Letteratura scientifica selezionata sul tema "Epidemiology"

RESUMO Objetivo: avaliar a implantação dos Núcleos Hospitalares de Epidemiologia. Método: trata-se de estudo quantitativo, descritivo, avaliativo, do tipo normativo. Realizou-se em nove núcleos hospitalares de Epidemiologia. Obtiveram-se os dados por meio de questionário autoaplicável e formulário. Apresentaram-se os resultados em forma de tabelas. Resultados: agruparam-se os resultados em matriz de julgamento e o somatório dos pontos obtidos determinou a adequação da implantação. Conclusão: constatou-se, pelo estudo, que a implantação dos Núcleos Hospitalares de Epidemiologia, não ocorreu de forma satisfatória. Descritores: Vigilância Epidemiológica; Hospital; Serviços de Saúde; Enfermagem; Epidemiologia; Pesquisa Sobre Serviços de Saúde.ABSTRACT Objective: to evaluate the implantation of the Hospital Epidemiology Centers. Method: this is a quantitative, descriptive, evaluative, normative study. It was carried out in nine hospital centers of Epidemiology. The data was obtained through a self-administered questionnaire and form. Results were presented in the form of tables. Results: the results were grouped in the trial matrix and the sum of the points obtained determined the adequacy of the implantation. Conclusion: It was verified, by the study, that the implantation of the Hospital Epidemiology Centers, did not occur in a satisfactory way. Descriptors: Epidemiological Surveillance; Hospital; Health services; Nursing; Epidemiology; Health Services Research.RESUMEN Objetivo: evaluar la implantación de los Núcleos Hospitalarios de Epidemiología. Método: se trata de estudio cuantitativo, descriptivo, evaluativo, del tipo normativo. Se realizó en nueve núcleos hospitalarios de Epidemiología. Se obtuvieron los datos por medio de cuestionario autoaplicable y formulario. Se presentaron los resultados en forma de tablas. Resultados: se agruparon los resultados en matriz de juicio y la suma de los puntos obtenidos determinó la adecuación de la implantación. Conclusión: se constató, por el estudio, que la implantación de los Núcleos Hospitalarios de Epidemiología, no ocurrió de forma satisfactoriaDescriptores: Monitoreo Epidemiológico; Hospital; Servicios de Salud; Enfermería; Epidemiología; Investigación em Servicios de Salud.

Abstract Epidemiology should aim to improve population health; however, no consensus exists regarding the activities and skills that should be prioritized to achieve this goal. We performed a scoping review of articles addressing the translation of epidemiologic knowledge into improved population health outcomes. We identified 5 themes in the translational epidemiology literature: foundations of epidemiologic thinking, evidence-based public health or medicine, epidemiologic education, implementation science, and community-engaged research (including literature on community-based participatory research). We then identified 5 priority areas for advancing translational epidemiology: 1) scientific engagement with public health; 2) public health communication; 3) epidemiologic education; 4) epidemiology and implementation; and 5) community involvement. Using these priority areas as a starting point, we developed a conceptual framework of translational epidemiology that emphasizes interconnectedness and feedback among epidemiology, foundational science, and public health stakeholders. We also identified 2–5 representative principles in each priority area that could serve as the basis for advancing a vision of translational epidemiology. We believe an emphasis on translational epidemiology can help the broader field to increase the efficiency of translating epidemiologic knowledge into improved health outcomes and to achieve its goal of improving population health.

Purpose Epidemiology is the study of the distribution and determinants of disease and other health-related events in populations. An understanding of epidemiology among audiologists is important for ear and hearing health care practice. This tutorial presents an overview of the fundamental concepts of epidemiology for the practicing audiologist and audiology students. Method The authors provide an overview of epidemiology and focus on its applicability to audiology. The most common epidemiologic study designs, measures of occurrence, and measures of association are highlighted and discussed. Concepts related to p values, confidence intervals, confounding, and bias are introduced. Finally, the authors discuss screening as a means to control adverse hearing health outcomes. Conclusions Epidemiologic approaches are of value to the audiologist involved in the evidence-based decision processes of planning, monitoring, and treating individuals with ear and hearing problems. For audiologists to make practice recommendations based on epidemiologic data, they need insight into epidemiologic study design and interpretation of data from these studies. Understanding the fundamentals of epidemiology and applying epidemiologic principles to the clinical practice of audiology can increase the quality of care individuals receive.

Abstract Increasing diverse engagement in the Society for Epidemiologic Research (SER) will positively impact the field of epidemiology. As the largest and longest-running epidemiologic society in North America, SER has long been a pioneer in promoting diversity and inclusion. A recent survey of SER members, however, showed there is still room for improving diversity, inclusion, representation, and participation in the Society. In this commentary, as members of both the SER and the Johns Hopkins Bloomberg School of Public Health Department of Epidemiology’s Inclusion, Diversity, Equity, Anti-Racism, and Science (Epi IDEAS) Working Group, we recommend 4 goals for the SER Annual Meeting and beyond: 1) convene epidemiologic researchers with diverse backgrounds and ideas; 2) promote an inclusive environment at the SER Annual Meeting; 3) develop, compile, and disseminate best practices to honor diversity in epidemiologic research; and 4) increase prioritization of health disparities research and methods. We also suggest strategies for achieving these goals so that SER can better include, support, and elevate members from historically disadvantaged groups. While our recommendations are tailored specifically to SER, the greater epidemiologic and academic communities could benefit from adopting these goals and strategies within their professional societies and conferences.

In 1994, the Instituto de Salud Carlos III (ISCIII; Carlos III Health Institute) of the Spanish Ministry of Health and the Consumer (MSC) created the Programa de Epidemiología Aplicada de Campo (PEAC; Applied Field Epidemiology Programme). The programme is managed by the Centro Nacional de Epidemiología (National Epidemiological Centre) in collaboration with the Escuela Nacional de Sanidad (National School of Health), and supported by General Direction for Health and Consumer of MSC and the Health Councils (Consejerías de Sanidad) of the autonomous regions. The PEAC runs a masters degree programme in applied field epidemiology, in which degrees are conferred by the National School of Health. As PEAC is a national programme, it forms a part of the European Program for Intervention Epidemiology Training (EPIET) and is a member of the Network Training for Epidemiology Public Health Intervention (TEPHINET), the association of 27 regional and national programmes of the acting Intervention Epidemiology Training Programs.

AbstractThe laboratory plays a major role in the epidemiology program's efforts to minimize nosocomial infections in healthcare institutions. This article will describe some of the interactions between the laboratory and the epidemiology program, and will identify resources and procedures that the laboratory needs to achieve epidemiologic goals.

Abstract In the last third of the 20th century, etiological epidemiology within academia in high-income countries shifted its primary concern from attempting to tackle the apparent epidemic of noncommunicable diseases to an increasing focus on developing statistical and causal inference methodologies. This move was mutually constitutive with the failure of applied epidemiology to make major progress, with many of the advances in understanding the causes of noncommunicable diseases coming from outside the discipline, while ironically revealing the infectious origins of several major conditions. Conversely, there were many examples of epidemiologic studies promoting ineffective interventions and little evident attempt to account for such failure. Major advances in concrete understanding of disease etiology have been driven by a willingness to learn about and incorporate into epidemiology developments in biology and cognate data science disciplines. If fundamental epidemiologic principles regarding the rooting of disease risk within populations are retained, recent methodological developments combined with increased biological understanding and data sciences capability should herald a fruitful post–Modern Epidemiology world.

Abstract The Department of Epidemiology at Johns Hopkins School of Hygiene and Public Health was founded in 1919, with Wade Hampton Frost as inaugural chair. In our Centennial Year, we review how our research and educational programs have changed. Early years focused on doctoral education in epidemiology and some limited undergraduate training for practice. Foundational work on concepts and methods linked to the infectious diseases of the day made major contributions to study designs and analytical methodologies, largely still in use. With the epidemiologic transition from infectious to chronic disease, new methods were developed. The Department of Chronic Diseases merged with the Department of Epidemiology in 1970, under the leadership of Abraham Lilienfeld. Leon Gordis became chair in 1975, and multiple educational tracks were developed. Genetic epidemiology began in 1979, followed by advances in infectious disease epidemiology spurred by the human immunodeficiency virus/acquired immune deficiency syndrome epidemic. Collaborations with the Department of Medicine led to development of the Welch Center for Prevention, Epidemiology, and Clinical Research in 1989. Between 1994 and 2008, the department experienced rapid growth in faculty and students. A new methods curriculum was instituted for upper-level epidemiologic training in 2006. Today’s research projects are increasingly collaborative, taking advantage of new technologies and methods of data collection, responding to “big data” analysis challenges. In our second century, the department continues to address issues of disease etiology and epidemiologic practice.

