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Botulism

Updated : March 11, 2024





Background

BoNT, an exo-neurotoxin produced by the bacteria Clostridium botulinum, is the cause of the uncommon but potentially fatal disease of widespread, flaccid paralysis known as botulism.

Numerous additional botulism etiologies, such as wound botulism, inhalational botulism, and iatrogenic botulism have been described since the disease was first identified as a foodborne phenomenon in Belgium and Germany there in the 1800s.

Botulism can be treated with weeks of mechanical breathing and some other resource-intensive therapy until the body’s neuromuscular signaling mechanisms heal, even though the administration of polyvalent antitoxin to botulinum neurotoxin slows down the disease’s clinical progression.

The world’s military organizations are very interested in botulinum neurotoxin since it is the most lethal poison currently in use and is very easy to create, store, and distribute.

Epidemiology

The National Botulism Surveillance System was created by the Centers for Disease Control and Prevention (CDC) in 1973 to track botulism cases across the country. An average of 162 cases of botulism per year were reported in the five years between 2011 and 2015.

The proportions of each form of botulism varied from seventy-one to eighty-eight percent in cases of newborn botulism, one to 20 percent in cases of foodborne botulism, five to ten percent in cases of wound botulism, and one to four percent in cases of botulism of other or unknown origin.

The overall number of botulism cases and the proportional shares of each subgroup have largely remained constant for the past ten years, with the exception of sporadic, significant outbreaks (for example, a foodborne botulism outbreak across Ohio in April 2015 that resulted in 27 instances alone).

There has only ever been one incidence of iatrogenic botulism throughout the U.s, which was brought on by the use of an illegal, heavily contaminated type of BoNT; there were no recorded cases of botulism caused by bioterrorism.

Botulism has a low mortality rate. Even before the 1950s, sixty to seventy percent of cases of foodborne botulism resulted in death. Between 1975 and 2009, there were 3,618 cases of botulism, 109 deaths, and an overall fatality rate of 3.0 percent.

A total of 2352 infant botulism incidents resulted in 18 [below 1 percent] fatalities, 854 incidents resulted in 61 [7.1 percent] deaths, 359 incidents resulted in 18 [5.0 percent] deaths, and 53 incidents resulted in 12 [22.6 percent] deaths.

Anatomy

Pathophysiology

One 150 kDa protein known as botox neurotoxin has a 50 kDa light strand and then a 100 kDa heavy string that is joined by something like a singular disulfide bond. Depending on identification via polyclonal serum, BoNT can be divided into eight different serotypes, numbered A (BoNT/A) across H (BoNT/H). Human disease is caused by toxin subtypes A, B, E, and sporadically F, G, and H. BoNT/A and BoNT/B are to blame for the extreme case that is recorded across the Us.

Dual toxin-producing C. botulinum strains have been discovered, albeit the majority of strains only produce one toxin serotype. The most potent toxin is type A, followed by type B by BoNT. Depending on the sort of exposure, the poison enters the bloodstream through a different route. In newborn botulism, a weak immune system enables the spread of toxin-producing C. botulinum cultures in the bronchioles or digestive tract after spore inhalation or ingestion.

When BoNT is released, it crosses the mucosal barrier (either the pulmonary or intestinal epithelium) through transcytosis and enters the bloodstream. Food-borne botulinum, which is absorbed in the digestive tract identical to newborn botulism, is caused by ingesting produced toxins in inadequately stored food.

The most prevalent cause of subcutaneous injection of spore-contaminated illicit substances is wound botulism, which is caused by C. botulinum spores’ maturation in damaged tissue tissues and the discharge of BoNT into surrounding circulation. After entering the bloodstream, BoNT goes to the spontaneous motor as well as autonomic Neuromuscular junctions and attaches to their presynaptic nerve endings.

The toxin’s heavy chain moiety stimulates endocytosis, which is followed by the release of the light chain into the cytosol. The SNARE (SNAP-25, syntaxin, or VAMP) polypeptide combination, which is necessary for the union of acetylcholine-containing vesicles with the presynaptic terminal, has serotype-specific receptors that the light chain seeks out and split.

Fusion enables postsynaptic membrane depolarization and acetylcholine exocytosis at the NMJ. BoNT causes flaccid paralysis by separating all those fusion structures, which limits muscular contraction and prevents presynaptic acetylcholine discharge. All BoNT serogroups exhibit the downstream side effect of flaccid paralysis due to a lack of acetylcholine production at the neuromuscular junctions, irrespective of serotype-specific variations in target locations.

