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1
Petersson, Ramona. "Molecular epidemiology of tuberculosis." Stockholm : Umeå universitet, 2009. http://diss.kib.ki.se/2009/978-91-7409-456-5/.
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Kulaga, Sophie. "Molecular epidemiology of tuberculosis transmission." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84278.
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We conducted a molecular epidemiologic study of tuberculosis (TB) transmission during the years 1996--98 on the Island of Montreal. By combining public health data on the 528 reported cases with IS6110 DNA fingerprints for 430, we detected an overall low frequency of transmission manifesting as secondary cases of active disease. We also identified an important sub-group of TB patients who harbour isolates with matching patterns. Depending on the matching criterion used we attributed between 6% (95% CI: 4, 9%) and 22% (95% CI: 18, 27%) of TB cases to recent transmission; the vast majority of active TB disease reflects infection acquired at an earlier time and/or a different place. However, Haitian-born TB patients yielded a disproportionately high frequency of isolates belonging to matching "clusters" (21%; 95% CI: 13, 32%), while, other foreign-born patients have disproportionately low numbers of clustered isolates (5%; 95% CI: 3, 9%).The classical interpretation of such results is that there is more ongoing transmission within this immigrant sub-group. We explored an alternative hypothesis: that M. tuberculosis isolates from Haitian-born patients demonstrate reduced genetic diversity reflecting TB transmission patterns in their previously isolated country of origin---hence that a bacterial founder effect accounts for the higher frequency of matching fingerprints. Using a recently introduced measure of fingerprint similarity, genetic distance, we assessed the extent of pattern diversity. The median nearest genetic distance (NGD) was 130 months (inter-quartile range (IQR): 98--201 months) among the 47 distinct isolates from Haitian-born patients; among the non-Haitian foreign-born, the median NGD for the 191 distinct isolates was 128 months (IQR: 103--170 months). Hence the overall genetic heterogeneity of M. tuberculosis organisms among Haitian-born Montrealers was as great as that among a group of patients born in 70 other countries. Local transmission among the Haitian-born remains the most likely scenario.
We demonstrated that a continuous measure, such as genetic distance, may also permit researchers to address a challenge to the interpretation of M. tuberculosis molecular typing results: how to determine whether highly similar, non-identical fingerprint patterns in fact reflect underlying "matches." The distribution of NGD for isolates initially classified as identical (10--27 months), similar (15--108 months) and unique (40--244 months) suggested a possible cut-point of 40 months. Use of this cut-point labelled 19% of isolates as "clustered", suggesting that 14% of Montreal TB cases reflected transmission during the study period.
3
Shrivastava, Jaya. "Molecular epidemiology of Schistosoma japonicum." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414227.
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Taweenan, Weerapol. "Molecular epidemiology of Giardia duodenalis." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539914.
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Giardia duodenalis is a parasitic protozoan that affects the gastrointestinal tract, causing abdominal disorders of various animals and humans. To date, G. duodenalis has been genotypically divided into seven groups (assemblages), namely A to G, found in different host ranges. Whilst assemblages C to G are specific genotypes affecting restricted animal hosts, assemblages A and B parasitise both humans and a number of animal species, and have been considered as having zoonotic potential. The main objective of the current study was to investigate the molecular epidemiology of G. duodenalis in animals and humans in the UK. The current study also evaluated multilocus genotyping and determined the protein changes between assemblages A and B.
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Parkar, Unaiza. "Molecular epidemiology of Blastocystis infections." Thesis, Parkar, Unaiza (2016) Molecular epidemiology of Blastocystis infections. PhD thesis, Murdoch University, 2016. https://researchrepository.murdoch.edu.au/id/eprint/33832/.
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Blastocystis is an enteric protist and one of the most frequently reported parasitic infections in humans and a variety of animal hosts worldwide. The genus Blastocystis consists of numerous genetically distinct groups, referred to as subtypes (STs). Some STs are highly host specific, while others display moderate or low host specificity. Therefore, the aims of this study were to determine the prevalence amongst various animal hosts (captive, free-ranging and wild), genetic diversity and zoonotic potential of Blastocystis. As polyparasitism is considered to be the norm in wildlife, the final aim of this study was to develop a molecular-based diagnostic method for the simultaneous detection of Blastocystis, Cryptosporidium sp. and Giardia duodenalis in Australian native fauna.
These aims were achieved by sampling captive animals and their keepers from the Perth Zoo. Also, animal samples were obtained from other zoos in Australia and Europe. Samples from free-ranging and wild non-human primates (NHPs) and Australian native fauna were also included in this study. All samples were screened for Blastocystis using Polymerase Chain Reaction (PCR), followed by phylogenetic analyses to characterise these isolates in order to determine the genetic diversity and zoonotic potential of isolates within the Blastocystis genus.
Blastocystis was detected in 13 species of animals from the Perth Zoo. It was also detected in NHPs from Belgian zoos. All wild and free-ranging NHP and Australian wildlife populations also harboured Blastocystis. This study describes the first reports of Blastocystis in the elephant, giraffe, Javan lutung, quokka, southern hairy nosed wombat and western grey kangaroo.
Similarly, 12 Blastocystis STs, including six novel STs (STs 11 – 13 and 18 – 20), were identified in humans and animal hosts sampled as part of this study. Blastocystis STs 1, 2, 18 and 19 were identified in captive NHPs. However, STs 2, 8 and 20 were identified in wild NHPs. Australian native animals at the Perth Zoo harboured STs 1, 12 and 13, whereas free-ranging animals from Karakamia Sanctuary (KS) and wild animals from the Upper Warren Region (UWR) harboured STs 1 – 4 and 7. Captive elephants and giraffes from Australian and European zoos harboured STs 11 and 12, respectively.
Higher prevalence of Blastocystis amongst zoo keepers and sequence homology of isolates from zoo keepers and animals at the Perth Zoo provide evidence of the zoonotic potential of Blastocystis. High prevalence amongst zoo keepers may be due to close contact between the animals and the zoo keepers, and other tasks carried out by the zoo keepers, such as cleaning of enclosures. Similarly, some Blastocystis isolates from Australian wildlife were also homologous to human isolates, and it seems that these hosts are natural hosts for the zoonotic ST 4.
Other parasites, such as strongyle nematodes and coccidia were detected using microscopy. Various species of Australian wildlife are known to harbour these and other parasites, including zoonotic parasites, such as Cryptosporidium sp. and Giardia duodenalis. As polyparasitism is considered to be the norm in wildlife, a multiplex PCR (mPCR) was developed to detect Blastocystis, Cryptosporidium and Giardia simultaneously from Australian wildlife. This mPCR was evaluated against other diagnostic methods routinely used for the detection of these parasites, such as microscopy and nested PCRs. The multiplex PCR showed comparative and/or greater sensitivity and specificity to routinely utilised nested PCRs. The major advantages of the multiplex PCR are that it is less labour intensive and is cost effective in comparison to the nested PCRs used to amplify each parasite.
In conclusion, the host range and genetic diversity of Blastocystis is much greater than previously anticipated. Some STs and/or subgroups of STs appear to be highly host specific, while others display moderate or low host specificity. Also, some STs which have a broad host range may be zoonotic. This study also provides further insight into polyparasitism amongst Australian wildlife.