Abstract As in other areas of epidemiology, researchers studying physical activity and cancer have begun to include laboratory analyses of biological specimens in their studies. The incorporation of these “biomarkers” into epidemiology has been termed molecular epidemiology and is an approach primarily developed to study chemical carcinogens. Thus far, there has been no discussion in the field on how the established molecular epidemiologic framework might be adapted for research into physical activity, what methodologic needs exist, what the goals of such an approach might be, and what limitations exist. This article relates the literature on molecular epidemiology to the needs of physical activity research and tries to set research priorities for the field as it moves in this new direction. Although this approach will be very useful for investigating the mechanisms through which physical activity exerts effects, there are several challenges for physical activity epidemiologists in adapting molecular epidemiologic approaches. Primarily, there are currently no available biomarkers that might be considered measures of exposure or biologically effective dose. In addition, most available biomarkers of intermediate effects have been tested in training studies at activity levels much higher than those seen in population-based epidemiologic studies. Thus, it is not clear whether these biomarkers are valid at lower activity levels. Furthermore, the nature of the relationship between activity and many available biomarkers depends very much on the context of the activity. Addressing these issues should be a priority if we are to develop a molecular epidemiologic paradigm for studying physical activity.

Taenia solium i Taenia saginata són dos paràsits zoonòtics que causen teniasi en persones (hoste definitiu) i cisticercosi en porcí i boví (hoste intermediari), respectivament. A Europa, T. saginata ha estat present durant segles, tanmateix hi ha poca informació sobre l’ocurrència i impacte d’aquest agent zoonòtic. T. solium es considera absent a Europa però les dades existents sobre aquest paràsit són escasses. En conseqüència, les dades sobre la incidència i prevalença de T. saginata i T. solium en persones i animals a Europa són incompletes i es troben fragmentades. En aquest context, la present tesi va tenir per objectiu general avançar en el coneixement de l’epidemiologia de T. saginata i T. solium a Europa. L’estudi I d’aquesta tesi va consistir en una revisió sistemàtica d’estudis publicats entre 1990 i 2014 que va tenir com a objectiu compilar el coneixement actual sobre l’epidemiologia, impacte i control de la cisticercosi bovina a Europa. Els resultats d’aquest estudi van indicar que existeix una mancança de dades epidemiològiques completes i actualitzades en la majoria de països, especialment en els països de l’Est d’Europa. A més a més, es va concloure que la falta d’informació epidemiològica limita el desenvolupament d’estratègies de vigilància basades en risc i es va recomanar la realització d’estudis de factors de risc per guiar aquestes estratègies. En l’estudi II es va actualitzar el coneixement de l’epidemiologia de T. saginata i T. solium en persones i animals a Europa Occidental a través d’una revisió sistemàtica de literatura científica i grisa publicada entre 1990 i 2015. Igualment, es va realitzar una cerca de dades sobre casos a través d’experts locals en els diferents països. Els resultats van indicar que és necessari millorar tant la detecció com la notificació de les teniasis humanes a Europa Occidental. A més a més, es van identificar casos de persones portadores de la forma adulta de T. solium, casos de cisticercosi humana sospitosos de ser autòctons i casos de T. solium en porcí sense confirmació molecular. Aquestes troballes, juntament amb un augment de la migració des d’àrees on T. solium és endèmic, podrien constituir un risc per a la salut pública i mereixen una major atenció. A més a més, aquest estudi va concloure que els casos sospitosos de T. solium en porcs haurien de confirmar-se amb tècniques moleculars, que tant les teniasis com la cisticercosi humana haurien de ser notificables i que s’hauria de millora la vigilància i notificació en animals. L’estudi III va tenir com a objectiu estimar la prevalença i distribució espacial de la cisticercosi bovina (2008–2015) i l’impacte de T. saginata en sanitat animal i humana (2013–2015) en el nord-est d’Espanya (Catalunya). Durant 2008–2015 es va detectar una prevalença a escorxador de 0.010%. A partir dels registres de moviments de bovins es va identificar el lloc on els animals s’haurien infectat amb una major probabilitat i es va investigar la seva distribució espacial. Tenint en compte la granja on la infecció s’hauria produït amb més probabilitat, es van detectar dos conglomerats. El nombre de pacients amb diagnòstic de teniasi en atenció primària durant 2013–2016 va ser petit (41–63/any) suggerint que el risc en salut pública de T. saginata en l’àrea d’estudi és baix. L’impacte econòmic de T. saginata a Catalunya durant 2013–2015 es va calcular considerant els costos de la inspecció postmortem, les pèrdues causades pel decomís i congelació de canals i els costos associats a casos de teniasis. Els resultats obtinguts van indicar que l’impacte econòmic de T. saginata s’atribueix principalment a la inspecció postmortem i que el desenvolupament d’estratègies de vigilància basades en risc podria ser útil per reduir aquest cost. Els resultats també van evidenciar la importància de tenir en compte la traçabilitat dels animals per al desenvolupament d’aquesta estratègia.
Taenia solium y Taenia saginata son dos parásitos zoonóticos que causan teniasis en personas (hospedador definitivo) y cisticercosis en cerdos y en ganado vacuno (hospedador intermediario), respectivamente. En Europa, T. saginata ha estado presente durante siglos, sin embargo hay poca información acerca de la ocurrencia e impacto de este agente zoonótico. T. solium se considera ausente en Europa pero los datos existentes sobre este parásito son escasos. En consecuencia, los datos sobre la incidencia y prevalencia de T. saginata y T. solium en personas y animales en Europa son incompletos y se encuentran fragmentados. En este contexto, la presente tesis tuvo por objeto general avanzar en el conocimiento de la epidemiología de T. saginata y T. solium en Europa. El estudio I de esta tesis consistió en una revisión sistemática de estudios publicados entre 1990 y 2014 que tuvo como objetivo compilar el conocimiento actual sobre la epidemiología, impacto y control de la cisticercosis bovina en Europa. Los resultados de este estudio indicaron que existe una carencia de datos epidemiológicos completos y actualizados en la mayoría de países, especialmente en los países del Este de Europa. Además, se concluyó que la falta de información epidemiológica limita el desarrollo de estrategias de vigilancia basadas en riesgo y se recomendó la realización de estudios de factores de riesgo para guiar dichas estrategias. En el estudio II se actualizó el conocimiento de la epidemiología de T. saginata y T. solium en personas y animales en Europa Occidental a través de una revisión sistemática de literatura científica y gris publicada entre 1990 y 2015. Así mismo, se realizó una búsqueda de datos sobre casos a través de expertos locales en los diferentes países. Los resultados indicaron que es necesario mejorar tanto la detección como la notificación de las teniasis humanas en Europa Occidental. Además, se identificaron casos de personas portadoras de la forma adulta de T. solium, casos de cisticercosis humana sospechosos de ser autóctonos y casos de T. solium en cerdos sin confirmación molecular. Estos hallazgos, junto con un aumento de la migración desde áreas donde T. solium es endémico, podrían constituir un riesgo para la salud pública y merecen una mayor atención. Además, este estudio concluyó que los casos sospechosos de T. solium en cerdos deberían confirmarse con técnicas moleculares, que tanto las teniasis como la cisticercosis humana deberían ser notificables y que se debería mejorar la vigilancia y notificación en animales. El estudio III tuvo como objetivo estimar la prevalencia y distribución espacial de la cisticercosis bovina (2008–2015) y el impacto de T. saginata en sanidad animal y humana (2013–2015) en el noreste de España (Cataluña). Durante 2008–2015 se detectó una prevalencia en matadero de 0.010%. A partir de los registros de movimientos de bovino se identificó el lugar donde los animales se habrían infectado con mayor probabilidad y se investigó su distribución espacial. Teniendo en cuenta la granja en la que con mayor probabilidad se habría producido la infección, se detectaron dos conglomerados. El número de pacientes con diagnóstico de teniasis en atención primaria durante 2013–2016 fue pequeño (41–63/año) sugiriendo que el riesgo en salud pública de T. saginata en el área de estudio es bajo. El impacto económico de T. saginata en Cataluña durante 2013–2015 se calculó considerando los costes de la inspección postmortem, las pérdidas causadas por el decomiso y congelación de canales y los costes asociados a casos de teniasis. Los resultados obtenidos indicaron que el impacto económico de T. saginata se debe principalmente a la inspección postmortem y que el desarrollo de estrategias de vigilancia basadas en riesgo podría ser útil para reducir dicho coste. Los resultados también evidenciaron la importancia de tener en cuenta la trazabilidad de los animales para el desarrollo de dicha estrategia.
Taenia solium and Taenia saginata are two zoonotic parasites that cause taeniosis in humans (definitive host) and cysticercosis in pigs and cattle (intermediate host), respectively. In Europe, T. saginata has been present for centuries but data showing the occurrence and burden of this zoonotic agent are scarce. T. solium is considered absent in Europe but data about this parasite in this region are limited. In consequence, data on T. saginata and T. solium occurrence in humans and animals in Europe are incomplete and fragmented. In this context, the general aim of this thesis was to advance the knowledge of the epidemiology of T. saginata and T. solium in Europe. In study I a systematic review of studies published between 1990 and 2014 was conducted to present the current knowledge on the epidemiology, impact and control of bovine cysticercosis in Europe. The results of this study indicated that there is a lack of complete and updated epidemiological data in most countries, especially in eastern Europe. Moreover, it concluded that this lack of information is a limitation to guide risk-based interventions against the disease. Conducting studies on risk factors was recommended in order to guide such strategies. In study II, the knowledge on the epidemiology of T. saginata and T. solium in humans and animals in western Europe was updated by undertaking a systematic review of scientific and grey literature published from 1990 to 2015. Additionally, data about disease occurrence were actively sought by contacting local experts in the different countries. The results of this study indicated that the detection and reporting of human taeniosis in western Europe needs to be improved. Furthermore, the study identified reports of T. solium tapeworm carriers, of suspected autochthonous cases of human cysticercosis and of suspected cases of T. solium in pigs without molecular confirmation. These findings, combined with the increased migration from T. solium endemic areas, may constitute a public health risk that deserves further attention. Moreover, in this study it was concluded that suspected cases of T. solium in pigs should be confirmed by molecular methods, that both taeniosis and human cysticercosis should be notifiable and surveillance and reporting in animals should be improved. Study III of this thesis aimed to estimate the prevalence and spatial distribution of bovine cysticercosis (2008–2015) and the burden from T. saginata upon the animal and human sectors (2013–2015) in northeastern Spain (Catalonia). During 2008–2015 a mean prevalence of 0.010% was detected at slaughter. Cattle movement history was used to identify the place where cattle most likely became infected and to investigate its spatial distribution. Based on the farm where the infection was acquired with highest probability, two significant bovine cysticercosis clusters were detected in Catalonia. The number of patients diagnosed with taeniosis in primary care during the period 2013–2016 was low (41–63/year) suggesting that the public health risk of T. saginata in the study area is low. The economic impact of T. saginata in Catalonia during 2013–2015 was estimated considering costs of meat inspection, losses due to carcass condemnation and freezing and taeniosis-associated costs. The results obtained indicated that the economic impact due to T. saginata was mainly attributed to meat inspection and suggested that developing and implementing a risk-based surveillance is needed to lower these costs. Results also indicated that cattle movements need to be taken into account in the development of such a strategy.

