Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:16Z No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:45Z (GMT) No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-28T11:44:45Z (GMT). No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-15 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / INTRODUCTION: Routine infant immunization with meningococcal C conjugate vaccine (MenC-V) started in Brazil in November 2010, administered at three, five and 12 months of age with no catch-up for older age-groups. However, by March 2010, a vaccination campaign with MenC-V was performed in Salvador in individuals under five years-old, and from 10 to 24 yearsold. In São Paulo state, the outbreaks occurred in teenagers and young adults prompting one-time vaccination campaign from 2010 to 2014 targeting these age-groups. OBJECTIVE: To assess the direct and indirect impact (herd effect) of vaccination on invasive meningococcal disease (MD) for capsular group C (MenC) four years after the introduction of MenC-V in three scenarios: i) Brazil as a whole (routine vaccination in childhood only); ii) Brazil except for Salvador (vaccination campaign with teenagers during the year of MenC-V introduction); and iii) São Paulo state (vaccination campaign for adolescents and young adults during 2010-2014 to control outbreaks). METHODS: We performed an ecological quasi-experimental design from 2008 to 2014 using data from the National Reference Laboratory for Meningitis, and data from the National Information System for Notifiable Diseases. A deterministic linkage was performed between the two databases to improve the accuracy of the detection of MD, especially in capsular groups. An interrupted time-series analysis was conducted using the Holt-Winters technique to control for pre-existing trends and seasonal variations. The MenC vaccination impact was evaluated as the percentage of reduction in the incidence rates of MenC in the post-vaccination period (2012 to 2014), using the pre-vaccination period (2008 to 2010) to estimate what would be expected on the post-vaccination period, whether the vaccination had not been introduced. For Salvador, we analyzed the effect of the vaccination on the number of MenC cases. RESULTS: A total of 18,136 invasive MD cases were analyzed. For Brazil as a whole, the vaccination reduced 67.4% (lower 95%CI 42.5%) the rates for MenC for infants under 12 months, 92.3% (lower 95%CI 77.7%) for the age-group 12-23 months, and 65.7% (lower 95%CI 28%) for children aged 2-4 years. Indirect impact (20-24.7%) was observed in the age-group 5-19 years. When excluding Salvador from the analysis of Brazil, the indirect impact was observed only for children in the age-group 5-9 years. In the scenario of São Paulo state, similarly to Brazil, significant impact was observed in the target age-groups, in addition to indirect impact in the age group 5-9 years. In Salvador, in addition to the effect on the vaccinated population a sharp and sustainable decline of MenC cases was observed in all age-groups not target for vaccination. Overall, 1,170 cases of MenC were averted in Brazil after the introduced of Men-C vaccination. CONCLUSION: The strategy of catch-up for adolescents and young adults, especially during the year of MenC-V introduction may lead to rapid and sustainable herd effect. / A vacina meningocócica conjugada contra o grupo capsular C (MenC-V) foi introduzida no calendário de imunização infantil brasileiro em novembro de 2010, sendo administrada aos três, cinco e 12 meses de idade sem catch-up para os demais grupos etários. Entretanto, em março de 2010, uma campanha de vacinação com MenC-V foi realizada em Salvador para indivíduos menores de cinco anos de idade e de 10 a 24 anos. No estado de São Paulo os surtos ocorreram em adolescentes e adultos jovens, determinando campanhas de vacinações de bloqueio nessa faixa etária nos anos de 2010 a 2014. OBJETIVO: Avaliar o impacto direto e indireto (rebanho) da vacinação nas taxas de incidência de doença meningocócica (DM) invasiva pelo grupo capsular C (MenC) após quatro anos da introdução da MenC-V em três cenários: i) Brasil como um todo (imunização de rotina somente de crianças); ii) Brasil exceto Salvador (campanha de vacinação em adolescentes no ano de introdução da MenCV); e iii) estado de São Paulo (vacina de rotina na infância e vacinações de bloqueio em adolescentes e adultos jovens para controlar surtos). MÉTODOS: Foi realizado um estudo ecológico quasi-experimental para avaliar o impacto da vacinação em série histórica de 2008 a 2014 usando os bancos de dados do Laboratório Nacional de Referência para Meningites Bacterianas, Instituto Adolfo Lutz (IAL) e o Sistema de Informação de Agravos de Notificação (Sinan). Um processo de vinculação (linkage) determinístico entre as duas bases foi realizado para melhorar a acurácia da detecção de casos de DM, especialmente de grupo capsulares. Uma análise de série temporal interrompida foi conduzida utilizando a técnica de Holt-Winters para controlar por tendência pré-existente e variações sazonais. O desfecho foi taxa de MenC. O impacto da vacinação foi avaliado pelo percentual de redução da incidência de MenC no período pós-vacinal (2012 a 2014), utilizando o período pré-vacinal (2008 a 2010) para estimar o que seria esperado no período pós-vacinal, caso a vacinação não tivesse sido introduzida. Para Salvador foi analisado o efeito