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Andrés, Vergés Cristina. "Los Picornavirus. De la levedad a la gravedad." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669845.
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Minetti, Corrado. "The epidemiology and molecular epidemiology of Giardiasis in North West England." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2006698/.
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Giardiasis, cause by the parasitic protozoan Giardia duodenalis, is one of the most common infectious gastrointestinal diseases in humans worldwide. However, its true population burden and epidemiology and in particular its zoonotic transmission potential are still poorly understood. Furthermore, G. duodenalis is not a uniform parasite but a complex of seven genetic assemblages or cryptic species (named A to G) that infect humans and a variety of domesticated and wild animals, and that can only be distinguished using molecular genotyping methods. Although there is some evidence that the two Giardia assemblages infecting humans (namely A and B) may differ in their virulence and major transmission routes, data are still scarce. In the UK, several studies suggested that giardiasis is considerably under-diagnosed and a few data are available on the genetic diversity of the parasite causing infection and disease in this country. We investigated the burden, clinical outcomes, risk factors and molecular diversity of giardiasis in North West England using both a descriptive and analytical approach. In Chapter 2, we analysed the self-reported clinical and exposure data collected over four years from clinical cases of giardiasis in Central Lancashire, as part of an enhanced surveillance program on the illness. The resulting average disease rate of 22.5 cases/100,000 population was high when compared to the available national figures. Giardiasis was particularly abundant in adults in their 30s and children under five, and the disease rate in males was significantly higher than in females. Furthermore, the clinical picture of the cases confirmed the high morbidity associated with this infection particularly in terms of the length of illness and severity of symptoms. Only 32% of the cases reported foreign travel during the exposure window. The results suggested the presence of a hidden burden of disease in adults and males, and indicated that local transmission of Giardia can be more common than expected. In Chapter 3, we performed a case-control study to determine the significant risk factors for symptomatic giardiasis in North West England, by recruiting clinical cases of Giardia and age and sex matched controls from Central and East Lancashire and Greater Manchester. The multivariable logistic regression analysis done on 118 cases and 226 controls revealed that overall travelling abroad (particularly to developing countries) was an important risk factor for the illness (OR 9.59). Following the exclusion of participants that reported foreign travel, four risk factors were significant for the acquisition of giardiasis: going to a swimming pool (OR 2.67), changing nappies (OR 3.38), suffering irritable bowel syndrome (OR 3.66) and drinking un-boiled water from the tap (OR 8.17). The results indicated the important role of swimming pools and contact with children in nappies for the transmission of the parasite. In Chapter 4, whole faecal DNA was extracted from the faecal samples of the cases part of the surveillance and case-control studies and the Giardia assemblages and sub-assemblages causing infection were determined using PCR amplification and DNA sequencing of up to four parasite genes (beta-giardin, glutamate dehydrogenase, triose-phosphate isomerase and small-subunit ribosomal RNA). The majority of infections (64%) were caused by assemblage B, followed by assemblage A (33%), whereas mixed-assemblage infections were rare (3%). The majority of the assemblage A isolates belonged to the sub-assemblage AII and showed completed identity with previously described isolates, and six multi-locus genotypes were identified. The level of genetic sub-structuring as revealed by phylogenetic analysis was significantly higher in assemblage B isolates compared with A isolates: a higher proportion of novel assemblage B sequences was detected compared to what was observed in assemblage A isolates. A high number of assemblage B sequences showed heterogeneous nucleotide positions that prevented the unambiguous assignment to a specific sub-assemblage. Up to 17 different assemblage B multi-locus genotypes were found. The molecular genotyping results showed that Giardia assemblage B was responsible for the majority of the clinical infections and confirmed the occurrence of a high diversity of parasite multi-locus genotypes. In Chapter 5, we integrated the epidemiological and the molecular data generated by the enhanced surveillance and case-control studies and we studied the clinico-epidemiological differences between cases infected with Giardia assemblage A or B. Our results showed a difference in the age prevalence between the two assemblages, with assemblage A being more common in older cases. Cases infected with assemblage B reported a series of symptoms more frequently than cases infected with assemblage A, as well as reporting a longer illness. Although the exposure profile of the cases largely overlapped between the two assemblages, two different types of exposures were reported more frequently in the two groups of cases: keeping a dog in assemblage A cases and the presence in the household of children and children at nursery in assemblage B cases. The results suggested that assemblage A could have a major zoonotic reservoir, whereas assemblage B could be transmitted more commonly via the human-to-human route.
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Punyapornwithaya, Veerasak. "Molecular epidemiology of mycoplasma mastitis outbreak." Pullman, Wash. : Washington State University, 2010. http://www.dissertations.wsu.edu/Dissertations/Spring2010/v_punyapornwithaya_042110.pdf.
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Ragonnet, Manon Lily. "Molecular Epidemiology of HIV in Canada." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20215.
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With over 35 million people currently infected, the World Health Organization considers HIV a global pandemic. HIV is characterized by a high mutation rate, which allows it to evade the host immune system and develop resistance to drugs. However, this extraordinary adaptive ability may also be the key to HIV’s demise. Through the field of phylodynamics, the evolutionary behavior of the virus is being studied in an attempt to control the epidemic. In this thesis, three papers are presented in which we analyze sequences generated through the Canadian HIV Strain and Drug Resistance Surveillance program. In chapter 2 we validate a classifier which distinguishes between recent and established infections based on the proportion of mixed bases observed in population-based pol sequences. Our results will help identify recent infections and improve incidence calculations. In chapter 3, we investigate immune-induced patterns in HIV that are shared by patients of the same ethnicity. An understanding of the forces shaping HIV evolution is instrumental to the development of a vaccine relevant to the Canadian epidemic. In chapter 4, we present preliminary results of a historical reconstruction of HIV across the provinces of Canada. This analysis will highlight strategies that have succeeded or failed in controlling the epidemic. Furthermore, our work will establish whether non-B subtypes of HIV are an increasing threat to Canadian public health. Overall, this thesis provides the first country-wide evolutionary and phylogenetic analysis of the HIV epidemic.
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Tu, Elise Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Molecular epidemiology and detection of norovirus." Publisher:University of New South Wales. Biotechnology & Biomolecular Sciences, 2008. http://handle.unsw.edu.au/1959.4/41562.
