The next patient was a middle aged woman who had been intubated and ventilated but who looked otherwise pretty well. [You get a feel for how unwell a patient is just by standing at the end of their bed and observing; equipment, medications, drains and tubes, as well as the colour and appearance of the patient are all clues.]
“This lady has Guillain-Barre Syndrome, so no infection issues” said the Critical Care Registrar moving past the end of the bed.
Guillain-Barre Syndrome is a rare neurological syndrome of progressive weakness that usually recovers with supportive care. It is thought to be autoimmune in nature.
“How did she present?” asked the Microbiologist doing his normal “I’m looking for trouble” kind of thing.
Humouring the Microbiologist the Registrar explained that the patient had presented with progressive difficulty swallowing and speaking following an episode of diarrhoea and vomiting. She had become so weak they had needed to ventilate her.
“This sounds like sausage poisoning” said the Microbiologist
“Oh sorry,” replied the Microbiologist realising he had spoken out loud (Microbiologists sometimes do this; it is believed to be a symptom of being stuck in the Lab or at a computer so they develop the habit of talking to themselves!).
“This could be botulism. Has she eaten anything odd recently; home preserved foods or tins of food that might have gone off?” he clarified.
“I have no idea,” replied the Registrar starting to remember all of the exam stuff he had learned in the past and realising the Microbiologist might be on to something after all, “but her husband is around and we could ask him.”
What is botulism?
Botulism is a serious, but fortunately rare, neurological condition caused by a neurotoxin from the bacterium Clostridium botulinum. The name of the bacterium comes from the Latin for sausage (botulus) because the first described outbreak occurred in the 1820s in Germany when hundreds of people became ill after eating sausages contaminated with bacteria… hence “sausage poisoning”.
Clostridium botulinum is a Gram-positive anaerobic bacterium (it cannot survive in the presence of oxygen). It is found all over the World in the environment, especially in soil. It produces heat-stable spores which are resistant to drying and require high temperatures to kill (120oC for 5 minutes) and can survive for weeks and months in the environment.
Spores require certain environmental conditions to germinate or “hatch” into toxin-producing bacteria:
- Reduced oxygen (anaerobic) atmosphere
- Slightly acidic water (pH 4.6-6.5)
- Temperature 25-37oC
Many outbreaks of botulism are related to food, but not all strains of C. botulinum cause the food to look spoiled, it can look and taste normal… scary huh?!
Botulinum toxin binds to the nerve synapse (junction) affecting sensory and motor nerves. After binding the toxin is taken up into the neurons where it inhibits the release of all sorts of compounds involved in nerve transmission, essentially blocking nerve conduction leading to paralysis and eventually death.
Botulinum toxin is the most potent bacterial toxin, and possibly the most potent toxin of any kind! In old animal studies botulinum toxin has been shown to be 1.6 million times more lethal than curare (a naturally occurring neurotoxin used by indigenous Amazonian tribes as a poison for hunting) and 33 million times more lethal than cyanide (how do I know this stuff?!?...argh…reading!)
As if that isn’t bad enough, botulinum toxin is also a potential agent of bioterrorism in that it has been estimated that only 1g of aerosolised toxin could kill up to 1.5 million people!
But before you panic, making botulinum toxin into a terrorist agent is not easy and is more likely to kill the person trying to develop it. Not only that but chlorinated water inactivates the toxin within about 20 minutes, as does heating to 80oC, so it isn’t that stable really.
What types of botulism are there?
There are different types of presentation of botulism depending on how the bacterium or toxin is acquired.
- Infantile botulism occurs when a child eats C. botulinum spores usually from soil or dust. Spores are like the seeds of a bacterium but NOTE not all types of bacteria produce these spores. Historically infantile botulism was related to contaminated honey which was smeared on dummies or pacifiers; botulism is the reason why infants are advised not to eat honey! Once swallowed the spores germinate into free living bacteria in the child’s gut, these bacteria produce toxin which is then absorbed systemically into the body. The bacteria can colonise an infants’ gastrointestinal tract as children have a slower gut transit time and more suitable gut environmental conditions compared to adults, which is faster and more hostile towards the bacteria. In the USA there are about 75 cases of infantile botulism a year; there were 2 cases of infantile botulism in the UK in 2013 (this is the most up-to-date data I could find!).
- Foodborne botulism is caused by the ingestion of preformed botulinum toxin. Most cases are related to inadequately preserved, or prepared, homemade foods. Implicated foods include home-tinned fruit, veg and fish, and home fermented tofu and bean products. Apparently there have been 197 reported foodborne outbreaks of botulism in the USA between 1920 and 2014; in 2013 there was 1 case of foodborne botulism in the UK.
