Sarcoplasmic reticulum calcium handling in unbranched, immediately post-necrotic fast-twitch mdx fibres is similar to wild-type littermates.

NEW FINDINGS: What is the central question of this study? What are the early effects of dystrophin deficiency on sarcoplasmic reticulum Ca2+ handling in the mdx mouse? What is the main finding and its importance? In the mdx mouse, Ca2+ handling by the sarcoplasmic reticulum is little affected by the absence of dystrophin when looking at fibres without branches that have recently regenerated after massive myonecrosis. This has important implications for our understanding of Ca2+ pathology in the mdx mouse. ABSTRACT: There is a variety of results in the literature regarding the effects of dystrophin deficiency on the Ca2+ handling properties of the sarcoplasmic reticulum (SR) in the mdx mouse, an animal model of Duchenne muscular dystrophy. One possible source of variation is the presence of branched fibres. Fibre branching, a consequence of degenerative-regenerative processes such as muscular dystrophy, has in itself a significant influence on the function of the SR. In this study, we attempted to detect early effects of dystrophin deficiency on SR Ca2+ handling by using unbranched fibres from the immediate post-necrotic stage in mdx mice (recently regenerated after massive necrosis). Using kinetically corrected fura-2 fluorescence signals measured during twitch and tetanus, we analysed the amplitude, rise time and decay time of Δ[Ca2+ ]i in unfatigued and fatigued fibres. Decay was also resolved into SR pump and SR leak components. Fibres from mdx mice were similar in all respects to fibres from wild-type littermates apart from: (1) a smaller amplitude of the initial spike of Δ[Ca2+ ]i during a tetanus; and (2) a mitigation of the fall in Δ[Ca2+ ]i amplitude during the course of fatigue. Our findings suggest that the early effects of a loss of dystrophin on SR Ca2+ handling in mdx mice are subtle, and we emphasize the importance of distinguishing between Ca2+ pathology that is attributable to lack of dystrophin and Ca2+ pathology that is attributable to muscle degeneration.

The Role of the Gastrointestinal Tract in Toxigenic Clostridium tetani Infection: A Case-Control Study.

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.

Clinical outcomes and healthcare costs of inpatients with tetanus in Korea, 2011-2019.

BACKGROUND: Tetanus is a rare, vaccine-preventable but extremely serious disease. We investigated the recent trend of the clinical outcomes and medical costs for inpatients with tetanus in South Korea over 10 years. METHODS: We conducted a retrospective review to determine the clinical factors and medical costs associated with tetanus at two national university hospitals in South Korea between January 2011 and October 2019. RESULTS: Forty-nine patients were admitted for tetanus (mean age, 67.0 years [range, 53.0-80.0 years]; 32 women [57.1%]). All the patients had generalized tetanus, and 5 (10.2%) died during hospitalization. The median duration from symptom onset to hospital admission was 4 days. Trismus (85.7%) was the most common symptom, and the median hospital stay was 39 days. Thirty-two patients (65.3%) required mechanical ventilation, and 20 (40.8%) developed aspiration pneumonia. The median total healthcare cost per patient was US $18,011. After discharge, 35 patients (71.4%) recovered sufficiently to walk without disability. CONCLUSIONS: Tetanus requires long hospital stays and high medical expenditures in South Korea; however, the vaccination completion rate is low. Medical staff should therefore promote medical advice and policies on the management of tetanus to the general South Korean population.

Generalized, non-neonatial tetanus is a highly fatal disease in Afghanistan: A case series study.

