Caprylate/chromatography process to produce highly purified tetanus immune globulin from human plasma.

While tetanus toxoid vaccination has reduced the incidence of tetanus in the developed world, this disease remains a substantial health problem in developing nations. Tetanus immune globulin (TIG) is used along with vaccination for prevention of infection after major or contaminated wounds if vaccination status cannot be verified or for active tetanus infection. These studies describe the characterisation of a TIG produced by a caprylate/chromatography process. The TIG potency and presence of plasma protein impurities were analysed at early/late steps in the manufacturing process by chromatography, immunoassay, coagulation and potency tests. The caprylate/chromatography process has been previously shown to effectively eliminate or inactivate potentially transmissible agents from plasma-derived products. In this study, the caprylate/chromatography process was shown to effectively concentrate TIG activity and efficiently remove pro-coagulation factors, naturally present in plasma. This TIG drug product builds on the long-term evidence of the safety and efficacy of TIG by providing a product with higher purity and low pro-coagulant protein impurities.

Clinical findings and response to treatment of 17 cases of tetanus in horses (2012-2021).

Tetanus is a distressing and often fatal disease caused by exotoxins released by the bacterium Clostridium tetani. Clostridium tetani is a commensal of the gastrointestinal tract of humans and domestic animals, and its spores are highly resistant to environmental changes, acid, and alkali and may persist in the soil for many years. The disease is characterized by generalized muscular rigidity and spasms, hyperesthesia, convulsions, respiratory arrest, and death. Horses are the most susceptible domestic animals. Treatment is typically directed towards elimination of the source of the toxin, neutralization of any unbound toxin, establishment of antitoxin immunity, control of neuromuscular derangements, and relief of pain. This study described the clinical findings and therapeutic protocols of 17 horses with tetanus, treated between March 2012 and December 2021. The diagnosis of tetanus was based on the history and clinical examination findings of the animals. All horses received a treatment pattern composed of the administration of tetanus serum (50,000 UI, intravenously, followed by three injections of the same dose at 48-h intervals), procaine penicillin (25,000 UI kg, intramuscularly, BID, for 10 days), and muscle relaxant (acepromazine 0.02-0.05 mg/kg, intramuscularly, BID, for 8 days). Support therapy based on hydroelectrolytic replacements, feeding via a nasogastric tube, and assistance in the maintenance of the quadrupedal position were performed when needed. The mortality rate observed in this report was 23.52%. Early diagnosis associated with the instituted treatment contributed the most to the animal recovery.

O tétano é uma doença angustiante e frequentemente fatal, causada por exotoxinas liberadas pela bactéria Clostridium tetani. Clostridium tetani é um microrganismo comensal do trato gastrointestinal do homem e de animais domésticos, e seus esporos são altamente resistentes às mudanças ambientais, ácidas e alcalinas, podendo persistir no solo por muitos anos. A doença é caracterizada por rigidez muscular generalizada e espasmos, hiperestesia, convulsões, parada respiratória e morte. O cavalo é a espécie de animal doméstico mais suscetível. O tratamento é tipicamente direcionado à eliminação da fonte da toxina, neutralização de qualquer toxina não ligada, estabelecimento de imunidade à antitoxina, controle de distúrbios neuromusculares e alívio da dor. Os achados clínicos e protocolos terapêuticos de 17 cavalos com tétano tratados durante o período de março de 2012 a dezembro de 2021 são descritos. O diagnóstico de tétano baseou-se na história e nos achados do exame clínico dos animais. Todos os cavalos receberam padrão de tratamento, composto pela administração de soro tetânico (50.000UI, por via intravenosa, seguido de três outras aplicações da mesma dose em intervalos de 48 horas), penicilina procaína (25.000UI kg, intramuscular, BID, por 10 dias) e relaxante muscular (acepromazina 0,02-0,05 mg kg, por via intramuscular, BID, por oito dias). Foram realizadas terapia de suporte baseada em reposições hidroeletrolíticas, alimentação por sonda nasogástrica e auxílio na manutenção da posição quadrúpede, quando necessário. A mortalidade observada neste estudo foi de 23,52%. O diagnóstico precoce associado ao tratamento instituído foram os fatores que mais contribuíram para a recuperação dos animais.

Effectiveness and safety of tetanus vaccine administration by intramuscular vs. subcutaneous route in anticoagulated patients: Randomized clinical trial in primary care.

