Dissertations / Theses on the topic 'Rubeole congenitale'

The Newfoundland Department of Health administers several rubella vaccination programs for the prevention of congenital rubella syndrome (CRS). This study examined the effectiveness of these programs by reviewing rubella susceptibility in the population at risk for CRS, assessing the predictive value of a rubella vaccination record, and evaluating the effectiveness of the postnatal rubella vaccination program.
From 1989 to 1993, rubella susceptibility in women aged 15 to 44 averaged 4.6% overall, but was significantly higher in women aged 15 to 19 years, averaging 14%. The positive predictive value of a rubella vaccination record was 92% overall, but it differed by type of vaccine product and vaccine viral strain; 99% for any monovalent rubella vaccine, compared to 81% for recipients of HPV-77 DE-5 strain MR (measles rubella) or MMR (measles mumps rubella) vaccine. The postnatal rubella vaccination program failed to provide testing for 13% of pregnant women in the province in 1992, and 10% of susceptible women in 1992 were not subsequently vaccinated.
These results suggest that women of childbearing age in Newfoundland remain at risk of having children with CRS. The rubella vaccination record is not adequate proof of immunity for some of these women, and the postnatal vaccination program requires some improvement in order to prevent cases of CRS in the future.

As a model for studying apoptosis associated with pathogenesis of congenital rubella syndrome, bicistronic rubella virus (RUBV) replicons expressing an antibiotic resistance gene in the presence (925-IN) or absence (IN-IN) of RUBV capsid protein (C) were constructed. Apoptosis was assessed by detection of caspase activation, chromatin fragmentation, and flow cytometry. 925-IN cells grew similarly to Vero, but IN-IN cells demonstrated caspase activation, chromatin fragmentation and cell cycle arrest. Whereas Vero cells transfected with P150 exhibited rapid apoptosis not detected in transfected Vero cells stably expressing C, neither exhibited cell cycle alterations, indicating a cell cycle stall not associated with apoptosis. Finally, two human epithelial cells, HEK293 and A549, transfected with P150 failed to exhibit apoptosis, indicating that while replicon-transfected Vero cells are useful for studying apoptosis and cell cycle arrest, the results are not applicable to other cell types.

>Magister Scientiae - MSc
Despite widespread rubella virus (RV) vaccination programs, annually RV still causes severe congenital defects in an estimated 100,000 children globally. A concerted attempt to eradicate RV is currently underway and analytical tools to monitor the global decline of the last remaining RV lineages will be useful for assessing the effectiveness of this endeavour. Importantly, RV evolves rapidly enough that much of its epidemiological information might be inferable from RV genomic sequence data. Using BEASTv1.8.0, I analysed publically available RV sequence data to estimate genome-wide and gene-specific nucleotide substitution rates, to test whether the current estimates of RV substitution rates are representative of the entire RV genome. During these investigations, I specifically accounted for possible confounders of nucleotide substitution rate estimates, such as temporally biased sampling, sporadic recombination, and natural selection favouring either increased or decreased genetic diversity (estimated by the PARRIS and FUBAR methods) at nucleotide sites within RV nucleic acid secondary structures (predicted by the NASP method). I determined that RV nucleotide substitution rates range from 1.19×10-3 substitutions/site/year (in the E1 region) to 7.52×10-4 substitutions/site/year (in the P150 region). I found that these differences between nucleotide substitution rate estimates in various RV gene regions are largely attributable to temporal sampling biases, such that datasets containing a higher proportion of recently sampled sequences will tend to have inflated estimates of mean substitution rates. Although there exists little evidence of positive selection or natural genetic recombination in RV, I revealed that RV genomes possess extensive biologically functional nucleic acid secondary structures and that purifying selection acting to maintain these structures contributes substantially to variations in estimated nucleotide substitution rates across RV genomes. Although both temporal sampling biases and purifying selection favouring the conservation of RV nucleic acid secondary structures have an appreciable impact on substitution rate estimates, I find that these biases do not preclude the use of RV sequence data to date ancestral sequences and evaluate the associated RV phylodynamics. The combination of uniformly high substitution rates across the RV genome and strong temporal signal within the available sequence data enabled me to analyse the epidemiological and demographical dynamics of this virus during these attempts to eradicate it. By implementing a generalized linear model (GLM) and symmetrical model of discretized phylogeographic spread, I was able to identify several predictive variables of geographical RV spread and detect transmission linkages between distinct geographical regions. These results suggest that, in addition to strengthened vaccination strategies, there also needs to be an increased effort to educate people about the effects of vaccination and risks of RV infection.

