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Journal of Veterinary Diagnostic... Mar 2020Tetanus is a neurologic disease of humans and animals characterized by spastic paralysis. Tetanus is caused by tetanus toxin (TeNT) produced by , an environmental... (Review)
Review
Tetanus is a neurologic disease of humans and animals characterized by spastic paralysis. Tetanus is caused by tetanus toxin (TeNT) produced by , an environmental soilborne, gram-positive, sporulating bacterium. The disease most often results from wound contamination by soil containing spores. Horses, sheep, and humans are highly sensitive to TeNT, whereas cattle, dogs, and cats are more resistant. The diagnosis of tetanus is mainly based on the characteristic clinical signs. Identification of at the wound site is often difficult.
Topics: Animals; Animals, Domestic; Clostridium tetani; Mammals; Tetanus
PubMed: 32070229
DOI: 10.1177/1040638720906814 -
Journal of Neurochemistry Sep 2021Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and... (Review)
Review
Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and germinate into a vegetative bacterium that releases a toxin, termed tetanus neurotoxin (TeNT). TeNT enters the general circulation, binds to peripheral motor neurons and sensory neurons, and is transported retroaxonally to the spinal cord. It then enters inhibitory interneurons and blocks the release of glycine or GABA causing a spastic paralysis. This review attempts to correlate the metalloprotease activity of TeNT and its trafficking and localization into the vertebrate body to the nature and sequence of appearance of the symptoms of tetanus.
Topics: Animals; Brain; Humans; Neurotoxins; Peripheral Nerves; Spinal Cord; Tetanus; Tetanus Toxin; Tetanus Toxoid
PubMed: 33629408
DOI: 10.1111/jnc.15330 -
MBio Aug 2020Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of proteins,...
Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens.
Topics: Animals; Antibodies, Bacterial; Escherichia coli; Female; Mice; Mice, Inbred ICR; Mutation; Recombinant Proteins; Tetanus; Tetanus Toxoid; Vaccination; Vaccine Potency
PubMed: 32788381
DOI: 10.1128/mBio.01668-20 -
Vaccines Feb 2022The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include... (Review)
Review
The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include those produced by type C and , both of which are characterized by enterocolitis. The main histotoxic diseases are gas gangrene, Tyzzer disease, and infectious necrotic hepatitis. Gas gangrene is produced by one or more of the following microorganisms: type A, , and type A, and it is characterized by necrotizing cellulitis and/or myositis. Tyzzer disease is produced by and is mainly characterized by multifocal necrotizing hepatitis. Infectious necrotic hepatitis is produced by type B and is characterized by focal necrotizing hepatitis. The main neurotoxic clostridial diseases are tetanus and botulism, which are produced by and , respectively. Tetanus is characterized by spastic paralysis and botulism by flaccid paralysis. Neither disease present with specific gross or microscopic lesions. The pathogenesis of clostridial diseases involves the production of toxins. Confirming a diagnosis of some of the clostridial diseases of horses is sometimes difficult, mainly because some agents can be present in tissues of normal animals. This paper reviews the main clostridial diseases of horses.
PubMed: 35214776
DOI: 10.3390/vaccines10020318 -
Toxins May 2022and are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for... (Review)
Review
and are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for flaccid and spastic paralysis, respectively. The main habitat of these toxigenic bacteria is the environment (soil, sediments, cadavers, decayed plants, intestinal content of healthy carrier animals). can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism. More rarely, colonizes wounds, whereas tetanus is always a result of wound contamination by The synthesis of neurotoxins is strictly regulated by complex regulatory networks. The highest levels of neurotoxins are produced at the end of the exponential growth and in the early stationary growth phase. Both microorganisms, except E, share an alternative sigma factor, BotR and TetR, respectively, the genes of which are located upstream of the neurotoxin genes. These factors are essential for neurotoxin gene expression. and share also a two-component system (TCS) that negatively regulates neurotoxin synthesis, but each microorganism uses additional distinct sets of TCSs. Neurotoxin synthesis is interlocked with the general metabolism, and CodY, a master regulator of metabolism in Gram-positive bacteria, is involved in both clostridial species. The environmental and nutritional factors controlling neurotoxin synthesis are still poorly understood. The transition from amino acid to peptide metabolism seems to be an important factor. Moreover, a small non-coding RNA in , and quorum-sensing systems in and possibly in , also control toxin synthesis. However, both species use also distinct regulatory pathways; this reflects the adaptation of and to different ecological niches.
Topics: Animals; Botulinum Toxins; Botulism; Clostridium botulinum; Clostridium tetani; Humans; Neurotoxins
PubMed: 35737025
DOI: 10.3390/toxins14060364 -
British Medical Bulletin 2015The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of... (Review)
Review
INTRODUCTION
The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care.
SOURCES OF DATA
Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications.
AREAS OF AGREEMENT
The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world.
AREAS OF CONTROVERSY
Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization.
AREAS TIMELY FOR DEVELOPING RESEARCH
It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses.
Topics: Coinfection; Female; HIV Infections; Humans; Malaria; Pregnancy; Prenatal Exposure Delayed Effects; Tetanus; Tetanus Toxoid; Vaccination
PubMed: 26598719
DOI: 10.1093/bmb/ldv044 -
Viruses Jul 2023This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics... (Review)
Review
This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, , . The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.
Topics: Humans; Immunoglobulins; Globulins; Immunization, Passive; Vaccines; Communicable Diseases; Antibodies, Viral
PubMed: 37515229
DOI: 10.3390/v15071543