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1.
Med Clin (Barc) ; 159(3): 147-151, 2022 Aug 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35725637

RESUMO

BACKGROUND: Tetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions. METHODS: This is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995-2019. Epidemiological and clinical data were obtained from the patient's medical records. RESULTS: A total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died. DISCUSSION: The incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men.


Assuntos
Tétano , Idoso , Clostridium tetani , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tétano/diagnóstico , Tétano/epidemiologia , Tétano/terapia
2.
Toxins (Basel) ; 14(6)2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35737025

RESUMO

Clostridium botulinum and Clostridium tetani 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). C. botulinum can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, C. botulinum can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism. More rarely, C. botulinum colonizes wounds, whereas tetanus is always a result of wound contamination by C. tetani. 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 C. botulinum 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. C. botulinum and C. tetani 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 C. tetani, and quorum-sensing systems in C. botulinum and possibly in C. tetani, also control toxin synthesis. However, both species use also distinct regulatory pathways; this reflects the adaptation of C. botulinum and C. tetani to different ecological niches.


Assuntos
Toxinas Botulínicas , Botulismo , Clostridium botulinum , Animais , Toxinas Botulínicas/genética , Toxinas Botulínicas/metabolismo , Botulismo/microbiologia , Clostridium botulinum/genética , Clostridium botulinum/metabolismo , Clostridium tetani/genética , Clostridium tetani/metabolismo , Humanos , Neurotoxinas/genética , Neurotoxinas/metabolismo
3.
Toxins (Basel) ; 14(1)2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-35051008

RESUMO

BACKGROUND: Ensuring consistency of tetanus neurotoxin (TeNT) production by Clostridium tetani could help to ensure consistent product quality in tetanus vaccine manufacturing, ultimately contributing to reduced animal testing. The aim of this study was to identify RNA signatures related to consistent TeNT production using standard and non-standard culture conditions. METHODS: We applied RNA sequencing (RNA-Seq) to study C. tetani gene expression in small-scale batches under several culture conditions. RESULTS: We identified 1381 time-dependent differentially expressed genes (DEGs) reflecting, among others, changes in growth rate and metabolism. Comparing non-standard versus standard culture conditions identified 82 condition-dependent DEGs, most of which were specific for one condition. The tetanus neurotoxin gene (tetX) was highly expressed but showed expression changes over time and between culture conditions. The tetX gene showed significant down-regulation at higher pH levels (pH 7.8), which was confirmed by the quantification data obtained with the recently validated targeted LC-MS/MS approach. CONCLUSIONS: Non-standard culture conditions lead to different gene expression responses. The tetX gene appears to be the best transcriptional biomarker for monitoring TeNT production as part of batch-to-batch consistency testing during tetanus vaccine manufacturing.


Assuntos
Clostridium tetani/genética , Clostridium tetani/metabolismo , Neurotoxinas/biossíntese , Neurotoxinas/genética , Toxoide Tetânico/biossíntese , Toxoide Tetânico/normas , Sequência de Bases , Células Cultivadas , Regulação Bacteriana da Expressão Gênica
4.
J Microbiol Biotechnol ; 32(1): 91-98, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34818665

RESUMO

Tetanus is a potentially fatal public health illness resulted from the neurotoxins generated by Clostridium tetani. C. tetani is not easily culturable and culturing the relevant bacteria from infected wounds has rarely been useful in diagnosis; PCR-based assays can only be conducted at highly sophisticated laboratories. Therefore, a real-time recombinase polymerase amplification assay (Exo-RPA) was constructed to identify the fragments of the neurotoxin gene of C. tetani. Primers and the exo probe targeting the conserved region were designed, and the resulting amplicons could be detected in less than 20 min, with a detection limit of 20 copies/reaction. The RPA assay displayed good selectivity, and there were no cross-reactions with other infectious bacteria common in penetrating wounds. Tests of target-spiked serum and pus extract revealed that RPA is robust to interfering factors and has great potential for further development for biological sample analysis. This method has been confirmed to be reliable for discriminating between toxic and nontoxic C. tetani strains. The RPA assay dramatically improves the diagnostic efficacy with simplified device architecture and is a promising alternative to real-time PCR for tetanus detection.