O objetivo deste estudo é estimar o risco de infecção congênita pelo vírus da vacina contra rubéola e estimar o risco de ocorrência de aborto, baixo peso e prematuridade nas gestantes suscetíveis e imunes para rubéola identificando os fatores de risco associados a estes eventos. Embora não tenham havido manifestações clínicas compatíveis com SRC, observou-se uma ocorrência aumentada de baixo peso ao nascer e prematuridade entre os RN infectados quando comparados com as crianças não infectadas também nascidas de mães susceptíveis. No modelo final das análises utilizando a regressão logística multivariada, entretanto, a suscetibilidade para rubéola não esteve associada com a ocorrência de baixo peso e nem com prematuridade. Estes resultados sugerem que a recomendações de não vacinar gestantes para rubéola ainda deve ser mantida
The objective of this study is to evaluate the risk of congenital infection due to rubella vaccine virus and the occurrence of premature labor, miscarriage, and low birth weight in susceptible and immune pregnant women vaccinated during pregnancy, identifying the risk factors associated. We observe a high incidence of low birth weight and prematurity in the infected newborns, when compared with the children not infected, also born of susceptible mothers. In the final model of the logistic regression we didn't find association with rubella susceptibility and the predictors miscarriage, low birth weight and premature labor. These results suggest that the recommendations to not vaccinate pregnant women against rubella must be sustained

INTRODUÇÃO: Em 1999 e 2000, a ocorrência de surtos de rubéola, com maior acometimento entre adultos jovens, refletiu no aumento da síndrome da rubéola congênita. Como estratégia de controle da doença, foram realizadas campanhas de vacinação contra a rubéola em mulheres em idade fértil em vários Estados do País. Em razão das controvérsias existentes na literatura geradas quanto ao emprego da vacina de vírus vivos atenuados em gestantes, não se recomendou sua utilização durante a gravidez e até um mês após a aplicação da vacina. No entanto, 6.473 mulheres foram inadvertidamente vacinadas no Estado de São Paulo, sendo encaminhadas a serviços de referência para acompanhamento dessas gestações, dentre eles, o HCFMUSP. OBJETIVO: Este estudo buscou descrever as características clínicas e epidemiológicas das gestantes atendidas no HCFMUSP e obter os resultados dessas gestações. MÉTODO: Foi realizado um estudo epidemiológico descritivo, utilizando-se como fonte de dados as notificações das gestantes inadvertidamente vacinadas contra a rubéola e atendidas no HCFMUSP entre novembro de 2001 a dezembro de 2002. Para obter o desfecho das gestações, utilizou-se a base de dados dos nascidos vivos do Município de São Paulo (SINASC). RESULTADOS: No HCMFUSP, foram atendidas e notificadas 409 gestantes. Destas, 49,1% foram vacinadas no primeiro mês de gravidez e 26,2% engravidaram até um mês após a vacinação. Em relação a condição sorológica durante o pré-natal, 16,9% das gestantes apresentaram sorologia reagente para rubéola. Do relacionamento com a base de dados do SINASC, foram localizados os dados do parto de 63,3% das gestantes, sendo detectadas duas malformações congênitas no SINASC e um abortamento, porém, não se pode atribuir estes resultados à vacina, pois, as sorologias das mães não permitem determinar se estas mulheres eram realmente suscetíveis. CONSIDERAÇÕES FINAIS: O estudo apresentou o fluxo de informação estabelecido frente a um evento inusitado. Além disso, o uso de bases de dados secundárias contribuiu para o aprimoramento dos dados coletados, resultando na melhora da qualidade das informações. Os Núcleos de Epidemiologia Hospitalar são fundamentais na articulação entre a equipe assistencial e o Sistema de Vigilância e colaboram para discussão na padronização de Sistemas de Informação para permitir melhor integração entre as informações geradas pelos Serviços de Saúde.
