Caracterización del polirribosilribitol fosfato por cromatografía de exclusión molecular de alta eficacia con detección ultravioleta / Characterization of polyribosylribitol phosphate by high efficiency size exclusion chromatography with ultraviolet detection

Haemophilus influenzae tipo b es un importante patógeno del hombre causante de varias de las enfermedades invasivas en niños menores de cinco años, contra el cual fueron autorizadas las vacunas glicoconjugadas a partir del polirribosilribitol fosfato. Quimi-Hib® es la primera y única vacuna contra este patógeno que utiliza el polisacárido obtenido por síntesis química. El Ingrediente Farmacéutico Activo es producido por el Centro de Ingeniería Genética y Biotecnología y se obtiene a partir de su conjugación al toxoide tetánico. En el presente reporte se hizo una caracterización del polirribosilribitol fosfato mediante la técnica de cromatografía de exclusión molecular de alta eficacia con detección ultravioleta a 215 nm. En el estudio se evaluaron tres lotes y se determinó el perfil de elución en una columna SuperdexTM 75 10/300 GL Increase con un porciento de pureza de 77,42 ± 8,97 y una masa molar promedio de 7.381 Da ± 210,93. La principal impureza presente en el polirribosilribitol fosfato es el dimetilsulfóxido, disolvente utilizado en la reacción de activación con el éster N-hidroxisuccinimidilo del ácido β-maleimidopropiónico. El polirribosilribitol fosfato se purificó por filtración con un Amicon Ultra-15 de 2.000 Da hasta una pureza de 99,1 por ciento y se conjugó al toxoide tetánico. El rendimiento de la reacción de conjugación con el polisacárido purificado fue de 30,0 por ciento 1,77 el cual no muestra diferencias significativas con el control que fue 33,7 por ciento ± 3,57 demostrándose que el dimetilsulfóxido no afecta el desempeño de la reacción de conjugación(AU)

Haemophilus influenzae type b is an important human pathogen causing some invasive diseases in children less than five years of age. Glycoconjugate vaccines based on polyribosylribitol phosphate have been licensed against this bacterium. Quimi-Hib® is the first and only vaccine against this pathogen using the chemically synthesized polysaccharide. The Active Pharmaceutical Ingredient is produced by the Center for Genetic Engineering and Biotechnology and is obtained from its conjugation to tetanus toxoid. In the present report a characterization of polyribosylribitol phosphate was performed by high performance molecular exclusion chromatography with ultraviolet detection at 215 nm. Three batches were evaluated in the study and the elution profile was determined on a SuperdexTM 75 10/300 GL Increase column with a purity percentage of 77.42 ± 8.97 and an average molecular weight of 7,381 Da ± 210.93. The main impurity present in polyribosylribitol phosphate was dimethylsulfoxide, the solvent used in the activation reaction with N-hydroxysuccinimidyl ester of β-maleimidopropionic acid. Polyribosylribitol phosphate was purified by filtration using a 2,000 Da cut-off Amicon Ultra-15 to a purity of 99.1 percent and conjugated to tetanus toxoid. The yield of the conjugation reaction with the purified polysaccharide was 30.0 percent ± 1.77 which shows no significant difference with the control which was 33.7 percent ± 3.57 demonstrating that dimethylsulfoxide does not affect the performance of the conjugation reaction(AU)

Tétano acidental em Santa Catarina: Evolução temporal e perfil sociodemográfico da última década / Accidental tetanus in Santa Catarina: temporal trend and sociodemographic profile in the last decade

