Equine Tetanus Antitoxin Research Articles

Evaluating the effect of equine tetanus antitoxin on mortality rates of dogs affected by tetanus

PICO Question In dogs with tetanus, does administering the equine tetanus antitoxin compared to not administering the antitoxin reduce mortality rates? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three studies were reviewed for this Knowledge Summary, all of which were retrospective case-control studies. Strength of evidence Weak. Outcomes reported There was no difference in survival to discharge between dogs treated and dogs not treated with equine tetanus antitoxin. Conclusion The current literature suggests that administering the equine tetanus antitoxin to dogs affected by tetanus had no positive or negative effect on mortality rates, though the level of evidence amongst the literature is weak. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Safety of equine tetanus antitoxin for prophylactic use in Ethiopia: a retrospective multi-center study

BackgroundTetanus remains a severe life-threatening infectious disease and neurological disorder in many parts of the world, where immunization programs are suboptimal. Any human injury or trauma has the possibility of getting infected with Clostridium tetani which is the sole causative bacterium of tetanus. Evidence is available that TAT may cause anaphylaxis and late serum sickness, while there has been no study conducted in Ethiopia. The Ethiopian Ministry of Health standard treatment guideline recommends tetanus prophylaxis for all tetanus-prone wounds. This study aimed to evaluate the safety of TAT administration in adults exposed to tetanus-prone wounds in Ethiopia.MethodsThe target product of this study was the equine tetanus antitoxin developed and manufactured by the ViNS Bioproducts Limited, India (Code: 130202084, A.W.No: 15/AAW/PI/02.00, DT: 25.04.2016). The product is delivered with the dose of 1000/1500 IU intramuscularly or subcutaneously to individuals at risk of tetanus infection for prophylactic purposes. The study was carried out in 11 healthcare facilities in Addis Ababa, Ethiopia, that had a relatively high clients load for tetanus-prone wounds. Medical records of patients with tetanus-prone wounds who received the equine TAT were reviewed retrospectively for any adverse events following immunization according to the World Health Organization (WHO) definition for adverse events following immunization (AEFI).ResultsThere were more than 20,000 patients treated for trauma in the facilities from 2015 to 2019. Upon revision of available registration books, we identified 6000 charts to be eligible for the study, of which 1213 charts that had complete and reliable data on the AEFI profile of the TAT were included in the final analysis. The median age of the study participants was 26 years (IQR = 11 years, age range: 18–91 years) and 78% (949) were male. The tetanus-prone wounds resulted mainly from stab (44%, 535) and blunt force (30%, 362), and the most common sites of wounds were hand (22%, 270) and head (21%, 253). The most and least frequently occurring types of wounds were open wounds (77%, 930) and organ system injury (0.003%, 4), respectively. The mean time of presenting at health facilities from the onset of trauma was 2.96 h. Of the total 1231 participants, one male participant who presented within 3 h after experiencing a wound on his nose at the workplace had a severe local reaction immediately after injection of the TAT. No AEFI was recorded for the other participants.ConclusionsThe adverse event following immunization of the equine tetanus antitoxin produced by the ViNS Bioproducts Limited was very rare. A regular review of the product’s safety performance and systematic collection and analysis of adverse event reports are important to ensure the safety of the product.

Establishment of an equine tetanus antitoxin reference standard for veterinary use in Japan

To establish the first National Veterinary Assay Laboratory (NVAL) equine tetanus antitoxin reference standard for veterinary use, we manufactured vials of a candidate antitoxin. These were quality tested for moisture content, vacuum, colour, clarity, and the presence of foreign objects. Ultimately, 115 quality-controlled vials were prepared. To estimate the antitoxin potency of the candidate standard, three different laboratories conducted parallel line assays alongside the existing antitoxin standard. These potency estimates ranged from 38 to 42 IU. This activity was maintained for two years after manufacture, as compared with a fresh vial. No statistically significant non-linearity or non-parallelism of the regression lines was observed (p > 0.05). Statistical assessment of inter- and intra-laboratory variability revealed acceptable coefficients of variation of 3.2% and 2.4–3.1%, respectively. Based on these results, the potency of the potential reference standard was calculated at 40 units of antitoxin activity per 1-mL vial. Vials of this preparation were distributed for use as the first equine tetanus antitoxin reference standard for veterinary use in September 2015.