INTRODUCTION: In the years 1999 and 2000, rubella outbreaks reaching mostly young adults resulted in an increased number of cases of Congenital Rubella Syndrome in Brazil. State Vaccination Campaigns aiming at women at childbearing age were promoted around the country to control the disease, recommending that vaccination of pregnant women should be avoided and pregnancy should be postponed for at least a month after vaccination. Despite the recommendations, 6.473 pregnant women were accidentally vaccinated in the State of São Paulo and therefore sent to reference obstetrical services for prenatal care. A study was conducted to describe the cases assisted at the University of São Paulo, School of Medicine, General Hospital and notified to Public Health and also to obtain information on the pregnancy outcomes. METHODS: This descriptive epidemiological study used notification by the Hospital Epidemiology Service as source of information on pregnant women accidentally vaccinated against rubella that received care from November 2001 to December 2002 at the School of Medicine, General Hospital. The City of São Paulo Newborn Database was searched for pregnancy outcomes. RESULTS: Among the 409 notified cases, 49,1% were women accidentally vaccinated during fist trimester of pregnancy and 26,2% women that became pregnant within less than a month after vaccination. Positive serological tests were found in 16,9% of women during prenatal care. Newborn data base search yielded pregnancy outcome for 63,3%. The findings of 2 cases of Congenital Rubella Syndrome and 1miscarriage cannot be surely attributed to vaccination because immediate previous immunization status was unknown. CONCLUSIONS: The study described the information flow established for an unexpected adverse event and the use of secondary data to improve quality of information. Hospital Epidemiology Services have a fundamental role in connecting health assisting professionals to Public Surveillance Systems and in setting standards for information generated by Health Assistance.

OBJETIVOS: Avaliar os efeitos da rubéola durante a gestação, sobre o feto, o recém-nascido e a criança. CASUÍSTICA E MÉTODO: Analisamos 35 gestantes com suspeita de rubéola que foram divididas em dois grupos. Grupo 1: 15 pacientes que apresentaram quadro clínico com comprovação sorológica. Grupo2: 20 pacientes com IgM positiva na rotina pré-natal, na ausência de quadro clínico. O seguimento ultrasonográfico mensal foi realizado em todas as pacientes e as do grupo 1 foram encaminhadas também para propedêutica invasiva. Foram também realizadas a ecocardiografia fetal e a Dopplervelocimetria. As placentas foram submetidas a exame anátomo-patológico. Os recém-nascidos vivos foram avaliados através de exame clínico e sorológico, além do potencial evocado auditivo, ultra-sonografia de crânio, fundo de olho e ecocardiografia pós-natal. RESULTADOS: No grupo 1: a infecção fetal ocorreu em 9 casos, sendo que o risco de transmissão vertical entre 2 a 14 semanas foi de 64,9%. A malformação ocorreu em 37,5% dos infectados. A ultrasonografia revelou crescimento intra-uterino retardado simétrico em todos os fetos infectados que atingiram o terceiro trimestre, tendo se iniciado, em média com 25,1 semanas. A cordocentese foi realizada em 9 pacientes e, todos os casos infectados, apresentavam IgM positiva e eritroblastose no sangue de cordão. A PCR no líquido amniótico foi positiva em todos os 3 casos em que ela foi realizada. 50% das placentas dos fetos infectados apresentava sinais sugestivos de infecção viral. A idade gestacional média do parto entre os infectados foi de 33,8 semanas e o peso médio ao nascimento foi 1365,6g.Todos os 6 nascidos-vivos infectados foram classificados como pequenos para a idade gestacional e apresentaram disacusia. A sobrevida entre os infectados, num seguimento pós-natal médio de 35,2 meses, foi de 62,5%. No grupo 2: a infecção não foi comprovada em nenhum dos recém-nascidos vivos, porém em um caso pudemos demonstrar a infecção congênita pelo vírus de Epstein-Barr. CONCLUSÕES: A transmissão vertical da rubéola no primeiro trimestre parece poder variar entre as populações, bem como a presença dos defeitos associados à infecção. Tanto o diagnóstico invasivo, como o ultrasonográfico apresentaram boa sensibilidade e especificidade. Pudemos estabelecer o padrão de crescimento fetal associado à infecção. A presença isolada de IgM positiva para rubéola na gestação não teve boa correlação com a presença de infecção neonatal, porém pode se associar à presença de outras infecções congênitas.
