EM@3AM: Botulism

Author: Sofi Rodriguez, DO (EM Resident Physician, UTSW, Dallas, TX) // Reviewed by: Kapil Sharma, MD (EM Attending Physician, UTSW, Dallas, TX); Kerollos Shaker, MD (Medical Toxicology Fellow, UTSW, Dallas, TX); Brit Long, MD (@long_brit)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.


A 3-month-old female is brought into your ED by her mother for constipation and decreased PO intake for 3 days. She was born full term without complications and is breastfed along with some soft foods. When asking about changes in diet, her mother states they only eat organic and grow most of their own food on their farm. They also can some food to prevent spoiling.

Examination reveals BP 90/60, HR 120, T 98F oral, RR 30, SpO2 98% on RA. It takes longer than expected for her to open her eyes, and she appears to have head lag. She will not feed while in the ED despite multiple attempts.

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?


Diagnosis: Botulism

 

Background

  • Botulism is a rare but life-threatening neuro-paralytic disease caused by the neurotoxin formed by the bacterium Clostridium botulinum.
  • First documented cases of botulism poisoning occurred in Germany in the 1820s, referred to as “sausage poisoning” [1].
  • The organism was named Bacillus botulinus after the Latin word for sausage, botulus [1].
  • Botulinum toxin is the most potent bacterial toxin and thought to be the most potent known poison. Minimum lethal dose in mice has been shown to be 0.0003mcg/kg [2].
  • One gram of aerosolized botulism toxin is estimated to be able to kill at least 1.5 million people and is therefore a potential bioterrorism agent [3].

 

Pathophysiology

  • C. botulinum is a rod-shaped, gram-positive, spore-forming, obligate anaerobic bacteria  found on the surface of seafood, fruits and vegetables and also exists in soil [4].
  • C. botulinum spores are heat resistant and can survive 100°C for five or more hours, and spores can be destroyed by heating to 120°C for five minutes. Therefore, all home canned goods should be boiled for 10 minutes prior to consumption [5].
  • When in favorable environmental conditions such as reduced oxygen exposure, appropriate temperature, and pH less than 7, the spores will germinate and grow into bacilli [5].
  • The bacilli can produce neurotoxin that can target motor and sensory neurons and can block the cholinergic neuromuscular innervation of striated and smooth muscles as well as the cholinergic innervation of the tear, salivary, and sweat glands [6].
  • Botulinum toxin can affect both excitatory and inhibitory synapses but is more active in excitatory neurons. Owing to its large size, there is limited passage of the botulism toxin through the blood brain barrier [2].

 

There are many types of botulism but the three most common types are: infant botulism, foodborne botulism, wound botulism.

Infant botulism

  • Results from intestinal colonization by C. botulinum, which produces a neurotoxin that blocks presynaptic cholinergic transmission, affecting skeletal and smooth muscle and autonomic function [7].
  • Affects infants between one week and 12 months of age, but most commonly between two and eight months of age with the median age of onset of three to four months [8, 9].
  • Infants typically present with constipation and poor feeding followed by progressive hypotonia and weakness [9].

Foodborne botulism

  • Caused by ingestion of food contaminated by pre-formed botulinum toxin. Toxin types A, B, and E have been associated with foodborne botulism. Most cases of botulism occur due to home-canned foods [10-12].
  • In the United States, the highest rates of foodborne botulism are reported among Alaskans as a result of ingestion of aged fish and marine mammals [13, 14].
  • Prison brew (also known as moonshine, hooch, or bootleg), an alcoholic beverage made by fermenting fruit and sugar in water with bread or potato, has been identified as a major source of outbreaks within prison populations [15-17].

Wound botulism

  • C. botulinum can infect wounds and produce neurotoxin in vivo. This is typically associated with puncture wounds and deep space infections, due to the anaerobic environment which allows spores to germinate [18, 19].
  • Wound botulism is associated with injection drug use, particularly with “black tar” heroin and subcutaneous or intramuscular injection [18, 19].

 

History and exam

History:

  • Detailed history should be performed including history of home canning, exposure to other possible food sources (including honey in infants <12 months of age), injection drug use, and trauma.

Exam:

  • Physical examination should include a tick check, as patients with tick paralysis can present similarly. In contrast to some polyneuropathies that botulism could be mistaken for (eg, Guillain-Barré syndrome), reflexes are typically normal in patients with botulism unless the affected muscle group is completely paralyzed [20]
  • The United States Centers for Disease Control and Prevention (CDC) has also suggested that the following be considered as key features of the botulism syndrome:
    • Absence of fever
    • Symmetric neurologic deficits
    • Normal sensorium and mental status
    • Normal or slow heart rate and normal blood pressure
    • Absence of sensory deficits, with the exception of blurred vision [21]

 

Differential: Myasthenia Gravis, Lambert-Eaton Syndrome, Guillain-Barré syndrome, poliomyelitis, heavy metal intoxication, tetrodotoxin and shellfish poisoning, tick paralysis, and antimicrobial-associated paralysis.

