Caracterización de la hipotonía-hiporrespuesta post vacuna pentavalente y tamizaje del neurodesarrollo en niños bajo 6 años de edad, 2013-2018, Uruguay / Characterization of hypotonia-hyporesponsiveness after pentavalent vaccine and neurodevelopmental screening in children under 6 years of age, 2013-2018, Uruguay

INTRODUCCIÓN: La hipotonía-hiporrespuesta (HHR) es uno de los efectos adversos supuestamente atribuibles a la vacunación e inmunización de tipo neurológico más notificados. El impacto a largo plazo a nivel del neurodesarrollo no es completamente conocida. OBJETIVO: Caracterizar los eventos de HHR post vacuna pentavalente notificados entre 2014 y 2018 al Ministerio de Salud Pública (MSP) de Uruguay. Realizar el tamizaje del neurodesarrollo de los que al momento de la evaluación tenían menos de 6 años de edad. METODOLOGÍA: Estudio descriptivo de las notificaciones al Sistema Nacional de Farmacovigilancia del MSP. Se realizó el tamizaje del neurodesarrollo con la Guía Nacional para la Vigilancia del Desarrollo. RESULTADOS: 30 casos, la mayoría de breve duración, en las primeras horas post primera dosis y con recuperación espontánea. Requirieron hospitalización 29. Se realizó el tamizaje del neurodesarrollo en 16. La media de tiempo entre el evento y esta evaluación fue 2 años y 2 meses. Fue normal la prueba de tamizaje en 15. En uno se detectó un retraso del lenguaje. CONCLUSIONES: Los episodios de HHR se presentaron con características similares a las descritas en la bibliografía. A pesar de las limitaciones del estudio, no se encontraron retrasos ni desvíos del desarrollo en los niños evaluados.

BACKGROUND: Hypotonic-hyporesponsive episodes (HHE) is one frequently reported neurologic adverse effect supposedly attributable to vaccination and immunization. Its long-term impact on neurodevelopment is not completely known. AIM: To characterize the post-pentavalent vaccine HHE events reported to the Uruguayan Ministry of Health (M of H) between 2014 and 2018. To perform neurodevelopment screening of those who were under 6 years of age at the time of evaluation. METHODS: Descriptive study of the reports made to the National Farmacosurveillance System of the M of H. Neurodevelopment screening was performed using the National Guidelines for Developmental Surveillance. RESULTS: 30 cases were studied. Most cases occurred after the first doses, were of short duration and during the first hours after vaccination, with spontaneous recovery. Median time between the event and this evaluation was 2 years and 2 months. Screening tests were normal in 15. Delay in the language area was detected in one case. CONCLUSIONS: HHE events had similar characteristics to those described in the literature, with no severe short-term complications. Despite the limitations of the present study, no delays nor deviations were found in the development of the children who were evaluated.

Internações sensíveis à atenção primária específicas de mulheres / Sensitive female-specific hospitalization in primary care

Objetivou-se analisar as internações por condições sensíveis à atenção primária (ICSAP) específicas em mulheres e os fatores que determinam ou influenciam a ocorrência dessas internações (fatores socioeconômicos, sociodemográficos e controle de saúde) por meio de um inquérito de morbidade hospitalar realizado com amostra de 429 mulheres internadas em hospitais conveniados ao Sistema Único de Saúde. O percentual de ICSAP foi 49,42% (n = 212), com destaque para as internações específicas do sexo feminino 19,35% (n = 83). Associaram ao risco de internar por CSAP: idade superior a 60 anos, baixa escolaridade, internação prévia, realização de controle regular de saúde, falta de vínculo com a Estratégia Saúde da Família (ESF) e ser gestante. As causas evidentes foram as condições relacionadas à gravidez, ao parto e ao puerpério e às inflamações nos órgãos pélvicos femininos. Os resultados sugerem falhas no atendimento ambulatorial que deveria ser oportuno e resolutivo no contexto da saúde da mulher.

The scope of this paper was to analyze female-specific sensitive hospitalization occurring in primary care conditions and factors that determine or affect the occurrence of such hospitalizations (social, economic and demographic factors; health control). Analysis was performed by surveys on hospital morbidity with a sample of 429 females attended in Unified Health System (SUS) contracted hospitals. The sensitive hospitalizations percentage in primary care reached 49.42% (n = 212), highlighting female-specific hospitalization at 19.35% (n = 83). Hospitalization risks comprised elderly people over sixty, low schooling, previous hospitalizations, normal health control, lack of association with the Family Health Strategy and pregnancy. Evident causes were related to conditions of pregnancy, childbirth, post-partum and inflammations of the female pelvic organs. Results suggested flaws in outpatient attendance that should be adequate and provide solutions in women’s health.

Immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b conjugate combination vaccine (pentaxim™) with hepatitis B vaccine.