OBJECTIVES: Our aim was to analyse rubella effects on the fetus, new-born and child. MATERIAL AND METHODS: We analysed 35 patients with suspicious rubella during pregnancy. According to presence or absence of symptoms they were divided in two groups. Group 1: 15 patients presenting rash in which serology was positive. Grupo2: 20 symptomless patients found to have positive IgM during routine prenatal care. Monthly ultrasonographic evaluation was accomplished in all patients and in group 1 they were also offered prenatal invasive testing. Fetal echocardiography and Dopplers were performed. After birth, the placentas were submitted to pathological examination. The liveborn babies had clinical and serological examination. Auditory tests, brain scan, fundoscopy and postnatal echocardiography were also performed. RESULTS: In group 1: fetal infection occurred in 9 cases and vertical transmission between 2 to 14 weeks was 64,9%. Malformation was present in 37,5% of infected cases. Ultrasound revealed symmetrical intra-uterine growth retardation in all infected fetuses that reached the third trimester, and started around 25,1 weeks. Cordocentesis was accomplished in 9 cases and all the infected ones, presented positive IgM and erythroblastosis in cord blood. PCR in the amniotic fluid was positive in all 3 cases it was performed. 50% of the infected fetuses placentas presented signs of viral infection. The average gestacional age of delivery among infected cases was 33,8 weeks and medium birth weight was 1365,6g. All 6 liveborn infected babies were small for gestacional age and presented deafness. Survival among infected cases was 62,5%, medium follow-up was 35,2 months. In group 2: the infection was not demonstrated in any of neonates, although we could demonstrate a congenital infection caused by the Epstein-Barr virus. CONCLUSIONS: Vertical transmission of the rubella in the first trimester seems to vary among different populations, as well as the presence of the associated defects in the new-born. Invasive diagnosis and ultrasonographic follow-up presented good sensitivity and specificity. We could establish the pattern of fetal grown associated to the infection. The isolated presence of a positive rubella IgM in pregnancy did not correlated with congenital rubella, but it can be related to other congenital infections.

