Materiały źródłowe

• #1 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  Botulism is a critical neurologic syndrome characterized by acute neuroparalytic manifestations resulting from a neurotoxin secreted by Clostridium botulinum. The toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. Toxin binding blocks acetylcholine release, resulting in weakness, flaccid paralysis, and, often, respiratory arrest. Cure occurs following sprouting of new nerve terminals. […] Clostridium botulinum produces 8 distinct neurotoxins, including types A through G and the potent F/A Hybrid. Among these, types A, B, E, and occasionally F and F/A Hybrid can impact human health. These botulinum toxins are highly toxic proteins that can withstand degradation from stomach acid and proteolytic enzymes. Type F/A Hybrid is considered the most potent toxin among them.

• #2 Botulism – StatPearls – NCBI Bookshelf

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

  Botulism is a rare but life-threatening neuroparalytic syndrome caused by the botulinum neurotoxin, most often produced by the bacterium Clostridium botulinum. […] The toxin’s mode of entry into the bloodstream depends on the type of exposure. In infant botulism, the lack of a robust immune system allows the proliferation of toxin-elaborating clostridial colonies in the digestive tract or bronchioles following ingestion or inhaling spores. Once released, BoNT crosses the mucosal barrier intestinal or pulmonary into the circulation through transcytosis. In foodborne botulism, the preformed toxin from improperly stored food is similarly absorbed in the intestinal tract. Wound botulism is the result of spore germination in devitalized tissue, most commonly as a result of subcutaneous injection of spore-contaminated illicit drugs, with the release of BoNT into the local circulation.

• #3

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10171130/

  Clostridium botulinum, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and the causative agent of botulism. […] The BoNT, regarded as the most potent biological substance known, is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis. […] Additionally, the ability to form endospores is critical to the pathogenicity of the bacteria. […] Disease transmission is often facilitated via the metabolically dormant spores that are highly resistant to environment stresses, allowing persistence in the environment in unfavourable conditions. […] Infant and wound botulism infections are initiated upon germination of the spores into neurotoxin producing vegetative cells, whereas foodborne botulism is attributed to ingestion of preformed BoNT.

• #4 Botulism – UpToDate

  https://www.uptodate.com/contents/botulism/print

  Botulism is a rare but potentially life threatening neuroparalytic syndrome resulting from the action of a neurotoxin elaborated by the bacterium Clostridium botulinum. […] The microbiology, pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of botulism will be discussed here. […] The causative organism – C. botulinum is a gram-positive, rod-shaped, spore-forming, obligate anaerobic bacterium. […] C. botulinum spores are heat resistant and can survive 100°C at one atmosphere for five or more hours. However, spores can be destroyed by heating to 120°C for five minutes. […] When appropriate environmental conditions are present, the spores will germinate and grow into toxin-producing bacilli.

• #5 Clostridium botulinum: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/clostridium-botulinum.html

  C. botulinum forms oval-shaped, metabolically dormant endospores which are highly resistant to environmental stressors and allow persistence in unfavourable conditions. […] Germination of the spores under favourable conditions results in vegetative growth of C. botulinum and production of BoNT (botulinum neurotoxins), the primary virulence factor and the causative agent of botulism. […] Botulism is a rare but severe, and potentially fatal, neuroparalytic disease caused by BoNT produced during germination of C. botulinum spores. […] BoNT binds to the neuromuscular junction and blocks excitatory synaptic transmission by inhibiting acetylcholine release, causing flaccid paralysis. […] Foodborne botulism is the classic form of botulism and is caused by the ingestion of preformed BoNT in contaminated food.

• #6

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10171130/

  The overall mechanism of action is summarised in Figure 5. […] The BoNT SNARE protein targets include the vesicle associated membrane protein (VAMP otherwise known as synaptobrevin), syntaxin, and the synaptosomal-associated protein of 25 kDa (SNAP-25). […] Evidence strongly supports that the long duration of BoNT/A intoxication results from the retention of the toxin within the nerve termini. […] However, some data suggests that short nature of the BoNT/A SNAP-25 truncation may play a contributing factor to its prolonged action. […] The expression and production of BoNT is growth phase dependent, peaking at late exponential-early stationary phase and rapidly declining through stationary phase. […] In addition to the neurotoxin, a key virulence factor in the pathogenesis of C. botulinum and prevalence of botulism, is the sporulation and germination survival strategy. […] Germination is the process of spore recrudescence to neurotoxin producing vegetative cells, crucial to the pathogenesis of C. botulinum and botulism.

• #7

  https://www.who.int/news-room/fact-sheets/detail/botulism

  Clostridium botulinum is a bacterium that produces dangerous toxins (botulinum toxins) under low-oxygen conditions. […] Botulinum toxins block nerve functions and can lead to respiratory and muscular paralysis. […] Spores produced by the bacteria Clostridium botulinum are heat-resistant and exist widely in the environment, and in the absence of oxygen they germinate, grow and then excrete toxins. […] Botulinum toxins are ingested through improperly processed food in which the bacteria or the spores survive, then grow and produce the toxins. […] The symptoms are not caused by the bacterium itself, but by the toxin produced by the bacterium. […] C. botulinum is an anaerobic bacterium, meaning it can only grow in the absence of oxygen. […] The growth of the bacteria and the formation of toxin occur in products with low oxygen content and certain combinations of storage temperature and preservative parameters.

