| Summary: | <p>As the leading cause of bacterial gastroenteritis, <em>Campylobacter</em> represents a significant public health burden; however, our knowledge of its epidemiology in low- and middle-income countries remains limited. Recent studies have demonstrated the power of whole-genome sequencing (WGS) for public health microbiology. The primary aim of this thesis was to exploit WGS to improve our understanding of the epidemiology of <em>Campylobacter</em> from the Republic of South Africa, a middle-income country.</p> <p>In the first half of this thesis, <em>in silico</em> approaches were developed to evaluate diagnostic assays and methods of species identification. Large-scale analyses of publicly available WGS data identified a robust real-time PCR assay for the detection of <em>Campylobacter jejuni</em> and <em>Campylobacter coli</em>, the primary causes of human campylobacteriosis. Evaluation of <em>in silico</em> speciation methods demonstrated that the <em>atpA</em> gene and ribosomal multilocus sequence typing can be used to identify <em>Campylobacter</em> from WGS data.</p> <p>The second half of this thesis extended concepts developed in the first half to investigate the epidemiology of <em>Campylobacter</em> from animals and humans from South Africa. Isolates from a study of <em>Campylobacter</em> from free-range broiler carcasses belonged to the agriculture-associated ST-828 lineage, but were atypically homogenous and differed at only 46/1,513 (3%) loci, providing novel insights into clonal infections in chickens. Analyses of human disease isolates collected in Cape Town in 1991, 2011, and 2012 confirmed that the local epidemiology of <em>Campylobacter</em> is distinct from that of high-income countries: in addition to major agriculture-associated <em>C. jejuni</em> and <em>C. coli</em> lineages, a putative novel <em>C. jejuni</em> subsp. <em>jejuni/C. jejuni</em> subsp. <em>doylei</em> hybrid clade and genetically diverse <em>C. jejuni</em> subsp. <em>doylei</em> and <em>C. upsaliensis</em> isolates were identified.</p> <p>This work delivers further evidence of the utility of WGS for clinical microbiology, presents approaches that address general problems in <em>Campylobacter</em> diagnostics and public health microbiology, and provides insights into the epidemiology of this important group of pathogens in South Africa.</p>
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