Rubella vaccination of unknowingly pregnant women: the São Paulo experience, 2001.

BACKGROUND: Rubella vaccination is contraindicated during pregnancy. During mass immunization of women of childbearing age against rubella, women unknowingly pregnant may be vaccinated. To evaluate the effects of rubella vaccination during pregnancy, the Brazilian state of São Paulo conducted a follow-up study of pregnant women vaccinated during a rubella campaign in 2001. METHODS: Women vaccinated during pregnancy were reported to a national surveillance system. In the state of São Paulo, follow-up of vaccinated women included household interviews. Serum samples from vaccinated women were tested for antirubella antibodies to classify susceptibility to rubella infection. Children born to susceptible mothers were tested for evidence of congenital rubella infection and evaluated for signs of congenital rubella syndrome. RESULTS: The São Paulo State Health Department received 6473 notifications of women vaccinated during pregnancy. Serology performed for 5580 women identified 811 (15%) that were previously susceptible. Incidence of spontaneous abortion or stillbirth among previously susceptible vaccinated women was similar to women with prior immunity. Twenty-seven (4.7%) of 580 newborns tested had evidence of congenital rubella infection; none had congenital rubella syndrome. CONCLUSIONS: Mass rubella vaccination of women of childbearing age was not associated with adverse birth outcomes or congenital rubella syndrome among children born to women vaccinated during pregnancy.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Clinical bioethics.

Clinical bioethics was born out of the need to introduce different ethical values involved in the relationships among physician, patient and health institutions which are outside the technical-scientific framework of routine medical practice. Physicians tend to adopt the norms and rules provided for in the Medical Ethics Code to guide the exercising of their professional practice. However, it has recently become challenging to apply these norms to all conduct since some issues faced in the professional practice are simply not provided for by such norms. Ethical consideration in practice drawing solely on the medical ethics code in Brazil has proved insufficient, both in the context of universal issues such as organ transplants, start and end-of-life, as well as in addressing specific issues such as allocation of funds for health. Clinical bioethics employs clinical cases and situations as an instrument for discussion. These discussions entail analysis of not only the facts and circumstances surrounding each case, but also the values which lead to patients, health teams and institutions opting to recommend, accept or refuse a given conduct.

Varicella vaccines and measles, mumps, rubella, and varicella vaccine.

OBJECTIVES: To present an up-to-date review of studies investigating the efficacy, adverse events and vaccination regimens of the varicella vaccine and the new presentation combined with the vaccine for measles, mumps and rubella. SOURCES OF DATA: Bibliographic review of the MEDLINE and LILACS databases covering the period 1999 to 2006. SUMMARY OF THE FINDINGS: The varicella vaccine protects 70 to 90% of immunized children against any form of varicella zoster infection, but the efficacy against severe forms is higher (95 to 98%). This is a well-tolerated vaccine that causes few reactions. Since the vaccine was licensed, there have been three confirmed cases of transmission of the vaccine virus by domestic contacts to previously healthy people, who went on to develop mild disease. Despite evidence that the protection offered by this vaccine can wane over a number of years, it is not yet possible to state that a second dose is warranted, bearing in mind exposure to wild virus. After universal vaccination the chances of natural stimulation should drop and it is very probable that booster doses will become necessary. A measles, mumps, rubella, and varicella vaccine has recently been licensed that combines vaccines for measles, mumps, rubella and varicella in a single product with high rates of seroconversion. CONCLUSIONS: The Brazilian Society of Pediatrics recommends the varicella vaccine for children from 1 year on. We hope that the measles, mumps, rubella, and varicella vaccine will soon be available in Brazil, since combined vaccines facilitate wider vaccination coverage.

[Visceral leishmaniasis: clinical and laboratorial aspects]. / Leishmaniose visceral: aspectos clínicos e laboratoriais.