La protéine tyrosine kinase c-Src est surexprimée et activée dans de nombreux cancers. De manière remarquable, Src est activé dans plus de 80% des adénocarcinomes coliques où il joue un rôle dans la carcinogenèse et la progression vers un phénotype métastatique. c-Src et son homologue viral v-Src activent un grand nombre de voies cellulaires permettant à la tumeur de proliférer, de résister à la mort cellulaire et d’acquérir des capacités accrues de migration et d’angiogenèse. Au cours de ma thèse nous avons mis en évidence un mécanisme inattendu d’échappement à l’apoptose de fibroblastes murins surexprimant de manière stable v-Src et de plusieurs lignées tumorales humaines (coliques en particulier) présentant une activité c-Src dérégulée. Nous avons montré que Src stimule la dégradation protéasomedépendantede la protéine Bik, un membre pro-apoptotique de la famille Bcl-2, connu pour être un suppresseur de tumeurs. Cette régulation post-traductionnelle du niveau d’expression de Bik est à l’origine d’une forte résistance de la voie mitochondriale de l’apoptose. L’inhibition de l’activité kinase de Src ou le blocage de la dégradation de Bik par le protéasome permettent de restaurer des concentrations normales de la protéine Bik dans les cellules transformées et de les restaurer efficacement l’apoptose. En revanche, l’inhibition des protéines anti-apoptotiques de la famille Bcl-2 par l’ABT-737 semble moins efficace. Par ailleurs, nous avons également contribué à mettre en évidence le rôle anti-migratoire et anti-invasif du lithium sur des cellules transformées par Src. Le mécanisme moléculaire mis en jeu implique l’activation redox des protéines tyrosine phosphatases cellulaires. Enfin, nous avons participé à l’étude de peptides mimant les hélices centrales d’insertion de Bax, Bcl-xL et Bid, représentant les trois sous-groupes de protéines de la famille Bcl-2. Nous avons comparé leur comportement vis-à-vis d’une monocouche lipidique mimant la membrane mitochondriale externe ainsi que leur capacité à perméabiliser des mitochondries isolées. Nos résultats nous ont permis de proposer que les fragments centraux d’insertion membranaire des protéines Bcl-2 seraient directement impliqués dans la divergence fonctionnelle des différents sous groupes qui composent la famille
C-Src tyrosine kinase is overexpressed and activated in a number of cancers. Remarkably, Src is deregulated in more than 80% of colorectal adenocarcinoma, playing a role in carcinogenesis and progression toward a metastatic phenotype. c-Src and v-Src activate a large number of intracellular pathways which allow the tumor to proliferate, to evade the cell death machinery and to acquired enhanced migratory and angiogenic abilities. During my PhD, we discovered an unknown mechanism to evade apoptosis developed by murine fibroblasts stably overexpressing v-Src and by some human tumor cell lines with c-Srcb deregulation. We have shown that Src stimulate the proteasomal degradation of the Bik protein, a proapoptotic member of the Bcl-2 family proteins known to act as a tumor suppressor. This post-translationnal regulation of the Bik protein expression level leads to a strong resistance of the mitochondrial pathway of apoptosis. Inhibition of the Src kinase activity or of the Bik proteasome-dependent degradation restore normal levels of the Bik protein and efficiently resensitize these cells to apoptosis. Inhibition of the antiapoptotic Bcl-2 proteins by ABT737 seems to be less efficient in these cells. We also contribute to show that lithium suppresses motility and invasivity of v-Src transformed cells. The molecular mechanism involve a redox activation of the protein tyrosine phosphatases. Finally, we compared the membrane behavior and the ability to permeabilize mitochondria of synthetic peptides derived from the central helical hairpin of Bax,Bcl-xL and Bid. We showed that these structurally analogous domains have distinct membrane behavior which could account for the functional divergence between the Bcl-2 family members

Rubella virus (RV) is an enveloped, positive sense, single stranded RNA virus in the family Togaviridae. The virus consists of a host derived lipid bilayer membrane, two trans-membrane proteins E1 and E2, and the C protein which together with viral RNA forms the icosahedral nucleocapsid. RV causes natural infections in humans only, where it can lead to a variety of pathological conditions. The most severe outcome, Congenital Rubella Syndrome (CRS), occurs when the fetus is infected in the first trimester of gestation. RV can be isolated from CRS patients at birth and is believed to establish a persistent infection. Although congenital RV infection remains of clinical importance it also provides a rare opportunity for studying the effects of intrauterine viral infection on the human fetus. This thesis examines the hypothesis that intrauterine infection with RV can establish immunological tolerance which is reflected in the serological response