Severe tetanus following ulcerated skin cancer: Case report.

RATIONALE: Tetanus is usually caused by wound infection with Clostridium tetani after acute injuries. Skin cancer wound is a rarely reported cause of tetani infection. It is difficult to be diagnosed and mistaken for other brain lesions. PATIENT CONCERNS: A 49-year-old man presenting with the only symptom of repeated convulsions was admitted to our department. He had an ulcerated skin cancer on the right buttock that had been excised in another hospital 1 month before admission, leaving the wound unhealed. He was suspected of having a metastatic brain tumor early, but exhibited a negative cranial CT-scan. DIAGNOSIS: Tetanus was diagnosed when he was observed to have sudden convulsions after sensory stimulation such as noise, light, or touch. INTERVENTIONS: Despite administration of a high dose of diazepam and phenobarbitone, continuous generalized rigidity with laryngospasm still occurred. Instead, when propofol was intravenously infused, the spastic convulsion completely stopped. Tracheotomy and mechanical ventilation were performed. OUTCOMES: The patient gradually recovered in 2 weeks. LESSONS: Tetanus is rarely infected through the wound of an ulcerated skin cancer. Early diagnosis can only be based on accurate assessment of clinical manifestations, and propofol infusion appears to be more effective in anti-convulsion management for patients with tetanus. Routine vaccination to prevent tetanus in patients with ulcerated skin cancer should be considered in the future clinical work.

Heart Rate Variability as an Indicator of Autonomic Nervous System Disturbance in Tetanus.

Autonomic nervous system dysfunction (ANSD) is a significant cause of mortality in tetanus. Currently, diagnosis relies on nonspecific clinical signs. Heart rate variability (HRV) may indicate underlying autonomic nervous system activity and represents a potentially valuable noninvasive tool for ANSD diagnosis in tetanus. HRV was measured from three 5-minute electrocardiogram recordings during a 24-hour period in a cohort of patients with severe tetanus, all receiving mechanical ventilation. HRV measurements from all subjects-five with ANSD (Ablett Grade 4) and four patients without ANSD (Ablett Grade 3)-showed HRV was lower than reported ranges for healthy individuals. Comparing different severities of tetanus, raw data for both time and frequency measurements of HRV were reduced in those with ANSD compared with those without. Differences were statistically significant in all except root mean square SD, indicating HRV may be a valuable tool in ANSD diagnosis.

Functional outcome and muscle wasting in adults with tetanus.

BACKGROUND: In many countries, in-hospital survival from tetanus is increasing, but long-term outcome is unknown. In high-income settings, critical illness is associated with muscle wasting and poor functional outcome, but there are few data from resource-limited settings. In this study we aimed to assess muscle wasting and long-term functional outcome in adults with tetanus. METHODS: In a prospective observational study involving 80 adults with tetanus, sequential rectus femoris ultrasound measurements were made at admission, 7 days, 14 days and hospital discharge. Functional outcome was assessed at hospital discharge using the Timed Up and Go test, Clinical Frailty Score, Barthel Index and RAND 36-item Short Form Health Survey (SF-36) and 3 and 6 months after discharge using the SF-36 and Barthel Index. RESULTS: Significant muscle wasting occurred between hospital admission and discharge (p<0.01), particularly in severe disease, where a median 23.49% (interquartile range 10.01-26.07) reduction in rectus femoris cross-sectional area occurred in those with severe (Ablett grades 3 and 4) disease. Muscle mass at discharge was related to objective and subjective measures of physical and emotional function at discharge and 3 and 6 months after discharge. In patients >70 y of age, functional recovery at 6 months was reduced compared with younger patients. Hospital-acquired infection and age were risk factors for muscle wasting. CONCLUSIONS: Significant muscle wasting during hospitalization occurred in patients with tetanus, the extent of which correlates with functional outcome.

The role of the single interchains disulfide bond in tetanus and botulinum neurotoxins and the development of antitetanus and antibotulism drugs.