• #8 Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 | MMWR

  https://www.cdc.gov/mmwr/volumes/70/rr/rr7002a1.htm

  The characteristic flaccid paralysis results from blocking acetylcholine transmission across the neuromuscular junction by inhibition of acetylcholine release from the presynaptic motor neuron terminal. […] All toxin types produce a similar clinical syndrome of cranial nerve palsies followed by descending symmetric flaccid paralysis of variable severity and extent through similar pharmacological mechanisms at the neuromuscular junction. […] Toxin serotypes A, B, E, and (more rarely) F cause human disease. […] Toxin type A produces the most severe syndrome, with the highest proportion of patients requiring mechanical ventilation. […] Toxin type B usually causes milder disease than type A. […] The large molecular size of the botulinum toxin likely precludes its crossing the blood-brain barrier to the central nervous system. […] Recovery, which takes weeks to months, occurs after sprouting of new nerve terminals.

• #9 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  Botulism is a critical neurologic syndrome characterized by acute neuroparalytic manifestations resulting from a neurotoxin secreted by Clostridium botulinum. The toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. Toxin binding blocks acetylcholine release, resulting in weakness, flaccid paralysis, and, often, respiratory arrest. Cure occurs following sprouting of new nerve terminals. […] Clostridium botulinum produces 8 distinct neurotoxins, including types A through G and the potent F/A Hybrid. Among these, types A, B, E, and occasionally F and F/A Hybrid can impact human health. These botulinum toxins are highly toxic proteins that can withstand degradation from stomach acid and proteolytic enzymes. Type F/A Hybrid is considered the most potent toxin among them.

• #10 Botulism – StatPearls – NCBI Bookshelf

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

  Botulism is a rare but life-threatening neuroparalytic syndrome caused by the botulinum neurotoxin, most often produced by the bacterium Clostridium botulinum. […] The toxin’s mode of entry into the bloodstream depends on the type of exposure. In infant botulism, the lack of a robust immune system allows the proliferation of toxin-elaborating clostridial colonies in the digestive tract or bronchioles following ingestion or inhaling spores. Once released, BoNT crosses the mucosal barrier intestinal or pulmonary into the circulation through transcytosis. In foodborne botulism, the preformed toxin from improperly stored food is similarly absorbed in the intestinal tract. Wound botulism is the result of spore germination in devitalized tissue, most commonly as a result of subcutaneous injection of spore-contaminated illicit drugs, with the release of BoNT into the local circulation.

• #11 Clostridium botulinum: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/clostridium-botulinum.html

  C. botulinum forms oval-shaped, metabolically dormant endospores which are highly resistant to environmental stressors and allow persistence in unfavourable conditions. […] Germination of the spores under favourable conditions results in vegetative growth of C. botulinum and production of BoNT (botulinum neurotoxins), the primary virulence factor and the causative agent of botulism. […] Botulism is a rare but severe, and potentially fatal, neuroparalytic disease caused by BoNT produced during germination of C. botulinum spores. […] BoNT binds to the neuromuscular junction and blocks excitatory synaptic transmission by inhibiting acetylcholine release, causing flaccid paralysis. […] Foodborne botulism is the classic form of botulism and is caused by the ingestion of preformed BoNT in contaminated food.

• #12 Clostridium botulinum: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/clostridium-botulinum.html

  Wound botulism occurs by contamination of a wound with spores from BoNT-producing Clostridium species in the environment and subsequent germination of these spores, followed by in situ production of BoNT and absorption into the bloodstream. […] Infant botulism results almost exclusively from spore ingestion and subsequent growth and toxin production in the intestine. […] Adult intestinal botulism is a rare form of botulism caused by the intestinal colonization by C. botulinum, followed by in vivo BoNT production in a manner similar to infant botulism. […] Inhalation botulism does not occur in nature but has been reported among laboratory workers exposed to aerosolized BoNT. […] Iatrogenic botulism results from injection of supratherapeutic concentrations of BoNT for cosmetic and/or therapeutic purposes and is characterized by muscle weakness along with the other classic symptoms of botulism.

• #13 About Botulism | Botulism | CDC

  https://www.cdc.gov/botulism/about/index.html

  Botulism is a rare but serious illness caused by a toxin that attacks the body’s nerves. […] The toxin is made by Clostridium botulinum and sometimes Clostridium butyricum and Clostridium baratii bacteria (germs). […] The spores usually do not cause people to become sick, even when they’re eaten. But under certain conditions, these spores can grow and make one of the most lethal toxins known. […] The conditions in which the spores can grow and make toxin are: Low-oxygen or no oxygen (anaerobic) environment, Low acid, Low sugar, Low salt, A certain temperature range, A certain amount of water. […] For example, improperly home-canned, preserved, or fermented foods can provide the right conditions for spores to grow and make botulinum toxin. […] Wound botulism can happen if the spores get into a wound and make a toxin.

• #14 About Botulism | Botulism | CDC

  https://www.cdc.gov/botulism/about/index.html

  For reasons we do not understand, some infants get botulism when the spores get into their intestines, grow, and produce the toxin. […] Iatrogenic botulism can happen if too much botulinum toxin is injected for cosmetic reasons, such as for wrinkles. […] Adult intestinal toxemia is also known as adult intestinal colonization. This kind of botulism is very rare. It can happen if the spores of the bacteria get into an adult’s intestines, grow, and produce the toxin (similar to infant botulism).

