Dissertations / Theses on the topic 'Applied Epidemiology'

This thesis presents the projects and activities I have undertaken throughout 2016-2017 to fulfil the requirements of the Master of Philosophy - Applied Epidemiology (MAE). My placement was shared between OzFoodNet Victoria (within the Victorian Department of Health and Human Services) and the Microbiological Diagnostic Unit Public Health Laboratory (MDU). This shared placement provided me with the unique opportunity to experience the different day-to-day workings of a state health department and a public health reference laboratory, while also experiencing the multitude of ways in which these two organisations work together to protect the health of the Victorian public. In my placement at MDU I completed an evaluation of the Victorian Hospital Pathogens Surveillance Scheme (VHPSS). This scheme has been running since 1988 and collects information on invasive bacterial and fungal infections and their antimicrobial sensitivities in the Victorian population. My evaluation highlighted the value of the VHPSS in collecting information on pathogens not captured by any other surveillance system in Victoria, and made a number of recommendations to improve the function and focus of the scheme, especially in the context of increasing concerns surrounding antimicrobial resistance nationally and globally. In my placement with OzFoodNet Victoria I was involved in the investigation of multiple clusters and outbreaks of enteric disease. In particular, I coordinated the investigation of an outbreak of Salmonella Typhimurium at a Melbourne café which was linked to the consumption of hollandaise sauce. This outbreak highlighted the dangers of improper food handling in preparing and storing partially-cooked egg products, and the limited knowledge many people have about the risks of consuming these foods. Following another Salmonella outbreak, I conducted an epidemiological study on the proportion of outbreak cases who developed symptoms of transient or chronic sequelae following their infection. In particular, this study collected information on symptoms of post-infectious irritable bowel syndrome (PI-IBS) and reactive arthritis (ReA). This study found that in the six months following their Salmonella infection, 18% of study participants experienced new gastrointestinal symptoms consistent with PI-IBS, and 11% of participants experienced new joint symptoms consistent with ReA. Many of these participants were still experiencing these symptoms a year after their Salmonella infection, indicating the development of chronic disease. I also conducted analyses on data from the Victorian Food Frequency Survey. This survey collected information on the consumption of approximately 250 food items in 4008 well Victorian people, so that their food consumption frequencies could be compared to information from Salmonella case interviews (and interviews for cases of other enteric pathogens such as Campylobacter and Shiga-toxin producing Escherichia coli) to assist in generating hypotheses to try and identify sources of infection. I translated this data into an accessible format for use in outbreak investigations, and examined the demographic consumption patterns of various high-risk food items to determine who might be most at risk of infection. These projects, alongside the teaching activities and scientific communications presented in this thesis, fulfil the requirements of the MAE program and will contribute to the public health of Victorians.

Genetic epidemiology is the study of the joint action of genes and environmental factors in determining the phenotypes of diseases. The twin study is a classic and important epidemiological tool, which can help to separate the underlying effects of genes and environment on phenotypes. Twin data have been widely examined using traditional methods to genetic epidemiological research. However, they provide a rich sources information related to many complex phenotypes that has the potential to be further explored and exploited. This thesis focuses on two major genetic epidemiological approaches: familial aggregation analysis and linkage analysis, using twin data from TwinsUK Registry. Structural equation modelling (SEM) is a conventional method used in familial aggregation analysis, and is applied in this research to discover the underlying genetic and environmental influences on two complex phenotypes: coping strategies and osteoarthritis. However, SEM is a confirmatory method and relies on prior biomedical hypotheses. A new exploratory method, named MDS-C, combining multidimensional scaling and clustering method is developed in this thesis. It does not rely on using prior hypothetical models and is applied to uncover underlying genetic determinants of bone mineral density (BMD). The results suggest that the genetic influence on BMD is site-specific. Haseman-Elston (H-E) regression is a conventional linkage analysis approach using the identity by descent (IBD) information between twins to detect quantitative trait loci (QTLs) which regulate the quantitative phenotype. However, it only considers the genetic effect from individual loci. Two new approaches including a pair-wise H-E regression (PWH-E) and a feature screening approach (FSA) are proposed in this research to detect QTLs allowing gene-gene interaction. Simulation studies demonstrate that PWH-E and FSA have greater power to detect QTLs with interactions. Application to real-world BMD data results in identifying a set of potential QTLs, including 7 chromosomal loci consistent with previous genome-wide studies.

A selective blood agar (SBA) and a selective blood enrichment broth (SBEB) containing polymyxin (5,000 iu/l), trimethoprim (10 mg/i), rifampicin (10 mg/l) and cyclohexamide (100 mg/l) have been developed. Results from a comparison with four other media showed that the SBA gave the most isolations and was the most selective. Enrichment culture using SBEB achieved additional isolations. The SBEB was used in a most probable number (MPN) method which detects as few as 10 campylobatters/tOO ml of water. A glass microfibre filtration system was even more sensitive. A blood-free non-selective agar (BFNSA) containing charcoal (0.4%), ferrous sulphate (0.025%) and sodium pyruvate (0.025%) was also developed. These supplements were shown to detoxify rather than enrich the basal medium. A blood-free selective agar (BFSA) was produced by incorporating cephazolin (10 mg/i) and sodium deoxycholate (0.1%). This medium and the SBA gave similar isolation rates from faecal specimens when incubated at 42 0C for 42h but the BFSA was less selective. A blood-free selective enrichment broth (BFSEB) containing sodium metabisulphite (0.05%) gave slightly fewer Campylobacter isolations than the SEES when evaluated with various types of specimens and was also less selective. Maximum isolation rates were achieved by incubating broths at 42 0C and subculturing after 24h and 42h. Growth studies of three Campylobacter strains in four enrichment brothc incubated at 37 0C and 420C produced different growth curves. However, the mean generation time (approx 90 mins) was fairly constant. Studies on the gaseous requirements of campylobacters showed that atmospheres. containing S - 10% 02 and 1 - 10% CO2 facilitate growth. Satisfactory microaerobic conditions were produced by the evacuation-replacement technique and gas generating envelopes but not by candle jars. A biotyping scheme has been developed which differentiates Campylobacter spp. and is useful for epidemiological purposes. Environmental surveys have shown: i) that animal carcasses and equipment in abattoirs were frequently contaminated with campylobacters whilst similar samples from butchers' shops were free from campylobacters; ii) that frozen chickens were the main source of campylobacters in a hospital kitchen and that environmental contamination was uncommon; and iii) river water frequently contains Campylobacter spp., serotypes and biotypes associated with human infection and sewage effluent discharge is an important source of these organisms.

In this thesis, I present work conducted as a Master of Philosophy (Applied Epidemiology) (MAE) Scholar based at the OzFoodNet sentinel site at Hunter New England Population Health. During my placement, I was involved in a number of public health investigations both locally and in the Western Pacific region. The MAE core competency requirements and the epidemiological skills that I developed through my field placement are demonstrated in the following chapters. I was fortunate to be at the coalface of public health in my placement at the Local Health District and was able to be involved in a number of outbreak investigations. I led an investigation of an outbreak of Campylobacter in a rural community in New South Wales. This investigation included a retrospective cohort study with the aim of characterising cases and identifying the source of infection to prevent further illness. Data were collected on food and animal exposures prior to the first onset of illness in the community. We found no statistically significant food exposures, however this was complicated by near universal exposure to some food items. A review of cooking processes identified undercooked chicken as the likely source of infection in this outbreak. I was also involved in local outbreaks of gastroenteritis associated with a primary school and a Salmonella Typhimurium outbreak associated with a restaurant. In addition, I was involved in an investigation of paediatric severe acute respiratory infections requiring admission to intensive care units as a part of a World Health Organization deployment to Fiji in May 2016. I conducted an epidemiological project examining environmental risk factors for human infection with Salmonella serovar Wangata in north east New South Wales. I designed and administered a case-control study in three Local Health Districts. Data on environmental exposures were collected for cases and two separate control groups: cases of Salmonella Typhimurium and community controls from the neighbourhood of cases. This project included a large data analysis component, with separate multivariable logistic regression models developed to analyse environmental exposures in each control group. Whole genome sequencing was used to examine the relatedness between human isolates and environmental specimens collected as a part of this project. During my deployment to Fiji in May 2016, I was involved in the surveillance of infectious diseases following Tropical Cyclone Winston. I co-evaluated the Early Warning Alert and Response System (EWARS in a Box) with fellow MAE Scholar, Meru Sheel. Nine syndromes were reported to the EWARS system from 34 sentinel sites in Fiji. The web based EWARS system utilised smartphone reporting and was considered simple, acceptable and generally useful for users. Recommendations were made to improve the layout and interpretation of surveillance reports and to enhance operating procedures and guidelines for surveillance officers. This was the first time the EWARS in a Box system had been implemented in a Pacific Island Country and the experiences of the system in Fiji can be used to assist other countries in the region who are experiencing humanitarian disasters.

In this thesis, I present the projects and activities I have undertaken as a Master of Philosophy in Applied Epidemiology (MAE) Scholar in Victoria between February 2016 and November 2017. I was placed with the Environmental and Genetic Epidemiology Research Group at the Murdoch Childrens Research Institute (MCRI), and the Communicable Disease Epidemiology and Surveillance Unit at the Victorian Department of Health and Human Services (DHHS). At MCRI I worked on the Barwon Infant Study, a birth cohort study designed to investigate how early life environment can influence the development of immune disorders and neurodevelopmental outcomes. At DHHS, I had the opportunity to lead an outbreak investigation, undertake an evaluation of a public health surveillance system, and an epidemiological study. Through these placements I experienced the day-to-day activities of a research institute and a state public health unit. At MCRI I conducted a data analysis on the prevalence of aero-allergen sensitisation in infancy in the Barwon region in Victoria. Sensitisation to aero-allergens in infancy is considered rare and as a result few studies report the prevalence in infants. My data fills this gap in the literature using data from a population-derived cohort study. I reported the findings of this study at the Training Programs in Epidemiology and Public Health Interventions Network Global Scientific Conference, and the Australasian Epidemiological Association Conference in 2017. My surveillance evaluation involved the first stakeholder consultation of the Influenza Complications Alert Network (FluCAN), which was established in 2009 as part of Australia’s response to the A(H1N1/09) pandemic in order to provide sentinel surveillance of influenza requiring hospitalisation. As part of the evaluation I made a number of recommendations to improve the usefulness and operation of the surveillance system many of which have already been implemented. I presented the outcomes of this evaluation to key stakeholders at the annual National Influenza Surveillance Committee in 2017. I conducted an epidemiological study on Shiga toxin-producing Escherichia coli (STEC) using 15 years of Victorian data. The primary aims of this project were to describe the epidemiology of STEC in Victoria and to investigate the length of exclusion of cases in ‘high-risk’ groups (including food handlers, child and health care workers, and children attending child care) by diagnostic method. The results of this study will inform Victoria’s policy regarding the exclusion of cases in these ‘high-risk’ groups from workplaces and child care. I also conducted an outbreak investigation, including a case-control study in order to identify the source of an outbreak of Salmonella Typhimurium at a Melbourne café. The results of the case-control study indicated that hollandaise sauce was the likely cause of the outbreak and led to public health action. The high proportion of cases hospitalised in this outbreak demonstrates the serious health implications of salmonellosis and the potential consequences of deficient storage and food handling processes for high-risk food products such as hollandaise sauce. In this thesis, I present my experience of the MAE program, and demonstrate my fulfillment of the requirements of the program and the contribution my work has made to public health in Victoria.