A large number of bacterial toxins consist of active and cell binding protomers linked by an interchain disulfide bridge. The largest family of such disulfide-bridged exotoxins is that of the clostridial neurotoxins that consist of two chains and comprise the tetanus neurotoxins causing tetanus and the botulinum neurotoxins causing botulism. Reduction of the interchain disulfide abolishes toxicity, and we discuss the experiments that revealed the role of this structural element in neuronal intoxication. The redox couple thioredoxin reductase-thioredoxin (TrxR-Trx) was identified as the responsible for reduction of this disulfide occurring on the cytosolic surface of synaptic vesicles. We then discuss the very relevant finding that drugs that inhibit TrxR-Trx also prevent botulism. On this basis, we propose that ebselen and PX-12, two TrxR-Trx specific drugs previously used in clinical trials in humans, satisfy all the requirements for clinical tests aiming at evaluating their capacity to effectively counteract human and animal botulism arising from intestinal toxaemias such as infant botulism.

Pediatric Tetanus in Central Pennsylvania.

Approximately 20% of the nationally reported tetanus infections in children aged 0 to 14 years that occurred in the United States between 2005 and 2015 were treated at Penn State Children's Hospital. With an electronic medical record search, we identified 5 cases of pediatric tetanus; 100% of these cases occurred in unimmunized children. Their median length of stay was 10 days, and the costs were significant.

Tetanic Facilitation of Neuromuscular Transmission by Adenosine A2A and Muscarinic M1 Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters.

BACKGROUND/AIMS: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A2A and muscarinic M1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition. METHODS: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500-750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated. RESULTS: Activation of A2A and M1 receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 µmol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 µmol/L) and phorbol 12-myristate 13-acetate (PMA; 10 µmol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 µmol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 µmol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 µmol/L) was also prevented by HC-3 (4 µmol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 µmol/L). CONCLUSION: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A2A and M1 receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative.

Historical links between toxinology and immunology.

Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children. Glenny demonstrated the efficacy of the secondary immune response compared to the primary one. Ramon described anatoxins that allowed the elaboration of effective vaccines and discovered the use of adjuvant to boost the antibody response. Similar approaches were later made for the tetanus toxin. Studying antitoxin antibodies Ehrlich demonstrated, for the first time, the transfer of immunity from mother to newborns. In 1989 Marrack and Kappler coined the concept of 'superantigens' to characterize protein toxins that induce T-lymphocyte proliferation, and cytokine release by both T-lymphocytes and antigen presenting cells. More recently, immunotoxins have been designed to kill cancer cells targeted by either specific antibodies or cytokines. Finally, the action of IgE antibodies against toxins may explain their persistence through evolution despite their side effect in allergy.

Clinical Serum Therapy: Benefits, Cautions, and Potential Applications.

Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.

Can inorganic phosphate explain sag during unfused tetanic contractions of skeletal muscle?

We test the hypothesis that cytosolic inorganic phosphate (Pi) can account for the contraction-induced reductions in twitch duration which impair summation and cause force to decline (sag) during unfused tetanic contractions of fast-twitch muscle. A five-state model of crossbridge cycling was used to simulate twitch and unfused tetanic contractions. As Pi concentration ([Pi]) was increased from 0 to 30 mmol·L-1, twitch duration decreased, with progressive reductions in sensitivity to Pi as [Pi] was increased. When unfused tetani were simulated with rising [Pi], sag was most pronounced when initial [Pi] was low, and when the magnitude of [Pi] increase was large. Fast-twitch extensor digitorum longus (EDL) muscles (sag-prone, typically low basal [Pi]) and slow-twitch soleus muscles (sag-resistant, typically high basal [Pi]) were isolated from 14 female C57BL/6 mice. Muscles were sequentially incubated in solutions containing either glucose or pyruvate to create typical and low Pi environments, respectively. Twitch duration was greater (P < 0.05) in pyruvate than glucose in both muscles. Stimuli applied at intervals approximately three times the time to peak twitch tension resulted in sag of 35.0 ± 3.7% in glucose and 50.5 ± 1.4% in pyruvate in the EDL (pyruvate > glucose; P < 0.05), and 3.9 ± 0.3% in glucose and 37.8 ± 2.7% in pyruvate in the soleus (pyruvate > glucose; P < 0.05). The influence of Pi on crossbridge cycling provides a tenable mechanism for sag. Moreover, the low basal [Pi] in fast-twitch relative to slow-twitch muscle has promise as an explanation for the fiber-type dependency of sag.