to RV. The study on RV-specific tolerance may help in the understanding by which mechanism self-recognition is established in the human. The induction of immunological tolerance may also be an important mechanism in viral persistence and play a role in chronic inflammatory disorders such as Rubella Associated Arthritis (RAA). A comprehensive study of the antibody mediated immunity of healthy individuals responding to postnatal infection with RV is compared to that of CRS patients. Assays were developed to measure antibody quantity, affinity and kinetics of the antibody response to whole virus as well as that to the individual RV structural proteins, E1, E2 and C. The viral proteins were purified from whole RV preparation by differential centrifugation followed by preparative SDS-PAGE under non-reducing conditions. Separated proteins were analyzed for their structural integrity by assaying their biological activity. RV protein-specific ELISAs were developed and used for antibody quantitation and in IgG affinity assays using the chaotropic elution technique. Biological activity of sera was assayed by HAl assay. The specificity of antibodies to linear and topographic epitopes was investigated by using reducing and non-reducing Western blotting. Observations made during the development of protein separation protocols have led to the description of an uncoating mechanism for RV. While establishing ELJSA protocols, improved buffers were developed by including heat denatured blocking proteins and studies on a novel anti-RV IgG ELISA, which will give a more accurate assessment of protective immunity than ELISA technology used to date, were initiated. Results indicate that CRS patients can produce similar amounts of IgG than control patients if measured by whole RV ELISA. Group differences were detected at the level of the protein specific responses. CRS patients exhibited significantly lower levels and had reduced affinities of E1-specific antibodies. The most consistent feature of this patient population was their inability to produce IgG to linear epitopes of the E1 protein. The potential role of the tolerization of anti-E1 Th cells due to the exposure of the immature fetal immune system to RV is discussed. A model is proposed which can accommodate the fmdings on serological and lymphoproliferative immune responses of CRS patients and which supports the hypothesis that congenital RV infection in the early gestational period leads to viral antigen tolerization. Tolerance to the immunodominant E1 protein may lead to a sufficient depression in responder T and B cells in order to allow chronic, low grade RV replication.

Rubella virus (RUBV) is a significant human pathogen. RUBV infection takes an enormous toll due to congenital rubella syndrome (CRS), a constellation of birth defects including blindness, hearing defects and mental retardation. Little is known about RUBV-induced teratogenesis due to the absence of useful models. This research is now enabled by the availability of human embryonic stem cells (hESCs) and hESC-derived precursor cell lines. Human neural progenitor cells (hNPCs) serve as a particularly relevant model due to the symptoms and complications of CRS related to neural system development. The overarching question addressed in this dissertation is: what is the mechanism underlying the development of neurological abnormalities seen in CRS? In this context, we investigated the cellular responses of hNPCs to RUBV infection comprehensively by: 1) assessing susceptibility of the cells to RUBV infection; 2) analyzing the effect of infection on cell proliferation; and 3) examining the impact of RUBV infection on differentiation of hNPCs into neuronal and astroglial lineages . We found that hNPCs are susceptible to RUBV infection and that the percentage of infected cells closely mimics CRS in which few cells harbor virus. The virus was able to persist in culture for up to one month without significant alteration of cell morphology and stemness marker expression. In addition, RUBV infection moderately attenuated the proliferation of undifferentiated hNPCs by triggering cell cycle arrest, but not apoptosis or other cell death events commonly seen upon virus infection. This lack of apoptosis appeared to be due in part to virus-induced anti-apoptotic suppression. Interestingly, the virus only had a marginal effect on the induction of cell differentiation into both neuronal and astroglial phenotypes. In fact, RUBV infection promoted terminal differentiation of the culture due to depletion of precursor cells. With differentiation, viral replication was suppressed. We thus propose a model for RUBV-induced neurological defects in which the virus acts by depleting precursor cell pools. The results of this study provide clues for elucidating the mechanisms of RUBV teratogenicity at the cellular level and serves as a potential reference study for elucidating mechanisms of teratogenesis induced by other infectious agents.