Objective: To obtain immunogenicity and safety data for a pentavalent combination vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate). Design: Multicenter, open, Phase III clinical study. A DTaP-IPV//PRP~T vaccine (PentaximTM) was given at 6,10,14 weeks of age; and Hepatitis B vaccine at 0,6,14 or at 6,10,14 weeks of age. Immunogenicity assessed 1 month post-3rd dose; safety assessed for 30 minutes by the investigator, then by parents and investigators to 8 days and 30 days post-vaccination. Setting: Tertiary-care hospitals. Participants/patients: 226 healthy Indian infants (6 weeks of age). Main outcome measures: Immunogenicity and safety. Results: Immunogenicity was high for each vaccine antigen, and similar to a historical control study (France) following a 2,3,4 month of age administration schedule. Post-3rd dose, 98.6% of subjects had anti-PRP ³0.15 mg/mL and 90.0% had titers ³1.0 mg/mL; the anti-PRP GMT was 4.1 µg/mL. Seroprotection rates for diphtheria and tetanus (³0.01 IU/mL) were 99.1% and 100%; and 100%,99.1% and 100%, for polio types 1,2 and 3 (³8 [1/dil]) respectively. Anti-polio GMTs were 440.5,458.9, and 1510.7 (1/dil) for types 1,2 and 3 respectively. The vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 93.7% for PT and 85.7% for FHA; the 2-fold increase was 97.1% and 92.4%. Vaccine reactogenicity was low with adverse reaction incidence not increasing with subsequent doses. Conclusion: The DTaP-IPV//PRP~T vaccine, given concomitantly with monovalent hepatitis B vaccine, was highly immunogenic at 6, 10 and 14 weeks of age in infants in India. The vaccine was well tolerated.

Congenital rubella syndrome in infants of women vaccinated during or just before pregnancy with measles-rubella vaccine.

BACKGROUND & OBJECTIVE: Measles and Rubella Control Campaign was conducted in Iran in December 2003 targeting both males and females 5 to 25 yr old using measles-rubella vaccine. During the campaign, some pregnant women received vaccine during the first trimester of pregnancy or some others became pregnant shortly thereafter. The goal of this study was to evaluate the risk of congenital rubella syndrome (CRS) among the infants born to the vaccinated mothers. METHODS: A total of 106 pregnant women, who had received vaccine during the first trimester of pregnancy or become pregnant less than three months after vaccination were included in the study for comparison 40 pregnant women without rubella vaccine were also included. The mothers' blood samples at the time of delivery, infants' cord blood and blood samples at the end of the second month of birth of sixty children whose parents agreed about blood sampling, were tested for rubella IgM and IgG antibodies using ELISA method. RESULTS: There were 107 live births in the exposed group and 42 in the control group. Serological study showed no IgM rubella antibody in the maternal and infant cord blood; it was not found in the second blood specimens of 60 infants tested at 8 wk of age. IgG rubella antibody was positive in all infants' cord blood but it decreased in the second blood specimens of the infants. None of the children exhibited signs of congenital rubella syndrome. INTERPRETATION & CONCLUSION: Finding of our study showed that none of the infants born to mothers vaccinated by MR vaccine during the first trimester of pregnancy or had become pregnant within three months after vaccination, had CRS.

Erythema multiforme following vaccination in an infant.

Erythema multiforme is a cutaneous reaction pattern precipitated by varied agents, notably herpes simplex and drugs. It predominantly occurs in adolescents and young adults but may be seen at other ages also. While vaccination is rarely a precipitating factor for erythema multiforme, it may occasionally be seen in infants and children. We report here a case of a two month-old infant with lesions of erythema multiforme minor appearing after two weeks following vaccination for DPT, Hepatitis B and influenza.

Análise dos eventos adversos pós-vacinais ocorridos em Teresina / Analysis of after-vacination side-effects occurred in Teresina

Este estudo trata do perfil dos eventos adversos pós-vacinais ocorridos em Teresina em 2006. Os dados foram coletados mediante a aplicação de formulário com 73 participantes em 18 Unidades Básicas de Saúde. Os resultados mostram que as vacinas que mais produziram eventos adversos foram a tetravalente, BCG e DPT. Os eventos mais freqüentes foram: febre, episódio hipotônico hiporresponsivo, irritabilidade e manifestações locais moderadas. Dentre as condutas adotadas pelos profissionais de saúde, aproximadamente 80 por cento foram adequadas. Os menores de ano foram os mais acometidos pelos eventos. Todos os eventos evoluíram para a cura. Conclui-se que a ação de vacinação ainda continua requerendo capacitação constante dos profissionais da área. Sugere-se aprofundar o conhecimento com relação ao manejo, diagnóstico, investigação e tratamento.

This study focuses the profile of the adverse events after-vaccine occurrences in Teresina in 2006. The data had been collected by means of the form application with 73 participants in 18 Basic Units of Health. The results show that the vaccines that had more produced events adverse had been tetravalente, BCG and DPT. The events most frequent had been: fever, hiporresponsivo hipotonic episode, moderate irritability and local manifestations. Amongst the behaviors adopted for the health professionals, 80 percent had been approximately adjusted. The year minors had been accomitted by the events. All the events had evolved for the cure. It was concluded that the action of vaccination still continues requiring constant qualification of the professionals of the area. It is suggested to deepen the knowledge with relation to the handling, diagnosis, inquiry and treatment.

