Human Antitetanus Immunoglobulin Research Articles

Tetanus Presented as Hemiparesis and Facial Dystonia

We report a case of tetanus presenting as the facial dystonia and hemiparesis with complete recovery and video accompanied follow-up. A 78-year-old male, who sustained an abrasion to his right forearm, presented with dysarthria, dysphagia, prominent involuntary painful muscle spasms in the face, blepharospasm, risus sardonicus, trismus (lockjaw), neck muscle rigidity and mild weakness of the distal right upper extremity. The combined treatment of human antitetanus immunoglobulin, tetanus vaccine, penicillin, metronidazole and diazepam were given with no effect. He continued to worsen and due to the risk of the respiratory failure (finally not developed) he was sent to the Intensive Care Unit. The combined treatment was continued, and his symptoms started to improve within 2 weeks. As the muscle rigidity has been improving, the patient developed significant right hemiparesis. The imaging of the brain and cervical spine found no significant pathology. At the follow-up visits the patient presented only slightly impaired dexterity of the right hand that gradually resolved. There are many reports of unusual presentations of tetanus, however, hemiparesis is uncommon, and to our knowledge, only one case was reported in the literature. We highlight the variability of clinical presentation of tetanus, the need to consider tetanus in cases of rapidly evolving muscle spasms following peripheral injuries and provide the guidelines on tetanus prophylaxis.

Pharmacological management of tetanus: an evidence-based review.

Tetanus is becoming rarer in both industrialized and developing nations due to an effective vaccination program. In 2010, the World Health Organization estimated there was a 93% reduction in newborns dying from tetanus worldwide, compared to the situation in the late 1980s. Due to its rarity, many diagnostic delays occur as physicians may not consider the diagnosis until the manifestations become overt. Without timely diagnosis and proper treatment, severe tetanus is fatal (mortality is also influenced by the comorbidities of the patient). The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. It is difficult to conduct trials on different treatment modalities in tetanus due to both logistical and ethical reasons. However, it is imperative that physicians are aware of the best evidence-based treatment strategies currently available to improve the outcome of patients. This review concentrates on analyzing the current evidence on the pharmacological management of tetanus.

明らかな外傷を認めなかった破傷風の2例

Tetanus develops following inoculation of damaged human tissue with Clostridium tetani which transforms into a vegetative rod-shaped bacterium and produces the tetanospasmin. Usually we make a diagnosis of tetanus based on typical symptoms and history of trauma. But, when patients have no noticeable history of trauma, we have to diagnose tetanus on the basis of the clinical course and symptoms. We report herein on two cases of tetanus without a clear history of trauma. The first patient visited us with the chief complaints of pain in the neck and shoulder, and difficulty in opening the mouth. Based on these symptoms, we diagnosed tetani in the first stage and we started treatment, consisting mainly of human anti-tetanus immunoglobulin on the first day. The second patient also had typical symptoms of tetanus. However, he rejected the use of human anti-tetanus immunoglobulin on the first day. Because his symptoms worsened on the 2nd day, we insisted that he used it. On the 5th hospital day he developed partial opisthotonus of neck. However he recovered without tracheotomy or intratracheal intubation.

Picoliter droplet microfluidic immunosorbent platform for point-of-care diagnostics of tetanus

We have developed a sensitive, specific, rapid and low cost picoliter microsphere-based platform for bioanalyte detection and quantification. In this method, a biological sample, biosensing microspheres, and fluorescently labeled detection (secondary) antibodies are co-encapsulated to capture the analyte (here: human anti-tetanus immunoglobulin G) on the surface of the microsphere in microfluidic pL-sized droplets. The absorption of the analyte and detecting antibodies on the microsphere concentrate the fluorescent signal in correlation with analyte concentration. Using our platform and commercially available antibodies, we were able to quantify anti-tetanus antibodies in human serum. In comparison to standard bulk immunosorbent assays, the microfluidic droplet platform presented here reduces the reagent volume by four orders of magnitude, while fast reagent mixing reduces the detection time from hours to minutes. We consider this platform to be a major leap forward in the miniaturization of immunosorbent assays and to provide a rapid and low cost tool for global point-of-care.