Inhibition of collagenase breakdown of equine corneas by tetanus antitoxin, equine serum and acetylcysteine.

To determine whether tetanus antitoxin, equine serum, and acetylcysteine, which are currently used in the treatment of equine corneal ulcer, inhibit the digestion of equine corneal collagen when exposed to collagenase in vitro. Corneas from 40 adult horses. Sections of equine corneas were incubated with saline, a solution of bacterial collagenase in saline, bacterial collagenase in saline plus equine tetanus antitoxin, bacterial collagenase in saline plus equine serum, or bacterial collagenase in saline plus acetylcysteine. Each one of the collagenase inhibitors was tested at different concentrations. The degree of corneal collagen digestion was determined by concentrations of hydroxyproline released into the incubation media and/or by weight loss of the cornea. Corneas exposed to collagenase released a significant (0.05 level) large amount of hydroxyproline (43.1 +/- 2.3 microg/mL/100 mg cornea/5 h) and decreased cornea weight by up to 89%. Blood serum (200 microL/mL), purified albumin or globulin fractions of serum, tetanus antitoxin (120 units/mL), and acetylcysteine (20 mg/mL) when used at the highest concentrations blocked collagenase digestive activity by approximately 50%. Dilution of inhibitors decreased corneal protection and linearly increased corneal weight loss. Purified equine serum albumin and globulin fractions were equally effective in protecting corneas. This experiment indicates that tetanus antitoxin, serum and acetylcysteine equally protected corneas from collagenase digestion, in vitro. However, a clinical trial is needed to establish relative therapeutic value.

Quantitation of commercial equine tetanus antitoxin by competitive enzyme-linked immunosorbent assay

In the USA, the potency of commercially prepared equine tetanus antitoxin is determined by the method outlined in the Code of Federal Regulations, Title 9, Part 113.451. In the current test, commercial equine tetanus antitoxin is tested by a toxin neutralization test in guinea pigs. The in vivo test measures antitoxin content through effectiveness of protection of guinea pigs injected with diluted mixtures of antitoxin and a standard toxin. A competitive enzyme-linked immunosorbent assay, designed as an in vitro alternative to the in vivo test, measures antitoxin content based on a competitive reaction between standard or unknown serum and murine monoclonal antibody specific for tetanus toxin. The monoclonal antibody used in the assay delayed death in mouse passive protection studies and reacted with the C fragment of tetanus toxin. No cross-reaction was observed when the antibody was tested with the toxins of Clostridium chauvoei, C. novyi, C. perfringens, or C. sordellii. The in vitro test will measure the antitoxin content of serum samples containing 100–1500 units of antitoxin. Tetanus antitoxin titers obtained by the competitive enzyme-linked immunosorbent assay compared favorably with the toxin neutralization test conducted in guinea pigs. The in vitro assay serves as a feasible alternative to the in vivo test because it can be completed in less time, is reproducible, and eliminates the use of test animals.

Quantitation of commercial equine tetanus antitoxin by competitive enzyme-linked immunosorbent assay.

In the USA, the potency of commercially prepared equine tetanus antitoxin is determined by the method outlined in the Code of Federal Regulations, Title 9, Part 113.451. In the current test, commercial equine tetanus antitoxin is tested by a toxin neutralization test in guinea pigs. The in vivo test measures antitoxin content through effectiveness of protection of guinea pigs injected with diluted mixtures of antitoxin and a standard toxin. A competitive enzyme-linked immunosorbent assay, designed as an in vitro alternative to the in vivo test, measures antitoxin content based on a competitive reaction between standard or unknown serum and murine monoclonal antibody specific for tetanus toxin. The monoclonal antibody used in the assay delayed death in mouse passive protection studies and reacted with the C fragment of tetanus toxin. No cross-reaction was observed when the antibody was tested with the toxins of Clostridium chauvoei, C. novyi, C. perfringens, or C. sordellii. The in vitro test will measure the antitoxin content of serum samples containing 100-1500 units of antitoxin. Tetanus antitoxin titers obtained by the competitive enzyme-linked immunosorbent assay compared favorably with the toxin neutralization test conducted in guinea pigs. The in vitro assay serves as a feasible alternative to the in vivo test because it can be completed in less time, is reproducible, and eliminates the use of test animals.