The newborn screening for congenital hypothyroidism (CR) started in the West in the sixties. The guidelines for screening were introduced in the majority of western countries some 30 years ago and were adapted in 1997 by the World Health Organization. The United Arab Emirates (UAE) started newborn screening for CH in 1998 and was considered one of the leading countries in the Middle East to apply this programme nationwide. Before newborn screening for CH in the UAE, little was known about the epidemiology of the disease in this part of the world which shares the same epidemiological pattern of the Gulf region and the Middle East This nationwide study investigated the epidemiological pattern of CH in the UAE in terms of assessment of biological and environmental components and their significance in the relatively increased incidence of the disease in this community compared to the worldwide incidence (1:30004000). This study employed radioimmunoassay technique used by the newborn screening programme to measure the capillary Thyroid Stimulating Hormone (TSR) for all newborns at the week of age. In addition, chemical and radiological techniques were employed to screen for positive cases. Firstly, cases detected have been studied in terms of prevalence of the disease in the UAE in relation to other parts of the world and the definition of the epidemiological components and its association to the prevalence of the disease. The study included the investigation of the genotypic pattern of congenital hypothyroidism in the UAE among certain cases with familial dyshormonogesis phenotype. The results show high incidence of the disease compared to the worldwide incidence and also it showed a specific epidemiological pattern. Secondly, the study employed the data obtained in newborn screening for CH in a longitudinal study of TSR pattern of the population and its use to monitor the iodine uptake of this population. This part of study also studied other important implications of the TSR pattern which included the TSR surge and the prevalence of sub clinical cases in which TSH is the main monitor. Thirdly, the study evaluated the controversial issues in the newborn screening programme in the preanalytic and post-analytic phases of the programme. The role of incorporation of the pre and post analytical quality control of the programme in reduction of the morbidity of the disease. Nevertheless, this study provides an overview for the epidemiological pattern of congenital hypothyroidism in the UAE and forms a basic epidemiologic background for further detailed studies that would focus on the clinical aspect and prognostic outcome of the disease. It may be concluded that the clinical picture of congenital hypothyroidism has changed dramatically since newborn screening was instituted in the UAE. Population-based registers and linked-databases can provide very useful information for evaluating screening programmes, and extending current knowledge of the epidemiology of congenital hypothyroidism. This is the first epidemiological study of CH in the UAE in which data from population-based registries were linked, the epidemiologic patterns and associated factors are more representative. The study delineates the significantly increased incidence of congenital hypothyroidism compared to the universal incidence and the clear correlation of this incidence with certain risk factors. Some of these are local which pertain to this area of the world and end in constituting this specific epidemiological pattern.

The main objective of this dissertation is to study numerical methods and applications of structured population models. In Chapter 1, a quasilinear hierarchically size-structured population model is presented. In this model the growth, mortality and reproduction rates are assumed to depend on a function of the population density. The solutions to this model can become singular (measure-valued) in finite time even if all the individual parameters are smooth. Therefore, in this chapter we developed a first order finite difference scheme to compute these measure-valued solutions. Convergence analysis for this method was provided. We also developed a high resolution second order scheme to compute the measure-valued solution of the model and performed a comparative study between the two schemes. In Chapter 2, a model that describes the dynamics of a frog population infected with chytridiomycosis disease is presented. Chytridiomycosis is an emerging disease caused by the fungal pathogen Batrachochydrium dendrobatidis (Bd) that poses a serious threat to frog populations worldwide. Several studies have shown that inoculation of bacterial species Janthinobacterium lividum (Jl) can mitigate the impact of the disease. However, there are many questions regarding this interaction that are unknown. Therefore, a mathematical model of a frog population infected with chytridiomycosis was developed to investigate how the inoculation of Jl could reduce the impact of Bd on frogs. The model also illustrates the important role of temperature in the diseases epidemiology. The model simulation results suggest possible control strategies for Jl to limit the impact of Bd in various scenarios. Finally, in Chapter 3, concluding remarks and discussion on our future work is provided.

Abstract Probabilistic reasoning under uncertainty suits well to analysis of disease dynamics. The stochastic nature of disease progression is modeled by applying the principles of Bayesian learning. Bayesian learning predicts the disease progression, including prevalence and incidence, for a geographic region and demographic composition. Public health resources, prioritized by the order of risk levels of the population, will efficiently minimize the disease spread and curtail the epidemic at the earliest. A Bayesian network representing the outbreak of influenza and pneumonia in a geographic region is ported to a newer region with different demographic composition. Upon analysis for the newer region, the corresponding prevalence of influenza and pneumonia among the different demographic subgroups is inferred for the newer region. Bayesian reasoning coupled with disease timeline is used to reverse engineer an influenza outbreak for a given geographic and demographic setting. The temporal flow of the epidemic among the different sections of the population is analyzed to identify the corresponding risk levels. In comparison to spread vaccination, prioritizing the limited vaccination resources to the higher risk groups results in relatively lower influenza prevalence. HIV incidence in Texas from 1989-2002 is analyzed using demographic based epidemic curves. Dynamic Bayesian networks are integrated with probability distributions of HIV surveillance data coupled with the census population data to estimate the proportion of HIV incidence among the different demographic subgroups. Demographic based risk analysis lends to observation of varied spectrum of HIV risk among the different demographic subgroups. A methodology using hidden Markov models is introduced that enables to investigate the impact of social behavioral interactions in the incidence and prevalence of infectious diseases. The methodology is presented in the context of simulated disease outbreak data for influenza. Probabilistic reasoning analysis enhances the understanding of disease progression in order to identify the critical points of surveillance, control and prevention. Public health resources, prioritized by the order of risk levels of the population, will efficiently minimize the disease spread and curtail the epidemic at the earliest.

This work presents a novel size-structured model to mathematically describe the transmission dynamics of Mycobacterium marinum in an aquatic environment. Biological background on the formation of the model is discussed in Chapter 1. In Chapter 2, the model is developed and consisted of a system on nonlinear partial differential equations coupled to three nonlinear ordinary differential equations. The weak solution is defined and current numerical work on structured models is discussed.

In Chapter 3, a first-order method is developed to approximate the solution to the model, and in Chapter 4, a second-order high resolution method is developed. Theoretical foundations for both methods are established. Also, convergence to the unique weak solution is verified for both methods.

In Chapters 3 and 4, the numerical results begin with showing each method is in fact of the appropriate order for a simple version of the model, and then with the full nonlinear version. Chapter 3 continues the numerical results section with preliminary studies on the key features of this model, such as various forms of growth rates (indicative of possible theories of development), and conditions for competitive exclusion or coexistence as determined by reproductive fitness and genetic spread in the population. In Chapter 4, we compare the first and second-order methods to show the computational benefits that come with a second-order method. We also demonstrate that the model can be a tool to understand surprising or nonintuitive phenomena regarding competitive advantage in the context of biologically realistic growth, birth, and death rates.

Efficient management of epidemics is one of the primary motivations for computational modelling of disease dynamics. Examples range from reactive control measures, where the resources used to manage the epidemic in real time may be limited to prophylactic control measures such as deployment of genetically resistant plant varieties, which may lead to economic trade-offs. In such situations the question is how should resources for disease control be deployed to ensure the efficient management of the epidemic. Mathematical models are a powerful tool to investigate such questions since experiments are usually infeasible and the primary aim of this thesis is to study selected mathematical models of disease control to improve the current understanding of their behaviour. We initially analyse the dynamical behaviour that arises from incorporating an economic constraint into two simple, but widely used epidemic models with reactive control. Despite the selection of simple models, the addition of constrained control leads to mathematically rich dynamics, including the coexistence of multiple stable equilibria and stable limit cycles arising from global bifurcations. We use the analytical understanding obtained from the simple model to explore how to allocate a limited resource optimally between a number of separate populations that are exposed to an epidemic. Initially, we assume that the allocation is done at the beginning and cannot be changed later. We seek to answer the question of how the resource should be allocated efficiently to minimise the long-term number of infections. We show that the optimal allocation strategy can be approximated by a solution to a knapsack-type problem, that is the problem of how to select items of varying values and weights to maximise combined value without going over certain combined weight. The weights and values are given as functions of the population sizes, initial conditions, and the disease parameters. Later, we relax the assumptions to allow for reallocation and use the understanding of the dynamics gained from the simple models in the beginning to devise a new continuous time reallocation strategy, which outperforms previously considered approaches. In the final part of the thesis, we focus on plant disease and study a model of prophylactic control using a genetically resistant variety. We consider a trade-off where the genetic resistance carries with it a fitness penalty and therefore reduces yield. We identify the conditions on the parameters under which the resistant variety should be deployed and investigate how these change when the outbreak is uncertain. We show that deploying the resistant variety reduces the probability of an outbreak occurring and therefore can be optimal even when it would not be optimal to deploy it during the outbreak.