- Wound botulism is caused when C. botulinum grows in soft tissue, usually as an abscess. By far the most common reason for this is intravenous drug use; this is actually the only situation where I have seen botulism (although it can extremely rarely occur in wounds in non-IVDUs). IVDUs can either accidentally, or “deliberately” (to give themselves intramuscular drugs), miss the vein and the resulting abscess can potentially contain C. botulinum spores which then germinate and produce toxin. Sometimes the abscess can be very small or hidden (e.g. under a tattoo) so a careful search is required to find any abscess that might need surgical drainage.
- Iatrogenic botulism occurs when botulinum toxin used for medical or cosmetic reasons is accidentally injected into the blood stream, causing botulism. Needless to say this is a quick route to disaster; fortunately most people with this type of botulism “know” they have been exposed (remember: taking a good clinical history is vital) and can be treated quickly and therefore survive this otherwise “fast-track” route.
How does botulism present?
Botulism presents with bilateral cranial nerve palsies and symmetrical weakness that descends from the cranial nerves to affect the rest of the body. Other features include:
- Absence of fever (although this is potentially an infection, the damage is done by a toxin to which there is no-immune response and therefore no inflammatory response)
- The neurological deficits are symmetrical, affecting both sides of the body equally
- Paralysis descends to involve the upper then lower body, with progressive respiratory problems as well as urinary retention and constipation.
- The patient is alert throughout the illness (making it even more terrifying!)
- The cranial nerves most often involved are III (oculomotor), IV (trochlear) and VI (abducens) causing visual disturbance, but facial weakness and difficulty swallowing and speaking are also common
- Foodborne botulism is often associated with a prodrome of diarrhoea and vomiting, abdominal pain and sore-throat
How do you diagnose botulism?
The initial diagnosis of botulism is clinical; botulism should be considered in any patient with symmetrical descending paralysis irrespective of risk factors. If you don’t think about it you’ll miss it!
To confirm the diagnosis the bacterium has to be grown or the toxin identified from a tissue, stool, vomit or serum sample (yep, even vomit can be an appropriate sample some of the time!). If Clostridium botulinum is grown (or present in the sample) then toxin production can be confirmed using PCR.
Toxin detection in serum uses a mouse assay, performed by a specialist laboratory in London. This is not a test to be undertaken lightly as it involves injecting laboratory mice with serum, treating some mice and not others, and seeing if the untreated mice develop botulism. None of the mice survive this test! It is essential that the serum sample is taken from the patient before they are treated with antitoxin (and within 3 days of onset of symptoms) as antitoxin can make the test invalid.
How is botulism treated?
Treatment of botulism involves supportive care (including ventilation if necessary) and antitoxin.
Antitoxin is the main treatment of botulism and needs to be given as soon as possible, but after a serum sample is taken! The antitoxin binds to the toxin itself preventing it from binding to the nerve. It does not reverse any symptoms that have already occurred but it does prevent further paralysis. In the UK, botulinum antitoxin is acquired from the Public Health England Duty Doctor at Colindale.
Antibiotics are not recommended for infantile and foodborne botulism as the antibiotics can damage the bacteria, releasing even more toxin, making the patient much sicker! For wound botulism where there has already been surgical debridement to remove as much of the bacteria as possible, Benzylpenicillin OR Metronidazole should be given to deal with the residual infection otherwise the bacterium just grows again. Antibiotics also make no difference to iatrogenic botulism as there are no bacteria present, just the toxin.
With good supportive care the patient usually recovers; the mortality is 5-8% in developed countries. Long-term sequela with residual weakness is uncommon.
The best way of avoiding botulism is to avoid risky behaviour. Don’t give honey to babies, don’t eat food from cans that have gone off or where the can has “blown” (become distended due to gas formation inside the can), and don’t needlessly inject drugs (okay, that’s an obvious one!).
The Critical Care Registrar went off to find the patients husband. Further questioning revealed that the patient was a keen gardener who liked to preserve the fruit she grew. She had recently started tinning some of her fruit in an attempt to make it last over the winter…
The Registrar and the Microbiologist looked at each other with growing concern… it was going to be a long day… The Microbiologist went straight off to cancel the tinning machine on his wife’s Christmas List, she’s an avid allotmenteer who jams and preserves her produce but no she can “can” the idea of starting tinning!