Die vorliegende Arbeit hatte das Ziel, die Korrelation zwischen der Avidität der Anti-Masern-IgG-Antikörper und deren In-Vitro-Neutralisationsfähigkeit zu untersuchen, sowie mittels Datenbankanalyse die Seroprävalenz von schützenden Antikörpern gegen Masern und den Impfstatus der Kinder- und Jugendlichen festzustellen. Die lineare Korrelation zwischen Neutralisationsfähigkeit und Avidität war in dieser Stichprobe schwach (ρ=0,240, p=0,006). Für hohe IgG Konzentrationen über 1000 mIU/ml fand sich eine mittlere Korrelation zwischen Avidität und Neutralisationstiter (ρ=0,612; p<0,001). Bei den untersuchten Jahren von 1997 bis 2013 zur Seroprävalenz (n=8611) wiesen im Durchschnitt 93,4 % der Patienten IgG-Konzentrationen im positiven Bereich (>200 mIU/ml) auf. In allen Jahrgängen lag der Anteil über 90 %. Zur Ermittlung des Impfstatus wurde eine Stichprobe 2- bis 18-Jähriger aus dem Jahr 2012 untersucht. Insgesamt hatten 81,1 % die erste Masernimpfung erhalten. Die zweite Masernimpfung erhielten noch 59,7 % der Kinder und Jugendlichen.

Objetivo: Descrever os casos de síndrome febril exantemática, identificados no estado de São Paulo entre 2000 e 2004, visando identificar possíveis resíduos de fonte de infecção do sarampo. Métodos: Estudo descritivo. As definições são as utilizadas pelo Plano de Eliminação do Sarampo. O estudo incluiu casos notificados à vigilância da síndrome febril exantemática apresentando anticorpos IgM para sarampo pelas técnicas de ELISA e/ou ELISA de captura. Descreveram-se os aspectos clínicos e epidemiológicos segundo características de tempo, espaço e pessoa. Resultados: Estudaram-se 463 casos possíveis de sarampo; 64,1% e 29,8% foram classificados, respectivamente, como casos expostos e não expostos à vacina; 15,3% apresentaram clínica específica para sarampo e 12,1% apresentaram complicações. Os grupos etários mais representados foram: 9 a 11 meses (36,5%), um ano (32,8%) e cinco anos ou mais (15,2%). A distribuição no espaço e no tempo não sugere a ocorrência de casos relacionados entre si. Entre o final de 2000 e o início de 2002, os casos não expostos à vacina mantiveram-se em patamares elevados, coincidindo com a identificação de dois casos importados de sarampo. Conclusão: as limitações do estudo não permitem análises conclusivas a respeito da circulação do vírus do sarampo no estado de São Paulo, mas o estudo aponta para a necessidade da investigação exaustiva de possíveis resíduos de fontes de infecção entre: menores de nove meses, primo vacinados contra o sarampo abaixo de 10 meses, mulheres em idade fértil e casos não expostos à vacina contra o sarampo. / Objective: To describe cases of febrile exanthematic syndrome reported in the State of São Paulo between 2000 and 2004, in order to identify possible measles residual source of infection. Methods: A descriptive study, using the same definitions of Measles Elimination Plan. The study included reported cases of febrile exanthematic syndrome surveillance with antibody of IgM class by ELISA and/or capture ELISA techniques. The clinical and epidemiological characteristics were described in terms of time, space and personal characteristics. Results: 463 possible cases of measles were analyzed: 64.1% and 29.8% were classified, respectively, as exposed and unexposed to vaccine; 15.3% presented specific measles clinical and 12.1% presented clinical complications. The age groups most represented were: 9 to 11 months (36.5%), one year (32.8%) and five years old or over (15.2%). The temporal and spatial distribution did not suggest the presence of a chain of transmission of febrile exanthematic disease. Between the end of 2000 and the beginning of 2002, high levels of cases unexposed to vaccine were maintained, which coincided with the identification of two imported cases of measles. Conclusion: The limitations of the study did not allow conclusive analyses regarding the circulation of the measles virus in the State, but the study points towards the need to carry out exhaustive investigations on possible residual sources of infection among: infants under nine months old, first vaccinated against measles before the age of 10 months, women of fertile age and cases unexposed to anti-measles vaccine.

