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.

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)

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.

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

?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

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.

Chemical quality of purified tetanus antitoxin and anti-rabies serum produced at the Institute of Vaccine (IVAC), from 1997-2001

59 batches of purified tetanus antitoxin and 20 batches of anti-rabies serum (1997-2001) produced at IVAC Nha Trang were tested for: pH, total nitrogen, merthiolate content, sodium chloride content. In general, all the batches met the minimum requirements of the manufacture. However in order to improve the quality of the sera additional requirements should be set up