• #15

  https://www.who.int/news-room/fact-sheets/detail/botulism

  C. botulinum will not grow in acidic conditions (pH less than 4.6), and therefore the toxin will not be formed in acidic foods. […] The botulinum toxin has been found in a variety of foods, including low-acid preserved vegetables, such as green beans, spinach, mushrooms, and beets; fish, including canned tuna, fermented, salted and smoked fish; and meat products, such as ham and sausage. […] Although there are several possible sources of infection for infant botulism, spore-contaminated honey has been associated with a number of cases. […] Wound botulism occurs when the spores get into an open wound and are able to reproduce in an anaerobic environment. […] Inhalation botulism exhibits a similar clinical footprint to foodborne botulism. […] Following inhalation of the toxin, symptoms become visible between 13 days, with longer onset times for lower levels of intoxication.

• #16 Botulinum toxin – Wikipedia

  https://en.wikipedia.org/wiki/Botulinum_toxin

  The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide. […] The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family, which is responsible for fusion. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.

• #17 Botulism- Etiology, Pathogenesis, Treatment and Prevention

  https://microbiologynotes.org/botulism-etiology-pathogenesis-treatment-and-prevention/

  Botulism is an intoxication caused by neurotoxins produced by Clostridium botulinum, which adversely affects the synapses of the peripheral nervous system. […] Clostridium botulinum toxin is made up of 150,000 Da progenitor protein (A-B toxins). Consists of a small subunit (light or A chain) with zinc- endopeptidase activity and large subunit B is nontoxic. The toxin forms a complex with nontoxic proteins that protect neurotoxins during the passage through the digestive tract. The carboxyl-terminal portion of the toxin, heavy chain interacts with specific sialic acid receptors along with glycoproteins present on the outer surface of motor neurons and triggers endocytosis of the toxin. The neurotoxin remains at the neuromuscular junction, acidification of the endosome triggers the N- terminal, and heavy chain-mediated release of the light chain. The botulinum endopeptidase inactivates the proteins that regulate the release of acetylcholine, by blocking the neurotransmission at peripheral cholinergic synapses. […] The botulinum toxin prevents the fusion of ACh to the neural cytoplasmic membrane which results in the clinical presentation of botulinum i.e., flaccid paralysis. […] Botulinum toxin inhibits the fusion of ACh to the cell cytoplasmic membrane results in flaccid paralysis.

• #18

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10171130/

  The classical structure of the BoNTs. […] The receptor-bound toxin then enters the presynaptic cell via receptor mediated endocytosis (RME). […] The neurotransmitter refilling of the synaptic vesicles creates an acidic pH, causing a structural change of the heavy-chain translocation domain to form a pore-like structure, which allows translocation of the unfolded light chain from the vesicle to the neuronal cytosol. […] In the cytosol, the interchain di-sulphide bond is reduced, releasing the catalytic light chain of the toxin, which subsequently folds to allow specific cleavage of their SNARE targets. […] The SNARE proteins are part of the neurotransmitter exocytosis machinery, which allows fusion of the neurotransmitter vesicle and the neural membrane. […] Cleavage of these SNARE proteins blocks neurotransmitter release into the neuromuscular junction, preventing postsynaptic excitation.

• #19 Botulinum toxin – Wikipedia

  https://en.wikipedia.org/wiki/Botulinum_toxin

  Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. The toxin causes the disease botulism. […] Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent. […] Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to presynaptic surface of neurons that use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis. […] Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to flaccid paralysis.

• #20 Botulism – StatPearls – NCBI Bookshelf

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

  Once in the bloodstream, BoNT travels to and binds presynaptic nerve terminals of the voluntary motor and autonomic neuromuscular junctions (NMJ). The toxin’s heavy chain moiety promotes endocytosis, after which the light chain is cleaved and released into the cytosol. The light chain targets and cleaves serotype-specific targets of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors, SNARE (ie, synaptosomal-associated protein-25 [SNAP-25], vesicle-associated membrane protein, or syntaxin) polypeptide complex, proteins required for fusion of acetylcholine (ACh)-containing vesicles with the presynaptic membrane. […] By cleaving these fusion complexes, BoNT blocks presynaptic ACh release and inhibits muscle contraction, causing flaccid paralysis. Despite differences in target sites, all BoNT serotypes share the downstream syndrome of flaccid paralysis secondary to failure of ACh release at the NMJ.

• #21 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions. Toxins are absorbed from the stomach and small intestine, where they remain stable despite digestive enzymes. Subsequently, they are hematogenously disseminated to peripheral cholinergic nerve terminals (neuromuscular junctions, postganglionic parasympathetic nerve terminals, peripheral ganglia). The toxin is endocytosed by the neuron and then is allowed to cleave proteins essential for neurotransmitter release. The toxin does not cross the blood-brain barrier, likely secondary to its large size, however, it may be transported to the central nervous system axonally. […] Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the disease course. Later complications include paralytic ileus, severe constipation, and urinary retention.

