<p>Anthropogenic effects on ecosystems have expanded in their scope and intensity, with significant consequences for global environmental, wildlife and human health. As human encroachment into wildlife habitat grows, habitat degradation and fragmentation intensify, leading to increased contact among wildlife, humans and domestic animals. Due to this increasing frequency of interaction, and the emergence of several high-profile diseases, global concern has grown over the risk of emerging infectious disease from zoonotic origins. </p><p>Due to Madagascar's rampant rate of human population growth and deforestation, its incredible species diversity, the widespread presence of domestic and invasive species, and its evolutionary isolation, it can be viewed as a high risk region for potential disease emergence. There is a need for assessment of the zoonotic and reverse zoonotic disease potential within this country. </p><p>To contribute to this assessment, consistent baseline health monitoring provides an effective tool for evaluating wildlife health and preparing for future disease occurrences. Limited, disconnected surveys of lemur health have occurred, yet there remained a need for more extensive, country-wide evaluations that also addresses invasive species, domestic animal and human health, as well shifting patterns of environmental and climatic change. </p><p>This research has investigated the connections among human, animal (both domestic and wildlife) and ecosystem health in Madagascar. I have examined current trends in anthropogenically-driven environmental change in Madagascar--including deforestation, illegal logging of precious hardwoods, mining, hunting, and agriculture--and evaluated how this change affects patterns of lemur, domestic animal and human health by evaluating a suite of health measures and parasite prevalence and richness. I have also examined how predicted global climate changes may influence the spatial patterns of lemur parasites and human infectious disease by assessing their shifts in distributions and geographic extent. </p><p>To assess the risk of disease transmission among lemur, domestic animal and human hosts, I have modeled the areas of geographic overlap among these parasites and their hosts and identified high-risk areas for disease emergence using geospatial analysis. This information can help to develop predictive statistical and spatial tools, which can inform both environmental management and public health planning. </p><p>Through this work, I have evaluated the severe loss of distribution that rosewood species have undergone, which highly qualifies them for international trade protection. We predicted areas of high risk for future logging, many of which occurred within protected areas in the biodiverse northeast. </p><p>Secondly, I have compiled the most comprehensive record of parasites of lemurs to date. Building upon the Prosimian Biomedical Survey Project data and the published literature, we have recorded 88 parasites that have been documented in lemurs. These are composed of helminths, bacteria, ectoparasites and protozoa. Of the 23 focal parasite species studied more in depth in this study, we noted high variability in prevalence measures for unique parasites at different sites. Parasite coinfection occurred quite commonly, with up to as many as 7 parasites concurrently. On average, lemur parasites tend to be less species-, genus-, or family-specific than other parasites across all primates. </p><p>Thirdly, I documented highly significant differences in health measures from two populations of Indri that exist under differing levels of anthropogenic pressure. Of note, the parasite richness, leukocyte count and differential, and nickel and cobalt levels were significantly higher in the more exposed population, while the total protein measures were significantly lower. These data suggest that the exposed population experiencing more anthropogenic pressure suffered from elevated health and nutritional stress. </p><p>Fourthly, I have documented strong correlations among environmental drivers (temperature, precipitation and landscape-scale features) and lemur parasite distributions. Striking shifts in their distributions are predicted to occur with projected climate change in Madagascar, including an expansion of helminth, virus and ectoparasite distributions, but a contraction of bacteria distributions due to warming and drying in the south. </p><p>Fifthly, I have examined 10 human and domestic animal parasites that hold great consequence for lemur, human and domestic animal health in Madagascar. I have similarly demonstrated strong correlations among environmental drivers (temperature, precipitation and landscape-scale features) and the distributions of these human parasites. Shifts in the distributions are also predicted to occur with projected climate change, including an expansion of helminth parasites, and a contraction of viruses and bacteria due to warming and drying in the south. I have identified areas of high risk for the transmission of parasites from human hosts to lemurs, as well as conversely from lemur hosts to humans. These risk indices will serve to highlight geographic areas at particular risk, and will also help to direct limited funds and staff to those areas most in need of attention. </p><p>Sixthly, I have demonstrated a need to train a growing cadre of One Health professionals from many different disciplines. I have offered several suggestions to integrate One Health training into graduate education, and have identified several geographic regions of potential to be a Center of One Health Excellence, of which the North Carolina Triangle area is one of great promise.</p> / Dissertation