Big data has enabled an entirely new approach to solving and understanding problems. With the popularity of social media, data is created by individuals. We believe that embedded in the big data of social media, like Twitter, is the documentation of self-reporting illness. Through analysis of keywords in tweets geo-tagged to Puerto Rico, we seek to model the outbreak of Chikungunya fever, with initial correlations of around 0.86. Collected tweets were then divided into categories and treated as independent variables for Lasso regression. Although we train on imperfect suspected numbers for the outbreak from the Pan-American Health Organization (PAHO), we analyze the coefficients to understand the social implications behind both social media disease reporting and awareness in Puerto Rico. We see different phases of Twitter volumes pre-, during and post-initial outbreak. News and government tweets decrease during subsequent outbreaks when we see a corresponding relative increase of self-reporting tweets. Especially when applied to epidemiology, big data isn't about finding the perfect answer, but instead, about discovering the underlying story. This thesis is about the story of a Chikungunya outbreak in Puerto Rico from the eyes of Twitter.
Applied Mathematics

Sleep undergoes important changes during adolescence and many teenagers experience problems sleeping. These in turn affect adolescents´ academic, physical and psychosocial functioning. Moreover, there are some indications that sleep problems in this age group may be increasing, possibly as a consequence of societal changes, e.g., internet availability. Research on adolescents´ sleep is growing, but more epidemiological studies are needed to clarify the prevalence of poor sleep, long and short-term outcomes associated with it, and potential risk and protective factors to target in preventive interventions. The aim of this dissertation was to contribute to each of these goals; Study I investigated the longitudinal association between sleep problems, defined as symptoms of insomnia, and school absenteeism; Study II explored the prevalence of poor sleep, defined as sleep deficit, in an adolescent population and psychosocial and contextual factors associated with it, including emotional and behavioral problems, stress, sleep hygiene and technology use; finally, Study III evaluated the short-term effects of a novel universal school-based intervention to improve adolescents´ sleep health. The findings show that poor sleep was strongly related to adolescents´ functioning, including emotional and behavioral problems and school attendance, and that sleep deficit was prevalent in adolescents. This supports the need for prevention. Moreover, sleep deficit was associated with stress, technology use and arousal at bedtime, which may represent important barriers to sleep. A preventive intervention targeting these barriers to promote adolescents´ sleep health was successful with the individuals most at risk. However, it remains to be seen whether these changes will be maintained after the intervention and whether incidence of sleep problems will be lower relative to a control group. Implications for theory and practice are discussed.

Neisseria meningitidis is a gram negative, and sometimes encapsulated, diplococcus that causes devastating disease worldwide. For the worldwide genetic surveillance of N. meningitidis, the gold standard for profiling the bacterium uses genetic loci found around the genome. Unfortunately, the software for analyzing the data for these profiles is difficult to use for a variety of reasons. This thesis shows my suite of tools called the Meningococcus Genome Informatics Platform for the analysis of these profiling data. To better understand N. meningitidis, the CDC Meningitis Laboratory and other world class laboratories have adopted a whole genome approach. To facilitate this approach, I have developed a computational genomics assembly and annotation pipeline called the CG-Pipeline. It assembles a genome, predicts locations of various features, and then annotates those features. Next, I developed a comparative genomics browser and database called NBase. Using CG-Pipeline and NBase, I addressed two open questions in N. meningitidis research. First, there are N. meningitidis isolates that cause disease but many that do not cause disease. What is the genomic basis of disease associated versus asymptomatically carried isolates of N. meningitidis? Second, some isolates' capsule type cannot be easily determined. Since isolates are grouped into one of many serogroups based on this capsule, which aids in epidemiological studies and public health response to N. meningitidis, often an isolate cannot be grouped. Thus the question is what is the genomic basis of nongroupability? This thesis addresses both of these questions on a whole genome level.

Raman spectroscopy has been successfully employed in the classification of breast pathologies involving basis spectra for chemical constituents of breast tissue and resulted in high sensitivity (94%) and specificity (96%) (Haka et al, 2005). Motivated by recent developments in nonparametric regression, in this work, we adapt stacking, boosting, and dynamic ensemble learning into a nonparametric regression framework with application to Raman spectroscopy analysis for breast cancer diagnosis. In Chapter 2, we apply compound estimation (Charnigo and Srinivasan, 2011) in Raman spectra analysis to classify normal, benign, and malignant breast tissue. We explore both the spectra profiles and their derivatives to differentiate different types of breast tissue. In Chapters 3-5 of this dissertation, we develop a novel paradigm for incorporating ensemble learning classification methodology into a nonparametric regression framework. Specifically, in Chapter 3 we set up modified stacking framework and combine different classifiers together to make better predictions in nonparametric regression settings. In Chapter 4 we develop a method by incorporating a modified AdaBoost algorithm in nonparametric regression settings to improve classification accuracy. In Chapter 5 we propose a dynamic ensemble integration based on multiple meta-learning strategies for nonparametric regression based classification. In Chapter 6, we revisit the Raman spectroscopy data in Chapter 2, and make improvements based on the developments of the methods from Chapter 3 to Chapter 4. Finally we summarize the major findings and contributions of this work as well as identify opportunities for future research and their public health implications.

Despite advances in mosquito management, mosquito-borne disease in the United States is still of relevant public health concern and vector control is a top priority in preventing transmission of pathogens. Insecticide barrier sprays have become a common tool for suppression of mosquitoes in single-homeowner backyards. The application of the synthetic pyrethroid, lambda-cyhalothrin to perimeter vegetation with a backpack sprayer has been shown to significantly suppress mosquito levels for around 6 weeks. In an attempt to lengthen the effective duration of treatment, the IGR, pyriproxyfen, was added to a backpack mist blower with lambda-cyhalothrin, as adult mosquitoes exposed to pyriproxyfen have been shown to disseminate it to oviposition sites and to experience lowered fecundity. This treatment was compared to lambda-cyhalothrin alone and to a water control. Mosquito populations were sampled using CO2-baited CDC light traps, CDC gravid traps, human landing rates, and ovitraps. Leaf bioassays were performed. The following summer, the same treatments were applied with a truck-mounted mist blower to tree lines in Central Kentucky, to test the efficacy of an application method that could be used on large properties. Finally, bioassays were performed with water sampled from pyriproxyfen-treated containers, exposed to field conditions to test for residual efficacy.

An important prerequisite for running a successful insurance business is to predict risk. By forecasting the future in as much detail as possible, competitive advantages are created in terms of price differentiation. This work aims at using spatial point processes to provide a proposal for how the geographical position of the customer can be used in developing risk differentiation tools. For spatial variation in claim frequency an approach is presented which is common in spatial epidemiology by considering a group of policyholders, with and without claims, as a realisation of a multivariate Poisson point process in two dimensions. Claim costs are then included by considering the claims as a realisation of a point process with continuous marks. To describe the spatial variation in relative risk, demographic and socio-economic information from Swedish agencies have been used. The insurance data that have been used come from the insurance company If Skadeförsäkring AB, where also the work has been carried out. The result demonstrates problems with parametric modelling of the intensity of policyholders, which makes it difficult to validate the spatial varying intensity of claim frequency. Therefore different proposals of non-parametric estimation are discussed. Further, there are no tendencies that the selected information is able to explain the variation in claim costs.
En viktig förutsättning för att kunna bedriva en framgångsrik försäkringsverksamhet är att prediktera risk. Genom att på en så detaljerad nivå som möjligt kunna förutse framtiden skapas konkurrensfördelar i form av prisdifferentiering. Målet med detta arbete är att med hjälp av spatiala punktprocesser ge ett förslag på hur kunders geografiska position kan utvecklas som riskdifferentieringsverktyg. För spatial variation i skadefrekvens presenteras ett tillvägagångssätt som är vanligt inom spatial epidemiologi genom att betrakta en grupp försäkringstagare, med och utan skador, som en realisering av en multivariat Poissonprocess i två dimensioner. Skadekostnaderna inkluderas sedan genom att betrakta skadorna som en punktprocess med kontinuerliga märken. För att beskriva spatial variation i relativ risk används demografisk och socioekonomisk information från svenska myndigheter. De försäkringsdata som använts kommer från If Skadeförsäkring AB, där också arbetet har utförts. Resultatet påvisar problem med att parametriskt modellera intensiteten för försäkringstagare, vilket medför svårigheter att validera den skattade spatiala variationen i skadefrekvens, varför olika ickeparametriska förslag diskuteras. Vidare upptäcktes inga tendenser till att variationen i skadekostnad kan förklaras med den utvalda informationen.

Le SAHOS présente une prévalence de 5.9% à 79% dans la population générale de plus de 35 ans mais reste sous diagnostiqué. Le traitement de référence des formes modérées à sévère reste en 2019 la Pressions Positive Continue (PPC). Le bénéfice à la PPC implique une observance suffisante du patient, cette observance étant conditionnée par de multiples facteurs dont les effets secondaires liés à l’interface (fuite entre autres et conséquences de ces fuites). Au cours de cette thèse, nous démontrons la faisabilité du dépistage du SAOS par signal Jawac® dans la population générale.L’analyse des résultats des patients de la cohorte Interface-vent traités par PPC au long cours, souligne que les effets secondaires tels que rapportés par ces patients (dont certains associés aux fuites) sont associés à l’observance et à la somnolence alors que les données machines (index d’apnée hypopnée résiduel et fuites machines) ne le sont pas. Cette absence d’association entre données machine pouvant faire l’objet d’un télésuivi (tel que proposé dans l’algorithme ATS 2013) et observance du patient a été confirmé pour le sous-groupe de patient de la cohorte respectant les critères d’appareillage machine et d’interface de l’algorithme ATS 2013.Les travaux de collaborations ont par ailleurs permis d’aborder la thématique des fuites rapportées par la machine sous deux autres aspects. Tout d’abord, il a été démontré que le mode auto-piloté ou constant de la PPC n’a aucun effet sur le niveau de la fuite rapportée par la machine (alors que l’interface faciale et le niveau de pression machine ont un impact). L’étude des déterminants des fuites au cours d’une nuit d’enregistrement polygraphique a permis de souligner l’hétérogénéité des déterminants de ces fuites non intentionnelles au niveau individuel et la difficulté pour certains patterns de fuites à trouver un consensus de traitement de la fuite
Sleep Apnea syndrome (SAS) is a common sleep disorder with a prevalence ranging from 5.9% to 79.2% in European general populations over 35 years of age old but remains under diagnosed. Continuous positive airway Pressure (CPAP) remains the treatment reference for moderate to severe forms of SAS in 2019. CPAP benefits depend on sufficient patient adherence, which is conditioned by multiple factors, including interface related side effects (leakage and their consequences, among others).In this thesis, we demonstrate the feasibility of OSA screening with Jawac® signaling in the general population. The analysis of the long-term CPAP-treated patient results in the interface-vent cohort highlighted that side-effects reported by these patients (some associated with leakage) are associated with compliance and sleepiness, while machine data (residual apnea/hypopnea index and machine leakage) are not.This lack of association between machine data (that could be monitored as proposed in the ATS 2013 algorithm) and patient compliance was confirmed for the patient subgroup of the cohort respecting the machine criteria and interface equipment of the ATS 2013 algorithm.Collaborative work has also made it possible to address the issue of leaks reported by the machine under two other aspects. First of all, it has been shown that the auto- or constant mode of the CPAP has no effect on the level of the leak reported by the machine (while the oro-nasal interface and the pressure level machine have an impact). By studying determinants of leaks during a night of polygraphic recording, the heterogeneity of unintentional leak determinants at the individual was demonstrated. Finding a consensus for how to quantify leak patterns remains a challenge in the field