Etiology

The gram-positive, spore-forming, obligatory anaerobic bacterium Clostridium botulinum, rod-shaped, produces an Exo neurotoxin, which has systemic effects and causes the neuroparalytic condition known as botulism. The toxin is also occasionally produced by other Clostridium species, including Clostridium butyricum and Clostridium baratii.

A heterogeneous and widespread class of bacteria known as C. botulinum is typically split into four categories (categories I, II, III, or IV) depending on physiologic traits. Soil, shellfish, marine sediment, vegetables, and fruits can all be quickly and readily isolated from C. botulinum.

In anaerobic, substrate-rich circumstances, it produces heat-resistant pollen that germinates to become bacilli that produce toxins. Due to its great potency and toxicity, botox neurotoxin is regarded as the most lethal toxin now in use. Its fatal dose (LD50) ranges from 1 to 3 ng (nanograms) of toxin per kilogram (kg) of body mass, making it the deadliest toxin currently in use.

The permanent suppression of acetylcholine release at the presynaptic nerve ending of the body’s NMJs causes flaccid paralysis associated with botulism. In addition to systemic release of the toxin in vivo, as in the cases of baby and wound botulism, botulism can be contracted from exposure to the pre-formed toxin through incorrectly food stored, bioterrorism, or iatrogenic injection.

Genetics

Prognostic Factors

The prognosis may vary depending on the type of botulism like foodborne, baby, or wound. Infant botulism is typically less severe than foodborne botulism. Whereas wound botulism might present with different complications based on the severity of the infection and the time of treatment. 

The prognosis may be affected by the severity of symptoms at the time of presentation. Individuals with early-stage botulism or mild symptoms may fare better than individuals with advanced paralysis or severe symptoms. 

Clinical History

Age Group:  

Infant botulism primarily affects infants under the age of one year, particularly those between 2 weeks and 6 months old.  

While foodborne botulism can affect individuals of any age, adults are more commonly affected than children.  

 

 

Associated Comorbidity or Activity:   

Botulism may be more common in people whose immune systems have been compromised by diseases like HIV, cancer, or immunosuppressive treatments.  

An environment that supports the growth of Clostridium botulinum bacteria can be produced by factors that change the normal bacterial flora in the gut or have an impact on gut motility. 

The risk of complications from botulism may be increased by respiratory disorders that weaken respiratory muscles or decrease lung function, especially when respiratory paralysis occurs. 

 

Acuity of Presentation:  

After eating tainted food, symptoms usually appear 12 to 36 hours later, though they might appear hours or even days before. 

The symptoms may appear suddenly and include confused vision, trouble swallowing and speaking, weakness, and paralysis of the muscles. This is known as an acute presentation. 

Lethargy, weak crying, constipation, and poor eating are some of the early signs that might develop into respiratory difficulties and muscle weakness. 

Physical Examination

  • Cranial Nerve Dysfunction: Examination may reveal bilateral ptosis, diplopia, and decreased pupillary response to light. 
  • Facial Weakness: Patients may exhibit facial weakness, including weakness of facial muscles leading to a mask-like appearance or drooping of the corners of the mouth. 
  • Muscle Weakness and Paralysis: Patients may demonstrate generalized weakness and fatigue, which can progress to paralysis. 
  • Respiratory Distress: Severe cases of botulism can lead to respiratory muscle paralysis, resulting in respiratory distress, shallow breathing, and respiratory failure. 
  • Autonomic Dysfunction: Autonomic dysfunction can result in dry mouth and dry eyes. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

  • Guillain-Barré Syndrome (GBS): Usually originating in the legs and progressing upward, GBS is an autoimmune disease that causes progressive muscular weakening and paralysis. 
  • Myasthenia Gravis (MG): MG is an autoimmune disease marked by weariness and muscle weakness, particularly after prolonged muscle use. 
  • Stroke: Stroke frequently affects one side of the body and manifests as abrupt weakness or paralysis. It could also result in visual abnormalities and trouble speaking. 
  • Lambert-Eaton Myasthenic Syndrome (LEMS): LEMS is a neuromuscular disorder characterized by muscle weakness and fatigue, especially in the proximal muscles. It is often associated with small cell lung cancer. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

