Botulism (Potential Bioterrorism Agent)

Queensland Health Guidelines for Public Health Units

Revision History

• Disclaimer
• Infectious Agent
• Notification Criteria
• Notification Procedure
• Lab Aspects
• Reporting to NOCS
• Objectives of surveillance
• Public Health Significance and Occurrence
• Clinical Features
• Reservoir
• Mode of Transmission
• Incubation Period
• Period of Communicability
• Susceptibility and Resistance
• Management
• Preventive Measures
• Summary
• References

Infectious Agent

Clostridium botulinum is a spore-forming anaerobic bacillus. Botulism is caused by the neurotoxins produced by Clostridium botulinum. Of the recognised subtypes of neurotoxin, types A, B, E, rarely F and possibly G cause human illness.

Notification Criteria

The case should be reported to the Public Health Unit if there is clinical evidence regardless of whether there is laboratory definitive evidence for botulism or if identified as a case of acute flaccid paralysis

Clinical evidence

A clinically compatible illness (eg. diplopia, blurred vision, muscle weakness, paralysis, death, or constipation poor feeding, difficulty swallowing, an altered cry, loss of head control and hypotonia in infant botulism).

Laboratory definitive evidence

1.    Isolation of Clostridium botulinum in a clinical sample
OR
2.    Detection of Clostridium botulinum toxin in blood or faeces.

Community Outbreak Criteria    

1.    Two or more associated confirmed cases (confirmed outbreak)
OR
2.    Two or more associated suspected cases OR one confirmed case and one associated suspected case (suspected outbreak).

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Notification Procedure

Pathology Laboratories
To notify (i) on receipt of request for examination (except for wound botulism) and (ii) on microbiological or toxicological confirmation, by telephone or facsimile.

Attending Medical Practitioners/Medical Superintendents (or Delegates)
To notify all cases of acute flaccid paralysis on clinical diagnosis by telephone or facsimile.

C. botulinum is a ‘prescribed contaminant’ under the Food Act 2006 and Food Regulation 2006[1]. This means that if it is identified in food intended to be sold it must be immediately notified verbally to the chief executive of Queensland Health and reported in writing (using the approved form) within 24 hours by the person who has identified the contaminant and/or the person who was intending to sell the food.

Laboratory Aspects

Laboratory tests include detection of neurotoxin in clinical and food samples, detection of the organism and isolation from clinical and food samples.
The specimens required depend on the clinical presentation and include[2]

The gold standard test for botulinum is the mouse bioassay, which tests for A, B, E and F toxin subtypes^[3]. A positive result will usually be available within 24 – 48 hours of receipt of the specimen at Queensland Health Forensic and Scientific Services. For faeces samples, this is then confirmed by PCR.

* Blood and faeces should be collected from the patient as soon as possible after the onset of symptoms. It is preferable to collect blood (and faeces if possible) before administration of antitoxin. Blood is drawn into a plain specimen tube without anticoagulant. Ideally, 15-20mL serum and 25-50g faeces should be collected. 2mL of serum should be obtained from infants and as much faeces as possible[4]. Faecal sampling is important for the detection of C. botulinum and toxin as positive food samples may not be available

Reporting to NOCS

Reporting
Only confirmed cases should be reported.

Confirmed case
A confirmed case requires laboratory definitive evidence AND clinical evidence.

Suspected case
A suspected case requires clinical evidence only.

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Objectives of Surveillance

1. To monitor the epidemiology of botulism in Queensland to inform preventive strategies.
2. To identify cases, outbreaks and implicated food sources to enable prompt public health response

Public Health Significance and Occurrence

Botulism occurs worldwide. It is a rare but serious intoxication resulting from exposure to the toxins produced by C. botulinum.  Exposure may occur via ingestion, inhalation or percutaneously through a break in the skin, giving rise to the different forms of botulism. These are: foodborne (classical); intestinal (infant); wound; and inhalation.  The intestinal form is the most common and usually affects infants under 1 year, but can affect adults with altered GI anatomy and microflora and/or who are immunocompromised. In both the intestinal and wound form, the bacteria enter the body, multiply, and then release toxin.  In the foodborne and inhalational forms, toxin itself enters the body. The disease is highly lethal without treatment. With intensive therapy, mortality should be less than 5% but recovery may take months.