Branches of science such as epidemiology, clinical epidemiology, statistics and various statistical methods are by ground for activity of epidemiological-manager indicators. Incidence and prevalence are numbered among epidemiological-manager indicators. In condition of hospital Pelhřimov are these indicators written, analyzed and predicated for department of hospitalized in years 2005 -- 2007. At the same time is appraised use of capacities department of hospitalized, is made analyse and estimation of most often treated diagnosis and is watched progress their average time of treatment. The watching indicators are by one of series others records for manager decision-making by control of hospital.

Dance greatly contributes to social, cultural and economic development, as well as entertainment and recreational physical activity. There are many different motivators and benefits to dance participation at the recreational, elite student and professional level. There is also a risk of injury at all levels of dance practise and any injury has the potential for significant consequences. In order to effectively prevent injuries it is critical to understand their magnitude and characteristics. However, there is a paucity of data relating to dance participation and injuries in the recreational dancer, as well as research investigating injuries in professional dancers across all different styles and employment situations. Therefore, six studies were conducted in this thesis, which aimed to develop a better understanding of the epidemiology of injuries across the full spectrum of dance participation. This thesis addressed current gaps in the literature, including the incorporation of recreational dancers and the use of high quality nationally representative data. It also contributed to the local professional dance industry through Safe Dance IV, which incorporated a broader scope of professional dancers than previous Australian studies. Overall this thesis highlighted the high prevalence of injuries in dance and emphasised that injury prevention and management are important considerations for all levels of dancers.

Orientador: Maria da Luz Rosario de Sousa
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Nos últimos anos houve uma evidente mudança na epidemiologia e no padrão da doença cárie. Neste contexto, métodos tradicionais de diagnóstico podem estar subestimando as lesões de cárie, principalmente em superfícies oclusais. Esta pesquisa teve como objetivo verificar a prevalência de lesões de cárie oculta oclusal em escolares de 12 a 15 anos de idade através de métodos complementares de diagnóstico em levantamentos epidemiológicos. A amostra constituiu-se de 179 escolares de 12 a 15 anos matriculados em 20 escolas públicas de Piracicaba. Após o exame visual (EV) segundo os critérios da OMS, (1997) 1290 dentes sem sinal de cavitação na superfície oclusal foram reavaliados por meio do exame visual com secagem prévia (EVS); exame radiográfico (ER) e com o auxílio do aparelho Diagnodent (DD). A média do Índice CPO- D na população estudada foi de 2,3 e 32,5% dos escolares estavam livres de cárie segundo EV. Das 1290 superfícies examinadas no exame visual, 918 superfícies oclusais foram diagnosticadas como hígidas. Destas, 241 (26,3%) apresentaram imagem radiolúcida sugerindo cárie em dentina pelo ER. Das 41 superfícies que apresentaram escurecimento da dentina sob esmalte íntegro, 25 também apresentaram imagem radiolúcida sugerindo cárie em dentina. Incluindo as lesões em dentina diagnosticadas pelo ER o CPO-D dos escolares seria de 3,1, e apenas 13,4% dos escolares estariam livres de cárie. A prevalência de cárie oculta foi de 56,4%, com média de 1,68 superfícies oclusais afetadas por escolar. Quando comparados os resultados do exame com o aparelho Diagnodent em relação ao Exame Radiográfico, a sensibilidade foi de 64% e a especificidade de 74%. Diante desses resultados, conclui-se que a prevalência de lesões de cárie oculta oclusal obtida através de levantamentos epidemiológicos sem o uso de métodos auxiliares está sendo subestimada. Sendo assim, estudos epidemiológicos que busquem estimar este subestimação são importantes para contribuir para o planejamento dos serviços de saúde bucal. O Diagnodent pode ser indicado como método auxiliar ao diagnóstico de lesões de cárie ao exame visual, na impossibilidade de utilização do exame radiográfico
Abstract: In recent years there has been a clear change in the epidemiology and pattern of dental caries. In this context, traditional methods of diagnosis may be underestimating caries lesions, mainly at occlusal surfaces. The aim of this research was to verify the occlusal hidden caries prevalence in surveys and if laser fluorescence may be indicated to be used in surveys for its diagnosis. The sample comprehended 1290 occlusal surfaces of permanent molars, examined in 179 students, aged 12-15. The methods used were: Visual Inspection (VI), Visual Inspection with previous drying (VID), bitewing radiography (BI) and laser fluorescence by Diagnodent. The mean DMFT value was 2.3, and 32.5% of the students were free from caries on the VI. From the 918 surfaces scored as clinically sound on VI, 41 demonstrated grayish discolouration under sound enamel by VID, and 241 demonstrated dentine radiolucency on BI. From the 41 surfaces which demonstrated darkening dentin under sound enamel, 25 demonstrated dentin radiolucency. Including the dentin lesions diagnosis on BI, the mean DMFT was 3.1 and 13.4% of the students were free from caries. The occlusal hidden caries prevalence was 56.4% with an average of 1.68 affected occlusal surfaces by each student. When compared the results of Diagnodent with BI, the sensitivity was 64% and the specificity was 74%. From these results we can conclude that the occlusal hidden caries prevalence in surveys must be considered and the Diagnodent, in this case, can be used as an auxiliary tool on Visual Inspection, but not as a substitute of Bitewing Radiographic
Mestrado
Cariologia
Mestre em Odontologia

