Thimerosal exposure (from tetanus-diphtheria vaccine) during pregnancy and neurodevelopment of breastfed infants at 6 months.

AIM: We studied the effect on neurodevelopment of infants who are exposed to thimerosal in tetanus-diphtheria (Td) vaccines during pregnancy. METHODS: We compared Gesell Developmental Schedules (GDS) of exclusive breastfed infants at 6 months born to mothers who received Td (1 to 3 doses) against those who were born to mothers who did not take such vaccines. RESULTS: Compared with the group of infants not exposed to ethylmercury in utero, the infants of exposed mothers showed no significant difference in neurodevelopment delays. Although there was a significant correlation between hair-Hg of mothers and hair-Hg of neonates (Spearman r = 0.353; p = 0.0011), there was no significant correlation between the level of in utero exposure to ethylmercury in Td vaccines and neonate's hair-Hg concentrations (Spearman r = 0.060; p = 0.5922). However, regression analysis showed that GDS at 6 months was significantly associated with total mercury concentration of neonate's hair but was not sensitive to the number of vaccines taken by the mother. CONCLUSION: Early neurodevelopment of exclusively breastfed infants is sensitive to in utero exposure to mercury, but maternal thimerosal exposure in tetanus-diphtheria vaccines per se cannot portend clinical neurodevelopment delays measured by GDS at 6 months.

Safety and immunogenicity of a meningococcal (Groups A, C, Y, W-135) polysaccharide diphtheria toxoid conjugate vaccine in healthy children aged 2 to 10 years in Chile.

Immune responses to meningococcal conjugate (Menactra; MCV-4) and plain polysaccharide (Menomune-A/C/Y/W-135; PSV-4) vaccines against serogroups A, C, Y, and W-135 were assessed in 220 of 1037 Chilean children aged 2 to 10 years participating in a comparative safety trial. Both vaccines were generally well tolerated. Geometric mean serum bactericidal antibody (SBA) titers 28 days postvaccination were comparable in both groups for all four serogroups. Seroconversion was evident in > 97% of MCV-4 and > 90% of PSV-4 vaccinees who tested seronegative at baseline. Menactra safely induced broad and robust immune responses against serogroups A, C, Y and W-135 in this population.

Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines.

We randomly assigned 150 newborn infants to receive diphtheria and tetanus toxoids (DT) or Hib oligosaccharide conjugate (HbOC) at birth to determine whether exposure to the Haemophilus influenzae type b (Hib) conjugate vaccines' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate (PRP-T) at 2, 4, and 6 months of age. Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age. No serious adverse reactions were associated with neonatal vaccination. Administration of HbOC at birth did not lead to earlier or higher antibody levels. Newborn immunization with DT did not prime children for enhanced antibody responses. Moreover, Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age. Diphtheria antibody levels, but not tetanus antibody levels, were also lower in children immunized with DT at birth. We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease. Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines, and may lead to suppression of Hib and diphtheria antibody responses.

Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.

We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

Evaluación de la reactogenicidad de las vacunas duple importadas y cubanas (con iguales dosis de toxoides) / Assessing the reactogenicity of cuban and iported duple vacines (with the same dose of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y el tétanos, importada y de producción nacional(con iguales dosis de toxoides); en un grupo de escolares se comparan los efectos colaterales producidos por las preparaciones utilizadas. Se determina el estado inmunitario previo a la vacunación con respecto a la difteria y tétanos, así como el incremento de los títulos de antitoxinas. Se utiliza el método ultra micro ELISA(UME)en el sistema ultra micro analítico(SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar lasinvestigaciones y utilizar el método UME el SUMA

Vacunas duple. estudio de la reactogenicidad e inmunogenicidad de las preparaciones importada y cubanas (con diferentes dosis de toxoides) / Duplex vaccine: study on reactogenicity and imunogenicity of cuban and imported preparations(with different doses of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y tétanos, importadas y de producción nacional(con diferentes dosis de toxoides), en un grupo de 40 escolares. Se comparan los efectos colaterales producidos por las preparaciones utilizadas. Sedetermina el estado inmunitario previo a la vacunación con respecto a la difteria y el tétano, así como el incremento de los títulos de antitoxina. Se utiliza el método ultra micro ELISA(UME) en el sistema ultra micro analítico (SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar las investigaciones y utilizar el método UME en el SUMA, para los trabajos de terreno

