Edge/ Emerging and Unique Concepts and Practice

Further outcome and epidemiologic studies on the impact of BIV and heptavalent antitoxin will need to be done.

Investigating different strains of spores.30

Controversies and Gaps in the Evidence-Based Knowledge

N/A

References

  1. Fenicia L, Anniballi F. Infant botulism. Ann Ist Super Sanita. 2009;45(2):134–46.
  2. Simpson LL. Molecular pharmacology of botulinum toxin and tetanus toxin. Annu Rev Pharmacol Toxicol. 1986;26:427–53.
  3. Rinaldi RJ, Skalsky A, Chaviano K. Neuromuscular Conditions [Internet]. 2021 [cited 2022 Nov 6]. Available from: https://connect.springerpub.com/content/book/978-0-8261-4707-3/chapter/ch23
  4. Feigin And Cherry’s Textbook Of Pediatric Infectious Diseases 2 Volume 7e [Internet]. [cited 2022 Nov 6]. Available from: http://archive.org/details/feigin-and-cherrys-textbook-of-pediatric-infectious-diseases-2-volume-7e
  5. Hauschild AHW. Epidemiology of Human Foodborne Botulism. In: Clostridium Botulinum. CRC Press; 1993.
  6. National Botulism Surveillance | Botulism | CDC [Internet]. 2021 [cited 2022 Nov 6]. Available from: https://www.cdc.gov/botulism/surveillance.html
  7. Thompson JA, Glasgow LA, Warpinski JR, Olson C. Infant botulism: clinical spectrum and epidemiology. Pediatrics. 1980 Dec;66(6):936–42.
  8. Arnon SS, Midura TF, Damus K, Thompson B, Wood RM, Chin J. Honey and other environmental risk factors for infant botulism. J Pediatr. 1979 Feb;94(2):331–6.
  9. Holst SW Elisabet. Spädbarnsbotulism – skäl att inte ge honung till barn under ett år [Internet]. Läkartidningen. 2017 [cited 2022 Nov 28]. Available from: https://lakartidningen.se/klinik-och-vetenskap-1/artiklar-1/fallbeskrivning/2017/07/spadbarnsbotulism-skal-att-inte-ge-honung-till-barn-under-ett-ar/
  10. Rick JR, Ascher DP, Smith RA. Infantile Botulism: An Atypical Case of an Uncommon Disease. Pediatrics [Internet]. 1999 May 1 [cited 2022 Nov 6];103(5):1038–9. Available from: https://doi.org/10.1542/peds.103.5.1038
  11. Simpson LL. Identification of the major steps in botulinum toxin action. Annu Rev Pharmacol Toxicol. 2004;44:167–93.
  12. Hauschild AH. Clostridium botulinum toxins. Int J Food Microbiol. 1990 Mar;10(2):113–24.
  13. Botulism – UpToDate [Internet]. [cited 2022 Nov 6]. Available from: https://www.uptodate.com/contents/botulism?search=infant%20botulism&source=search_result&selectedTitle=1~18&usage_type=default&display_rank=1#H21
  14. Kumar R, Dhaliwal HP, Kukreja RV, Singh BR. The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems. Semin Neurol. 2016 Feb;36(1):10–9.
  15. Midura TF. Update: infant botulism. Clin Microbiol Rev [Internet]. 1996 Apr [cited 2022 Nov 6];9(2):119–25. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC172885/
  16. Chatham-Stephens K, Fleck-Derderian S, Johnson SD, Sobel J, Rao AK, Meaney-Delman D. Clinical Features of Foodborne and Wound Botulism: A Systematic Review of the Literature, 1932–2015. Clin Infect Dis [Internet]. 2018 Jan 15 [cited 2022 Nov 6];66(suppl_1):S11–6. Available from: https://doi.org/10.1093/cid/cix811
  17. Varma JK, Katsitadze G, Moiscrafishvili M, Zardiashvili T, Chokheli M, Tarkhashvili N, et al. Signs and symptoms predictive of death in patients with foodborne botulism–Republic of Georgia, 1980-2002. Clin Infect Dis Off Publ Infect Dis Soc Am. 2004 Aug 1;39(3):357–62.