外傷歴がなく開口障害で発症した破傷風例

We report a patient with a sore throat and trismus associated with tetanus. The 71-year-old man had a sore throat and so consulted the hospital. However, no abnormal physical or fiberscopic findings were noted except for a high CPK level (438 U/l) in the serum. CT and MRI did not demonstrate abnormal findings. He showed trismus and convulsion after 6 days, and was then diagnosed with tetanus. Respiratory care involving intubation and the administration of Penicillin G (24 million units/day for 11 days) and human anti-tetanus immunoglobulin were performed, resulting in cure without any sequelae. We should consider tetanus in patients with a sore throat and trismus because one quarter of tetanus patients show no injury history.

Tetanus in a Subcutaneous Drug Abuser: Ineffectiveness of Intrathecal Baclofen

This report discusses the issues involved in the diagnosis and management of tetanus. A 29-year-old female with a history of illicit drug use presented with progressive tetany secondary to an abscess on her forearm from subcutaneous injections. She was managed in the intensive care unit for 29 days and was discharged to the ward. The main issue in her management was control of tetanic episodes interfering with ventilation and resistant to intrathecal baclofen. Other therapeutic strategies aimed at reducing spasms included magnesium, atracurium, pancuronium, midazolam, propofol and dantrolene. We conducted searches on Medline, PUBMED and the Cochrane Database of Systematic Reviews using the following terms: tetanus, treatment, therapy, drug abuse, magnesium, baclofen and human anti-tetanus immunoglobulin (hAIG). The current strategies involved in treating tetanus are discussed.

Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route

Objective To evaluate the effect of intrathecal therapy with human antitetanus immunoglobulin on clinical progression of and mortality from tetanus.Design Randomised controlled trial.Setting Intensive care unit of a university hospital,...

外傷歴のない破傷風例

A 63-year old woman who complained of severe dysphagia visited our hospital. A physical examination revealed rigidity of the sternocleidomastoid muscle. Laryngoscopy showed pooling of saliva at the bilateral pyrif orm sinus of the hypopharynx. Three days later, she complained of trismus. At that time, she was diagnosed with tetanus without a history of trauma. She was admitted and received human antitetanus immunoglobulin (3000 unit) at once and benzylpenicillin for 10 days intravenously. Opisthotonus, airway obstruction and circulatory disturbance did not occur. The patient recovered without tracheal intubation, mechanical ventilation or a tracheotomy. Although tetanus is rare in Japan, otorhinolaryngologists may encounter a patient with tetanus.

The First International Standard for Antitetanus Immunoglobulin, Human; Pharmaceutical Evaluation and International Collaborative Study

Abstract. The First International Standard (IS) for Antitetanus Immunoglobulin, Human (coded 26/488) was established by the WHO Expert Committee on Biological Standardization in October 1992 on the basis of an extensive pharmaceutical evaluation and an international collaborative study. Fifteen laboratories from 15 countries performed the toxin neutralization assay in vivo in the study. Twelve laboratories also performed an alternative in vitro assay. The new International Standard is a purified human immunoglobulin containing antibodies which are able to neutralize tetanus toxin. This new standard replaces the Second International Standard for Tetanus antitoxin, Equine, for testing of human antitetanus immunoglobulin preparations used clinically as well as for titration of human serum samples for tetanus antitoxin. The new International Standard was assigned a potency of 120 International Units (IU) of Tetanus Antitoxin per ampoule on the basis of its calibration in terms of the International Unit defined by the Second International Standard for Tetanus Antitoxin, Equine by toxin neutralization assay in vivo. The same preparation was also established as the first European Pharmacopoeia Standard for Antitetanus Immunoglobulin, Human by the European Pharmacopoeia Commission, Biological Standardization Programme in March 1993.