Design: Prospective, double-blind clinical trial comparing tetanus-diphtheria vaccine administration routes, intramuscular (IM) vs. subcutaneous (SC) injection, in patients with oral anticoagulants. ISRCTN69942081. Study population: Patients treated with oral anticoagulants, 15 health centers, Vigo (Spain). Sample size, 117 in each group. Outcome variables: Safety analysis: systemic reactions and, at the vaccine administration site, erythematic, swelling, hematoma, granuloma, pain.Effectiveness analysis: differences in tetanus toxoid antibody titers.Independent variables: route, sex, age, baseline serology, number of doses administered. Analysis: Following the CONSORT guidelines, we performed an intention-to-treat analysis. We conducted a descriptive study of the variables included in both groups (117 in each group) and a bivariate analysis. Fewer than 5% of missing values. Imputation in baseline and final serology with the median was performed. Lost values were assumed to be values missing at random. We conducted a descriptive study of the variables and compared routes. For safety, multivariate logistic regression was applied, with each safety criterion as outcome and the independent variables. Odds ratios (ORs) were calculated. For effectiveness, a generalized additive mixed model, with the difference between final and initial antibody titers as outcome. Due to the bimodal distribution of the outcome, the normal mixture fitting with gamlssMX was used. All statistical analyses were performed with the gamlss.mx and texreg packages of the R free software environment. Results: A previously published protocol was used across the 6-year study period. The breakdown by sex and route showed: 102 women and 132 men; and 117 IM and 117 SC, with one dose administered in over 80% of participants. There were no differences between groups in any independent variable. The second and third doses administered were not analyzed, due to the low number of cases. In terms of safety, there were no severe general reactions. Locally, significant adjusted differences were observed: in pain, by sex (male, OR: 0.39) and route (SC, OR: 0.55); in erythema, by sex (male, OR: 0.34) and route (SC, OR: 5.21); and in swelling, by sex (male, OR: 0.37) and route (SC, OR: 2.75). In terms of effectiveness, the model selected was the one adjusted for baseline serology.

Tétanos generalizado: Una amenaza persistente, reporte de tres casos y revisión de la literatura / Generalized tetanus: A persistent threat, review of the literature and report of three cases

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.

A novel single-domain antibody multimer that potently neutralizes tetanus neurotoxin.

Tetanus antitoxin, produced in animals, has been used for the prevention and treatment of tetanus for more than 100 years. The availability of antitoxins, ethical issues around production, and risks involved in the use of animal derived serum products are a concern. We therefore developed a llama derived single-domain antibody (VHH) multimer to potentially replace the conventional veterinary product. In total, 28 different tetanus neurotoxin (TeNT) binding VHHs were isolated, 14 of which were expressed in yeast for further characterization. Four VHH monomers (T2, T6, T15 and T16) binding TeNT with high affinity (KD < 1 nM), covering different antigenic domains as revealed by epitope binning, and including 3 monomers (T6, T15 and T16) that inhibited TeNT binding to neuron gangliosides, were chosen as building blocks to generate 11 VHH multimers. These multimers contained either 1 or 2 different TeNT binding VHHs fused to 1 VHH binding to either albumin (A12) or immunoglobulin (G13) to extend serum half-life in animals. Multimers consisting of 2 TeNT binding VHHs showed more than a 10-fold increase in affinity (KD of 4-23 pM) when compared to multimers containing only one TeNT binding VHH. The T6 and T16 VHHs showed synergistic in vivo TeNT neutralization and, when incorporated into a single VHH trimer (T6T16A12), they showed a very high TeNT neutralizing capacity (1,510 IU/mg).

Vacuna antitetánica adyuvada en alúmina en inmunización simultánea por vías mucosa y parenteral / Alum adjuvant tetanus vaccine in simultaneous immunization by mucosal and parenteral routes

