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Molecular epidemiology of pneumococcal infections

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dc.contributor.advisor Klugman KP en
dc.contributor.author McGee L en
dc.date.accessioned 2016-09-22T11:14:08Z
dc.date.available 2016-09-22T11:14:08Z
dc.date.created 1995 en
dc.date.submitted 2001 en
dc.identifier.uri http://hdl.handle.net/20.500.11892/106317
dc.description.abstract This thesis examines the molecular epidemiology of isolates of <i>Streptococcus pneumoniae</i> from various countries in the world, especially from those areas where little or no epidemiological data have previously been available. Various DNA molecular fingerprinting techniques were evaluated for their ability to differentiate pneumococcal strains. The inclusion of DNA-typing techniques in surveillance projects has allowed the identification of a number of pneumococcal genetic lineages that have achieved massive geographic spread across both national and international boundaries. The most widely spread of these is the Spain<sup>23F</sup>-l clone, Prior to the work of this thesis the clone was known to have spread to the USA and to South Africa. The study reported herein was the original description of the spread of this clone to Asia. It has subsequently disseminated widely in Asia and in South America. That study also highlighted the use of AP-PCR in the differentiation of strains and confirmed reports of the ability of the pneumococcus to transfer capsular genes resulting in the switch of serotypes within clones. Studies in day-care centres have shown not only increased prevalence of the pneumococcus among children but also the frequent carriage of resistant strains. An investigation of the molecular relatedness of pneumococci among DCC attendees in Israel revealed unique clones which rapidly disseminated among children, with some clones persisting for weeks and months before being replaced by new strains. Data from this study also showed that antibiotic resistant clones were more frequently isolated in the DCC population, spread more widely amongst the children than did the antibiotic susceptible clones, and persisted for a longer time. Epidemiological information from many developing countries that include the majority of the world's children is lacking. Two separate studies were carried out to investigate the clonality of pneumococci isolated from China. In both studies penicillin resistance was identified as being relatively low compared to other Asian countries and unique clones were identified using BOX-PCR and PFGE. In the Beijing study (the first in the Western literature to report on the susceptibility on pneumococci from China) a multi-resistant serotype 23F and a macrolide-resistant serotype 6A were identified as unique clones circulating in Beijing. Nine major clones were identified among the pneumococci from Shanghai and were all unrelated to the described international clones. An analysis of the macrolide resistance determinants from both studies showed the majority of strains possessing a MLSB mechanism of resistance. Strains that possessed both the <i>erm</i>(B) and <i>mef</i>(A) genes were also identified, suggesting that both ribosomal modification and efflux can play an active role in macrolide resistance in a single strain. Molecular typing of isolates from a study in N. Ireland shows that the majority of penicillin-resistant pneumococci belong to the Spain<sup>9V</sup>-3 clone, suggesting that the increase in resistance over the past few years could be due to the import and spread of this multi-resistant clone. Data from this study also identified fluoroquinolone-resistant pneumococci belonging to the Spain<sup>23F</sup>-l, Spain<sup>6B</sup>-2 and Spain<sup>9V</sup>-3 clones. A global molecular-based study on pneumococci from the Alexander Project showed that the majority of strains from this worldwide collection belonged to three major Spanish clones: Spain<sup>23F</sup>-l, Spain<sup>6B</sup>-2 and Spain<sup>9V</sup>-3. Data from that study also describes the emergence of fluoroquinolone resistance in strains belonging to the Spain<sup>23F</sup>-l and Spain<sup>9V</sup>-3. South Africa remains one of the focal countries for antibiotic resistance in the pneumococcus. A study on macrolide-resistant strains from the private sector showed that the majority of strains had a MLSB phenotype and identified a unique serotype 19F clone harbouring both the <i>erm</i>(B) and <i>mef</i>(A) genes. There are subsequent data that this clone might also have spread globally. The emergence of antibiotic-resistant pneumococci worldwide has necessitated the need for global surveillance and guidelines for the standardization of pneumococcal clones. The Pneumococcal Molecular Epidemiology Network was established in 1997 with this aim. This chapter details the role of the Pneumococcal Diseases Research Unit and the use of BOX-PCR in the characterization of 16 international antibiotic-resistant pneumococcal clones. The work of this thesis has thus contributed to our understanding of the local, national and international spread of multiresistant pneumococci. en
dc.language English en
dc.title Molecular epidemiology of pneumococcal infections en
dc.type Doctoral degree en
dc.description.degree PhD (Science) en


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