Duration of post-vaccination immunity to yellow fever in volunteers ten years after a dose-response study - A complementary study.

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose-response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477.

Actual Clinical Practice Assessment: A Rapid and Easy-to-Use Tool for Evaluating Cognitive Decline Equivalent to Dementia.

Background Screening tests reveal the early signs of cognitive decline, enabling better self-care and preparation for the future. We developed and evaluated the accuracy of a rapid (20 s) and easy-to-use tool called ONSEI, assessing the cognitive decline equivalent to dementia in actual clinical practice by correlating clinical diagnoses with the ONSEI classification. Methods In this retrospective observational study, data were collected from individuals who visited three neurosurgical clinics in neighboring prefectures of Tokyo, Japan. ONSEI analysis was performed using a smartphone or tablet. The tool adopts a machine-learning algorithm using the speaker's age, time-orientation task score, and acoustic features of spoken responses to that task. Significant differences in accuracy, sensitivity, and specificity were evaluated by Fisher's exact test. Results The overall classification accuracy of ONSEI was 98.1% (p<0.001). The sensitivity and specificity were 97.3% (p<0.001) and 98.5% (p<0.001), respectively. The proportion of correct classifications was consistent across different age groups. Conclusion ONSEI showed high classification accuracy for dementia in cognitively normal individuals in actual clinical practice, regardless of the facility at which the tests were conducted or the age of the participants. Thus, ONSEI can be useful for dementia screening and self-care.

Pela reconquista das altas coberturas vacinais / For the return of high vaccination coverage / Para la recuperación de altas coberturas de vacunación

O declínio global das coberturas vacinais levou a Organização Mundial da Saúde (OMS), em 2019, a definir a hesitação vacinal como uma das dez maiores ameaças mundiais à saúde pública. No Brasil, a queda da cobertura vacinal teve início em 2012, acentuando-se a partir de 2016, e sendo agravada pela pandemia de COVID-19. O alerta da baixa cobertura vacinal vem acompanhado pela reintrodução de doenças imunopreveníveis como o sarampo. O retorno de doenças até então eliminadas, como a poliomielite, pode agravar a crise sanitária ainda em curso. Mesmo sendo reconhecido como um dos mais efetivos programas de imunizações do mundo e dos esforços permanentes, o Programa Nacional de Imunizações enfrenta um cenário extremamente adverso no que tange às coberturas vacinais. Este artigo descreve o Projeto pela Reconquista das Altas Coberturas Vacinais (PRCV) e a estratégia de trabalhar na ponta do sistema, executada nos territórios, que vem sendo implementada desde 2021 e já começa a apresentar resultados promissores. O PRCV foi organizado em três eixos temáticos com atuação compartilhada e ações específicas, a saber: vacinação; sistemas de informação; comunicação e educação. Os resultados já alcançados permitem afirmar que é possível conseguir a reversão das baixas coberturas vacinais, a partir da articulação de ações estruturais e interinstitucionais, com o fortalecimento das políticas públicas e desenvolvimento de medidas de curto, médio e longo prazos. Os fatores mais potentes do PRCV são sua abordagem junto aos profissionais da ponta, o pacto social pela vacinação, e a estruturação de redes locais de apoio às imunizações.

The global decline in vaccine coverage led the World Health Organization (WHO) in 2019 to define vaccine hesitation as one of the world's top ten threats to public health. In Brazil, the drop in vaccination coverage began in 2012, increasing from 2016, and was aggravated by the COVID-19 pandemic. The warning of low vaccination coverage is accompanied by the reintroduction of immunopreventable diseases such as measles. The return of diseases so far eradicated, such as polio, can aggravate the ongoing health crisis. Despite the Brazilian National Immunization Program being recognized as one of the most effective worldwide and its continuous efforts, it is facing an extremely challenging scenario regarding immunization coverage. This article describes the Project for the Regaining of the High Vaccination Coverage (PRCV) and the strategy of working at the frontline, conducted in the local level, which has been implemented since 2021 and is already starting to show promising results. The PRCV was organized in three thematic axes with shared and specific actions, including: vaccination; information systems; communication and education. The outcomes achieved allow us to affirm that it is possible to reverse the low vaccination coverage, based on the articulation of structural and interinstitutional actions, with the strengthening of public policies and development of short-, medium-, and long-term measures. The most powerful factors of the PRCV are its approach to frontline professionals, the social pact for vaccination, and the establishment of local support networks for vaccinations.