Vacunas duple: estudio de la reactogenicidad e inmunogenicidad de las preparaciones importada y cubanas (con diferentes dosis de toxoides) / Duplex vaccine: study on reactogenicity and immunogenicity of cuban and imported preparations(with different doses of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y tétanos, importadas y de producción nacional(con diferentes dosis de toxoides), en un grupo de 40 escolares. Se comparan los efectos colaterales producidos por las preparaciones utilizadas. Sedetermina el estado inmunitario previo a la vacunación con respecto a la difteria y el tétano, así como el incremento de los títulos de antitoxina. Se utiliza el método ultra micro ELISA(UME) en el sistema ultra micro analítico (SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar las investigaciones y utilizar el método UME en el SUMA, para los trabajos de terreno

Evaluación de la reactogenicidad de las vacunas duple importadas y cubanas (con iguales dosis de toxoides) / Assessing the reactogenicity of cuban and imported duple vacines (with the same dose of toxoid)

Se realiza un estudio de la reactogenicidad e inmunogenicidad de vacunas combinadas contra la difteria y el tétanos, importada y de producción nacional(con iguales dosis de toxoides); en un grupo de escolares se comparan los efectos colaterales producidos por las preparaciones utilizadas. Se determina el estado inmunitario previo a la vacunación con respecto a la difteria y tétanos, así como el incremento de los títulos de antitoxinas. Se utiliza el método ultra micro ELISA(UME)en el sistema ultra micro analítico(SUMA). Se comprueba la tolerancia y poder inmunogénico de las vacunas. Se recomienda continuar lasinvestigaciones y utilizar el método UME el SUMA

Adelantos terapéuticos en lepra / Progress in leprosy therapeutic

Se comentan los recientes aportes terapéuticos, dividiéndose el trabajo en los siguientes capítulos: I)Resistencia bacteriana a los diversos fármacos, en especial a la D.D.S. en su forma secundaria, así como la primaria. Dosis a emplear con la monoterapia. Causas de aparición de la resistencia (tratamiento irregular y/o bajas dosis). II) Asociación medicamentosa: sus ventajas y los principales esquemas en enfermos vírgenes y en casos de resistencia a las sulfonas. III) Tratamiento de la reacción leprosa. IV) Inmunoterapia en lepra: sus objetivos, los medios más comúnmente empleados, sus riesgos y efectos colaterales

Adelantos terapéuticos en lepra / Progress in leprosy therapeutic

Se comentan los recientes aportes terapéuticos, dividiéndose el trabajo en los siguientes capítulos: I)Resistencia bacteriana a los diversos fármacos, en especial a la D.D.S. en su forma secundaria, así como la primaria. Dosis a emplear con la monoterapia. Causas de aparición de la resistencia (tratamiento irregular y/o bajas dosis). II) Asociación medicamentosa: sus ventajas y los principales esquemas en enfermos vírgenes y en casos de resistencia a las sulfonas. III) Tratamiento de la reacción leprosa. IV) Inmunoterapia en lepra: sus objetivos, los medios más comúnmente empleados, sus riesgos y efectos colaterales

Efectos secunarios de la vacuna contra la difteria, tétanos y tosferina / Secondary effects of the vaccine against diphteria, tetanus and whooping cough

Se investigaron las reacciones sistémicas y locales posteriores a la inmunización con vacuna contra la difteria, tétanos y tosferina (DPT). Se determinaron los efectos secundarios en 730 niños entre 2 meses y 5 años con 11 meses, en las 48 horas siguientes. Se encontró a 13% de niños libres de efectos adversos. El 87% inmunizados presentó efecto colateral, siendo la incidencia: fiebre, 66.03% ; malestar, 37.81%; disminución del apetito, 25.07%; transtornos del sueño, 20.41%; vómitos, 7.94% y llanto contínuo, 7.67%. En relación a efectos locales: dolor, 41.64%; enrojecimiento, 20.08% y nódulos subcutáneos, 20.14%. Ninguno de los niños presentó convulsiones, episodios hipotónicos o daño neurológico inmediato. Se colocaron dos tipos de vacuna DPT: la del Laboratorio Connaught (canadiense) y la del Instituto de Higiene (venezolana). No hubo direrencia significativa en la aparición de efectos secundarios entre ambas, excepto para el dolor logal (P<0.0s) con la vacuna nacional. Efectos obtenidos en relación con la edad y número de dosis: hubo aumento significativo de vómitos con la menor edad (P<0.01) así como incremento del dolor local a mayor edad (p<0.01). A pesar de las diversas controversias originadas por el uso de la vacuna DPT, consideramos que los beneficios derivados de la vacuna supran ampliamente los riesgos atribuibles a ella, por esto, apoyamos la recomendación de inmunizar rutinariamene a la población susceptible.

Relationship of pertussis immunization to the onset of neurologic disorders: a retrospective epidemiologic study.