Introdução: O tétano acidental é definido como uma doença não contagiosa e prevenível com vacinação, decorrente da ação de exotoxinas do Clostridium tetani, desencadeando um estado de hiperexcitabilidade do sistema nervoso central, em pacientes não neonatais. O número de casos no país está reduzindo; contudo, a mortalidade é elevada. Dessa forma, o presente estudo objetivou avaliar o perfil e a tendência temporal da ocorrência de tétano acidental no estado de Santa Catarina, no período de 2008 a 2018. Métodos: Estudo observacional do tipo ecológico com a população do estado de Santa Catarina, sendo excluídos os residentes com idade de 0 a 4 anos. O número de notificações e as variáveis clínico-epidemiológicas foram extraídos da base de dados da Diretoria de Vigilância Epidemiológica do estado de Santa Catarina (DIVE) e do Departamento de Informática do Sistema Único de Saúde (DATASUS). Resultados: Observou-se uma maior ocorrência do tétano acidental em homens; faixa etária entre os 50 e 64 anos; residentes de zonas urbanas. O principal desfecho foi a cura. Notou-se uma correlação significativa (p<0,05) para a redução da incidência de casos nos seguintes grupos: sexo feminino e idosos a partir dos 80 anos. Conclusão: Denota-se que, apesar de possuir uma forma simples de profilaxia, o tétano acidental persiste como um problema de saúde pública e, portanto, deve-se investir em estratégias para aumentar a cobertura vacinal, em especial, nos grupos de maior incidência.

Introduction: Accidental tetanus is defined as a non-communicable disease preventable by vaccination; it is caused by exotoxins produced by Clostridium tetani, triggering a state of central nervous system hyperexcitability in non-neonatal patients. The number of cases in the country is decreasing, but mortality rates are high. This study thus aimed to evaluate the profile and temporal trend of the occurrence of accidental tetanus in the state of Santa Catarina between 2008 and 2018. Methods: This is an observational ecological study performed with the population of the state of Santa Catarina, excluding residents aged 4 years or less. The number of reported cases and clinical and epidemiological variables were extracted from databases of the Epidemiological Surveillance Department of the State of Santa Catarina (DIVE) and the Informatics Department of the Unified Health System (DATASUS). Results: We observed a higher occurrence of accidental tetanus among men, people aged between 50 and 64 years, and individuals living in urban areas. The main outcome observed in this study was cure. We noticed a significant correlation (p<0.05) for a reduction in cases among the following groups: women and older adults aged 80 years or older. Conclusion: Despite its simple prophylaxis, accidental tetanus remains a public health problem; investments should thus be made in strategies that increase vaccination coverage, especially considering groups with higher incidence rates.

Tetanus vaccination in pregnant women: a systematic review and meta-analysis of the global literature.

OBJECTIVES: This study aimed to determine the effect of several factors on the uptake of tetanus vaccination in pregnant women. STUDY DESIGN: This is a systematic review and meta-analysis of the global literature. METHODS: The search strategy was carried out in the EMBASE and MEDLINE (Pubmed) databases, without language restrictions. The databases were searched from the beginning until May 2020. Fixed and random effect models were applied according to the methodological heterogeneity between the included studies. The I2 test was performed to assess the magnitude of the heterogeneity. The results were presented as a grouped odds ratio (OR) with a 95% confidence interval (CI) and a significance level of 0.05. RESULTS: The initial search strategy generated 14,349 original articles. In total, 31 studies met all inclusion criteria and 20 articles were included in the meta-analysis. The grouped and subgroup analyses showed a significant association between tetanus vaccination and the following factors: higher number of prenatal visits (OR: 2.00; 95% CI: 1.17-3.42), higher maternal age (OR: 1.24, 95% CI: 1.02-1.50), being single (OR: 1.41; 95% CI: 1.20-1.65), professional vaccine guidance (OR: 9.00; 95% CI: 1.81-44.75) and uptake of influenza vaccine (OR: 5.87; 95% CI: 1.39-24.73). CONCLUSIONS: The uptake of tetanus vaccine in pregnant women is associated with various factors. The identification of these factors is an important step towards the implementation of public health strategies aimed at improving immunisation against tetanus in pregnant women.

Factors associated with tetanus vaccination in pregnant women living in Minas Gerais State, Brazil: A cross-sectional study.

