Made available in DSpace on 2014-07-29T15:25:13Z (GMT). No. of bitstreams: 1 TESE ANA LUIZA NETO JUNQUEIRA 2009.pdf: 346064 bytes, checksum: dd50393164905524036f6c970157aff8 (MD5) Previous issue date: 2009-08-13 / This study is the first randomized controlled clinical trial for assessing the immunogenicity and reatogenicity of the Butang® vaccine in full term newborns, who were given the first vaccine dose within the first 12 hours of life, comparing two regions of application for the vaccine: anterolateral thigh (ALT) and ventrogluteal (VG). Butang® response was assessed in 224 newborns who were given the vaccine in the VG region and 250 in the ALT one. Both groups were similar regarding gender, weight, timing interval between doses of the vaccine and maternal characteristics. When comparing Butang® immunogenicity, we verified that the proportion of babies who developed anti-HBs protecting titres after three vaccine doses in the VG region was of 97.8% (IC 95%: 94.8 99.3) with geometric mean titer (GMT) of 427.5 mUI/mL (IC 95%: 344.9 530.0), similar to those who were given in the ALT region (97.6%; IC 95%: 94.8 99.1; GMT: 572.0 mUI/mL; IC 95%: 471.1 694.6), which provides evidence that this place is appropriate for hepatitis B vaccination. Eleven newborns did not respond to Butang®, being six of them vaccinated in the VG region and five in the ALT. The most of them were male, one factor which seems to interfere with hepatitis B vaccine response. We verified an increasing proportion of local reactions and fever according to the number of doses given. In addition, after the third dose the proportion of induration (4.0 vs. 11.4) was higher among babies who were given the vaccine in the ALT region when compared to those who were given in the VG region (p < 0,05). No association was observed concerning maternal anti-HBs titres and newborn vaccine response. The evidences of this study showed that the VG region is a safe and immunogenic site to hepatitis B vaccine administration in newborns. / Este estudo trata-se do primeiro ensaio clínico randomizado controlado, para avaliação da imunogenicidade e reatogenicidade da vacina Butang® em recém-nascidos a termo, que receberam a primeira dose da vacina nas primeiras doze horas de vida, comparando duas regiões de aplicação do imunógeno: ventro glútea (VG) e vasto lateral da coxa (VLC). A resposta à Butang® foi avaliada em 224 RN vacinados na região VG e 250 na VLC. Os dois grupos foram semelhantes quanto ao sexo, peso, intervalo de tempo entre as doses da vacina e características maternas. Ao comparar a imunogenicidade da Butang®, verificou-se que a proporção de crianças que desenvolveu títulos protetores de anti-HBs após a vacinação na região VG foi de 97,8% (IC 95%: 94,8-99,3) com média geométrica dos títulos (GMT) de anti-HBs de 427,5 mUI/mL (IC 95%: 344,9 530,0), sendo semelhante às vacinadas na região VLC (97,6%; IC 95%: 94,8 99,1; GMT: 572,0 mUI/mL; IC 95%: 471,1 694,6), evidenciando, portanto, esses locais como apropriados para a administração do imunógeno. Onze RN não responderam à Butang® com títulos protetores, sendo que cinco foram vacinados na região VG e seis na VLC. A maioria dessas crianças era do sexo masculino, um fator que parece interferir na resposta vacinal contra hepatite B. Em geral, observou-se uma proporção maior de reações locais e febre de acordo com o número de doses recebidas. Além disso, após a terceira dose da vacina, a proporção de enduração foi menor (4,0 vs. 11,4) em crianças vacinadas na região VG do que nas vacinadas na VLC (p < 0,05). Não foi observada qualquer associação entre títulos de anti-HBs maternos e resposta vacinal dos seus conceptos. As evidências deste estudo mostram que a região VG é um local seguro e imunogênico para a administração da vacina contra hepatite B em lactentes.

Thesis (Dr. P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / "May 2007." Includes bibliographical references.

