Reações de hipersensibilidade a vacinas / Hypersensitivity reactions to vaccines

O desenvolvimento e a ampliação do uso das vacinas durante décadas contribuíram para o controle e erradicação de doenças infecciosas, causando um grande impacto na saúde pública no mundo. A análise de segurança das vacinas percorre criteriosos processos e fases dos estudos clínicos, um dos pilares essenciais para aprovação regulatória e utilização do produto na população. O evento supostamente atribuído à vacinação e imunização (ESAVI), terminologia atual, é definido como qualquer ocorrência médica indesejada após a vacinação que possui, ou não, uma relação causal com o uso de uma vacina ou outro imunobiológico. Cabe ressaltar que eventos adversos mais raros ou inesperados, incluindo os eventos de hipersensibilidade, poderão ocorrer na fase pós-comercialização, quando as vacinas são aplicadas em milhões de pessoas. Neste artigo, serão discutidos os principais aspectos relacionados aos eventos adversos de hipersensibilidade pós-vacinais de interesse do especialista, e os desafios frente ao reconhecimento do agente causal e conduta a ser adotada. Além disso, serão revisados os potenciais alérgenos presentes nas vacinas de uso rotineiro para auxiliar o profissional de saúde na identificação de pacientes com potencial de risco de ESAVI por tais componentes. A atualização do conhecimento acerca da segurança e dos benefícios das vacinas pelos profissionais de saúde, sobretudo em populações especiais, contribui para condutas em imunização mais apropriadas, reduzindo o risco de exposição a um possível alérgeno em pessoas comprovadamente alérgicas às vacinas ou a alguns dos seus componentes, além de evitar contraindicações desnecessárias em eventos coincidentes ou não graves.

The expansion of vaccine use and development in recent decades has contributed to the control and eradication of infectious diseases, causing a major impact on public health worldwide. Vaccine safety analysis, which involves careful processes and clinical study, is one of the essential pillars of regulatory approval and use in the population. In current terminology, events supposedly attributable to vaccination and immunization (ESAVI) are defined as any unwanted medical occurrence after vaccination that may or may not have a causal relationship with vaccines or other immunobiologicals. It is noteworthy that rare or unexpected adverse events, including hypersensitivity, can occur during the post-marketing phase, when vaccines are administered to millions of people. In this article, we will discuss the main aspects of post-vaccine hypersensitivity events of interest to specialists and challenges to recognizing the causal agent and appropriate clinical practice. Potential allergens in routine vaccines will also be reviewed to help health professionals identify patients with a potential risk of ESAVI due to such components. Updating health professionals' knowledge about the safety and benefits of vaccines, particularly in special populations, can contribute to more appropriate clinical practice regarding immunization, reducing the risk of exposure to possible allergens in people with allergies to vaccines or their components, avoiding unnecessary contraindications in coincidental or non-serious events.

Evaluation of Immunogenicity and Safety of the New Tetanus-Reduced Diphtheria (Td) Vaccines (GC1107) in Healthy Korean Adolescents: A Phase II, Double-Blind, Randomized, Multicenter Clinical Trial

This phase II clinical trial was conducted to compare the immunogenicity and safety of a newly developed tetanus-reduced diphtheria (Td) vaccine (GC1107-T5.0 and GC1107-T7.5) and control vaccine. This study was also performed to select the proper dose of tetanus toxoid in the new Td vaccines. Healthy adolescents aged between 11 and 12 yr participated in this study. A total of 130 subjects (44 GC1107-T5.0, 42 GC1107-T7.5 and 44 control vaccine) completed a single dose of vaccination. Blood samples were collected from the subjects before and 4 weeks after the vaccination. In this study, all subjects (100%) in both GC1107-T5.0 and GC1107-T7.5 groups showed seroprotective antibody levels (> or = 0.1 U/mL) against diphtheria or tetanus toxoids. After the vaccination, the geometric mean titer (GMT) against diphtheria was significantly higher in Group GC1107-T5.0 (6.53) and GC1107-T7.5 (6.11) than in the control group (3.96). The GMT against tetanus was 18.6 in Group GC1107-T5.0, 19.94 in GC1107-T7.5 and 19.01 in the control group after the vaccination. In this study, the rates of local adverse reactions were 67.3% and 59.1% in GC1107-T5.0 and GC1107-7.5, respectively. No significant differences in the number of adverse reactions, prevalence and degree of severity of the solicited and unsolicited adverse reactions were observed among the three groups. Thus, both newly developed Td vaccines appear to be safe and show good immunogenicity. GC1107-T5.0, which contains relatively small amounts of tetanus toxoid, has been selected for a phase III clinical trial.