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Norovirus (NoV) is a major cause of infectious human viral gastroenteritis. Detection is important to understanding the epidemiology of NoV and the viral dynamics of NoV infection which is poorly understood. In 2006, a marked increase in gastroenteritis outbreaks occurred worldwide. During this period, a total of 231 stool samples were obtained from patients with acute gastroenteritis from Australia and New Zealand. A total of 186 isolates of NoV were detected and sequenced to determine the genotype and relatedness to known epidemic NoV GII.4 variants. Two GII.4 variants, 2006a and 2006b, were identified in 61.8% and 11.3%, in these cases, respectively. Thus, the increase in NoV gastroenteritis in 2006 was linked to the emergence of two novel co-circulating GII.4 variants, 2006a and 2006b. During an outbreak in an aged-care facility, stool samples were collected from the onset of illness to cessation of viral excretion. Here, viral shedding peaked in the acute stage of illness and continued for an average of 28.7 days. The viral decay rate was 0.76 per day. Prolonged asymptomatic shedding of NoV was detected in the elderly. A quality control for the assessment of molecular based viral assays for NoV and other RNA viruses is necessary to meet current testing requirements. Available controls only monitor the RNA and DNA amplification steps. An MS2 bacteriophage BioBallTM with 100 pfu was evaluated and applied as a multi-purpose phage control. It was assessed as a quality control, in comparison to MS2 phage stock, to validate MS2 phage assays. Furthermore, MS2 BioBallTM was used as a process control for the molecular detection of RNA viruses. It validated every performed step, determined if the assay worked and its sensitivity. Thus, MS2 BioBallTM offered uniformity, stability and reproducibility across molecular based viral detection systems. Overall, this thesis provided valuable insight into the molecular epidemiology of NoV in the southern hemisphere and nature of NoV infections in the elderly. The MS2 BioBallTM provides standardisation and quality control of viral RNA assays. Understanding the genetic diversity and viral dynamics of NoV will be crucial to developing effective intervention and treatment strategies, and ultimately lead to reduced viral gastroenteritis worldwide.
11
Sloane, Julia Yvette. "Molecular epidemiology of Arcobacter in cattle." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533924.
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Li, Zhen, and 李珍. "Molecular epidemiology of carbapenem-resistant enterobacteriaceae." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B5016286X.
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Dissemination of Carbapenem-Resistant Enterobacteriaceae (CRE) has raised a new challenge for health organizations all over the world. Acquisition of carbapenemase genes is the most worrisome among these CRE isolates.
This study was constructed to investigate the dissemination of CRE isolates in Hong Kong and also to characterize plasmids harboring carbapenemase genes.
CRE isolates were collected from public hospitals in Hong Kong from August 2006 to June 2012. Antimicrobial susceptibility of all CRE isolates was tested using disc diffusion method. Screening of carbapenemase genes (blaNDM , blaKPC, blaIMP, blaVIM and blaOXA-48) and ESBL genes (blaCTX-M and blaSHV) were also performed. Clonal relatedness was studied by multi-locus sequence typing. Characterization of plasmids was carried out by conjugation, S1-PFGE, hybridization and plasmid replicon typing.
A total of 69 CRE isolates were collected including 50 K. pneumoniae, 15 E. coli, 2 E. cloacae, 1 E. aerogenes and 1 C. freundii. Eighteen carbapenemase producing Enterobacteriaceae were isolated from different patients with travel histories among these 69 isolates. Four K. pneumoniae were detected to carry blaKPC genes on different transferable plasmids as follows: 50 kb, IncX3 plasmid (ST258); 70 kb, un-typeable plasmid (ST258); 130 kb, un-typeable plasmid (ST11) and 140 kb, un-typeable plasmid (ST11). blaIMP genes were also detected in four CRE isolates to be harbored by different plasmids or located on chromosome: ST11 K. pneumoniae (50 kb, IncN), ST1 K. pneumoniae (150 kb, IncA/C), E. cloacae (130 kb, IncN-L/M) and ST899 K. pneumoniae (chromosomal located).
NDM-1 (New Delhi Metallo enzyme) producing E. coli (n = 5), K. pneumoniae (n = 2), E. aerogenes (n = 1), E. cloacae (n = 1) and C. freundii (n =1) were also found in this study. Eight of them were isolated from patients travelled to different provinces of China blaNDM-1 was found to be carried by transferable plasmids in all ten isolates: IncX3 (n = 7, 50 kb), IncL/M (n = 1, 88 kb), IncA/C2 (n = 1, 140 kb) and FIIY- FIBS (n = 1, 110kb). Six of the seven IncX3 plasmids showed identical digestion profile while the other one only had two bands different from others using Restriction fragment length polymorphism (RFLP) analysis.
An IncX3 plasmid pNDM-HN380 from a K. pneumoniae strain CRE380 was completely sequenced using Genome Sequencer FLX (Roche, USA). pNDM-HN380 was a 54,035 bp circular plasmid with 52 open reading frames (ORFs). The backbone of pNDM-HN380 was identical to those previous described IncX plasmids pIncX-SHV (accession number JN247852) and pEC14_35 (accession number JN935899). The blaNDM-1 gene was carried on an ISAba125 and IS26 flanked transposon-like element. And this element except IS26 and an interrupted ISAba125 was found to be identical to pNDM-BJ01 (accession number JQ001791).
In conclusion, this is the first we describe a blaNDM-1 carrying IncX3 plasmid. This IncX3 plasmid was found to be predominant in the dissemination of blaNDM-1 in China. Future study of the nationwide dissemination of carbapenemase genes and also the novel IncX3 plasmids is needed.published_or_final_version
Microbiology
Master
Master of Philosophy
13
Mok, Sin-yee, and 莫倩儀. "Molecular epidemiology of coronaviruses in animals." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193535.
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As the animals are an ongoing source of the coronaviruses, more and more bird coronaviruses were found as Deltacoronavirus recently, their abilities to fly over a long distances from place to place increase the potential of spreading the CoVs to other animals. Therefore it is a need to study and investigate the CoVs circulating in different animals. In this study, a total of 2792 samples from 103 cats, 96 dogs, 19 dolphins, 20 sea lions, 6 seals, 4 red pandas, 4 giant pandas, 4 Asian small-clawed otters, 9 tortoises, 7 monkeys, 2 bears, 2 capybaras, 231 Horses, 94China rodents were screened for the presence of coronaviruses using pan-CoVs PCR primers targeting the partial RdRp gene of coronaviruses. We also particularly looked for Deltacoronaviruses (Group 4 coronaviruses), using Group 4 CoVs consensus primers. Thirteen stray cat samples, including samples 01-03 and 05-14, one stray dog sample (sample 04) and one rodent sample (sample 15) were found to be positive for CoVs. However, none of the samples were found to be positive using Group 4 CoVs consensus primers. The DNA sequence of partial RdRp of sample 05-14 were identical and sample 02-03 also had a sequence identity of 100% while sample 01 had slightly different in the RdRp DNA sequence with the others. Phylogenetic analysis based on the DNA sequence of partial RdRp revealed that sample 01-14 belonged to Alphaconoavirus, sample 02-03 formed a cluster with FCoV-UU31 (95% nucleotide identities), sample 01 clustered together with FCoV-black (98% nucleotide identities), sample 04 and 05-14 being more closely-related to CCoV-S378 (96% nucleotide identities) and FCoV-UU7(98% nucleotide identities) respectively. However, sample 15 formed a distinct cluster with MHV-1(89% nucleotide identities) within Betacoronavirus. All the thirteen isolates (sample 01-03, 05-14) within Alphaconoavirus were identical in terms of their partial RdRp amino acid sequence while sample 04 had 100% identity to CCoV-S378 and sample 015 had 90% identity to MHV-1.The phylogenetic analysis of the partial RdRp amino acid sequence also revealed similar result as the DNA sequence. To sum up, coronavirus is more common in cats rather than in dogs, rodents, horses and other mammals examined in this study. However, none of the Detacoronavirus was found from all the animal samples.published_or_final_version
Microbiology
Master
Master of Medical Sciences
14
Lau, Siu Ha. "Molecular epidemiology of pathogenic escherichia coli." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517731.