La disminución global de las coberturas de vacunación llevó a la Organización Mundial de la Salud (OMS), en 2019, a definir la vacilación de la vacunación como una de las diez mayores amenazas para la salud pública en el mundo. En Brasil, la caída de la cobertura de vacunación comenzó en 2012, se acentuó a partir de 2016 y se vio agravada por la pandemia de COVID-19. La alerta de baja cobertura vacunal va acompañada de la reintroducción de enfermedades prevenibles por vacunación como el sarampión. El regreso de enfermedades hasta ahora eliminadas, como la poliomielitis, puede agravar la crisis sanitaria aún en curso. A pesar de ser reconocido como uno de los programas de inmunización más efectivos del mundo y de los esfuerzos permanentes, el Programa Nacional de Inmunización enfrenta un escenario extremadamente adverso en lo que se refiere a las coberturas vacunales. Este artículo describe el Proyecto por la Reconquista de las Altas Coberturas Vacunales (PRCV) y la estrategia de trabajo al final del sistema, ejecutada en los territorios, que se implementa desde 2021 y ya comienza a mostrar resultados prometedores. El PRCV fue organizado en tres ejes temáticos con actuación compartida y acciones específicas, a saber: vacunación; sistemas de Información; comunicación y educación. Los resultados ya alcanzados permiten afirmar que es posible lograr la reversión de las bajas coberturas vacunales, a partir de la articulación de acciones estructurales e interinstitucionales, con el fortalecimiento de las políticas públicas y desarrollo de medidas de corto, mediano y largo plazo. Los factores más potentes del PRCV son su abordaje junto a los profesionales de la punta, el pacto social por la vacunación, y la estructuración de redes locales de apoyo a las inmunizaciones.

Vacinas / Vaccines

Apresenta breve histórico sobre o desenvolvimento de vacinas, o que são as vacinas e porque vacinamos. Comenta sobre a vanguarda do Brasil nos programas de vacinação no século XXI

Vaccines for neglected and emerging diseases in Brazil by 2030: the valley of death and opportunities for RD& I in Vaccinology 4. 0 / Vacunas en Brasil para enfermedades emergentes y olvidadas en 2030: el valle de la muerte y oportunidades para RD& I en Vacunología 4. 0 / Vacinas para doenças negligenciadas e emergentes no Brasil até 2030: o vale da morte e oportunidades para PD& I na Vacinologia 4. 0

Abstract: We examine the implications of the very low competitiveness of the Brazilian vaccine RD&I system, which precludes the development of all the important vaccines required by the National Immunization Program (NIP), severely impacting the healthcare of the population. In a country dramatically affected by COVID-19 pandemic and by an exponential increase in emerging and neglected diseases, particularly the poor, these RD&I constraints for vaccines become crucial governance issues. Such constraints are aggravated by a global scenario of limited commercial interest from multinational companies in vaccines for neglected and emerging diseases, which are falling into a "valley of death," with only two vaccines produced in a pipeline of 240 vaccines. We stress that these constraints in the global pipeline are a window of opportunity for vaccine manufacturers in Brazil and other developing countries in the current paradigm transition towards Vaccinology 4.0. We conclude with recommendations for a new governance strategy supporting Brazilian public vaccine manufacturers in international collaborations for a sustainable national vaccine development and production plan by 2030.

Resumen: Examinamos las implicaciones de la muy baja competitividad del sistema brasileño de ID&I de vacunas, que imposibilita el desarrollo de todas las vacunas importantes, requeridas por el Progrma Nacional de Inmunización (PNI), con impactos muy graves en la salud de la población de un país con 200 millones de habitantes. En un país gravemente afectado por la pandemia de COVID-19 y por enfermedades emergentes y olvidadas que afectan particularmente a los pobres, estas restricciones del ID&I para vacunas es, de hecho, un asunto crucial de gobierno. Estas limitaciones locales se han visto agravadas por un escenario global de interés comercial limitado, por parte de las compañías multinacionales, en vacunas para enfermedades emergentes y olvidadas, que están cayendo en un "valle de la muerte", con solamente dos vacunas producidas a nivel global frente a 240 vacunas. Identificamos en estas limitaciones globales una ventana de oportunidad para los fabricantes de vacunas en Brasil y otros países en desarrollo dentro del paradigma actual de transición hacia la Vacunología 4.0. Concluimos con recomendaciones de una nueva estrategia de gobierno que apoye a los fabricantes brasileños de vacunas públicas en colaboraciones internacionales para el plan nacional de desarrollo y producción sostenible de vacunas en 2030.