da MenC-V no número de casos de MenC. RESULTADOS: Um total de 18.136 casos de DM invasiva foram analisados. Para o Brasil como um todo, a vacinação reduziu significativamente a DM por MenC na faixa etária alvo, com redução de 67,4% (limite inferior do IC95% 42,5%) em menores de 12 meses, 92,3% (limite inferior do IC95% 77,7%) para faixa etária de 12-23 meses e 65,7% (limite inferior do IC95% 28%) em crianças de 2-4 anos, e efeito rebanho foi observado na faixa etária de 5 a 19 anos com 20-24,7%. Quando se exclui Salvador na análise do Brasil, impacto indireto significativo foi observado somente em crianças de 5-9 anos. No cenário São Paulo, semelhante ao Brasil, observou-se impacto estatisticamente significante nas faixas etárias alvo do PNI, além do efeito rebanho na faixa etária de 5-9 anos de idade. Para Salvador, o impacto da vacinação apresentou um declínio acentuado e sustentável em todas as faixas etárias fora do alvo da vacinação. Ao todo, 1.170 casos de MenC foram evitados no período estudado. CONCLUSÃO: A estratégia de vacinação de catch-up em adolescentes e adultos jovens, especialmente no ano de introdução da MenC-V, promoveu um rápido e sustentável rebanho.

Problématique : L’amélioration de l’accessibilité financière aux soins de santé est essentielle pour réduire la morbidité et de la mortalité infantile dans les pays à ressources limitées. Cependant, les preuves disponibles sur la relation entre un accès accru aux soins et l’amélioration la santé infantile, dans le long terme, demeurent insuffisantes et parfois inconnues. Dans le contexte spécifique de la région du Sahel au Burkina Faso où les niveaux élevés de morbidité et de malnutrition coïncident avec un faible recours aux soins, une intervention de santé publique associant la gratuité des soins à l’amélioration de la qualité des soins et à la prise en charge de la malnutrition dans la communauté a été mise en œuvre en septembre 2008. Objectifs : En utilisant des approches statistiques et épidémiologiques appliquées aux données transversales et de séries chronologiques, cette thèse vise à apporter une meilleure compréhension de la façon dont la présence de l’intervention dans les communautés peut augmenter et maintenir l’utilisation des services de santé à long terme et améliorer la santé des enfants de moins de cinq ans. Les objectifs spécifiques sont : 1) évaluer le maintien à long terme des effets de l’intervention sur l’utilisation des services de santé chez les enfants de moins de cinq ans, 2) évaluer l’effet contextuel de l’intervention, quatre ans après le début de sa mise en œuvre, sur la probabilité de survenue d’une maladie et sur la probabilité d’utilisation des services de santé chez les enfants de moins de cinq ans, et 3) évaluer l’effet contextuel de l’intervention, quatre ans après le début de sa mise en œuvre, sur le retard de croissance chez les enfants de moins de cinq ans. Méthodes : Les données proviennent du système national d’information sanitaire, d’une enquête rétrospective sur les services de santé ainsi que d’une enquête de ménages réalisée quatre ans après le début de l’intervention dans 41 villages du district d’intervention et 51 villages du district de comparaison. Nous avons utilisé un plan quasi expérimental à séries temporelles interrompues avec groupe de comparaison pour évaluer les effets immédiats et à long terme de l’intervention sur les taux d’utilisation des services de santé. Ensuite, un plan d’étude transversale post-intervention avec un groupe de comparaison nous a permis d’évaluer l’effet contextuel de l’intervention sur la probabilité de survenue d’une maladie, sur la probabilité d’utilisation des services de santé et sur le retard de croissance chez les enfants de moins de cinq ans. La stratégie analytique a combiné la méthode de pondération par les scores de propension pour équilibrer les covariables entre les deux groupes, la modélisation binomiale négative à effets mixtes, les régressions linéaire et logistique multiniveaux. Résultats : L’intervention de gratuité des soins associée à l’amélioration de la qualité des soins et à la prise en charge de la malnutrition dans la communauté était associée à l’augmentation et au maintien de l’utilisation des services de santé au-delà de quatre ans (ratio des taux d’incidence = 2,33 ; IC 95 % = 1,98 – 2,67). En outre, comparativement aux enfants vivant dans le district de contrôle, la probabilité d’utiliser les services de santé était de 17,2 % plus élevée chez les enfants vivant dans le district d’intervention (IC 95 % = 15,01–26,6) ; et de 20,7 % plus élevée lorsque l’épisode de maladie était sévère (IC 95 % = 9,9–31,5). Ces associations étaient significatives, quels que soient la distance par rapport aux centres de santé et le statut socio-économique du ménage. Par ailleurs, alors que le contexte de résidence expliquait 9,36 % de la variance du retard de croissance (corrélation intraclasse = 9,36 % ; IC 95 % = 6,45–13,38), la présence de l’intervention dans les villages n’explique que 2 % de la variance du retard de croissance. Cependant, nous n’avons pas pu démontrer que la présence de l’intervention dans les communautés était associée à une réduction de la probabilité de survenue d’un épisode de maladie (Différentiel des probabilités = 4.4 ; IC 95% = -1.0 – 9.8), ni à une amélioration significative de l’état nutritionnel des enfants de moins de cinq ans (RC = 1,13 ; IC 95 % = 