• #22 Foodborne Botulism: Clinical Diagnosis and Medical Treatment

  https://www.mdpi.com/2072-6651/12/8/509

  The bont-producing clostridia generate a polypeptide toxin (150,000 Daltons) that acts specifically on neuromuscular junctions and cholinergic sites within the autonomic nervous system (all ganglionic synapses and post-ganglionic parasympathetic synapses) by binding to receptors located on the presynaptic membrane. After that, by endocytosis and through a complex processes [e.g., translocation of light chain (Lc) into the cytosol and cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), by the metalloproteinase activity of the Lc] the toxin blocks the normal calcium-associated quantal release of acetylcholine from the presynaptic nerve terminals: this process is irreversible. […] From the clinical point of view, cranial nerves and muscles are primarily involved during the first neurological stage of intoxication.

• #23 Botulinum Toxin: Overview, History, Mechanism of Action

  https://emedicine.medscape.com/article/325451-overview

  Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect. This mechanism laid the foundation for the development of the toxin as a therapeutic tool. […] Recovery occurs through proximal axonal sprouting and muscle re-innervation by formation of a new neuromuscular junction. De Paiva and colleagues suggest that eventually the original neuromuscular junction regenerates. […] BoNT-A and BoNT-E cleave synaptosome-associated protein (SNAP-25), a presynaptic membrane protein required for fusion of neurotransmitter-containing vesicles. […] BoNT-B, BoNT-D, and BoNT-F cleave a vesicle-associated membrane protein (VAMP), also known as synaptobrevin. […] BoNT-C acts by cleaving syntaxin, a target membrane protein.

• #24 Botulinum toxin – Wikipedia

  https://en.wikipedia.org/wiki/Botulinum_toxin

  The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide. […] The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family, which is responsible for fusion. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.

• #25

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10171130/

  The overall mechanism of action is summarised in Figure 5. […] The BoNT SNARE protein targets include the vesicle associated membrane protein (VAMP otherwise known as synaptobrevin), syntaxin, and the synaptosomal-associated protein of 25 kDa (SNAP-25). […] Evidence strongly supports that the long duration of BoNT/A intoxication results from the retention of the toxin within the nerve termini. […] However, some data suggests that short nature of the BoNT/A SNAP-25 truncation may play a contributing factor to its prolonged action. […] The expression and production of BoNT is growth phase dependent, peaking at late exponential-early stationary phase and rapidly declining through stationary phase. […] In addition to the neurotoxin, a key virulence factor in the pathogenesis of C. botulinum and prevalence of botulism, is the sporulation and germination survival strategy. […] Germination is the process of spore recrudescence to neurotoxin producing vegetative cells, crucial to the pathogenesis of C. botulinum and botulism.

• #26 Botulism – StatPearls – NCBI Bookshelf

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

  Once in the bloodstream, BoNT travels to and binds presynaptic nerve terminals of the voluntary motor and autonomic neuromuscular junctions (NMJ). The toxin’s heavy chain moiety promotes endocytosis, after which the light chain is cleaved and released into the cytosol. The light chain targets and cleaves serotype-specific targets of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors, SNARE (ie, synaptosomal-associated protein-25 [SNAP-25], vesicle-associated membrane protein, or syntaxin) polypeptide complex, proteins required for fusion of acetylcholine (ACh)-containing vesicles with the presynaptic membrane. […] By cleaving these fusion complexes, BoNT blocks presynaptic ACh release and inhibits muscle contraction, causing flaccid paralysis. Despite differences in target sites, all BoNT serotypes share the downstream syndrome of flaccid paralysis secondary to failure of ACh release at the NMJ.

• #27 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions. Toxins are absorbed from the stomach and small intestine, where they remain stable despite digestive enzymes. Subsequently, they are hematogenously disseminated to peripheral cholinergic nerve terminals (neuromuscular junctions, postganglionic parasympathetic nerve terminals, peripheral ganglia). The toxin is endocytosed by the neuron and then is allowed to cleave proteins essential for neurotransmitter release. The toxin does not cross the blood-brain barrier, likely secondary to its large size, however, it may be transported to the central nervous system axonally. […] Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the disease course. Later complications include paralytic ileus, severe constipation, and urinary retention.

• #28 Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 | MMWR

  https://www.cdc.gov/mmwr/volumes/70/rr/rr7002a1.htm

  The characteristic flaccid paralysis results from blocking acetylcholine transmission across the neuromuscular junction by inhibition of acetylcholine release from the presynaptic motor neuron terminal. […] All toxin types produce a similar clinical syndrome of cranial nerve palsies followed by descending symmetric flaccid paralysis of variable severity and extent through similar pharmacological mechanisms at the neuromuscular junction. […] Toxin serotypes A, B, E, and (more rarely) F cause human disease. […] Toxin type A produces the most severe syndrome, with the highest proportion of patients requiring mechanical ventilation. […] Toxin type B usually causes milder disease than type A. […] The large molecular size of the botulinum toxin likely precludes its crossing the blood-brain barrier to the central nervous system. […] Recovery, which takes weeks to months, occurs after sprouting of new nerve terminals.