OBJECTIVES: To describe the clinical features and outcomes of a case series of adult tetanus and illustrate inadequacies in confronting this preventable disease. DESIGN AND METHODS: This study retrospectively evaluated 24 relatively severe, confirmed cases of tetanus, diagnosed between March 2017 and December 2018, in Kabul Antani Hospital, Afghanistan. RESULTS: Regarding the source of the infection: 18 patients (75%) had a history of injuries, 1 had a history of a dog bite and 1 was an intravenous drug user; 4 patients had no external injuries or wounds. Dysphagia was the main clinical manifestation for which patients sought medical treatment (50%). Of the 12 patients who died, 7 presented with confusion and seizure, 1 with acute kidney injury, and 2 with pneumonia. CONCLUSIONS: Mortality due to tetanus is high in Afghanistan (Case Fatality Rate (CFR) 50%)), suggesting an urgent need for vaccination policy and programs, post-exposure protocols, and facilities equipped for the treatment of adult tetanus. The Ministry of Public Health of Afghanistan should seek to improve the accessibility, distribution and recording of tetanus immunization through vaccination.

A case of iliopsoas hematoma as a complication of tetanus in a patient who did not receive anticoagulant therapy.

BACKGROUND: The specific clinical feature of tetanus is whole body muscle spasms. These spasms are intensely painful and sometime lead to some injuries. Vertebral fractures have been reported as a common complication of tetanus, however iliopsoas hematoma is a rare complication. We describe a case of iliopsoas hematoma in a tetanus patient who had not been treated with any anticoagulant or antiplatelet agents. CASE PRESENTATION: A 72-year-old female patient was transferred to our hospital 7 days after the onset of tetanus. An iliopsoas hematoma was identified in her right iliopsoas muscle on computed tomography. There was no extravasation; thus, the hematoma improved with conservative therapy. There were no episodes that suggested a bleeding tendency, or no factors associated with hemorrhagic conditions. CONCLUSION: This is the first report of iliopsoas hematoma as a complication in a tetanus patient who did not received anticoagulation therapy. The possibility of IPH as a complication of tetanus should be considered before and during the administration of anticoagulation therapy.

Tetanus presenting primarily as periocular discomfort in a patient who underwent surgery for sleep apnea: A case report and brief literature review.

RATIONALE: Tetanus is caused by a neurotoxin (tetanospasmin) secreted by a spore forming gram-positive, anaerobic rod-shaped motile bacillus, Clostridium tetani. The most common symptoms of tetanus are trismus (100%), dysphagia (70.5%), dysarthria (35.2%), and neck stiffness (29.4%). Respiratory failure, laryngeal spasm, seizure, chest pain, nausea/vomiting, opisthotonus, back pain, and rigid abdominal wall can also be observed during progression of the disease. However, there has been no report of periocular discomfort as an initial manifestation after endoscopic sleep surgery in a patient with tetanus. Here, we report a patient who underwent endoscopic sleep surgery with a concurrent diagnosis of tetanus infection presenting with atypical periocular discomfort as the initial symptom. PATIENT CONCERNS: A 63-year-old man complaining of sleep apnea, snoring, and daytime sleepiness visited our department. He subsequently underwent sleep surgery (anterior pharyngoplasty with tonsillectomy, septoplasty, microdebrider-assisted inferior turbinoplasty, and an endoscopic sinus surgery) for the treatment of his newly diagnosed obstructive sleep apnea. After 3 weeks of surgery, he visited the outpatient clinic of our department with right side periocular discomfort. DIAGNOSES: Four days after presenting with periocular discomfort, he was diagnosed with tetanus by presenting trismus, jaw pain, dysphagia, and ptosis at an emergency department of a different hospital. INTERVENTIONS: Tetanus immunoglobulin and antibiotics were administered. OUTCOMES: His symptoms then resolved after a month without sequelae. LESSONS: Although periocular discomfort is atypical and is not uncommon after nasal and oral surgeries, care should be taken when patients present with periocular pain because it could be a rare initial symptom of tetanus.

[Post-circumcision Tetanus: Epidemiological, Clinical, Prognostic and Evolutionary Aspects of 16 Cases Collected at the Department of Infectious and Tropical Diseases in Fann Hospital (Dakar)]. / Tétanos postcirconcision : à propos de 16 cas colligés à la Clinique des maladies infectieuses du CHNU de Fann (Dakar).