La macroautophagie, appelée ici autophagie, est un processus de dégradation lysosomale qui joue un rôle clé dans l'immunité en dégradant des micro-organismes intracellulaires mais également en activant des réponses immunitaires. Cependant, de nombreux virus ont développé des stratégies pour inhiber, utiliser voire détourner l'autophagie à leur propre bénéfice. L'objectif de cette thèse a été d'analyser la place de l'autophagie dans l'infection par le virus de la rougeole (VR). Ce travail démontre que les souches atténuées du VR utilisent plusieurs voies moléculaires successives d'induction d'autophagie dans les cellules infectées. En effet, elles sont capables d'induire une première vague d'autophagie très précoce mais transitoire par l'engagement de l'une des isoformes de leur récepteur d'entrée CD46. Après un bref retour à l'état basal, une deuxième vague d'autophagie est induite par l'interaction de la protéine virale non structurale C avec la protéine cellulaire autophagique IRGM. La formation de syncytia conduit à une troisième voie d'induction d'autophagie qui permet de maintenir l'autophagie mise en place. Cette autophagie soutenue est exploitée par le VR afin de limiter la mort des cellules infectées, ce qui promeut la production de particules virales. Les souches virulentes du VR, incapables de lier CD46, et utilisant comme récepteur d'entrée la protéine CD150, n'induisent que l'autophagie tardive qui est également utilisée pour favoriser la production de particules virales infectieuses. Ce travail de thèse montre donc que l'induction d'une autophagie soutenue lors de l'infection par le VR promeut l'infection, principalement en limitant la mort cellulaire / Macroautophagy, thereafter referred to as autophagy, is a lysosomal degradation which plays a key role in immunity by directly degrading intracellular pathogens but also by favouring innate and adaptive immune responses. However, several viruses have evolved strategies to inhibit, exploit or even hijack autophagy for their own benefit. The aim of this thesis was to analyse the role of autophagy in the course of measles virus (MeV) infection. This work demonstrates that attenuated strains of MeV induce successive autophagy signalling in infected cells, via distinct and uncoupled molecular pathways. First, attenuated MeV strains are able to induce a first early and transient wave of autophagy through the engagement of one of the isoform of their cellular receptor CD46. Soon after infection, a new autophagy signalling is initiated by the interaction of the non-structural MeV protein C with the cellular autophagic protein IRGM. Strikingly, this second autophagy signalling can be sustained overtime within infected cells via a third autophagy input resulting from cell-cell fusion and the formation of syncytia. Sustained autophagy is exploited by MeV to limit the death of infected cells and to improve infectious viral particle formation. Interestingly, virulent strains of MeV, which do not use CD46 as a cellular receptor but use CD150, are unable to induce the early autophagy wave, whereas they induce and exploit the late and sustained autophagy. Thus, this work demonstrates that the induction of a sustained autophagy during MeV infection promotes infectivity, mostly by limiting cell death. Overall, this work describes an unusual and complex interplay between autophagy and MeV

Objetivo: Descrever os casos de síndrome febril exantemática, identificados no estado de São Paulo entre 2000 e 2004, visando identificar possíveis resíduos de fonte de infecção do sarampo. Métodos: Estudo descritivo. As definições são as utilizadas pelo Plano de Eliminação do Sarampo. O estudo incluiu casos notificados à vigilância da síndrome febril exantemática apresentando anticorpos IgM para sarampo pelas técnicas de ELISA e/ou ELISA de captura. Descreveram-se os aspectos clínicos e epidemiológicos segundo características de tempo, espaço e pessoa. Resultados: Estudaram-se 463 casos possíveis de sarampo; 64,1% e 29,8% foram classificados, respectivamente, como casos expostos e não expostos à vacina; 15,3% apresentaram clínica específica para sarampo e 12,1% apresentaram complicações. Os grupos etários mais representados foram: 9 a 11 meses (36,5%), um ano (32,8%) e cinco anos ou mais (15,2%). A distribuição no espaço e no tempo não sugere a ocorrência de casos relacionados entre si. Entre o final de 2000 e o início de 2002, os casos não expostos à vacina mantiveram-se em patamares elevados, coincidindo com a identificação de dois casos importados de sarampo. Conclusão: as limitações do estudo não permitem análises conclusivas a respeito da circulação do vírus do sarampo no estado de São Paulo, mas o estudo aponta para a necessidade da investigação exaustiva de possíveis resíduos de fontes de infecção entre: menores de nove meses, primo vacinados contra o sarampo abaixo de 10 meses, mulheres em idade fértil e casos não expostos à vacina contra o sarampo. / Objective: To describe cases of febrile exanthematic syndrome reported in the State of São Paulo between 2000 and 2004, in order to identify possible measles residual source of infection. Methods: A descriptive study, using the same definitions of Measles Elimination Plan. The study included reported cases of febrile exanthematic syndrome surveillance with antibody of IgM class by ELISA and/or capture ELISA techniques. The clinical and epidemiological characteristics were described in terms of time, space and personal characteristics. Results: 463 possible cases of measles were analyzed: 64.1% and 29.8% were classified, respectively, as exposed and unexposed to vaccine; 15.3% presented specific measles clinical and 12.1% presented clinical complications. The age groups most represented were: 9 to 11 months (36.5%), one year (32.8%) and five years old or over (15.2%). The temporal and spatial distribution did not suggest the presence of a chain of transmission of febrile exanthematic disease. Between the end of 2000 and the beginning of 2002, high levels of cases unexposed to vaccine were maintained, which coincided with the identification of two imported cases of measles. Conclusion: The limitations of the study did not allow conclusive analyses regarding the circulation of the measles virus in the State, but the study points towards the need to carry out exhaustive investigations on possible residual sources of infection among: infants under nine months old, first vaccinated against measles before the age of 10 months, women of fertile age and cases unexposed to anti-measles vaccine.