  • Supportive Care: Patients with respiratory muscle paralysis may require mechanical ventilation to maintain adequate oxygenation and ventilation.  
  • Fluid and Electrolyte Management: Intravenous fluids may be administered to maintain hydration and electrolyte balance, particularly if swallowing difficulties are present. 
  • Botulinum Antitoxin: The mainstay of specific treatment for botulism is the administration of botulinum antitoxin. Antitoxin is derived from horse serum and works by neutralizing circulating botulinum toxin.  
  • Avoidance of Antibiotics: Antibiotics are not routinely recommended for the treatment of botulism, as they may increase the release of botulinum toxin from bacterial cells and worsen symptoms.  

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of non-pharmacological approach for Botulism

  • Food Safety Practices: Follow recommended canning procedures and guidelines to ensure that home-canned foods are safely processed and sealed to prevent the growth of Clostridium botulinum bacteria. 
  • Use of Acidification and Thermal Processing: Acidification or thermal processing can inhibit the growth of botulinum toxin-producing bacteria in canned foods. 
  • Inspection of Canned Foods: Inspect commercially canned foods for signs of damage, bulging, or leaks before consumption. Do not consume canned foods that appear spoiled or have an unusual odor, as they may contain botulinum toxin. 
  • Proper Wound Care: Practice good wound care and hygiene to prevent wound botulism. Clean and disinfect wounds promptly and seek medical attention for any signs of infection or inflammation. 
  • Environmental Cleanliness: Maintain cleanliness in food preparation areas, particularly when handling raw meats and vegetables.  

Use of Botulinum Antitoxin

Botulinum antitoxin is derived from horse serum and works by neutralizing circulating botulinum toxin.  

  • Antitoxin: It should be administered as soon as botulism is suspected, without waiting for confirmatory laboratory tests. 

Use of Antibiotics

Penicillin G: It is a preferred medication for botulism in wounds. causes bacterial death in sensitive microbes by interfering with the formation of cell wall mucopeptide during active multiplication. 

Use of Intervention with a procedure in treating Botulism

  • Mechanical ventilation: Ventilator settings and parameters are adjusted based on the patient’s respiratory mechanics and gas exchange requirements. 
  • Parameters such as tidal volume, respiratory rate, positive end-expiratory pressure (PEEP), and fraction of inspired oxygen (FiO2) are titrated to achieve adequate oxygenation and ventilation while minimizing ventilator-induced lung injury.
  • Once the patient’s respiratory function improves and they show signs of weaning readiness, a gradual weaning process from mechanical ventilation is initiated.  

Use of phases in managing Botulism

  • Recognition and Diagnosis: Early recognition of botulism is crucial for prompt initiation of treatment. Healthcare providers should be aware of the clinical features and risk factors associated with botulism and consider the diagnosis in patients presenting with characteristic symptoms such as muscle weakness, cranial nerve palsies, and autonomic dysfunction. 
  • Acute Phase Management: The mainstay of treatment for botulism is the administration of botulinum antitoxin, which helps neutralize circulating botulinum toxin.  
  • Monitoring for Complications: Patients with botulism should be closely monitored for complications such as respiratory failure, aspiration pneumonia, and autonomic dysfunction. 
  • Recovery and Rehabilitation: Once patient’s condition stabilizes, they may require rehabilitation therapy to regain strength, mobility, and function. 

Medication

 

botulinum antitoxin, heptavalent 

Indicated for non-infant botulism that occurs naturally:


Before administering, dilute 20 mL intravenous infusion to a 1:10 ratio with 0.9% NaCl



 

botulism immune globulin iv 

(in infants is caused by either toxin type A or type B):

Below 1 yr: 100 mg/kg Intravenous infusion; give at 25 mg/kg/hr over first 15 mins; when well tolerated, gradually increase to 50 mg/kg/hr. Above 1 yr: not indicated The reconstituted product has at least 15 IU/mL of antibodies against the type A botulinum toxins and at least 2.7 IU/mL of antibodies against type B toxins.



Dose Adjustments

Renal Impairment Reduce the rate and concentration of infusion.

botulinum antitoxin, heptavalent 

Local epidemiology divisions can be consulted
BabyBIG (protects against both forms of botulism toxin) can be obtained by calling the California Infant Botulism Programme.
Type F child botulism has been treated using heptavalent botulinum antitoxin. Future instances of newborn botulism may also be treated with it on a case-by-case basis.



