The problem of changing scale in models of a system is relevant in many different fields. In this thesis we investigate the problem in models of biological systems, particularly infectious disease spread and population dynamics. We investigate this problem using the process algebra \emph{Weighted Synchronous Calculus of Communicating Systems} (WSCCS). In WSCCS we can describe the different types of individual in a population and study the population by placing many of these individuals in parallel. We present an algorithm that allows us to rigorously derive mean field equations (MFE) describing the average change in the population. The algorithm takes into account the Markov chain semantics of WSCCS such that as the system being considered becomes larger, the approximation offered by the MFE tends towards the mean of the Markov chain. The traditional approach to developing population level equations of a system involves making assumptions about the behaviour of the entire population. Our approach means that the population level dynamics explained by the MFE are a direct consequence of the behaviour of individuals, which is more readily observed and measured than the behaviour of the population. In this way we develop MFE models of several different systems and compare the equations obtained to the traditional mathematical models of the system.

<b>Background</b>: The world is at risk of epidemics of novel and reemerging infectious diseases. These may be national, regional or international as in the case of Nipah, African Viral Haemorrhagic Fevers, SARS and H1N1 respectively. It is crucial that public health and clinical research is conducted in such epidemics. Yet the conduct of heath research during rapidly evolving epidemics or disasters represents an enormous challenge. In addition to the large number of practical challenges to undertaking such research there are also major ethical issues to consider. However, there is very little understanding of these ethical issues and very little empirical evidence of the views of patients, their families, society and key stakeholders. <b>Objective</b>: To collect and analyse data on ethical considerations arising in the setting of research on rapidly evolving epidemics posed by the urgent and unpredictable nature of epidemics. <b>Design</b>: The study was conducted in Oxford University Clinical Research Unit (OUCRU), Viet Nam and 3 other hospitals in Viet Nam with experience of epidemics. Data were collected by semi-structured interviews with key stakeholders representing research staff, IRB members, patients/family members and study sponsors/funders who have participated in or reviewed research projects on infectious diseases including SARS, H5N1, H1N1, dengue and Hand, Foot, Mouth disease. <b>Result</b>: A total of 64 interviews with all key stakeholders were conducted. Analysis of the ethical problems/challenges discussed in the interviews led to the identification of three themes 1) International research collaboration, 2) IRB review and 3) Consent. These tended to arise at three levels of relationship: macro (between institutions internationally), meso (within and between institutions nationally) and micro (within institutions and between health professionals and patients). <b>Conclusion</b>: The issues and types of considerations and their relative importance were raised and/or valued differently by the members of different key stakeholder groups due to their role and experience in research participation. Some of the issues raised also related to health research in other settings. However, many were unique to the setting of rapidly evolving epidemics. Addressing these issues is crucial for successful and appropriate research in the context of epidemics. It is inevitable that epidemics of emerging and reemerging infectious diseases will occur in the future and there is a clear need to undertake crucial scientific research in such settings. It is therefore imperative that we understand the challenges and ethical issues surrounding such research. It is desirable that further research into the ethical challenges identified in this thesis takes place in the inter-epidemic period in order to better prepare for the next epidemic.

Les facteurs déterminant l’épidémiologie et la sévérité de la Dengue restent mal connus. La compréhension de la dynamique des épidémies est indispensable au management de la lutte anti-vectorielle et des futures stratégies vaccinales. Dans un premier travail, la caractérisation moléculaire de 181 souches de Dengue-1 a permis de déterminer l’origine des épidémies en Polynésie Française (2001, 2006) et d’identifier un phénomène de ré-émergence. La fixation d’une mutation (E-S222T) en période endémique pourrait refléter une adaptation du virus au moustique. A l’échelle intra-hôte, la diversité des populations virales était significativement inférieure en cas de forme sévère suggérant une relation entre diversité génétique virale et clinique.Dans un second travail, cette relation a été confirmée (Bolivie, épidémie de Dengue-1, 2009) et l’importance de la composition des populations virales dans le sang capillaire a été soulignée. Dans un troisième travail, nous avons étudié l’influence du climat sur les épidémies de Dengue (Nouvelle Calédonie, 1971-2010) et développé un modèle prédictif de risque épidémique utilisable par les autorités de santé. / The determinant factors of Dengue epidemiology and severity remain unclear. Understanding the epidemic dynamics is crucial to manage vector control and vaccine strategies in the future. In a first work, the molecular characterization of 181 Dengue-1 strains allowed to determine the origin of Dengue outbreaks in French Polynesia (2001, 2006) and to identify a phenomenom of re-emergence. A mutation (E-S222T) has been fixed during the endemic period that may reflect viral adaptation to the mosquito. At the intra-host scale, the genetic variability was significantly lower in patients experiencing severe forms. This suggests a relationship between the diversity of viral populations within hosts and the clinical presentation of the disease.In a second work, this connection has been confirmed (Bolivia, 2009 Dengue-1 outbreak) and the importance of the composition of viral populations in the capillary blood has been underlined.In a third work, the influence of climate on Dengue epidemics has been studied (New Caledonia, 1971-2010) and a predictive model of epidemic risk usable by the health authorities has been developed.