La carga de enfermedad y las muertes relacionadas con la malaria han disminuido a nivel global, principalmente gracias a las mejoras en la implementación de las intervenciones para prevenir y tratar la malaria, y en particular al uso de las mosquiteras impregnadas con insecticidas de larga duración y al tratamiento de los episodios clínicos con terapias combinadas con artemisinina. El reciente aumento de los fondos mundiales destinados a financiar los esfuerzos de control de la malaria ha permitido que la mayoría de la población pobre que vive en países endémicos de malaria tenga acceso a medidas de prevención, a diagnóstico en caso de sospecha de malaria y a terapias combinadas con artemisinina. De acuerdo a los datos de 104 países recopilados por la OMS en el Informe Mundial sobre el Paludismo del 2012, se estima que se evitaron 274 millones de casos de malaria y 1.1 millones de muertes relacionadas con la malaria. El éxito de las medidas de control actuales ha reactivado el objetivo de la eliminación de la malaria y su erradicación del globo. Sin embargo, la mayor parte de los logros globales se deben a la reducción de enfermos graves y muertes debidos a Plasmodium falciparum, principalmente en los países africanos. Fuera de África, la mayoría de las regiones endémicas de malaria cuentan con más de una especie del parásito Plasmodium. Medidas actuales como las mosquiteras impregnadas con insecticidas de larga duración y las terapias combinadas de artemisinina se han mostrado más eficaces contra P. falciparum que contra Plasmodium vivax. En la mayoría de los países endémicos donde P. vivax y P. falciparum coexisten, con programas eficaces de control de la malaria, parece haberse producido un incremento proporcional de la prevalencia de P. vivax, sustituyendo a P. falciparum como especie predominante. P. vivax es más difícil de controlar que P. falciparum a causa de la fase hepática de P. vivax llamada hipnozoito. Los hipnozoitos pueden permanecer inactivos en el hígado durante largos períodos de tiempo antes de volver a activarse para reinfectar la sangre y causar una recaída de malaria por P. vivax en el huésped humano. En las regiones tropicales los hipnozoitos se activan rápidamente, y son comunes las recaídas múltiples a intervalos de cerca de 3 semanas, mientras que en las zonas subtropicales las recaídas pueden producirse con intervalos más largos (de 8 a 10 meses). Lograr la eliminación y erradicación de la malaria será difícil sin la erradicación de los hipnozoitos del hígado, especialmente en regiones endémicas con transmisión de la malaria perenne como Papúa Nueva Guinea. Actualmente, la primaquina es el único fármaco autorizado en el mercado que tiene efecto sobre los hipnozoitos. Las terapias combinadas de artemisinina, aunque son muy eficaces contra la infección en fase sanguínea de ambos Plasmodium, no tienen ningún efecto sobre los hipnozoitos. Una de las estrategias para la eliminación de la malaria es la administración masiva de medicamentos. Sin embargo, para que esta estrategia sea eficaz en áreas endémicas de P. vivax, debe incluir la primaquina en el régimen de tratamiento para así erradicar los hipnozoitos en el hígado, pero el uso indiscriminado de este fármaco puede conllevar problemas de seguridad importantes. Los futuros posibles sustitutos de la primaquina deben ser fármacos con una fase de eliminación terminal larga con el fin de proporcionar una profilaxis post-tratamiento eficaz para detener la transmisión de P. vivax, previniendo las recaídas desde el hígado. La mayoría de las infecciones por P. vivax en niños mayores y adultos como resultado de las recaídas por activación del hipnozoito en el hígado son asintomáticas. Por otro lado, la gametogénesis (producción de gametos, los estadios infectivos responsables de la transmisión desde el humano al siguiente mosquito vector) de P. vivax ocurre de forma espontánea con el desarrollo de la infección en fase sanguínea, hecho que lleva a una gametocitemia temprana que incrementa la probabilidad de transmisión a mosquitos antes incluso de la aparición de síntomas y por tanto del tratamiento de los casos sintomáticos. Se ha demostrado que la primaquina también es el único fármaco eficaz contra los gametocitos de estadío V de P. falciparum, los verdaderos responsables de la transmisión en esta especie El uso de la primaquina para la administración masiva de medicamentos será, por lo tanto, una herramienta efectiva para la prevención de la transmisión de P. vivax y P. falciparum. En la actualidad se desconoce la contribución de los hipnozoitos a la carga de infección y enfermedad por P. vivax, especialmente en los niños que viven en zonas de alta endemicidad. La primaquina, el único fármaco efectivo contra los hipnozoitos de P. vivax y P. ovale conocido, existe desde hace más de 60 años pero, sin embargo, se sabe muy poco de su seguridad y tolerabilidad en los niños, la población que sufre la mayor carga de infección y enfermedad por P. vivax. Incluso en su uso en adultos, todavía no se sabe mucho acerca de la dosificación y modo de acción. Existen importantes limitaciones en el uso de la primaquina en regímenes de tratamiento de la malaria. En primer lugar, el riesgo letal de anemia hemolítica grave asociada al tratamiento con primaquina para las personas con las variantes graves de deficiencia de deshidrogenasa de glucosa-6-fosfato (G6PD). En segundo lugar, la falta de un test de diagnóstico rápido barato, fiable y accesible para detectar la deficiencia de G6PD durante la actividad clínica rutinaria, así como durante el ejercicio preventivo de administración masiva de medicamento. En Papua Nueva Guinea, varios estudios de cohorte longitudinales han demostrado que P. vivax es la causa más común de infección y enfermedad por malaria en los niños menores de 3 años de edad, mientras que P. falciparum predomina como causa de morbilidad en niños de 3 a 10 años de edad. La enfermedad clínica secundaria a P. vivax tiene su punto culminante a los 3 años de edad. A pesar de que la prevalencia de la infección por P. vivax y P. falciparum son similares en el grupo de mayor edad, los niños con infección de P. vivax permanecen asintomáticos o presentan enfermedad clínica leve. No hay variación estacional en la prevalencia de P. vivax en comparación con la de P. falciparum. Esto puede ser debido a las recaídas por activación de los hipnozoitos en el hígado, que contribuyen a la reinfección de la fase sanguínea, sin requerir la transmisión mediante el vector anofelino. Esta tesis presenta datos de dos estudios de cohortes longitudinales en niños de 1 a 10 años de Papua Nueva Guinea con niveles normales de G6PD para evaluar el efecto de la primaquina sobre los hipnozoitos en el hígado. Los objetivos eran dos: El primero: determinar la contribución de las recaídas de la activación desde los hipnozoitos a la carga de infección y enfermedad por P. vivax en los niños que viven en una zona de alta transmisión de malaria, después de un pre-tratamiento con primaquina. El segundo: evaluar la seguridad y tolerabilidad del uso de la primaquina en los niños como pre-tratamiento en el terreno. Tras los estudios de cohortes, se estudiaron las propiedades farmacocinéticas de una dosis única de primaquina en niños de Papua Nueva Guinea para evaluar la viabilidad de un eventual tratamiento corto con dosis altas de primaquina para la cura radical de la malaria por P. vivax. Estos estudios constituyen la base de esta tesis. En el primer estudio, niños de entre 1 y 5 años con G6PD normal fueron seleccionados y distribuidos aleatoriamente en tres grupos: grupo control sin medicación pre-tratamiento; grupo pre-tratado con artesunato + primaquina, y aquellos solamente tratados con artesunato. Las dosis de tratamiento se administraron bajo observación directa, y siempre junto con comida. Los niños fueron seguidos activamente cada dos semanas durante los primeros tres meses, luego mensualmente hasta nueve meses haciendo detección de casos con infección de malaria asintomática y de casos clínicos. La detección pasiva de casos se hizo mediante las enfermeras establecidas en las clínicas locales durante la duración total del estudio. Los resultados de este estudio de cohorte muestran que el pre-tratamiento con artesunato más primaquina (14d, 0.5 mg) redujo la incidencia de malaria por P. vivax en un 49% durante los 3 primeros meses (p = 0.031) y un 19% para los meses 4 a 9 (p = 0,25). También redujo el tiempo de la primera detección por microscopía óptica y por PCR de los casos positivos por infección en un 57% y 48%, respectivamente (p < 0,001), en comparación con el grupo que sólo tomó artesunato. El efecto preventivo del pre-tratamiento en el grupo de primaquina se limitó a los primeros 3 meses de seguimiento y el 30% de los niños sufrieron una reinfección a las 2 semanas de seguimiento. En el segundo estudio, se realizó un ensayo aleatorizado, doble ciego, controlado con placebo para estudiar el efecto de la primaquina en niños de 5 a 10 años de edad con niveles normales de G6PD. Todos los niños del estudio recibieron cloroquina en los días 1 a 3, y arteméter lumefantrina en los días 15 a 17 días de la fase de pre-tratamiento. Los niños fueron asignados aleatoriamente en dos grupos para recibir primaquina o placebo, juntamente con cloroquina. Todas las dosis pre-tratamiento se administraron bajo observación directa y junto con comida utilizando el mismo programa de seguimiento del primer estudio. Los resultados del segundo estudio muestran que el pre-tratamiento con primaquina redujo el riesgo de adquirir una infección en fase sanguínea nueva en un 78% (p<0.0001), y de enfermedad clínica en un 68% (p<0.0035). La edad se asoció con un riesgo menor de presentar episodios clínicos causados por P. vivax de cualquier densidad (p<0.0167) y de alta densidad (p<0.016). La mayoría de reinfecciones ocurrieron durante las 12 semanas de pre-tratamiento. El tercer estudio, diseñado para monitorear la seguridad y la tolerabilidad del tratamiento con primaquina en los niños del estudio, se llevó a cabo durante la fase de seguimiento de los dos estudios de pre-tratamiento de cohortes. Se utilizó un cuestionario semi-estructurado de todos los posibles eventos adversos a medicamentos antes de la toma de la dosis de primaquina. Todas las dosis de primaquina se administraron con alimentos excepto en el grupo de edad más joven, en el que los niños fueron amamantados/alimentados por las madres. Los resultados de este estudio mostraron que se necesitaban 14 dosis diarias de 0.5mg/kg de primaquina para garantizar la seguridad y la tolerabilidad en los niños de ambos estudios de cohortes. En ninguno de ellos hubo eventos adversos graves y/o abandonos asociados con la toma de primaquina. En los niños que reportaron náuseas o vómitos debido a la ingestión de primaquina, la recuperación fue casi inmediata a la ingesta de alimentos. A raíz de los estudios de cohortes, se estudiaron las propiedades farmacocinéticas de dos dosis únicas de primaquina en niños de Papua Nueva Guinea de entre 5 y 10 años de edad, para evaluar la viabilidad de un tratamiento corto, con regímenes de tratamiento con primaquina en dosis altas para la cura radical de malaria por P. vivax. Se evaluaron los perfiles de las dosis de 0.5 mg/kg y 1.0 mg/kg. Durante el reclutamiento, los niños del estudio fueron ingresados en el Centro de Salud durante 2 días para poder hacer un seguimiento exhaustivo y permitir la toma de muestras de sangre frecuentes. Durante todo este tiempo los participantes llevaron una cánula intravenosa permanente para tomar muestras de sangre. Las dosis de primaquina se co-administraron con alimentos. El estudio de monitorización de la seguridad y tolerabilidad mostró que ambas dosis de primaquina fueron bien toleradas, sin efectos adversos graves. No hubo cambios observados en los síntomas y la gravedad de las náuseas o dolores abdominales en ninguno de los grupos de dosificación de primaquina. No hubo diferencias entre los grupos en la concentración de hemoglobina y niveles de metahemoglobina. Los regímenes cortos de dosis altas simulados mostraron que las concentraciones de primaquina y carboxyprimaquina en plasma predichas y obtenidas no fueron significativamente mayores que las observadas en los estudios farmacocinéticos anteriores en adultos. Esto sugiere que tanto los regímenes de dosis de 0.5 mg/kg como de 1.0mg/kg de primaquina podrían ser evaluados con más detalle en estudios de seguridad y eficacia sobre terreno. Varios estudios hechos en el pasado sobre la primaquina reportaron un aumento de la eficacia de la primaquina cuando asociada a una droga con una fase de eliminación terminal larga. La primaquina es más eficaz cuando se administra conjuntamente con cloroquina debido a su efecto profiláctico post-tratamiento más largo, tal y como se muestra en el segundo estudio de cohortes. Los estudios también han demostrado que la dosis terapéutica de primaquina se basa en el efecto de la dosis total, y no en los intervalos de dosificación, ya que una mayor dosis diaria durante 7 días parece ser tan eficaz como el régimen de 14 días con eventos adversos mínimos cuando se co-administraron con comida. La actual dosis diaria de primaquina durante 14 días es más eficaz cuando se administra en las condiciones de investigación con la observación directa de la ingesta del fármaco, mientras que en la vida real, debido a la falta de cumplimiento, el tratamiento con primaquina tiene un efecto más reducido. Un tratamiento corto con altas dosis de primaquina compatible con el régimen de 3 días de aplicación de las terapias combinadas con artemisinina sería óptimo para mejorar el cumplimiento durante el tratamiento de rutina y facilitar la administración como administración masiva de medicamentos para la eliminación de la malaria. Por tanto, el último artículo de esta tesis revisa el posible uso de la primaquina como herramienta no sólo de control sino que también para la eliminación de la malaria en el contexto de una zona como Papúa Nueva Guinea. Los resultados de estas cohortes longitudinales y los estudios de dosis de primaquina contribuirán al conocimiento científico sobre la epidemiología y el manejo de P. vivax, la seguridad del uso de primaquina en niños y a la mejora del cumplimiento de las tomas preventivas del fármaco. Esta será una herramienta útil para el control y eliminación del paludismo para combatir los hipnozoitos en el hígado del huésped humano. La estrategia de la administración masiva de medicamentos tendría potencialmente capacidad para detener la transmisión de la malaria no sólo eliminando hipnozoitos de P. vivax en el hígado, sino también los gametocitos en fase V de P. falciparum.
Globally, the burden of malaria related disease and deaths has decreased in the last 10 years, mainly due to interventions for malaria prevention and treatment with long lasting insecticide treated bed nets and the artemisinin combination therapies, respectively. The recent increase in Global funding for malaria control efforts has enabled majority of impoverished populations living in malaria endemic countries to access preventative measures, diagnosis of presumptive malaria cases and artemisinin combination therapies. According to data summaries from 104m countries compiled by WHO in the 2012 malaria report, an estimated 274 million malaria cases were averted and 1.1 million lives saved from dying, from malaria related illness. The success of current control measures has once again, renewed the goal of malaria elimination and its eradication from the globe. However, most of the global achievements are due to reductions in severe disease and deaths from Plasmodium falciparum malaria mostly in African countries. Outside of Africa, most malaria endemic regions have more than one Plasmodium parasite species present. The current measures, using long lasting insecticide treated nets and artemisinin combination therapies are more effective against Plasmodium falciparum compared to P. vivax malaria. In most P. vivax endemic countries with effective malaria control programs, there has been a relative increase in the prevalence of P. vivax, replacing Plasmodium falciparum as the predominant species. P. vivax is more difficult to control than Plasmodium falciparum. This is due to the liver stages of P. vivax called hypnozoites. The hypnozoites remain dormant in the liver for prolonged periods of time before activation, to re-infect the blood leading to P. vivax relapse infection and malaria in the human host. In Tropical regions, the hypnozoites activate quickly, and multiple relapses commonly occur, at about 3 weekly intervals, while in the subtropics, relapses occur at about 8-10 month intervals. Achieving the goal of malaria elimination and eradication will be difficult without eradication of the hypnozoites from the liver, especially in endemic regions with perennial malaria transmission such as Papua New Guinea. Currently, primaquine is the only licensed drug in the market that has an effect upon the hypnozoites. The artemisinin combination therapies while highly effective against the blood stage infection of both Plasmodium falciparum and P. vivax, have no effect upon the hypnozoites. One of the strategies for malaria elimination is mass drug administration. However, for this strategy to be effective in P. vivax endemic areas, primaquine must be included in the treatment regimen to eradicate the hypnozoites from the liver. The partner drug of primaquine must have a long terminal elimination phase in order to provide effective post-treatment prophylaxis to prevent relapses from the liver to stop P. vivax transmission. Most P. vivax infections in older children and adults as a result of relapses from hypnozoite activation in the liver are asymptomatic. Moreover, the gametocytogenesis of P. vivax occur spontaneously with the development of blood stage infection leading to early gametocytemia with high probability of transmission to mosquitoes before treatment of symptomatic cases. Primaquine has also been shown to be the only drug effective against the gametocyte stage five of Plasmodium falciparum. Primaquine use for mass drug administration will therefore be an effective tool for preventing P. vivax and P. falciparum transmission. Currently, the contribution of the hypnozoites to the burden of P. vivax infection and disease especially in children living in highly endemic areas is not well understood. Primaquine, the only licensed drug known to be effective against the hypnozoites of P. vivax (and P. ovale) existed for over 60 years, yet very little is known of its safety and tolerability in children; the population with the highest burden of P. vivax infection and disease. Even in adult use, much is still not known about dosing and mode of action. There are major limitations to primaquine use in malaria treatment regimens. Firstly, the risk of severe life threatening haemolytic anaemia associated with primaquine treatment in persons with the severe variants of glucose- 6-phosphate dehydrogenase deficiency. Secondly, the lack of cheap and reliable, point of care rapid diagnostic test for glucose-6-phosphate dehydrogenase deficiency for routine use and during mass drug administrations. In Papua New Guinea, several longitudinal cohort studies have shown P. vivax to be the commonest cause of malarial infection and disease in children less than 3 years old; while Plasmodium falciparum accounts for the majority of malarial disease burden in children over 3-10 years old. The clinical disease of P. vivax peaks at 3 years of age. Even though the prevalence of infection with P. vivax and P. falciparum are similar in the older age group, children with P. vivax infection remain asymptomatic with less clinical illness. There is much less seasonal variation in P. vivax prevalence compared to that of P. falciparum. This may be due to relapses from hypnozoite activation in the liver contributing to blood stage re-infection. Two longitudinal cohort studies in G6PD normal Papua New Guinean children aged 1 to 10 years were carried out to assess the effect of primaquine on the hypnozoites in the liver. There were two aims for the cohort studies. Firstly, to determine the contribution of relapses from hypnozoite activation to the burden of P. vivax infection and disease in children living in an area of high malaria transmission, following treatment with primaquine. Secondly, to assess the safety and tolerability of primaquine use in the children as part of the cohort studies, drug treatment phase in the field. Following the cohort studies, pharmacokinetic profiles of two single high-dose primaquine in Papua New Guinean children were determined to assess the feasibility of short course, highdose primaquine treatment regimens for radical cure of P. vivax malaria. These studies form the basis of this thesis. In the first study, G6PD normal children aged 1-5 years old were screened and randomized into three groups: control group with no pre-treatment drugs; primaquine plus artesunate group; and those with artesunate only, as pretreatment. The treatment doses were administered by direct observed therapy with food. Children were followed actively every two weeks for the initial three months, then monthly up to nine months for asymptomatic malarial infection and clinical case detection. Passive case detection was done by nurses based at the local clinics throughout the study duration. The result from this cohort study show, pre-treatment with artesunate plus primaquine (14d, 0.5mg) reduced incidence of P. vivax malaria by 49% for the initial 3 months (p = 0.031) and 19% for months 4- 9 (p = 0.25); and reduced time to first light microscopy and PCR-positive infections by 57% and 48%, respectively (p < 0.001), when compared to the artesunate only group. The effect of pretreatment in the primaquine group was limited to the first 3 months of follow-up and 30% of children had re-infection by 2 weeks of follow-up. In the second study, a randomized, double-blind, placebo controlled trial of primaquine effect was performed in G6PD normal children aged 5 to 10 years old. All study children received chloroquine at days 1-3 and artemether lumefantrine at days 15-17 of the pre-treatment phase. The children were randomized to receive either primaquine or placebo, to be administered with chloroquine. All pre-treatment doses were administered by direct observed therapy with food using the same follow up schedule as study one. The results from this study show, pre-treatment with primaquine reduced the risk of acquiring a new blood stage infection by 78%, (p <0.0001), and clinical disease by 68%, (p <0.0035). Age was associated with a reduced risk of P. vivax clinical episodes of any density (p <0.0167) and high density (p <0.016). Most reinfections occurred within 12 weeks of pre-treatment. The third study, monitoring of safety and tolerability of primaquine treatment in the study children was performed during the pre-treatment phase of follow up in the two cohort studies. A semi-structured questionnaire of all possible drug adverse events was performed prior to primaquine dose ingestion. All primaquine doses were administered with food, however in the younger age group, children were fed by the mothers. The results from this field-based study show, 14 daily doses of 0.5mg/kg primaquine to be safe and well tolerated in children in both cohort studies. There were no serious adverse events and/or withdrawals of children associated with primaquine ingestion in the two cohorts studies. In children with reported nausea or vomiting due to primaquine ingestion, recovery was almost immediate upon food intake. Following on from the cohort studies, pharmacokinetic properties of two single-dose primaquine in Papua New Guinean children aged 5-10 years old was performed; to assess the feasibility of short course, high-dose primaquine treatment regimens for radical cure of P. vivax malaria. The profiles of single doses of primaquine 0.5mg/kg and 1.0mg/kg were assessed in the children. At recruitment, study children were admitted to the Health Centre for 2 days for close monitoring, and, to allow for frequent blood sampling. During all this time participants had indwelling intravenous cannula in place for blood sampling. The primaquine doses were co-administered with food. The safety and tolerability monitoring showed both primaquine doses were well tolerated, with no severe adverse events. There were no observed changes in symptoms and severity of nausea or abdominal pains in the two primaquine dosage groups. There was no betweengroup difference in haemoglobin concentration and methemoglobin levels. The simulated short course high dose regimens showed predicted plasma primaquine and carboxyprimaquine concentrations achieved were not significantly greater than those seen in previous pharmacokinetic studies of adults. This suggests both 0.5mg/kg and 1.0mg/kg primaquine dose regimens could be further assessed in safety and efficacy field studies. Several primaquine studies in the past observed the efficacy of primaquine enhanced by a partner drug with a long terminal elimination phase. Primaquine is more effective when coadministered with chloroquine due to its longer post-treatment prophylactic effect as shown in the second cohort study. Studies have also shown that the therapeutic dose of primaquine is based on the total dose effect, and not the dosing intervals. Indeed, a higher daily dose for 7 days was as effective as the 14 day regimen with minimal adverse events when coadministered with food. The current 14 day, daily dosing of primaquine is most effective when given in research conditions with direct observation of drug treatment; whereas in real life situations, due to poor compliance, primaquine treatment has a reduced effect. A shorter course of high dose primaquine treatment compatible with the 3 day dosing regimens of artemisinin combination therapies would be ideal; to improve compliance during routine treatment and easier to administer as mass drug administration for malaria elimination. Thus, the last manuscript of this thesis reviews the potential use of primaquine as a tool for control and eventually elimination of malaria in the PNG context. The results from these longitudinal cohorts and the primaquine dose studies will contribute to the scientific knowledge on P. vivax epidemiology and the safety of primaquine use in children and an attempt to improve compliance. This will be a useful tool for malaria control and elimination to tackle the hypnozoites in the liver of the human host. The mass drug administration strategy would have an effective arsenal to potentially, not only eliminate hypnozoites of P. vivax from the liver, but stage five gametocytes of P. falciparum as well, to stop malaria transmission.