El presente estudio trata del perfil de las ocurrencias adversas de la después-vacuna en Teresina en 2006. Los datos fueron recogidos por medio del uso un formulário a lo cual participaran 73 personas en 18 unidades básicas de salud. Los resultados demuestraran que las vacunas que tenían más ocurrencias adversas fueran la tetravalente, BCG y DPT. Las ocurrencias más frecuentes fueran: fiebre, episodio hipotônico hiporresponsivo, irritabilidad moderada y manifestaciones locales. Entre los comportamientos adoptados por los profesionales de salud, 80 por ciento fueran ajustados aproximadamente. Los menores de edad del año habían sido acometidos por los acontecimientos. Todos los acontecimientos fueran desarrollados para la cura. Se hay concluydo que la acción de la vacunación todavía continúa requiriendo la calificación constante de los profesionales de la área. Se sugiere para profundizar el conocimiento en relación a la dirección, a la diagnosis, a la investigación y al tratamiento.

Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine.

An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).

Safety and immunogenicity of Haemophilus influenzae type B vaccine given in combination with DTwP at 6, 10 and 14 weeks of age.

OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus conjugate Haemophilus influenzae type b vaccine (Act-Hib) when extemporaneously mixed and administered as a DTwP-Hib combination using an Indian DTwP vaccine (BE DTwP) in comparison with a licensed DTwP-Hib combination vaccine. METHODS: 378 healthy infants were enrolled and randomly allocated to receive either three doses, at 6, 10 and 14 weeks of age, of Act-Hib in combination with BE DTwP (Group A, n = 160), TetrAct-Hib (Group B, n = 160), or BE DTwP and Act-Hib as separate injections (Group C, n = 58). Sera collected before the first dose and one month after the third dose were tested for antibodies to vaccine antigens. Safety was determined using parental diary cards. RESULTS: Anti-Hib antibody concentrations indicative of short-term protection (> 0.15 g/ml) were elicited in all but one subject in Group A (99.3%), and all subjects in Groups B and C. The concentration of 1 g/ml, considered to provide long-term protection, was achieved in 96.7%, 100% and 98.2% of the infants in Groups A, B and C, respectively. All children displayed satisfactory responses to the three DTwP component antigens, TetrAct-Hib eliciting higher titers against diphtheria and tetanus than BE DTwP. No vaccine-associated serious adverse events occurred. The BE DTwP vaccine was associated with more reports of fever than TetrAct-Hib, but most symptoms were regarded as mild and all resolved without sequelae. CONCLUSIONS: Combining Act-Hib and a local DTwP vaccine did not affect the anti-Hib response. In countries where DTwP vaccine available for use in the EPI program is manufactured by a local or other developing country manufacturer, mixing it with lyophilised Act-Hib is a reasonable option though the immunogenicity may have to be documented before routine use. However, use of TetrAct-Hib combination vaccine would be preferable in view of its lower reactogenicity and superior immunogenicity with respect to diphtheria and tetanus.

Safety and immunogenicity of a Haemophilus influenzae type B polysaccharide-tetanus toxoid conjugate vaccine combined with diphtheria, tetanus and pertussis vaccines in Thai infants.

A randomized, open, multicenter trial was conducted to determine the safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid (PRP-T) conjugate vaccine combined with tetanus, diphtheria and pertussis (DTP) vaccine in 271 Thai infants born to mothers immunized against tetanus during pregnancy. Infants were immunized at approximately 2, 4 and 6 months of age with these vaccines. To determine if elevated levels of anti-tetanus toxin antibodies suppressed the anti-PRP antibody response, a second group of infants were immunized with PRP complexed with outer membrane proteins of Neisseria meningitidis (Pedvax HIB) in one limb at 2 and 4 months of age and DTP vaccine in the other limb at 2, 4 and 6 months of age. A third group of infants received only DTP vaccine at 2, 4 and 6 months of age. The occurrence of both local and systemic adverse reactions were comparable in all 3 groups. The geometric mean anti-tetanus antibody titer was > 1 IU/ml at baseline. Approximately 1 month after the administration of the third dose of vaccine, 98.5%, 99.3% and 9.7% of the children immunized with DTP+Pedvax HIB, DTP-PRP-T or DTP possessed > or = 0.15 microgram of anti-PRP antibody per ml. No child in the DTP group achieved > or = 1 microgram/ml while 74.2% and 89.3% did so after immunization with DTP+Pedvax HIB, or DTP-PRP-T, respectively (p < 0.05). Immune responses to diphtheria, tetanus and pertussis antigens were similar in all vaccine groups. These results demonstrate that elevated tetanus antibody titers do not diminish the anti-PRP antibody response following immunization with a PRP-T conjugate combined with DTP vaccine.