Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Submitted by Priscila Nascimento (pnascimento@icict.fiocruz.br) on 2012-12-04T11:37:37Z No. of bitstreams: 1 fernanda-martins.pdf: 786034 bytes, checksum: e059b45f6a12387864511efbf2ecfdbe (MD5) / Made available in DSpace on 2012-12-04T11:37:37Z (GMT). No. of bitstreams: 1 fernanda-martins.pdf: 786034 bytes, checksum: e059b45f6a12387864511efbf2ecfdbe (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil. / A combinação de vacinas é uma estratégia de grande relevância para o Programa Nacional de Imunizações. Através dela, é possível aumentar a proteção a múltiplas doenças em uma única vacina, bem como diminuir as constantes visitas ao posto de saúde. Contudo, uma das desvantagens em relação a esse tipo de estratégia é a possibilidade de ocorrer interferência antigênica entre os seus componentes,o que pode resultar na diminuição da resposta imunológica. Devido a este fato, foi realizada uma combinação com vacinas já presentes no calendário brasileiro de imunizações (DTP-Hib) a vacinas experimentais em desenvolvimento em Bio-Manguinhos (meningocócica B e meningocócica C conjugada), com a finalidade de apresentar uma nova perspectivade produto a esta unidade bem como estabelecer a correlação antigênica entre esses componentes, comparando metodologias já padronizadas para este fim à metodologia alternativa (ELISA), além de avaliar a pirogenicidade e a interferência entre os componentes vacinais utilizados na combinação. A resposta imunológica aos componentes vacinais foiavaliada em camundongos suíços, NIH e cobaias Short-Hair pelo ELISA (VME, polissacarídeo C, PRRP, Bordetella pertussis) e os testes de soroneutralização in vivo(componentes tetânico e diftérico). Todos os componentes vacinais avaliados pelo ELISA induziram soroconversão nos animais 30 dias após a última imunização. Quando comparadas à vacina combinada completa, somente a resposta imunológica ao polissacarídeo C sofreu interferência de algum componente vacinal. Após novas combinações davacina meningocócica C conjugada às outras vacinas, pode-se concluir que avacinas DTP e Hib interagem positivamente na resposta daquela vacina. Em relação à soroneutralização in vivo, houve uma diminuição da potência dos componentes tetânicoe diftérico quando cobaias Short-Hair foram imunizadas com a vacina DTP-Hib combinada às vacinas meningocócicas B e C conjugada. Em contrapartida, na quantificação de IgG total em camundongos suíços imunizados com as duas combinações (DTP-Hib e DTP-Hib/B/C), não ocorreu diferença significativa entre os dois grupos. O teste de pirogenicidade realizado em coelhos comprovou que, quando combinadas entre si, às vacinas são capazes de aumentar a temperatura destes animais, provavelmente, devido àpresença de Bordetella pertussise VME de Neisseria meningitidisgrupo B. Apesar de não ter sido possível à comparação com ostestes padronizados, o ELISA mostrou-se muito satisfatório na pesquisa da resposta imunológica em camundongos. Embora preliminares, os resultados são muito importantes, pois introduzem novas perspectivas para a realização de outras combinações que atendam as demandas requisitadas pelo Programa Nacional de Imunizações. / The combination of vaccines is a great relevance strategy to the National Immunization Program. It enables increase protection to multiple diseases in a single injection, as well as reduces constant visits to health care. However, a disadvantage of this strategy is antigenic interference among vaccine components, resulting in immune response decreased. Due to this fact, a combination between vaccines of Brazilian immunization calendar (DTP-Hib) and experimental vaccines developed in Bio-Manguinhos (meningococcal B and meningococcal C conjugate) wasperformed, in order to present a new perspective of product to this unit and establish the antigenic correlation of these components, comparing standardized methodologies with alternative methodology (ELISA), besides evaluating pyrogenicity and interference ofcombined vaccine components. The immune response to vaccine components was evaluated in Swiss and NIH mice and Short-Hair guinea pigs by ELISA (OMV, polysaccharide C, PRP, Bordetella pertussis) and in vivoneutralization test (tetanus and diphtheria components). All vaccine components assessed by ELISA induced seroconversion rates 30 days after the last immunization in animals. The complete combined vaccine, interfered in the immune response to polysaccharide C. After new combinations of meningococcal C conjugate vaccine to other vaccines, we concluded that DTP and Hib vaccines induce a positive interaction in immune response to that vaccine. Regarding in vivoneutralization, there was a decrease of tetanus and diphtheria components potency when Short-Hair guinea pigs were immunized with DTP-Hib combined to B and C meningococcal conjugate vaccines. In contrast, when total IgG in Swiss mice immunizedwith the two combinations (DTP-Hib and DTP-Hib/B/C) was quantified, no significant difference was observed. Pirogenicity test in rabbits proved that complete combined vaccine increase the temperature of these animals, probably due to the presence of Bordetella pertussisand Neisseria meningitidisgroup B outer membrane vesicle. Although it was not possible comparision with standardized test, ELISA was a satisfactory test in studing immune response in mice. Although preliminary, the results are important because introduce new perspectives for other combinations could be done to atempt the required demands of National Immunization Program.