• #29 Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 | MMWR

  https://www.cdc.gov/mmwr/volumes/70/rr/rr7002a1.htm

  The characteristic flaccid paralysis results from blocking acetylcholine transmission across the neuromuscular junction by inhibition of acetylcholine release from the presynaptic motor neuron terminal. […] All toxin types produce a similar clinical syndrome of cranial nerve palsies followed by descending symmetric flaccid paralysis of variable severity and extent through similar pharmacological mechanisms at the neuromuscular junction. […] Toxin serotypes A, B, E, and (more rarely) F cause human disease. […] Toxin type A produces the most severe syndrome, with the highest proportion of patients requiring mechanical ventilation. […] Toxin type B usually causes milder disease than type A. […] The large molecular size of the botulinum toxin likely precludes its crossing the blood-brain barrier to the central nervous system. […] Recovery, which takes weeks to months, occurs after sprouting of new nerve terminals.

• #30 Botulism – StatPearls – NCBI Bookshelf

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

  The BoNT is absorbed into the bloodstream from either a foodborne, wound, intestinal, or inhalational exposure and moves to the peripheral cholinergic nerve terminals, which include the NMJs, postganglionic parasympathetic nerve endings, and peripheral ganglia. […] The BoNT binds to the neuron, is internalized by endocytosis, and moves to the cytosol. Then, it cleaves the proteins that release Ach at the nerve junctions, and by inhibiting the release of Ach, it blocks the transmission of the neurotransmitter across the junction, resulting in flaccid paralysis. BoNT does not cross the blood-brain barrier; the BoNT binds irreversibly to the nerve terminal, and recovery only occurs when new nerve terminals have sprouted. This process may take weeks to months.

• #31 Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 | MMWR

  https://www.cdc.gov/mmwr/volumes/70/rr/rr7002a1.htm

  The characteristic flaccid paralysis results from blocking acetylcholine transmission across the neuromuscular junction by inhibition of acetylcholine release from the presynaptic motor neuron terminal. […] All toxin types produce a similar clinical syndrome of cranial nerve palsies followed by descending symmetric flaccid paralysis of variable severity and extent through similar pharmacological mechanisms at the neuromuscular junction. […] Toxin serotypes A, B, E, and (more rarely) F cause human disease. […] Toxin type A produces the most severe syndrome, with the highest proportion of patients requiring mechanical ventilation. […] Toxin type B usually causes milder disease than type A. […] The large molecular size of the botulinum toxin likely precludes its crossing the blood-brain barrier to the central nervous system. […] Recovery, which takes weeks to months, occurs after sprouting of new nerve terminals.

• #32 Foodborne Botulism: Clinical Diagnosis and Medical Treatment

  https://www.mdpi.com/2072-6651/12/8/509

  Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. […] The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. […] The different types of BoNT and the quantity ingested do not influence the toxic mechanism that result quite similar, this latest influences instead the onset (time) of the first clinical manifestations and the severity of the toxidrome.

• #33 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions. Toxins are absorbed from the stomach and small intestine, where they remain stable despite digestive enzymes. Subsequently, they are hematogenously disseminated to peripheral cholinergic nerve terminals (neuromuscular junctions, postganglionic parasympathetic nerve terminals, peripheral ganglia). The toxin is endocytosed by the neuron and then is allowed to cleave proteins essential for neurotransmitter release. The toxin does not cross the blood-brain barrier, likely secondary to its large size, however, it may be transported to the central nervous system axonally. […] Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the disease course. Later complications include paralytic ileus, severe constipation, and urinary retention.

• #34 Botulism – StatPearls – NCBI Bookshelf

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

  The BoNT is absorbed into the bloodstream from either a foodborne, wound, intestinal, or inhalational exposure and moves to the peripheral cholinergic nerve terminals, which include the NMJs, postganglionic parasympathetic nerve endings, and peripheral ganglia. […] The BoNT binds to the neuron, is internalized by endocytosis, and moves to the cytosol. Then, it cleaves the proteins that release Ach at the nerve junctions, and by inhibiting the release of Ach, it blocks the transmission of the neurotransmitter across the junction, resulting in flaccid paralysis. BoNT does not cross the blood-brain barrier; the BoNT binds irreversibly to the nerve terminal, and recovery only occurs when new nerve terminals have sprouted. This process may take weeks to months.

• #35 Foodborne Botulism: Clinical Diagnosis and Medical Treatment

  https://www.mdpi.com/2072-6651/12/8/509

  Recovery may occur only by formation of new axon terminals, with the regenerating axon (sprouting) forming contacts at the original synaptic sites. The time of recovery depends on entity of neuromuscular block associated with neurogenic atrophy (chemo-denervation) and on the regeneration speed of nervous terminals and of presynaptic membranes. […] The foodborne botulism form is well known in humans and is characterized by a neurological toxidrome consequence of the voluntary motor and autonomic cholinergic junctions’ blockade induced by the toxin. […] The commonest form of botulism has historically been the foodborne, consequently the most known and described typical toxidrome of botulism refers to this form. […] The diagnosis of botulism is mainly based on clinical suspicion, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is crucial to confirm the clinical diagnosis, particularly in relation to regulatory agencies and to identify the different BoNTs involved and the source of intoxication. […] The main goal of the antitoxin treatment is to neutralize the free circulating toxins still unbound at presynaptic level of nerve endings.