OBJECTIVE: To compare the clinical and laboratorial data before and after the treatment of patients with visceral leishmaniasis admitted to a pediatric hospital in a nonendemic area, highlighting the importance of recognizing visceral leishmaniasis in pediatric patients. METHODS: Clinical, laboratorial and treatment data of 78 patients with visceral leishmaniasis were evaluated from 1981 to 1992. We analyzed the average level of hemoglobin, leukocyte, neutrophil, platelet, albumin, gammaglobulin, class and subclass of immunoglobulin, size of the liver and spleen during the pre- and post-treatment using the paired t test. RESULTS: We included 78 patients with visceral leishmaniasis, 44 males, with age ranging from 8 months to 13.5 years. Sixty-one patients were from Bahia. Fever and splenomegaly were present in 96.1% and 100% of the cases, respectively. The parasitological diagnosis was obtained in 74/78 patients: 67 patients through smear and/or culture of bone marrow (85.7%), five through liver biopsy and two through spleen puncture. The hematological findings and serum albumin presented significant improvement at the end of treatment (P<0.001), differently from serum gammaglobulin levels (P=0.087). There was predominance of IgG1 subclass, with two patients presenting low levels of IgG2. Initial treatment used antimoniate in 67 cases and amphotericin B in five. Eleven patients (15.7%) needed a second treatment, and were considered cured after it. There was significant improvement in the liver and spleen size at the end of the treatment (P<0.001). One patient presented spontaneous remission and five died due to bleeding. CONCLUSIONS: In order to obtain accurate diagnosis and treatment, especially regarding health services of areas with low-incidence of visceral leishmaniasis, the diagnosis of patients with fever and visceromegaly, who come from endemic areas, should include visceral leishmaniasis.

A critical appraisal of the recommendations for the use of meningococcal conjugate vaccines.

OBJECTIVES: To assess the epidemiology of meningococcal disease (MD) in Brazil and the impact that recent evidence and lessons learned from the introduction of meningococcal C conjugate (MCC) vaccines into immunization programs may have on different strategies of vaccine use. SOURCES: Non-systematic review of the MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011. SUMMARY OF THE FINDINGS: Meningococcal disease is endemic in Brazil, with periodic occurrence of outbreaks. Most cases are associated with serogroup C and the highest incidence rates are observed in infants, encouraging the introduction of MCC vaccine in the National Immunization Program in 2010 for children under 2 years old. The introduction of MCC vaccines into immunization programs in Europe, Canada and Australia proved to be effective, with dramatic reduction in the incidence of serogroup C meningococcal disease, not only in the vaccinated, but also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was dependent on a combination of antibody persistence, immunologic memory and herd protection. Recent evidence indicating that antibody persistence is not long-lasting in young immunized children, and that immunologic memory is not fast enough to protect them against the disease, emphasize the importance of herd protection to maintain the population protected. CONCLUSIONS: The rapid decline of antibody titers in children vaccinated in the first years of life suggests the need to incorporate booster doses before adolescence, especially in locations like Brazil, where the immunization program did not incorporate catch-up campaigns including adolescents, lacking the herd immunity effect.

Ethical aspects of brain death and end-of-life.

Ethical issues surrounding brain death and end-of-life have not been afforded in Brazil the same attention as in many developed countries. There appears to be reluctance on the part of Brazilian doctors to limit or suspend procedures or treatment which prolongs life of patients in terminal phases of severe incurable illness, or to suspend the artificial means of supporting vegetative functions in cases of brain death outside the context of organ and tissue donation for transplant. Fears grounded in possible administrative (Regional Medical Councils) or legal repercussions, as well as ambiguous interpretations of religious precepts, partially explain this reluctance which often results in unnecessary prolonging of patient suffering. A recent resolution by the Federal Medical Council on end-of-life may offer doctors some guidance and confidence in dealing with highly complex ethical situations.

Questões éticas relativas à morte encefálica e terminalidade da vida não têm ainda no Brasil o mesmo destaque que em países desenvolvidos. Os médicos brasileiros parecem ter resistência em limitar ou suspender tratamentos ou procedimentos de prolongamento da vida em pacientes em fase terminal de doença grave e incurável, ou em suspender os meios artificiais da manutenção de funções vegetativas em casos de morte encefálica fora do contexto de doação de órgãos e tecidos para transplante. Receio quanto a possíveis sanções administrativas (Conselhos Regionais de Medicina) ou legais, além de duvidosas interpretações de preceitos religiosos explicam, ao menos parcialmente, essa relutância, que freqüentemente resulta em prolongamento desnecessário do sofrimento dos pacientes. Uma recente Resolução do Conselho Federal de Medicina sobre terminalidade de vida oferece aos médicos orientação sobre como lidar com algumas dessas questões de grande complexidade ética.