Introduction and Background: Measles, mumps and rubella (MMR) are infectious diseases, primarily of childhood, which cause significant mortality and morbidity globally. These infections are, however, vaccine preventable and there is potential for them to be eradicated worldwide through the strategic use of organised population immunisation programmes. Following the introduction of the MMR vaccination in the UK in 1988, uptake was initially good and a high level of population vaccination coverage was achieved. This was sustained until 1998 when a study by Dr Wakefield and colleagues was published in the Lancet suggesting the theoretical possibility of an association between MMR and Autism/bowel disease. Intense media coverage followed, uptake of MMR vaccine fell to less than 80% in Somerset, and community outbreaks of measles, which had almost been eliminated in the UK, began to reappear. The Wakefield study was subsequently discredited and was eventually retracted by the Lancet in 2010. In August 2008 the Chief Medical Officer announced a national MMR catch-up campaign, targeting all children between the age of 13 months and 18 years who had either not been vaccinated against measles, mumps and rubella, or had only partial immunisation. These children were invited again for vaccination and the campaign was completed in January 2009. This study was undertaken to explore, in depth, the quantitative data available in respect of the uptake of MMR at the time of the 2009 campaign, and also to provide new qualitative data in relation to the attitudes, beliefs and experience of MMR and immunisation services of parents who continued to decline MMR for their children after the 2009 campaign, in order to identify factors which affected parental decision-making, add to the wider knowledge base, and to use this knowledge to improve the future development of immunisation services in Somerset. Methods: The overall objective of the study was to investigate a number of social, demographic and geographic characteristics of parents and children associated with MMR uptake, to compare these characteristics within and between defined sub-sets of the Somerset population, and to explore the basis on which parents in Somerset make decisions in relation to MMR immunisation. The study design adopted was a ‘mixed methods’ approach comprising of a cross-sectional design with three sequential phases - an exploration of baseline epidemiological data; a survey conducted with parents of children who remained unimmunised after 2009; and finally, semi-structured interviews with a sub-set of these parents. Results: The key findings from the study are: Parents who decline MMR for their children are not a homogenous group, but consist of a number of sub-groups each of which have different motives, decision pathways and predicted outcomes in relation to potential to change their mind and accept MMR There are differences in geographic distribution between the two age groups investigated Whilst the ‘Wakefield’ study did, and still does have, an impact, it is not the only or most important factor in their continuing decision-making. There is evidence that health professionals have a key role in addressing parental concerns in respect of immunisation. GP practice was the most significant factor associated with uptake in the Phase 1 study, and this was further confirmed in interviews with parents. Parents make decisions through engagement, through communicating and relating to others and this offers a potential mechanism for health professionals to influence decisions through open engagement with parents. Discussion and Conclusions: Three parent sub-groups were identified (Single Vaccines; Medical Comorbidities and Natural Health). These sub-groups were further investigated and factors associated with the decision-making pathways of each group were identified. This resulted in the development of the ‘MMR Parent Engagement Framework’ as a tool for use by professionals in planning their interactions with parents to improve and encourage more open dialogue in order to positively influence parental decision-making in relation to accepting MMR or other vaccinations. From a commissioning perspective, embedding frameworks such as this in service specifications offers a more cost-effective approach to improving immunisation uptake than funding large, poorly targeted catch-up campaigns. It is therefore recommended that further research is undertaken to provide evidence of the effectiveness of the approach in practice, and to inform future commissioning decisions. Additional recommendations to improve the effectiveness and delivery of immunisation services are also made in respect of GP Practice specific factors, independent schools, ethnic minority communities, vaccine overload, media, and data validation. The study has already directly influenced changes in current practice at both a local and a national level.