Neonatal tetanus: a continuing challenge in the southeast of Turkey: risk factors, clinical features and prognostic factors.

Neonatal tetanus (NT) still causes significant mortality in developing countries, although in 1989 WHO adopted the goal of eliminating the disease by 1995-2000. To characterize the regional characteristics, clinical charts of 55 neonates (42 males and 13 females) admitted to the Pediatric Infectious Diseases Ward of Dicle University Hospital, Diyarbakir, Turkey with the diagnosis of NT from 1991 to 1997 were reviewed. Mean age at admittance was 8.9+/-4.3 days with a range of 3-25 days. Mean period for the appearance of first symptoms was 5.8 days ranging between 1 and 21 days. Mean birth weight of the patients was 3369+/-560g. All patients were from rural areas and were delivered at home by untrained traditional birth attendants with no prior antenatal healthcare services. Razor blade (55%), scissors (27%), and knife (18%) were the instruments used to cut the cord in non-hygienic conditions. No mothers had prior vaccination with tetanus toxoid during their pregnancy. Spasticity (76%), lack of sucking (71%), trismus (60%), fever (49%), omphalitis (44%), irritability (24%), risus sardonicus (22%), and opithotonus (15%) were the most common presenting signs and symptoms. Age at admission < 7.5 days and symptoms of onset <4.9 days, risus sardonicus and opisthotonus were associated with fatal outcome. All patients were treated with human tetanus immunglobulin or equine tetanus antitoxin where available, antibiotic therapy by penicillin G (100.000 U/kg/day) and intravenous high dose diazepam (40 mg/kg/day). Overall mortality rate was 40% (22 cases), without any equipment for mechanical ventilation. Health education of mothers and birth attendants, promotion of hospital delivery and prenatal tetanus immunization of all pregnant women particularly in rural areas are recommended, if NT is to be prevented.

Reflex sympathetic dystrophy: An adverse reaction to immunotherapy

Reflex sympathetic dystrophy (RSD) has recently been redefined as a complex group of disorders that may develop as a consequence of t rauma affecting the limbs with or without an obvious nerve lesion. It consists of pain and related sensory abnormalities, abnormal blood flow and sweating, abnormalities in the motor system, and changes in structure of both superficial and deep tissues (trophic changes)? RSD usually occurs after t rauma to the affected limb but may occur after a myriad of medical illnesses. 2 There are two case reports of RSD after vaccination with equine tetanus antitoxin?, 4 We believe this to be the first reported case after subcutaneous allergen immunotherapy.

Tetanus immune globulin.

To the Editor.— In his LETTER TO THE EDITOR (225:179, 1973), Dr. Milton H. Stern points to the recommendations indicating the use of tetanus immune globulin (human) in individuals not previously immunized against tetanus. An editorial reply states that immune globulin is not always readily available.... Dr. Stern's position is the more appropriate. Tetanus immune globulin is in adequate supply in the United States, at reasonable cost. It should be as available to physicians as is any other emergency medication that they might expect to use. Justification for the use of equine tetanus antitoxin must be rare, indeed, in the United States at the present.

DOUBLE-BLIND TRIAL OF EQUINE ANTITOXIN AND HUMAN IMMUNE GLOBULIN IN TETANUS NEONATORUM

130 infants with tetanus neonatorum were treated on a random basis with either 10,000 units of equine tetanus antitoxin (T.A.T.) or 500 units of human tetanus immune globulin (T.I.G.). 65 infants were in each treatment group. On the basis of mortality, and days in the hospital, days of gavage feeding, and days of sedation for the survivors, there was no significant difference in the treatment groups. The number and severity of complications were comparable for the two groups and no adverse reactions were observed in the 130 infants which could be attributed to either T.A.T. or T.I.G.