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are lethal and infectious neurodegenerative diseases of humans and animals. The misfolding of the normal, or cellular isoform of the prion protein (PrPC) into the abnormal disease-associated isoform of PrP (PrPSc) could change the properties of PrP, consequently, PrPSc has lethal infectivity to transmit diseases. The proteinaceous infectious particle consisting mainly of PrPSc is called prion. Transmissibility of prions is strongly influenced by multiple factors including PrP polymorphisms, species barriers (PrP sequence specificity) and prion strains (conformational specificity) by unknown mechanisms. Even though the ability of prions to cross a species barrier has been recognized, the precise mechanisms of interspecies prion transmission remain unclear. This dissertation research was conducted in order to learn more about the molecular mechanisms of conversion, propagation and transmission of PrPSc; about determinants of genetic susceptibility to infection in prion diseases; and about understanding those mechanisms, which might govern the zoonotic potential of prion diseases. First, we investigated the transmissibility risk of multiple strains of Chronic Wasting Disease, which is a cervid TSE, with humanized transgenic mice and showed that the transmission barriers between cervid and the humanized mice are high. Next, the structural factors underlying the species barrier of prion diseases were studied using cell culture systems by systematically introducing amino acid substitutions in the regions of PrP, where the most divergences of different PrP species are recognized. Thirdly, we investigated the effects of the genetic susceptibility to prions as well as conversion kinetics and properties of PrPSc using Tg mice expressing ovine PrP polymorphism (OvPrP) at codon 136 either alanine (A) or valine (V). The templating characteristics of OvPrPSc-V136 were dominant over OvPrPSc-A136 under co-expressions of OvPrPC-A136 and OvPrPC-V136. Finally, the function of PrP was studied in relation to the pathogenesis of Alzheimer’s disease. These studies demonstrated that the conformational compatibility between PrPC and PrPSc contributed to the conversion kinetics and species barrier. We concluded that the conformational compatibility of PrPC to PrPSc is controlled not only by the PrP sequence specificity but also by the tertiary structure of PrPC.

Master of Public Health / Department of Diagnostic Medicine/Pathobiology / Douglas Powell / Outbreaks of human illness have been linked to visiting settings with animal contact throughout developed countries. These outbreaks demonstrate that although contact with animals in public settings can provide educational and entertainment opportunities, the potential to spread disease exists if risk-reduction tools are not implemented, proper hygiene measures aren’t practiced, and precautions are not taken and reinforced. This thesis is divided into two parts. Part one is an observational study of hand hygiene tool availability and recommendations; frequency of risky behavior; and, handwashing attempts by visitors in Kansas and Missouri, U.S., petting zoos. Part two delineates best practices for organizing events where human-animal interactions are encouraged, in hopes it will lower the risk of zoonotic disease transmission. Handwashing signs and hand hygiene stations were available at the exit of animal-contact areas in 10/13 and 8/13 petting zoos respectively. Risky behaviors were observed being performed at all petting zoos by at least one visitor. Frequently observed behaviors were: children (10/13 petting zoos) and adults (9/13 petting zoos) touching hands to face within animal-contact areas; animals licking children’s and adults’ hands (7/13 and 4/13 petting zoos, respectively); and children and adults drinking within animal-contact areas (5/13 petting zoos each). Of 574 visitors observed for hand hygiene when exiting animal-contact areas, 37% (n=214) of individuals attempted some type of hand hygiene, with male adults, female adults, and children attempting at similar rates (32%, 40%, and 37% respectively). Visitors performed hand hygiene more often when a staff member was present within or at the exit to the animal-contact area (136/231, 59%) than when no staff member was present (78/343, 23%; P < 0.001, OR = 4.863, 95% CI = 3.380–6.998), and in petting zoos where animal contact occurred over a fence (188/460, 40.9%) as opposed to visitors entering an animals’ yard for contact (26/114, 22.8%; P < 0.001, OR = 2.339, 95% CI = 1.454–3.763). Inconsistencies existed in tool availability, signage, and supervision of animal- contact. Risk communication was poor, with few petting zoos outlining risks associated with animal-contact, or providing recommendations for precautions to be taken to reduce these risks. Recommendations made in the second part of this thesis were based on these observations, recent publications, and the suggestions of many health agencies. It focuses on what event planners can do to design and plan a safer event, and what staff working at the event should be aware of in order to inform visitors and lower the risk of zoonotic disease transmission. Part two discusses two primary tools to reduce risk of zoonotic disease transmission: sanitation and awareness of risk behaviors. Keeping facilities, animals, and visitors clean, and informing visitors of risky behaviors to avoid, while reinforcing positive messages within the animal- contact area, can lower the risk of zoonotic infection. Included with the second part, is a checklist (see appendix A) designed for visitors to assess whether an event that encourages human-animal interaction poses a high or low risk. By identifying possible risk factors, teachers and parents will be able to make an informed decision about the safety of the human-animal encounter.