Tetanus booster every 5 years: an unnecessary routine?

The various guidelines for the administration of tetanus toxoid and antitetanus immunoglobulin are not only complicated, but also have never been supported by any scientific experimental studies. This study has measured the antibody levels in a random sample of 157 patients presenting to an accident and emergency department. Levels were measured before and after boosting doses. The results show that, in the sample analyzed, even those patients who had their last 'booster' over 10 years ago, had a satisfactory immunoglobulin level. In fact, no patient in the study had a level below the 'protective level'. Bearing in mind the small number of patients in the study, it could be argued that the level of immunity against tetanus in the United Kingdom is likely to be higher than assumed. If this is proven to be correct, then the length of time between booster injections of toxoid can be extended and the use of Human Antitetanus Immunoglobulin can be further restricted.

Eosinophil membrane changes during interaction with antibody-coated non-phagocytosable surfaces.

Abstract Eosinophils attach themselves closely to large non-phagocytosable, antibody-coated targets, such as helminths, and release their granule contents directly on to the surface of the target. A model system has been developed in which human peripheral blood eosinophils flatten down and degranulate on to antibody-coated agar layers, which are too large to be phagocytosed. The agar layer contains tetanus toxoid antigen and the eosinophil chemotactic factor ala-glyser-glu (10 −6 M), and is coated with human antitetanus immunoglobulin. Changes in the organization of the eosinophil membrane proteins were detected by lactoperoxidase catalysed iodination. A protein of molecular weight 55,000 appeared at the cell surface as an early and specific consequence of interaction with antibody coated non-phagocytosable targets. The appearance of this protein preceded degranulation. A second protein of molecular weight 58,000, was seen when no chemotactic factor was present. In the complete system this protein may be blocked by the chemotactic factor. The role of these proteins in the attachment of eosinophils to antibody-coated targets is discussed.

The interaction of human eosinophils and neutrophils with non-phagocytosable surfaces: a model for studying cell-mediated immunity in schistosomiasis.

A model has been developed to simulate the surface of an antibody-coated schistosomulum. It consists of a layer of agar, containing antigen (tetanus toxoid) and a chemotactic factor (ECF). Some layers were coated with human anti-tetanus immunoglobulin. The mode of adherence of human eosinophils and neutrophils to these agar layers and the subsequent degranulation of the cells exactly paralleled the interaction of these cell types with antibody-coated schistosomula of Schistosoma mansoni. In particular, eosinophils made much more intimate contact than did neutrophils, and lysosomal enzymes were secreted extracellularly by direct fusion of granules with the plasma membrane of the cell. Biochemical evidence was also obtained for the secretion of enzymes during degranulation and the rate of enzyme release was found to be enhanced in the presence of specific antibody. This model, non-phagocytosable surface has the potential to provide basic information of the mode of action of effector cells in cell-mediated cytotoxic reactions against a wide range of parasites by incorporation of different factors into the agar layers.

Eosinophil interaction with antibody-coated, non-phagocytosable surfaces: changes in cell surface proteins.

Plasma membrane changes during the interaction of human eosinophils with large, antibody-coated, non-phagocytosable surfaces have been investigated in a model system. Human peripheral blood eosinophils were incubated with layers of agar into which teranus toxoid (ECF), were incorporated. Changes in organization of the eosinophil plasma membrane proteins during interaction with the agar layer were detected by lactoperoxidase-catalysed iodination with [125]iodide. A protein of apparent mol. wt 55 000 became newly accessible on the eosinophil surface as a specific consequence of interaction with antigen-antibody complexes in the agar layer. This protein appeared in the early attachnent phase of the interaction which preceded extracellular degranulation. Cytochalasin D enhanced its appearance, while Mg2+-deficiency prevented it. A second newly accessible protein of apparent mol. wt 58 000 was blocked when ECF was present and may therefore be a receptor for ECF. Other proteins of apparent mol. wt 68 000 and 46 000 newly appeared at the surface of eosinophils even after incubation in suspension, apparently as a consequence of the rapid cycling of membrane components which occurs in eosinophils.