Assuntos
Técnicas Bacteriológicas/métodos , Clostridium tetani/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Recombinases , Animais , Clostridium tetani/genética , Primers do DNA , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Tétano/diagnóstico , Tétano/microbiologia
5.
Biotechnol Adv ; 54: 107781, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34029623

RESUMO

Tetanus vaccination is of major importance for public health in most countries in the world. The World Health Organization indicated that 15,000 tetanus cases were reported in 2018 (Organization, World Health, 2019). Currently, vaccine manufacturers use tetanus toxin produced by Clostridium tetani fermentation in complex media. The complex components, commonly derived from animal sources, introduce potential variability in cultures. To achieve replicable fermentation and to avoid toxic or allergic reactions from animal-source compounds, several studies have tried to switch from complex to chemically defined media without affecting toxin titers. The present review introduces the current knowledge on i) C. tetani strain diversity, whole-genome sequences and metabolic networks; ii) toxin regulation and synthesis; and iii) culture media, cultivation processes and growth requirements. We critically reviewed the reported data on metabolism in C. tetani and completed comparative genomic and proteomic analyses with other Clostridia species. We integrated genomic data based on whole-genome sequence annotation, supplemented with cofactor specificities determined by protein sequence identity, in a new map of C. tetani central metabolism. This is the first data review that integrates insights from omics experiments on C. tetani. The overview of C. tetani physiology described here could provide support for the design of new chemically defined media devoid of complex sources for toxin production.


Assuntos
Clostridium tetani , Proteômica , Animais , Reatores Biológicos , Clostridium , Clostridium tetani/genética , Clostridium tetani/metabolismo , Toxina Tetânica/genética , Toxina Tetânica/metabolismo
6.
Acta neurol. colomb ; 37(4): 210-218, oct.-dic. 2021. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1349893

RESUMO

RESUMEN INTRODUCCIÓN: El tétanos es una enfermedad inmunoprevenible, ocasionada por la bacteria Clostridium tetani, desencadenando una enfermedad caracterizada por espasmos musculares, insuficiencia respiratoria y disautonomías, potencialmente mortal. MATERIALES Y MÉTODOS: Presentamos una serie de tres pacientes que consultaron al servicio de urgencias por presentar trismus, rigidez muscular generalizada y dificultad respiratoria, requiriendo manejo en la unidad de cuidados intensivos, con relajación muscular y administración intramuscular e intratecal de inmunoglobulina antitetánica, con evolución satisfactoria en todos los casos. DISCUSIÓN: Su tratamiento está divido en dos grandes secciones; la primera parte, el control de la infección y eliminación del agente causal, con lavado y desbridamiento de heridas, administración de antibióticos y neutralización de la neurotoxina. La segunda parte del tratamiento está en el soporte vital en la unidad de cuidados intensivos, con la administración de sedación, relajación muscular, control de disautonomías y manejo de complicaciones. CONCLUSIONES: El tétanos a pesar de los avances en vacunación aún es una enfermedad presente, cuyo diagnóstico y tratamiento rápido y adecuado, permite sobrevivir a los pacientes, como en los casos aquí reportados.


ABSTRACT INTRODUCTION: Tetanus is an immuno-preventable disease, produced by the bacterium Clostridium tetani, that causes a disease characterized by muscle spasms, respiratory insufficiency and life-threatening dysautonomia. MATERIALS AND METHODS: We present a series of three patients who consulted for trismus, muscle stiffness and respiratory failure, which required intensive care management, muscle relaxation, intramuscular and intrathecal administration of tetanus immu-noglobulin, with satisfactory outcomes in all the cases. DISCUSSION: Its treatment is divided into two main sections; the first part, the control of infection and elimination of the causative agent, with washing and debridement of wounds, administration of antibiotics and neutralization of the neurotoxin. The second part is life support in the intensive care unit, with the administration of sedation, muscular relaxation and control of dysautonomia and the management of complications. CONCLUSIONS: Despite the advances in vaccination, tetanus is still a present disease, whose diagnosis and rapid and adequate treatment allows patients to survive, as in the cases reported here.