Les zoonoses émergentes sont en augmentation au cours des dernières décennies. Ainsi, il y est urgent de comprendre les mécanismes de cette émergence, en particulier d’étudier les facteurs écologiques sous-jacents qui déterminent les transferts de ces maladies de l’animal à l’homme.Originaire d’Asie, le moustique tigre Aedes albopictus est arrivé au Brésil dans les années 80 et s’est établi dans 60% des villes brésiliennes. Les forêts brésiliennes sont considérées comme un point chaud de la biodiversité mondiale, abritant des centaines d'arbovirus zoonotiques. Ces forêts que, par fois, cercles des grandes agglomérations urbaines, souffrent de la transformation du paysage réalisé par l’homme, un terreau idéal pour l'apparition de zoonoses. Cette espèce représente une préoccupation majeure pour la transmission d’arbovirus épidémiques (Dengue, Chikungunya, Zika) mais également une menace potentielle pour l’émergence de maladies zoonotiques en raison de sa présence dans les interfaces ville / forêt, de son comportement alimentaire opportuniste et de sa compétence vectorielle pour nombreux virus. Ainsi, Ae. albopictus pourrait potentiellement jouer le rôle de vecteur pont pour le transfert en milieu urbain de arbovirus zoonotiques qui circulent dans les forêts brésiliennes. Dans cette étude, nous évaluons le potentiel de cette espèce à servir de vecteur de pont entre la faune et l'homme. Pour cette proposition (i) Nous avons effectué une recherche et une analyse bibliographiques portant sur trois éléments clés permettant d’évaluer la capacité de ce moustique à assurer le transfert interspécifique des arbovirus dans les zones sylvatiques : 1) la capacité à exploiter les sites de reproduction larvaire naturels, 2) le comportement alimentaire et 3) la compétence vectorielle pour les dif férentes arbovirus. (ii) Nous avons étudié sur le terrain la colonisation, la dispersion, le comportement trophic et l'impact sur la biodiversité d'Ae. albopictus dans l'interface ville / forêt au Brésil. Ce travail de terrain a été réalisé à partir de dix écosystèmes de fragments de forêts dans trois Biomes au Brésil: 1) Biome Amazonia dans la réserve forestière d'Adolpho Ducke à Manaus; 2) Biome Mata Atlantica dans la réserve forestière de Pedra Branca à Rio de Janeiro, dans les fragments de forêt urbaine à Salvador, Serra, Belo Horizonte et dans les fragments de forêt rurale à Domingos Martins, Simonésia, Casimiro de Abreu, Marica-RJ; Biome Cerrado dans la forêt de Morro dos Macacos à Goiania. Dans cette thèse nous avons confirmé qu’Ae. albopictus a la capacité de coloniser des sites de reproduction naturels avec un comportement alimentaire opportuniste et une claire préférence pour les sources de sang humain, suivi par d'autres mammifères et oiseaux. Nous observons que le processus de colonisation et de dispersion est limité à la bordure de la forêt avec un impact sur la composition des espèces dans ces environnements. Nous avons observé également que ce moustique est capable de transmettre 13 arbovirus dans notre recherche bibliografic, mais aucun arbovirus n’a été détecté chez des moustiques prélevés lors du travail de terrain. Globalement, nos résultats confirment et estiment le rôle potentiel d’Ae. albopictus comme vecteur pont des maladies zoonotiques aux interfaces forêt / ville au Brésil. Ces travaux ouvrent un domaine de recherche dans lequel de nouvelles investigations pourraient évaluer le risque potentiel de propagation des maladies zoonotiques des zones forestières aux zones urbaines, dans le but de limiter les futures émergences virales. / Zoonotic emerging diseases are increasing during the last decades. There is an urgent need to understand the mechanisms of this emergence, in particular to study the underlying ecological factors determining spill-over events, the transfer from animals to humans. Being native from Asia, the tiger mosquito Aedes albopictus arrived to Brazil in the 80’s being nowadays established in 60% of brazilian cities. Brazilian forests are considered a hotspot of wildlife biodiversity, harbouring hundreds of zoonotic arboviruses, suffering human landscape transformation and surrounding large urban cities, an optimal breeding ground for the emergence of zoonotic diseases. This species represents a major concern for the transmission of epidemic arboviruses (dengue, chikungunya, Zika) but also a potential threat for the emergence of zoonotic diseases due to its presence in urban/forest interfaces, its opportunistic feeding behavior and its vector competence to transmit numerous viruses. Thus, Ae. albopictus might potentially participate as a bridge vector for the transfer to urban environments of zoonotic arboviruses that are circulating on Brazilian forests. In this study we evaluate the potential of this species to act as a bridge vector between wildlife and humans. For this propose (i) we performed a bibliographic research and analysis focusing on three key components for assessing the ability of a mosquito to ensure interspecies transfer of arboviruses in sylvatic areas: 1) the capacity to exploit natural larval breeding sites, 2) blood-feeding behaviour and 3) the vector competence for arboviruses. (ii) We investigated from fieldwork the colonization, dispersion, host feeding and potential impact of biodiversity patterns of Ae. albopictus in the urban/forest interface in Brasil. This field work was realized from ten forest-fragments ecosystems in tree Brazilians Biome: Biome Amazonia in Adolpho Ducke forest reserve-Manaus; Biome Mata Atlantica in Pedra Branca forest reserve- Rio de Janeiro, in the urban forest fragment Salvador, Serra, Belo Horizonte and in the rural forest fragment Domingos Martins, Simonésia, Casimiro de Abreu, Marica-RJ; Biome Cerrado in Morro dos Macacos forest – Goiania. This work confirmed that Ae. albopictus has the capacity to colonize natural breeding sites with the opportunistic feeding behavior with a preference for human blood sources, followed by other mammals and birds. We observe that the colonization and dispersion process is limited to the edge forest with an impact in species composition in this environments. We observed that this mosquitos is vector competence for 13 arbovirus from bibliographic recherché, but no arbovirus was detected from fildework collected mosquitos. Globally our results confirm and estimates the potential role of Ae. albopictus to act as a bridge vector of zoonotic diseases at the forest/urban interfaces in Brazil. This work opens a research area in which further investigations may assess the potential spill-over risk of zoonotic disease from forested to urban areas with the aim to mitigate potential future viral emergences.

A Malária autóctone de Mata Atlântica é caracterizada por baixa incidência de casos com pouca ou nenhuma manifestação clínica e baixa parasitemia, tendo como principal agente etiológico o Plasmodium vivax (ou plasmódios muito semelhantes a este). O principal mosquito envolvido na transmissão é o Anopheles (Kerteszia) cruzii, cujas formas imaturas se desenvolvem na água acumulada nas imbricações das folhas de bromélias, vegetal muito abundante neste bioma. As formas adultas de An. cruzii tendem a viver e se alimentar com maior frequência na copa das árvores, comportamento conhecido como acrodendrofilia, no entanto, em diversas situações esta espécie tem sido observada em elevada densidade no estrato inferior da floresta. Evidências sugerem que a malária possa ser transmitida de forma zoonótica nestas áreas, uma vez que primatas das famílias Atelidae e Cebidae são encontrados portando plasmódios muito próximos geneticamente aos que infectam humanos e An. cruzii pode se alimentar do sangue de ambos os hospedeiros. O presente estudo teve como objetivo investigar a influência da composição e configuração da paisagem sobre as variações na abundância e no comportamento acrodendrófilo de An. cruzii e como estas variações atuam sobre a dinâmica de transmissão de malária na Mata Atlântica, considerando um cenário de transmissão zoonótica. Coletas entomológicas mensais foram conduzidas no período de março de 2015 a abril de 2017 em duas unidades de conservação situadas no município de São Paulo, ambas com histórico de malária autóctone. Em cada área foram selecionados pontos de coleta com diferentes graus de interferência antrópica e os mosquitos foram coletados utilizando armadilhas do tipo CDC e Shannon. Métricas de composição e configuração da paisagem foram mensuradas para cada ponto de estudo e modelos estatísticos foram utilizados para avaliar a relação entre estas métricas e variações na abundância e acrodendrofilia de An. cruzii. Foi proposto