A retrospective epidemiologic study examining the relationship of the time of onset of neurologic disorders with the time of pertussis immunization in two cohorts of children who received pertussis immunization at different ages is reported. Before April 1970, children in Denmark were vaccinated with diphtheria and tetanus toxoids with pertussis vaccine at 5, 6, 7, and 15 months of age. Since 1970, children were given monovalent pertussis vaccine at 5 and 9 weeks and at 10 months of age. A total of 554 cases of epilepsy with onset between 28 days and 24 months of age were reviewed, 286 from the 1967-1968 period and 268 from the 1972-1973 period. There was no relationship between the age of onset of epilepsy and the scheduled age of administration of pertussis vaccine. A total of 2199 children with febrile seizures were reviewed, 830 from the 1967-1968 period and 1369 from the 1972-1973 period. There was a statistical association between first febrile seizures and the scheduled age of administration of pertussis vaccine (p = 0.004). No relationship between pertussis immunization and the occurrence of central nervous system infections was noted.

Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine.

A conjugate vaccine (Dpo20) was made by direct coupling of diphtheria toxoid and oligosaccharides obtained by periodate oxidation of Haemophilus influenzae type b capsular polysaccharide. This approach gave a higher multiplicity of saccharides per protein and greater immunogenicity in infancy than our previously studied conjugates. Thirty-three healthy infants received three sequential injections, and no serious side effects were observed. When Dpo20 was given with diphtheria-tetanus-pertussis vaccine at ages 2, 4, and 6 months, the geometric mean titer of anticapsular antibody rose to 5.9 micrograms/ml at age 7 months. Dpo20 given at 3, 5, and 7 months raised the mean to 3.2 micrograms/ml at 7 months (after two injections) and 15.4 micrograms/ml at 10 months. The antibodies included IgG and were bactericidal in vitro. Thus, antibody activities potentially protective against invasive H. influenzae b infections were induced in the most susceptible age range. The infants also became primed for mature-for-age responses to (unconjugated) polysaccharide vaccine given as a booster at age 12 months.

Safety and immunogenicity of Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children 15 to 24 months of age.

To evaluate the safety and immunogenicity of the Haemophilus influenzae type b polysaccharide vaccine, PRP, and a new polysaccharide-diphtheria toxoid conjugate vaccine, PRP-D, a collaborative study was carried out in six centers in five states. Subjects were 585 infants 15 to 24 months of age. They were randomly assigned to receive a single dose of PRP or PRP-D vaccine. There were no significant differences in the rate of adverse reactions between the two vaccine groups. Minor local reactions occurred in 10.3% of PRP and 12.5% of PRP-D recipients, and fever in 27.4% of PRP and 23.8% of PRP-D recipients. All reactions resolved within 48 hours. Serum samples were obtained just before vaccination and after 1 month. Prevaccination antibody levels were similar for the PRP (0.035 micrograms/mL) and PRP-D (0.027 micrograms/mL) groups, with no differences in levels by age, sex, race, vaccine lot, or study site. Both groups had significant rises in geometric mean levels, but this difference was significantly greater for PRP-D (2.166 micrograms/mL) than for PRP (0.154 micrograms/mL). In addition, the percentage of responders as determined by three definitions (twofold titer rise, greater than 0.15 micrograms/mL, and greater than 1.0 micrograms/mL) was also significantly greater for PRP-D than PRP. In contrast to a marked age-related immunogenicity to PRP (P less than 0.001), there was no significant variation in immune response to PRP-D by age. PRP-D conjugate vaccine appears to be as safe and significantly more immunogenic than PRP vaccine for children vaccinated at 15 to 24 months of age.

History of convulsions and use of pertussis vaccine.

Data on 2062 reports from the Monitoring System for Adverse Events Following Immunization, Centers for Disease Control (CDC), were analyzed to compare the risk of a personal or family history of convulsions in children who had a neurologic adverse event after receipt of diphtheria-tetanus-pertussis (DTP) vaccine with those who had a nonneurologic adverse event. Children with a neurologic event after DTP vaccine had a 7.2 times higher risk for personal history of convulsions (95% confidence limits 4.5 to 11.5) and a 4.5 times higher risk for family history of convulsions (95% confidence limits 3.1 to 6.7) than did children with an adverse event that did not affect the nervous system. Children with either a febrile or nonfebrile convulsion after receipt of DTP were significantly more likely to have a personal history of convulsions than children with a nonneurologic adverse event (P less than 0.0001). Children with a febrile convulsion after receipt of DTP but not children with nonfebrile convulsions were significantly more likely to have a family history of convulsions than those with a nonneurologic adverse event. It is recommended that pertussis vaccination be deferred in children with a personal history of a convulsion until it can be determined that an evolving neurologic disorder is not present. If such disorders are found, these children should be given the combined pediatric diphtheria and tetanus toxoids (DT) vaccine to complete the series.