Giardiasis, cause by the parasitic protozoan Giardia duodenalis, is one of the most common infectious gastrointestinal diseases in humans worldwide. However, its true population burden and epidemiology and in particular its zoonotic transmission potential are still poorly understood. Furthermore, G. duodenalis is not a uniform parasite but a complex of seven genetic assemblages or cryptic species (named A to G) that infect humans and a variety of domesticated and wild animals, and that can only be distinguished using molecular genotyping methods. Although there is some evidence that the two Giardia assemblages infecting humans (namely A and B) may differ in their virulence and major transmission routes, data are still scarce. In the UK, several studies suggested that giardiasis is considerably under-diagnosed and a few data are available on the genetic diversity of the parasite causing infection and disease in this country. We investigated the burden, clinical outcomes, risk factors and molecular diversity of giardiasis in North West England using both a descriptive and analytical approach. In Chapter 2, we analysed the self-reported clinical and exposure data collected over four years from clinical cases of giardiasis in Central Lancashire, as part of an enhanced surveillance program on the illness. The resulting average disease rate of 22.5 cases/100,000 population was high when compared to the available national figures. Giardiasis was particularly abundant in adults in their 30s and children under five, and the disease rate in males was significantly higher than in females. Furthermore, the clinical picture of the cases confirmed the high morbidity associated with this infection particularly in terms of the length of illness and severity of symptoms. Only 32% of the cases reported foreign travel during the exposure window. The results suggested the presence of a hidden burden of disease in adults and males, and indicated that local transmission of Giardia can be more common than expected. In Chapter 3, we performed a case-control study to determine the significant risk factors for symptomatic giardiasis in North West England, by recruiting clinical cases of Giardia and age and sex matched controls from Central and East Lancashire and Greater Manchester. The multivariable logistic regression analysis done on 118 cases and 226 controls revealed that overall travelling abroad (particularly to developing countries) was an important risk factor for the illness (OR 9.59). Following the exclusion of participants that reported foreign travel, four risk factors were significant for the acquisition of giardiasis: going to a swimming pool (OR 2.67), changing nappies (OR 3.38), suffering irritable bowel syndrome (OR 3.66) and drinking un-boiled water from the tap (OR 8.17). The results indicated the important role of swimming pools and contact with children in nappies for the transmission of the parasite. In Chapter 4, whole faecal DNA was extracted from the faecal samples of the cases part of the surveillance and case-control studies and the Giardia assemblages and sub-assemblages causing infection were determined using PCR amplification and DNA sequencing of up to four parasite genes (beta-giardin, glutamate dehydrogenase, triose-phosphate isomerase and small-subunit ribosomal RNA). The majority of infections (64%) were caused by assemblage B, followed by assemblage A (33%), whereas mixed-assemblage infections were rare (3%). The majority of the assemblage A isolates belonged to the sub-assemblage AII and showed completed identity with previously described isolates, and six multi-locus genotypes were identified. The level of genetic sub-structuring as revealed by phylogenetic analysis was significantly higher in assemblage B isolates compared with A isolates: a higher proportion of novel assemblage B sequences was detected compared to what was observed in assemblage A isolates. A high number of assemblage B sequences showed heterogeneous nucleotide positions that prevented the unambiguous assignment to a specific sub-assemblage. Up to 17 different assemblage B multi-locus genotypes were found. The molecular genotyping results showed that Giardia assemblage B was responsible for the majority of the clinical infections and confirmed the occurrence of a high diversity of parasite multi-locus genotypes. In Chapter 5, we integrated the epidemiological and the molecular data generated by the enhanced surveillance and case-control studies and we studied the clinico-epidemiological differences between cases infected with Giardia assemblage A or B. Our results showed a difference in the age prevalence between the two assemblages, with assemblage A being more common in older cases. Cases infected with assemblage B reported a series of symptoms more frequently than cases infected with assemblage A, as well as reporting a longer illness. Although the exposure profile of the cases largely overlapped between the two assemblages, two different types of exposures were reported more frequently in the two groups of cases: keeping a dog in assemblage A cases and the presence in the household of children and children at nursery in assemblage B cases. The results suggested that assemblage A could have a major zoonotic reservoir, whereas assemblage B could be transmitted more commonly via the human-to-human route.