um modelo matemático de transmissão zoonótica que permitiu observar, por meio de simulações, como a dinâmica de transmissão da malária é influenciada por variações na abundância e acrodendrofilia do vetor. Os resultados obtidos sugerem que a perda de vegetação natural e aumento das áreas de borda levam a uma redução na abundância de An. cruzii mas favorecem uma maior atividade desta espécie próximo ao solo. As análises baseadas no modelo teórico corroboram com observações anteriores, apontando que as variações na acrodendrofilia do vetor podem ter um papel importante na dinâmica de transmissão de plasmódios entre símios e humanos na Mata Atlântica. Em condições nas quais An. cruzii tende a se alimentar quase exclusivamente na copa das árvores ou quase exclusivamente próximo ao solo a transmissão zoonótica parece não se sustentar, ainda que a abundância do vetor seja elevada. De outra forma, condições nas quais An. cruzii se desloque com maior frequência entre os estratos copa e solo tendem a favorecer a transmissão zoonótica, sendo que quanto maior o deslocamento menor é a abundância relativa do vetor necessária para que um símio infectado gere mais do que um caso novo na população de humanos suscetível ou vice-versa. / The autochthonous Malaria of the Atlantic Forest is characterized by a low incidence of cases with little or no clinical manifestation and low charge of parasites in the blood stream, being Plasmodium vivax (or plasmodiums very similar to it) the main etiologic agent. The main mosquito involved in transmission is the Anopheles (Kerteszia) cruzii, whose immature forms develop in the water held in bromeliads, which are very abundant plants in this biome. The adult forms of An. cruzii prefer to live and feed on the treetops, a behavior known as acrodendrophily, however, in several situations this species has been observed in high density near the ground of the forest. Some evidences suggest that malaria can be transmitted zoonotically in these areas, since monkeys of Atelidae and Cebidae families are found carrying plasmodiums very close to those that infect humans and An. cruzii can feed on the blood of both hosts. This study aimed to investigate the influence of the landscape composition and configuration on the variations in the abundance and acrodendrophic behavior of An. cruzii and how these variations affect the dynamics of malaria transmission in the Atlantic Forest, considering a zoonotic transmission scenario. Monthly entomological collections were conducted from March 2015 to April 2017 in two conservation units located in the municipality of São Paulo, Brazil, where human and simian malaria occurs. In each area, collection points with different degrees of anthropic intervention were selected and mosquitoes were collected using CDC and Shannon traps. Metrics of landscape composition and configuration were measured for each study point and generalized linear models were used to evaluate the relationship between these metrics and variations in abundance and acrodendrophily of An. cruzii. It was proposed a mathematical model of zoonotic transmission that allowed to observe, through simulations, how the dynamics of malaria transmission is influenced by variations in the abundance and acrodendrophily of the vector. The results suggest that loss of natural vegetation and increase in edge effect lead to a reduction in the abundance of An. cruzii but favor a higher activity of this species near the ground level. The analyzes based on the theoretical model corroborate previous observations, pointing out that the variations in the acrodendrophily of the vector may play an important role in the dynamics of plasmodium transmission between monkeys and humans in the Atlantic Forest. In situations in which An. cruzii seeks to feed almost exclusively on the treetops or in situations where it feeds almost exclusively near the ground, the zoonotic transmission does not seem to occur, even in situations of high abundance of the vector. Otherwise, conditions in which An. cruzii moves more frequently between canopy and ground level tend to favor zoonotic transmission, and the more vertical movement occurs, the lower is the needed relative abundance of the vector for an infected monkey to generate more than a new case in the susceptible human population or vice versa.