Among causes of flaccid paralysis, botulism is distinctive because of the early involvement of cranial nerves, the symmetric descending paralysis, and the lack of sensory neuropathy.

 

Diagnostics

  • Botulism should be suspected in a patient with acute onset of signs and symptoms of a cranial neuropathy and symmetric descending weakness, particularly in the absence of fever.
  • In infants, botulism should be suspected when there is acute onset of weak suck, ptosis, inactivity, and constipation (eg, floppy baby syndrome).
  • The presumptive diagnosis can be made on clinical findings alone.
  • In a study that included 241 cases of botulism recorded in the National Botulism Surveillance Database in the United States, three clinical criteria (lack of fever, at least one specific symptom of cranial neuropathy, and at least one specific sign of cranial neuropathy) were met in 89 percent of patients [22].
    • The specificity of these three criteria is unknown, and the absence of one of these criteria does not rule out the possibility of botulism, however, this tool could be helpful for clinicians to prompt consideration of botulism earlier in the course of disease.
  • Meningismus, headache, altered mental status, and fever are usually absent in botulism. If present, another condition should be considered and lumbar puncture performed.
  • Tensilon (edrophonium) tests, if available, should not be conducted, as they are often falsely positive in patients with botulism [23].
  • The diagnosis of botulism is confirmed by identification of toxin in serum, stool, vomitus, or food sources which requires one to four days and anaerobic cultures often take up to six days for growth and identification of the organism.
  • These confirmatory tests do not yield timely results, therefore, the decision to administer antitoxin should be based on the presumptive clinical diagnosis of botulism and not be delayed while awaiting results of confirmatory diagnostic studies.

 

Management

  • Close clinical evaluation of ventilation, perfusion, and upper airway compromise in the ICU setting along with frequent arterial blood gas measurement.
  • Intubation should be considered for those patients with a vital capacity less than 30 percent of predicted.
  • Mortality is due to respiratory muscle weakness. Prompt intubation with mechanical ventilation will dramatically reduce this risk.
  • If the clinical suspicion for botulism is high and symptoms are progressing, antitoxin should be administered as soon as possible and should not be delayed while awaiting results of diagnostic studies.
  • Data informing the efficacy of botulinum antitoxin are limited and uncontrolled but demonstrate a benefit [24].
  • In a meta-analysis of 61 studies and case series of patients with botulism, antitoxin was associated with a reduction in mortality (odds ratio [OR] 0.22, 95% CI 0.17-0.29), although there was substantial heterogeneity across studies [24].
  • Equine serum heptavalent botulism antitoxin is used to treat children older than one year of age and adults; human-derived botulism immune globulin is used for infants less than one year of age [24].
  • In the United States, the clinician should contact the state health department immediately for assistance with the decision of whether botulism antitoxin is indicated and to obtain a supply of antitoxin.
  • Antibiotic therapy is unproven by clinical trials but widely used and recommended for wound botulism after antitoxin has been administered [25]
    • Penicillin G (3 million units IV every four hours in adults) provides effective coverage of clostridial species and is frequently used.
    • Metronidazole (500 mg IV every eight hours) is a possible alternative for penicillin-allergic patients.

 

Complications

  • Respiratory failure is the primary cause of death in these patients. Consider early intubation.
  • Overall, most patients with prompt hospitalization and respiratory care can expect a complete or nearly complete recovery with return to previous level of functioning [26].

 

Disposition

  • All suspected botulism patients should be admitted for close monitoring to an ICU.

 

Public health evaluation: In the United States, clinicians caring for patients with suspected botulism should contact the state health department for assistance with the clinical and laboratory evaluation. State public health officials can reach the CDC clinical emergency botulism service at 770-488-7100. For suspected infant botulism occurring in any state, the California Department of Health Services, Infant Botulism Treatment and Prevention Program should be contacted (www.infantbotulism.org or 510-231-7600).

 

Take home points

  • Botulism is a rare but potentially life-threatening neuro-paralytic syndrome caused by a neurotoxin produced by Clostridium botulinum.
  • Several forms of botulism exist. The most common are infant botulism, foodborne botulism, and wound botulism.
  • Consider intubation in patients with compromised upper airway integrity or vital capacity less than 30 percent of predicted.
  • If suspicion of botulism is high, admit to ICU, and give antitoxin prior to confirmation of diagnosis.