• #36 Botulinum Toxin: Overview, History, Mechanism of Action

  https://emedicine.medscape.com/article/325451-overview

  Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect. This mechanism laid the foundation for the development of the toxin as a therapeutic tool. […] Recovery occurs through proximal axonal sprouting and muscle re-innervation by formation of a new neuromuscular junction. De Paiva and colleagues suggest that eventually the original neuromuscular junction regenerates. […] BoNT-A and BoNT-E cleave synaptosome-associated protein (SNAP-25), a presynaptic membrane protein required for fusion of neurotransmitter-containing vesicles. […] BoNT-B, BoNT-D, and BoNT-F cleave a vesicle-associated membrane protein (VAMP), also known as synaptobrevin. […] BoNT-C acts by cleaving syntaxin, a target membrane protein.

• #37 Botulinum toxin – Wikipedia

  https://en.wikipedia.org/wiki/Botulinum_toxin

  The seven toxin serotypes (A-G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences. […] While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members. The A, B, and E serotypes cause human botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months).

• #38 NEWS SCAN: Cost of select-agent research, drug-resistant Salmonella, botulism mechanism, avian flu in Mongolia, rotavirus vaccine safety | CIDRAP

  https://www.cidrap.umn.edu/antimicrobial-stewardship/news-scan-cost-select-agent-research-drug-resistant-salmonella-botulism

  Study uncovers key mechanism in foodborne botulism. Japanese researchers writing in the Journal of Cell Biology report that they have discovered how botulinum toxin crosses from the gastrointestinal tract into the blood in foodborne botulism cases. They write that the nontoxic components of botulinum toxin, including hemagglutinin (HA), protect the toxin from the acid and enzymes found in the digestive tract. The team determined that HA binds epithelial cadherin, thereby blocking it from mediating cell-to-cell adhesion and disrupting the epithelial barrier. They also found that this mechanism is species-specific in that botulinum toxin HA binds human, bovine, and mouse epithelial cadherin, but not the cadherin found in rats or chickens.

• #39

  https://resou.osaka-u.ac.jp/en/research/2015/20150217_1

  The botulinum neurotoxin complex is known to cause fatal food poisoning. […] This group’s research has clarified that hemagglutinin (HA), one of the nontoxic components of a botulinus toxin complex, binds to GP2, a membrane protein expressed on M cells in the intestinal epithelium, by which botulinus toxin invades the body through M cells. […] To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse the intestinal epithelial barrier. […] Here we show that serotype A1 L-PTC, which has high oral toxicity and makes the predominant contribution to causing illness, breaches the intestinal epithelial barrier from microfold (M) cells via an interaction between haemagglutinin (HA), one of the non-toxic components, and glycoprotein 2(GP2). […] HA strongly binds to GP2 expressed on M cells, which do not have thick mucus layers.

• #40

  https://resou.osaka-u.ac.jp/en/research/2015/20150217_1

  The botulinum neurotoxin complex is known to cause fatal food poisoning. […] This group’s research has clarified that hemagglutinin (HA), one of the nontoxic components of a botulinus toxin complex, binds to GP2, a membrane protein expressed on M cells in the intestinal epithelium, by which botulinus toxin invades the body through M cells. […] To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse the intestinal epithelial barrier. […] Here we show that serotype A1 L-PTC, which has high oral toxicity and makes the predominant contribution to causing illness, breaches the intestinal epithelial barrier from microfold (M) cells via an interaction between haemagglutinin (HA), one of the non-toxic components, and glycoprotein 2(GP2). […] HA strongly binds to GP2 expressed on M cells, which do not have thick mucus layers.

• #41

  https://resou.osaka-u.ac.jp/en/research/2015/20150217_1

  Our finding provides the basis for the development of novel antitoxin therapeutics and delivery systems for oral biologics. […] Botulinum neurotoxin complex (type A) breaches the intestinal epithelial barrier from microfold (M) cells via an interaction between hemagglutinin (HA), one of the nontoxic components, and glycoprotein 2(GP2).

• #42 Infant Botulism – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/infant-botulism

  Infant botulism results from ingestion of Clostridium botulinum spores, their colonization of the large intestine, and toxin production in vivo. […] Unlike food-borne botulism, infant botulism is caused by ingestion of spores, not by ingestion of a preformed toxin. […] Finding C. botulinum toxin or organisms in the stool establishes the diagnosis of infant botulism. […] Specific treatment of infant botulism is with human botulism immune globulin (BabyBIG), which is available from the Infant Botulism Treatment and Prevention Program (IBTPPcall 510-231-7600 or visit the IBTPP web site). This antitoxin is derived from pooled human donors who have high titers of antibodies to A and/or B toxin. […] Antibiotics are not given because they may lyse C. botulinum in the gut and increase toxin availability.

• #43 Infant Botulism – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/infant-botulism

  Infant botulism results from ingestion of Clostridium botulinum spores, their colonization of the large intestine, and toxin production in vivo. […] Unlike food-borne botulism, infant botulism is caused by ingestion of spores, not by ingestion of a preformed toxin. […] Finding C. botulinum toxin or organisms in the stool establishes the diagnosis of infant botulism. […] Specific treatment of infant botulism is with human botulism immune globulin (BabyBIG), which is available from the Infant Botulism Treatment and Prevention Program (IBTPPcall 510-231-7600 or visit the IBTPP web site). This antitoxin is derived from pooled human donors who have high titers of antibodies to A and/or B toxin. […] Antibiotics are not given because they may lyse C. botulinum in the gut and increase toxin availability.