Objective To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. Design To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an expansion phase. Methods Major HIV-related risk factors that may change due to the GEC were identified and a dynamic mathematical transmission model was developed and used to forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3 years. Results In Cambodia, the total numbers of HIV diagnoses are not expected to be largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due to potential changes in behavior, may not be observed by the surveillance system. In PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education programs are the factors that may be of greatest concern in both settings. A reduction in the rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to 7.5% after 3 years). Conclusions The GEC is likely to have a modest impact on HIV epidemics. However, there are plausible conditions under which the economic downturns can noticeably influence epidemic trends. This study highlights the high importance of maintaining funding for HIV programs.

Doctor of Philosophy
Department of Electrical and Computer Engineering
Caterina Maria Scoglio
We have analytically discovered the existence of two global epidemic invasion thresholds in a directed meta-population network model of the United States cattle industry. The first threshold describes the outbreak of disease first within the core of the livestock system while the second threshold describes the invasion of the epidemic into a second class of locations where the disease would pose a risk for contamination of meat production. Both thresholds have been verified through extensive numerical simulations. We have further derived the relationship between the pair of thresholds and discovered a unique dependence on the network topology through the fractional compositions and the in-degree distributions of the transit and sink nodes. We then addressed a major challenge for epidemiologists and their efforts to model disease outbreaks in cattle. There is a critical shortfall in the availability of large-scale livestock movement data for the United States. We meet this challenge by developing a method to estimate cattle movement parameters from publicly available data. Across 10 Central States of the US, we formulated a large, convex optimization problem to predict the cattle movement parameters which, having minimal assumptions, provide the best fit to the US Department of Agriculture's Census database and follow constraints defined by scientists and cattle experts. Our estimated parameters can produce distributions of cattle shipments by head which compare well with shipment distributions also provided by the US Department of Agriculture. This dissertation concludes with a brief incorporation of the analytic models and the parameter estimation. We approximated the critical movement rates defined by the global invasion thresholds and compared them with the average estimated cattle movement rates to find a significant opportunity for epidemics to spread through US cattle populations.

One of the most prevalent inherited diseases is cystic fibrosis. This disease is caused by a mutation in a membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is known to function as a chloride channel that regulates the viscosity of mucus that lines the ducts of a number of organs. Generally, most of the prevalent mutations of CFTR are located in one of two nucleotide binding domains, namely, the nucleotide binding domain 1 (NBD1). However, some mutations in nucleotide binding domain 2 (NBD2) can equally cause cystic fibrosis. In this work, a hierarchical graph is built for NBD2. Using this model for NBD2, we examine the consequence of single point mutations on NBD2. We collate the wildtype structure with eight of the most prevalent mutations and observe how the NBD2 is affected by each of these mutations.

Lung cancer has been considered one of the leading causes of deaths while cancer re- mains the second most common cause of deaths in the USA. Understanding the behavior of a disease over time could yield important information to make decisions about the disease. Statistical models could provide crucial clues and help to make a decision about the dis- ease, budget allocation, evaluation, and implement prevention. Longitudinal trend analysis of the diseases helps to understand long term effects and nature. Cholesterol level is one of the most contributing risk factors for Coronary Heart Disease. Studying cholesterol statistically helps to know more about its nature and provides crucial information to mitigate its effectiveness in diagnosing its impact to public health. In our study, we have analyzed lung cancer mortality in the USA based on age at death, period at death, and birth cohort to investigate its nature in longitudinal effects. The attempt has been made to estimate mortality rate based on age for different age groups and to find the relative risk of mortality due to period effect and relative risk due to birth cohort for lung cancer in the United States. Our statistical analysis and modeling are based on the data obtained from Surveillance Epidemiology and End Results (SEER) program of the United States. We have also investigated the probabilistic behavior of average cholesterol level based on gender and ethnicity. The study reveals significant differences with respect to the distribution they follow and their basic inferences which could be beneficial to draw conclusions in various ways in addressing related issues. At the same time, the change of cholesterol level over time for an individual might be a good source to study the association of cholesterol level, coronary heart disease and their effects on age. The cholesterol data is obtained from inter-university Consortium for Political and Social Research and National Health and Nutrition Examination Survey (NHANS) of the United States. Understanding the average change in total serum cholesterol level over time as people get older could be vital to explore it. We have studied the longitudinal behavior of the association of sex and time with cholesterol level. It is observed that age, sex, and time have an individual effect and can impact differently upon collective considerations. Their adverse effect in increasing cholesterol level could promote to worsen the cholesterol re- lated issues and hence heart related diseases. We believe our study pivots knowing more about target population of cholesterol level and helps to have the useful inference about cholesterol levels for public health. Finally, we also analyzed the average cholesterol data using a functional data analysis approach to understand its nature and effect on age. Since functional data analysis approach presents more flexibility in modeling, it could provide more insight in studying cholesterol level.

Bentham’s 1832 Greatest Happiness Principle states that the greatest happiness for the greatest amount of people should be the goal of public policy. When people are asked what they wish for in life, health and happiness are consistently mentioned. This thesis examines the relationship between health and happiness. However, as happiness is difficult to consistently operationalize across different studies and scientific disciplines, life satisfaction is used as a proxy for happiness. This thesis studies the relationship between health and life satisfaction with a particular focus on the directionality of the relationship and the tentative processes indicated to be involved with this process. This study is accomplished through a literary review of the scientific literature related to life satisfaction, its neural correlates and their relationship with physical health. This study is modelled on the top-down, bottom-up and bidirectional debate within the larger Subjective Well-Being (SWB) literature. The results indicate that the correlation between life satisfaction and health appears to be robust, but the exact directionality and causality is unclear and difficult to establish with a literary review, with only predictive ability of life satisfaction on later physical health or vice versa established. Furthermore, the results appear to indicate that the central process linking this relationship is resilience - the ability to adaptively respond to stressors. Enhancing resiliency through psychological interventions may be a method to promote happiness and health in individuals as well as in society as a whole.

Ovarian cancer (OC) is the fifth most common cancer among women and has the highest mortality of any cancer of the female reproductive system. The majority (61%) of OC cases are diagnosed at a distant stage. Because diagnoses occur most commonly at a late-stage and prognosis for advanced disease is poor, research focusing on the development of effective OC screening methods to facilitate early detection in high-risk, asymptomatic women is fundamental in reducing OC-specific mortality. Presently, there is no screening modality proven efficacious in reducing OC-mortality. However, transvaginal ultrasonography (TVS) has shown value in early detection of OC. TVS presents with the possibility of false positive results which occur when a women receives an abnormal TVS screening test result that is deemed benign following repeat testing (about 7% of the time). The purpose of this dissertation was to evaluate the impact of false positive TVS screening test results on a variety of psychological and behavioral outcomes using mixed and trajectory statistical modeling. The three specific aims of this dissertation were to 1) compare psychological and behavioral outcomes between women receiving normal and false positive results, 2) identify characteristics of women receiving false positive results associated with increased OC-specific distress and 3) characterize distress trajectories following receipt of false positive results. Analyses included a subset of women participating in an experimental study conducted through the University of Kentucky Ovarian Cancer Screening Program. 750 women completed longitudinal assessments: 375 false positive and 375 normal results. Mixed and group-based trajectory modeling were used to evaluate the specific aims. Results suggest women receiving false positive TVS result experience increased OC-specific distress compared to women receiving normal results. Among those receiving false positives, less education, no history of an abnormal screening test result, less optimism and more social constraint were associated with increased OC-specific distress. Family history was associated with increased distress among women with monitoring informational coping styles. Three distinct trajectories characterize the trajectory of distress over a four-month study period. Although decreasing over time, a notable proportion of women experience sustained high levels of OC-specific distress.

This paper aims to provide the grounds for a biopsychosocial understanding of the underpinnings of conspiracy theorist ideation by studying research articles from different scientific disciplines. Cross-disciplinary concurring results are presented and discussed, as well as some examples of how conspiracy theories have been used during the 20th century. Also discussed is how this is used in political discourse in the populist climate of today, with the rise of radical right-wing movements, the justification of “alternative facts” from higher governmental ranks, and religious fundamentalism, making it a societal issue of possible big magnitude. Neurological similarities was found between religiousness and proneness to conspiracy theory ideation, and the articles concerning neural correlates therefore stem from research on religious individuals due to the lack of neuro-biopsychological research on actual conspiracy theorists. Since conspiracy theory ideation has shown the ability to cause negative consequences it is also advised that governmental agencies and society as a whole revise its stance on populism and the spread of flawed information, in order to maintain an open society. Also presented are a few ideas on how to begin countering the rise of populism.