Análise crítica das recomendações do uso das vacinas meningocócicas conjugadas / A critical appraisal of the recommendations for the use of meningococcal conjugate vaccines

OBJETIVOS: Analisar a epidemiologia da doença meningocócica no Brasil e o impacto que as recentes evidências acumuladas com a incorporação das vacinas meningocócicas C conjugadas nos programas de imunização podem ter nas diferentes estratégias de uso dessas vacinas. FONTES DOS DADOS: Revisão nas bases de dados MEDLINE, SciELO e LILACS no período de 2000 a 2011. SÍNTESE DOS DADOS: No Brasil, a doença meningocócica é endêmica, com ocorrência periódica de surtos. Os maiores coeficientes de incidência ocorrem em lactentes, sendo o sorogrupo C responsável pela maioria dos casos, motivando a introdução da vacina meningocócica C conjugada no Programa Nacional de Imunizações, em 2010, para crianças menores de 2 anos. A introdução das vacinas meningocócicas C conjugadas nos programas de imunização na Europa, Canadá e Austrália mostrou-se efetiva, com dramática redução na incidência de doença causada pelo sorogrupo C, não apenas nos vacinados, mas também em não vacinados. A efetividade em longo prazo dessas vacinas mostrou-se dependente de uma combinação de persistência de anticorpos, memória imunológica e proteção indireta. Recentes evidências indicando que a persistência de anticorpos não é duradoura em crianças pequenas imunizadas e que a memória imunológica não é rápida o suficiente para protegê-las contra a doença enfatizam a importância da proteção indireta para manutenção da população protegida. CONCLUSÕES: A rápida queda de títulos de anticorpos em crianças vacinadas nos primeiros anos de vida sugere a necessidade de incorporarmos doses de reforço antes da adolescência, especialmente em locais como o Brasil, onde ainda não contamos com o efeito da proteção indireta da população.

OBJECTIVES: To assess the epidemiology of meningococcal disease (MD) in Brazil and the impact that recent evidence and lessons learned from the introduction of meningococcal C conjugate (MCC) vaccines into immunization programs may have on different strategies of vaccine use. SOURCES: Non-systematic review of the MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011. SUMMARY OF THE FINDINGS: Meningococcal disease is endemic in Brazil, with periodic occurrence of outbreaks. Most cases are associated with serogroup C and the highest incidence rates are observed in infants, encouraging the introduction of MCC vaccine in the National Immunization Program in 2010 for children under 2 years old. The introduction of MCC vaccines into immunization programs in Europe, Canada and Australia proved to be effective, with dramatic reduction in the incidence of serogroup C meningococcal disease, not only in the vaccinated, but also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was dependent on a combination of antibody persistence, immunologic memory and herd protection. Recent evidence indicating that antibody persistence is not long-lasting in young immunized children, and that immunologic memory is not fast enough to protect them against the disease, emphasize the importance of herd protection to maintain the population protected. CONCLUSIONS: The rapid decline of antibody titers in children vaccinated in the first years of life suggests the need to incorporate booster doses before adolescence, especially in locations like Brazil, where the immunization program did not incorporate catch-up campaigns including adolescents, lacking the herd immunity effect.

Immunogenicity and safety of a new Vero cell rabies vaccine produced using serum-free medium.

The immunogenicity and safety of a new human rabies vaccine, produced in Vero cells by a process that does not require supplementation with human or animal derived components in production, were assessed. Thus, the objective is to produce a safer vaccine at a lower cost. A total of 296 volunteers was divided into two groups: Group 1, which received the study vaccine, and Group 2, which received the Vero cells vaccine produced by Sanofi Pasteur. Five doses were given on days 0, 3, 7, 14 and 28. Blood samples for determination of rabies virus neutralizing antibodies were collected on days 0, 14, 38 and 90. The geometric mean titers (GMT) were much higher than 0.5 IU/ml in both groups on days 14, 38 and 90, indicating seroconversion according to the World Health Organization. In Group 1, however, the GMTs were higher than in Group 2, the difference being statistically significant in the two last samples. There was no statistical difference between the groups in the ratio of individuals with titers > or =0.5 IU/ml in each sample. Pain at the injection site was the most common adverse reaction and occurred most often in Group 1 (p < 0.001). All cases had a favorable evolution. There were no severe adverse reactions. It was concluded that the new vaccine is safe and immunogenic.

DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children.

This multicentre study was designed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria, tetanus, and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b (DTPw-HB/Hib) administered as either a syringe mix or as separate injections in 400 Latin American children. Both vaccine regimens were equally well tolerated and elicited post-primary excellent seropositivity rates at or close to 100% for all five component antigens. With regard to HB, 100% of subjects in the combined vaccination group, and 98.8% subjects in the separate injection vaccination group reached seroprotective antibody concentrations (>or=10 mIU/ml) 1 month after the primary vaccination course. Equally high anti-PRP antibody concentrations were reached 1 month after vaccination, with 100% of seroprotected subjects in the combined vaccination group (antibody concentrations >or=0.15 microg/ml), against 99.4% in the separate injection vaccination group. Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course, just prior to booster vaccination. Finally, a significant increase of all antibody concentrations could be observed after the booster vaccination, since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose. These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes.