This retrospective, descriptive study carried out in the Infectious Diseases Department of CHNU, Fann from 1st January 2012 to 3st December 2016 aimed to describe the epidemiological aspects and the course of post-circumcision tetanus and to formulate public health recommendations. During our study period, 16 cases of post-circumcision tetanus were collected out of a total of 452 patients with tetanus, equivalent to a rate of 3.5%. The median age was 8 years (3-40). None of the patients had a vaccination card. In 63% of cases, circumcision was performed at home, by a practitioner whose qualification was not documented in 63% of cases. All signs of tetanus were found with trismus (100%), dysphagia (63%) and paroxysms (88%). These were mostly Mollaret stage II forms in 14 cases, and grade 3 Dakar score in 7 cases. The median duration of hospitalization was 10 days [6-15]. Mechanical or infectious complications were noted in two cases, with a lethality rate of 13%. Post-circumcision tetanus is a reality in Senegal. Good community awareness, continuous training of staff and implementation of vaccination catch-up strategies for children of circumcised age should eradicate this form of tetanus.

Cette étude rétrospective descriptive, réalisée à la Clinique des maladies infectieuses du CHNU de Fann du 1er janvier 2012 au 31 décembre 2016 avait pour but de décrire les aspects épidémiologiques et évolutifs du tétanos postcirconcision et de formuler des recommandations en termes de prévention. Durant la période d'étude, 16 cas de tétanos postcirconcision ont été colligés sur un total de 452 patients atteints de tétanos, soit une fréquence hospitalière de 3,5 %. L'âge médian était de huit ans (3­40). Aucun des patients ne disposait de carnet de vaccination. Dans 63 % des cas, la circoncision a été effectuée à domicile, par un praticien dont la qualification n'a pas été documentée dans 63 % des cas. Tous les signes du tétanos ont été retrouvés avec le trismus (100 %), la dysphagie (63 %) et les paroxysmes (88 %). Il s'agissait surtout de formes de moyenne gravité classées au stade II de Mollaret dans 14 cas, et au score 3 de Dakar dans sept cas. La durée médiane d'hospitalisation était de dix jours [6­15]. Des complications mécaniques ou infectieuses ont été notées dans deux cas, avec une létalité de 13 %. Le tétanos postcirconcision est une réalité au Sénégal. Une bonne sensibilisation de la communauté, la formation continue du personnel et la mise en place de stratégies de rattrapage vaccinal des enfants en âge d'être circoncis devraient permettre d'éradiquer cette forme de tétanos.

Retrospective evaluation of 155 adult equids and 21 foals with tetanus in Western, Northern, and Central Europe (2000-2014). Part 1: Description of history and clinical evolution.

OBJECTIVE: To describe clinical data of hospitalized adult equids and foals with tetanus. DESIGN: Multicenter retrospective study (2000-2014). SETTING: Twenty Western, Northern, and Central European university teaching hospitals and private referral centers. ANIMALS: One hundred fifty-five adult equids (>6 months) and 21 foals (<6 months) with tetanus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information on geographic, annual and seasonal data, demographic- and management-related data, clinical history, clinical examination and blood analysis on admission, complications, treatments, and outcomes were described and statistically compared between adults and foals. The described cases were often young horses. In 4 adult horses, tetanus developed despite appropriate vaccination and in 2 foals despite preventive tetanus antitoxin administration at birth. Castration, hoof abscesses, and wounds were the most common entry sites for adults; umbilical cord infections and wounds for foals. Stiffness was the commonest observed initial clinical sign. Blood analyses frequently revealed an inflammatory response, hemoconcentration, muscle damage, azotemia, negative energy balance, liver damage, and electrolyte and acid base disturbances. Common complications or clinical signs developing during hospitalization included dysphagia, dyspnea, recumbency, hyperthermia, seizures, hyperlipemia, gastrointestinal impactions, dysuria, and laryngeal spasms. Cases were supported with wound debridement, antimicrobial treatment, tetanus antitoxin, muscle spasm and seizure control, analgesia, anti-inflammatory drugs, fluid therapy, and nutritional support. Mortality rates were 68.4% in adult horses and 66.7% in foals. Foals differed from adult horses with respect to months of occurrence, signalment, management-related data, potential causative events, clinical signs on admission, blood analysis, complications, and severity grades. CONCLUSIONS: This is the first study that rigorously describes a large population of equids affected by tetanus. The information provided is potentially useful to clinicians for early recognition and case management of tetanus in adult horses and foals. Tetanus affects multiple organ systems, requiring broad supportive and intensive care. Neonatal and adult tetanus in the horse should be considered as distinct syndromes, as in human medicine.