El tétanos es causado por Clostridium tetani, bacteria Gram+ esporulada que produce una potente neurotoxina. Las vacunas parenterales producen IgG antitoxina tetánica (anti TT) protectores en múltiples dosis inductoras y de reactivación; vax-TET® es una vacuna cubana parenteral adsorbida en alúmina. La IgAS (secretora), principal anticuerpo protector mucoso, sólo es inducida por la vía mucosa. La vía oral, la inducción de IgA y su papel protector no han sido exploradas. SinTimVaS se aplica por vía mucosa y parenteral simultánea que induce IgG sistémica similares a la vía parenteral y adiciona de respuesta de IgA mucosa. Evaluamos el efecto de vax-TET® aplicado en SinTimVaS en ratones Balb/c y exploramos la influencia del adyuvante sobre la inducción de IgA anti TT. SinTimVaS indujo similares respuestas de IgG anti TT séricas que dos dosis de vax-TET® intramusculares; pero superiores a una dosis. Tres dosis de vax-TET® orales no indujeron IgG anti TT sérica, mientras que la adyuvación con el adyuvante Finlay Cocleato 1 (AFCo1) sí la indujeron. No se logró determinar la inducción de IgA anti TT mucosa con ninguna de las formulaciones adjuvadas con alúmina; pero si con la formulación AFCo1+TT. Podemos concluir que vax-TET® en SinTimVaS funcionó de forma similar a la inmunización parenteral establecida, por lo que sería posible reducir los esquemas multidosis con formulaciones de adyuvantes más potentes y se confirma que se requieren potentes adyuvantes para inducir IgA mucosa(AU)

Tetanus is caused by Clostridium tetani, a sporulated Gram+ bacterium that produces a potent neurotoxin. Parenteral vaccines produce protective tetanus antitoxin (anti TT) IgG in multiple induction and reactivation doses; vax-TET® is a Cuban parenteral vaccine adsorbed onto alumina. IgAS (secretory), the main mucosal protective antibody, is only induced by the mucous membrane. The oral route, the induction of IgA and its protective role have not been explored. SinTimVaS is applied by simultaneous mucosal and parenteral route that induces systemic IgG similar to the parenteral route and adds an IgA mucosal response. We evaluated the effect of vax-TET® applied in SinTimVaS in Balb/c mice and we explored the influence of adjuvant on the induction of anti-TT IgA. SinTimVaS induced similar serum anti TT IgG responses to two intramuscular doses of vax-TET®; but higher than one dose. Three doses of oral vax-TET® did not induce serum anti-TT IgG, whereas adjuvanted with adjuvant Finlay Cocleate 1 (AFCo1) did induce it. It was not possible to determine the IgA anti-TT mucous induction with any of the formulations adjuvanted with alumina; but with the formulation AFCo1 + TT it was induced. We can conclude that vax-TET® in SinTimVaS worked in a similar way to the established parenteral immunization, so it would be possible to reduce the multi-dose vaccination schemes with more potent adjuvant formulations and it is confirmed that powerful adjuvants are required to induce mucosal IgA(AU)

Tetanus antitoxin potency assessment by surface plasmon resonance and ToBI test.

Potency testing of tetanus antitoxin must be performed in vivo, in a very painful, stressful and prone to high variability assay. It is, therefore, mandatory to find alternatives to this kind of potency assessment. Immunochemical tests as ELISA or ToBI test are already available but usually results in a poor correlation to the in vivo protection. Considering research and development of mono and oligoclonal antibodies against tetanus and the improvement of equine polyclonal antitoxin production and control, we developed an alternative instrumental test for tetanus antitoxin by using surface plasmon resonance. Tetanus antitoxin from hyperimmune equine sera (16 batches) were tested and the results indicated excellent concordance and correlation to the in vivo test (Lin's ρ = 0.9). This innovative approach should now be improved in order to extend it to oligoclonal and monoclonal human antibodies aiming to replace mice for the potency assessment of tetanus antitoxin especially during research and development steps.

Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018).

BACKGROUND: Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease-associated virus [TDAV]; non-primate hepacivirus [NPHV]) and equine parvovirus (EqPV-H) are present in equine blood products; the TDAV, NPHV, and EqPV-H have been suggested as potential causes of serum hepatitis. OBJECTIVE: To determine the prevalence of these viruses in horses with equine serum hepatitis. ANIMALS: Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals. METHODS: In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV-H by PCR. RESULTS: Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4-12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6-8.6 weeks, and 3 horses received allogenic stem cells 6.4-7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV-positive. Six of 14 serum samples were EPgV-positive. All liver samples were NPHV-negative and EPgV-negative. EqPV-H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT-associated cases, and all 10 samples were EqPV-H positive. CONCLUSIONS AND CLINICAL IMPORTANCE: We demonstrated EqPV-H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV-H and eliminate EqPV-H-infected horses from their donor herds.