Background: Immunization in pregnant women is essential to help controlling and avoiding preventable diseases. Aim: Analyzing some factors associated with non-vaccination against tetanus in pregnant women who gave birth in maternity hospitals in Belo Horizonte City, Minas Gerais State, Brazil. Methods: Cross-sectional study carried out with database deriving from the research titled "Born in Belo Horizonte: Survey on childbirth", which was developed in public and private hospitals. Sample was calculated by taking into consideration the total number of births recorded in each investigated maternity hospital - the final sample comprised 481 mothers. Descriptive population statistics were used for data analysis purposes, whereas Poisson regression model was used to estimate factors associated with non-vaccination against tetanus during pregnancy. Results: The prevalence of puerperal women subjected to at least 2 doses of tetanus vaccine reached 59.2%. Adjusted analyses have shown that not living with a partner has increased by 1.58 times the prevalence of women who did not take tetanus vaccine, on average; that the prevalence of women who were not vaccinated has decreased by 0.65 times after each prenatal consultation, on average; that prenatal consultations with nurses have reduced by 0.52 times the prevalence of women who did not take the tetanus vaccine, on average. Conclusion: Almost half of puerperal women were not vaccinated against tetanus during pregnancy. It is essential identifying specific groups to help implementing and expanding preventive actions, such as immunization for pregnant women. Despite advances in public health policies, authorities still face challenges to expand vaccination coverage in the investigated state, as well as to strengthen the national immunization program to help increasing tetanus vaccination rates among pregnant women.

Tétanos generalizado en adulto. Reporte de caso / Adult generalized tetanus. Case report

RESUMEN Fundamento: El tétanos es una enfermedad infecciosa causada por las esporas de la bacteria Clostridium tetani que afecta el sistema nervioso. La inmunización contra esta enfermedad ha permitido reducir la morbilidad y la mortalidad en Cuba por esa causa. Los pocos casos reportados son pacientes sin previa vacunación contra el tétanos, por lo que constituye de interés para la comunidad científica el reporte de aquellos que desarrollan esa enfermedad después de haber sido vacunados. Objetivo: Describir el caso de un paciente con diagnóstico de tétanos generalizado a pesar de que ya había sido vacunado contra esa enfermedad. Presentación del caso: Paciente de 33 años, con el antecedente de haber sido vacunado contra el tétanos, al cual le diagnosticaron tétanos generalizado, por lo se decidió su ingresó en la unidad de cuidados intensivos. Clínicamente se manifestó por contracciones musculares generalizadas y rigidez, los síntomas y signos neurológicos tuvieron una duración de 4 semanas. A pesar de las complicaciones el paciente egresó con adecuada calidad de vida. Conclusiones: La presentación de este caso busca concientizar en la comunidad científica la importancia de considerar el diagnóstico de tétanos en pacientes ya vacunados, lo cual es poco frecuente y obliga a actuar con prontitud.

ABSTRACT Background: Tetanus is an infectious disease caused by the bacterium Clostridium tetani spores which affects the nervous system. In Cuba, immunization against this disease has made it possible to reduce morbidity and mortality from this cause. The few cases reported are patients without prior vaccination against tetanus, so is the interest to the scientific community the reporting of those who develop this disease after having been vaccinated. Objective: To describe a patient´s case with a generalized tetanus diagnosis despite has already been vaccinated against this disease. Case report: A 33-year-old patient, with a history of has been vaccinated against tetanus, and diagnosed with generalized tetanus, so it was decided he to be admitted to the intensive care unit. Clinically manifested by generalized muscle contractions and stiffness, the neurological symptoms and signs lasted 4 weeks. Despite the complications, the patient discharged from hospital with an adequate life quality. Conclusions: This case presentation searches for raising awareness in the scientific community about the importance of considering the diagnosis of tetanus in previous vaccinated patients, which is rare and requires quickness of action.

Diseño de un programa de análisis de peligros y puntos críticos control (HACCP) para la producción de toxoide tetánico / Design of a program of hazard analysis and critical control point (HACCP) for production of Tetanus Toxoid