Os parasitas pertencentes ao gênero Leishmania têm distribuição ubíqua. Este táxon inclui Leishmania infantum chagasi, agente etiológico da leishmaniose visceral nas Américas, uma zoonose negligenciada cujas metodologias diagnósticas acumulam uma série de limitações, requerendo a validação e padronização de metodologias diagnósticas satisfatórias. Vários fatores estão relacionados à patogênese causada por este protozoário, entre eles a catepsina L-like, uma cisteíno protease envolvida em processos regulatórios metabólicos e infecciosos. Portanto, este trabalho teve como objetivo avaliar a eficácia do gene de catepsina L-like isoforma CPA como alvo de diagnóstico molecular e como marcador filogenético que permita a compreensão das variações intraespecíficas e elucidem a história evolutiva de L. infantum chagasi no Brasil. Foram utilizados 44 isolados de L. infantum chagasi de diferentes estados brasileiros. Os fragmentos do gene de catepsina L-like foram amplificados, purificados, sequenciados, alinhados manualmente e analisados por métodos filogenéticos de máxima parcimônia e inferência bayesiana. As sequências geradas foram usadas para pesquisar e sintetizar iniciadores a serem usados em reações específicas para o parasita alvo. O gene de catepsina L-like não mostrou variabilidade intraespecífica entre os isolados analisados, sugerindo um evento recente de introdução do mesmo nas Américas. O par de iniciadores propostos amplificou o DNA alvo de isolados de L. infantum chagasi, sendo efetivo na amplificação de DNA em concentrações de até 10-11g / &micro;l. O marcador proposto não apresentou reações cruzadas com outros hemoparasitas de importância clínica. Quando utilizado para o diagnóstico em um painel de amostras clínicas de cães, obteve-se uma frequência de positividade de 49,03% (102/208), contrastando com o valor de 14,42% (30/208) obtido com o marcador para o gene do espaçador ribossomal interno ITS. Quando testado em amostras de flebotomíneos se obteve um valor de 6,25% e em amostras de pacientes humanos o valor foi de 14,28%. Os marcadores também foram eficazes em amplificar DNA extraído de amostras de urina, de sangue fixado em papel filtro e mesmo em amostras de swab de lesões conjuntivas. Este conjunto de parâmetros permite inferir que o CatLeish- PCR é sensível e específico para o diagnóstico de L. infantum chagasi podendo ser aplicado tanto em pesquisas clínicas quanto em inquéritos epidemiológicos de vigilância. / The parasites belonging to the Leishmania genus have a wide distribution. This taxon includes Leishmania infantum chagasi, the etiologic agent of Visceral Leishmaniasis in the Americas, a neglected zoonosis that requires the validation and standardization of satisfactory diagnostic methodologies. Several factors are related to the pathogenesis caused by this protozoan, as Catepsin L-like, a cysteine protease involved in regulatory and infectious processes. Given this information this work aimed to evaluate the effectiveness of Cathepsin L-like isoform CPA as a target for molecular diagnosis and as a phylogenetic marker that allows understanding the intraspecific variations and the evolutionary history of L. infantum chagasi in Brazil. We used 44 isolates of L. infantum chagasi from different Brazilian states. The cathepsin L-like gene fragments were amplified, purified, sequenced, manually aligned and analyzed by maximum parsimony and Bayesian inference methods. The sequences generated were researched to construction of oligonucleotide primers to be used in reactions specific to the target parasite. The Cathepsin L-like gene did not show intraspecific variability among the isolates analyzed, suggesting a recent event of introduction of the same in the Americas. The pair of proposed primers amplified the target DNA of L. infantum chagasi isolates, being effective in DNA amplification at concentrations of up to 10-11g/&micro;l. The proposed marker did not present cross-reactions with other hemoparasites of clinical importance. When used for the diagnosis in a panel of clinical samples of dogs obtained a positive frequency of 49.03% (102/208), against the 14.42% (30/208) to ribosomal ITS marker. Samples of sandflies obtained a value of 6.25% and in humans the value was 14.28%. The markers were also effective in blood samples fixed on filter paper and even in samples from conjunctival lesion swabs. This set of parameters allows to infer that CatLeish-PCR is a sensitive and specific marker for the diagnosis of L. infantum chagasi in clinical and epidemiological surveys.