Tetanus antitoxin potency assessment by surface plasmon resonance and ToBI test

Potency testing of tetanus antitoxin must be performed in vivo, in a very painful, stressful and prone to high variability assay. It is, therefore, mandatory to find alternatives to this kind of potency assessment. Immunochemical tests as ELISA or ToBI test are already available but usually results in a poor correlation to the in vivo protection. Considering research and development of mono and oligoclonal antibodies against tetanus and the improvement of equine polyclonal antitoxin production and control, we developed an alternative instrumental test for tetanus antitoxin by using surface plasmon resonance. Tetanus antitoxin from hyperimmune equine sera (16 batches) were tested and the results indicated excellent concordance and correlation to the in vivo test (Lin's Ró=0.9). This innovative approach should now be improved in order to extend it to oligoclonal and monoclonal human antibodies aiming to replace mice for the potency assessment of tetanus antitoxin especially during research and development steps.

Functional and proteomic comparison of different techniques to produce equine anti-tetanus immunoglobulin F(ab')2 fragments.

Tetanus is still a major cause of human deaths in several developing countries. In particular, the neonatal form remains a significant public health problem. According to the World Health Organization, administration of tetanus toxoid is recommended for neonatal tetanus patients. Furthermore, tetanus antitoxin or anti-tetanus immunoglobulin (Ig) are used for mild case or intensive care. This paper discusses a novel purification technique for improving equine anti-tetanus Ig production. First, equine plasma dealt with two steps salting out with ammonium sulfate; second, ultrafiltration concentration liquid purified by one successive protein G based affinity chromatography steps; finally, the purified F(ab')2 fragments was characterized using biochemical and proteomic methods and shown to be pure and homogeneous. Compared with the original technique product, specific activity increased by 80% (about 90,000 IU/g) and recovery of F(ab')2 is approximately equal 75%. Furthermore, Proteomic profiling of total technique process is demonstrated by nano-HPLC-MS and bioinformatics analysis. New technique to produce equine anti-tetanus immunoglobulin F(ab')2 fragments from crude plasma in high quality and yield. And it also could be used for industrial amplification.

[Chinese expert consensus on tetanus immunization].

Tetanus is an acute specific infection caused by obligate anaerobes, which is still a serious public health problem. Tetanus bacterium is an obligate anaerobic bacterium, widely distributed in nature, which can exist in dust, soil, human or animal excrement. The bacteria invade the body primarily through the skin or mucosal wounds, and most commonly in trauma and burn patients, unclean newborns, and unsafe surgical instruments. Exotoxin produced by tetanus bacteria can cause temporary changes in the central nervous system, manifested as systemic skeletal muscle persistence and paroxysmal spasm, severe cases of laryngospasm, asphyxia, lung infections and organ failure, which is a very serious and potentially fatal disease. This article is an expert consensus on the tetanus immunologic defense, aiming to aid the clinical decision making after open injury. According to epidemiological investigation of tetanus, types of injured population, wound exposure and misunderstandings of immunologic defense, the key measures to prevent tetanus are good wound management and immunization. This statement describes a preventive framework of tetanus immunization, including the tetanus immunization programs of infants, pregnant women, potentially high-risk population, immunodeficiency patients and children born to HIV-infected mothers. This consensus only provides academic guidance, the treatment of the patient must be based on the prevailing medical conditions.

Chinese expert consensus on tetanus immunization / 中华外科杂志

Tetanus is an acute specific infection caused by obligate anaerobes, which is still a serious public health problem. Tetanus bacterium is an obligate anaerobic bacterium, widely distributed in nature, which can exist in dust, soil, human or animal excrement. The bacteria invade the body primarily through the skin or mucosal wounds, and most commonly in trauma and burn patients, unclean newborns, and unsafe surgical instruments. Exotoxin produced by tetanus bacteria can cause temporary changes in the central nervous system, manifested as systemic skeletal muscle persistence and paroxysmal spasm, severe cases of laryngospasm, asphyxia, lung infections and organ failure, which is a very serious and potentially fatal disease. This article is an expert consensus on the tetanus immunologic defense, aiming to aid the clinical decision making after open injury. According to epidemiological investigation of tetanus, types of injured population, wound exposure and misunderstandings of immunologic defense, the key measures to prevent tetanus are good wound management and immunization. This statement describes a preventive framework of tetanus immunization, including the tetanus immunization programs of infants, pregnant women, potentially high-risk population, immunodeficiency patients and children born to HIV-infected mothers. This consensus only provides academic guidance, the treatment of the patient must be based on the prevailing medical conditions.