El toxoide tetánico es una neurotoxina modificada que induce la formación de una antitoxina protectora contra la enfermedad denominada tétanos. Este antígeno es obtenido a partir de procesos fermentativos con la bacteria anaerobia Clostridium tetani y es utilizado para la formulación de vacunas simples y combinadas inactivadas. Con el propósito de atender a las recomendaciones y regulaciones de la Organización Mundial de la Salud (OMS), el objetivo de este trabajo fue diseñar un Programa de Análisis de Peligros y Puntos Críticos de Control (HACCP) en la producción del antígeno Toxoide Tetánico, desde la recepción de la cepa certificada en el área de producción hasta el almacenamiento del toxoide tetánico purificado. Para ello, inicialmente se evaluó el cumplimiento de los prerequisitos (BPM, POES, BPL). Posteriormente, se procedió al diseño del plan HACCP mediante la ejecución de las 5 tareas preliminares y la aplicación de los 7 principios, conforme a la metodología descrita por la OMS. A partir del análisis de peligros en todas las etapas del proceso de producción del toxoide tetánico se identificaron 3 puntos críticos de control: detoxificación, filtración estéril final y almacenamiento de toxoide tetánico purificado. Se establecieron los límites críticos, los procedimientos de vigilancia, las acciones correctivas, los procedimientos de verificación y de documentación. La propuesta tiene como fin garantizar la calidad e inocuidad del producto elaborado, la protección del personal involucrado en el proceso y del medio ambiente con miras a la obtención de la certificación como laboratorio productor de vacunas

Tetanus toxoid is a modified neurotoxin that induces the formation of protective antitoxin of the disease called tetanus. This antigen is obtained from fermentation processes with anaerobic bacteria Clostridium tetani and it is used to formulate simple and combined inactivated vaccines. In order to meet the recommendations and regulations of World Health Organization (WHO), the aim of this work was to design a Program of Hazard Analysis and Critical Control Points (HACCP) in the production of antigen Tetanus Toxoid, starting from the receipt of the certified strain in the production area through the storage of purified tetanus toxoid. For this, initially fulfilling the prerequisites (GMP, SSOP and GLP) was evaluated. Subsequently, we proceeded to design HACCP plan by running 5 preliminary tasks and application of the 7 principles, according to the methodology described by WHO. From the hazard analysis at all stages of the production process of tetanus toxoid three critical control points were identified: detoxification, final sterile filtration and storage of purified tetanus toxoid. Critical limits, monitoring procedures, corrective actions, verification and documentation procedures were established. The proposal aims to assure the quality and safety of the final product, the protection of personnel involved in the process and the environment, with a view to obtaining certification as a vaccine production laboratory

Tétanos secundario a mordedura y arañazo de gato en una paciente previamente vacunada / Tetanus after cat scratch and bites in a previously immunized patient

Tetanus is declining due to vaccination, professional labor management and appropriate wound care. Tetanus cases have been reported despite immunization. We report the case of a previously healthy 21 years old female patient that presented a mild generalized tetanus requiring admission after mild and recurrent cat scratch and bites. She had received six vaccine shots during childhood, and a booster dose five years earlier after a rabbit bite. Symptoms appeared seven weeks after the last contact, and included headache, muscle spasms and mild opisthotonus. Laboratory evaluation, including CSF analysis and microbiological investigation, as well as imaging studies were all normal. The patient received 6,000 IU of human antitoxin immunoglobulin. No autonomic manifestations or respiratory compromise were registered. Symptoms resolved rapidly and she was discharge after seven days with an order to complete a tetanus toxoid immunization schedule with three doses. Conclusions. Tetanus is possible in urban settings with a declining epidemiologic curve of disease in previously immunized patients. Severity of disease is modulated by previous vaccination.

El tétanos está en declinación gracias a la vacunación, manejo profesional del parto y el cuidado apropiado de las heridas. Se han reportado casos a pesar de la inmunización. Presentamos el caso clínico de una mujer previamente sana de 21 años que presentó un tétanos generalizado leve, luego de repetidas mordeduras y arañazos de su gato. Había recibido su esquema completo de seis dosis de vacuna antitetánica en la infancia y un refuerzo hacía cinco años luego de una mordedura por conejo. Los síntomas aparecieron siete semanas después del último contacto e incluyeron cefalea, espasmos musculares y opistótonos leve. La evaluación de laboratorio, incluyendo un estudio del LCR e imágenes fueron normales. La paciente recibió inmunoglobulina humana antitetánica. No hubo manifestaciones autonómicas ni compromiso respiratorio. Los síntomas regresaron rápidamente y se dio de alta a los siete días con indicación de completar tres dosis de vacuna antitetánica. Conclusiones: El tétanos es posible en ambientes urbanos con una curva epidemiológica en descenso en pacientes previamente inmunizados. La gravedad del cuadro es modulada por la vacunación previa.

Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients.

Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia / Epidemiological and economic impact of tetanus vaccination in Colombian adults

OBJETIVO: Evaluar el potencial impacto epidemiológico y económico de la vacunación antitetánica en la población colombiana mayor de 15 años de edad, con dosis de refuerzo cada 10 años. MÉTODOS: Se realizó un análisis de costo-efectividad de la vacunación con refuerzo cada 10 años contra el tétanos en Colombia, comparándola con la actual estrategia (2, 4, 6, 18 y 60 meses). La carga de enfermedad se estimó con base en tres fuentes oficiales de datos. Se realizó un modelo de Markov desde la perspectiva del tercer pagador. El horizonte temporal fue el tiempo de vida de una persona. Se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: En Colombia se notifican anualmente entre 30 y 48 casos de tétanos que ocasionan entre 9,6 y 10,1 muertes. Si bien la vacunación con refuerzo resultó costo-efectiva para toda la población (el costo por año de vida ajustado por discapacidad [AVAD] evitado fue de US$ 11 314 en toda la población), al discriminar los resultados por género no sería costoefectiva en las mujeres (el costo por AVAD evitado en hombres fue de US$ 4 903, y en mujeres de US$ 22 332). CONCLUSIONES: Este es el primer estudio que evalúa la costo- efectividad de una dosis de refuerzo cada 10 años de la vacuna contra el tétanos en un país en desarrollo. La aplicación de esta medida sería costo-efectiva en Colombia, especialmente para los hombres. Las diferencias en los resultados por género obliga a que cualquier decisión de implementación deba tener en cuenta la vacunación actual en mujeres en edad fértil.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Perfil clínico-social das gestantes atendidas numa unidade docente-assistencial baseada no modelo de saúde da família / Clinical and social profile of pregnant women attended in a teaching-care unit based on the model of health of the family / Perfil clínico y social de las mujeres embarazadas atendidas en unaunidad docente -asistencial basado en el modelo de salud de la familia

O objetivo do estudo foi traçar o perfil clínico-social das gestantes atendidas numa unidade docente-assistencial baseada no modelo de saúde da família. Foi realizado um estudo descritivo, para o qual se utilizaram prontuários e estabeleceram-se as seguintes variáveis:idade, grau de escolaridade, peso, altura, paridade, exames laboratoriais de pré-natal, doenças identificadas no pré-natal ou anteriores à gestação, tabagismo, alcoolismo, planejamento da gravidez, aceitação da gravidez, apoio familiar, apoio do companheiro e auto imagem. Foram avaliados 104 prontuários e a média de idade das pacientes era de 24,2 maios ou menos 5,9 anos e a mediana de 24 anos. A pressão arterial (PA) tinha uma média de 105,9 mais ou menos 11,2 mmHg na sistólica e67,3 mais ou menos 10,6 mmHg na diastólica. Quanto à vacinação antitetânica, em 44,2por cento dos prontuários não havia o registro sobre a sua realização. Dos prontuários que continham o registro, 41,4por cento das gestantes tinham sido vacinadas havia menos de cinco anos, 22,4por cento entre cinco e 10 anos e 36,2por cento havia mais de 10 anos. A urocultura foi positiva em 22,9por cento. A gravidez foi planejada por 25,3por cento das pacientes, 61,1por cento tinham medo do parto. Concluiu-se que a população tem características de baixo risco gestacional, mas está exposta ao risco de bacteriúria assintomática. A estrutura corporal está com parâmetros normais. Há falhas na vacinação antitetânica. A maiorparte das gestações não foi planejada, as mulheres têm medo de apresentar problemas com o feto e têm medo do parto, contudo são apoiadas pela família.

