It’s no secret that cases of botulism hit the headlines in September 2023. We’ve already covered this subject in our blog columns, knowing that these dreaded toxins are part of the arsenal of malevolent terrorists. Please refer to 3 articles: Clostridium botulinum [1] and biological warfare CBRN, Poisons Old and New: [2] the Navalny Affair, and How did Reinhard Heydrich [3] die? A CBRN-related event?
What are we talking about?
Although botulism is now a rare disease that only reappears after major errors in the (usually family) management of food preservation, it is no less serious, with a high mortality rate when treatment is not immediate.
In this section, we’ll review a few essential concepts to help prevent a festive family meal from turning into an awful tragedy.
We will then analyze the positive applications of a better understanding of botulinum toxins and their applications in the medical field.
Part 1: The disease
Clostridium botulinum
It is in the “foodborne botulism” form that the disease is most widespread. It is caused by ingestion of a powerful neurotoxin, “botulinum toxin” (formerly known as “botulinum toxin”). This toxin is produced by a bacterium known as “Clostridium botulinum”. A strict anaerobic bacterium (it is killed by oxygen in the air), it is Gram-positive, lives and multiplies in soil, which is why it can be found in soil, on raw fruit and vegetables, and on meat and fish.
The bacterium synthesizes spores, which are forms of resistance capable of spreading in the environment, including soil, rivers and seas.
It takes its name from the Latin “botulus” meaning “animal gut”, in reference to the black pudding that poisoned the inhabitants of the German duchy of Württemberg in 1870.
The foods involved
The bacterium synthesizes its toxin in family preserves such as vegetables like green beans, spinach, mushrooms, and beet. It is also found in canned fish such as canned tuna, fermented salted or smoked fish, canned sardines, and meat products such as ham and sausages. Thanks to highly controlled processes, industrially prepared foods are rarely involved.
By multiplying in the poorly preserved product, the bacterium synthesizes its toxin, which is then ingested by the consumer (the bacterium no longer exists). Rather than “intoxication”, we prefer to use the term “intoxination” (toxin poisoning). In the case of the Tchi Tchin Wine Bar in Bordeaux, the culprit was clearly canned sardines.
The symptoms
They are caused by the action of botulinum toxin. Acting on the nervous system, it is one of the neurotoxins. Symptoms appear within 12 to 36 hours, sometimes up to 8 days, (and last from 4 hours to 8 days) after exposure.
The first symptoms are marked fatigue, dry mouth, difficulty swallowing or speaking, blurred vision and difficulty breathing. This is followed by a descending flaccid paralysis that can lead to respiratory failure.
Vomiting, diarrhea, constipation, and abdominal swelling may also occur. The disease may progress to a feeling of weakness in the neck and arms, after which the respiratory and lower-body muscles are affected. There is no fever or loss of consciousness. Without treatment, the disease can be fatal in 5 to 10% of cases. The disease cannot be transmitted from sick to healthy people and is not contagious.
Other botulisms
Infantile botulism. Infants under 6 months of age can ingest C. botulinum spores, which can germinate in the intestine, as they do not yet have the immune defenses capable of stemming this phenomenon, which are in place in older people. The foodstuff most frequently implicated in this case is honey.
Botulism by inhalation. Aerosolized toxin is inhaled, resulting in botulism whose clinical signs are equivalent to those of foodborne botulism.
Wound botulism. In this case, the toxin penetrates a wound and passes directly into the bloodstream. The last 2 forms of botulism can be caused by terrorist acts. See the article “How did Reinhard Heydrich die? A CBRN-related event?”
Treatment: antitoxin
Once the toxin has been detected in the serum, stool or food, the antitoxin must be administered as quickly as possible, before it binds to synaptic receptors, and treatment with controlled mechanical ventilation may be necessary for several weeks or even months. As the ingested food no longer contains bacteria (except in the case of infantile botulism), antibiotic therapy is unnecessary.