Twenty-four cases of botulism were reported in Australia between 1991 and 2015.
Botulinum toxin is a potential bioterrorism agent. Although the greatest threat may be by aerosol use, the more likely threat may be via the deliberate contamination of food or drink. When responding to a case, investigators should be mindful of the possibility of deliberate intoxication.

Clinical Features

A neuroparalytic progressive disorder, clinical features are similar across the different forms[5,6,7].

• Foodborne

Early symptoms are often marked fatigue, weakness, and vertigo.  Blurred vision, dry mouth and difficulty swallowing follow as the cranial nerves become involved. Flaccid paralysis continues, symmetrical and descending.  There is no fever and no loss of consciousness.  Paralysis of respiratory muscles can cause respiratory arrest and death without mechanical ventilation. Most cases recover, if diagnosed and treated promptly. Recovery may take months.

• Intestinal botulism

This form usually occurs in infants <1 year old and typically begins with constipation.  Other symptoms include: poor feeding, difficulty swallowing, an altered cry, loss of head control and hypotonia.  Illness ranges from mild with gradual onset to sudden infant death. An adult form occurs rarely in immunocompromised patients and is associated with altered bowel flora from antimicrobial use or in those with anatomical or functional bowel abnormality.

• Wound botulism

A rare disease, normally associated with severe trauma, it occurs when spores get into an open wound and reproduce in an anaerobic environment. Symptoms are similar to the foodborne form, but may take up to 2 weeks to appear.

• Inhalational botulism

Has only been reported in laboratory workers. In these cases, neurological symptoms were the same as in foodborne botulism, but the incubation period was longer. All affected people recovered within 2 weeks after antitoxin treatment. Studies suggest that following inhalational exposure, there would be an irritant upper airway prodrome followed by variable onset of different degrees of paralysis in different people.

• Iatrogenic botulism

Recommended doses of botulinum toxin used for use in cosmetic and medical treatments are too low to cause systemic disease. However, injection of high doses of an unapproved botulinum toxin may result in severe adverse events. Clinical manifestations are similar to other forms of botulism, with symmetrical cranial nerve palsies followed by descending, symmetric flaccid paralysis of voluntary muscles, which may progress to respiratory compromise and death.

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Reservoir

Sources and reservoirs for Clostridia spores include soil, mud, water, and the intestinal tracts of animals[8]. In humans, contaminated food items associated with botulinum toxin include[9]:

• For infants: Honey, home-canned vegetables and fruits, corn syrup.
• For children and adults: Home-canned foods with a low acid content, improperly canned commercial foods, home-canned or fermented fish, herb-infused oils, baked potatoes in aluminium foil, cheese sauce, bottled garlic, foods held warm for extended periods of time.

These spores, which are very resistant to a number of environmental stresses such as heat and high acid, can become activated in anaerobic environments, low acidity (pH greater than 4.6), high moisture content, and in temperatures ranging from 3°C to 43°C. In hostile environmental conditions, the heat-resistant spores enable the bacteria to survive in a dormant state until conditions become more favourable.

Mode of Transmission

• Ingestion of toxin-contaminated food which was not adequately cooked prior to consumption eg. improperly canned or preserved food consumed without further/adequate heating.
• Ingestion of C. botulinum spores, colonisation of the gut with the organism and subsequent production of toxins. Sources of the spores include foods and dust.
• Wound contamination (under anaerobic conditions) - usually via soil or gravel, but also occurs in injecting drug users. C. botulinum spores germinate and produce toxin in the wound.
• Inhalation of aerosolised toxin in a deliberate release or laboratory accident.
• There is no evidence of person-to-person transmission.

Incubation Period

Period of Communicability

Despite the excretion of organisms in the faeces of intestinal botulism patients for weeks to months after onset of illness, no instance of secondary person-to-person transmission has been documented. Foodborne botulism patients typically excrete the toxin for shorter periods.

Susceptibility and Resistance

Everyone is susceptible to intoxication. Intestinal botulism is almost always in infants <12 months of age.

Management

Cases

Investigation

• Investigate all notifications of testing request to ascertain whether there is a clinically compatible illness.
• If suspected case facilitate testing and notify CDB
• For suspected and confirmed cases try to identify the source of toxin and identify others who may have been exposed to it.

Treatment

• Foodborne, inhalation, intestinal and wound botulism: supportive treatment with access to intensive care management, and antitoxin
• In addition for wound botulism surgical treatment of contaminated wound, and appropriate antibiotics to prevent/manage secondary infections may also be considered

Antibiotics do not improve the course of the disease; aminoglycoside antibiotics may synergistically exacerbate the neuromuscular blockade.