Tétano acidental no idoso: situação em Minas Gerais / Accidental tetanus among the elderly: situation in Minas Gerais

O tétano é uma doença infecciosa, não contagiosa, causadapelo Clostridium tetani,que, embora atualmente seja apontadocomo passível de erradicação, ainda gera grandes impactoshumanos, sociais e econômicos principalmente sobre osidosos. Realizou-se um estudo de caráter descritivo, cujoobjetivo foi conhecer o perfil epidemiológico dos casosconfirmados de tétano acidental em idosos, comparado àpopulação geral, no Estado de Minas Gerais, nos anos de2001 a 2006, identificando variáveis associadas às diferençasna distribuição da incidência e letalidade da doença. Dos225 casos da doença notificados à Secretaria de Estado daSaúde de Minas Gerais por meio do Sistema de Informaçõesde Agravos de Notificação, 84 (37,3%) ocorreram emidosos, de modo que a incidência entre os idosos varioude 0,46 (2006) a 1,07 casos por 100.000 habitantes (2003),sendo a média 0,83 casos por 100.000 habitantes. A incidênciaentre os idosos mostrou-se superior à registradanas demais faixas etárias, exceto no ano 2006. O sexomasculino foi o grupo mais atingido em todas as faixasetárias. Nos idosos, observa-se que as atividades que maisse destacaram foram: aposentado, do lar e trabalhadoresrurais, e que 44,0% deles adquiriram o bacilo na própriaresidência. A letalidade da doença entre eles foi 46,4%,mostrando-se superior à média para o período estudadoque é de 36,9%. O coeficiente de mortalidade por tétanoacidental nos idosos (0,39 óbitos/ 100.000 hab.) é cerca deseis vezes maior do que a média na população total (0,07óbitos/100.000 hab.). Constatou-se que o idoso é o grupopopulacional mais susceptível a adoecer e morrer pelo tétanono Estado. É necessária a intensificação das ações deimunoprofilaxia, evitando-se as oportunidades perdidas devacinação de modo a obter a prevenção e o controle desseimportante agravo em saúde pública.

Tetanus is a non-contagious infectious disease caused by Clostridium tetani. Although there are now indications that eradication of tetanus is possible, it continues to have a large human, social and economic impact, particularly among the elderly. A descriptive study was conducted with the aims of ascertaining the epidemiological profile of confirmed cases of accidental tetanus among elderly individuals, compared with the general population, in the state of Minas Gerais between 2001 and 2006, and identifying variables possibly associated with the differences in the incidence and fatality rates of the disease. There were 225 cases of the disease registered in the Notifiable Disease Information System of the Minas Gerais State Health Authority. Of these 225 cases, 84 (37.3%) occurred among elderly people. The incidence among the elderly ranged from 0.46 to 1.07 cases per 100,000 inhabitants (2006 and 2003, respectively), with a mean of 0.83 cases per 100,000 inhabitants. The incidence among the elderly was greater than what was registered among other age groups, except in 2006. Males were the group most affected in all age groups. Among the elderly, most were retired, worked in their own homes or were rural laborers. 44.0% of them acquired the bacillus in their own homes. The case-fatality rate was 46.4% among the elderly people, which was higher than the general mean for the study period (36.9%). The mortality coefficient for accidental tetanus among the elderly (0.39 deaths/100,000 inhabitants) was around six times greater than that for the general population (0.07 deaths/100,000 inhabitants). We concluded that elderly people are the population group most susceptible to becoming ill with and dying from tetanus in the state of Minas Gerais. It is necessary to intensify the immunoprophylactic measures, in order to avoid missed opportunities for vaccination and achieve prevention and control of this important public health hazard.

Prevenção de acidentes com material biológico entre estudantes de enfermagem / Prevención de accidentes con material biológico entre estudiantes de enfermería / Prevention of accidents involving biological material among nursing students

Trata-se de estudo descritivo, epidemiológico, com abordagem quantitativa, que buscou investigar situação vacinal, recebimento de informações sobre biossegurança, fatores que favorecem a ocorrência de acidentes com material biológico e sugestões para preveni-los. Um questionário autoaplicável foi respondido por 355 estudantes de enfermagem de três instituições de ensino superior do interior paulista, em 2007. Quanto à vacinação, 310(87,3%) apresentavam esquema completo contra hepatite B e 336(94,7%) contra difteria e tétano; 330(93%) estudantes receberam informações sobre biossegurança antes do início das atividades práticas; 294(82,9%) responderam que existem fatores ambientais ou psicossociais que favorecem a ocorrência de acidentes; 76(21,4%) sugerem a educação permanente/continuada como forma de prevenção e outros 70(19,7%) o uso de equipamento de proteção individual e conscientização sobre seu uso. Instituições de ensino e saúde devem prestar atenção nas condições de aprendizado do aluno em campo de ensino prático.