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Glatzel, Markus. "Epidemiology and molecular pathology of prion diseases /." Zürich, 2003. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253382.
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Hays, John Philip. "The molecular epidemiology of human coronaviruses 229E." Thesis, University of Leicester, 1997. http://hdl.handle.net/2381/29826.
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A combined human coronavirus 229E/OC43 nested multiplex nucleocapsid gene PCR and South-western blotting protocol was developed and utilised to screen clinical specimens for the presence of human coronaviruses 229F and human coronaviruses OC43. Clinical specimens comprised 100 nasal washings obtained from children with asthma at the Leicester Royal Infirmary, Leicester, U.K. in 1990 and 200 nasal secretions obtained from adults presenting with the common cold in Kumasi, Ghana, in 1993. Fourteen of the U.K. clinical specimens were found to contain human coronaviruses (12 human coronavirus 229E and 2 human coronavirus OC43) whilst 43 of the African clinical specimens were found to contain human coronaviruses (26 human coronavirus 229E and 17 human coronaviruses OC430). A nested human coronavirus 229E spike gene cycle sequencing PCR protocol was also developed and utilised to generate sequence data from the spike genes of chronologically and geographically distinct human coronaviruses 229E (these chronologically and geographically distinct human coronavirus 229E isolates comprising :- a) reference human coronavirus 229E American Type Culture Collection (ATCC) strain VR-74, b) U.K. human coronavirus 229E isolate LR! 281 and c) African human coronavirus 229E isolate A162). Sequence data was obtained from approximately 90% of the spike genes of these isolates. When the resultant human coronavirus 229E spike gene sequences were translated into protein and compared with one another, it was found that the translated human coronavirus spike protein sequences were relatively similar between these chronologically and geographically distinct isolates. These results may indicate that spike gene variation is not a major factor in the aetiology of human coronavirus 229E re-infection.
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Zetsma, Julia Wendelina. "Molecular diagnosis and epidemiology of Mycoplasma pneumoniae." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/83311.
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Ho, Yat-man Alex, and 何逸敏. "Molecular epidemiology of multidrug-resistant Acinetobacter baumannii." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197078.
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Acinetobacter baumannii is an important nosocomial pathogen worldwide because of its remarkable ability to acquire antibiotic resistance. The global emergences of multidrug-resistant A. baumannii (MDR-AB) clones are predominated by a number of widely disseminated clones, namely clonal complex (CC) 1, CC2, and CC3. In early 2010, we reported two major clones of MDR-AB, designated HKU1 and HKU2 belong to sequence types (ST) 96 and ST92, widely disseminating in our hospitals. ST92 is a predominant clone that is prevalent in more than 30 countries, whereas ST96 has been identified recently and is geographically confined to certain parts of China. Our previous study only investigated the isolates collected in the year 2005-2006. We therefore extended our investigation over a six-year period (2005-2010) to generate a more complete picture of the molecular epidemiology and resistance mechanisms in A. baumannii.
Firstly, we performed the susceptibility test on various antimicrobial agents and employed molecular methods to characterize the epidemiology of the target A. baumannii isolates. For the entire study period, increased resistance rates were noted for the seven antimicrobial agents, namely imipenem, piperacillin-tazobactam, cefoperazone, ticarcillin-clavulanate, ciprofloxacin, gentamicin and amikacin (P <0.01). Worryingly, an increased trend was also observed for the pandrug-resistant rate, from 0.2% in the year 2005-2006, to 1.9-2.9% in the year 2007-2008 and up to 6.0-8.1% in the year 2009-2010 (chi square for trend, P <0.001). Pulsed-field gel electrophoresis and multilocus sequence typing (PFGE/MLST) categorized 100 out of 108 (92.6%) isolates into four clones (PFGE/MLST), namely HKU2/ST92 (n = 14), HKU3/ST254 (n = 73), HKU4/ST137 (n = 5), and HKU5/ST362 (n = 8), respectively. PCR showed that 88.9% (96/108) of the amikacin-resistant isolates were armA positive and all isolates were found to harbour at least one of the OXA-type carbapenemases with frequencies as follows: OXA-51-like (98/108, 90.7%), OXA-23-like (85/108, 78.7%), OXA-58-like (9/108, 8.3%) and OXA-24-like (8/108, 7.4%).
Secondly, we compared the biological fitness of the circulating clones by performing the doubling time and adhesion experiment. The results demonstrated that HKU3/ST254 has a higher capability for replication and adherence to human bronchial epithelial cells. Together with the higher antibiotic resistance rate, the selective advantages in terms of biological fitness may facilitate the clonal expansion and wide dissemination of this lineage.
Finally, whole genome sequence data showed a high amount of resistance genes intermixed with various insertion sequence (IS) elements, integrons and transponsons clustering inside the resistance islands. The presence of a second genomic resistance island conferring aminoglycoside and sulphonamide resistance, additional loci outside the resistance islands harbouring resistance genes and the high amount of antibiotic efflux pumps in various A. baumannii genomes demonstrated that resistance islands contribute a significant part to the multidrug-resistant phenotype in A. baumannii but are not the only factor. The correlation analysis further demonstrated the significance of IS elements in the dissemination of antibiotic resistance genes in the A. baumannii genomes. As a whole, whole genome sequence data may provide an informative and efficient approach to generating a more comprehensive picture to study the resistance mechanism of the epidemic strains.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
19
Brook, Emily Jane. "The molecular epidemiology of cryptosporidiosis in cattle." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437515.
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Abbas-Ghavimi, Khosro. "Molecular epidemiology of Neisseria gonorrhoeae in Scotland." Thesis, University of Aberdeen, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400672.
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The incidence of Gonococcal infection in Grampian region was the highest in Scotland in 1992, 1993 and 1994. Despite a considerable decrease in 1994, it remained more than twice that of the whole country. Grampian also differed from other regions in that 1A isolates were commoner, accounting for around 78%, 73% and 75% of isolates; the 1A-2 serovar was particularly common. The proportion of 1B isolates in Grampian (22%, 27% and 25%) was low compared with the other centres where 1B accounted for around 70% of all isolates (Young & Moyes, 1996). Seventy-six 1992, 1993 and 1994 clinical isolates of various serotypes were obtained from the Scottish Neisseria gonorrhoeae Reference Laboratory including 40 strains from Grampian and 36 strains from Lothian. Genomic DNA was subjected to pulsed-field gel electrophoresis (PFGE) after digestion with low-frequency cleavage (LFC) endonucleases Nhe I and Spe I. The restriction patterns generated were reproducible, stable and easy to read. PFGE was compared to restriction endonuclease analysis (REA) with high-frequency cleavage (HFC) endonuclease Hind III, and 16S rDNA ribotyping with EcoR I. The comparison of phenotypic based typing methods and DNA-based typing techniques to study the 76 N. gonorrhoeae isolates in the present study indicate that the DNA-based methods are more discriminatory. However, the patterns obtained by NheI and Spe I PFGE analysis were easily interpreted, reliable and more discriminatory than those of Hind III REA. The finding of this study clearly demonstrate the potential of PFGE as a high discriminatory tool, as compared to MAb-based serotyping, auxotyping, S/A classification, 16S rDNA ribotyping and REA for studying the molecular epidemiology of gonorrhoea.