• #44 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  Wound botulism results when wounds are contaminated with C botulinum spores. Wound botulism has developed rarely after cesarean delivery, following traumatic injury that involved soil contamination, and more commonly among injection drug users (particularly those who use black-tar heroin). The wound may appear deceptively benign. Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and to produce neurotoxin, which then disseminates hematogenously. Symptoms develop after an incubation period of 4-13 days, with a median 6.5 days. The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.

• #45 Botulism: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/213311-overview

  Wound botulism results when wounds are contaminated with C botulinum spores. Wound botulism has developed rarely after cesarean delivery, following traumatic injury that involved soil contamination, and more commonly among injection drug users (particularly those who use black-tar heroin). The wound may appear deceptively benign. Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and to produce neurotoxin, which then disseminates hematogenously. Symptoms develop after an incubation period of 4-13 days, with a median 6.5 days. The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.

• #46 Botulism Antitoxin | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/37505

  Botulinum toxin binds irreversibly to presynaptic nerve endings at neuromuscular junctions. Through receptor-mediated endocytosis, the toxin enters the cell and cleaves SNARE proteins, which are necessary for releasing acetylcholine into the synaptic cleft. Blockade of voluntary motor and autonomic cholinergic junctions leads to xerostomia (dry mouth), blurry vision, diplopia, dysphonia, dysarthria, dysphagia, and other muscle weakness. The most concerning clinical manifestation is when blockade affects respiratory muscles leading to respiratory failure.[1] […] HBAT works by binding botulism toxin in the blood. In the Clinical Pharmacology Review submitted by Cangene, the reported that the polyclonal antibody fragments (F(ab)2 and Fab) bind free botulinum toxin, which then prevents the toxin from being internalized at the post-synaptic cholinergic receptor. Because antitoxin only binds free botulinum toxin, it prevents the progression of symptoms but does not reverse any paralysis already present.[12] […] Prior formulations had non-fragmented antibodies derived from inoculated horses. While these are larger molecules than the new HBAT formulation, the fragmented antibody is less immunogenic and has less risk for serious adverse effects.[9]

• #47 Foodborne Botulism: Clinical Diagnosis and Medical Treatment

  https://www.mdpi.com/2072-6651/12/8/509

  Recovery may occur only by formation of new axon terminals, with the regenerating axon (sprouting) forming contacts at the original synaptic sites. The time of recovery depends on entity of neuromuscular block associated with neurogenic atrophy (chemo-denervation) and on the regeneration speed of nervous terminals and of presynaptic membranes. […] The foodborne botulism form is well known in humans and is characterized by a neurological toxidrome consequence of the voluntary motor and autonomic cholinergic junctions’ blockade induced by the toxin. […] The commonest form of botulism has historically been the foodborne, consequently the most known and described typical toxidrome of botulism refers to this form. […] The diagnosis of botulism is mainly based on clinical suspicion, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is crucial to confirm the clinical diagnosis, particularly in relation to regulatory agencies and to identify the different BoNTs involved and the source of intoxication. […] The main goal of the antitoxin treatment is to neutralize the free circulating toxins still unbound at presynaptic level of nerve endings.

• #48 Botulism Antitoxin | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/37505

  Botulinum toxin binds irreversibly to presynaptic nerve endings at neuromuscular junctions. Through receptor-mediated endocytosis, the toxin enters the cell and cleaves SNARE proteins, which are necessary for releasing acetylcholine into the synaptic cleft. Blockade of voluntary motor and autonomic cholinergic junctions leads to xerostomia (dry mouth), blurry vision, diplopia, dysphonia, dysarthria, dysphagia, and other muscle weakness. The most concerning clinical manifestation is when blockade affects respiratory muscles leading to respiratory failure.[1] […] HBAT works by binding botulism toxin in the blood. In the Clinical Pharmacology Review submitted by Cangene, the reported that the polyclonal antibody fragments (F(ab)2 and Fab) bind free botulinum toxin, which then prevents the toxin from being internalized at the post-synaptic cholinergic receptor. Because antitoxin only binds free botulinum toxin, it prevents the progression of symptoms but does not reverse any paralysis already present.[12] […] Prior formulations had non-fragmented antibodies derived from inoculated horses. While these are larger molecules than the new HBAT formulation, the fragmented antibody is less immunogenic and has less risk for serious adverse effects.[9]

• #49

  https://insight.jci.org/articles/view/132891

  Botulinum neurotoxins (BoNTs) are potent neuroparalytic toxins that cause mortality through respiratory paralysis. […] The clinical syndrome of botulism results from peripheral blockade of neurotransmission at neuromuscular junctions, autonomic ganglia, and parasympathetic and sympathetic nerve endings. […] Recovery of neuromuscular function occurs once LC activity is eliminated, cleaved SNARE proteins have been replaced with intact SNARE proteins, and functional motor end-plates have regenerated (if atrophy has occurred). […] Based on the molecular and cellular toxicokinetics of intoxication, a comprehensive therapeutic paradigm for botulism would include (a) broad-spectrum antitoxins to terminate exposure, (b) intracellular antidotes to block LC proteolysis of SNARE proteins, and (c) symptomatic treatments that enhance neuromuscular function and mitigate muscle weakness, with mechanical ventilation administered as needed to ensure survival.

