Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6 percent and 98.4 percent of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100 percent seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7 percent, 100 percent and 99.9 percent, respectively, for DTP/Hib-BM, three lots altogether and 99.2 percent, 100 percent and 100 percent for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil

The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and ³60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies ³0.1 IU/mL) was present in 84 percent of the individuals, 15 percent had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 1 percent were susceptible (antibodies <0.01 IU/mL). Full tetanus protection (antibodies ³0.1 IU/mL) was present in 79 percent of the participants, 18 percent had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 3 percent were susceptible (antibodies <0.01 IU/mL). The geometric mean of diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8 percent) were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.

Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population.

Placental malaria infection jeopardizes pregnancy outcome, and its influence may also impair the transplacental transfer of some antibodies. Two hundred and thirteen Gambian mother-baby pairs were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinaemia on transplacental transfer of measles and tetanus antibodies in Gambian population. Placental blood and tissue were collected for placental malaria diagnosis. Cord and maternal sera were tested for total IgG concentration by laser nephelometry and for IgG antibody to tetanus toxoid and measles by ELISA. The prevalence of placental malaria infection was 51.1%. Mothers whose placentae were parasitized had a significantly higher mean total serum IgG (22.0 g/L vs 11.3 g/L, p < 0.001) and measles antibody level (4.02 IU/mL vs 1.21 IU/mL, p < 0.01), but not tetanus antibody, than mothers with non-parasitized placentae. Results of multiple regression analysis showed that placental malaria infection and maternal hypergammaglobulinaemia were associated with the reduction of 72% (95% CI 67.84) and 86% (95% CI 76.91) in transplacental transfer of measles antibody respectively but did not influence the transfer of tetanus antibody. It is concluded that the combined influence of placental malaria infection and maternal hypergammaglobulinaemia is significantly associated with the transfer of impaired measles antibody in this population.

Serological response to immunization with tetanus toxoid.

A total of two hundred women were immunized with tetanus toxoid vaccine. Two batches of toxoid prepared at the Institute of Public Health (IPH), Dhaka and one batch of imported vaccines, were being used by the EPI in Bangladesh for immunization. Each hundred women were immunized by IPH and imported vaccine. Two human doses were given in one month interval. Blood samples from all the study subjects were collected on the day of 1st dose and one month after second dose. Both the preimmunized sera and the sera after vaccination were tested to determine the antibody titre against tetanus toxoid by the haemagglutination method. The preimmunized sera showed the presence of protective antibody in 50(25%) subjects who had the history of previous immunization. Including these initial antitoxin positive cases the seroconversions found among 95% and 96% of the study population respectively after immunization with IPH and imported toxoids, which were 93.05% and 94.87% when these 50 subjects were excluded. No significant difference (p = 1.0) was observed between the immunity of the subjects after receiving IPH and imported vaccine. Antibody titre of initial tetanus-antitoxin positive cases raised eight folds after getting more doses. The result gave fair indication of the antigenicity of all the toxoids used in the study.

Vaccines: World Health Organization versus Federal Drug Administration recommended formula

Vaccines produced in accordance with WHO formulas, differ in concentration from those used in United States according to FDA formulas. We aimed to compare the immunogenicity of both formulas. Infants who were 6 weeks old were randomly put into 3 groups to receive 3 doses of vaccines at 6 weeks, 3 months and 5 months of age. The vaccines consisted of Haemophilus influenzae type b vaccine, diphtheria-tetanus-pertussis and oral polio vaccine. Antibody levels for polyribosylribitol phosphate [PRP], tetanus, diphtheria and poliovirus were measured 1 month after the third dose of vaccines. Although diphtheria and tetanus antigens in the FDA formula are half the concentration of the WHO formula, anti-tetanus and anti-diphtheria antibodies were significantly higher. No difference was found between groups regarding oral poliovirus vaccine

Production of an effective anti-Bothrops-tetanus mixed hyperimmune serum of equine origin

The present investigation reveals the possibility of simultaneous immunization of horses with Bothrops or Crotalus snake venoms and Tetanus antigens for the production of anti-Bothrops-Tetanus or anti-Crotalus-Tetanus mixed serum, with high titers of the respective specific antibodies. Bothrops antivenoms with an average neutralizing titer of 4.16 mg venom/ml were obtained from plasma of horses with titers lower than 0.5 mg venom/ml when Tetanus antigens were not used. This suggests the existence of a synergism between Bothrops venoms and Tetanus antigens in the stimulation of the antibody response. The pooled plasma of the animal had a neutralizing titer of 21.0 mg/ml reference Bothrops venoms and 3,300 IU/ml to Tetanus antigens after purification by enzymatic digestion and ammonium sulphate precipitation. These experiments lead us to conclude that Bothrops envenomation therapy can be successfully performed using Anti-Bothrops-Tetanus serum also serving as Tetanus prophylaxis. anti-Crotalus-Tetanus serum can also be produced, although it is not of medical interest as Crotalus envenomation rarely results in local necrotizing lesions.