This quantitative, descriptive, epidemiological study investigated vaccination status, receipt of biosafety information, factors favoring accidents with biological material, and suggestions for accident prevention. A self-applied questionnaire was answered by 355 nursing students from three higher education institutions in Sao Paulo in 2007. As regards vaccination, 310 students (87.3%) had received the complete schedule against hepatitis B and 336(94.7%), against diphtheria and tetanus; 330(93%) had received biosafety information before starting practical activities; 294(82.9%) responded that psychosocial and environmental factors can favor the occurrence of accidents; 76(21.4%) suggested permanent/continuous education as a means of prevention; and 70(19.7%) suggested using personal protective equipment and awareness-building on such use. Educational and health institutions should to give attention to student learning conditions during practical teaching.

Es un estudio descriptivo, epidemiológico, con enfoque cuantitativo, que buscó investigar el estado de vacunación, recepción de información sobre bioseguridad, factores que favorecen ocurrencia de accidentes con material biológico y sugerencias para evitarlos. Un cuestionario autoaplicado fue respondido por 355 estudiantes de enfermería de tres instituciones de educación superior en Sao Paulo-Brasil, en 2007. Cuanto a la vacunación, 310(87,3%) presentaban el programa completo contra hepatitis B y 336(94,7%) contra difteria y tétano; 330(93%) estudiantes recibieron información sobre bioseguridad antes del inicio de las actividades prácticas; 294(82,9%) respondieran que existen factores psicosociales y ambientales que favorecen la ocurrencia de accidentes; 76(21,4%) sugieren educación continuada como medio de prevención y otros 70(19,7%) el uso de equipo de protección personal y sensibilización sobre su uso. Instituciones educativas y de salud deben prestar atención a las condiciones de aprendizaje de los estudiantes en el campo de la enseñanza práctica.

Eventos adversos pós-vacina dupla adulto em trabalhadores da construção civil / Eventos adversos post vacuna doble adulto en trabajadores de la construcción civil / Adverse events post adult diphtheria-tetanus vaccination on civil construction workers

Estudo longitudinal prospectivo sobre avaliação da ocorrência de reações no sítio de aplicação da vacina dupla adulto contra difteria e tétano (dT) realizado no município de Três Lagoas, MS, no período de setembro a outubro de 2008. Participaram 1291 trabalhadores de uma empresa de construção civil, com idade de 18 a 68 anos, cujas vacinas foram administradas sem antissepsia prévia do local de aplicação. As reações adversas foram avaliadas 48 horas após o procedimento. Diante das avaliações, não se constataram eventos adversos locais pós-vacinação sendo que em apenas dois casos houve relato de linfadenopatia na região axilar. O estudo apresentou evidências que corroboram as recomendações do Ministério da Saúde relativas a essa prática vacinal.

This longitudinal prospective study aimed at assessing the occurrence of reactions to adult diphtheria-tetanus vaccine (dT) in the application site, carried out in Três Lagoas,MS, Brazil between September and October, 2008 Participants totaled 1,291 workers from a civil construction enterprise aged between 18 and 68, who were vaccinated without previous skin antisepsis of the application site. Adverse reactions were evaluated 48 hours after the procedure. The assessment did not show adverse events on the site after vaccination, and only two cases were reported for lymphadenopathy in the axillary region. The study presented evidence that support the recommendations of the Ministry of Health related to this vaccination practice.

Estudio longitudinal prospectivo que objetivó evaluar la ocurrencia de reacciones en el sitio de aplicación de la vacuna doble adulto (dT), realizado en la ciudad de Três Lagoas, MS, Brasil, entre setiembre y octubre de 2008. Participaron 1291 trabajadores de una empresa de construcción civil, con edad entre 18 y 68 años, cuyas vacunas fueron aplicadas sin antisepsia previa del sitio de aplicación. Las reacciones adversas fueron evaluadas 48 horas después del procedimiento. Ante las evaluaciones, no se constataron eventos adversos locales post-vacunación, siendo que solo en dos casos hubo relato de linfadenopatía en la región axilar. El estudio presentó evidencias que corroboran las recomendaciones del Ministerio de la Salud relativas a esa práctica de vacunación.

Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level ( or =0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

The immunogenicity and reactogenicity of Td booster vaccination in Korean preadolescents, aged with 11-12 years old / 소아과

PURPOSE: This study was undertaken to evaluate the immunogenicity and reactogenicity of Td booster immunization in early preadolescents of Korea. METHODS: Healthy preadolescents, who had been vaccinated with 4 or 5 doses of DTaP vaccines until 6 years old age, were enrolled in this study from August 2006 to April 2007 . Diphtheria and tetanus anti-toxoid antibodies in sera were measured by ELISA just before vaccination and 4 weeks after vaccination to evaluate immunogenicity. Local and systemic adverse reactions observed for 4 weeks after vaccination to access reactogenicity. RESULTS: 183 preadolescents were enrolled and mean age was 11.40+/-0.51 years old. All subjects achieved seroprotective diphtheria and tetanus anti-toxoid antibodies (titers > or =0.1 IU/mL) after Td booster vaccination. Among 183 vaccinees, 73.8% showed local adverse reactions and 37.2% systemic adverse reactions. Pain at injection site (66.1%) was the most common local reaction, and the most commonly shown systemic reaction was myalgia (17.5%). The adverse reactions were spontaneously relieved within three days after vaccination. CONCLUSION: Td vaccine in this study was high immunogenic and showed an acceptable tolerance in Korean preadolescents. Td booster vaccination at 11 -12 years old is the most effective method to increase compliance of the vaccination and to decrease the incidence of diphtheria and tetanus.

Application of fermentor technology in production of diphtheria toxin

The present study shows the production of diphtheria toxoid in fermentor as compared to old static method of production. With using 451 glass fermentor which has the provision for growth of the organisms under controlled conditions with regard to temperature, pH, aeration and addition of maltose which can be automatically monitored and maintain microorganism growth toxin production and recording all of the conditions during growth. We succeeded to produce diphtheria toxin with 115 Lf [Rammon flucolation titer] within 40h time period in a minimum possible space, then the toxin was detoxified with formaldehyde, concentrated and purified and finally quality controlled and compared with toxin produced with static method. Fermentor production showed a remarkable increase in volume, titer and immunogenecity in a shorter period of time, lower contamination and minimum labor work and requirements. Therefore this technique can be industrially used for production of diphtheria Toxin [DT] and Diphtheria Pertussis Toxin [DPT] vaccines

Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1 percent of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9 percent were fully protected (antibodies ³0.1 IU/mL). One individual (0.5 percent) was non-immune to diphtheria and 86 percent were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001) and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014). Full immunity against tetanus (antibodies ³0.1 IU/mL) was higher among individuals with up-to-date vaccination (93.1 percent) when compared to those with not up-to-date records (75 percent, Fisher's exact test: P = 0.001). All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001) and for diphtheria (r² = 0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Administration of tetanus toxoid [TT] to pregnant women versus tetanus and reduced diphtheria [Td]: a randomized controlled

We conducted a clinical trial to compare the immunogenicity, reactogenicity and efficacy of Tetanus Toxoid [TT] and the combined Tetanus and reduced Diphtheria [Td] in pregnant women residing four rural communities in Egypt. The study has been designed as a randomized controlled trial. Pregnant women in each of the four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured by the Egyptian Company for Biological Products and Vaccines [VACSERA] in Egypt. A total of 131 pregnant women were enrolled at the time of their antenatal care visit [at the beginning of their fifth gestational month] to one of four health units in Abu Homos district, Beheira Governorate, Egypt. Previously un-immunized women received at random 2 doses of TT or Td eight weeks apart during their pregnancy. Active outpatient follow-up for adverse events was done on the third day after each dose. Local [pain, redness and swelling] or general [fever, malaise and headache or body aches] reactions during the 3-day post-dosing interval served as the primary safety end point. Blood was collected 3 times from each subject to detect antibody level against tetanus and diphtheria by ELISA. The first sample was collected immediately before the first dose, the second before the 2[nd] dose and the third sample one week after delivery. Active surveillance home visits to all study participants were conducted twice. The first home visit was during the first week after delivery and the second one month after labor to report the health status of the mother and the baby. A total of 122 pregnant women received 2 correct doses had inter-dose intervals within the allowable range and provided 3 samples of blood, were included in per protocol analysis [62 in the TT group and 60 in the Td group]. There was no statistically significant inter group difference in the percentage of subject reporting the primary safety endpoint [fever, malaise, body ache, headache] or local reactions at the site of injection as redness and swelling, during the 3-day after each dose. There was a statistically significant greater reporting of pain at injection site in the Td group after dose I and II compared to the TT group. Home visits revealed normal mothers and babies on clinical examination in both groups. However, more babies in the TT group suffered from physiological jaundice. All women in the two groups acquired protective immunity for tetanus, determined as possession of neutralizing antibodies at titre>0.10 IU/ml after completing vaccination. However, the geometric mean titres of tetanus post dose I and II were significantly higher in vaccinees in the TT group [P<0.001]. For diphtheria, post vaccination seroprotection [titre>0.10 lU/ml] was significantly higher in the group received Id than the TT group. Geometric mean Titres of diphtheria post dose II were significantly higher in vaccinees in the Td compared to the other group [P<0.0001]. These finding demonstrared that the use o Td vaccine improves immunogenicity for both tetanus and diphtheria over the use of 'IT vaccine alone and may be recommended to replace TT in immunization of pregnant women.