Aquesta tesi proporciona dades sobre la prevalença de la resistència antibiòtica en Mycoplasma genitalium i suggereix la implementació de noves estratègies terapèutiques per fer front a les infeccions causades per aquest patogen de transmissió sexual. A través d’una anàlisi exhaustiva de la infecció en el nostre entorn, aquest estudi ofereix reflexions globals al voltant de la infecció per M. genitalium i els seus mecanismes de resistència antimicrobiana. El capítol 1 actualitza i resumeix l’evidència clínica i epidemiològica en relació a la infecció , destacant alhora alguns aspectes bàsics de la fisiologia i la patogènesi del bacteri. El capítol 2 “Antibiotic resistance: where are we now?” proporciona estimacions sobre la resistència a macròlids i fluoroquinolones en M. genitalium a Barcelona, Espanya, a través d’un estudi de cohorts realitzat entre l’any 2016 i el 2017. A més, el capítol revisa i descriu l’evolució regional i europea de la resistència antibiòtica en M. genitalium durant l’última dècada. D’altra banda, el capítol 3 “Mycoplasma genitalium: should we screen and how?” i el capítol 4 “Transmission dynamics in Mycoplasma genitalium” se centren en les infeccions asimptomàtiques, aprofundint en la prevalença de M. genitalium, així com en les resistències antibiòtiques en la població asimptomàtica, tot revelant la dinàmica de transmissió de la infecció. Finalment, el capítol 5 resumeix les principals conclusions de la tesi, culminant amb la proposta d’un nou algoritme terapèutic basat en els resultats i evidències obtinguts al llarg d’aquest treball.
Esta tesis proporciona las primeras estimaciones en relación a la resistencia antibiótica en Mycoplasma genitalium y sugiere la implementación de nuevas estrategias terapéuticas para hacer frente a las infecciones causadas por este patógeno de transmisión sexual. A través de un análisis exhaustivo de la infección en nuestro entorno, este estudio ofrece reflexiones globales en torno a la infección por M. genitalium y sus mecanismos de resistencia antimicrobiana. El capítulo 1 actualiza y resume la evidencia clínica y epidemiológica en relación a la infección, destacando también algunos aspectos básicos de la fisiología y patogénesis de la bacteria. El capítulo 2 “Antibiotic resistance: where are we now?” proporciona estimaciones sobre la resistencia a macrolidos y fluoroquinolonas en M. genitalium en Barcelona, España, a través de un estudio de cohortes realizado entre 2016 y 2017. Además, el capítulo revisa y describe la evolución regional y Europea de la resistencia antibiótica en M. genitalium durante la última década. Por otro lado, el capítulo 3 “Mycoplasma genitalium: should we screen and how?” y el capítulo 4 “Transmission dynamics in Mycoplasma genitalium” se centran en las infecciones asintomáticas, profundizando en la prevalencia de M. genitalium y las resistencias antibióticas en población asintomática, y revelando la dinámica de transmisión de la infección. Finalmente, el capítulo 5 resume las principales conclusiones de la tesis, culminando con la propuesta de un novedoso algoritmo terapéutico basado en los resultados y evidencias obtenidos a lo largo de este trabajo.
This thesis provides the first antibiotic resistance estimates in Mycoplasma genitalium in Spain and suggests the implementation of novel treatment strategies against infections caused by this sexually transmitted pathogen. This study offers, through a comprehensive analysis of the infection in our settings, global insights regarding M. genitalium infection and its antimicrobial resistance mechanisms. Chapter 1 updates and summarizes the clinical and epidemiological evidence regarding the infection, highlighting also some basic aspects of the physiology and pathogenesis of the bacterium. Chapter 2 "Antibiotic resistance: where are we now?" provides estimates regarding macrolide and fluoroquinolone resistance in M. genitalium in Barcelona, Spain, through a cohort study performed between 2016 and 2017. Additionally, the chapter reviews and describes the regional and European evolution of antibiotic resistance in M. genitalium in the last decade. On the other hand, chapter 3 "Mycoplasma genitalium: should we screen and how?" and chapter 4 "Transmission dynamics in Mycoplasma genitalium" are focused on asymptomatic infections, addressing the prevalence of M. genitalium and antimicrobial resistance among asymptomatic individuals, and revealing the transmission dynamics of the infection. Finally, chapter 5 summarizes the main conclusions of this thesis work, culminating with the proposal of a novel treatment algorithm based on the results and the evidence obtained along this manuscript.
Universitat Autònoma de Barcelona. Programa de Doctorat en Microbiologia