Estudo clínico do tétano: revisäo; 1994 / Clinical aspects of tetanus: review

O autor fez uma revisäo sobre o tétano abordando os principais estudos referentes a etiologia, epidemiologia, patologia, diagnóstico, quadro clínico, diagnósticos diferenciais, exames laboratoriais subsidiários, tratamento, complicaçöes e profilaxias

Prevalence of diphtheria and tetanus antibodies in young adults in Delhi.

A total of 574 blood samples collected mainly from adult males, on a random basis, were tested for diphtheria and tetanus antibodies by Indirect Haemagglutination (IHA) test to find out the percentage of individuals with protective titres (> or = 0.015 IU/ml). A total of 502 (87.5 per cent) and 437 (76.2 per cent) of these had protective titres against diphtheria and tetanus respectively. The vaccination status of these subjects against diphtheria and tetanus was not ascertainable. The relevance of these findings is discussed.

Inmunidad contra el tétano en 150 madres y sus recién nacidos

El Tétano neonatal es aún una enfermedad importante que causa alta morbi-mortalidad en los niños recién nacidos en paises en vías de desarrollo como Guatemala, a pesar del alto sub-registro que se observa especialmente en áreas rurales. En Guatemala en 1985 se reportó una incidencia general de Tétanos de 2.59 por 100.000 habitantes. El objetivo principal de este estudio fue evaluar la inmunidad contra el Tétano en dos regiones: urbana, la Ciudad de Guatemala y rural en el Departamento de Zacapa. En la Ciudad de Guatemala se estudiaron 100 madres y sus recién nacidos, 50 fueron vacunados con dos dosis y 50 sin vacuna. En el área de Zacapa se estudiaron 50 madres y sus recién nacidos, 28 con dosis, 15 con una dosis y 7 sin vacuna. La inmunidad contra el Tétano se hizo determinado el título de anticuerpos anti-tetánicos con una dilución 1:20 con la Técnica del Ensayo Inmunoenzimático en Fase Solida ELISA. Los resultados de este estudio fueron en: la Ciudad de Guatemala, de 50 madres y sus recién nacidos con dos dosis el 96% tuvieron anticuerpos positivos y las 50 madres y sus recién nacidos sin vacuna el 8% tuvieron anticuerpos positivos. En el área rural de Zacapa, de las 28 madres vacunadas con 2 dosis, el 96.4% de los recién nacidos tuvieron anticuerpos positivos, de las 25 madres con una dosis el 40% de los recien nacidos tuvo anticuerpos positivos y de los 7 sin vacuna el 14% tuvo anticuerpos positivos. Este estudio demuestra que el 96% de las madres y sus recién nacidos están protegidos contra el Tétanos después de dos dosis de vacuna antitetánica durante el embarazo, con una dosis la protección de la madre y los recién nacidos baja 40% y sin vacuna tienen ambos una protección de 10%. Para el control del Tétanos es importante vacunar contra esta enfermedad a las madres antes y durante el embarazo. Si las entidades encargadas de salud en el país hacen un esfuerzo adecuado, quizá podrían erradicar el Tétanos Neonatal antes del año 2000, como es una de las metas de la OMS

Changes of Tetanus Specific IgG, IgM and IgG Subclasses after DPT Vaccination

We evaluated tetanus specific IgG, IgM, IgG subclasses after DPT vaccination in infants and children. Tetanus toxoid specific IgG, IgM IgG subclasses were measured to characterize the isotope profile of antibody against tetanus toxoid. The values of the tetanus specific IgG in the positive group were significantly increased compared to those of the control group, and were significantly increased after two inoculation. Tetanus specific IgG was very low in adults and neonates. In our tetanus specific IgG subclasses study, forty-five of 56 cases (80%) showed predominantly IgG1 antibody responses to tetanus toxoid, while twenty-five of 56 cases (45%) showed IgG4 responses. Both IgG1 and IgG4 responses were demonstrated in 17 cases (30%). So we suggest that IgG was mainly involved in humoral immune response after DPT vaccination, and IgG1 may play an important role among IgG subclasses. IgG4, alone or together with IgG1, can also play a role in immune response to tetanus toxoid.