A Dengue avança como um problema social cada vez mais expressivo. Por isso, foi desenvolvido este estudo cujos objetivos foram conhecer os significados da Dengue para os Enfermeiros da Atenção Primária à Saúde de Alfenas, Minas Gerais, bem como identificar forças restritivas e propulsoras para o controle da doença. Tratou-se de uma Pesquisa de Representação Social, de abordagem qualitativa, que adotou a Teoria das Representações Sociais e o Método do Discurso do Sujeito Coletivo como o referencial teórico-metodológico. O trabalho de campo contemplou entrevistas individuais aos Enfermeiros nas Unidades de Atenção Primária à Saúde do Município, entre junho e julho de 2015; os depoimentos foram gravados, transcritos e posteriormente analisados/apresentados por meio do Método do Discurso do Sujeito Coletivo. Os 17 profissionais de nível superior em enfermagem eram do sexo feminino e a média das idades foi de 40 anos; observou-se mediana de cinco anos de atuação na Atenção Primária à Saúde, sendo a maioria destas Enfermeiras integrantes de Equipes de Saúde da Família urbanas; três entrevistadas já tinham sido acometidas por Dengue. Do sujeito coletivo emergiram as seguintes Representações Sociais: desconforto enorme, problema de saúde pública, descuido das pessoas, consequência da falta de educação, doença viral, preocupação e medo, doença grave, doença causada pela picada do mosquito, epidemia, doença de país pobre, mais uma doença para a gente cuidar e uma guerra. Em relação ao controle da Dengue, foram reconhecidos como dificultadores: a falta de conscientização da população, a resistência e falta de responsabilidade das pessoas, a alta proliferação do mosquito, a grande quantidade de foco, os boatos, a falta de informação sobre a doença em si, o desconhecimento da causa, a capacitação dos Agentes de Controle de Endemias e a falta de mais cobrança dos Agentes Comunitários de Saúde; como facilitadores, o trabalho de orientação e de conscientização, a educação da população, a consciência das pessoas, o saneamento básico, as parcerias das Equipes de Saúde da Família com os Agentes de Controle de Endemias, a cobrança da população, a capacitação e a remuneração dos Agentes de Controle de Endemias e o dever da população. O conhecimento das Representações Sociais sobre a Dengue é importante para a compreensão da sua causalidade e para o enfrentamento do problema de Saúde Pública/Saúde Coletiva na atualidade. Do estudo emergiram valores e símbolos do sujeito coletivo de Enfermeiros da Atenção Primária à Saúde de Alfenas-MG sobre a Dengue e o enfrentamento da epidemia, que contribuíam com a inteligência dos serviços de saúde, por se tratar de profissionais que atuam na linha de frente do Município, promovendo o enfrentamento da doença. / Dengue advances as an increasingly significant social problem. Thus, this study was developed with the aim to learn the meanings of Dengue for primary health care nurses from Alfenas, in the state of Minas Gerais; and to identify limiting and driving forces for its control. A social representation study was developed, with a qualitative approach, and the adoption of the social representation theory as its theoreticalmethodological framework. Field work consisted of individual interviews with nurses from the primary health care units of the city, between June and July of 2015; which were recorded, transcribed and later analyzed and presented by means of the discourse of the collective subject method. The 17 professionals interviewed had a nursing undergraduate degree, were women and had a mean age of 40 years. They presented a median length of activity in primary health care of five years, with most nurses being members of urban family health teams; and three nurses had already been infected by the Dengue virus. The collective subject resulted in the following social representations: extreme discomfort, public health problem, people\'s negligence, consequence of the lack of education, viral disease, concern and fear, severe disease, disease caused by a mosquito bite, epidemic, poor country\'s disease, one more disease for us to care for, and a war. According to the nurses, factors that make the control of Dengue difficult include: the population\'s lack of awareness, people\'s resistance and lack of responsibility, the mosquitoes\' rapid spread, the high amount of focuses, rumors, lack of information on the disease, lack of knowledge on its cause, lack of qualification of workers of endemic diseases control, and lack of supervision on the work of community health workers. Factors that facilitate the disease control include the work to guide, educate and raise people\'s awareness, basic sanitation, partnerships of family health teams and endemic diseases control workers, demanding the population\'s commitment, better qualification and remuneration of endemic diseases control workers and the population\'s duty being served. Knowledge about social representations on Dengue is important to understand its causality and to cope with this current public health problem. This study managed to give rise to values and symbols of the collective subject of primary health care nurses from Alfenas on Dengue and the coping with the epidemic, which contributed to enhance the intelligence of health services, since these professionals work at the frontline of the city, promoting the fight against the disease.