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Forrester, Naomi Lynne. "Molecular epidemiology of rabbit haemorrhagic disease virus." Thesis, University of Liverpool, 2005. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422106.
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Evans, Jason Thomas. "Molecular epidemiology of tuberculosis in the Midlands." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3416/.
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Data from this thesis has extended our understanding of the molecular epidemiology and transmission of Mycobacterium tuberculosis in the Midlands. A novel DNA fingerprinting method called Mycobacterial Interspersed Repetitive Units containing Variable Number Tandem Repeats (MIRU-VNTR) typing provided equivalent results when compared to the current gold standard for DNA fingerprinting (IS6110 RFLP). To improve our understanding of TB in the Midlands, MIRU-VNTR typing was then developed to be assayed by non-dHPLC for the first time. Using this high-throughput rapid method a prospective and universal typing study was undertaken. This work identified the predominance of the Euro-American and East African Indian global clades in the Midlands and linked them to particular human population groups using novel software based on names. DNA fingerprinting also discovered the most prevalent single strain in the Midlands. This strain is geographically restricted to the West Midlands within the UK and globally. From this geographical association, we have called this strain the "Mercian" strain. The Mercian strain was not associated with patients who originated from the Indian Sub-Continent but was significantly associated with UK-born, Black Caribbean patients in Wolverhampton. These findings show that strains have been imported into the Midlands from around the world and there has also been continued transmission of these and other strains which may have been present in the Midlands for years. Molecular tools developed in this thesis will have regional, national, and international impact on TB control.
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Barr, Beverly Bell Brown. "Molecular epidemiology of herpes simplex virus infections." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/19152.
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Kazwala, Rudovick Reuben. "Molecular epidemiology of bovine tuberculosis in Tanzania." Thesis, University of Edinburgh, 1996. http://hdl.handle.net/1842/30335.
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A study on molecular epidemiology of bovine tuberculosis in man and cattle in Tanzania was carried out with two components. The first component was based on field investigation of tuberculosis in cattle and man in Arusha region, in the north and in the Usangu Plains in the Southern Highlands of Tanzania. The second component involved laboratory analysis of strains acquired from field study by both conventional and molecular biology techniques. The IS986 and mtp40 multiplex PCR developed in the course of this study was able to different M. bovis from M. tuberculosis. DNA fingerprinting of all the strains cultured was carried out using restriction fragment length polymorphism (RFLP) and spoligotyping techniques. Strains of M. bovis from man from Arusha gave similar DNA fingerprints to those from cattle, while the human M. bovis, strains from other places gave different fingerprints from those from cattle. M. tuberculosis strains were found to belong to three clusters, with one cluster containing over 60% of the strains. Intersegment PCR, a molecular typing technique developed in the current study was able to differentiate strains but the results were influenced by the concentration of template DNA. A fragment of RAPD PCR found only in M. bovis and absent in M. tuberculosis and other atypical mycobacteria was cloned and sequenced. The DNA sequence of the cloned fragment was found to match a M. tuberculosis cosmid, which also matched rfbE gene of Yersinia enterocolitica. Specificity testing revealed hybridization to M. tuberculosis as well. The findings of the above studies have shown the existence of M. bovis infection in man and cattle in Tanzania. The study has also shown the zoonotic importance of infection in the two populations which necessitates a veterinary/medical approach to the control of the disease in Tanzania. Furthermore, it has been shown that molecular biology techniques are better epidemiological tools in studies of zoonotic conditions such as tuberculosis. The study was unable to find a specific DNA element for M. bovis. This observation concurs with others which have found 100% homogeneity between species of the M. tuberculosis complex.
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Coffey, Tracey Jean. "Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae." Thesis, University of Sussex, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357230.
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Ng, Josephine Su Yin. "Molecular epidemiology and metabolomic characterisation of Cryptosporidium." Thesis, Ng, Josephine Su Yin (2017) Molecular epidemiology and metabolomic characterisation of Cryptosporidium. PhD thesis, Murdoch University, 2017. https://researchrepository.murdoch.edu.au/id/eprint/38641/.
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This thesis examined the molecular epidemiology of the important enteric parasite, Cryptosporidium in Australia with particular reference to cryptosporidiosis in Aboriginal communities, outbreaks, zoonotic transmission and also conducted the first metabolomics analysis of Cryptosporidium.
Chapter 3 revealed striking differences in the epidemiology of Cryptosporidium between Aboriginal and non-Aboriginal people, with notification rates among Aboriginal people up to 50 times higher. Aboriginal people were predominantly infected with C. hominis subtype IdA15G1 and non-Aboriginal people were predominantly infected with C. hominis subtype IbA10G2. Chapters 4 and 5 explored the epidemiology of outbreaks with the C. hominis IbA10G2 subtype, the major subtype identified in all outbreaks.
Chapter 6 examined zoonotic transmission of Cryptosporidium species in rural NSW. Three species of Cryptosporidium were detected in calves; C. parvum, C. bovis and C. ryanae and two in humans; C. parvum and C. bovis. Subtyping identified the concurrence of C. parvum subtypes between calves and humans and this coupled with the identification of the cattle-specific C. bovis in humans and calves provides supportive evidence of zoonotic transmission.
Chapter 7 developed a reproducible faecal extraction method for untargeted gas chromatography-mass spectrometry (GC-MS) analysis and identified distinct differences in faecal metabolite profiles between infected and un-infected individuals. However, as the metabolome is sensitive to external perturbations, a more controlled metabolomics analysis of faecal metabolite profiles was conducted in Chapter 8 using experimentally infected mice. Despite the differences in faecal metabolite profiles between Cryptosporidium infected humans and mice, metabolomic analysis in both studies was still able to clearly differentiate between infected and uninfected hosts, as well as provide information on the metabolic activity of the parasite during the infection based on faecal metabolite profiles.
The finding of this thesis will greatly assist in our understanding of molecular epidemiology of Cryptosporidium in Australia and the biochemistry of this important parasite.
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Suttie, Annika. "The molecular epidemiology of influenza in Cambodia." Thesis, Federation University Australia, 2019. http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/173785.
