Genome evolution and epidemiology of human pathogens
<p>Understanding the transmission dynamics of infectious diseases is important to well-informed public health policy, responsive infection control and individual patient management. The on-going revolution in whole-genome sequencing provides unprecedented resolution for detecting evidence of r...
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| Format: | Thesis |
| Language: | English |
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2013
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| _version_ | 1797112508452962304 |
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| author | Dearlove, BL |
| author2 | Wilson, DJ |
| author_facet | Wilson, DJ Dearlove, BL |
| author_sort | Dearlove, BL |
| collection | OXFORD |
| description | <p>Understanding the transmission dynamics of infectious diseases is important to well-informed public health policy, responsive infection control and individual patient management. The on-going revolution in whole-genome sequencing provides unprecedented resolution for detecting evidence of recent transmission and characterising population-level transmission dynamics. In this thesis, I develop and apply evolutionary approaches to investigating transmission, focusing on three globally important pathogens.</p> <p>Hepatitis C virus (HCV) is a major cause of liver disease affecting 150 million people and killing 350,000 annually. I conducted a meta-analysis of twentieth-century HCV epidemics, finding that the age of the epidemic can be predicted by genetic diversity. Using the coalescent, I fitted classic susceptible-infected (SI), susceptible-infected-susceptible (SIS) and susceptible-infected-recovered (SIR) epidemiological models. Most epidemics showed signatures of SI dynamics, but three, from Argentina, Hong Kong and Thailand, revealed complex SIR dynamics.</p> <p>Norovirus is the leading viral cause of diarrhoea, estimated to cost the NHS around £115 million annually. I analysed whole norovirus genomes via a stochastic transmission model, finding that up to 86% of hospital infection was attributable to transmission from another patient in the hospital. In contrast, the rate of new introductions to hospital by infected patients was extremely low (<0.0001%), underlining the importance of ward management during outbreaks.</p> <p><em>Campylobacter</em> is the most commonly identified cause of bacterial gastroenteritis worldwide. I developed a zoonotic transmission model based on phylogeography approaches to test whether three strains previously associated with multiple host species were in fact aggregates of strongly host-restricted sub-strains, or genuine generalists. Members of the same strain isolated from different host species were often more closely related than those isolated from the same host species. I estimated 419, 389 and 31 zoonotic transmissions in ST-21, ST-45 and ST-828 respectively, strongly supporting the hypothesis that these strains are adapted to a generalist lifestyle.</p> |
| first_indexed | 2024-03-07T08:25:05Z |
| format | Thesis |
| id | oxford-uuid:af385d35-ca1a-4f4c-ae1a-0ad954cab928 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:25:05Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:af385d35-ca1a-4f4c-ae1a-0ad954cab9282024-02-14T11:10:30ZGenome evolution and epidemiology of human pathogensThesishttp://purl.org/coar/resource_type/c_db06uuid:af385d35-ca1a-4f4c-ae1a-0ad954cab928EpidemiologyVirusesGenetics (medical sciences)Infectious diseasesEvolution (zoology)EnglishOxford University Research Archive - Valet2013Dearlove, BLWilson, DJDonnelly, PJ<p>Understanding the transmission dynamics of infectious diseases is important to well-informed public health policy, responsive infection control and individual patient management. The on-going revolution in whole-genome sequencing provides unprecedented resolution for detecting evidence of recent transmission and characterising population-level transmission dynamics. In this thesis, I develop and apply evolutionary approaches to investigating transmission, focusing on three globally important pathogens.</p> <p>Hepatitis C virus (HCV) is a major cause of liver disease affecting 150 million people and killing 350,000 annually. I conducted a meta-analysis of twentieth-century HCV epidemics, finding that the age of the epidemic can be predicted by genetic diversity. Using the coalescent, I fitted classic susceptible-infected (SI), susceptible-infected-susceptible (SIS) and susceptible-infected-recovered (SIR) epidemiological models. Most epidemics showed signatures of SI dynamics, but three, from Argentina, Hong Kong and Thailand, revealed complex SIR dynamics.</p> <p>Norovirus is the leading viral cause of diarrhoea, estimated to cost the NHS around £115 million annually. I analysed whole norovirus genomes via a stochastic transmission model, finding that up to 86% of hospital infection was attributable to transmission from another patient in the hospital. In contrast, the rate of new introductions to hospital by infected patients was extremely low (<0.0001%), underlining the importance of ward management during outbreaks.</p> <p><em>Campylobacter</em> is the most commonly identified cause of bacterial gastroenteritis worldwide. I developed a zoonotic transmission model based on phylogeography approaches to test whether three strains previously associated with multiple host species were in fact aggregates of strongly host-restricted sub-strains, or genuine generalists. Members of the same strain isolated from different host species were often more closely related than those isolated from the same host species. I estimated 419, 389 and 31 zoonotic transmissions in ST-21, ST-45 and ST-828 respectively, strongly supporting the hypothesis that these strains are adapted to a generalist lifestyle.</p> |
| spellingShingle | Epidemiology Viruses Genetics (medical sciences) Infectious diseases Evolution (zoology) Dearlove, BL Genome evolution and epidemiology of human pathogens |
| title | Genome evolution and epidemiology of human pathogens |
| title_full | Genome evolution and epidemiology of human pathogens |
| title_fullStr | Genome evolution and epidemiology of human pathogens |
| title_full_unstemmed | Genome evolution and epidemiology of human pathogens |
| title_short | Genome evolution and epidemiology of human pathogens |
| title_sort | genome evolution and epidemiology of human pathogens |
| topic | Epidemiology Viruses Genetics (medical sciences) Infectious diseases Evolution (zoology) |
| work_keys_str_mv | AT dearlovebl genomeevolutionandepidemiologyofhumanpathogens |