There are 2 types of antitoxin
1- Heptavalent botulinum antitoxin (BAT), is indicated for the treatment of botulism contracted through injury and foodborne botulism. (A, B, C, D, E, F, G). BAT is obtained from horses immunized with C. botulinum toxins of types A, B, C, D, E, F, and G. The antibodies react specifically with and neutralize circulating botulinum toxins (i.e. neurotoxins not bound to neurons).
2- Botulism immune globulin (BabyBIG®): Botulism immune globulin (BIG-IV); (BabyBIG®), is an anti-botulinum toxin antibody preparation of human origin indicated for the treatment of infantile botulism caused by type A or B toxins in babies under one year of age.
Canning and botulism prevention
Preparing canned food at home is no trivial matter. Hygiene must be strictly observed. In the event of an error, cases of botulism are rarely isolated and occur within family groups.
Foods that come into contact with soil can contain C. botulinum spores: vegetables, fish (marine sediments also contain C. botulinum) and cured meats, especially pork, as the animal naturally harbors the bacterium in its intestines. Vacuum-packed or canned foods are the most frequently contaminated (very often family preserves, vegetables, artisan hams, sausages, dried or smoked fish, etc.).
The cold chain: this is essential for preserving unsterilized vacuum-packed foods. It also requires effective cleaning of the refrigerator and hands and avoidance of contact between cooked and raw products.
Sterilization of canned foods: heat at the boiling temperature of water (100°C) kills vegetative bacteria, but the spores are resistant, sometimes for several hours. C. botulinum spores, in a humid environment, are killed after 30 minutes at 120°C, a higher temperature than boiling water. Heating a product in a jar removes the air from the container, putting the product in anaerobic conditions favorable to bacterial growth. The same applies to unsterilized products stored under vacuum. In fact, a tight-fitting lid and a click on opening are the key to successful sterilization: when a product is poorly sterilized, bacteria start to grow again, producing gas (which is generally foul-smelling) and lifting the lid.
Note that the toxin is destroyed by heat and that heating the food for ten minutes after opening the jar eliminates it: this is why cooking green beans after opening the can is an additional safety factor.
One foodstuff is particularly sensitive: “home-made” ham. It is well known that you should “kill the pig” when it is fasting; in fact, if the pig is slaughtered while it is still digesting, it may have C. botulinum in its blood, which is part of its normal intestinal flora (postprandial bacteremia). When the animal dies, the blood no longer circulates and the muscles are no longer oxygenated. The strict anaerobic bacillus settles in and develops its toxin, which is consumed with the ham.
You can also play around with canning temperatures. Acidic products can be stored at room temperature, while others should be kept at a maximum of 14°C to prevent the multiplication of germs.
Part 2: Botulinum toxin and its therapeutic applications
Toxin structure and mode of action
The botulinum toxin produced by C. botulinum exists in 7 different serotypes: A, B, C [C1, C2], D, E, F and G, but human botulism is mainly due to serotypes A, B and E.
The molecules are synthesized as a single chain (150 kD), then cleaved to form a 2-chain molecule with a disulfide bridge.
Protoxin structure and activation to active toxin
Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on cholinergic nerve endings and decreasing acetylcholine release, thus causing a neuromuscular blocking effect.
Medical applications of botulinum toxin
Once perceived as the most lethal substance known to man, botulinum toxin (BT) is now recognized for its role in improving patients’ quality of life in many aspects of healthcare. The clinical uses of botulinum toxin A extend far beyond cosmetic procedures, such as the softening of facial wrinkles, for which it is best known; botulinum toxin’s ability to block neuromuscular transmission is used to manage hyperhidrosis, chronic migraine, urinary incontinence, cervical dystonia and many others.
Since BT causes weakness and paralysis of the muscle concerned, it can be useful in cases where muscular hyperactivity is the primary cause.
Modern use of BT as a medical treatment began in the early 1970s, when clinicians began using type A serotype to treat strabismus In 1989, the FDA approved (Botox®) for a variety of uses, including strabismus, hemifacial spasm (hyperstimulation of the facial nerve resulting in lateral movements of the mouth and eye) and blepharospasm (contraction of the eyelid muscles) ; 13 years later, the FDA approved BT for aesthetic purposes
The various products used in the United States are as follows: AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®).