Soroprevalência da hepatite B e avaliação da resposta imunológica à vacinação contra a hepatite B por via intramuscular e intradérmica em profissionais de um laboratório de saúde pública / Hepatitis B seroprevalence and evaluation of immune response to hepatitis B vaccination using intramuscular and intradermal routes in public health laboratory employees

OBJETIVOS: Determinar a prevalência dos marcadores da hepatite B (HBsAg e anti-HBs) e avaliar a resposta à vacinação contra hepatite B por via intradérmica (ID) em profissionais de saúde que não responderam à vacinação por via intramuscular (IM). MÉTODO: Todos os funcionários do Instituto Adolfo Lutz (IAL) foram convidados a participar do estudo. Amostras de soro foram colhidas no momento da administração da primeira dose de vacina (Engerix® B) e o HBsAg e o anti-HBs foram pesquisados, utilizando-se kits comerciais (Laboratórios Abbott®). Aos funcionários que não responderam à vacinação convencional (três doses por via IM) foram oferecidas doses de 5µg da mesma vacina por via ID. RESULTADOS: Foram envolvidos nesse estudo 404 funcionários do IAL, dos quais dois (0,5 por cento) eram HBsAg e 42 (10,5 por cento), anti-HBs reagentes. Dos 360 voluntários com sorologia negativa, 316 (87,8 por cento) receberam três doses de vacina (IM) e, desses, 259 colheram soros para avaliação pós-vacinal. Do total, 242 (93,4 por cento) apresentaram anticorpos acima de 10 UI/L após completarem o esquema inicial. Foram administradas duas doses de reforço, porém sete funcionários permaneceram sem resposta imunológica. A vacinação intradérmica foi realizada em cinco voluntários, e todos produziram anticorpos após a utilização dessa via de administração. CONCLUSÕES: A prevalência da hepatite B não foi maior nessa população do que na população geral. A vacinação por via intradérmica pode ser uma boa alternativa na imunização de pessoas que não respondem ao esquema convencional.

OBJECTIVES: To determine the prevalence of HBsAg and anti-HBs and to evaluate the response of intradermal hepatitis vaccination in healthcare workers non-responsive to previous repeated intramuscular vaccination. MATERIAL AND METHOD: All of the employees from Instituto Adolfo Lutz were invited to participate on this study. Serum samples were obtained and HBsAg and anti-HBs were detected using commercial kits (Abbott® Laboratories). Employees were submitted to the conventional three-dose vaccination by intramuscular route. To those employees who did not respond to intramuscular vaccination, 5 µg doses of Engerix® B were then administered by intradermal route up to nine doses. RESULTS: Four hundred and four healthcare workers were enrolled in this study. Initially, two (0.5 percent) and 42 (10.4 percent) were HBsAg and anti-HBs reagent, respectively. Among the 360 negative volunteers, 316 (87.8 percent) received three vaccine doses and in 259 of them, serum samples were collected to evaluate vaccine efficacy. Among them, 242 (93.4 percent) showed antibodies titer higher than 10 UI/l. Intradermal vaccination was carried out in five volunteers and all of them responded to this vaccine administration route. CONCLUSION: The prevalence of hepatitis B was not higher than in general population. Intradermal vaccine administration could be a good alternative in people that did not respond to previous intramuscular route.

Vacinas contra varicela e vacina quádrupla viral / Varicella vaccines and measles, mumps, rubella, and varicella vaccine

OBJETIVOS: Apresentar uma revisão atualizada sobre os estudos de eficácia, eventos adversos e esquema vacinal da vacina contra varicela e a nova apresentação combinada com a vacina contra sarampo, caxumba e rubéola. FONTES DOS DADOS: Revisão bibliográfica utilizando a base de dados MEDLINE e LILACS no período de 1999 a 2006. SíNTESE DOS DADOS: A vacina contra varicela tem uma eficácia entre 70 a 90 por cento contra a infecção e 95 a 98 por cento de proteção contra as formas graves. É uma vacina bem tolerada e pouco reatogênica. Após o seu licenciamento, foram comprovados apenas três casos de transmissão do vírus vacinal de pessoas previamente saudáveis para contatos domiciliares, que desenvolveram doença leve. Apesar das evidências de que a proteção conferida pela vacina pode diminuir com o passar dos anos, ainda não é possível afirmar que seja necessário, no momento, a aplicação de uma segunda dose, tendo em vista a exposição ao vírus selvagem. Após a vacinação universal, as chances de estímulo natural deverão diminuir, e muito provavelmente será necessário a aplicação de doses de reforço. Recentemente foi licenciada a vacina quádrupla viral, um produto combinado com a vacina contra sarampo, caxumba, rubéola e varicela com elevadas taxas de soroconversão. CONCLUSÃO:A vacina contra varicela é recomendada pela Sociedade Brasileira de Pediatria (SBP) para as crianças a partir de 1 ano de idade. Esperamos que, em breve, a vacina quádrupla viral esteja disponível no Brasil, pois o uso de vacinas combinadas possibilita uma maior cobertura vacinal.