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Avian influenza viruses (AIVs) represent a risk to the health of humans and animals. The prevalence of AIVs in live bird markets in Cambodia is among the highest in the world, being detected in 45.5% of tested poultry in 2015. To better understand the potential risk presented by AIVs, this thesis investigated the genetic characteristics of AIVs circulating in Cambodia between 2014 to 2018; focusing on subtypes that pose the greatest risk to human and animal health (H5, H7 and H9). Highly pathogenic (HP) H5N1 clade 2.3.2.1c viruses and low pathogenic H9N2 BJ/94-like h9-4.2.5 clade viruses were the most frequently detected subtypes, and circulate endemically in Cambodia’s domestic poultry. Co-infections were detected and facilitated the production of two novel reassortant H5N1 AIVs with single genes from H9N2 viruses. Additionally, numerous intrasubtypic reassortment events were detected for H5 and H9 AIVs. This is concerning as reassortment events can rapidly produce novel viruses of public health risk. Phylogenetic analyses showed some genes of the Cambodian H5, H7 and H9 AIVs clustered with zoonotic viruses, suggesting a common origin. There are parallels between H5N1 and H9N2 AIVs detected in Cambodia and Vietnam, likely facilitated through the illegal trade of live poultry and/or the migration of wild birds. Molecular analyses showed H9 AIVs have major markers associated with adaptation to mammals; though during the study period the only human AIV cases were the result of HP H5N1. Molecular markers of resistance to adamantine antivirals was observed in 3% of H5 and 41% of H9 AIVs; however, both subtypes remain susceptible to first line antiviral treatment, neuraminidase inhibitors. The data presented in this thesis demonstrates that circulation of Cambodian AIVs represents a risk for the emergence of novel viruses. Interventions are urgently needed to mitigate the threat posed to poultry and humans.Doctor of Philosophy
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Gill, Lyndell R. "Moraxella (Branhamella) Catarrhalis: A Molecular Epidemiology Study." Digital Commons @ East Tennessee State University, 1995. https://dc.etsu.edu/etd/2684.
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Moraxella (Branhamella) catarrhalis is the third-most-frequently isolated microorganism associated with acute exacerbations of chronic bronchitis in patients during their stay at the Mountain Home VA Medical Center (MHVAMC). In order to develop a practical, epidemiologically-meaningful typing method for M. (B.) catarrhalis, we tested two methods based on analysis of chromosomal DNA for typeability, reproducibility, and ability to differentiate between unrelated strains (discriminatory power, D). M. (B.) catarrhalis isolants from MHVAMC from 7/1/87-6/30/88 were grown overnight in broth and embedded in agarose. DNA was isolated by standard methods. The DNA was subjected to: (1) restriction endonuclease digestion (with either Bgl II or Pme I) followed by pulsed-field gel electrophoresis (PFGE) and (2) restriction endonuclease digestion (with Hae III), followed by horizontal gel electrophoresis, Southern transfer and hybridization with a M. (B.) catarrhalis-specific DNA probe (M46). Reliable and reproducible patterns were produced from 144 of 159 isolants (91%) using Hae III, 155 of 159 (97%) using Pme I, and all isolants using Bgl II. Three clusters of isolants, Groups A (n = 18), B (n = 18), and C (n = 12) were detected. Within each group, isolants were identical by all typing methods tested. Chart review revealed no apparent epidemiologic link for Group A, while in Group B, 16 of 18 patients were housed on two wards, and in Group C, all cases occurred within two months, suggesting epidemiologic links within Groups B and C. Comparisons of results from isolants from various wards and isolants from outpatients were used to determine D of each method. Digestion with Pme I followed by PFGE was the most discriminating technique (D = 0.978) followed by Bgl II with PFGE (D = 0.962), then M46 probe hybridization (D = 0.929). The restriction endonucleases Pme I and Bgl II were highly discriminating and useful in the epidemiologic typing of M. (B.) catarrhalis. While useful, the M46 probe following Hae III digestion was not as discriminating.
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林一普 and Yi-pu Lin. "Molecular epidemiology of influenza viruses from Southern China." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31233806.
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So, Yung-chun, and 蘇雍竣. "Molecular epidemiology of toxigenic Clostridium difficile in HongKong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46632220.
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Lastoria, Leticia Chamma [UNESP]. "Colonização por Staphylococcus aureus em pessoas vivendo com HIV/AIDS acompanhadas em um serviço ambulatorial de referência em Botucatu (SP): prevalência, resistência à meticilina e epidemiologia molecular." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/140292.
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Staphylococcus aureus resistente à meticilina (Methicillin-resistant S. aureus, MRSA) é cada vez mais reconhecido como uma ameaça para pessoas vivendo com HIV/AIDS (PVHA). No entanto, a magnitude da colonização por MRSA varia entre diferentes países e regiões geográficas. Nós realizamos um estudo que teve por objetivo identificar a prevalência e os fatores de risco para colonização por S. aureus como um todo e MRSA em PVHA residindo em cidades de pequeno porte do interior do Estado de São Paulo. Isolados de MRSA foram caracterizados por Eletroforese em Gel de Campo Pulsado (Pulsed-Field Gel Electrophoresis, PFGE) e tiveram o Cassete Cromossômico Estafilocóccico (Staphylococcal Chromosome Cassete, SCC) mec tipado. Análise espacial foi realizada para identificar agregados geográficos e correlação com indicadores socioeconômicos. No primeiro momento, realizamos um estudo de prevalência pontual coletando swab nasal e de orofaringe de 368 PVHA atendidas em ambulatório de referência em Botucatu, SP. Sessenta e sete sujeitos residentes na cidade sede foram seguidos com coletas em dois outros momentos, e tiveram seus contactantes domiciliares também investigados para colonização. As taxas de prevalência de S. aureus e MRSA no primeiro levantamento foram 25,8% e 2,7%. A colonização por S. aureus foi negativamente associada com o uso de antibióticos beta-lactâmicos e drogas ilícitas. Por outro lado, fatores de risco para MRSA incluíam uso de crack e internação hospitalar recente. Inquéritos repetidos identificaram novos casos de colonização por MRSA, mas nenhum sujeito apresentou positividade em mais de uma ocasião. Quatro clusters foram identificados na PFGE, agrupando sujeitos em diferentes níveis – domicílio, cidade, região. Dos 19 isolados caracterizados, apenas um não carreava o SCCmec tipo IV. Análise espacial identificou hot spots par sujeitos colonizados com S. aureus, mas não conseguimos ligar esse padrão a indicadores sócio-econômicos. Em conclusão, nós idenficamos baixa – mas relevante – prevalência de MRSA em PVHA. Foram identificados tanto fatores de risco tradicionalmente associados a aquisição na comunidade quanto outros ligados a exposição a hospitais, de modo que as rotas predominantes de transmissão não puderam ser determinadas com base epidemiológica.
Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized as a threat for people living with HIV/AIDS (PLWHA). However, the magnitude of asymptomatic MRSA colonization in that group varies among different countries and geographic regions. We conducted a study that aimed at identifying the prevalence and risk factors for both overall S. aureus and MRSA colonization among PLWHA attending in small cities from inner São Paulo State, Brazil. MRSA isolates were characterized using Pulsed-Field Gel Electrophoresis (PFGE), and submitted to typing of the Staphylococcal Chromosome Cassete (SCC)mec. Spatial analysis was performed to search for geographical clusters and correlation with socioeconomic indicators. In a first point prevalence survey, nasal and oropharyngeal swabs of 368 people were collected. Sixty-seven subjects from the main city (Botucatu) were surveyed for colonization in two other occasions, and had swabs collected from household members. The prevalence rates for S. aureus and MRSA in the first survey were 25.8% and 2.7%. The overall S. aureus colonization was negatively associated with the use of beta-lactams and of illicit drugs. On the other hand, MRSA colonized subjects were more likely to use crack and to have been admitted to a hospital during the past year. Repeated surveys found additional cases of MRSA colonization, but all subjects were positive in only one occasion. Four PFGE clusters were characterized, grouping subjects in household, city and region level. Of 19 total MRSA isolates, only one did not harbor SCCmec type IV. Spatial analysis detected hot spots of S. aureus colonized subjects from Botucatu, but that finding could not be linked to socio-economic indicators. In conclusion, we found small but relevant prevalence of MRSA among PLWHA. Community and healthcare-associated risk factors were identified, so that predominant routes of transmission could not be determined on epidemiological grounds.