Restriction         
Nil

Counselling
The case should be advised of the nature of the infection and its mode of transmission. Specific advice should be given if home food canning is implicated.

Antitoxin therapies

Antitoxin therapies should be considered if any suspicion of botulism. Under no circumstances should treatment be delayed while awaiting results of laboratory investigations and clinical observations.

Babybig©

Human derived anti-botulism toxin immunoglobulin or BabyBIG© is approved by the United States Food and Drug Administration for the treatment of infant (<1 year of age) botulism type A and B. First line treatment with BabyBIG© within 7 days of admission has shown to significantly reduce length of hospital stay. (6) The California Department of Public Health’s infant botulism treatment and prevention program offers access to BabyBIG© internationally on assessment. BabyBIG© has been imported and administered in Australia and can be considered on a case by case basis. Refer to https://www.infantbotulism.org/contact/international.php.

Botulism Antitoxin (BAT)

An intravenous heptavalent form of equine antitoxin [Botulism Antitoxin heptavalent (A,B,C,D,E,F,G) – Equine, Cangene Corp, Canada] is indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulism neurotoxin serotypes A, B, C, D, E ,F, or G in adults and paediatric patients. Treatment with heptavalent BAT will not reverse paralysis, but will help stop disease progression.

BAT is available from the National Medical Stockpile (NMS). For further information on accessing medicinal products in the NMS refer to Accessing medicinal items on the NMS. The use of heptavalent BAT is governed by the Therapeutics Goods Administration (TGA) Special Access Scheme and recommendations on the use in paediatric and adult patients should be in line with manufacturer’s instructions.

A 15-year systematic safety review of BAT product use demonstrated the benefits of BAT treatment on morbidity and mortality from botulism infection in intensive care settings outweighed potential adverse events.(7) The efficacy of heptavalent BAT has not established in paediatrics and limited safety data are available (see product information).

Further information:

California Department of Public Health - Infant botulism treatment and prevention program

US Food and Drug Administration - BAT (Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G) – (Equine)

References

1. Bennett, J.E., Dolin, R. and Blaser, M.J., 2014, Principles and practice of infectious diseases. Elsevier Health Sciences.
2. U.S Food and Drug Administration, 2018, BAT [Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) – (Equine)], viewed 21 October 2024, available https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/bat-botulism-antitoxin-heptavalent-b-c-d-e-f-g-equine
3. Department of Health, 2007, Botulism Laboratory Case Definition, PHLN, viewed 20 April 2016, available http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-phlncd-botulism.htm
4. Ferreira, J. L., S. Maslanka, E. Johnson, and M. Goodnough. 2003, Detection of botulinal neurotoxins A, B, E, and F by amplified enzyme-linked immunosorbent assay. J. AOAC Int. 86:314-33
5. Klaassen, Curtis D., Editor, 2008, Casarett and Doull’s Toxicology: The Basic Science of Poisons. 7th Edition, New York: McGraw-Hill Companies, Inc.
6. Payne JR, Khouri JM, Jewell NP, Arnon SS. Efficacy of Human Botulism Immune Globulin for the Treatment of Infant Botulism: The First 12 Years Post Licensure. J Pediatr. 2018 Feb;193:172–7.
7. Parrera GS, Astacio H, Tunga P, Anderson DM, Hall CL, Richardson JS. Use of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)—(Equine) (BAT®) in Clinical Study Subjects and Patients: A 15-Year Systematic Safety Review. Toxins. 2021 Dec 27;14(1):19.
8. PHLN, 2006, Botulism Laboratory Case Definition; BC Centre for Disease Control July 2015, Management of specific diseases, Botulism.
9. Queensland Government, 2006, Food Act and Food Standards Code, cited 20 April 2016, Available https://www.health.qld.gov.au/public-health/industry-environment/food-safety/regulation/act-standards
10. Queensland Health, 2006, Foodborne Illness Outbreak Management Guidelines, viewed 20 April 2016, available http://disease-control.health.qld.gov.au/Condition/703/gtm.js
11. Sobel, J., 2005, Botulism. Clinical Infectious Diseases, 41(8), pp.1167-1173.
12. U.S. Department of Health & Human Services, FoodSafety - Botulism, viewed 20 April 2016, available http://www.foodsafety.gov/poisoning/causes/bacteriaviruses/botulism/