Saúde pública, bioética e eqüidade / Public health, bioethics and equity

Sugere por quais bases éticas deve a bioética guiar o debate da distribuiçäo de recursos escassos. Por meio de uma análise da ética da responsabilidade individual e pública e de uma apresentaçäo do debate sobre a alocaçäo de recursos em alguns países industrializados, tais como Alemanha, França, Espanha e Estados Unidos, defende o princípio de que a eqüidade deva ser melhor avaliada pelos estudiosos de bioética e saúde pública

A bioética no século XXI / Bioethics in the 21st century

Säo analisados dois assuntos que, supöe-se, comporäo no início do século XXI a pauta básica das preocupaçöes dos governos dos diferentes países e das comissöes dos congressos bioéticos internacionais: a saúde pública e coletiva e a engenharia genética. Em relaçäo à saúde pública e coletiva, enfatiza que a eqüidade é a base ética que deve guiar o processo decisório da alocaçäo de recursos. Quanto à engenharia genética, chama a atençäo para alguns abusos na utilizaçäo dos testes preditivos em genética humana e alerta para os perigos do endeusamento da técnica e para radicalizaçäo irracional do seu uso

Leishmaniose visceral: aspectos clínicos e laboratoriais / Visceral leishmaniasis: clinical and laboratorial aspects

Objetivo: comparar os dados clínicos e laboratoriais no pré e pós-tratamento de pacientes portadores de leishmaniose visceral (LV), admitidos em hospital pediátrico localizado em área näo-endêmica, destacando a importância do reconhecimento da LV na faixa etária pediátrica. Métodos: avaliaçäo dos dados clínicos, laboratoriais e de tratamento de pacientes portadores de LV no período compreendido entre 1981 e 1992, comparando-se os valores médios de hemoglobina, leucócitos, neutrófilos, plaquetas, albumina, gamaglobulina, classes e subclasses de imunoglobulinas, tamanho do fígado e baço antes e após o tratamento, utilizando-se o teste "t" para amostras pareadas. Resultados: foram incluídos 78 pacientes, com idade variando entre 8 meses e 13,5 anos, sendo 44 casos do sexo masculino e 61 provenientes da Bahia. Febre e esplenomegalia estavam presentes em 96,1 por cento e 100 por cento dos casos, respectivamente. O diagnóstico parasitológico foi obtido em 74/78 pacientes, com positividade pelo mielograma e/ou mielocultura em 67 casos (85,7 por cento), 5 pela biópsia hepática e 2 pela punçäo esplênica. Os valores hematológicos e a albumina sérica apresentaram melhora significante ao término do tratamento (p<0,001), o mesmo näo ocorrendo com a gamaglobulina sérica (p=0,087). Houve predomínio da subclasse IgG1, com dois pacientes apresentando níveis reduzidos de IgG2. O tratamento inicial utilizou antimonial em 67 casos e Anfotericina B em 5. Onze pacientes (15,7 por cento) necessitaram segundo esquema de tratamento, com resoluçäo em todos os casos. Houve melhora significativa do tamanho do fígado e baço ao término do tratamento (p <0,001). Um paciente apresentou resoluçäo espontânea, e cinco faleceram por sangramento. Conclusöes: os autores alertam para a inclusäo da LV na suspeita diagnóstica de pacientes pediátricos apresentando febre e visceromegalia, provenientes de áreas endêmicas, para a adequada abordagem diagnóstica e tratamento, especialmente em serviços de saúde de regiöes de baixa incidência desta endemia

Simpósio: pesquisa em seres humanos / Symposium: research in humans

Opçäo do Conselho Editorial da Revista Bioética, por meio de um levantamento de dados junto à instituiçöes de saúde e pesquisadores, conhecer a situaçäo atual de funcionamento dos Comitês de Ética em Pesquisa, de como se está fazendo, sob a consideraçäo dos aspectos éticos, a pesquisa em seres humanos e quais os mecanismos institucionais que estäo sendo utilizados para controlá-la. Aborda temas como implicaçöes filosóficas na reflexäo discurso e açäo dos comitês de ética; as comissöes de ética hospitalares e a institucionalizaçäo da bioética em Portugal; experiências de comitês de ética em hospitais brasileiros; comitês de ética em pesquisa em seres humanos; e proposta de diretrizes éticas para pesquisas