Actualización de la situación epidemiológica de difteria, tétanos y tétanos neonatal / Update of the epidemiological situation in diphtheria, tetanus and neonatal tetanus

La difteria es una enfermedad producida por el bacilo Corynebacterium diphtheriae, gram positivo aerobio no esporulado, no encapsulado e inmóvil. Es de distribución mundial y con brotes epidémicos en algunos países. Es una enfermedad bacteriana, inmunoprevenible y de notificación universal, obligatoria e inmediata en Chile. En nuestro país la historia natural de la enfermedad cambió drásticamente con la introducción de las vacunas pertussis toxoide diftérico (D.T) en el año 1955 y posteriormente la incorporación de toxoide tetánico en el año 1974 (D.P.T.). El inicio de la disminución en la curva epidemiológica se presenta aproximadamente desde 1961, pero el marcado decrecimiento se registra en el año 1967 (7,4 casos por 100.000 hab.). El año 1996 registra el último caso en una niña de 1 año. Sin duda los avances en la salud pública chilena, particularmente las coberturas de vacunación óptimas, deben ser sostenidos en el tiempo. El tétanos es una enfermedad aguda inmunoprevenible inducida por una exotoxina del bacilo Clostridium tetani, bacilo gram positivo, anaerobio y formador de esporas. Es de notificación universal, obligatoria y diaria en Chile. Es de distribución mundial y con brotes epidémicos en algunos países. En Chile la historia natural de la enfermedad cambió drásticamente con la introducción de las vacunas pertussis y toxoide diftérico (D.T.) y pertussis, toxoide diftérico, toxoide tetánico (D.P.T.). Se comenzó a aplicar la vacuna D.T en el año 1955, y el año 1974 la D.P.T. El inicio de la disminución en la curva epidemiológica se presenta aproximadamente desde 1964, pero el marcado decrecimiento se registra en el año 1966 (0,5 casos por 100.000 hab.). El año 2006 registra una tasa de 0,04 casos por 100.000 hab., con una tendencia a la concentración de casos a nivel de las regiones de Los Lagos, Coquimbo y Araucania. No se han registrado casos de tétanos neonatal desde el año 1996.

Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil

Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20°C until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18 percent of the individuals were susceptible to diphtheria and 94 percent were susceptible to tetanus. After one Td dose, 78 percent became fully immune to diphtheria, 13 percent attained basic immunity, and 9 percent were still susceptible to the disease. In contrast, 79 percent remained susceptible to tetanus, 4 percent had basic immunity and 17 percent were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

Immunogenicity test of tetanus component in adsorbed vaccines by toxin binding inhibition test

Samples from 20 lots of diphtheria-tetanus (adult use dT) vaccine and from 20 lots of diphtheria-tetanus-pertussis (DTP) vaccine were used to standardize and validate the in vitro toxin binding inhibition (ToBI) test for the immunogenicity test of the tetanus component. The levels of tetanus antitoxin obtained by ToBI test were compared to those obtained using the toxin neutralization (TN) test in mice routinely employed to perform the quality control of the tetanus component in adsorbed vaccines. The results ranged from 1.8 to 3.5 IU/ml for dT and 2 to 4 IU/ml for DTP by ToBI test and 1.4 to 3 IU/ml for dT and 1.8 to 3.5 IU/ml for DTP by TN in mice. These results were significantly correlated. From this study, it is concluded that the ToBI test is an alternative to the in vivo neutralization procedure in the immunogenicity test of the tetanus component in adsorbed vaccines. A substantial refinement and a reduction in use of animals can be achieved

An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.