Tetanus Immune Globulin (Human)

To the Editor:— Over one year ago, the pharmacology committee at Nassau Hospital investigated the high incidence of serum reactions which resulted from the use of equine and bovine tetanus antitoxin (TAT) for prophylaxis. In spite of careful skin-testing and desensitization, whenever the skin tests were positive, serum reactions frequently occurred. Some were quite severe and required hospitalization, and some occurred when the skin test was negative. Patients who had previous passive immunization with equine TAT and had a history of having had a reaction, were given bovine TAT following a skin test. All patients who had an allergic history were usually tested with both bovine and equine TAT. To avoid the reactions, patients who had positive skin tests with TAT of equine or bovine origin, or patients who gave a history of serum sickness or allergy, were given tetanus immune globulin of human origin. The product used was Hyper-Tet

Serum sickness and plasmacytosis: A clinical, immunologic and hematologic analysis

A mild case of serum sickness following an injection of equine tetanus antitoxin is reported. During the illness there was a plasmacytosis amounting to 30 per cent of the white cells in the peripheral blood. Three months after the illness, a skin test with equine serum produced an intense local reaction and the reappearance of plasmacytosis. Precipitating antibody was demonstrated against three types of equine globulins, two of which are known to carry antibodies. The patient's precipitins were γ 2-globulins, while her hemagglutinins were both γ 2- and γ 1-globulins. Skin sensitizing antibody was also found and it sedimented with the 7S globulins. In four cases of serum sickness with 1 to 3 per cent plasmacytosis and in four cases without plasmacytosis, antibodies were found to have developed to the same horse serum antigens, and no distinction could be made between the two groups in respect to the classes of antibodies developed. All patients had 7S antibody, whereas 19S antibody was found only in two. No single immunologic factor could be correlated closely with plasmacytosis.

The use of bovine antitoxin for the prophylaxis of tetanus

1. 1. Bovine tetanus antitoxin has been used with safety in selected persons known to give severe anaphylactic reactions to horse serum. 2. 2. The only indication for the use of equine tetanus antitoxin occurs in those cases where the person is known to be, or can be demonstrated to be, sensitive to the bovine but not to the equine preparation. Thus far no such cases have been reported. 3. 3. Persons undergoing an allergic study should be tested routinely with equine and bovine sera. This should be done by the scratch method only to avoid as far as possible the sensitizing of the patient to the serum. If the patient is sensitive to both sera, he should be immunized by means of tetanus toxoid, the precautions suggested by Cooke and his associates 5 being carefully observed.

Tetanus in a serum-sensitive patient successfully treated with a new despeciated antiserum

The successful treatment of tetanus is reported in a patient who was markedly sensitive to the regular commercial tetanus antitoxin. The treatment was accomplished with a new equine tetanus antitoxin, despeciated by partial digestion with taka diastase. The mild degree of allergic reaction is especially noteworthy.

Local serum sickness in man following the intracutaneous injection of small amounts of antiserums

Ten or twelve normal adults were injected intracutaneously in the forearm with 0.1 c.c. of undiluted immune serum derived from four species of animals and with two globulin antibody solutions. Local serum sickness characterized by wheals, erythema, and itching occurred as follows: 1. 1. Horse antipneumococcus Type I serum produced a severe, protracted local serum sickness in eight of the twelve individuals tested. 2. 2. Sheep antistreptococcus hemolyticus serum produced a severe reaction in nine of the subjects and a slight reaction in one. 3. 3. Rabbit antipneumococcus Type I serum produced a slight local reaction in only one individual. 4. 4. Bovine diphtheria antitoxin serum produced a strong reaction in two and a moderate or slight reaction in six. 5. 5. Equine tetanus antitoxin globulin elicited only two moderate and three slight reactions. 6. 6. Bovine tetanus antitoxin globulin produced the mildest possible reaction in three individuals. It is possible that the local serum sickness reaction may be helpful in studying the tendency of a therapeutic serum to produce serum sickness.