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No. of bitstreams: 2 Dissertação - Luana Rocha da Cunha Rosa - 2018.pdf: 2963447 bytes, checksum: 815df889754ae2ebd98618b9edc622ab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-05 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Despite the impact of the hepatitis B virus (HBV) worldwide in diverse populations, investigations have focused on urban groups with few studies targeting the rural population. In Brazil, manual sugarcane cutters are rural workers exposed to multiple challenging conditions that increase their vulnerability to HBV. The objective of this study was to investigate the epidemiology of hepatitis B in manual sugar cane cutters from the States of Goiás and Paraíba. This is a multicentric analytical cross-sectional study carried out in the states of Goiás and Paraíba, in the Midwest and Northeast regions of Brazil, respectively. Data collection took place in 2016, and 937 sugarcane cutters aged 18 or over were recruited. All subjects were interviewed and tested for the detection of hepatitis B serological markers (HBsAg, anti-HBs and anti-HBc) by enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate analyses with logistic regression were used to identify association between HBV exposure and sociodemographic and behavioral variables. This study was approved by the Research Ethics Committee of the Federal Universities of Goiás and Paraíba. All participants (n = 937) were male, mostly young adults (68.9%), with an average age of 35.4 years, and natives of the Northeast Region of the country (85.7%). Of the total, 78.8% reported monthly income less than BRL$2,000.00 (about USD$540) and almost half (47.4%) declared four years of education or less. Among the participants, 49.4% started sexual activity early, aged between 7 and 15 years; 77.2% reported history of alcohol use; 29.6% reported experience living in shared housing; 39.8% reported two or more sexual partners in the last year; and 46.5% reported not having used a condom in the same period. In addition, 45.8% shared sharp personal hygiene instruments; 55.0% reported previous hospitalization, and 53.9% had at least one work related accident. The overall prevalence of HBV exposure was 15.9% (95% CI: 13.7% - 18.4%). The HBsAg marker was detected in seven individuals, all of whom presented at least one risk behavior for hepatitis B. Only 20.6% (n = 193, 95% CI: 23.1% - 23.3%) tested positive for isolated anti-HBs, indicating previous vaccination. It was observed that reports of two or more sexual partners in the last 12 months and history of hospital admission (p<0.05) were predictors of HBV exposure, confirming these routes of parenteral and sexual transmission. These results demonstrate the need for effective hepatitis B prevention strategies among sugarcane cutters, focusing on timing, supply and administration of hepatitis B vaccine. / Apesar do grande impacto do vírus da hepatite B (HBV) em todo mundo, investigações têm se concentrado em grupos urbanos, sendo poucos estudos voltados para a população rural. No Brasil, os cortadores de cana-de-açúcar manual compõem um grupo de trabalhadores rurais expostos a um cenário multifatorial, que os tornam vulneráveis ao HBV. O objetivo deste estudo foi investigar a epidemiologia da hepatite B em cortadores de cana-de-açúcar manual dos Estados de Goiás e Paraíba. Trata-se de uma investigação multicêntrica, de corte transversal e analítico, realizada nos Estados de Goiás e Paraíba, Região Centro-Oeste e Nordeste do Brasil, respectivamente. A coleta de dados ocorreu em 2016 e foram recrutados 937 cortadores de cana-de-açúcar, com idade igual ou acima de 18 anos. Todos os indivíduosforam entrevistados e testados para a detecção dos marcadores sorológicos da hepatite B (HBsAg, anti-HBs e anti-HBc), por meio do ensaio imunoenzimático (ELISA). Análises univariada e múltipla, por meio da regressão logística, foram utilizadas para identificar associação entre exposição ao HBV e variáveis sociodemográficas e comportamentais. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa das Universidades Federais de Goiás e Paraíba. Todos os cortadores de cana (n=937) eram do sexo masculino, majoritariamente adultos jovens (68,9%), com idade média de 35,4 anos e naturais da Região Nordeste do país (85,7%). Do total, 78,8% referiram renda mensal inferior a R$ 2.000,00 (dois mil reais) e quase a metade dos participantes (47,4%) declarou quatro anos de estudo ou menos. Entre os participantes, 49,4% iniciaram a atividade sexual precocemente, com idade entre 7 e 15 anos; 77,2% relataram ingestão de bebida alcoólica; 29,6% informaram experiência em moradia compartilhada; 39,8% afirmaram dois ou mais parceiros sexuais no último ano; e 46,5% mencionaram não ter utilizado o preservativo em igual período. Além disso, 45,8% compartilharam material cortante de higiene; 55,0% referiram história de internação hospitalar e 53,9% sofreram acidente no trabalho. A prevalência global de exposição ao HBV foi de 15,9% (IC 95%: 13,7% - 18,4%). O marcador de infecção HBsAg foi detectado em sete indivíduos, todos apresentaram pelo menos um comportamento de risco para hepatite B. Somente 20,6% (n=193; IC 95%: 18,1% - 23,3%) apresentaram títulos de anti-HBs isolado, indicando vacinação prévia. Observou-se que relato de dois ou mais parceiros sexuais nos últimos doze meses e história de internação hospitalar (p<0,05) foram preditores para a exposição ao HBV, ratificando as vias de transmissão parenteral e sexual. Esses resultados mostram a necessidade de estratégias efetivas de prevenção da hepatite B entre os cortadores de cana, com foco na oportunidade, oferta e administração da vacina contra hepatite B.

Made available in DSpace on 2014-07-29T15:28:53Z (GMT). No. of bitstreams: 1 TESE ANA LUIZA NETO JUNQUEIRA 2009.pdf: 346064 bytes, checksum: dd50393164905524036f6c970157aff8 (MD5) Previous issue date: 2009-08-13 / This study is the first randomized controlled clinical trial for assessing the immunogenicity and reatogenicity of the Butang® vaccine in full term newborns, who were given the first vaccine dose within the first 12 hours of life, comparing two regions of application for the vaccine: anterolateral thigh (ALT) and ventrogluteal (VG). Butang® response was assessed in 224 newborns who were given the vaccine in the VG region and 250 in the ALT one. Both groups were similar regarding gender, weight, timing interval between doses of the vaccine and maternal characteristics. When comparing Butang® immunogenicity, we verified that the proportion of babies who developed anti-HBs protecting titres after three vaccine doses in the VG region was of 97.8% (IC 95%: 94.8 99.3) with geometric mean titer (GMT) of 427.5 mUI/mL (IC 95%: 344.9 530.0), similar to those who were given in the ALT region (97.6%; IC 95%: 94.8 99.1; GMT: 572.0 mUI/mL; IC 95%: 471.1 694.6), which provides evidence that this place is appropriate for hepatitis B vaccination. Eleven newborns did not respond to Butang®, being six of them vaccinated in the VG region and five in the ALT. The most of them were male, one factor which seems to interfere with hepatitis B vaccine response. We verified an increasing proportion of local reactions and fever according to the number of doses given. In addition, after the third dose the proportion of induration (4.0 vs. 11.4) was higher among babies who were given the vaccine in the ALT region when compared to those who were given in the VG region (p < 0,05). No association was observed concerning maternal anti-HBs titres and newborn vaccine response. The evidences of this study showed that the VG region is a safe and immunogenic site to hepatitis B vaccine administration in newborns. / Este estudo trata-se do primeiro ensaio clínico randomizado controlado, para avaliação da imunogenicidade e reatogenicidade da vacina Butang® em recém-nascidos a termo, que receberam a primeira dose da vacina nas primeiras doze horas de vida, comparando duas regiões de aplicação do imunógeno: ventro glútea (VG) e vasto lateral da coxa (VLC). A resposta à Butang® foi avaliada em 224 RN vacinados na região VG e 250 na VLC. Os dois grupos foram semelhantes quanto ao sexo, peso, intervalo de tempo entre as doses da vacina e características maternas. Ao comparar a imunogenicidade da Butang®, verificou-se que a proporção de crianças que desenvolveu títulos protetores de