OBJECTIVES: Measles and rubella are nationally notifiable, vaccine-preventable diseases targeted for elimination by the Pan American Health Organization (PAHO). To support national and international elimination efforts, surveillance optimization is important to ensure rapid case detection, document endemic transmission interruption, identify susceptible populations and inform immunization strategies. While current national surveillance captures confirmed-case data, its performance cannot be assessed using PAHO-recommended surveillance indicators as suspect-case investigation data are required for their estimation. In Canada, the investigation of clinically-suspect measles-like illness (MLI) is highly dependent on laboratory evidence, providing an opportunity to use laboratory data to estimate MLI investigation rates. The Measles and Rubella Surveillance (MARS) pilot project was developed to address existing surveillance challenges with the central hypothesis that (I) ‘it is feasible to develop and implement a real‐time, web‐based measles and rubella surveillance system in the Canadian setting’, and the following sub‐hypotheses: (II) ‘implementation of real‐time surveillance in MARS pilot provinces will result in increased timeliness of national measles and rubella surveillance when compared with established confirmed-case surveillance’, and (III) ‘it is possible to use augmented laboratory data to estimate the performance of national measles and rubella surveillance using adapted PAHO indicators’. METHODS: A MARS application was designed to support centralized real-time measles/ rubella investigation reporting and alerting with integration of non-nominal laboratory and epidemiological data, then developed and piloted using the web-based Canadian Network for Public Health Intelligence platform in British Columbia, Alberta and Newfoundland from June/2011-May/2012. Pre- and post-pilot laboratory surveys were conducted to retrospectively assess national surveillance performance in ‘outbreak’ and ‘non-outbreak’ settings during the 2005‐2011 and pilot years using various surveillance indicators and attributes. Measles IgM serology testing was used as a laboratory-based proxy for MLI investigation to support indicator estimation. RESULTS: Real-time, integrated surveillance was successfully implemented in MARS pilot provinces as modeled within the context of established reporting roles, and surveillance indicators and attributes were estimated using augmented laboratory data. MARS surveillance was more timely than confirmed-case surveillance, and real-time MARS reports exceeded all laboratory-related PAHO targets evaluated: 100% met ‘sample collection’ and ‘receipt’ timelines, and 91.7% met ‘result' timelines (Targets:≥80%); 99.8% of all MLI investigations were discarded (Target:≥95%). A national ‘non-outbreak’ baseline rate of 14 MLI investigations/100 000 population was estimated, whereas MARS pilot sites averaged 22 MLI investigations/100 000 population during the pilot year. While ‘non-outbreak’ investigation rates varied between provinces, all annual provincial and national rates estimated for the 2005‐2011 and MARS pilot years exceeded the PAHO investigation target of ≥2 suspected cases/100 000 population in settings attempting elimination. CONCLUSIONS: The MARS model supported more timely and integrated national measles and rubella surveillance, and enabled indicator‐based performance assessment. Results underscore the importance of laboratory data when evaluating and documenting surveillance performance to support elimination efforts. Consideration should be given to national MARS implementation and its use as a model adaptable to the case-based surveillance of other nationally notifiable diseases.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
To complete the Pharmaceutical Sciences Integrated Masters, the Curricular Internship unit aims to provide to the future pharmacist the opportunity to contact for the first time with the professional universe, allowing the theoretical knowledge acquired application in the different pharmaceutical fields in a work context. In this context, between September of 2017 and February of 2018, I had opportunity to do an internship in Community Pharmacy and another in Hospital Pharmacy. This report, structured through a SWOT Analysis, aims to retrospectively analyze my experience as a student, highlighting the main strengths, weaknesses, threats, and opportunities identified at each internship. Rubella is an acute, infectious exanthematous disease caused by rubella virus, a RNA virus which belongs to the genus Rubivirus, a member of the Togaviridae family. It is transmitted through respiratory secretions and although it does not produce detectable clinical manifestations in 25% to 50% of the cases, when symptomatic is characterized by a slight maculopapular eruption, often associated with low fever, lymphadenopathy and joint pain. It is usually a benign and self-limiting infection in children and adults, although when acquired by non immune pregnant women, particularly during the first trimester of pregnancy, it can bring innumerable complications to the fetus development, including miscarriage, fetal death, or result in a series of congenital malformations that characterize Congenital Rubella Syndrome. The differential diagnosis of rubella is unreliable due to its non-specific clinical symptoms. Therefore the laboratory tests practice is important to confirm the diagnosis and the surveillance of postnatal and congenital infections, essential for the prevention of Congenital Rubella Syndrome. Due to the development of very effective and safe rubella vaccines, vaccination can prevent this disease. The implementation of preventive vaccination campaigns has allowed the control of the disease in several developed countries, having already ended the endemic transmission of the virus in America and being in the process of elimination in Europe. Despite considerable progresses in rubella control, it remains an endemic disease in many developing countries and is still a major cause of preventable fetal malformations. This monograph discusses the most characteristic and relevant aspects related to the epidemiology and pathogenicity of the rubella virus, the postnatal infection implications, including during gestation and congenital infection, techniques used in diagnosis, as well as prevention and control measures of the disease.