The objective of the study was to trace the clinical profile of pregnant women from a teaching-care unit based on the model of the familyïs health. A descriptive study was carried out using charts and the following variables were studied: age, level of education, weight, height, parity, pre-natal laboratory tests, diseases identified in pre-natal or prior to pregnancy, smoking, alcoholism, planning of pregnancy, acceptance of the pregnancy, family support, support of companion and self-image. One-hundred and four medical records were evaluated and the average age of the patients was 24.2 more or less 5.9 years and a median of 24years. Blood pressure (BP) was an average of 105.9 more or less 11.2 mmHg for systolic and 67.3 more or less 10.6 mmHg for diastolic blood pressure. There was no record of tetanus vaccination in 44.2percent of the records. Of the medical records that recorded a vaccination, 41.4percent of pregnant women had been vaccinated had records that were less than five years-old, 22.4percent of the records were between five and 10 years-old and 36.2percent were older than 10 years. Urine culture was positive in 22.9percent of cases. Pregnancy was planned by 25.3percent of the patients, 61.1percent were afraid of childbirth. It was concluded that the population has the characteristics of low-risk pregnancy, but is exposed to the risk of asymptomatic bacteriuria. The body structurewas within normal parameters. There are flaws in tetanus vaccination. In large part, the pregnancies were not planned, the women were afraid to present problems with the fetus, and they were afraid of giving birth, however they were supported by a family.

El objetivo del estudio fue trazar el perfil clínicosocial de las mujeresembarazadas atendidas en una unidad escuelaasistencial basada en el modelo de salud de la familia. Estudio de tipo descriptivo, para el cual se utilizaron históricos médicos estableciendo las siguientes variables: edad, nivel de educación, peso, talla, paridad, pruebas de laboratorio, prenatal, enfermedades identificadas en el prenatal o antes del embarazo, tabaquismo, alcoholismo, planificación prenatal, aceptación del embarazo, apoyo familiar, apoyo del compañero y su autoimagen. Fueron evaluados 104 históricos médicos y el promedio de edad de los pacientes era 24,2 más o menos 5,9 años y una mediana de 24 años. La presión arterial (PA) presentó un promedio de 105,9 más o menos 11,2 mmHg para la sistólica y 67,3 más o menos 10,6 mmHg para la diastólica. En cuanto a la vacunación contra el tétanos, en 44,2por ciento de los históricos no había constancia de su aplicación. Los históricos médicos que contienen que contienen dicho registro, 41,4por ciento de las mujeres embarazadas habían sido vacunadas en un periodo menor de cinco años, 22,4por ciento entre 5 y 10 años y 36,2por ciento hacía más de 10 años. El análisis de orina fue positivo en 22,9por ciento. El embarazo fue planeado por 25,3por ciento de las pacientes, 61,1por ciento tenían miedo del parto. Se concluye que la población tiene características de bajo riesgo de preñez, pero está expuesta al riesgo de la bacteriuria asintomática. La estructura corporal está con los parámetros normales. Hay fallas en la vacunación contra el tétanos. La mayor parte de los embarazos no fueron planeados, las mujeres tienen miedo de tener un feto con problemas, así como miedo al parto. Sin embargo, reciben apoyo familiar.

Proteção do recém-nascido contra o tétano pela imunização ativa da gestante com antitoxina tetânica: estudo original de 1953 / Protection of newborn infants against tetanus by active immunization of the pregnant women with tetanus antitoxin: the 1953 original study

OBJETIVO: Determinar, em cobaias prenhes e em gestantes, a produção de antitoxina tetânica induzida pela aplicação da anatoxina tetânica e estudar a sua passagem para o recém-nascido. MÉTODOS: Na primeira fase, em estudo experimental, cobaias prenhes foram vacinadas com duas doses de toxóide tetânico em um intervalo de 15 dias, seguida da dosagem de anticorpos na cobaia imunizada, na prole ao nascer e 15 dias após o nascimento. Outro grupo de animais previamente vacinado recebeu uma dose de reforço 30 dias antes do parto, medindo-se o nível de anticorpos na cobaia e na prole. Na segunda fase, em ensaio clínico, as gestantes humanas foram vacinadas com três injeções de anatoxina tetânica, com um intervalo de 30 dias, em qualquer período da gravidez, medindo-se, a seguir, a antitoxina tetânica. Nos recém-nascidos, os anticorpos foram medidos ao nascer e aos 15 dias de vida. RESULTADOS: O título de antitoxina no sangue da prole de cobaias vacinadas com anatoxina tetânica foi elevado ao nascimento e aos 15 dias de vida. A dose de reforço provocou elevação do título basal. Nas gestantes, a aplicação de três doses de toxóide antitetânico conferiu imunidade a 95% dos recém-nascidos estudados. Os recém-nascidos de mães vacinadas apresentaram títulos elevados de antitoxina que persistiram por mais de 15 dias de vida. CONCLUSÕES: A vacinação durante a gestação foi acompanhada de títulos protetores de antitoxina contra o tétano tanto nos filhotes de cobaias quanto nos recém-nascidos humanos.