Epidemiologists rely on human interaction networks for determining states and dynamics of disease propagations in populations. However, such networks are empirical snapshots of the past. It will greatly benefit if human interaction networks are statistically predicted and dynamically created while an epidemic is in progress. We develop an application framework for the generation of human interaction networks and running epidemiological processes utilizing research on human mobility patterns and agent-based modeling. The interaction networks are dynamically constructed by incorporating different types of Random Walks and human rules of engagements. We explore the characteristics of the created network and compare them with the known theoretical and empirical graphs. The dependencies of epidemic dynamics and their outcomes on patterns and parameters of human motion and motives are encountered and presented through this research. This work specifically describes how the types and parameters of random walks define properties of generated graphs. We show that some configurations of the system of agents in random walk can produce network topologies with properties similar to small-world networks. Our goal is to find sets of mobility patterns that lead to empirical-like networks. The possibility of phase transitions in the graphs due to changes in the parameterization of agent walks is the focus of this research as this knowledge can lead to the possibility of disruptions to disease diffusions in populations. This research shall facilitate work of public health researchers to predict the magnitude of an epidemic and estimate resources required for mitigation.

A Dengue avança como um problema social cada vez mais expressivo. Por isso, foi desenvolvido este estudo cujos objetivos foram conhecer os significados da Dengue para os Enfermeiros da Atenção Primária à Saúde de Alfenas, Minas Gerais, bem como identificar forças restritivas e propulsoras para o controle da doença. Tratou-se de uma Pesquisa de Representação Social, de abordagem qualitativa, que adotou a Teoria das Representações Sociais e o Método do Discurso do Sujeito Coletivo como o referencial teórico-metodológico. O trabalho de campo contemplou entrevistas individuais aos Enfermeiros nas Unidades de Atenção Primária à Saúde do Município, entre junho e julho de 2015; os depoimentos foram gravados, transcritos e posteriormente analisados/apresentados por meio do Método do Discurso do Sujeito Coletivo. Os 17 profissionais de nível superior em enfermagem eram do sexo feminino e a média das idades foi de 40 anos; observou-se mediana de cinco anos de atuação na Atenção Primária à Saúde, sendo a maioria destas Enfermeiras integrantes de Equipes de Saúde da Família urbanas; três entrevistadas já tinham sido acometidas por Dengue. Do sujeito coletivo emergiram as seguintes Representações Sociais: desconforto enorme, problema de saúde pública, descuido das pessoas, consequência da falta de educação, doença viral, preocupação e medo, doença grave, doença causada pela picada do mosquito, epidemia, doença de país pobre, mais uma doença para a gente cuidar e uma guerra. Em relação ao controle da Dengue, foram reconhecidos como dificultadores: a falta de conscientização da população, a resistência e falta de responsabilidade das pessoas, a alta proliferação do mosquito, a grande quantidade de foco, os boatos, a falta de informação sobre a doença em si, o desconhecimento da causa, a capacitação dos Agentes de Controle de Endemias e a falta de mais cobrança dos Agentes Comunitários de Saúde; como facilitadores, o trabalho de orientação e de conscientização, a educação da população, a consciência das pessoas, o saneamento básico, as parcerias das Equipes de Saúde da Família com os Agentes de Controle de Endemias, a cobrança da população, a capacitação e a remuneração dos Agentes de Controle de Endemias e o dever da população. O conhecimento das Representações Sociais sobre a Dengue é importante para a compreensão da sua causalidade e para o enfrentamento do problema de Saúde Pública/Saúde Coletiva na atualidade. Do estudo emergiram valores e símbolos do sujeito coletivo de Enfermeiros da Atenção Primária à Saúde de Alfenas-MG sobre a Dengue e o enfrentamento da epidemia, que contribuíam com a inteligência dos serviços de saúde, por se tratar de profissionais que atuam na linha de frente do Município, promovendo