Com vista à conclusão do Mestrado Integrado em Ciências Farmacêuticas, a unidade de Estágio Curricular visa oferecer ao futuro farmacêutico a oportunidade de contactar pela primeira vez com o universo profissional, permitindo-lhe aplicar em contexto laboral a formação teórica adquirida nas diferentes áreas do medicamento. Neste âmbito, entre setembro de 2017 e fevereiro de 2018 tive a oportunidade de realizar um estágio em Farmácia Comunitária e um outro em Farmácia Hospitalar. O presente relatório, estruturado sob a forma de análise SWOT, tem o objetivo de analisar retrospetivamente a minha experiência enquanto estagiária, destacando os principais pontos fortes, pontos fracos, ameaças e oportunidades identificados em cada um dos estágios.A rubéola é uma doença exantemática aguda, infeciosa, provocada pelo vírus da rubéola, um vírus RNA pertencente ao género Rubivirus, membro da família Togaviridae. É transmitida através de secreções respiratórias e embora não produza manifestações clínicas percetíveis em 25% a 50% dos casos, quando sintomática caracteriza-se por uma ligeira erupção maculopapular, associada frequentemente a febre baixa, linfadenopatia e dores articulares. É geralmente uma infeção benigna e autolimitada em crianças e adultos, porém, quando adquirida por mulheres grávidas não imunes, particularmente durante o primeiro trimestre da gestação, pode trazer inúmeras complicações para o feto em desenvolvimento, incluindo aborto espontâneo, morte fetal ou resultar numa série de malformações congénitas que caracterizam a Síndrome de Rubéola Congênita. O diagnóstico diferencial da rubéola não é confiável devido aos seus sintomas clínicos inespecíficos, pelo que a prática de exames laboratoriais é importante para a confirmação do seu diagnóstico e a vigilância das infeções pós-natal e congênita, fundamental para a prevenção da Síndrome de Rubéola Congénita. Devido ao desenvolvimento de vacinais muito eficazes e seguras contra a rubéola, esta doença pode ser prevenida por vacinação. A implementação de campanhas preventivas de vacinação permitiu o controlo da doença em vários países desenvolvidos, tendo já sido interrompida a transmissão endémica do vírus na América e estando em processo de eliminação na Europa. Apesar dos consideráveis progressos no controlo da rubéola, esta continua a ser uma doença endémica em muitos países em desenvolvimento e ainda uma das principais causas de malformações fetais evitáveis. Nesta monografia foram abordados os aspetos mais característicos e relevantes relativos à epidemiologia e patogenicidade do vírus da rubéola, as implicações da infeção pós-natal, inclusive durante a gestação e da infeção congénita, as técnicas utilizadas no diagnóstico e ainda as medidas de prevenção e controlo da doença.