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The Ecological Context of Diseases of Public Health Importance Thesis Submitted in Accordance with the Requirements of the Unive

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The Ecological Context of Diseases of Public Health Importance Thesis Submitted in Accordance with the Requirements of the Unive The ecological context of diseases of public health importance Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Bethany Anne Levick May 2017 Preface I hereby declare that this thesis consists of my own work, unless otherwise stated, and has not previously been submitted to the University of Liverpool or any other University in application of a higher degree. This text does not exceed 100,000 words and meets the formatting requirements of the University of Liverpool. Contents Abstract .......................................................................................................................... 5 Acknowledgements ........................................................................................................ 6 Author contribution ........................................................................................................ 7 List of tables ................................................................................................................... 8 Chapter 2 .................................................................................................................... 8 Chapter 3 .................................................................................................................... 8 Chapter 4 .................................................................................................................... 8 Chapter 5 .................................................................................................................... 9 List of figures ............................................................................................................... 10 Chapter 1 .................................................................................................................. 10 Chapter 3 .................................................................................................................. 10 Chapter 4 .................................................................................................................. 11 Chapter 5 .................................................................................................................. 11 1. Ecological field data provides insights into disease ecosystems with implications for public health. ................................................................................................................ 13 1.1 Yersinia pestis epizootics in a community of wild rodents in Kazakhstan. .. 13 1.2 Onchocerciasis associated epilepsy in the Democratic Republic of Congo. 20 1.3 References ..................................................................................................... 24 2. The Perfect Burrow, but for what? Identifying local habitat conditions promoting the presence of host and vector species in the Kazakh plague system. ....................... 27 2.1. Introduction ....................................................................................................... 27 2.2. Aims and hypotheses ......................................................................................... 29 2.3. Methods ............................................................................................................. 29 2.4. Results ............................................................................................................... 37 2.5. Discussion ......................................................................................................... 41 2.6. References ......................................................................................................... 46 3. Predicting gerbil occupancy: a metapopulation model, and assessment of population connectivity. ................................................................................................................. 50 3.1. Introduction ....................................................................................................... 50 3.2. Aims and hypotheses ......................................................................................... 54 3.3. Methods ............................................................................................................. 55 3.4. Results ............................................................................................................... 61 3.5. Discussion ......................................................................................................... 69 3.6. References ......................................................................................................... 74 4. Distribution and dynamics of Y. pestis isolates lacking the fraction 1 (F1) antigen in a wild rodent population. ............................................................................................. 76 4.1 Introduction ........................................................................................................ 76 4.2 Aims and hypotheses .......................................................................................... 77 4.3 Methods .............................................................................................................. 77 4.4 Results ................................................................................................................ 81 4.5 Discussion .......................................................................................................... 89 4.6 References .......................................................................................................... 92 5. Onchocerciasis associated epilepsy in the Democratic Republic of Congo ............ 97 5.1 Introduction ........................................................................................................ 97 5.2. Aim and hypotheses ........................................................................................ 100 5.3 Methods ............................................................................................................ 100 5.4 Results .............................................................................................................. 105 5.5 Discussion ........................................................................................................ 117 5.6 References ........................................................................................................ 121 6. Discussion .............................................................................................................. 125 6.1 References ........................................................................................................ 133 Appendices ................................................................................................................. 137 Abstract The ecological context of diseases of public health importance Bethany Levick The prevention and control of infectious disease continues to be a central priority for human public health. Two infectious agents, the bacterium Yersinia pestis and the filarial nematode Onchocerca volvulus have been responsible for significant public health burden in many populations, and challenges remain in the control and prevention of them both. With known environmental and climatic drivers, vector based transmission and in the case of Y. pestis, zoonotic reservoirs, fully characterising the ecological context of both diseases is vital to properly understanding their epidemiology. In the present study, ecological field data is utilised to investigate this, towards improving predictions and designing control strategies. Despite being contrasting infectious agents, the role of spatial scale and resolution are identified to be vital aspects of both investigations. Ultimately, the importance of a holistic approach to infectious disease epidemiology is highlighted across both systems. In humans and some other animals, infection with Yersina pestis causes the disease plague. Although human infections are now limited to the hundreds annually, they disproportionately affect individuals in lower income settings and as such are still of public health concern. A number of wild rodent species tolerant to infection with Y. pestis act as reservoirs for the bacterium, from which it can transmit into less tolerant susceptible populations. To this end, much research has focused on predicting periods of high infection prevalence (epizootic outbreaks) in the reservoir species in order to predict and prevent transmission events into less tolerant populations. One such reservoir species is the great gerbil, Rhombomys opimus, residing across the pre Balkhash desert in Kazakhstan. Y. pestis prevalence in this population is known to be strongly associated with the gerbil population size. The present study aims to resolve current ability to predict the gerbil population. Burrow level environmental properties are identified to be predictors of gerbil presence at, and long term occupancy of burrows. Gerbil occupancy of burrows could not be replicated using standard metapopulation approaches, nor related to the connectivity of the burrow. Atypical strains of Y. pestis lacking the fraction 1 (F1) surface antigen are isolated and found to be common in the gerbil population. This antigen is highly immunogenic and has a role in virulence determinance. However, no significant hetereogeneities in their distribution or associations with epidemiological outputs could be identified. In several African countries with endemic levels of infection with Onchocerca volvulus, an unusually high prevalence
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