Chinese expert consensus on tetanus immunization / 中华外科杂志

Tetanus is an acute specific infection caused by obligate anaerobes, which is still a serious public health problem. Tetanus bacterium is an obligate anaerobic bacterium, widely distributed in nature, which can exist in dust, soil, human or animal excrement. The bacteria invade the body primarily through the skin or mucosal wounds, and most commonly in trauma and burn patients, unclean newborns, and unsafe surgical instruments. Exotoxin produced by tetanus bacteria can cause temporary changes in the central nervous system, manifested as systemic skeletal muscle persistence and paroxysmal spasm, severe cases of laryngospasm, asphyxia, lung infections and organ failure, which is a very serious and potentially fatal disease. This article is an expert consensus on the tetanus immunologic defense, aiming to aid the clinical decision making after open injury. According to epidemiological investigation of tetanus, types of injured population, wound exposure and misunderstandings of immunologic defense, the key measures to prevent tetanus are good wound management and immunization. This statement describes a preventive framework of tetanus immunization, including the tetanus immunization programs of infants, pregnant women, potentially high-risk population, immunodeficiency patients and children born to HIV-infected mothers. This consensus only provides academic guidance, the treatment of the patient must be based on the prevailing medical conditions.

Literature Analysis of 2 636 Cases of Adverse Drug Reaction Induced by Tetanus Antitoxin / 中国药房

OBJECTIVE:To investigate general regularity and characteristics of tetanus antitoxin (TAT) induced by ADRs,in order to provide reference for rational drug use in the clinic.METHODS:Domestic and foreign literatures on ADRs induced by TAT were retrieved,and related information of 2 636 case of ADR were analyzed statistically.RESULTS:Among patients whose gender and age were recorded,male with ADR induced by TAT was more than female,mainly aged 15-35 years old,accounting for 70.32 ％ (289/411);28.28 ％ (56/198) used water for injection;ADR occurred within 30 min after medication in 5.84％ (154/2 636)cases;main ADR were lesion of skin and its appendents,circulatory system damage,systemic reaction damage.Main clinical manifestations were urticaria,rash,chest tightness and anaphylaetic shock,etc.Ten cases died and 7 cases had sequelae;the rest were all recovered and cured after symptomatic treatment.CONCLUSIONS:TAT has a higher proportion of allergic reactions,especially anaphylactic shock,but great importance should be attached to rare auditory and vestibular dysfunction,visual impairment,elevated white blood cell count and other ADR.It is suggested to strengthen medication monitoring and used drugs strictly in accordance with drug package inserts so as to promote rational drug use.

Tétanos Infantil: Reporte de un Caso / Tetanus Child: a Case Report

El tétanos, enfermedad infecciosa aguda causada por el bacilo Clostridium Tetani, actualmente constituye una patología infrecuente en Bolivia gracias al Programa Nacional de Inmunización. Representa un problema de salud pública por su elevada tasa de letalidad que alcanza el 50%. Por lo que se considero muy útil la descripción de esta patología rara pero vigente mediante el análisis de este caso clínico presentado en el Hospital del Niño "Manuel Ascencio Villarroel". Presentamos el caso clínico, de un niño de dos años de edad con antecedente de caída a un pozo, con esquema de vacunación completo, se hospitalizo y se valoro como síndrome de casi ahogamiento y encefalopatía hipóxica - hipoxémica. En el 6° día de internación presento sintomatología compatible y se hace el diagnostico de tétanos generalizado. Se dio tratamiento con: Inmunoglobulina antitetánica, sedación, Vitamina K, Penicilina Sódica y Metronidazol.

Tetanus, acute infectious disease caused by bacillus Clostridium Tetani, is now a rare pathology in Bolivia through the National Immunization Program. It represents a public health problem because of its high fatal¡ty rate reaches 50%. As I find very useful description of this rare condition, but existing by analysis of this case report presented at the Children's Hospital "Manuel Ascencio Villarroel". We report the case of child a two year old with a history of falling into a pit, with complete vaccination, was hospitalized and is valued as a syndrome of near drowning, and hypoxic encephalopathy - hypoxemic. In the 6th day of hospitalization presented symptoms suggestive and the diagnosis of generalized tetanus. Treatment was given: tetanus immunoglobulin, sedation, vitamin K, Sodium Penicillin and Metronidazole.