El gènere Legionella va ser descobert el 1976 a arran d’un brot de pneumònia per Legionella pneumophila a Philadelphia (Estats Units) que va causar més d’una vintena de morts. Des d’aleshores, s’han publicat nombrosos estudis per conèixer més d’aquest peculiar bacteri. El gènere Legionella és un gènere present a la natura i amb un reservori principalment relacionat amb el medi aquàtic. S’estima que les seves concentracions a la natura són baixes però poden augmentar en sistemes d’aigua artificials. A l’inici de la dècada dels 1980, Rowbotham va veure que el gènere era capaç de multiplicar-se intracel·lularment a l’interior de protozous. A més, els protozous podien fer de reservori i ajudar a la disseminació de la malaltia. I així, va proposar una nova idea al camp de la microbiologia: bacteris com el gènere Legionella podien parasitar organismes unicel·lulars com les amebes i utilitzar els mateixos processos i estratègies per infectar els macròfags humans. El mecanisme de transmissió inclou la inhalació d’aerosols que continguin el bacteri i que un cop arriben als alvèols pulmonars, poden causar legionel·losi, sobretot en determinats grups de risc en la població. Amb l’era de la genòmica, aquest concepte s’ha estudiat en profunditat i s’ha vist que no només utilitzen els mateixos processos per infectar humans, sinó que manipulen les funcions de l’hoste amb proteïnes “impostores” per poder replicar-se i créixer en detriment de l’hoste. Així, utilitzen proteïnes amb motius eucariotes molt similars a les de l’hoste per dur a terme les seves funcions. Però la vida del gènere Legionella encara pot ser molt més complicada. A part de ser un bacteri intracel·lular, pot formar part de complexos biofilms o passar a un estat més resistent al qual anomenem VBNC. Així doncs, el gènere té múltiples estratègies per protegir-se i per sobreviure a la natura i, conseqüentment, es poden colonitzar els sistemes d’aigua artificials. Per evitar la disseminació i les elevades concentracions de legionel·la en aquests sistemes, s’han descrit una sèrie de mesures preventives de control d’instal·lacions i de desinfecció en continu de l’aigua. La concentració baixa d’aquests bacteris a l’aigua és la principal mesura preventiva per evitar possibles brots i disseminació de la legionel·losi. Malgrat aquestes mesures, les colonitzacions persistents en edificis d’alt risc encara són un problema de Salut Pública degut a la complexa biologia del microorganisme. L’estudi en profunditat d’aquests bacteris intracel·lulars d’aquesta tesi és clau per entendre la seva complexa ecologia i per aplicar estratègies efectives per una bona prevenció.
Legionella genus was discovered after a pneumonia outbreak in Philadelphia (United States) in 1976 that caused up to twenty deaths. Since then, many research studies have been conducted to clarify different aspects of these peculiar bacteria. Legionella spp. are present naturally in different environmental ecosystems with special mention to aquatic environments. Their concentration in those habitats are estimated to be low but this may change when they are in more comfortable environmental conditions such as in man-made water systems. In the early 1980s, Rowbotham discovered that Legionella spp is capable of multiplying intracellularly inside protozoa. Moreover, they act as an environmental reservoir and can help to disseminate these bacteria. This discovery led him to a new perspective in Microbiology: Legionella genus can parasite unicellular eukaryotes like FLA and use the same processes and strategies to infect human macrophages. Aerosols containing these bacteria are responsible for the transmission of the disease and they cause LD when they arrive to the lung alveoli, especially in immunocompromised people. These concepts have been studied since then and they have been amplified using genomic techniques. Legionella spp not only they use the same processes for infecting humans but also, they can hijack important host functions and cell pathways using their “eukaryotic-like” proteins or proteins with eukaryotic domains. Those proteins mimicry the ones present in host cell pathways to manipulate host functions to the pathogen’s advantage. However, Legionella life cycle can be even more complicated. Apart from being intracellular bacteria, they can be part of complex biofilms or change into a more resistant form known as VBNC. These bacteria have several and different strategies to protect them and to survive in nature and, consequently, in colonized artificial water systems. To avoid high concentrations of Legionella in water systems and to avoid LD dissemination, many prevention strategies and disinfection methods have been described and regulated by law. Maintenance of low concentrations of Legionella in water is the key to prevent outbreaks and LD cases. Despite all these measures, there are buildings permanently colonized by Legionella spp which are still a concern for Public Health authorities. The need for studying these bacteria is what is done in this thesis and it is important to have a broader picture and to understand their complex ecology and, ultimately, to apply effective prevention strategies.