Resumo: Examinamos as implicações da competitividade tão baixa do sistema brasileiro de pesquisa, desenvolvimento e inovação (PD&I) de vacinas, que impede o desenvolvimento de todas as vacinas importantes requeridas pelo Programa Nacional de Imunizações (PNI), prejudicando gravemente a saúde da população. Em um país seriamente afetado pela pandemia de COVID-19 e por um aumento exponencial de doenças emergentes e negligenciadas, principalmente entre os brasileiros pobres, essas restrições de PD&I quanto às vacinas tornam-se questões cruciais de governança. Essas restrições são agravadas por um cenário global de interesse comercial limitado por parte das empresas multinacionais de vacinas para doenças negligenciadas e emergentes, que estão caindo em um "vale da morte", com apenas duas vacinas produzidas em um pipeline de 240 vacinas. Ressaltamos que essas restrições na produção global constituem uma janela de oportunidade para os fabricantes de vacinas no Brasil e em outros países em desenvolvimento na atual transição de paradigma para a Vacinologia 4.0. Concluímos com recomendações para uma nova estratégia de governança em suporte aos fabricantes públicos de vacinas no Brasil em colaborações internacionais para um plano nacional de desenvolvimento e produção de vacinas que seja sustentável até 2030.

Produção da vacina antipoliomielite no Brasil: o papel de Bio-Manguinhos / Production of polio vaccine in Brazil: the role of Bio-Manguinhos

Nesse capítulo se trata da contribuição decisiva do Instituto de Tecnologia de Imunobiológicos para os resultados alcançados no Brasil, que se refletiram no âmbito internacional. O instituto realizou importantes aperfeiçoamentos no processo de produção da vacina antipoliomielite oral e empreendeu esforços pioneiros em busca da autossuficiência nacional na fabricação deste antígeno, de modo a evitar riscos de desabastecimento e assegurar o suprimento regular do produto para os programas de saúde do país.

Produção da vacina antipoliomielite no Brasil: o papel de Bio-Manguinhos / Production of polio vaccine in Brazil: the role of Bio-Manguinhos

Neste capítulo se trata da contribuição decisiva do Instituto de Tecnologia em Imunológicos para os resultados alcançados no Brasil, que se refleteriam no âmbito internacional. O instituto realizou importantes aperfeiçoamentos no processo de produção da vacina antipoliomielite oral e empreendeu esforços pioneiros em busca da autossuficiência nacional na fabricação deste antígeno, de modo a evitar riscos de desabastecimento e assegurar o suprimento regular do produto para os programas de saúde do país.

Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

Zika puzzle in Brazil: peculiar conditions of viral introduction and dissemination: a review

This article discusses the peculiar conditions that favoured the unexpected introduction of Zika virus into the poorest northeastern region of Brazil in 2015, its speed of transmission to other Brazilian states, other Latin American countries and other regions, and the severity of related neurological disorders in newborns and adults. Contrasting with evidence that Zika had so far caused only mild cases in humans in the last six decades, the epidemiological scenario of this outbreak in Brazil indicates dramatic health effects: in 2015, an increase of 20-fold in notified cases of microcephaly and/or central nervous system (CNS) alterations suggestive of Zika congenital infection, followed by an exponential increase in 2016, with 2366 cumulative cases confirmed in the country by the end of December 2016. A significant increase in Guillain-Barré syndrome in adults has also been reported. Factors involved in viral dissemination, neural pathogenesis and routes of transmission in Brazil are examined, such as the role of social and environmental factors and the controversies involved in the hypothesis of antibody-dependent enhancement, to explain the incidence of congenital Zika syndrome in Brazil. Responses to the Zika outbreak and the development of new products are also discussed.

Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation - technological development issues

This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.