OBJECTIVE: To measure, in pregnant guinea pigs and women, the production of tetanus antitoxin, induced by vaccination with tetanus toxin, and to study the transmission of these antibodies to the offspring. METHODS: In an experimental design, pregnant guinea pigs were vaccinated with two doses of tetanus toxoid with a 15-day interval followed by determination of antibodies in the immunized guinea pig, in the offspring at birth and after 15 days of life. One group of guinea pigs received a booster dose of tetanus toxoid 30 days before delivery and the immunization status of dam and offspring was also studied. In a clinical trial, pregnant women were vaccinated in any period of gestation with three doses of tetanus toxoid with a 30-day interval; the antibody levels were measured in the mother and in the newborn infant at birth and at the 15th day of life. RESULTS: The antibody levels of guinea pigs offspring immunized with tetanus toxoid during gestation were elevated at birth and at the 15th day of life. These levels were elevated by the booster dose 30 days prior to delivery. In pregnant women, the immunization with three doses of tetanus toxoid was followed by immunity in 95% of the studied infants studied. The newborn infants of vaccinated women presented elevated levels of antibodies at birth and at 15th day of life. CONCLUSIONS: Vaccination during gestation was followed by protective levels of antibodies in guinea pigs and in newborn infants.

Yolanda Irureta de Milá de la Roca Creadora del Fermentador "Caracas" Valioso aporte en la lucha contra el tétano en Venezuela

Yolanda Irureta Story de Milá de la Roca nació el 9 de enero de 1923 en Puerto España (Trinidad). Ocupó diversos cargos en el Instituto Nacional de Higiene, en la División de Elaboración de Productos Biológicos, en las secciones de Vacuna Antivariólica y Toxoide Tetánico, así como en el Departamento de Vacunas Bacterianas, ocupando el cargo de Microbiólogo Jefe hasta su jubilación en 1983. En la década de los setenta, Yolanda Irureta y su equipo asumen el reto de aumentar la producción de Toxoide Tetánico para satisfacer la creciente demanda de este producto, por parte del Ministerio de Sanidad y Asistencia Social (MSAS). Después de 18 meses de trabajo creativo lograron desarrollar un equipo bautizado como Fermentador "Caracas", el cual permitió triplicar la producción de Toxoide Tetánico. El aspecto más resaltante de esta adaptación radica en su sencillez y facilidad de fabricación, el bajo costo de sus componentes y la facilidad de mantenimiento. En aquella ocasión, el Presidente de la República donó el exceso de producción a Costa Rica, Honduras y Bolivia. En 1977, los expertos de la Organización Mundial de la Salud consideraron al laboratorio de Toxoide Tetánico del Instituto Nacional de Higiene "Rafael Rangel" (INH "RR") como el mejor de América Latina. Debido a su valiosa contribución a la tecnología, el CONICIT les otorgó el Premio de Desarrollo Tecnológico, en el año 1979. El 9 de marzo de 1982, el Fermentador "Caracas" logra obtener la patente número 4.318.992, en USA, asegurando así que el INH "RR" conserve los derechos legales sobre esta tecnología, y se reconozca la propiedad intelectual a sus verdaderos autores.