Assuntos
Tétano , Toxina Tetânica , Relatos de Casos , Antitoxina Tetânica , Revisão , Clostridium tetani
7.
Lakartidningen ; 1182021 11 26.
Artigo em Sueco | MEDLINE | ID: mdl-34826328

RESUMO

Tetanus (lockjaw) is a potentially life-threatening disease caused by a neurotoxin produced by the spore forming bacterium Clostridium tetani. The incidence has decreased substantially the last decades in most high-income countries, much due to well established vaccination programs. However, although uncommon, tetanus still remains a reality in Sweden. The condition is diagnosed based on clinical parameters and is hard to distinguish from many other more common differential diagnoses. Lack of vaccine induced antibodies is the most important risk factor for developing tetanus. Here we present a patient who developed tetanus two weeks following a puncture wound, but who was initially misdiagnosed with wake-up stroke. The case illustrates the importance of reviewing a patient's tetanus vaccine history, which determines what prophylactic measures are adequate to take, especially following potentially contaminated wounds.


Assuntos
Tétano , Clostridium tetani , Humanos , Fatores de Risco , Suécia/epidemiologia , Tétano/diagnóstico , Tétano/prevenção & controle , Toxoide Tetânico
8.
Am J Trop Med Hyg ; 105(2): 494-497, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181568

RESUMO

Tetanus arises from wound contamination with Clostridium tetani, but approximately one fifth of patients have no discernable entry wound. Clostridium tetani is culturable from animal feces, suggesting the gastrointestinal tract could be an endogenous reservoir or direct-entry portal, but human data are lacking. In this study of 101 Vietnamese adults with tetanus and 29 hospitalized control subjects, admission stool samples were cultured for C. tetani. Anti-tetanus toxin antibodies were measured by ELISA. Clostridium tetani toxigenicity was evaluated using polymerase chain reaction and sequencing. Toxigenic C. tetani was cultured from stool samples in 50 of 100 (50%) tetanus cases and 12 of 28 (42.9%) control subjects (P = 0.50), and stool samples of 44 of 85 (52.4%) tetanus cases with clinically identified wounds compared with 6 of 15 (47.6%) patients without clinically identified wounds (P = 0.28). Nine of 12 (75%) control subjects with toxigenic C. tetani in their stool samples lacked protective antibody concentrations. These findings fail to show evidence of an association between gastrointestinal C. tetani and tetanus infection, but emphasize the importance of increasing vaccination coverage.


Assuntos
Clostridium tetani , Tétano , Adulto , Animais , Estudos de Casos e Controles , Clostridium tetani/isolamento & purificação , Clostridium tetani/patogenicidade , Trato Gastrointestinal/microbiologia , Humanos , Pessoa de Meia-Idade , Tétano/diagnóstico , Tétano/patologia , Toxina Tetânica/sangue
9.
Sci Rep ; 11(1): 12134, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108521

RESUMO

Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)-reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix-reactive antibodies provided enhanced protection compared to the use of each antibody alone.


Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Clostridium tetani/isolamento & purificação , Leucócitos Mononucleares/imunologia , Metaloendopeptidases/imunologia , Toxina Tetânica/imunologia , Tétano/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Monoclonais/sangue , Anticorpos Neutralizantes/sangue , Humanos , Camundongos , Tétano/sangue , Tétano/microbiologia
10.
Top Companion Anim Med ; 44: 100535, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933700