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK459273/

Botulism – StatPearls – NCBI Bookshelf (nih.gov) 

Botulism (who.int) 

Botulism

Updated : March 11, 2024




BoNT, an exo-neurotoxin produced by the bacteria Clostridium botulinum, is the cause of the uncommon but potentially fatal disease of widespread, flaccid paralysis known as botulism.

Numerous additional botulism etiologies, such as wound botulism, inhalational botulism, and iatrogenic botulism have been described since the disease was first identified as a foodborne phenomenon in Belgium and Germany there in the 1800s.

Botulism can be treated with weeks of mechanical breathing and some other resource-intensive therapy until the body’s neuromuscular signaling mechanisms heal, even though the administration of polyvalent antitoxin to botulinum neurotoxin slows down the disease’s clinical progression.

The world’s military organizations are very interested in botulinum neurotoxin since it is the most lethal poison currently in use and is very easy to create, store, and distribute.

The National Botulism Surveillance System was created by the Centers for Disease Control and Prevention (CDC) in 1973 to track botulism cases across the country. An average of 162 cases of botulism per year were reported in the five years between 2011 and 2015.

The proportions of each form of botulism varied from seventy-one to eighty-eight percent in cases of newborn botulism, one to 20 percent in cases of foodborne botulism, five to ten percent in cases of wound botulism, and one to four percent in cases of botulism of other or unknown origin.

The overall number of botulism cases and the proportional shares of each subgroup have largely remained constant for the past ten years, with the exception of sporadic, significant outbreaks (for example, a foodborne botulism outbreak across Ohio in April 2015 that resulted in 27 instances alone).

There has only ever been one incidence of iatrogenic botulism throughout the U.s, which was brought on by the use of an illegal, heavily contaminated type of BoNT; there were no recorded cases of botulism caused by bioterrorism.

Botulism has a low mortality rate. Even before the 1950s, sixty to seventy percent of cases of foodborne botulism resulted in death. Between 1975 and 2009, there were 3,618 cases of botulism, 109 deaths, and an overall fatality rate of 3.0 percent.

A total of 2352 infant botulism incidents resulted in 18 [below 1 percent] fatalities, 854 incidents resulted in 61 [7.1 percent] deaths, 359 incidents resulted in 18 [5.0 percent] deaths, and 53 incidents resulted in 12 [22.6 percent] deaths.

One 150 kDa protein known as botox neurotoxin has a 50 kDa light strand and then a 100 kDa heavy string that is joined by something like a singular disulfide bond. Depending on identification via polyclonal serum, BoNT can be divided into eight different serotypes, numbered A (BoNT/A) across H (BoNT/H). Human disease is caused by toxin subtypes A, B, E, and sporadically F, G, and H. BoNT/A and BoNT/B are to blame for the extreme case that is recorded across the Us.

Dual toxin-producing C. botulinum strains have been discovered, albeit the majority of strains only produce one toxin serotype. The most potent toxin is type A, followed by type B by BoNT. Depending on the sort of exposure, the poison enters the bloodstream through a different route. In newborn botulism, a weak immune system enables the spread of toxin-producing C. botulinum cultures in the bronchioles or digestive tract after spore inhalation or ingestion.

When BoNT is released, it crosses the mucosal barrier (either the pulmonary or intestinal epithelium) through transcytosis and enters the bloodstream. Food-borne botulinum, which is absorbed in the digestive tract identical to newborn botulism, is caused by ingesting produced toxins in inadequately stored food.

The most prevalent cause of subcutaneous injection of spore-contaminated illicit substances is wound botulism, which is caused by C. botulinum spores’ maturation in damaged tissue tissues and the discharge of BoNT into surrounding circulation. After entering the bloodstream, BoNT goes to the spontaneous motor as well as autonomic Neuromuscular junctions and attaches to their presynaptic nerve endings.

The toxin’s heavy chain moiety stimulates endocytosis, which is followed by the release of the light chain into the cytosol. The SNARE (SNAP-25, syntaxin, or VAMP) polypeptide combination, which is necessary for the union of acetylcholine-containing vesicles with the presynaptic terminal, has serotype-specific receptors that the light chain seeks out and split.