o enfrentamento da doença. / Dengue advances as an increasingly significant social problem. Thus, this study was developed with the aim to learn the meanings of Dengue for primary health care nurses from Alfenas, in the state of Minas Gerais; and to identify limiting and driving forces for its control. A social representation study was developed, with a qualitative approach, and the adoption of the social representation theory as its theoreticalmethodological framework. Field work consisted of individual interviews with nurses from the primary health care units of the city, between June and July of 2015; which were recorded, transcribed and later analyzed and presented by means of the discourse of the collective subject method. The 17 professionals interviewed had a nursing undergraduate degree, were women and had a mean age of 40 years. They presented a median length of activity in primary health care of five years, with most nurses being members of urban family health teams; and three nurses had already been infected by the Dengue virus. The collective subject resulted in the following social representations: extreme discomfort, public health problem, people\'s negligence, consequence of the lack of education, viral disease, concern and fear, severe disease, disease caused by a mosquito bite, epidemic, poor country\'s disease, one more disease for us to care for, and a war. According to the nurses, factors that make the control of Dengue difficult include: the population\'s lack of awareness, people\'s resistance and lack of responsibility, the mosquitoes\' rapid spread, the high amount of focuses, rumors, lack of information on the disease, lack of knowledge on its cause, lack of qualification of workers of endemic diseases control, and lack of supervision on the work of community health workers. Factors that facilitate the disease control include the work to guide, educate and raise people\'s awareness, basic sanitation, partnerships of family health teams and endemic diseases control workers, demanding the population\'s commitment, better qualification and remuneration of endemic diseases control workers and the population\'s duty being served. Knowledge about social representations on Dengue is important to understand its causality and to cope with this current public health problem. This study managed to give rise to values and symbols of the collective subject of primary health care nurses from Alfenas on Dengue and the coping with the epidemic, which contributed to enhance the intelligence of health services, since these professionals work at the frontline of the city, promoting the fight against the disease.

“Strange Bedfellows” examines how the political economy of Medicaid and hospital provision shaped the social, political, and thus material response to the HIV/AIDS epidemic in the United States. By doing so, this study explores the consequences of a decade-plus shift that began in the late 1960s, wherein federal, state, and local policymakers deemphasized epidemic preparedness and acute care in favor of downsized hospitals, increased outpatient services, and more “personal responsibility.” Over the course of seven chapters, the study links the transformation of Medicaid into a welfare medicine program; federal health planning’s shift from the pursuit of equality to cost-cutting; the role that anti-inflation policy played in curtailing subsidies for hospitals and clinics, which reduced access to acute care; the diminution of civil rights protections for quality healthcare; and the effects these developments had on the response to HIV/AIDS. Challenging the notion that the HIV/AIDS epidemic was unforeseen and, thus, impossible to plan for, the study demonstrates how a series of purposeful decisions by presidential administrations, Congress, state legislatures, and city officials led to chronic underinvestment in public and voluntary hospitals that served poor people and people of color. A story of the neoliberal transformation of the Medicaid program and public and voluntary safety net hospitals, this dissertation illustrates how healthcare and welfare politics intertwined from the mid-1960s to the new millennium in ways that confounded the United States’ epidemic preparedness. A healthcare system focused on chronic disease by the 1960s and cost cutting in the 1970s could not cope with an emergent infectious disease like HIV/AIDS.