La tuberculose MDR/XDR (multi et ultrarésistante aux antituberculeux) causée par Mycobacterium tuberculosis constitue un problème de santé publique mondial. L’étude et l’identification des mutations responsables de la résistance sont des facteurs clés pour le contrôle et la surveillance de la tuberculose MDR/XDR. L’expansion de lignée L2/Beijing, une famille de souches originaire du Sud-Est de la Chine (Guangxi) potentiellement plus virulente, complique la maitrise de cette maladie. Dans ce contexte, nous avons développé le TB-EFI et le TB IS-NTF/RINT, deux méthodes moléculaires rapides, multiplexées et haut débit (développées sur le système Luminex xMap), prêtes à utilisation. Nous avons initié le développement d’une méthode moléculaire par la sélection de marqueurs moléculaires pertinents en vue de la discrimination des souches Beijing par la technique MLPA-Beijing. Le TB-EFI est un test qui permet d’identifier les mutations fréquentes (polymorphismes de nucléotides simples) dans les gènes associés à la résistance des souches de Mycobacterium tuberculosis aux antituberculeux de deuxième ligne dont la Fluoroquinolone, les Injectables, et à l’antituberculeux de première ligne, l’Ethambutol. Le TB-EFI pourrait être un test utilisable dans les études rétrospectives en vue du suivi de la résistance d’une population. Le test IS-NTF/RINT est un test spécifique aux souches Beijing qui type la séquence d’insertion IS6110 au sein du locus NTF (Ancien/moderne) et détecte les mutations responsables de la résistance de ces souches à la Rifampicine et l’Isoniazide (les deux antibiotiques principaux de première ligne). Ce test est d’une importance capitale pour l’identification et le contrôle des souches épidémiques, mais aussi pour une vision sur l’évolution du phénomène de résistance dans le temps et l’espace. Il est peu discriminant pour la différenciation des souches Beijing. En vue d’une discrimination complète et précise des souches Beijing, nous avons proposé un lot de SNP qui serviront pour la technique MLPA-Beijing. Par ailleurs, ces méthodes ainsi que le spoligotypage sur microbille, nous ont permis d’effectuer des études d’épidémiologie moléculaire de la tuberculose au Kazakhstan, en Nouvelle Guinée Papouasie, en Italie, au Mozambique, au Pérou. Les techniques développées dans cette thèse pourraient contribuer de manière significative au contrôle de la tuberculose XDR dans les zones « hot-spot », et à la surveillance mondiale de l’évolution des souches Beijing spécialement des souches MDR épidémiques
MDR / XDR (multidrug and extensively resistant to tuberculosis) TB caused by Mycobacterium tuberculosis is still a global public health problem. The study and identification of mutations responsible for resistance are important factors for the control and surveillance of MDR / XDR TB. The expansion of the L2 / Beijing lineage, a family of strains originating from South-East of China (Guangxi) and potentially more virulent, complicates the control of this disease. In this context, we have developed TB-EFI and TB IS-NTF / RINT, two high-speed, multiplexed and high-throughput molecular methods ready to use (developed on the Luminex xMap system). We initiated the development of a molecular method by the selection of relevant molecular markers for the discrimination of Beijing strains by the MLPA technique. TB-EFI is a test that identifies frequent mutations (single nucleotide polymorphisms) in the genes associated with the resistance of Mycobacterium tuberculosis strains to second-line anti-TB drugs including Fluoroquinolone, Injectable, and first-line antituberculosis drug, Ethambutol. TB-EFI may be used in retrospective studies to monitor resistance in a population. The IS-NTF / RINT test is a test specific to Beijing strains that types the IS6110 insertion sequence within the NTF locus (Ancient / Modern) and detects the mutations responsible for the resistance of these strains to Rifampicin and Isoniazid (the two leading primary antibiotics). This test is of paramount importance for the identification and control of epidemic strains, but also for a vision on the evolution of the phenomenon of resistance in time and space. It is not very discriminating among Beijing strains. In view of complete and precise discrimination of the Beijing strains, we have proposed a set of SNPs that will be used for a technique that will be called MLPA-Beijing. In addition, these methods as well as spoligotyping on microbeads allowed us to carry out molecular epidemiological studies of tuberculosis in Kazakhstan, Papua New Guinea, Italy, Mozambique and Peru. The techniques developed in this thesis could contribute significantly to the control of XDR tuberculosis in hot-spot areas, and to the global monitoring of the evolution of Beijing strains especially epidemic MDR strains

Doutoramento em Matemática
A relação entre a epidemiologia, a modelação matemática e as ferramentas computacionais permite construir e testar teorias sobre o desenvolvimento e combate de uma doença. Esta tese tem como motivação o estudo de modelos epidemiológicos aplicados a doenças infeciosas numa perspetiva de Controlo Ótimo, dando particular relevância ao Dengue. Sendo uma doença tropical e subtropical transmitida por mosquitos, afecta cerca de 100 milhões de pessoas por ano, e é considerada pela Organização Mundial de Saúde como uma grande preocupação para a saúde pública. Os modelos matemáticos desenvolvidos e testados neste trabalho, baseiam-se em equações diferenciais ordinárias que descrevem a dinâmica subjacente à doença nomeadamente a interação entre humanos e mosquitos. É feito um estudo analítico dos mesmos relativamente aos pontos de equilíbrio, sua estabilidade e número básico de reprodução. A propagação do Dengue pode ser atenuada através de medidas de controlo do vetor transmissor, tais como o uso de inseticidas específicos e campanhas educacionais. Como o desenvolvimento de uma potencial vacina tem sido uma aposta mundial recente, são propostos modelos baseados na simulação de um hipotético processo de vacinação numa população. Tendo por base a teoria de Controlo Ótimo, são analisadas as estratégias ótimas para o uso destes controlos e respetivas repercussões na redução/erradicação da doença aquando de um surto na população, considerando uma abordagem bioeconómica. Os problemas formulados são resolvidos numericamente usando métodos diretos e indiretos. Os primeiros discretizam o problema reformulando-o num problema de optimização não linear. Os métodos indiretos usam o Princípio do Máximo de Pontryagin como condição necessária para encontrar a curva ótima para o respetivo controlo. Nestas duas estratégias utilizam-se vários pacotes de software numérico. Ao longo deste trabalho, houve sempre um compromisso entre o realismo dos modelos epidemiológicos e a sua tratabilidade em termos matemáticos.
The relationship between epidemiology, mathematical modeling and computational tools allows to build and test theories on the development and fighting of a disease. This thesis is motivated by the study of epidemiological models applied to infectious diseases in an Optimal Control perspective, giving particular relevance to Dengue. It is a subtropical and tropical disease transmitted by mosquitoes, that affects about 100 million people per year and is considered by the World Health Organization as a major concern for public health. The mathematical models developed and tested in this work, are based on ordinary differential equations that describe the dynamics underlying the disease, including the interaction between humans and mosquitoes. An analytical study is made related to equilibrium points, their stability and basic reproduction number. The spreading of Dengue can be attenuated through measures to control the transmission vector, such as the use of specific insecticides and educational campaigns. Since the development of a potential vaccine has been a recent global bet, models based on the simulation of a hypothetical vaccination process in a population are proposed. Based on the Optimal Control theory, we have analyzed the optimal strategies for using these controls and respective impact on the reduction / eradication of the disease during an outbreak in the population considering a bioeconomic approach. The formulated problems are numerically solved using direct and indirect methods. The first discretize the problem turning it into a nonlinear optimization problem. Indirect methods use the Pontryagin Maximum Principle as a necessary condition to find the optimal curve for the respective control. In these two strategies several numerical software packages are used. Throughout this study, there was a compromise between the realism of epidemiological models and their mathematical tractability.