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Lam, Tsan-yuk Tommy. "Molecular evolution and epidemiology of influenza A virus." Click to view the E-thesis via HKUTO View the Table of Contents & Abstract, 2010. http://sunzi.lib.hku.hk/hkuto/record/B44137084.
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Puig, Vives Montserrat. "Breast cancer epidemiology: mammographic screening and molecular subtypes." Doctoral thesis, Universitat de Girona, 2015. http://hdl.handle.net/10803/289426.
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The aim of this thesis is to carry out an in-depth study of various aspects of breast cancer epidemiology. Firstly, we have confirmed that DCIS incidence in Girona has increased over recent decades. Proportions of screen-detected cancers, interval cancers and non-screen-detected cancers during the start-up phase of the mammographic screening programme were found to be 42.2%, 5.8% and 52.2%, respectively. Secondly, we have found that luminal A-like was the most frequent subtype associated with the best survival rate, while triple-negative breast cancer was related to the lowest survival rate. Importantly, we have concluded that breast cancer molecular subtype defined by IHC biomarkers provides prognostic value, regardless of age, tumour size, histological grade, lymph node involvement and method of detection. Finally, we have demonstrated that method of detection also provides prognostic value regardless of age, tumour size, histological grade, lymph node involvement and breast cancer molecular subtype defined by IHC biomarkers.L’objectiu d’aquesta tesi és realitzar aprofundir en diversos aspectes de l'epidemiologia del càncer de mama. Hem confirmat que la incidència del DCIS a Girona ha augmentat en les últimes dècades. Les proporcions dels càncers detectats mitjançant el programa de cribratge, fora d’aquest i els càncers d'interval van ser del 42,2%, 52,2% i 5,8%, respectivament. Per altra banda, el subtipus amb la supervivència més elevada i més baixa van ser el luminal A-like i el triple negatiu, respectivament. És important destacar que el subtipus molecular de càncer de mama definit per biomarcadors determinats amb tècniques d’IHC proporciona valor pronòstic, independentment de l'edat, la mida, el grau histològic, l’afectació dels ganglis i el mètode de detecció. Finalment, hem demostrat que el mètode de detecció del càncer també proporciona valor pronòstic independentment de l'edat, la mida, el grau histològic, l'afectació dels ganglis i el subtipus molecular.
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Sak, Sei Chung. "Molecular epidemiology of DNA repair and bladder cancer." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446441.
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Tjon, Grace Marjorie Soei Joen. "Molecular epidemiology of hepatitis A in the Netherlands." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2006. http://dare.uva.nl/document/30401.
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Sjöström, Karin. "Molecular epidemiology of pneumococcal carriage and invasive disease /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-094-7/.
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Siliņš, Ilvars. "Molecular epidemiology of human papillomavirus and cervical cancer /." Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-7349-091-1/.
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Bashash, Morteza. "Molecular epidemiology of gastric and esophageal cancer survival." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/30666.
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Introduction: Gastric and esophageal cancers are among the deadliest forms of cancer. Studies of human cancer susceptibility examine factors associated with the incidence of disease. Studies of human cancer prognosis and prediction examine factors associated with disease outcomes. This dissertation is about molecular and other factors that affect survival of gastric and esophageal cancer patients. Methods: Population-based registry data linked with patient outcome data was used to describe the epidemiology of gastric and esophageal cancers in BC; to compare survival of cancer patients in BC, and Ardabil, Iran and to describe differences in survival of BC patients of different ethnicity. The ethnicity of patients was determined based on lists of names corresponding to each ethnic group. A prospective cohort study was conducted to examine the effect of genetic polymorphisms in TIMP (1-4) and MMP (2, 7 and 9) genes. Results: Analysis of cancer registry data points to several factors associated with gastric and esophageal cancer survival. Patients with gastric cardia experience worse survival compared to other gastric cancers. Ethnicity of gastric and esophageal cancer patients is associated with their survival. Gastric and esophageal cancer patients diagnosed in British Columbia have better survival compared to those daignosed in Adabil, Iran. Genetic polymorphisms are also associated with survival. My prospective study identified 4 genetic polymorphisms at TIMP-3 associated with survival of esophageal adenocarcinoma and gastroesophageal junction (GEJ). Conclusion: Besides established prognostic indicators, other factors affect survival of gastric and esophageal cancers. Differences in survival by ethnicity support the importance of ethnicity as a prognostic factor. Survival differences between BC and Ardabil are likely due to disease characteristics and patient factors, in addition to differences in healthcare systems. TIMP3 genetic polymorphisms are promising prognostic factors for adenocarcinoma of esophagus and GEJ. Modeling prognosis based on host factors, including ethnicity and genetic polymorphisms, is an emerging field of translational cancer research. More research is needed to fully explore the functional effects of TIMP3 polymorphisms, and to identify both genetic and lifestyle factors underlying the effect ethnicity on survival.
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Stark, Lisa. "Staphylococcus aureus : aspects of pathogenesis and molecular epidemiology." Doctoral thesis, Linköpings universitet, Institutionen för klinisk och experimentell medicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-97343.
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Staphylococcus aureus is a human commensal colonizing about 30 per cent of the population. Besides, it is a frequent cause of infections such as skin, wound and deep tissue infections and also more life-threatening conditions such as pneumonia, endocarditis and septicaemia. S. aureus may also cause different toxicoses. Moreover, this bacterium is one of the most common causes of nosocomial infections worldwide and an increase in antibiotic resistance, especially against methicillin, is seen. This underlines the importance to prevent and control outbreaks of S. aureus. The aims of this thesis were to increase the knowledge of S. aureus virulence and pathogenesis as well as to understand pattern of colonization and transmission. Various virulence factors operate together in the pathogenic process of S. aureus. The virulence of S. aureus was studied by the interaction with human umbilical vein endothelial cells (HUVEC) as a model. In paper I, we found that one bacterial isolate survived intracellularly and that 156 genes were differentially regulated in microarray analysis of HUVEC. The major part of these genes coded for proteins involved in innate immunity. In paper II, we wanted to explore possible differences in global gene expression patterns in HUVEC induced by invasive compared to colonizing isolates of S. aureus. We also used microarray to investigate possible differences in the presence of virulence genes between the two groups. The main finding was that virulent and commensal S. aureus did not differ in interaction with HUVEC and in the presence of virulence genes. All isolates survived intracellularly for days. Since no obvious differences in virulence between the two groups of isolates were found, we focused on epidemiology and transmission patterns. Colonization with S. aureus is an important risk factor for subsequent S. aureus infection. In paper III, we investigated S. aureus colonization and transmission among nursing home residents in three regions in the south of Sweden and used staphylococcal protein A (spa) typing as an epidemiological tool. A diverse distribution of different spa types was found and a majority of types were unique to one individual. Interestingly, we found a local accumulation of one spa type in one nursing home. Also common spa types were equally distributed in the different regions. We also noted that some individuals were colonized with two different spa types of S. aureus and in five of these cases there was one resistant and one non-resistant strain. The issue of multiclonal colonization and infection is highly important and clinical diagnostic laboratories do not routinely address this problem. Therefore, in paper IV a novel method to assess multiclonality of S. aureus was developed. It was based on denaturing gradient gel electrophoresis with the amplification of the spa gene. The method simultaneously separated eight different spa types. It also detected two spa types in an outbreak. In conclusion, we found no differences in virulence genes and in the interaction with HUVEC between commensal and invasive isolates. This indicates that any isolate of S. aureus might have a pathogenic potential. We also confirmed that some spa types are more successful colonizers with a potential to nosocomial spread. The method for detection of multiclonality of S. aureus is of importance in future epidemiological and clinical studies.