This thesis examines the politics of Zimbabwe's catastrophic cholera outbreak in 2008/09, which caused an unprecedented 98,000 cases and over 4,000 deaths. Epidemiologically, the outbreak can be explained by the breakdown of the country's water and sanitation systems. Such a reading, however, belies the byzantine political, economic and historical processes that precipitated the dysfunction of the water systems, that delineate the socio-spatial pattern of the outbreak and that account for the fragmented and inadequate response of the national health system. The complex causal factors and the far-reaching consequences of the outbreak indicate that cholera is a unique prism through which to view different political phenomena including the dilemmas and contradictions of political change, bureaucratic order, humanitarianism, crisis and citizenship in Zimbabwe. Drawing on extensive field research, I make three inter-locking arguments in this thesis. First, I argue that Zimbabwe's cholera outbreak was a 'man-made' disaster. It was the final stage of both path-dependent and contingent processes rooted in questions of political economy such as the collapse of public health infrastructure, failing livelihood strategies and violent repression. Second, I argue that cholera reproduced and exacerbated a multiplicity of socio-political crises pertaining to the legitimacy of the Zimbabwean state, the nature of structural inequalities in Zimbabwean society and fundamental flaws in the global humanitarian response to epidemics. Third, I look at the myriad meanings, memories and narratives the epidemic has left in its wake across public institutions and in civic life. I argue that cholera has been committed to historical memory as a health crisis, a political-economic crisis, and a social crisis as well as a crisis of expectations, history and social identity.

Made available in DSpace on 2016-01-26T12:51:52Z (GMT). No. of bitstreams: 1 renanmarino_dissert.pdf: 169975 bytes, checksum: c620ad3ab663f54b325212a54713d287 (MD5) Previous issue date: 2006-03-06 / The evolution of the medical practice passed by through several paradigms in the last two centuries: the medical police, as a result of the mercantilism; the urban medicine which integrated the poor people in the French productive structure; the English sanitarism, result of the industrial policy and the scientific medicine, subordinated to the economic system. The objective of this research is to demonstrate the effectiveness of Homeopathy in epidemics, having the Dengue disease as reference, with a conception of systemic health, no more fragmented or reductionist, in accordance with the new paradigm that promotes the empiric clinical approach as the fundamental guideline. This paradigm takes into account the physical, biological, psychological, cultural and social aspects of the human being according to an inter-relational and cientific vision. The Homeopathy, appeared in the end of the XVIII century, differently of the ones that suppose treating just of placebo effect, it has been proving its action, as well as its therapeutic effectiveness along extensive accumulated clinical practice. Results of a research made in São José do Rio Preto have pointed out favorably to the validity of the use of Homeopathy in collective health, by means of the implementation of a protocol directed toward the prophylaxis of Dengue epidemic. / A evolução da prática médica passou por diversos paradigmas nos dois últimos séculos: a polícia médica, como resultado do mercantilismo; a medicina urbana, que integrou os pobres na estrutura produtiva francesa; o sanitarismo inglês, resultado da política industrial e a medicina científica, subordinada ao sistema econômico. O objetivo desta pesquisa é demonstrar a eficácia da homeopatia em epidemias, tendo a dengue como referência, com uma concepção de saúde sistêmica, não mais fragmentada ou reducionista, alinhada com o novo paradigma, que promove a abordagem clínica empírica como diretriz fundamental, envolvendo os aspectos físico, biológico, psicológico, cultural e social do ser, em uma visão inter-relacional e com rigor científico. Homeopatia, surgida no final do século XVIII, diferentemente dos que supõem se tratar apenas de efeito placebo, tem comprovado sua ação, bem como sua eficácia terapêutica ao longo de extensa prática clínica acumulada. Resultados de pesquisa feita em São José do Rio Preto apontam favoravelmente para a validação do uso da homeopatia em saúde coletiva, por meio da uma implementação de um protocolo voltado para a profilaxia de epidemia de dengue.