RESUMO

Tetanus in dogs is a relatively uncommon neurological disease caused by the sporogenic bacillus Clostridium tetani. This disease is associated with prolonged hospitalization and mortality rates from 8%-50%. A 2-year-old, neutered male King Charles Spaniel and an approximately 8-months-old female Mongrel dog presented to Companion Animal Clinic with symptoms of muscle rigidity and generalized stiffness. A tentative diagnosis of generalized tetanus was made in both dogs. Treatment consisted of IV fluids, antibiotics (metronidazole), human tetanus antitoxin, analgesics and supportive care. Muscle relaxation was provided by midazolam. Acetylpromazine meleate was added to the treatment of the second dog to better control excitability. Each dog received magnesium therapy on the 10th and 3rd days, respectively; which was provided per os to the first dog and constant rate infusion (4 mg/kg/h) to the second dog. The addition of magnesium helped to increase muscle relaxation and increased the time interval between acetylpromazine administration. On the tenth day, magnesium sulfate was discontinued from the second dog and magnesium aspartate (12 mg/kg), twice a day, per os was administered in both animals. Further muscle relaxation was noted in both dogs with a substantial reduction of tetanus symptoms. Both dogs were discharged from Intensive Care Unit on the 14th and 13th day respectively with sole treatment of magnesium aspartate (12 mg/kg) orally, twice a day. Magnesium aspartate was continued for 14 days and 12 days respectively. Both dogs had progressive reduction of muscle rigidity and the first dog recovered completely. The second dog presented again with muscle rigidity and increased spinal reflexes after the discontinuation of magnesium aspartate, thus therapy with magnesium aspartate was started again and symptoms subsided after the second oral dose of magnesium. Therapy was continued for two more weeks during which muscle rigidity subsided and then was stopped. At that time, tetanus symptoms did not relapse and the dog was considered fully recovered. According to the findings of this case series, magnesium therapy may provide further muscle relaxation during the standard therapeutic protocol of tetanus in dogs. In addition, long term symptoms of the disease were adequately managed with the administration of magnesium aspartate, orally.


Assuntos
Doenças do Cão , Tétano , Animais , Clostridium tetani , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Magnésio/uso terapêutico , Sulfato de Magnésio , Masculino , Metronidazol , Tétano/tratamento farmacológico , Tétano/veterinária
11.
Sci Rep ; 11(1): 4157, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603121

RESUMO

Clostridium tetani produces the tetanus toxin (TeNT), one of the most powerful bacterial toxins known to humankind and responsible for tetanus. The regulation of toxin expression is complex and involves the alternative sigma factor TetR as well as other regulators. Here, a transcriptional analysis of the TeNT-encoding large plasmid of C. tetani identified a putative non-coding small RNA (sRNA), located in close vicinity of the 3' untranslated region of the tent gene. A northern blot experiment could identify a respective sRNA with a size of approx. 140 nucleotides. Sequence analysis showed that the sRNA contains a 14-nucleotide region that is complementary to a 5' located region of tent. In order to investigate the function of the sRNA, we applied a RNA interference approach targeting the sRNA in two C. tetani wild-type strains; the constructed antisense C. tetani strains showed an approx. threefold increase in both extracellular and total TeNT production compared to the respective wild-type strains. In addition, recombinant C. tetani strains were constructed that contained tent-locus harboring plasmids with and without the sRNA. However, the introduction of the tent-locus without the sRNA in a C. tetani strain lacking the wild-type TeNT-encoding large plasmid resulted in a lower TeNT production compared to the same strain with recombinant tent-locus with the sRNA. This suggests that the expression or the effect of the sRNA is modulated by the C. tetani genetic background, notably that of the wild-type TeNT-encoding large plasmid. In addition, some recombinant strains exhibited modulated growth patterns, characterized by premature bacterial cell lysis. Taken together, our data indicate that the sRNA acts as a negative regulator of TeNT synthesis, with a possible impact on the growth of C. tetani. We hypothesize that the role of this sRNA is to limit toxin levels in the exponential growth phase in order to prevent premature bacterial lysis.


Assuntos
Clostridium tetani/genética , RNA não Traduzido/genética , Toxina Tetânica/genética , Proteínas de Bactérias/genética , DNA Bacteriano/genética , Regulação Bacteriana da Expressão Gênica/genética , Plasmídeos/genética , Fator sigma/genética , Transativadores/genética
12.
Med Hypotheses ; 146: 110395, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341328

RESUMO

We present the hypothesis to the scientific community actively designing clinical trials and recommending public health guidelines to control the pandemic that - "Tetanus vaccination may be contributing to reduced severity of the COVID-19 infection" - and urge further research to validate or invalidate the effectiveness of the tetanus toxoid vaccine against COVID-19. This hypothesis was revealed by an explainable artificial intelligence system unleashed on open public biomedical datasets. As a foundation for scientific rigor, we describe the data and the artificial intelligence system, document the provenance and methodology used to derive the hypothesis and also gather potentially relevant data/evidence from recent studies. We conclude that while correlations may not be reason for causation, correlations from multiple sources is more than a serendipitous coincidence that is worthy of further and deeper investigation.