  18. Schreiner MS, Field E, Ruddy R. Infant botulism: a review of 12 years’ experience at the Children’s Hospital of Philadelphia. Pediatrics. 1991 Feb;87(2):159–65.
  19. Rossi M, Durrleman C, Hayat M, Roux CJ, Kossorotoff M, Gitiaux C, et al. Infant botulism: Report of a misleading case and important key messages. Arch Pediatr Organe Off Soc Francaise Pediatr. 2022 Jul;29(5):395–7.
  20. Kobayashi H, Fujisawa K, Saito Y, Kamijo M, Oshima S, Kubo M, et al. A botulism case of a 12-year-old girl caused by intestinal colonization of Clostridium botulinum type Ab. Jpn J Infect Dis. 2003 Apr 1;56(2):73–4.
  21. Johnson RO, Clay SA, Arnon SS. Diagnosis and management of infant botulism. Am J Dis Child 1960. 1979 Jun;133(6):586–93.
  22. Dumitru D, Amato AA, Zwarts MJ. Electrodiagnostic medicine [Internet]. 2nd ed. Philadelphia: Hanley & Belfus; 2002 [cited 2022 Dec 6]. 1 Online-Ressource (xi, 1524 pages). Available from: https://www.sciencedirect.com/science/book/9781560534334
  23. Cox N, Hinkle R. Infant Botulism. Am Fam Physician [Internet]. 2002 Apr 1 [cited 2022 Dec 6];65(7):1388–93. Available from: https://www.aafp.org/pubs/afp/issues/2002/0401/p1388.html
  24. Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. MMWR Recomm Rep [Internet]. 2021 May 7 [cited 2022 Dec 6];70(2):1–30. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112830/
  25. Arnon_1995_Infection_of_GI_tract_Chapt.pdf [Internet]. [cited 2022 Nov 6]. Available from: https://www.infantbotulism.org/readings/Arnon_1995_Infection_of_GI_tract_Chapt.pdf
  26. Brook I. Infant botulism. J Perinatol Off J Calif Perinat Assoc. 2007 Mar;27(3):175–80.
  27. Hatami F, Shokouhi S, Mardani M, Shabani M, Gachkar L, Alavi Darazam I. Early recovery of botulism: one decade of experience. Clin Toxicol [Internet]. 2021 Jul 3 [cited 2022 Nov 28];59(7):628–32. Available from: https://doi.org/10.1080/15563650.2020.1844225
  28. Witoonpanich R, Vichayanrat E, Tantisiriwit K, Wongtanate M, Sucharitchan N, Oranrigsupak P, et al. Survival analysis for respiratory failure in patients with food-borne botulism. Clin Toxicol [Internet]. 2010 Mar 1 [cited 2022 Nov 28];48(3):177–83. Available from: https://doi.org/10.3109/15563651003596113
  29. Van Horn NL, Street M. Infantile Botulism. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Dec 6]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK493178/
  30. DERMAN Y, KORKEALA H, SALO E, LÖNNQVIST T, SAXEN H, LINDSTRÖM M. Infant botulism with prolonged faecal excretion of botulinum neurotoxin and Clostridium botulinum for 7 months. Epidemiol Infect [Internet]. 2014 Feb [cited 2022 Nov 28];142(2):335–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151104/

Author Disclosure

Susan Apkon, MD
Sarepta, FibroGen and Capricor; No money received directly to me, institution received funding to administer the clinical trials; Clinical Trials PI
Scholar Rock and Biogen; No money received directly to me, institution received funding to administer the clinical trials; Clinical Trials Co-Investigator
Parent Project Muscular Dystrophy and American Board of PM&R; None; Boards of Directors

Denesh Ratnasingam, MD
Nothing to Disclose

Jeremy Roberts, MD
Nothing to Disclose