BT takes around 2 to 3 days to take effect, and up to 2 weeks in some cases. Effects last around 3 months, depending on the patient, dosage, technique, and muscle strength. It’s important for patients to understand that BT injections are a temporary treatment.
- Treatment of facial wrinkles: the areas most frequently affected by wrinkles and fine lines are the forehead, the glabella (frown lines), and the eye contour;
- Treatment of primary headaches: in Germany, cases have been reported of BT injections into neck and head muscles to relieve tension headaches. It has been shown that patients who receive BT injections for the treatment of chronic migraine at an early stage of their disease are more likely to achieve remission in the future;
- Treatment of hyperhidrosis: Hyperhidrosis, an idiopathic condition characterized by excessive sweating, can be treated with botulinum toxin. To treat hyperhidrosis, botulinum toxin is administered intradermally in several injections. BT blocks autonomic innervation of the sweat glands; this effect lasts from 3 to 6 months;
- Treatment of depression: patients who receive BT injections in the glabellar region to treat depression can see results for up to three months;
- Treatment of urinary incontinence: botulinum toxin can be used to induce chemical denervation of the detrusor muscle, responsible for the contraction during micturition that pushes urine from the bladder into the urethra. BT injections into the detrusor muscle have been shown to reduce the frequency of urinary incontinence episodes;
- Treatment of temporomandibular dysfunction: temporomandibular dysfunction (TMD) is characterized by jaw pain, crepitus and movement dysfunction. By specifically targeting the lateral pterygoid, it is possible to reduce popping and crepitus of the articular disc, thereby alleviating TMD symptoms.
Key facts
It’s worth noting that these numerous applications point to a definite improvement in well-being for a number of pathologies. However, much of this work is still experimental, with some applications approved by the FDA and others not yet. Contraindications include allergy, pregnancy, breastfeeding, body dysmorphia, keloid scarring and neuromuscular disorders. Moderate side effects may include blepharoptosis or eyebrow ptosis lasting up to 3 months. Most side effects depend on the provider and his or her training. Allergic reactions are rare, but range from rash to anaphylaxis.
Table from publication 3-
In France, the MA for BOTOX theoretically reserves it for the treatment of ocular spasms, bladder dysfunction, spastic torticollis, facial spasms or axillary hyperhidrosis.
For anti-aging, the MA covers the treatment of moderate to severe wrinkles on the forehead, glabella, and crow’s feet. Other uses are then the responsibility of the practitioner, outside the scope of the AMM.
However, only a few specialists are legally authorized to carry out botulinum toxin injections all over the body: these include doctors, cosmetic surgeons, and dermatologists.
For facial injections, neurologists, ophthalmologists, and facial surgeons (ENT and maxillofacial) are also authorized.
Finally, dental surgeons have limited authorization for the treatment of bruxism (masseter muscles) and the perioral region (lip wrinkles, for example). But they cannot treat forehead wrinkles or crow’s feet.
In France, the MA for BOTOX theoretically reserves it for the treatment of ocular spasms, bladder dysfunction, spastic torticollis, facial spasms or axillary hyperhidrosis.
For anti-aging, the MA covers the treatment of moderate to severe wrinkles on the forehead, glabella and crow’s feet. Other uses are then the responsibility of the practitioner, outside the scope of the AMM.
However, only a few specialists are legally authorized to carry out botulinum toxin injections all over the body: these include doctors, cosmetic surgeons, and dermatologists.
For facial injections, neurologists, ophthalmologists, and facial surgeons (ENT and maxillofacial) are also authorized.
Finally, dental surgeons have limited authorization for the treatment of bruxism (masseter muscles) and the perioral region (lip wrinkles, for example). But they cannot treat forehead wrinkles or crow’s feet.
When a practitioner injects botulinum toxin without authorization, he or she is outside the legal framework, which can pose a real problem in terms of insurance.
References
1- La manuel MSD [4], Botulisme, 2021
2- emedecine.medscape.com [5], Botulinum Toxin, Updated: Nov 30, 2022
3- Clinical Uses for Botulinum Toxin, [6] Olivia Jose BSN, RN, 2003
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