anti-HBs após a vacinação na região VG foi de 97,8% (IC 95%: 94,8-99,3) com média geométrica dos títulos (GMT) de anti-HBs de 427,5 mUI/mL (IC 95%: 344,9 530,0), sendo semelhante às vacinadas na região VLC (97,6%; IC 95%: 94,8 99,1; GMT: 572,0 mUI/mL; IC 95%: 471,1 694,6), evidenciando, portanto, esses locais como apropriados para a administração do imunógeno. Onze RN não responderam à Butang® com títulos protetores, sendo que cinco foram vacinados na região VG e seis na VLC. A maioria dessas crianças era do sexo masculino, um fator que parece interferir na resposta vacinal contra hepatite B. Em geral, observou-se uma proporção maior de reações locais e febre de acordo com o número de doses recebidas. Além disso, após a terceira dose da vacina, a proporção de enduração foi menor (4,0 vs. 11,4) em crianças vacinadas na região VG do que nas vacinadas na VLC (p < 0,05). Não foi observada qualquer associação entre títulos de anti-HBs maternos e resposta vacinal dos seus conceptos. As evidências deste estudo mostram que a região VG é um local seguro e imunogênico para a administração da vacina contra hepatite B em lactentes.

Les lymphocytes T CD4 (LT CD4) jouent un rôle central dans la régulation des réponses immunitaires vis-à-vis des agents infectieux et des vaccins. Cependant, leur différenciation in vivo est encore mal comprise et les caractéristiques des LT CD4 capables de persister à long terme tout en assurant une réponse immunitaire protectrice sont mal définies. L’approfondissement de ces connaissances est indispensable pour le développement de nouveaux vaccins. <p>Pour approcher cette question, nous avons utilisé deux approches expérimentales. La première est un suivi de la différenciation des LT CD4 au cours de la réponse immune primaire chez des sujets vaccinés contre l’hépatite B ;la deuxième est la caractérisation phénotypique et fonctionnelle des LT CD4 mémoires antigène(Ag)-spécifiques pendant la phase d’état. Cette analyse a été réalisée au sein des LT CD4 spécifiques d’Ag vaccinaux, l’Ag de surface du virus de l’hépatite B (HBs) et la toxine tétanique (TT), ainsi que ceux spécifiques des Ag du cytomégalovirus (CMV). Les LT CD4 Ag-spécifiques ont été mis en évidence par cytométrie de flux après marquage intracytoplasmique du ligand du CD40 (CD40L) exprimé en réponse à une stimulation de courte durée par l’Ag. Des expériences basées sur la stimulation par la toxine du syndrome du choc toxique et le marquage du segment Vbeta2 du récepteur des LT ont démontré la bonne sensibilité et spécificité de cette méthode.<p>Le suivi de la réponse primaire chez 11 donneurs jusqu’à plus d’un an après immunisation par le vaccin anti-hépatite B a permis d’établir un modèle de différenciation des LT CD4 Ag-spécifiques in vivo chez l’homme. Nous avons mis en évidence des LT CD4 spécifiques d’un nombre limité de peptides immunodominants de la protéine HBs suggérant une réponse de type oligoclonale. Grâce à l’utilisation d’un cytomètre neuf couleurs, nous avons mené une analyse détaillée de l’hétérogénéité de la population mémoire HBs-spécifique. L’expression du CCR7 permet de distinguer des cellules de type mémoire centrale (LTCM, CCR7+) et effectrice (LTEM, CCR7-) se distinguant notamment par leur capacité à migrer vers les ganglions lymphatiques ainsi que par leurs propriétés fonctionnelles. Nous avons montré l’existence de ces deux sous-populations au sein des cellules HBs-spécifiques mais par opposition à leur définition initiale, ces LTCM sont capables de produire des cytokines effectrices. La proportion importante de LTCM exprimant le Ki67 témoigne d’une activité proliférative persistante in vivo et suggère la capacité de ces cellules à s’auto-renouveler et éventuellement à alimenter le pool des LTEM. La proportion importante de LTCM exprimant la chaîne alpha du récepteur à l’IL-7 (CD127) suggère que ces cellules sont sensibles aux signaux émanant de l’IL-7, une cytokine dont le rôle dans le maintien de la mémoire lymphocytaire T est connu. Compte tenu de la relevance potentielle de ces caractéristiques uniques pour le développement de vaccins et de l’accumulation de travaux montrant l’avantage sélectif des LTCM à conférer une immunité