Thesis (MScAgric)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: This study looked at the incidence, etiology and epidemiology of core rot of apples in orchards situated in the Western Cape, South Africa. Core rot is a post-harvest disease, with three symptoms, namely mouldy core (MC), dry core rot (DCR) and wet core rot (WCR). These symptoms are caused by various pathogenic fungi, including Alternaria and Penicillium. Although MC is not economically important, DCR and WCR are, as they affect the flesh of the fruit. Core rot occurs worldwide in susceptible apple cultivars such as ‘Starking’ and ‘Red Delicious’. These cultivars have a wider, open calyx tube which results in an open core area. In South Africa, core rot of apples are important post-harvest diseases and losses of between 5 and 12% occur in apple cultivars. An in depth literature search was done on core rot including literature on each core rot symptom, the genuses Alternaria and Penicillium, molecular identification and techniques, disease incidence and its economic importance, various inoculum sources, pathogenicity of core rot organisms and integrated management of core rot. This study included two research chapters, with seven objectives, namely, to 1, determine the incidence of core rot in apples from commercial orchards both pre- and post-harvest; 2, to identify the causal organisms associated with core rot symptoms; 3, to identify potential sources of inoculum of core rot pathogens and determine whether there is synergism between Alternaria and Tarsonemus mites associated with core rot; and 4, to determine whether the fungicide Bellis®, used a full bloom application, can be used to manage core rot in South Africa; 5, to identify the species of Alternaria and Penicillium sampled from core rot symptomatic fruit and inoculum sources (air, apple mummies and mites), using morphological and molecular methods; 6, to compare Penicillium species isolated from pre- and post-harvest WCR symptomatic fruit, using molecular species identification methods and 7, to compare and to select the most reliable pathogenicity test for use in future research. The total decay incidence for Ceres is considerably higher than the previous losses indicated in literature. Pre-harvest core rot, which was confirmed by previous studies, had a higher incidence of each core rot symptom than previously indicated. The two most frequently isolated causal organisms were Alternaria and Penicillium. Other organisms isolated and then identified from the symptoms were Fusarium, Cladosporium, Epicoccum, Ulocladium, Stemphylium, Phoma, Botryosphaeria, Botrytis, Trichoderma, Verticillium, Paecilomyces and Gliocladium. Three inoculum sources, air, mummies and mites, were regarded as potential sources of infection for core rot. During this study the sources of infection were verified and core rot causing organisms were isolated from these sources. Alternaria was isolated from air inoculum samples, but was not found on the other two sources. This dismissed the hypothesis that there was a possible synergism between Alternaria and Tarsonemus mites. Penicillium species were isolated from all three sources, more frequently from the mummies and mites. Bellis® was applied three times during the bloom period. The subsequent results showed a significant difference between the control and Bellis® treated treatments with the treated fruit having a significant higher incidence than the controlled fruit. No control was observed with this result and managing core rot with only Bellis® is not advisable. Alternaria species were identified using the following genetic loci, ITS, OPA1-3, 2-1 and 10-2 as well as endoPG. Isolates from pre- and post-harvest symptoms and air inoculum were identified using each of the genetic loci. Alternaria arborescens was one of the species that was identified. The other isolates obtained were A. alternata, A. tenuissima, A. gaisen, A. dumosa, A. turkisafria and A. perangusta. Separating combined species was not possible. Another molecular technique, ISSR, was used to identify Alternaria species. This technique, after multiple re-runs, did not give consistent results and species could not be identified. Penicillium species were identified using the genetic loci ITS for isolates collected from pre- and post-harvest symptoms and inoculum sources. Thirteen clades were identified, including the species P. ramulosum, P. sp. (aff. cecidicola), P. sp (aff. dendriticum), P. expansum, P. paneum, P. solitum, P. crustosum , P. brevicompactum, P. novae-zeelandiae, P. glabrum and P. rugulosum. Penicillium expansum and P. ramulosum had the highest distribution between the isolates. Pre- and post-harvest WCR isolates were identified using the partial beta-tubulin PCR-RFLP method, and comparing different banding-patterns. The species identified using this method were P. expansum, P. ramulosum, P. sp. (aff. cecidicola), P. sp (aff. dendriticum), P. rugulosum, P. chermesinum and P. glabrum. Penicillium ramulosum and P. expansum had the highest incidence with P. ramulosum occurring more frequently pre-harvest than post-harvest and P. expansum occurring more frequently post-harvest. Five methods, previously published, were compared to select the most reliable pathogenicity test. The methods included surface wounding of an apple with colonised toothpicks, surface wound inoculated with a pipette, inoculation of an open mesoderm core cavity, deep and non-wounding of apple fruit with colonised toothpicks. The surface wounding with a colonised toothpick gave the most reliable results and can be used in industry as a pathogenicity test for Alternaria in apples. This study contributed to our understanding on the incidence and etiology of core rot in the Western Cape as well as in identifying inoculum sources from where infection can take place in the orchard. The results for the fungicide trial were not as anticipated and more research is required on selecting fungicides for the control of core rot in South African orchards. Although molecular techniques reduce the time in identifying fungal species, it is costly and mistakes can occur due to contamination. Identification of species can be incorrect when using a Genbank as the sequence information may be incorrect. Molecular techniques, though a good tool in identifying species, should be combined with morphological characteristics to ensure more accurate results.
AFRIKAANSE OPSOMMING: Hierdie studie het gekyk na die insidensie, etiologie en epidemiologie van kernvrot in appels vanuit boorde in die Wes-Kaap, Suid-Afrika. Kernvrot is ‘n na-oes iekte, met drie simptome, naamlik beskimmelde kern, droë kernvrot en nat kernvrot. Hierdie simptome word veroorsaak deur verskillende patogeniese swamme, insluitend Alternaria en Penicillium. Alhoewel beskimmelde kern nie ekonomies belangrik is nie, is droë en nat kernvrot wel belangrik, omdat hulle die vrug se vlees affekteer. Kernvrot kom wêreldwyd voor in vatbare kultivars soos ‘Starking’ en ‘Red Delicious’. Hierdie kultivars het ‘n wye, oop kelkbuis wat ‘n oop kern area veroorsaak. In Suid-Afrika is kernvrot van appels ‘n belangrike na-oes siekte en verliese tussen 5 en 12% kom voor in appel kultivars. ‘n In diepte literatuurstudie is gedoen omtrent kernvrot, insluitend literatuur omtrent elke kernvrot simptoom, die genera Alternaria en Penicillium, molekulêre identifikasie en tegnieke, siekte insidensie en sy ekonomiese impakte, verskillende inokulum bronne, patogenisiteit van kernvrot organismes en die geïntegreerde bestuur van kernvrot. Hierdie studie sluit in twee navorsings hoofstukke met sewe doelwitte, naamlik om 1, te bepaal wat die insidensie van kernvrot in appels is vanuit kommersiële boorde vir beide voor en na-oes; 2, om veroorsakende organismses wat met kernvrot simptome geassosieër is te identifiseer; 3, om potensiële inokulum bronne van kernvrot patogene te identifiseer en te bepaal of daar ‘n sinergisme tussen Alternaria en Tarsonemus myte, wat geassosieër is met kernvrot, is; 4, om te bepaal of die fungisied Bellis®, gebruik as ‘n volblom toediening, gebruik kan word om kernvrot in Suid-Afrika te beheer; 5, om die Alternaria en Penicillium spesies wat uit simptomatiese kernvrot vrugte en inokulum bronne geïsoleer is te identifiseer; 6, om Penicillium spesies, wat uit voor en na-oes nat kernvrot simptome geïsoleer is, te vergelyk deur gebruik te maak van molekulêre spesies identifiserings metodes en 7, om die betroubaarste patogenisiteits toets te vergelyk en selekteer vir toekomstige gebruik. Die totale bederfde insidensie vir Ceres is heelwat hoër as die vorige verliese wat aangedui is in literatuur. Vooroes kernvrot, wat deur vorige studies bevestig is, het ‘n hoër insidensie vir elke kernvrot simptoom gehad as wat voorheen aangedui is. Die twee geïsoleerde veroorsakende organismes wat die meeste voorgekom het was Alternaria en Penicillium. Ander organismes wat geïsoleer en geïdentifiseer is vanuit die simptome was Fusarium, Cladosporium, Epicoccum, Ulocladium, Stemphylium, Phoma, Botryosphaeria, Botrytis, Trichoderma, Verticillium, Paecilomyces en Gliocladium. Drie inokulum bronne, lug, gemummifiseerde vrugte en myte, is geag as potensiële bronne van infeksie vir kernvrot. Gedurende hierdie studie is hierdie bronne bevestig en kernvrot veroorsakende organismes is uit die bronne geïsoleer. Alternaria is geïsoleer vanuit die lug inokulum monsters, maar is nie geïsoleer vanuit die ander twee bronne nie. Dus die hipotese dat daar ‘n sinergisme tussen Alternaria en Tarsonemus myte is, is verwerp. Penicillium spesies is geïsoleer vanuit al drie bronne, maar meer gereeld vanuit die gemummifiseerde vrugte en die myte. Bellis® is drie keer gedurende die bot toegedien. Die daaropvolgende resultate het ‘n betekenisvolle verskil tussen die kontrole en Bellis® beheerde behandelings getoon, met die behandelde vrugte wat ‘n betekenisvolle hoër insidensie gehad het as die kontrole vrugte. Geen beheer is waargeneem nie en beheer van kernvrot met net Bellis® word nie aanbeveel nie. Alternaria spesies is geïdentifiseer deur die volgende genetise lokusse, ITS, OPA1-3, 2-1 en 10-1, asook endoPG. Isolate van voor en na-oes simptome en lug inokulum is geïdentifiseer deur elk van die genetiese lokusse. Alternaria arborescens is een van die spesies wat geïdentifiseer is. Ander isolate wat verkry is, was A. alternata, A. tenuissima, A. gaisen, A. dumosa, A. turkisafria and A. perangusta. Om gekombineerde spesies te skei was nie moontlik nie. ‘n Ander molekulêre tegniek, ISSR, was gebruik om Alternaria spesies te identifiseer. Hierdie tegniek, na menigte probeerslae, het nie konsekwente resultate gegee nie en spesies kon nie hiermee geïdentifiseer word nie. Penicillium spesies, versamel vanuit voor en na-oes simptome en inokulum bronne, is geïdentifiseer deur die genetiese lokus ITS. Dertien ‘clades’ is geïdentifiseer, insluitend die spesies P. ramulosum, P. sp. (aff. cecidicola), P. sp (aff. dendriticum), P. expansum, P. paneum, P. solitum, P. crustosum , P. brevicompactum, P. novae-zeelandiae, P. glabrum en P. rugulosum. Penicillium expansum en P. ramulosum het die hoogste distribusie tussen die isolate. Voor en na-oes nat kernvrot isolate is geïdentifiseer deur die deels beta-tubulin PCR-RFLP metode, en verskillende band patrone te vergelyk. Die spesies geïdentifiseer deur hierdie metode is P. expansum, P. ramulosum, P. sp. (aff. cecidicola), P. sp (aff. dendriticum), P. rugulosum, P. chermesinum en P. glabrum. Penicillium ramulosum en P. expansum het die hoogste insidensie gehad met P. ramulosum wat meer dikwels vooroes voorkom en P. expansum wat meer dikwels na-oes voorkom. Vyf metodes, wat voorheen gepubliseer is, is vergelyk om die betroubaarste patogenisiteits toets te selekteer. Die metodes sluit in die oppervlak wond van ‘n appel met ‘n gekoloniseerde tandestokkie, oppervlak wond geïnokuleer met ‘n pipette, inokulasie van ‘n oop mesoderm kern area, diep besering en nie-besering van die appel met gekoloniseerde tandestokkies. Die oppervlak besering met ‘n gekoloniseerde tandestokkie het die betroubaarste resultate gegee en kan in die industrie gebruik word as ‘n patogenisiteits toets vir Alternaria in appels. Hierdie studie het bygedra tot ons kennis van die insidensie en etiologie van kernvrot in die Wes-Kaap sowel as die identifisering van die inokulum bronne, van waar die infeksie in die boord kan plaasvind. Die resultate vir die fungisied proef was nie wat ons verwag het nie en meer navorsing word benodig om fungisiede te selekteer vir die beheer van kernvrot in Suid-Afrikaanse boorde. Alhoewel molekulêre tegnieke die tyd verminder om ‘n swam spesie te identifiseer, is dit wel duur en foute kan voorkom as gevolg van kontaminasie. Identifikasie van spesies kan verkeerd wees indien Genbank gebruik is, omdat die informasie daar nie altyd korrek is nie. Molekulêre tegnieke, alhoewel ‘n goeie manier om spesies te identifiseer, moet gekombineer word met morfologiese karakter eienskappe om akurate resultate te verseker.