Diversos trabalhos têm demonstrado a presença de peptídeos bioativos em hemolinfa de insetos e seu potencial uso como agentes terapêuticos. Este trabalho buscou identificar e isolar proteínas da hemolinfa de Lonomia obliqua com ação antiviral. A adição de hemolinfa antes da infecção reduziu o título de poliovírus de 1,5x107 TCID50/mL no cultivo controle para 4x105 TCID50/mL e em aproximadamente 100 vezes o título do sarampo. Após cromatografia de gel filtração, foram obtidos 3 pools de proteína. O pool responsável pela ação antiviral foi identificado (Pool 2), uma vez que reduziu em 87 vezes o título de poliovírus, e de 1,6x106 TCID50/mL para 2,7x105 TCID50/mL o título do sarampo. O Pool 2 foi fracionado por cromatografia de troca iônica. A fração responsável pela ação antiviral da hemolinfa de Lonomia obliqua frente ao poliovírus e sarampo foi identificada (RQ 3-4), esta proteína, de aproximadamente 20 kDa, tem ação sobre vírus envelopado (sarampo) e vírus desprovido de envelope viral (poliovírus). / Several works have demonstrated the presence of bioactive peptides in insect hemolymph and their potential use as therapeutic agents. This work sought to identify and purify proteins from Lonomia obliqua hemolymph with antiviral activity. The analyses demonstrated that the best time for hemolymph addition in the cell culture is before the infection, the poliovirus titer had reduced from 1.5x107 TCID50/mL to 4x105 TCID50/mL and for measles, the virus titer was about 100 times lower than the control. After gel filtration chromatography, the hemolymph was divided into 3 pools of protein. The pool responsible for the antiviral activity was identified (Pool 2), once it reduced to 87 times the poliovirus titer, and the measles titer from 1.6x106 TCID50/mL to 2.7x105 TCID50/mL. The Pool 2 was fractionated by ion-exchange chromatography. The fraction from Lonomia obliqua hemolymph responsible for the antiviral activity was identified - RQ 3-4, this protein of approximately 20 kDa, has antiviral effect on enveloped virus (measles) and on non enveloped virus (poliovirus).

In 1990 the Department of National Health and Population Development of South Africa launched a nationwide immunisation coverage campaign targetted mainly at measles. In order to measure the effect of the campaign on vaccination coverage rates for children pre- and post- campaign vaccination coverage surveys were performed using a modified EPI technique, stratified for race and urban/rural residence. The results in Natal/KwaZulu showed no significant changes in vaccination coverage rates as documented by Road-to-Health cards for any race, although the trend was towards a slight increase. The results bring into question the effectiveness of immunisation campaigns as a strategy for raising vaccination coverage levels, and having a sustained impact on the incidence of measles. Alternative strategies, such as the strengthening and expansion of existing primary health care services, and changes to the immunisation schedule for measles, should be considered. / Thesis (MMed.)-University of Natal, Durban, 1992.

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.

Finite-difference numerical methods are developed for the solution of some systems in the biomedical sciences; namely, a predator-prey model and the SEIR (Susceptible/Exposed/ Infectious/Recovered) measles model. First-order methods are developed to solve the predator-prey model and one second-order method is developed to solve the SEIR measles model. The predator-prey model is extended to one-space dimension to incorporate diffusion. The SEIR measles model is extended to one-space dimension to incorporate (i) diffusion, (ii) convection and (iii) diffusion-convection. The SEIR measles model is extended further to model diffusion in two-space dimensions. The reaction terms in these systems of partial differntial equations contain nonlinear expressions. Nevetheless, it is seen that the numerical solutions are obtained by solving a linear algebraic system at each time step, as opposed to solving a nonlinear algebraic systems, which is often required when integrating non-linear partial differential equations. The development of each numerical method is made in the light of experience gained in solving the system of ordinary differential equations for each system. The numerical methods proposed for the solution of the initial-value problem for the predator-prey and measles models are characterized to be implicit. However, in each case it is seen that the numerical solutions are obtained explicitly. In a series of numerical experiments, in which the ordinary differential equations are solved first of all, it is seen that the proposed methods have superior stability properties to those of the well-known, first-order, Euler method to which they are compared. Incorporating the proposed methods into the numerical solution of partial differential equations is seen to lead to economical and reliable methods for solving the systems.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, 2006. / Bibliyografya var.

Thesis (M.S.P.H.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 58 pages. Includes bibliographical references.