Tétanos: Todavía un problema de salud pública / Tetanus: still a public health problem

El tétanos es una enfermedad inmunoprevenible que todavía causa estragos en las naciones que no han logrado coberturas protectoras de vacunación. Su tasa de letalidad alcanza el 50 por ciento. Es necesario que nuestro personal de salud esté familiarizado con su prevención, diagnóstico, tratamiento y rehabilitación. Esta revisión tiene como objetivo presentar una actualización de conocimientos sobre esta importante enfermedad, haciendo énfasis en el diagnóstico y el tratamiento.El tétanos es una enfermedad aguda de distribución mundial y presentación esporádica, infrecuente en países industrializados. Por su elevada tasa de letalidad aún representa un problema de salud pública, en especial en regiones con programas preventivos deficientes.

Tetanus is an immune-preventable disease which still causes ravages in nations without protective vaccination coverage. Its lethality rate is almost 50%. It is necessary that healthpersonnel are familiarized with its prevention, diagnosis, treatment and rehabilitation. Tetanus is an acute illness of worldwide distribution, sporadic occurrence and low frequency inindustrialized countries. Due to its high lethality rate it still is a public health problem, especially in regions with deficient preventive programs. This review presents up to date knowledge on different aspects of this important disease, with emphasis on its diagnosis and treatment.

In vivo Evaluation of Single Dose Tetanus Toxoid Vaccine Formulation with Chitosan Microspheres.

Chitosan adsorbed microspheres containing tetanus toxoid were prepared in the size range of 10 mum to 75 mum, by emulsion-cross linking technique at different speeds of agitation. The amount of tetanus toxoid incorporated into chitosan microspheres were estimated by limes flocculation test and in vivo evaluation of tetanus toxoid adsorbed chitosan microspheres were determined by toxin neutralization method using albino mice. The results of in vivo release for the batches of 10 mum and 25 mum correlates with the results of in vitro in which both the batches passes the limit of IP standard (4 Lf) where as, for the batches of 50 mum and 75 mum, the in vitro release of tetanus toxoid was 2 Lf. But our in vivo studies for the batches of 50 mum and 75 mum fail to pass the limit stated in IP. The release of tetanus toxoid from the chitosan microspheres was found to be sustained for the period of 6 months.

?mprovement of purification procedure of tetanus antitoxin

The decoloration of purified sera was achieved by using 0.1% caprylic acid solution with pH 4.2 at 56oC. The technique can shorten the duration of purification processes

Production of purified tetanus antitoxin for thrapeutic purpose

The Institute of Vaccine and Biologicals has recently released on market a purified tetanus antitoxin. The average potency of the product reached  3.000 IU/ml. The N-protein content is  70mg/ml

Influencia de la temperatura, tiempo de conservación y valor absoluto de las muestras de suero en los resultados de la cuantificación de antitoxina tetánica / Influence of temperature, time of conservation, and absolute value of serum samples in quantification results of tetanus antitoxin

Se evaluó la precisión y exactitud del KIT UMELISA en la dosificación de IgG antitétanos. Se estudió la variabilidad de la concentración de anticuerpos en función del tiempo y la temperatura de almacenamiento en 34 donantes especiales de plasma hiperinmune antitetánico, inmunizados con la vacuna toxoide tetánica, de producción nacional, y sometidos a procedimientos de donación por plasmaféresis automatizada. Se escogieron dos grupos de estudio según la concentración de inmunoglobulinas séricas (< 10 UI/ml y > 10 UI/ml) y se trabajó con muestras conservadas a 30 ºC y de 2 a 8 ºC. Los test estadísticos utilizados en el procesamiento de la información arrojaron que la técnica es precisa y exacta, y que las mayores fluctuaciones ocurren cuando los títulos eran bajos y la conservación a temperatura entre 2 y 8 ºC.

Precision and accuracy of UMELISA kit in IgG tetanus antitoxin dosification was assessed. Concentration variability of antibodies was studied according to time and storage temperature in 34 special donors of tetanus antitoxin hyperimmune plasma immunized with tetanus antitoxin vaccine of national production and was subjected to procedures of donation for automated plasmapheresis. Two study group were chosen as to serum immunoglobulin concentration (<10 UI/ml and >10 UI/ml) and were worked with preserved samples at -30 ºC and of 2-8 ºC. Statistic test used in the processing of information showed that the technique was precise and accurate and that greater fluctuations occur when titles are low and the conservation is at 2-8 ºC.