The global disease scape is constantly shifting, influenced by demographic transitions, altering the balance of the burden of infectious and non‐communicable diseases. The epidemiological transitions can be divided into three stages: the first, an increase in infectious disease burden as populations settled, then grew into towns and cities providing conditions for infectious agents to maintain spread; the second transition follows industrialisation, changes in lifestyle, diet and improved sanitation whereby infectious diseases are reduced and non‐communicable disease (NCD) prevalence increases; the third transition describes the re‐emergence of infectious diseases as the AIDS epidemic and other emerging and re‐emerging disease outbreaks lead to an increasing burden of infectious diseases, particularly in developing countries. Analysis of the disease‐scape has been carried out using WHO Global Burden of Disease data and correlation to demographic factors calculated using World Bank Development Indicators. The balance of chronic NCDs and infectious diseases can be represented numerically as the unit rate of infectious to non‐communicable diseases. The rate, which indicates at which end the continuum lies can then be correlated to these demographic development indicators to assess the factors which are influential to the continuum. As the balance of infectious and non‐communicable diseases around the world alters, the focus of the advocacy at the global health level has been examined to assess if the trends follow that of the shifting continuum. This has been carried out through an assessment of the WHO World Health Assembly (WHA) resolutions adopted annually between 1948 and 2013 on the subject of infectious and/or non-communicable diseases. The principle of International health stemmed from the need to contain the international spread of communicable diseases, so it is not surprising that in the first decade of the WHO, 88% of the resolutions adopted for infectious and non‐communicable disease were adopted for infectious diseases. In the latest ten years of the WHO, 72% of the Assembly resolutions for infectious and non‐communicable diseases were focused on infectious diseases; this indicates that while there has been a shift in the balance, the adopted resolutions still focus heavily on infectious diseases. An example of how advocacy can elevate diseases to a higher position on the global health agenda is that of the Neglected Tropical Diseases. Following the Millennium Development Goals, this group of seventeen diseases has been highlighted as being “neglected” in terms of funding, research and political will. A review of the campaign to highlight this shows how global health advocacy can elevate diseases to a prominent position on the global health agenda. With this in mind, the advocacy for a sub‐group of Neglected Zoonotic Diseases has been examined at the WHA level. The results highlight the sporadic nature of support to control these diseases, and that activism for control of some of the major zoonotic diseases remains lacking. Rabies is explored as an example of a disease for which there are recommendations and support at the global level for the control and elimination of the disease, but for which barriers to control exist locally in endemic countries. The advocacy for diseases at the global health level has the possibility to impact the priorities of health care within individual nations. However the advocacy at this level may take time to reflect the changes within the disease‐scape. The impact of such advocacy is also limited by local political will, availability of resources and local cultural implications. Therefore there is a need to ensure that efforts to control diseases are tailored to specific populations and that resources are made available to support the advocacy.

Scant attention has been given to occupational health hazards of Australian veterinarians. This study aimed to identify the major risk factors for occupational injury and disease, emotional health and suicide rates of veterinarians. Qualitative in-depth interviews with 45 veterinarians were carried out which revealed that a significant proportion of veterinarians were both injured, stressed and had incurred zoonotic diseases. Data linkage of the names of registered veterinarians in Western Australia with four Health Department of Western Australia databases was undertaken to provide supportive statistics on the conditions identified as being important in the interviews. The results of this latter analysis were inconclusive. Therefore a self-administered questionnaire was developed, which collected quantitative data on injuries, disease, stress and risk factors from 419 veterinarians. Since the in-depth interviews had identified stress and suicide ideation as being very significant for many of those interviewed, the Kessler 10+ scale for measuring psychological distress was included in the self-administered questionnaire. The data linkage was unable to provide accurate data about numbers of deaths of veterinarians and the records of coroners in Victoria and Western Australia which provided data on 89 veterinarians, were analysed to determine suicide rates. Despite the interviews providing considerable information about rates and risk factors for injuries, disease and stress, no statistical analyses were undertaken because they provided insufficient data for quantitative analyses. / Nevertheless, statistics derived from the morbidity database using data-linkage, will be useful in comparing injuries in any future studies of this type. Data collected from the self-administered questionnaire were subjected to Chi square, and non-parametric tests and logistic regression analyses using multiple imputation for missing values. Age-standardised and age-specific rates (ASR) were calculated for data on suicide in veterinarians derived from coroners' records obtained from Western Australia and Victoria using the Rates Calculator developed by Codde.' The interviews and the survey of 464 veterinarians showed that a significant proportion of veterinarians incurred injuries and zoonotic diseases, and were highly stressed and distressed. The interviews showed that a significant proportion of veterinarians expected to be injured and/or contract zoonotic diseases. It is suggested that this acceptance may, in part, account for the number of injuries that occur. Some of these injuries, especially in mixed animal veterinarians, may be attributable to poor facilities on farms and a lack of competent support in restraint of animals. There needs to be a cultural change with regard to safety if injury is to be reduced. Using the Chi-squared analyses of the survey data, injury was associated with several risk factors including being a practice owner and being in mixed animal practice, being younger and with having taken drugs such as marijuana in the past 12 months. / When all these variables were input into a logistic regression model, several of these risk factors were eliminated providing only three risk factors as predictors of injury. These were: having a back injury; taking drugs in the previous 12 months; and being between 35 and 54 years of age. Having high distress levels was not a predictor for injury. Analyses of responses to the KlOi- scale in the self-administered questionnaire revealed that the proportion of highly distressed respondents was double that of the Western Australian, New South Wales and Australian general populations which supports the findings from the interviews. Logistic regression provided three predictors for distress: being less than 35 years of age, having taken drugs in the past 12 months, and having a back injury, however having other workplace injuries was not a predictor. The findings that the suicide rate in this study was about four times that of the general Australian adult population, should be of major concern and signal that there may be factors specific to the veterinary profession that account for this high rate. This study has shown that there are high levels of psychological distress in veterinarians, especially practitioners, which suggests that veterinary practice may, in itself, be a stressful occupation. However, it may also be that some individuals with a predilection for distress, are being recruited into the veterinary profession. / Better selection techniques for recruiting veterinary students using an aptitude test as well as interviews, could identify those who were unsuited for becoming veterinarians or who required additional mentoring and support upon graduation. This could reduce stress, distress and suicide in the veterinary profession. Overall, 17 recommendations were made directed at improving the quality of data collection to obtain more reliable statistical outcomes, and suggesting ways of reducing injury, distress and zoonotic disease in veterinarians.