Atualização em vacinas, imunizações e inovação tecnológica / Vaccines, immunization and technological innovation: an update

A erradicação da varíola foi a maior conquista da saúde pública mundial. E o binômio vacinas e imunizações continua a demonstrar alto desempenho na prevenção e no controle de outras doenças imunopreveníveis. As novas iniciativas globais em vacinação, como a GAVI, vêm possibilitando a introdução de novas vacinas e salvando vidas de milhares de crianças nos países mais pobres do mundo. O Programa Nacional de Imunizações (PNI) do Brasil também vem sendo fortalecido com a incorporação de novas vacinas no seu calendário de imunizações, como a vacina contra rotavírus, pneumococos conjugada, meningite meningocócica do sorogrupo C conjugada, além do H1N1 para as populações de maior risco. Com o descobrimento de novas vacinas de alto valor agregado, os grandes laboratórios multinacionais despertaram para este segmento farmacêutico e buscam a liderança da área, investindo maciçamente em inovação tecnológica, além de realizar fusões, aquisições e parcerias tecnológicas. O Brasil também vem se fortalecendo, tendo criado marcos reguladores e financiando projetos de inovação tecnológica e modernização da infraestrutura de produção.

The smallpox worldwide eradication was the major world public health achievement. The binomial vaccines and immunization continues to demonstrate very high performance in the prevention and control of other diseases preventable by vaccination. The new global initiatives on vaccination, such as GAVI, have made possible the introduction of new and important vaccines preventing million of children deaths in the poorest countries in the world. The National Immunization Program of Brazil is also being strengthened, with the introduction of several new vaccines into the basic calendar as rotavirus, pneumococcal and meningococcal conjugated and H1N1 in national campaign, covering the population at risk. With the discovery of high valued vaccines, the big pharmaceutical companies became interested in this area, investing heavily in technological innovation, making fusions, acquisitions and technological partnerships. Brazil has also established a new innovation policy, creating new laws as well as subsidizing projects in technological innovation and modernization of production infra-structure.

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.

Incidência de episódios hipotônicos-hiporresponsivos associados à vacina combinada DTP/Hib usada no Programa Nacional de Imunizações / Incidence of hypotonic-hyporesponsive episodes associated to the combined DTP/Hib vaccine used in Brazilian National Immunizations Program

OBJETIVO: Avaliar a segurança da vacina combinada de difteria-tétano-coqueluche de células inteiras e Haemophilus influenzae tipo b usada no Programa Nacional de Imunizações, e em especial a incidência de episódios hipotônicos-hiporresponsivos. MÉTODO: Acompanhamento de uma coorte de 21.064 lactentes (20.925 ou 99,7 por cento aderiram ao protocolo de estudo), nas 48 horas após a aplicação da vacina de difteria, tétano, coqueluche de células inteiras e Haemophilus influenzae tipo b em centros de saúde na cidade do Rio de Janeiro, para determinar e investigar eventos adversos graves, espontâneos e solicitados. Cada criança foi monitorada durante somente uma dose. RESULTADOS: A incidência de episódios hipotônicos-hiporresponsivos foi de 1:1.744 doses (casos confirmados) e de 1:1.495 doses (casos confirmados mais casos suspeitos). A taxa de incidência de convulsões foi de 1:5.231 doses. Não foram detectados casos de apnéia. Esses resultados são comparáveis àqueles relatados na literatura para a vacina contra difteria-tétano-coqueluche de células inteiras. CONCLUSÃO: A vacina contra difteria, tétano, coqueluche de células inteiras e Haemophilus influenzae tipo b em estudo pode ser usada com segurança no Programa Nacional de Imunizações, de acordo com as precauções e contra-indicações correntes.

OBJECTIVE:To evaluate the safety of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine used on the Brazilian National Immunizations Program, chiefly the incidence of hypotonic-hyporesponsive episodes. METHOD: Follow-up of a cohort of 21,064 infants (20,925 or 99.7 percent adhered to the study protocol), within 48 hours of vaccination with diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine in health care units in the City of Rio de Janeiro, to ascertain and investigate spontaneous and solicited severe adverse events. Each child was followed-up for one dose only. RESULTS: The rate of hypotonic-hyporesponsive episodes was 1/1,744 doses (confirmed cases) and 1/1,495 doses (confirmed plus suspect cases). The rate of convulsions was 1/5,231 doses. No cases of apnea were detected. These results are comparable to those found in the literature with diphtheria-tetanus-whole cell pertussis vaccine. CONCLUSION: The diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine under study can be safely used in the National Immunizations Program, according to the current precautions and contraindications.