0,83–1,54). Conclusion : Cette thèse souligne que la gratuité des soins associée à l’amélioration de la qualité des soins et à la prise en charge de la malnutrition dans la communauté est efficace pour augmenter et maintenir l’utilisation des services de santé et réduire les inégalités géographiques de recours aux soins. Cependant, cette intervention n’était pas associée à une amélioration des résultats de santé infantile. Bien que des études longitudinales rigoureuses soient nécessaires pour comprendre pleinement l’influence potentielle de cette intervention sur la morbidité, cette thèse plaide pour la nécessité d’agir simultanément sur les autres déterminants sociaux de la santé et d’intégrer, de manière synergique, des interventions spécifiques à la nutrition pour plus d’impact sur la santé infantile. / Introduction: Improving financial access to health care is believed to be essential for reducing the burden of child morbidity and mortality in resource-limited settings, but the available evidence on the relationship between increased access and health remains scarce and the long-term issues are still unknown. In the specific context of the Sahel region in Burkina Faso where high levels of morbidity and malnutrition coincide with low health care use, a pilot intervention for free health care including quality of care improvement and management of malnutrition at the community level was implemented in September 2008. Objectives: Using statistical and epidemiological approaches applied to cross-sectional and time series data, this thesis aims to provide a better understanding of how the presence of intervention in communities can increase and maintain long-term use of health services and improve the health of children under five years. The specific objectives are: 1) to evaluate the long-term effects of the intervention on the use of health services in children under the age of five, 2) to estimate the contextual effect of intervention on the probability of occurrence of and the likelihood of health services being used by children under five, four years after the start of its implementation, and 3) to evaluate the contextual effect of the intervention on stunting in children under five, four years after the start of its implementation. Methods: The data for the analyses were provided from a variety of sources including the national health information system, a retrospective health services survey, and a household survey conducted four years after the intervention onset in 41 villages in the intervention district and 51 villages in the comparison district. We used a quasi-experimental controlled interrupted time-series design group to analyze the immediate and long-term effects of the intervention on the rate of health services utilization in children under five. Then, a quasi-experimental post-test-only design that included a control group allowed us to evaluate the contextual effect of the intervention on the probability of occurrence of a disease, on the probability of use of health services, and stunting in children under five. The analytic strategy combined the propensity score weighting method to balance the covariates between the two groups, two-level mixed-effects negative binomial, and linear and logistic regression models to account for the hierarchical structure of data. Results: The intervention for free health care including quality of care improvement and management of malnutrition at the community level was associated with an increased and maintained use of health services beyond four years after the onset of intervention (incidence rate ratio = 2.33; 95% CI = 1.98–2.67). In addition, compared to children living in the comparison district, the probability of using health services was 17.2% higher among those living in the intervention district (95% CI = 15.0–26.6); and 20.7% higher when the illness episode was severe (95% CI = 9.9–31.5). These associations were significant regardless of the distance to health centers and the socio-economic status of households. In addition, inequalities in the use of care were less pronounced in the intervention villages compared to those in the control village. Finally, the results also showed that the residence context accounted for 9.36% of the variance in stunting (intra-class correlation = 9.36% ; 95% CI = 6.45–13.38), and only 2% of the variance in stunting was explained by the intervention. However, we could not demonstrate that the intervention in these communities was associated with a reduced probability of an illness occurring (AME=4.4 (95% CI: -1.0 – 9.8), nor with a significant improvement in the nutritional status among children under five (OR = 1.13; 95% CI = 0.83–1.54). Conclusion: This thesis underlines the importance that affordable health care, including quality of care, as well as improving the management of malnutrition at the community level, are effective in increasing and maintaining the use of health services and reduce geographical inequalities in the use of care. However, this intervention was not associated with improved child health outcomes. Although rigorous longitudinal studies are necessary to fully understand the potential influence of this intervention on morbidity, this thesis highlights the need to simultaneously act on other social determinants of health and to synergistically integrate nutrition-specific interventions for greater impact on child health.