Assuntos
COVID-19/prevenção & controle , Modelos Biológicos , Pandemias/prevenção & controle , SARS-CoV-2 , Toxoide Tetânico/farmacologia , Inteligência Artificial , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/farmacologia , Clostridium tetani/genética , Clostridium tetani/imunologia , Bases de Dados de Produtos Farmacêuticos , Reposicionamento de Medicamentos/estatística & dados numéricos , Humanos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Homologia de Sequência de Aminoácidos , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Toxina Tetânica/genética , Vacinação
13.
Int Immunopharmacol ; 91: 107297, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360088

RESUMO

Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs-T3, T7, and T9-6-completely protected mice from challenge with 2× LD50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.


Assuntos
Anticorpos Antibacterianos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Clostridium tetani/imunologia , Vacina contra Difteria e Tétano/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Imunogenicidade da Vacina , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Monoclonais/sangue , Anticorpos Neutralizantes/sangue , Especificidade de Anticorpos , Clostridium tetani/patogenicidade , Modelos Animais de Doenças , Epitopos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Tétano/imunologia , Tétano/microbiologia , Fatores de Tempo , Vacinação
14.
Dev Comp Immunol ; 114: 103841, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32861731

RESUMO

Tetanus toxoids (TT) commercially available for use in horses and livestock are commonly used to vaccinate elephants and rhinoceros that are in human care. Although recommendations for booster intervals have changed in human and horse protocols to reduce the risks associated with hyper-immunity (i.e. B-cell anergy and hypersensitivity reactions) these have generally not been adopted in zoo protocols. Additionally, there is no evidence to demonstrate commercial TT immunogenicity in rhinoceros. In this study, a preliminary analysis of rhinoceros antibody responses to TT was conducted, in addition to an exploration of the impact of various booster frequencies on antibody responses in elephant. Retrospective analysis of archived serum samples was conducted for 9 Asian elephants (Elephas maximus), 7 southern black (Diceros bicornis minor), one southern white (Ceratotherium simum simum), and two greater one-horned (Rhinoceros unicornis) rhinoceros. Pre-vaccination (baseline) samples and those following priming vaccination (rhinoceros only), annual and non-annual boosters were targeted. A commercially available competitive ELISA kit was used to quantify serum anti-TT antibodies. Average baseline and post-vaccination anti-tetanus antibody concentrations were greater in elephant (92 mg/L ± 42, n = 3, N = 3; 125 ± 76, n = 82, N = 9) than in rhinoceros (47 mg/L ± 39, n = 8, N = 8; 44 mg/L ± 37, n = 16, N = 7). Rhinoceros antibody concentrations did not differ markedly following vaccinations from their naturally acquired high pre-vaccination concentrations. Eight elephants demonstrated antibody maintenance for 3-5 years without a tetanus booster. Additionally, although five out of nine elephants developed local reactions consistent with delayed type IV hypersensitivity following some boosters, there was no association between high antibody concentrations and increased incidence of adverse reactions. In addition, no decrease in antibody concentrations was detected as a result of annual vaccination in elephants, though this does not entirely rule out potential for B-cell anergy.


Assuntos
Anticorpos Antibacterianos/sangue , Clostridium tetani/fisiologia , Elefantes/imunologia , Perissodáctilos/imunologia , Toxoide Tetânico/imunologia , Tétano/imunologia , Animais , Animais de Zoológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersensibilidade Tardia/etiologia , Imunização Secundária , Imunogenicidade da Vacina , Memória Imunológica , Estudos Retrospectivos , Toxoide Tetânico/efeitos adversos , Vacinação
15.
J Ind Microbiol Biotechnol ; 47(12): 1059-1073, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33175241