A epidemia de HIV/AIDS, que sofreu grandes mudanças em seus padrões clínicos e epidemiológicos, atingiu neste século sua estabilidade. Durante estes 30 anos os profissionais de saúde aprenderam muito sobre a doença e hoje esse aprendizado reflete-se em maior eficiência no diagnóstico e no tratamento da infecção pelo vírus e de suas manifestações oportunistas. As lesões orais associadas ao HIV são motivo de estudo desde os primeiros relatos da doença no início dos anos 80, e foram relacionadas ao sexo, idade, naturalidade, forma de exposição ao vírus e a padrões virológicos e imunológicos. Mas a pressão exercida pelas mudanças das características demográficas da epidemia sobre as manifestações bucais oportunistas do HIV não foi levada em consideração. A estabilidade da epidemia e o amadurecimento do conhecimento proporcionam um terreno propício para a avaliação da real prevalência dessas manifestações. Esta pesquisa tem como objetivo verificar como está este panorama no Brasil. Cento e quatro pacientes HIV+ em início de TARV foram avaliados clinicamente, e foram colhidos dados demográficos e exames laboratoriais, além da execução de sialometria e índice CPO-D. A população avaliada foi predominantemente masculina (78,8%) com média de 37,8 anos de idade. A via de transmissão do HIV foi sexual, sendo 57,7% através do sexo homo/bissexual e 38,4% com sexo heterossexual. 52,9 % souberam de sua soropositividade a menos de um ano. O CD4 médio foi de 223 céls/mm³ e a CV de 121.400 cópias/ml. As lesões extraorais foram diagnosticadas em 10,6% dos pacientes, sendo as hiperpigmentações de pele e mucosa (9,6%) e o aumento de glândulas salivares (0,96%) as lesões mais encontradas. A candidíase oral (49%) e a leucoplasia pilosa (41,3%) foram as lesões intraorais mais prevalentes. A xerostomia foi queixa de 46,6% e a hipossalivação foi diagnosticada em 18% e 48% dos pacientes, dependendo da metodologia utilizada para avaliação. O índice CPOD foi de 14,4, considerado alto pela OMS. A presença de lesões orais, candidíase e leucoplasia pilosa foram associadas à baixa imunidade e a presença de lesões orais e candidíase a cargas virais altas. A hipossalivação, avaliada através do fluxo salivar estimulado e representando principalmente a saliva da parótida, foi relacionado com níveis de CD8 alterados. Comparado com a literatura revisada, a prevalência de lesões orais associadas ao HIV apresenta-se alterada neste estudo, principalmente pela ausência de diagnóstico de neoplasias malignas e baixa prevalência de outras lesões orais associadas à aids. / HIV/AIDS epidemic, which has undergone major changes in their clinical and epidemiological patterns, in this century reached its stability. During these 30 years, much has been learned about the disease by health care professionals and nowadays, all this knowledge is reflected in greater efficiency in the diagnosis and treatment of virus infection and its opportunistic manifestations. HIV oral related lesions have been studied since the first reports of the disease in the earlies 80\'s, and were related to gender, age, place of birth, route of virus exposure, and virological and imunological patterns. Demographic changes of the disease over oral HIV opportunistic diseases have not been taken into consideration. The stability of epidemics and maturing of knowledge provide a fertile ground for the evaluation of the real prevalence of these manifestations. This research aims to verify this scenario in Brazil. A hundred and four HIV+ patients starting HAART were evaluated clinically, and demographic data and laboratory tests were collected, in addition to performing sialometry and DMFT index. The population was predominantly male (78,8%), average of 37,8 years old. The route of HIV transmission was sexual, 57,7% through homo/bisexual sex, and heterosexual sex, with 38,4%. 52,9% knew their HIV sero status to less than one year. The average CD4 was 223 cell/mm3 and CV of 121,400 copies/ml. Extra oral lesions were observed in 10,6% of patients, the skin and mucosal hyperpigmentation (9,6%) and enlargement of salivary glands (0,96%) were the lesions diagnosed. Oral candidiasis (49%) and oral hairy leukoplakia (41,3%) were the most prevalent intraoral lesions. Xerostomia was a complaining of 46,6% and hyposalivation was diagnosed in 18% and 48% of patients, depending on the methodology applied. The DMFT index was 14,4, considered high by WHO. Oral lesions, oral candidiasis and oral hairy leukoplakia were associated to low immunity and high viral load levels. Hyposalivation, evaluated by stimulated salivary flow (mainly, representing the saliva produced by parotid gland) was associated with altered levels of CD8. Compared to reviewed literature, oral lesions prevalence was considered altered in this research, notably the lack of diagnosis of malignant neoplasias and low prevalence of other lesions associated with aids. .