The Health Protection Branch of the Victorian Government Department of Health and Human Services monitors and responds to incidents that could adversely affect the health of Victorians. During 2014-2015, I completed a field placement with the branch, assisting with numerous public health investigations and responses. In doing so I fulfilled the requirements of the Master of Philosophy in Applied Epidemiology (MAE). The skills I gained are demonstrated in this thesis. Evaluation of a public health surveillance system is a core requirement for the MAE program. I evaluated Victoria’s surveillance and response to legionellosis, which includes both disease surveillance and environmental surveillance and response arms. I found little evidence to support the current practice of sampling and disinfecting cooling towers around the home and workplace for sporadic cases. Improved co-ordination between databases and strategic use of spatial software could help develop more targeted and useful approaches in the future. I embarked on two epidemiological projects. I designed a cross sectional study examining the prevalence of Legionella in domestic potable water and developed participant resources including letters to explain results, meeting the MAE requirement to communicate findings to a non-scientific audience. The study was not completed due to legal considerations; however the proposal and relevant participant resources are included as an appendix. I completed an epidemiological project estimating the number of notified sporadic Salmonella Typhimurium 9 Phage type 9 cases likely to be associated with a recurrent outbreak source during a five year period. I examined 301 clinical Salmonella isolates, including sporadic and outbreak isolates from a series of linked outbreaks, and used multi-locus variable number tandem repeat analysis and whole genome sequence results to estimate the number of isolates genetically linked to the outbreak strain. Outbreak cases accounted for just one third of all isolates estimated to be closely related to the main outbreak clade. This project inspired my lesson from the field, in which I taught MAE colleagues how to analyse MLVA data. I investigated an outbreak of Salmonella Typhimurium phage type 44 at a school function. I conducted a cohort study and interviewed twenty-nine out of thirty guests, of which ten were affected. Roast beef appetiser was the most likely food vehicle for Salmonella infection. Cross-contamination from raw eggs during preparation was a possible source. I analysed a public health dataset to assist a public health investigation into suspected antimony exposure in a rural mining town in Victoria. Residents were concerned about potential health effects from exposure to antimony dust from a local mine. Many sought urinary antimony testing to quantify exposure, with numerous elevated results. I used multivariate regression to examine risk factors for elevated urinary antimony and demonstrated residential proximity to the mine was not associated with urinary antimony results. Overwhelmingly, the largest risk factor for elevated results was the month of testing, consistent with false positive laboratory reports. This thesis documents my experience and capabilities gained during the MAE program, and demonstrates my contribution to protecting the public health of Victorians.

I completed my placement as a Masters of Philosophy in Applied Epidemiology scholar at the Department of Health and Human Services in Tasmania. I was attached to the Communicable Diseases Prevention Unit which sits in the Population and Environmental Health Services Branch. Tasmania is a small jurisdiction, both in size and population. This allowed my involvement in projects both in communicable diseases and environmental health. I describe the placement, my participation in the day to day activities of the Unit, my applied epidemiology projects to demonstrate a range of applied epidemiological skills. I evaluated the Tasmanian hepatitis C virus (HCV) surveillance system. This system has been operational since 1995 without review or development of objectives. This evaluation was focused on the usefulness of the system and its ability to achieve objectives proposed by an internal working group. The system was found to be stable, flexible and useful. The major recommendation to increase the usefulness of the system is to improve reporting of data to stakeholders for use in program development, evaluation and advocacy. In my epidemiological project I completed a data linkage study of rates of hospital admission and death in a cohort of Tasmanians with HCV. HCV notifications from the Tasmanian Notifiable Diseases Database were linked with statewide hospital admissions and death data. This project was the first time data linkage had been used on Tasmanian notification data and an objective of the study was to determine if this methodology was suitable. It was found to be useful with potential uses to explore co-infections among Tasmanians. I found the most common causes of admissions in this cohort were mental and behavioral conditions and injuries and poisoning. In completing my data analysis, I participated in an investigation into water tanks in Tasmania that had high water lead concentrations. We found the manufacturer had been using non-compliant construction materials. I coordinated the follow up of children with elevated blood lead concentrations. Water lead concentrations found in the water tanks were extremely high compared with findings from other Australian studies. A moderate association was found between water lead and blood lead concentrations. All children re-tested after they stopped drinking the contaminated water had a reduction in blood lead concentrations. I presented the preliminary findings from this investigation to the 2013 Annual OzFoodNet Meeting and final analysis to the 2014 National Environmental Health Association Conference. I participated in the investigation of a norovirus outbreak in Tasmania that was associated with locally grown oysters. Precautionary action was taken early in the investigation but the outbreak progressed rapidly and resulted in significant morbidity. I presented the investigative methods and findings from this outbreak to the 2014 Tasmanian Environmental Health Association Annual Conference. To fulfill the requirements of the program I prepared two teaching sessions. The "lessons from the field" case study was an introduction to data linkage for other MAE scholars in my cohort. I also prepared and taught a session on risk assessment in the context of outbreak investigation to the 2014 MAE scholars.

The Communicable Diseases, Epidemiology and Surveillance (CDES) branch, Victorian Government Department of Health and Human Services (DHHS), works closely with the Microbiological Diagnostic Unit Public Health Laboratory (MDU) to conduct surveillance of communicable diseases in Victoria. From February 2018 to December 2019, I attended field placements at both CDES and MDU. This thesis comprises projects which together meet the requirements for the Masters of Philosophy (Applied Epidemiology) (MAE). The projects include: an analysis to assess changes in the epidemiology of invasive pneumococcal disease in Victoria, 2008-2018; an evaluation of the surveillance of antimicrobial resistance in Victoria; a cross-sectional study of the genomic epidemiology of vancomycin-resistant enterococci, Victoria, November 2018; investigation of an outbreak of salmonellosis at a Mother's day lunch in regional Victoria, and recruitment of case-controls for a multi-jurisdictional outbreak investigation of hepatitis A. In addition, this thesis describes teaching activities undertaken as part of the MAE.

My initial field placement was with the Centre for Disease Control in the Northern Territory where I was employed by the Sexual Health and Blood Borne Virus unit, as the remote sexual health program manager for the Top End from April 2013 to March 2017. I commenced the Master of Philosophy (Applied Epidemiology) program in January 2016, while employed full time in the above position. The Sexual Health and Blood Borne Virus unit are responsible for surveillance, monitoring and management of sexually transmissible infections (STI), HIV and blood borne viruses (BBV) primarily affecting vulnerable Aboriginal populations living in remote communities. A key component of my role was to work with primary health care services in adopting a sexual health quality improvement program to increase STI/BBV testing, identify and treat infections promptly, follow up sexual contacts to minimise transmission and establish systems for improving STI/BBV management. I completed two projects that met core requirement for this degree during this placement. Firstly, I took the lead role on investigating a Salmonella Saintpaul outbreak linked to ready-made meals produced by a restaurant in the Darwin urban area. Secondly, I conducted a data analysis project assessing the epidemiology of hepatitis C in the NT from 1991 to March 2016 which coincided with the introduction of direct-acting antivirals (DAAs) which can cure hepatitis C. From March 2017 to the present, I've been employed by the Sydney local health district at RPA Sexual Health clinic. This thesis includes two projects I've completed that are relevant to this environment. The aim of the first project was to assess chlamydia and gonorrhoea positivity among sexual contacts exposed to these infections that attended publicly funded sexual health services from a variety of urban, inner regional and outer regional and remote areas. The aim of the project was to assess whether the evidence supported adopting a test-and-wait method thereby minimising antibiotic use. The second project was to evaluate the internal HIV surveillance and response system for patients diagnosed with HIV and ongoing care managed by the clinic with a key focus on the information management system used for electronic patient records. All the above projects meet the requirements of this degree.

In meeting the Master of Philosophy in Applied Epidemiology (MAE)'s, I completed two of my core projects at the Institute Pasteur of Cambodia (IPC), a non-governmental organization. The other two core projects I completed at the Ministry of Health's Cambodian Communicable Disease Control Department (CCDC), where I was later deployed to support Coronavirus Disease 2019 (COVID-19) contact tracing and surveillance. In this thesis, I demonstrate how I met the core competencies of the MAE program. In late November and early December 2019, a provincial health department notified CCDC about what they called a food poisoning event that had affected more than 200 people, and resulted in two deaths in a residential facility in a province of Cambodia. We conducted a case-control study. We found a strong association between eating cucumbers and illness. However, laboratory analysis failed to detect a causative agent. Toxicology testing was not conducted, and therefore we were unable to rule out contamination of the cucumbers. This project is described in chapter two, "An outbreak of unknown etiology associated with fresh cucumbers in a residential facility in Cambodia, 2019". We aimed at describing how malaria has evolved spatially from 2006 to 2019. We undertook a secondary analysis of existing malaria data from all public health facilities in Cambodia between 2006 and 2019 in combination with metadata. Overall, incidence fluctuated between 1.5 and 7.4 cases/1000 inhabitants per year. Malaria clusters were detected in seven northern provinces, along borders. We recommended that interventions aimed at preventing new infections of Plasmodium vivax and relapses should be prioritized. All confirmed malaria cases should be reported to Health Management Information System to avoid misleading trends. This project is detailed in chapter three, "Malaria in Cambodia: retrospective analysis of a changing epidemiology 2006-2019." I implemented and evaluated the RAI2 surveillance system as part of activities associated with a funded malaria project. Nine attributes, adapted from the US CDC guideline 2001, were used to assess the performance of the system. Usefulness was described based on the outcome of the evaluation of the other eight attributes. Simplicity, flexibility, acceptability, and stability were assessed using a short online survey with health center staff. Sensitivity, positive predictive value, data quality, and timeliness were assessed using document review and data from the RAI2 surveillance system. Findings suggested that the RAI2 surveillance system was simple, flexible, stable, timely but did not meet its primary objective. We recommended that the RAI2 surveillance system should be integrated into the national malaria information system and moved to be a real-time data collection. Additional exposure variables should be captured. I placed this project in chapter four, "Using Kobo Toolbox as a malaria project-based surveillance system in Cambodia: surveillance evaluation." My final project was to estimate the proportion of COVID-19 cases that were asymptomatic and understand how the asymptomatic transmission may occur. I analyzed data from 22 cases as part of a cluster of returned travelers, with what was believed to be a common exposure site. Their 491 uninfected contacts and ten infected contacts were also included in the analysis. The findings suggested asymptomatic cases made up a larger proportion of total cases within the cluster. This project is described in chapter five, "Coronavirus Disease 2019 asymptomatic transmission: A cluster review in Cambodia, 2020." Finally, other required activities presented in this thesis include an oral presentation, a scientific manuscript submitted to a peer-review journal, a literature review, a summary for a layperson, lessons learned from the field, and teaching.