RESUMO

Tetanus is a fatal disease caused by Clostridium tetani infections. To prevent infections, a toxoid vaccine, developed almost a century ago, is routinely used in humans and animals. The vaccine is listed in the World Health Organisation list of Essential Medicines and can be produced and administered very cheaply in the developing world for less than one US Dollar per dose. Recent developments in both analytical tools and frameworks for systems biology provide industry with an opportunity to gain a deeper understanding of the parameters that determine C. tetani virulence and physiological behaviour in bioreactors. Here, we compared a traditional fermentation process with a fermentation medium supplemented with five heavily consumed amino acids. The experiment demonstrated that amino acid catabolism plays a key role in the virulence of C. tetani. The addition of the five amino acids favoured growth, decreased toxin production and changed C. tetani morphology. Using time-course transcriptomics, we created a "fermentation map", which shows that the tetanus toxin transcriptional regulator BotR, P21 and the tetanus toxin gene was downregulated. Moreover, this in-depth analysis revealed potential genes that might be involved in C. tetani virulence regulation. We observed differential expression of genes related to cell separation, surface/cell adhesion, pyrimidine biosynthesis and salvage, flagellar motility, and prophage genes. Overall, the fermentation map shows that, mediated by free amino acid concentrations, virulence in C. tetani is regulated at the transcriptional level and affects a plethora of metabolic functions.


Assuntos
Aminoácidos , Clostridium tetani , Aminoácidos/metabolismo , Animais , Clostridium tetani/genética , Clostridium tetani/metabolismo , Clostridium tetani/patogenicidade , Humanos , Toxina Tetânica/biossíntese , Toxina Tetânica/genética , Transcriptoma
16.
J Int Med Res ; 48(10): 300060520963983, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33107774

RESUMO

Tetanus after gastrointestinal surgery is an extremely rare but very dangerous disease caused by infection with Clostridium tetani. Tetanus can occur due to bacterial infection during surgery or dressing change, or the bacteria may exist in the patient's intestines and be discharged with feces. This report describes a 71-year-old woman who developed tetanus 3 days after a hemorrhoidal ligation. Clinicians need to be aware of symptoms of C. tetani infection that might present in patients who have undergone gastrointestinal procedures.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Hemorroidas , Tétano , Idoso , Clostridium tetani , Feminino , Hemorroidas/cirurgia , Humanos , Ligadura/efeitos adversos
17.
Acta Chir Orthop Traumatol Cech ; 87(4): 292-296, 2020.
Artigo em Tcheco | MEDLINE | ID: mdl-32940226

RESUMO

Tetanus is a disease caused by tetanotoxin produced in necrotic wounds by Clostridium tetani. It is a very rare disease in Czechia due to successful and effective population-wide vaccination programme, despite the fact that spores of C. tetani are permanently present in the environment. Groups with the highest risk of clinical tetanus include elderly people, immunocompromised individuals, residents of foreign origin with unclear vaccination history, and unvaccinated children. We present four case studies of severe and mild form of tetanus, wound infection with the presence of C. tetani without the development of clinical tetanus in a fully vaccinated individual, and unexpected risk of tetanus in an unvaccinated child. Due to the rare occurrence of tetanus in Czechia, the clinical awareness of the risk of tetanus decreases as well as the clinical experience with diagnosis of early or mild forms of tetanus. Communication skills during the management of contaminated wounds play a critical role in the decision who should get tetanus anatoxin only and who should get antitetanus immunoglobulin along with the active immunization by tetanus anatoxin. Key words: etanus, Clostridium tetani, vaccination, postexposure prophylaxis, vaccine hesitancy, contaminated wounds.


Assuntos
Tétano , Idoso , Criança , Clostridium tetani , Humanos , Tétano/diagnóstico , Tétano/prevenção & controle , Toxoide Tetânico , Vacinação
18.
Med Hypotheses ; 141: 109779, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32387756

RESUMO

The novel coronavirus Covid-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against Covid-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics ("Spanish flu" 1918, "Asian flu" 1956 and "the Hong Kong flu" 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4 + memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4 + memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting "lung crash" until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the Covid-19 will occur.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Imunização Secundária , Imunogenicidade da Vacina , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adolescente , Adulto , Distribuição por Idade , Idoso , Linfócitos T CD4-Positivos/imunologia , COVID-19 , Criança , Pré-Escolar , Clostridium tetani/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Suscetibilidade a Doenças , Humanos , Imunoterapia Ativa , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Pessoa de Meia-Idade , Modelos Imunológicos , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , SARS-CoV-2 , Adulto Jovem
19.
Toxins (Basel) ; 12(5)2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429286