Fusion enables postsynaptic membrane depolarization and acetylcholine exocytosis at the NMJ. BoNT causes flaccid paralysis by separating all those fusion structures, which limits muscular contraction and prevents presynaptic acetylcholine discharge. All BoNT serogroups exhibit the downstream side effect of flaccid paralysis due to a lack of acetylcholine production at the neuromuscular junctions, irrespective of serotype-specific variations in target locations.

The gram-positive, spore-forming, obligatory anaerobic bacterium Clostridium botulinum, rod-shaped, produces an Exo neurotoxin, which has systemic effects and causes the neuroparalytic condition known as botulism. The toxin is also occasionally produced by other Clostridium species, including Clostridium butyricum and Clostridium baratii.

A heterogeneous and widespread class of bacteria known as C. botulinum is typically split into four categories (categories I, II, III, or IV) depending on physiologic traits. Soil, shellfish, marine sediment, vegetables, and fruits can all be quickly and readily isolated from C. botulinum.

In anaerobic, substrate-rich circumstances, it produces heat-resistant pollen that germinates to become bacilli that produce toxins. Due to its great potency and toxicity, botox neurotoxin is regarded as the most lethal toxin now in use. Its fatal dose (LD50) ranges from 1 to 3 ng (nanograms) of toxin per kilogram (kg) of body mass, making it the deadliest toxin currently in use.

The permanent suppression of acetylcholine release at the presynaptic nerve ending of the body’s NMJs causes flaccid paralysis associated with botulism. In addition to systemic release of the toxin in vivo, as in the cases of baby and wound botulism, botulism can be contracted from exposure to the pre-formed toxin through incorrectly food stored, bioterrorism, or iatrogenic injection.

The prognosis may vary depending on the type of botulism like foodborne, baby, or wound. Infant botulism is typically less severe than foodborne botulism. Whereas wound botulism might present with different complications based on the severity of the infection and the time of treatment. 

The prognosis may be affected by the severity of symptoms at the time of presentation. Individuals with early-stage botulism or mild symptoms may fare better than individuals with advanced paralysis or severe symptoms. 

Age Group:  

Infant botulism primarily affects infants under the age of one year, particularly those between 2 weeks and 6 months old.  

While foodborne botulism can affect individuals of any age, adults are more commonly affected than children.  

 

 

Associated Comorbidity or Activity:   

Botulism may be more common in people whose immune systems have been compromised by diseases like HIV, cancer, or immunosuppressive treatments.  

An environment that supports the growth of Clostridium botulinum bacteria can be produced by factors that change the normal bacterial flora in the gut or have an impact on gut motility. 

The risk of complications from botulism may be increased by respiratory disorders that weaken respiratory muscles or decrease lung function, especially when respiratory paralysis occurs. 

 

Acuity of Presentation:  

After eating tainted food, symptoms usually appear 12 to 36 hours later, though they might appear hours or even days before. 

The symptoms may appear suddenly and include confused vision, trouble swallowing and speaking, weakness, and paralysis of the muscles. This is known as an acute presentation. 

Lethargy, weak crying, constipation, and poor eating are some of the early signs that might develop into respiratory difficulties and muscle weakness. 

  • Cranial Nerve Dysfunction: Examination may reveal bilateral ptosis, diplopia, and decreased pupillary response to light. 
  • Facial Weakness: Patients may exhibit facial weakness, including weakness of facial muscles leading to a mask-like appearance or drooping of the corners of the mouth. 
  • Muscle Weakness and Paralysis: Patients may demonstrate generalized weakness and fatigue, which can progress to paralysis. 
  • Respiratory Distress: Severe cases of botulism can lead to respiratory muscle paralysis, resulting in respiratory distress, shallow breathing, and respiratory failure. 
  • Autonomic Dysfunction: Autonomic dysfunction can result in dry mouth and dry eyes. 
  • Guillain-Barré Syndrome (GBS): Usually originating in the legs and progressing upward, GBS is an autoimmune disease that causes progressive muscular weakening and paralysis. 
  • Myasthenia Gravis (MG): MG is an autoimmune disease marked by weariness and muscle weakness, particularly after prolonged muscle use. 
  • Stroke: Stroke frequently affects one side of the body and manifests as abrupt weakness or paralysis. It could also result in visual abnormalities and trouble speaking. 
  • Lambert-Eaton Myasthenic Syndrome (LEMS): LEMS is a neuromuscular disorder characterized by muscle weakness and fatigue, especially in the proximal muscles. It is often associated with small cell lung cancer.