Aboriginal and Torres Strait Islander populations in remote Western Australia (WA) face many challenges in relation to public health. It was in this setting that I was placed as a Master of Philosophy in Applied Epidemiology (MAE) scholar, based at the Kimberley Population Health Unit (KPHU), WA Country Health Service, where I had previously worked as a Medical Officer. In this thesis I present field epidemiology projects with a focus on remote Aboriginal and Torres Strait Islander health. These projects were designed to fulfil the key requirements of the MAE award. In investigating an acute public health problem, I lead the investigation and response to an outbreak of pandemic strain influenza A(H1N1) virus in a remote community in the northern Kimberley. Through this project, I fulfilled the requirement for an oral presentation at an international or national conference, by presenting on this work at the 7th Bi-regional Training Programs in Epidemiology and Public Health Interventions Network (TEPHINET) conference in Vietnam. I also developed a paper for publication in the peer reviewed scientific literature titled: "An outbreak of influenza A(H1N1)pdm09 in a remote Aboriginal community" which was accepted by the Australian and New Zealand Journal of Public Health. Further, I developed a lay summary of the outbreak report which was provided to the community affected by the outbreak, thus completing the MAE requirement of a report to a non-scientific audience. I provide an evaluation of a public health surveillance system, titled "Evaluation of the Western Australia Rheumatic Heart Disease Register". My major epidemiology project, which fulfilled the requirement to design and conduct an epidemiological study, was also in the field of rheumatic heart disease, but focussed on it's cause, acute rheumatic fever. This investigation of an acute rheumatic fever epidemic across WA was titled "Acute Rheumatic Fever Increase in Western Australia". To analyse a public health dataset, I used an existing clinical data set to examine practitioner and patient adherence to best practice guidelines for people with chronic heart failure attending primary health care services in the Kimberley region. This project was titled "Adherence with a Chronic Heart Failure Guideline in the Kimberley region, Western Australia". In addition to these projects, I completed a literature review as a requirement of the MAE award, titled: "Chronic Disease Management in Remote Aboriginal Communities in Australia". To achieve MAE teaching competencies, I was involved in several teaching sessions, including designing, coordinating and running a "lessons from the field" which focused on disease registers, and delivering a group teaching program to epidemiology and public health students titled: "Framework for Interpreting Time Series Data". During my MAE experience I contributed to the work of KPHU through these epidemiological projects. The work documented in this thesis contributed to the understanding of the epidemiology of communicable and non-communicable disease in the Aboriginal and Torres Strait Islander population in WA, with a particular focus on remote health and recommendations for improved health service delivery.

This thesis presents four projects along with additional public health experience to meet the competency requirements of the Master of Philosophy in Applied Epidemiology, undertaken at ACT Health in Canberra, working in the Communicable Disease Control section from February 2018 to December 2019. I undertook a cohort study following a cluster of gastrointestinal illness after a restaurant dinner. Bacillus cereus was identified as the likely cause. We identified inadequate hygiene practices and undocumented heating and cooling procedures which were rectified following our investigations. I presented this outbreak to the National Centre for Epidemiology and Population Health and to OzFoodNet at a face-to-face meeting. This outbreak was also published in the Communicable Disease Intelligence Journal in September, 2019. My data analysis project involved a descriptive review of 2009-2018 gonococcal notifications and antibiotic susceptibility test results. This study found that although notification rates have increased 5-fold since 2009, antibiotic resistance has not increased in the ACT. A key finding was a considerable difference in the proportion of notifications receiving a test of culture between sexual health specialists and GPs. I recommended ongoing education of GPs, particularly because heterosexual females have seen the largest rate rise in notifications since 2014 and they are primarily seen by GPs rather than sexual health specialists. This project was presented orally at the PHAA CDCC conference in Canberra in November 2019. For my epidemiological study I designed and implemented a 12-month study to estimate antenatal pertussis and influenza vaccination uptake in the ACT, and to describe key determinants of uptake. In my chapter I present an analysis of the first 6-months of study data. We found the highest self-reported uptake of antenatal vaccination currently reported in the Australian literature, 95% for pertussis and 74% for influenza. We found that those earning more are more likely to receive influenza vaccines and receive it for free in their workplace. I recommend addressing this access and affordability issue. This study was presented orally at the New Zealand Immunisation conference in September 2019 and as a poster presentation at the PHAA CDCC conference in Canberra in November 2019. My surveillance project involved developing a surveillance and response plan to control and manage the threat of antimicrobial resistance of N. gonorrhoea and shigella. Recommendations were made including: what data should be collected, how to capture the data using a new database system (REDCap), response guidelines upon identification of a multi-drug resistant case, and routine reporting. I also gained significant public health experience in contributing to the public health response for a number of small foodborne outbreaks, as well as measles, hepatitis A, typhoid and many Salmonella and Campylobacter investigations. This thesis presents my experiences and documents my competency to fulfil the requirements of the MAE and my contribution to frontline communicable disease control in the ACT and Australia.

This thesis details projects undertaken during my 22-month field placement in Australia and Cambodia. From February to December 2019, I undertook my MAE field placement at the Queensland Health Communicable Diseases Branch, which is responsible for the surveillance, prevention, and control of communicable diseases in Queensland. From January until late March 2020 I was based in Phnom Pehn, Cambodia, and undertook field placement with the Institut Pasteur Cambodia (IPC). IPC is a not-for-profit French foundation and manages one of only two laboratories in Cambodia. During this time, I was also seconded to support the Cambodian Ministry of Health COVID-19 response. On return to Australia in late March 2020, I was placed at the Doherty Institute in Melbourne and from July onwards was subsequently seconded on a part-time basis to the Victorian Department of Health and Human Services (DHHS) COVID-19 Public Health Intelligence team. My projects comprised: a multi-jurisdictional outbreak investigation of Salmonella Heidelberg, 2018-2019; investigating trends in the epidemiology of inter-seasonal influenza in Queensland, 2009-2019; exploring the feasibility of a surveillance mechanism for rapid viral suppression among those newly diagnosed with HIV in Queensland; and analysis of a malaria re-infection in a child cohort in Madang Province, Papua New Guinea, 2013. This thesis also describes other experiences and public health activities undertaken during my placements: involvement in trachoma screening and a sero-prevalence research project in Doomadgee, Northern Queensland; involvement in measles outbreak support activities in South Brisbane; data analysis support for a human leptospirosis case-control study in the Yangon Region, Myanmar; field epidemiological support to the Cambodian Ministry of Health in response to COVID-19; and involvement in COVID-19 outbreaks at the Victorian DHHS. These projects and experiences fulfil the core requirements of the Australian National University Master of Philosophy (Applied Epidemiology) program.tional University Master of Philosophy (Applied Epidemiology) program.

From 18 February 2019 to 26 February 2021 I undertook the Master of Philosophy in Applied Epidemiology at Menzies School of Health Research (Menzies) and Northern Territory Primary Health Network. Menzies is a research institute with a focus on improving Indigenous health and advancing global and tropical health. Primary Health Networks are non-government organisations that aim to improve the coordination of the primary health system, support the health workforce and introduce new health programs and services in line with community priorities. This thesis details the competencies undertaken during the MAE. The main projects that I completed are an evaluation of a novel antimicrobial surveillance system in northern Australia, an outbreak investigation of Clostridium perfringens among first responders to the Victorian Bushfires, a data analysis of potentially preventable hospitalisations (PPH) caused by cellulitis, and a sensitivity analysis of the Commonwealth's Health Care Homes (HCH) algorithm. Other competencies described in this thesis include a manuscript on the sensitivity analysis, presentations given, a low-literacy fact sheet, and peer-to-peer teaching materials. These competencies fulfil the core requirements of the MAE program.

Queensland Health's Communicable Diseases Branch is responsible for the monitoring, surveillance, prevention, and control of communicable diseases in Queensland. For the 22 months between February 2020 to December 2021, I undertook a field placement within the Communicable Diseases Branch. This thesis details the projects and experiences undertaken during this time. The projects include investigations of a COVID-19 outbreak commencing at a restaurant in southeast Queensland, a human salmonellosis outbreak associated with live backyard poultry in Australia, the establishment and evaluation of a SARS-CoV-2 test surveillance system used to identify SARS-CoV-2 resident testing in aged care facilities in Queensland, an analysis of site-specific chlamydia notifications in Queensland between 2000 to 2019, and an analysis to assess the effects of pneumococcal vaccination on invasive pneumococcal infection in Queensland between 2000 to 2020. Additionally, this thesis provides a description of other public health learnings and experiences gained during my placement, such as the establishment of the 'First few X' project in Queensland, participation in Queensland's trachoma screening program, my role in the Epi COVID-19 Team of Queensland's Public Health Incident Management Team (COVID-19), and my participation in teaching activities. The projects and experiences detailed in this thesis fulfil the core competencies of the Master of Philosophy (Applied Epidemiology) Program at the Australian National University.

The Communicable Diseases Branch (CDB) of Queensland Health has the role of protecting the health of Queenslanders through the monitoring, surveillance, and control of communicable diseases. From February 2016 to December 2017, I undertook a field placement within the CDB. This thesis details projects undertaken during this 22-month field placement. The projects comprise an investigation of a Q fever outbreak at an animal refuge clinic and veterinary clinic, the establishment of a surveillance system to identify newly acquired hepatitis C infections in Queensland, an analysis of vaccine breakthrough invasive pneumococcal disease in Queensland in children younger than 5 years of age, and an analysis of the risk of recurrent invasive pneumococcal disease in Queensland. Also described in this thesis are other public health experiences gained during my placement, including my role in teaching, an assessment of the need to include rheumatic heart disease as a notifiable condition in Queensland, a WHO Western Pacific Regional Office consultancy, and a lookback investigation of a dental clinic. Together, these projects and experiences fulfil the core requirements of the Master of Philosophy (Applied Epidemiology) program at Australian National University.