Retrospective evaluation of 155 adult equids and 21 foals with tetanus from Western, Northern, and Central Europe (2000-2014). Part 2: Prognostic assessment.

OBJECTIVE: To identify prognostic variables for adult equids and foals with tetanus. DESIGN: Multicenter retrospective study (2000-2014). SETTING: Twenty Western, Northern, and Central European university teaching hospitals and private referral centers. ANIMALS: One hundred fifty-five adult equids and 21 foals with tetanus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variables from history and clinical examination were statistically compared between survivors and nonsurvivors (adults: 49 survivors, 85 nonsurvivors; foals: 7 survivors, 10 nonsurvivors). Cases euthanized for financial reasons were excluded. Mortality rates in adults and foals were 68.4% and 66.7%, respectively. Variables associated with survival in adults included: standing, normal intestinal sounds and defecation, voluntarily drinking, eating soft or normal food, lower heart and respiratory rates, high base excess on admission, longer diagnosis time, treatment and hospitalization delay, and mild severity grade. Variables associated with death included: anorexia, dysphagia, dyspnea, low blood potassium concentration on admission, moderate and severe disease grading, development of dysphagia, dyspnea, recumbency and seizures during hospitalization, treatment with glycerol guaiacolate, intravenous fluids, and intravenous glucose solutions. Variables associated with survival in foals included standing on admission, voluntarily eating soft food and drinking, older age, and longer hospitalization delay. Outcome was not different between different tetanus antitoxin (TAT) dosages, although there was a trend of increasing survival rate with increasing TAT dosages. Cases with appropriate vaccination prior to development of tetanus were rare, but had improved outcome and shorter hospitalization. CONCLUSIONS: Prognosis for equine tetanus is poor with similar outcome and prognostic factors in foals and adults. The prognostic assessment of cases with tetanus provides clinicians with new evidence-based information related to patient management. Several prognostic indicators relate to the ability to eat or drink, and more severe clinical signs relate to poor outcome. Increasing intravenous dosages of TAT has no significant effect on outcome, but the positive trend identified may support a recommendation for high intravenous TAT dosages. Further evaluation is warranted.

Tetanus in adults: results of the multicenter ID-IRI study.

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

[PROPERTIES OF INDIVIDUAL CONTRACTILE RESPONSES WITHIN TETANUS OF RAT SLOW MUSCLE UNDER CONDITIONS OF MODULATION OF SARCOPLASMIC RETICULUM Ca²âº RELEASE].