protectrice, nous avons focalisé la dernière partie de ces recherches sur cette sous-population. Une étude transversale des LTCM spécifiques de plusieurs types d’Ag (éliminés (HBs et TT) ou persistants (CMV)) a été menée. Nos résultats montrent une hétérogénéité, variable selon l’Ag, de la capacité de ces cellules à produire des cytokines effectrices et de leur phénotype de différenciation. Cette donnée nouvelle soulève la possibilité que les LTCM soient hétérogènes dans leur capacité à conférer une immunité protectrice. L’acquisition du marqueur KLRG1 par une fraction des LTCM s’associe à une capacité accrue à produire des cytokines effectrices et à une expression élevée du CD127. La possibilité que ces cellules soient particulièrement aptes à conférer une immunité protectrice et durable est discutée, tout comme les mécanismes menant à leur génération et l’intérêt de ces connaissances pour la conception de nouveaux vaccins.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Alors que le contentieux des produits de santé n'a jamais été aussi fourni, l'application du régime spécial de responsabilité du fait des produits défectueux issu de la directive européenne du 25 juillet 1985, entraîne l'émergence d'un certain nombre d'incertitudes qui affectent directement le sort des demandes en réparation. Les incertitudes matérielles ont, pour la plupart reçu un traitement efficace par l'action conjuguée de la jurisprudence et du législateur. Si les outils juridiques traditionnels, tels que les présomptions ou la causalité alternative, ont permis de résoudre une partie non négligeable de ces incertitudes, les juges se sont également attachés à développer des outils nouveaux comme la balance bénéfice/risque ou encore la répartition de l'obligation à la dette selon les parts de marché. Cependant, si le développement de ces outils juridiques, plus adaptés aux spécificités des produits de santé, a permis d'apporter une solution efficace aux incertitudes matérielles, le traitement de l'incertitude scientifique, fondé sur les présomptions du fait de l'homme, n'apporte, toujours pas, de solutions satisfaisantes. L'étude du traitement des incertitudes dans le contentieux des produits de santé défectueux permet d'apprécier les acquis mais également les limites atteintes par l'utilisation de certains outils mis à la disposition des juges et qui se révèlent parfois inadaptés. L'intervention du législateur et la prise en compte des spécificités des produits de santé, permettraient de développer un système d'indemnisation adapté qui interviendrait de façon subsidiaire en cas d'échec de la voie contentieuse. / At a time when healthcare-product litigation is attaining record heights, the implementation into French law of the special liability regime for defective products, which derives from the European Council Directive of 25 July 1985, has led to the emergence of several grey areas of uncertainty which have a direct impact on the outcome of claims for compensation. Areas of material uncertainty have, for the most part, been effectively dealt with through the combined application of case law and the intervention of the legislator. While classic legal tools such as presumption and alternative causality provide a means to resolve a non-negligible part of these uncertainties, judges have also endeavoured to develop new tools, such as risk/utility test and market-share liability. Still, although the development of these legal tools - better suited as they are to the specific features of healthcare products - provide an effective solution to resolving areas of material uncertainty, the treatment of scientific uncertainty, which is based on presumptions of fact, does not always provide satisfactory solutions. The study of the legal treatment of uncertainty in healthcare-product litigation provides a means to assess the benefits but also the limitations of certain tools that are now available to judges but which at times prove inadequate. Intervention on the part of the legislator, while at the same time taking into account the specific features of healthcare products, could lead to the development of a suitable compensation system that could afford relief when litigation fails.