Neonatal tetanus associated with skin infection.

A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period.

[A rare complication of generalized tetanus: pulmonary embolism]. / Une complication exceptionnelle du tétanos généralisé: l'embolie pulmonaire.

Tetanus is a disease characterized by spastic paralysis and spasms. It is a serious pathology that requires treatment in the ICU. Mortality rate is primarily due to neurodegenerative and infectious complications. Thromboembolic complications are rare. To the best of our knowledge, pulmonary embolism has never occorred and been confirmed in patients with generalized tetanus. Our study reports the case of a patient with generalized tetanus complicated by fibrin, cruoric pulmonary embolism.

Low rates of vaccination in listed kidney transplant candidates.

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre-transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single-center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three-quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65-19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12-0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44-5.51, and OR 1.84, 95% CI 1.08-3.14, respectively). We found that the overall immunization rate against common vaccine-preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high-risk population.

An alternative treatment approach in tetanus: Botulinum toxin.

Tetanus is a preventable infectious disease caused by tetanus toxin (tetanospasmin) produced by Clostridium tetani. Tetanus is still an important health problem in low- and middle-income countries (LMICs). Botulinum toxin administration is a treatment approach that has been used in recent years to reduce rigidity and spasms in tetanus patients. This case report focuses on its efficacy.

Infections of the developing world.

Access to critical care is rapidly growing in areas of the world where it was previously nonexistent and where infectious diseases often comprise the largest disease burden. Additionally, with crowding, mass migrations, and air travel, infectious diseases previously geographically confined are quickly spread across the planet, often in shorter time frames than disease incubation periods. Hence, critical care practitioners must be familiar with infectious diseases previously confined to the developing world. This article reviews selected tropical diseases that are seen in diverse locales and often require critical care services.

Changes in electromyography and F wave responses in two cats with presumed local tetanus: implications for diagnosis and prognosis.

Two cases of focal tetanus in the cat are described. Clinical findings included severe muscular spasms of the pelvic limbs in one cat, and involvement of the thoracic limbs and muscles of the neck and face in the other. Electromyography in both cats showed spontaneous activity characterised by the presence of motor unit potentials. F waves, never previously reported in focal tetanus in animals, showed significantly increased F/M amplitude ratio in both cats and increased F wave duration in one cat. The electrodiagnostic findings provided relevant diagnostic and, possibly, prognostic information.

Tetanus: pathophysiology, treatment, and the possibility of using botulinum toxin against tetanus-induced rigidity and spasms.

Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection.

Fatal tetanus complicating an untreated mild open head injury: a case-illustrated review of cephalic tetanus.

BACKGROUND: Tetanus is now a rare disease in the Western world, but not so in developing countries. Cephalic tetanus, unlike some other local forms of the disease, is likely to be fatal. METHODS: We describe the clinical presentation of a case of fatal cephalic tetanus complicating an unattended open non-severe head injury with a review of the literature on the disease. RESULTS: Few cases of cephalic tetanus complicating head injury are found in the world literature, and many were diagnosed late. Cephalic tetanus from open or compound depressed skull fracture is even more rare. Our patient was a young male with an uncertain tetanus immunization history who sustained mild head injury (scalp laceration) and an unattended open depressed skull fracture in a motorcycle crash. He developed cephalic tetanus seven days later, presented late to our service, and died while being prepared for surgical debridement of his cranial wounds. At the immediate post-trauma medical contact, in an across-the-street "clinic," he had received suboptimal care for his head wound and inadequate tetanus prophylaxis. CONCLUSION: Cephalic tetanus is a rare form of the disease. Although it is preventable easily by well-established medical and surgical treatment paradigms, it continues to catch many clinicians disastrously unaware.