Further Reading:

FOAMed

https://wikem.org/wiki/Botulism

https://www.emrap.org/episode/infections/botulism

https://www.emrap.org/episode/emrap2019august/pediatricpearls

https://litfl.com/botulism/

 

References

1 Kerner J. Neue Beobachtungen uber die in Wurtemburg so haufig vorfallen Vergiftung durch den Genuss gerauchter Wurst. Tubingen, 1820. In: Food Infections and Food Intoxications, Damon SR (Ed), Williams and Wilkins, Baltimore 1928. p.67.

2 Middlebrook JL. Relative lethality of selected toxins. In: Ellenhorn’s Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2nd ed, Ellenhorn MJ, Schonwald S, Ordog G, et al (Eds), Williams and Wilkins, Baltimore 1997. p.1055.

3 Mcnally RE, Morrison MB, Berndt JE, et al. Effectiveness of medical defense interventions against predicted battlefield levels of botulinum toxin A, Science Applications International Corp, Joppa 1994.

4 Dowell VR Jr. Botulism and tetanus: selected epidemiologic and microbiologic aspects. Rev Infect Dis 1984; 6 Suppl 1:S202.

5 Bleck TP. Clostridium botulinum (botulism). In: Principles and Practice of Infectious Diseases, 6th ed, Mandel, GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, Philadelphia 2005. p.2822.

6 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; 36:10.

7 Sobel J. Botulism. Clin Infect Dis 2005; 41:1167.

8 Thompson JA, Glasgow LA, Warpinski JR, Olson C. Infant botulism: clinical spectrum and epidemiology. Pediatrics 1980; 66:936.

9 Thompson JA, Filloux FM, Van Orman CB, et al. Infant botulism in the age of botulism immune globulin. Neurology 2005; 64:2029.

10 Mazuet C, Ezan E, Volland H, et al. Toxin detection in patients’ sera by mass spectrometry during two outbreaks of type A Botulism in France. J Clin Microbiol 2012; 50:4091.

11 Bergeron G, Latash J, Da Costa-Carter CA, et al. Notes from the Field: Botulism Outbreak Associated with Home-Canned Peas – New York City, 2018. MMWR Morb Mortal Wkly Rep 2019; 68:251.

12 Ganapathiraju PV, Gharpure R, Thomas D, et al. Notes from the Field: Botulism Type E After Consumption of Salt-Cured Fish – New Jersey, 2018. MMWR Morb Mortal Wkly Rep 2019; 68:1008.

13 Fagan RP, McLaughlin JB, Castrodale LJ, et al. Endemic foodborne botulism among Alaska Native persons–Alaska, 1947-2007. Clin Infect Dis 2011; 52:585.

14 Austin JW, Leclair D. Botulism in the North: a disease without borders. Clin Infect Dis 2011; 52:593.

15 Centers for Disease Control and Prevention (CDC). Notes from the field: botulism from drinking prison-made illicit alcohol – Arizona, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:88.

16 McCrickard L, Marlow M, Self JL, et al. Notes from the Field: Botulism Outbreak from Drinking Prison-Made Illicit Alcohol in a Federal Correctional Facility – Mississippi, June 2016. MMWR Morb Mortal Wkly Rep 2017; 65:1491.

17 Rao AK, Walters M, Hall J, et al. Outbreak of Botulism Due to Illicit Prison-Brewed Alcohol: Public Health Response to a Serious and Recurrent Problem. Clin Infect Dis 2017; 66:S85.

18 Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA 1998; 279:859.

19 Peak CM, Rosen H, Kamali A, et al. Wound Botulism Outbreak Among Persons Who Use Black Tar Heroin – San Diego County, California, 2017-2018. MMWR Morb Mortal Wkly Rep 2019; 67:1415.

20 Hodowanec A, Bleck TP. Clostridium botulinum (Botulism). In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th ed, Bennett JE, Dolin R, Blaser MJ (Eds), Elsevier Saunders, Philadelphia 2015. p.2763.

21 Centers for Disease Control and Prevention. National Botulism Surveillance. https://www-cdc-gov.foyer.swmed.edu/botulism/surveillance.html (Accessed on September 21, 2020).

22 Rao AK, Lin NH, Griese SE, et al. Clinical Criteria to Trigger Suspicion for Botulism: An Evidence-Based Tool to Facilitate Timely Recognition of Suspected Cases During Sporadic Events and Outbreaks. Clin Infect Dis 2017; 66:S38.

23 Roland EH, Ebelt VJ, Anderson JD, Hill A. Infant botulism: a rare entity in Canada? CMAJ 1986; 135:130.

24 O’Horo JC, Harper EP, El Rafei A, et al. Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923-2016. Clin Infect Dis 2017; 66:S43.

25 American Academy of Pediatrics. Botulism and infant botulism (Clostridium botulinum). In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.294.

26 Gottlieb SL, Kretsinger K, Tarkhashvili N, et al. Long-term outcomes of 217 botulism cases in the Republic of Georgia. Clin Infect Dis 2007; 45:174.

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