The objective of this work is to provide a better understanding of helicopter accidents (rates, trends, and covariates) and to identify areas that deserve careful attention for accident prevention. Several questions were here investigated, including: (1) whether there are differences in accident rates for helicopters with different number of main rotor blades? (2) whether different engine types are associated with different accident rates, controlling for number of blades? And (3) whether there are seasonality effects in helicopter accident rates? To this effect, Record Linkage of two Federal data sources, the FAA civil helicopter registration data and the NTSB accident data, enabled the investigation of these and other questions. First, the accident rates and trend analysis highlighted the safety challenges that continue to face helicopters (significantly worse track record than commercial airlines, passenger cars, and motorcycles). Second, it was found that helicopter accident rates vary by number of rotor blades. Third, one result upended traditional wisdom, which posited that reciprocating engines are associated with higher accident rates; in its stead, it was shown that helicopter accident rates vary with engine type and number of blades, and that turboshaft are associated with significantly higher accident rates than reciprocating engines for the 4-, 5-, and 6-bladed helicopters. Furthermore, it was shown that helicopter accident rates display seasonality effect. Statistical significance and possible confounders for these results were discussed. The issues here examined deserve careful attention from the helicopter community, and several topics were identified as important areas for future work. Any serious effort to improve helicopter safety will entail action on multiple safety levers, including design, operational, and policy/inspection-related ones. All of these actions should be evidence-based, and they will require better helicopter accident investigations and better flight data.

Рассмотрены три этапа развития эпидемического процесса, где первый представлен фазами: профилактической, лечебно-диагностической и местно-резервной. Второй этап представлен дополнительной внешне-резервной фазой, а третий этап - фазой административного резерва. Такая связь отражает характеристики общего патологического процесса массовой заболеваемости неинфекционного генеза и ориентирует на мероприятия его ликвидации. Three stages of development of epidemic process where the first is presented by phases are considered: preventive, medical-diagnostic and local-reserve. The second stage is presented additional externally - a reserve phase, and the third stage - a phase of an administrative reserve. Such communication reflects characteristics of the general pathological process of mass incidence of noninfectious genesis and focuses on actions of its elimination.

Электронный образовательный ресурс составлен в соответствии с требованиями Федерального государственного образовательного стандарта высшего образования специальность 32.05.01 Медико-профилактическое дело, утвержденным приказом Министерства образования и науки Российской Федерации от 16 января 2017 г. №21, и с учетом требований профессионального стандарта 02.002 «Специалист в области медико-профилактического дела», утвержденного приказом Министерства труда и социальной защиты Российской Федерации от 25 июня 2015 г. №399н. Цель изучения курса – Дать обучающимся знания основ по военной эпидемиологии, выработать умения, необходимые для освоения выпускниками компетенций в соответствии с Федеральным государственным образовательным стандартом высшего образования, по специальности 32.05.01 – медико-профилактическое дело, способных и готовых к выполнению трудовых функций, требуемым профессиональным стандартом «Специалист в области медико-профилактического дела». Задачи изучения дисциплины: 1. формирование у выпускников знаний по теоретическим вопросам военной эпидемиологии; 2. подготовка специалиста, обладающего профессиональными компетенциями к самостоятельному проведению профилактической, организационно-управленческой деятельности в области военной эпидемиологии; 3. формирование у выпускника навыков самостоятельной работы с современными информационными технологиями обучения, работы с интернет - источниками; 4. подготовка специалиста, владеющего умениями использования нормативных документов для формулирования экспертных заключений по вопросам профилактики инфекционных заболеваний; 5. формирование у выпускника умения применять на практике знания доказательной медицины в военной эпидемиологии; 6. привлечение выпускников к научным исследованиям, направленным на решение фундаментальных и прикладных задач по вопросам эпидемиологии инфекционной и паразитарной патологии.