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Osei-Atweneboana, Mike Yaw 1966. "Molecular epidemiology of emerging ivermectin resistance in onchocerciasis." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111910.
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Onchocerciasis, commonly known as "River blindness" is a disease affecting over 37 million people, worldwide. It is caused by the parasitic nematode Onchocerca volvulus and transmitted by the blackfly vector of the genus Simulium. The drug ivermectin (IVM) is the principal means of controlling the disease. As a result of recent reports on sub-optimal response to ivermectin and genetic selection in O. volvulus, we carried out a 21 month epidemiological study to investigate the response of O. volvulus to repeated rounds of IVM treatments in 2501 subjects from 19 Ghanaian communities that have received between 6 and 18 annual treatments and one IVM naive community. Skin microfilaria (mt) assessments were done before IVM treatment and at days 30, 90, 180 and 364 post-IVM treatment. At day 90 after the second IVM treatment, nodulectomies were carried out on 140 patients and embryogrammes constructed on female worms. We found IVM is still an effective microfilaricide, with efficacy of 98-100%. However, its effect on adult worm fertility has been reduced. Day 90 and 180 post-treatment showed significantly higher (p<0.05) skin mf repopulation of 7.1% to 53.9%, and >100% of pretreatment counts at day 364 post-treatment in four communities compared with the other six communities, which had <80% of pretreatment mf counts on day 364. From these results we classified the 10 communities into good IVM response (four communities), intermediate IVM response (two communities), poor IVM response (three communities), and the previously IVM naive community. Nodule and worm viability and worm densities were significantly higher (p<0.05) in the poor response communities compared with the good response communities, with the intermediate falling between the two. Embryogramme analysis showed significantly higher reproductive activity and output in worms from poor response communities with up to 41% of females having live stretched mf in utero compared with good response communities which had no intra-uterine stretched mf. These results show evidence of lack of sustained response of adult O. volvulus to IVM in the poor response communities, manifested as a rapid return to fertility after IVM treatment. We conclude that IVM resistance is emerging in onchocerciasis and is manifested as a loss of effect of IVM on suppression of parasite reproduction.Beta tubulin isotype 1 gene has been shown to be linked to IVM treatment and selection in O. volvulus and veterinary nematodes. Genetic analysis of the full length genomic DNA sequence of beta-tubulin from worms obtained in the three IVM response categories and IVM naive community showed single nucleotide polymorphisms (SNPs) at 24 sites on the entire 3696 bp. The frequencies of eight SNPs were significantly different (p< 0.05) between the poor response communities and the good response/naive communities. Four SNPs, 183 T/G, 1188 T/C, 1309 CIT and 1545 A/G resulting in a genotype configuration GG/CC/TT/GG (183/1188/1309/1545) was significantly higher in the poor IVM response communities than the other communities. The phenotypic and genotypic analyses are consistent with a conclusion that IVM resistance has been selected. These four SNPs could be used to develop a genetic marker for early detection of IVM resistance. This study has shown for the first time that IVM resistance is emerging in Onchocerca volvulus and that there are genetic changes associated with IVM resistance which could be used for epidemiological monitoring for emerging resistance.
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Ali, Sayma. "The development of molecular methods for Cryptosporidium epidemiology." Thesis, Coventry University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418355.
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Twiddy, Sally Susanna. "The molecular epidemiology and evolution of dengue virus." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269490.
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Davis, Patricia. "The molecular evolution and genetic epidemiology of lyssaviruses." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433259.
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Tsolaki, Anthony George. "Molecular epidemiology of human-derived Pneumocystis carinii infection." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298612.
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Grove-White, David Hugh. "The molecular epidemiology of Campylobacter jejuni in ruminants." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501729.
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The prunary objective of this study was to describe the temporal and spatial aspects of the epidemiology of ruminant Campylobacter jejuni. The work presented in this thesis is nested within a larger multidisciplinary study investigating the epidemiology of human campylobacteriosis in Lancashire and will be used to quantify and descnbe the contribution ot ruminant derived Campylobacters to the human disease burden.
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Lam, Tsan-yuk Tommy, and 林讚育. "Molecular evolution and epidemiology of influenza A virus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44137084.
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De, Zoysa Aruni Shanika. "Transcontinental epidemiology and molecular characterisation of Corynebacterium diphtheriae." Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401083.
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HueÌ, SteÌphane. "Molecular epidemiology of HIV-1 in the UK." Thesis, University College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425339.
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Reid, Nicholas. "Clinical, microbiological and molecular epidemiology of Streptococcus pneumoniae." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311200.
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Streptococcus pneumoniae is a serious pathogen, responsible for a large proportion of cases of pneumonia, bacteraemia and meningitis. Restriction endonuclease analysis (REA) using Taq I and Hae III was evaluated to analyse the genetic relationships among 51 isolates of S. pneumoniae in four different serotypes. This method was used together with pulsed-field gel electrophoresis (PFGE) in the analysis of clinical isolates of bacteraemic S. pneumoniae in the Grampian region of Scotland during a two year period from 1993-5. A total of 104 isolates were collected, of which 93 were analysed by REA and 94 by PFGE. Sensitivities to eight commonly used antibiotics were determined for 99 isolates, and serotyping was performed by the relevant reference laboratory. Records were available for 92 patients and details of past medical history, primary site of infection and outcome were abstracted. Of the clinical isolates analysed, 1% were fully resistant to penicillin and 12% were resistant to erythromycin. The three most common serotypes were 14(23.5%), 4 (12.2%) and 23F (9.2%). The current vaccine, Pneumovax II, was calculated to provide 99.8% cover for the serotypes isolated. The overall incidence of bacteraemic infection was 10.3 per 100,000 population per year, and the mortality was 21.2%. Both the incidence and mortality increased exponentially with respect to age. In both serotype and clinically based studies, when analysed by REA and PFGE, isolates were primarily grouped into closely associated clusters of single serotypes. Some serotypes, such as 3, 6B and 14, were divided into genetically distinct subgroups. The genetics structure of the population was defined as being primarily clonal with evidence of a serotype change in one instance. An erythromycin resistant serotype 14 clone was described, and later discovered to be of the M phenotype. This clone was significantly associated with bacteraemic disease in the under 5 age group, and was demonstrated to be the current major cause of erythromycin resistance in the U.K.
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Strauss, Susanne. "Studies on the molecular epidemiology of human papillomaviruses." Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437780.
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