• #50

  https://insight.jci.org/articles/view/132891

  3,4-DAP is a selective potassium channel blocker that prolongs neuronal action potential duration, thereby increasing Ca2+ influx through presynaptic voltage-gated Ca2+ channels. […] Mechanistic studies conducted in BoNT-intoxicated primary neuron cultures and mouse diaphragms demonstrate that 3,4-DAP has multiple effects on the function of intoxicated nerve terminals, providing a plausible explanation for these variable clinical outcomes. […] Collectively, these findings suggest that 3,4-DAP could be effective as a symptomatic treatment for clinical botulism at multiple time points, independent of serotype, and with enhanced potency in cases of type A botulism. […] 3,4-DAP treatment restores respiration and extends survival in terminal BoNT/A-induced respiratory botulism. […] 3,4-DAP is effective against serotypes A, B, and E when administered at times of partial paralysis.

• #51

  https://insight.jci.org/articles/view/132891

  3,4-DAP has potential to be highly effective in treating symptoms of sublethal and low-dose intoxications. […] Given this broad temporal window for treatment, we propose that chronic administration of 3,4-DAP will reduce the severity and duration of neuromuscular weakness until patients have fully recovered, with greatest efficacy before and after peak paralysis. […] 3,4-DAP is a potentially important adjunct to the FDA-approved heptavalent botulism antitoxin (HBAT). […] 3,4-DAP works orthogonally to HBAT; therefore, the risks of adverse drug interactions are low. […] Collectively, these data make a compelling preclinical case for use of 3,4-DAP to treat a range of botulism symptoms.

• #52

  https://www.who.int/news-room/fact-sheets/detail/botulism

  Diagnosis is usually based on clinical history and clinical examination followed by laboratory confirmation including demonstrating the presence of botulinum toxin in serum, stool or food, or a culture of C. botulinum from stool, wound or food. […] Antitoxin should be administered as soon as possible after a clinical diagnosis. […] Prevention of foodborne botulism is based on good practice in food preparation particularly during heating/sterilization and hygiene. […] The vegetative forms of bacteria can be destroyed by boiling but the spores can remain viable after boiling even for several hours.

• #53 Botulism – Wikipedia

  https://en.wikipedia.org/wiki/Botulism

  Botulism is a rare and potentially fatal illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. […] The bacterial spores which cause it are common in both soil and water and are very resistant. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. […] The toxin acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetylcholine’s release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. This causes paralysis.

• #54 Botulism – Wikipedia

  https://en.wikipedia.org/wiki/Botulism

  In all cases, illness is caused by the botulinum toxin which the bacterium C. botulinum produces in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first. […] Botulinum toxin is broken into eight neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. […] Botulinum inhibits the release within the nervous system of acetylcholine, a neurotransmitter, responsible for communication between motor neurons and muscle cells. All forms of botulism lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. […] Botulinum toxin A and E specifically cleave the SNAP-25, whereas serotype B, D, F and G cut synaptobrevin. Serotype C cleaves both SNAP-25 and syntaxin. This causes blockade of neurotransmitter acetylcholine release, ultimately leading to paralysis.

• #55 Botulism – StatPearls – NCBI Bookshelf

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

  The BoNT is absorbed into the bloodstream from either a foodborne, wound, intestinal, or inhalational exposure and moves to the peripheral cholinergic nerve terminals, which include the NMJs, postganglionic parasympathetic nerve endings, and peripheral ganglia. […] The BoNT binds to the neuron, is internalized by endocytosis, and moves to the cytosol. Then, it cleaves the proteins that release Ach at the nerve junctions, and by inhibiting the release of Ach, it blocks the transmission of the neurotransmitter across the junction, resulting in flaccid paralysis. BoNT does not cross the blood-brain barrier; the BoNT binds irreversibly to the nerve terminal, and recovery only occurs when new nerve terminals have sprouted. This process may take weeks to months.

• #56 Botulism: Pathogenesis, Diagnosis and Prevention

  https://repository.pertanian.go.id/items/7342aa3e-ce92-40b2-a41e-81eae774066c

  Botulism is a potential lethal disease in animals as well as in human, a neuroparalytic disease caused by Clostridium botulinum toxin. […] Eight types of C. botulinum (A, B, C1, C2, D, E, F, G) have been recognized, each elaborating an immunologically distinct form of toxin. Botulinum neurotoxins are the most powerful biological toxins known and in some countries they have been studied and developed as biological weapon. […] Botulinum toxin produces clinical manifestations when either inhaled or ingested. After toxin is absorbed, it enters the bloodstream and travels to peripheral cholinergic synapses, primarily the neuromuscular junction. Once at these sites, botulinum toxin is internalized and enzymatically prevents the release of acteylcholine leads to paralysis. […] Laboratory diagnoses for botulism should include isolating C. botulinum and detecting of toxin in the patient. Rapid and sensitive detection of all types of botulinum toxin are needed. […] The botulismus prevention using vaccine induced a strong antibody response and could be remained protective for 12 months, while botulism treatment in animals is usually ineffective.

Zobacz więcej