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Botulism is caused by botulinum toxin which is a poison produced by the obligate anaerobic bacteria Clostridium botulinum, Clostridium baratii and Clostridium butyricum.
The organism is common in the soil and can survive in this environment in the form of a resistant spore. There are three naturally occurring forms of botulism, and botulism as a result of biological warfare.
This occurs when the spores of the organism C. botulinum have germinated and the bacteria have reproduced in an environment outside the body and produced toxin - this environment is usually a foodstuff:
- The adult then consumes the toxin itself when they eat the food, and this makes them ill with weakness and paralysis.
- Botulism in adults tends to occur when the spores have been sealed in an airtight environment such as tins or jars, particularly home-preserved foods which have been preserved in oil.
- The toxin is destroyed by normal cooking processes.
This has the same symptoms as other forms, but occurs when the organisms get into an open wound and are able to reproduce in an anaerobic environment. The most common cause of cases of botulism in infected wounds is intravenous drug use.
Botulism in children
Infant botulism is rare in most countries, almost unheard of in Africa, but in the USA it is the most common form of botulism. It occurs when the baby ingests spores which germinate to produce the bacterial cells that reproduce in the gut and release toxin. In most adults and older children, this would not happen because the natural defences which have developed in an adult gut would prevent the germination and growth of C. botulinum. In some babies, these defences have not yet developed, and so this gives the infection a chance to get a foothold and produce the toxin.
Botulinum toxin is regarded as the most lethal substance known. It is estimated that 1 gram could kill 1 million people. Several countries have tried to create a biological weapon from the toxin. The potential is for airborne or food dispersal. The toxin is neutralised by water treatment processes, making dispersal in this way unlikely.
It is uncommon in the UK:
- There were 4 laboratory reported cases of food-borne botulism between 2000-2006.
- There were 11 cases of wound botulism in 2007 - fewer than previous years. All cases occurred in heroin injectors. There was some geographical clustering of the cases during 2004, with most cases occurring in London and in the Yorkshire and Humberside regions of northeast England.
- There has only been one case of infant botulism since 2000.
There is acute symmetrical, descending, flaccid paralysis as a result of ingesting the neurotoxin.
These can occur between 2 hours and 8 days after exposure to the toxin, depending on dose and type of toxin. There are seven distinct serotypes currently defined A-G. Types A and B are the most potent. In infant botulism, some time may elapse between ingestion of the spores and the release of the toxin:
- They often begin with blurred vision.
- There may be difficulty in swallowing and speaking.
- There is sometimes diarrhoea and vomiting.
- There is descending weakness or paralysis, that may extend to complete flaccid paralysis.
- The patient remains alert.
- Acute onset of bilateral cranial nerve involvement.
- Failure of accommodation.
- Pupils fixed in mid position or dilated.
- Fever is unusual, as is loss of sensation.
- Descending form of acute inflammatory polyneuropathy.
- Guillain-Barré syndrome.
- Myasthenia gravis.
- Bulbar palsy.
Detection of toxin in:
- Vomit or gastric fluid
- Spirometry, pulse oximetry, vital capacity, and arterial blood gases should be measured.
- Respiratory failure can occur very rapidly.
- Recovery of ventilatory and upper airway muscle strength in patients who develop respiratory failure is most significant over the first 12 weeks.
- The time for recovery typically ranges from 30-100 days.
- Artificial respiratory support may be required for months in severe cases.
- Tracheostomy may be necessary to manage excess secretions.
This may be trivalent antitoxin (vs A, B, E) or polyvalent antitoxin for toxins A, B, C, D, E, and F also is available for specific outbreaks.
- Administer as soon as possible in patients who are symptomatic with high clinical suspicion of illness.
- An antitoxin may be beneficial, even when provided several weeks after toxin ingestion because circulating toxin has been detected in serum as long as 30 days later.
- Antitoxin will not neutralise toxin already bound to neuromuscular junctions; although antitoxin can slow disease progression, it has no effect on established neurological deficits.
Because only equine antitoxin is available, all patients must be tested for hypersensitivity to equine serum.
- 20% patients will experience some degree of serum sickness or hypersensitivity reaction, and anaphylaxis can also occur.
Recently, Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, was evaluated for safety and efficacy in treating infant botulism in a five-year, randomised, double-blind, placebo-controlled trial of 122 infants in the USA:
- Prompt treatment of infant botulism type A or type B was found to be safe and effective in shortening the length and cost of the hospital stay and the severity of illness.
Further evaluation has supported the initial findings.
Clinical improvement may take weeks to months, but most cases make a recovery. The disease can be fatal in 5-10% of cases. Symptoms often begin with blurred vision and difficulty in swallowing and speaking, but sometimes diarrhoea and vomiting can occur. The disease can go on to lead to further problems with vision, and paralysis.
There is no vaccine currently licensed against botulism:
- Vaccines do exist, but they are not effective against all the serotypes and it has not been possible to combine the seven vaccines into a single injection.
- Therefore, a vaccination programme involves multiple injections and booster shots.
- In the event of an attack, a patient would possibly need to be given as many as 21 injections.
A British company has successfully produced a thermally stable, rapidly injectable, pentavalent recombinant botulinum vaccine candidate, although the safety and efficacy of this product in humans has not been established.
Further reading and references
; Botulism, Medscape, May 2011
; Identification of the major steps in botulinum toxin action. Annu Rev Pharmacol Toxicol. 200444:167-93.
; Botulinum neurotoxin vaccines: past, present, and future. Crit Rev Immunol. 200727(4):303-18.
; Wound botulism in injectors of drugs: upsurge in cases in England during 2004. Euro Surveill. 2005 Sep10(9):172-4.
; Jane's Weapon's. Website dealing with chemical and biological warfare
; Health Protection Agency
; A review of WHO International Standards for botulinum antitoxins. Biologicals. 2006 Sep34(3):223-6. Epub 2006 Feb 20.
; Adult botulism type F in the United States, 1981-2002. Neurology. 2005 Dec 1365(11):1694-700.
; Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006 Feb 2354(5):462-71.
; Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Childrens Hospital Los Angeles. Pediatrics. 2007 Dec120(6):e1380-5.
; Botulism and vaccines for its prevention. Vaccine. 2009 Nov 527 Suppl 4:D33-9.
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