During direct stimulation of m. Soleus by trains of 5, 10 and 50 stimuli with a frequency of 20 Hz in control experiments (n = 16) a biphasic change was observed in the amplitude of the last contractile responses (LCRN) depending on N, where N is the number of individual contractile responses within the te- tanus. Thus, an initial decrease of LCRN amplitude (up to 54 ± 8 % for LCR5) was replaced by their subsequent growth (up 218 ± 14 % for LCR5o) associated with a significant shortening of their half-relaxation time relative to the initial response (to 44 ± 8 % for LCR50). Caffeine at concentrations of 5 mM (n = 6) and 10 mM (n = 4), at the background of developing characteristic stationary contracture respon- ses, increased LCR5 depression during the initial inhibitory phase (31 ± 8 % and 15 ± 4 %, respectively). The subsequent growth of LCRN amplitude was significantly lower than in the control (114 ± 18 % and 46 ± 9 % for LCR50 at 5 and 10 mM caffeine, respectively). LCR50 half-relaxation time during the action of both caffeine concentrations remained still considerably shorter than the individual responses recorded both in the presence of caffeine and in control. In contrast to the control and caffeine effects, LCR5 and 10 (to 143 ± 14 %) than was observed in the control muscle. Additionally, dantrolene enhanced muscle relaxation at rest. Caffeine (10 mM), at the background of dantrolene, restored the dynamics of changes of amplitude time characteristics of the last contractile responses to values close to the control. The time-amplitude characteristics of the extracellular AP recorded in individual muscle fibers in m. Soleus did not change significantly during tetanic stimulation under protocol similar to that used for mechanografical experiments. These data can be interpreted to support the previously suggested theory about the participation of <> as an additional mechanism of excitation-contraction coupling in skeletal muscle under conditions of tetanic stimulation [1, 2].

Tetanus after envenomations caused by freshwater stingrays.

Injuries caused by freshwater stingray are common in several regions of South America, although they are underreported. The riverside inhabitants are the main victims in the Amazonian and Midwest regions of South America. The fishermen are injured mainly in the new focus of colonization of the rivers by freshwater stingrays. With the increasing population in these regions, where freshwater stingrays are found, there has been a significant increase in injuries within the general population. The highest increase occurred among tourists from other regions, where these animals are not known, when visiting these areas. The envenomations from the stingray causes prolonged and intense pain, both local and regionally. Generally these are associated with other local inflammatory manifestations, such as swelling and erythema. The injury often progresses to necrosis and it is considered potentially tetanogenic. A secondary infection is also a frequent local complication and most frequently is caused by Aeromonas species, usually Aeromonas hydrophila. Herein we report the first 2 cases of tetanus after freshwater stingray injuries: a 51-year-old men who had tetanus and recovered without sequel and the second a 67-year-old men who had severe tetanus and a deep, necrotizing soft-tissue infection with sepsis, septic shock and evolution to death.

Tetanus in an unvaccinated laborer in Bahrain.

Mr. M.D.S., a 27-year-old Indian male, presented with complaints of diffuse body pain and spasms, 7 days after a needle penetrated his right foot at his place of work. He was diagnosed clinically with tetanus. The patient was electively intubated to protect the airway and transferred to an intensive care unit. In addition to his tetanus, he developed multiple hospital-acquired infections. After 34 days, he was successfully extubated and extensive physiotherapy commenced. He was discharged 10 days after extubation.

Rabies, tetanus, leprosy, and malaria.

The developing world is still endemic to rabies, tetanus, leprosy, and malaria. Globally more than 55000 people die of rabies each year, about 95% in Asia and Africa. Annually, more than 10 million people, mostly in Asia, receive postexposure vaccination against the disease. World Health Organization estimated tetanus-related deaths at 163000 in 2004 worldwide. Globally, the annual detection of new cases of leprosy continues to decline and the global case detection declined by 3.54% during 2008 compared to 2007. Malaria is endemic in most countries, except the US, Canada, Europe, and Russia. Malaria accounts for 1.5-2.7 million deaths annually. Much of the disease burden related to these four infections is preventable.

Clostridium novyi, sordellii, and tetani: mechanisms of disease.

Clostridia represent a diverse group of spore-forming gram positive anaerobes that include several pathogenic species. In general, diseases caused by clostridia are a result of intoxication of the infected host. Thus, clostridial toxins have been targeted for diagnostic, therapeutic, and preventive strategies against infection. Studying the mechanisms of action of clostridial toxins has not only shed light on the pathogenesis of infection but has provided important new insights into cell biology and immunology. A primary purpose of this manuscript is to provide a succinct review on the mechanisms of disease caused by intoxication by the pathogens Clostridium tetani, Clostridium novyi, and Clostridium sordellii.