RESUMO

Clostridium tetani produces a potent neurotoxin, the tetanus toxin (TeNT), which is responsible for an often-fatal neurological disease (tetanus) characterized by spastic paralysis. Prevention is efficiently acquired by vaccination with the TeNT toxoid, which is obtained by C. tetani fermentation and subsequent purification and chemical inactivation. C. tetani synthesizes TeNT in a regulated manner. Indeed, the TeNT gene (tent) is mainly expressed in the late exponential and early stationary growth phases. The gene tetR (tetanus regulatory gene), located immediately upstream of tent, encodes an alternative sigma factor which was previously identified as a positive regulator of tent. In addition, the genome of C. tetani encodes more than 127 putative regulators, including 30 two-component systems (TCSs). Here, we investigated the impact of 12 regulators on TeNT synthesis which were selected based on their homology with related regulatory elements involved in toxin production in other clostridial species. Among nine TCSs tested, three of them impact TeNT production, including two positive regulators that indirectly stimulate tent and tetR transcription. One negative regulator was identified that interacts with both tent and tetR promoters. Two other TCSs showed a moderate effect: one binds to the tent promoter and weakly increases the extracellular TeNT level, and another one has a weak inverse effect. In addition, CodY (control of dciA (decoyinine induced operon) Y) but not Spo0A (sporulation stage 0) or the DNA repair protein Mfd (mutation frequency decline) positively controls TeNT synthesis by interacting with the tent promoter. Moreover, we found that inorganic phosphate and carbonate are among the environmental factors that control TeNT production. Our data show that TeNT synthesis is under the control of a complex network of regulators that are largely distinct from those involved in the control of toxin production in Clostridium botulinum or Clostridium difficile.


Assuntos
Proteínas de Bactérias/genética , Clostridium tetani/genética , Regulação Bacteriana da Expressão Gênica , Toxina Tetânica/genética , Transativadores/genética , Proteínas de Bactérias/metabolismo , Carbonatos/metabolismo , Clostridium tetani/metabolismo , Redes Reguladoras de Genes , Fosfatos/metabolismo , Regiões Promotoras Genéticas , Toxina Tetânica/biossíntese , Transativadores/metabolismo , Transcrição Genética
20.
Ned Tijdschr Geneeskd ; 1642020 01 09.
Artigo em Holandês | MEDLINE | ID: mdl-32186824

RESUMO

BACKGROUND: Clostridium tetani is a gram-positive spore-forming bacterium that produces toxins and grows under anaerobic conditions. Infections with this bacterium can lead to local or generalised forms of tetanus. CASE DESCRIPTION: An 83-year-old man presented to the acute cardiac care unit with a painful left arm and jaw. Because the patient had a hypertonic left arm and was unable to open his mouth fully, the neurologist was consulted. The patient had been to the emergency department 9 days earlier for an infected wound after falling in the garden. He had not been actively or passively immunised against tetanus at that time. On inquiry, it appeared that the patient had also not been vaccinated as a child. We made a clinical diagnosis of tetanus. The patient was admitted and treated with tetanus immunoglobulin, metronidazole, diazepam and painkillers. He was also administered tetanus toxoid and the wound was cleaned. After 1 month and 7 months, the patient was again administered tetanus toxoid. CONCLUSION: Patients with a wound that may have come into contact with road grime, dirt or manure, should always be asked for their vaccination status, especially people from high-risk groups, such as the elderly.


Assuntos
Antibacterianos/uso terapêutico , Clostridium tetani , Dor/tratamento farmacológico , Tétano/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Idoso de 80 Anos ou mais , Braço/microbiologia , Humanos , Arcada Osseodentária/microbiologia , Masculino , Metronidazol/uso terapêutico , Dor/microbiologia , Tétano/microbiologia , Toxoide Tetânico/uso terapêutico , Infecção dos Ferimentos/microbiologia
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