title: Genomic Epidemiology for supporting Public Health in Australia
Creators: name: Peacock, Patrick
Publisher: name: The Australian National University
Year: 2025

description: This dissertation presents the work undertaken and results for the series of projects completed during my field placement to satisfy the requirements of the Master of Philosophy (Applied Epidemiology). My placement was facilitated at the Centre for Infectious Diseases and Microbiology - Public Health within the Institute for Clinical Pathology and Medical Research - NSW Health Pathology, Westmead Hospital, NSW. I worked alongside multiple reference laboratories including the Microbial Genomics Reference Laboratory, the Enteric Reference Laboratory, and the Antimicrobial Resistance Reference Laboratory in addition to collaborating with colleagues within the NSW Ministry of Health, Public Health Units and ACT Health. Genomics has become a powerful tool for the investigation of pathogens of public health interest. In late 2022 an aged-care facility in the ACT experienced an outbreak of COVID-19. Subsequent investigation identified multiple cases with a heavily mutated virus, indicative of molnupiravir-induced mutations. The antiviral medication, molnupiravir, saw widespread prescription rates in Australia, particularly in the aged care sector. While there have been suggestions in literature that molnupiravir treatment may not always result in non-viable virus, there had not been any epidemiological linked information confirming this to date. Treatment of Shigellosis cases are often complicated by antimicrobial resistance (AMR). Phenotypic AMR testing on Shigella spp. is not routinely performed by diagnostic laboratories nor is there a standardised panel of antimicrobials to test against. The NSW Ministry of Health requested a study to evaluate the feasibility of incorporating genotypic AMR prediction into the Shigellosis surveillance system. I performed analysis of the quality of current AMR data and compared the genotypic and phenotypic results for samples from 2022. A high degree of concordance was found and where inconsistencies were found, we requested the Antimicrobial Resistance Reference Laboratory to perform repeat phenotypic testing. The repeated results were concordant with our genotypic predictions giving further confidence in accuracy of genotypic predictions. It was recommended to incorporate reporting of genomic results as a part of longer trend analysis to inform empirical treatment while performing periodic phenotypic testing on samples to ensure genotypic predictions remain accurate and comprehensive. NSW has been prospectively sequencing all referred isolates of Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium since 2016. These serovars are responsible for most foodborne illness in NSW and while not common, can have severe disease presentations. I confirmed the hypothesis that S. Enteritidis is approximately twice more associated with severe disease than S. Typhimurium. I performed a further data analysis on the Salmonella dataset examining the proportions of AMR and multidrug resistance (MDR). This identified that whilst S. Enteritidis had a slightly higher proportion of any amount of AMR, S. Typhimurium had a higher proportion of MDR isolates. However, this higher proportion of MDR was biased by a subset of S. Typhimurium, multi-locus sequence type 34, having a very high (over 80%) proportion of multidrug resistance.