Giardia intestinalis is the most common parasite found in dogs and cats. It is traditionally diagnosed using a microscope. These methods include direct immunofluorescence, DIF, and zinc sulphate centrifugal flotation, ZnSO4 C-flotation. However, there are commercially available SNAP tests such as the FASTest® GIARDIA strip that is often used by dogs and cats owner to detect Giardia. The aim of this study was to compare the sensitivity, cost and labor intensity of these three methods for detection of Giardia. To investigate this, 150 samples from dogs and cats were examined at the National Veterinary Institute in Sweden. The samples were a mixture of diarrheic and non-diarrheic stool. Of the 150 stool samples 100 samples were examined with FASTest® GIARDIA strip while 150 samples were examined with DIF and ZnSO4 C-flotation. The results indicated that FASTest® GIARDIA strip had a sensitivity of 66.18 %, a cost of 100 Swedish crowns (SEK) per sample and was the easiest test to use. ZnSO4 C-flotation had a sensitivity of 89.90 %, cost 418.75 SEK and took about 15 minutes to perform. DIF had 100 % sensitivity and specificity and due to that it was used as a standard reference method. The cost for DIF was 300 SEK and took more than an hour to perform per sample. The conclusion from this study is that, FASTest® GIARDIA strip is not a recommended test for detection of Giardia despite their low cost and easiness to use. DIF and ZnSO4 C-flotation remain a better diagnostic option for detection of Giardia.

abstract: Avian influenzas are zoonoses, or pathogens borne by wildlife and livestock that can also infect people. In recent decades, and especially since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in 1996, these diseases have become a significant threat to animal and public health across the world. HPAI H5N1 has caused severe damage to poultry populations, killing, or prompting the culling of, millions of birds in Asia, Africa, and Europe. It has also infected hundreds of people, with a mortality rate of approximately 50%. This dissertation focuses on the ecological and socioeconomic drivers of avian influenza risk, particularly in China, the most populous country to be infected. Among the most significant ecological risk factors are landscapes that serve as “mixing zones” for wild waterfowl and poultry, such as rice paddy, and nearby lakes and wetlands that are important breeding and wintering habitats for wild birds. Poultry outbreaks often involve cross infections between wild and domesticated birds. At the international level, trade in live poultry can spread the disease, especially if the imports are from countries not party to trade agreements with well-developed biosecurity standards. However, these risks can be mitigated in a number of ways. Protected habitats, such as Ramsar wetlands, can segregate wild bird and poultry populations, thereby lowering the chance of interspecies transmission. The industrialization of poultry production, while not without ethical and public health problems, can also be risk-reducing by causing wild-domestic segregation and allowing for the more efficient application of surveillance, vaccination, and other biosecurity measures. Disease surveillance is effective at preventing the spread of avian influenza, including across international borders. Economic modernization in general, as reflected in rising per-capita GDP, appears to mitigate avian influenza risks at both the national and sub-national levels. Poultry vaccination has been effective in many cases, but is an incomplete solution because of the practical difficulties of sustained and widespread implementation. The other popular approach to avian influenza control is culling, which can be highly expensive and raise ethical concerns about large-scale animal slaughter. Therefore, it is more economically efficient, and may even be more ethical, to target the socio-ecological drivers of avian influenza risks, including by implementing the policies discussed here. / Dissertation/Thesis / Doctoral Dissertation Biology 2018