Eosinophil membrane changes during interaction with antibody-coated non-phagocytosable surfaces

Eosinophils attach themselves closely to large non-phagocytosable, antibody-coated targets, such as helminths, and release their granule contents directly on to the surface of the target. A model system has been developed in which human peripheral blood eosinophils flatten down and degranulate on to antibody-coated agar layers, which are too large to be phagocytosed. The agar layer contains tetanus toxoid antigen and the eosinophil chemotactic factor ala-glyser-glu (10 −6M), and is coated with human antitetanus immunoglobulin. Changes in the organization of the eosinophil membrane proteins were detected by lactoperoxidase catalysed iodination. A protein of molecular weight 55,000 appeared at the cell surface as an early and specific consequence of interaction with antibody coated non-phagocytosable targets. The appearance of this protein preceded degranulation. A second protein of molecular weight 58,000, was seen when no chemotactic factor was present. In the complete system this protein may be blocked by the chemotactic factor. The role of these proteins in the attachment of eosinophils to antibody-coated targets is discussed.

A Ten-year Retrospective Study of Tetanus at a Teaching Hospital in Bangladesh

Aims: To study the demographic, clinical features, treatment as well as outcomes of tetanus patients in the Bangladeshi population from 1994 to 2003. 
 Design: A retrospective descriptive study. Setting: A large public Medical college hospital with a regional as well as referral service. Materials and Methods: All cases of tetanus in adult patients from January 1994 to December 2003 were identified from the medical record at the hospital and these were then retrospectively reviewed. 
 Results: A total of 80 cases of tetanus were seen at the Faridpur Medical college hospital in the 10 years period with a mean of 8 cases per year. There were 55 male (68.75%) and 25 female (31.25%) patients. The mean age of the study population was 51.7±10.08 years. Most cases occurred in the age group of 60-69 years. Risk factor analysis revealed identifiable acute injury (puncture, prick/laceration) in 85%, CSOM (2.5%), surgery (2.5%), abortion (2.5%), skin ulcer (1.25%), burn (1.25%), child birth (1.25%), boil (1.25%). Thirty-two (40%) patients had medical wound care before hospital admission but none received tetanus immunoglobulin despite the absence of tetanus immunity. All the patients had the generalized type of disease. Body stiffness, trismus and dysphagia were the three commonest presenting complaints. All the patients with injury and wound (74/80) had their wound debrided. All the tetanus patients (80/80) received intravenous diazepam infusion as part of their management. Seventy two (90%) patients received intravenous crystalline penicillin. Sixty-five (81.25%) patients received intramuscular human antitetanus immunoglobulin and fourteen (17.5%) had tracheostomy performed. Inhospital complications were observed as respiratory (80%), cardiovascular (65%), gastrointestinal (57-5%), renal (33.37%), neurological (17.%) and others (22.5%). 
 There were eighteen deaths in hospital, accounting for overall mortality of 22.5% (18/80). Higher mortality were observed in age group above 50 years than the age group below 50 years (29.16% vs 12.5%, P<0.05), in female than the male (40% vs 14.54%, P<0.05), in farmer than nonfarmer (30.95% vs 13.15%, P<0.05), in patients who had short incubation period than those who had incubation period more than one week (53.33% vs 23.25%, P<0.05). 
 Conclusion: In general, tetanus remains in Bangladesh an important disease with substantial mortality that primarily affects unvaccinated or inadequately vaccinated individuals. Prevention during wound management of tetanus prone wounds was inappropriate in many patients. The elderly population may have the highest risk for tetanus since they may not have had tetanus toxoid immunization or regular booster injections. It is, however, highly preventable through both routine vaccination and appropriate wound management. Our case series show comparable pattern and outcome with other case series in the developing countries reported in the literatures.
 
 (J Bangladesh Coll Phys Surg 2007; 25 : 62-69)