Yolanda Irureta Story de Milá de la Roca was born on January 9, 1923 in Port of Spain, Trinidad. She joined the National Institute of Hygiene (NIH), as a staff member of the Division that manufactures human vaccines. Through the years she was promoted to various positions in the Smallpox Vaccine and Tetanus Toxoid Units, being Head of the Department of Bacterial Vaccines until her retirement in 1983. During the seventies, the Ministry of Health and Social Assistance increased their demand of Tetanus Toxoid. To fulfill this need, Yolanda Irureta and her team faced this challenge, working 18 months to develop a fermentor that allowed them to triplicate the production. The fermentor was named "Caracas" Fermentor and it has many important features. It is simple and economic; it is made up of parts that are easy to obtain and the maintainance cost are very low. At that time, the Venezuelan President donated the surplus of production to Costa Rica, Honduras and Bolivia. In 1977, experts of the World Health Organization considered the Tetanus Toxoid laboratory of National Institute of Hygiene "Rafael Rangel" (NIH"RR"), the best in Latin America. Due to their valuable contribution to technology, they received the 1979 CONICIT Award for Technological Development. On March 9, 1982, it was granted to the Caracas Fermentor, the U.S.A. patent number 4.318.992, securing to the NIH"RR" the exclusive rights to this technology and the intellectual property to theirs authors.

Situação vacinal daas mães de crianças que morreram por tétano neonatal em Minas Gerais, Brasil (1997-2002) / Vaccine status of mothers of children who died of neonatal tetanus in Minas Gerais, Brazil(1997-2002) / Situación vacunal de las madres de niños muertos por tétanos neonatal en Minas Gerais, Brasil (1997-2002)

Neste artigo buscou-se compreender, por meio do discurso de 19 mães de crianças que morreram por tétano neonatal no Estado de Minas Gerais, entre 1997 e 2002, as representações sobre os meios de prevenção da doença, destacando-se a vacina antitetânica, considerada o meio mais eficaz de proteção. Observou-se, entre outros achados, que um número significativo de mulheres em idade fértil, mesmo após vários anos do óbito do recém-nascido, permanecia sem o número de doses suficientes para proteção contra tétano neonatal e tétano acidental, o que aponta para oportunidades perdidas de vacinação.

This article intended to understand, by analyzing the discourse of 19 mothers of children who died from neonatal tetanus in the State of Minas Gerais, 1997-2002, the means of preventing the disease, especially anti-tetanus inoculation, which is considered the most effective protection. Among other findings, it was noted that a significant number of women at a fertile age, even many years after the death of their babies, had not had the necessary doses of vaccination against neonatal and accidental tetanus. This shows a loss of opportunities for vaccination.

La finalidad de este artículo fue comprender, por medio del discurso de 19 madres de niños que murieron por tétanos neonatal en el Estado de Minas Gerais entre 1997 a 2002, las representaciones sobre los medios de prevención de la enfermedad. Se destaca la vacuna antitetánica, considerada como el medio más eficaz de protección. Entre otros aspectos se observa que un número significativo de mujeres en edad fértil, aún varios años después del óbito del recién nacido, seguían sin el número de dosis suficientes para protección del tétanos neonatal y tétanos accidental, lo que indica que se pierden oportunidades de vacunación.

Obtención de la toxina tetánica a partir de hidrolizado de caseina de producción nacional

La producción de toxoide tetánico se realiza a partir de la toxina tetánica destoxificada y purificada por métodos químicos. Un buen rendimiento de la toxina tetánica reviste gran importancia, pues éste es fundamental para obtener el número de dosis necesarias a un bajo costo. Se presentan los resultados obtenidos en la producción de toxina tetánica a partir de hidrolizado de caseína de producción nacional, mediante la realización de pruebas químicas, microbiológicas e inmunológicas, y se comprueba que el rendimiento es superior al obtenido con el hidrolizado de caseína de importación (triptona T, Oxoid).

The production of the tetanus toxoid is developed from the chemically detoxified and purified tetanus toxin. A good yielding of the tetanus toxin has a great importances, since it is fundamental to obtain the amount of necessary doses at a low cost. Here the authors present the results of the production of the tetanus toxin from the nationally produced casein hydrolysate, through chemical, microbiological, and immunological tests, and it is confirmed that the yield is higher than the one obtained with the imported casein hydrolysate (triptone T, Oxoid).