The epidemiology of non-typhoidal Salmonella enterica in Australia and the impact of whole genome sequencing on public health surveillance and outbreak investigation

In Australia, the rates of reported non-typhoidal Salmonella enterica infections are amongst the highest in the industrialized world. Public health laboratories are increasingly adopting whole genome sequencing (WGS) of non-typhoidal Salmonella enterica isolates to characterize isolates for surveillance. In this thesis, I contribute to understanding the epidemiology of salmonellosis and provide evidence on the use of phylogenomic salmonellosis data for public health in Australia by examining trends in and sources of infection; costs-of-illness and costs of WGS; and impacts of WGS on surveillance and outbreak investigation. I analysed national surveillance data using negative binomial regression to show that most states and territories had significantly increasing trends of Salmonella Typhimurium notifications between 2000 and 2013. Geographic and age-specific analyses indicated the importance of foodborne transmission for Salmonella Typhimurium, while suggesting that other transmission pathways may be more important for non-Typhimurium serotypes. I found that 79% of the 990 Salmonella outbreaks in Australia between 2001 and 2016 were suspected or confirmed to be transmitted through contaminated food. Most outbreaks were due to Salmonella Typhimurium, and eggs or egg-containing foods were the most frequently identified food vehicles. I estimated the health care, lost productivity, and premature mortality costs of non-typhoidal Salmonella enterica and sequelae irritable bowel syndrome (IBS) and reactive arthritis (ReA) in Australia. Circa 2015, I estimated 90,833 salmonellosis cases, 4,312 hospitalizations, and 19 deaths at a cost of AUD 124.4 million (90% credible intervals 107.4-143.1 million) and AUD 146.8 million (90% CrI 127.8-167.9 million) when IBS and ReA were included. While WGS is more expensive than traditional Salmonella typing methods and polymerase chain reaction testing, it may result in cost savings if it can reduce case numbers through early detection of outbreaks and sources of infection. To examine the impacts of WGS on public health surveillance, prevention, and control, I conducted two studies. Firstly, concurrent WGS and multiple locus variable-number-tandem repeat analysis (MLVA) was performed on Salmonella Typhimurium isolated from residents of the Australian Capital Territory for a 5 month period. Compared to MLVA, I found that WGS was more sensitive, linking an additional 9% of isolates to at least one other isolate, and linking cases from seven outbreaks occurring over 5 months in three Australian states and territories. Secondly, I used phylogenomic and epidemiological risk factor data to characterize the epidemiology and disease reservoirs for Salmonella Mississippi and Salmonella Typhimurium definitive type 160 (DT160). Sequence and epidemiological data for isolates from humans, animal, and environmental sources identified plausible sources of human infection from wildlife and environmental reservoirs and showed Australian and New Zealand isolates in distinct clades for both serotypes. While the genetic relatedness of DT160 isolates suggested a common reservoir, source attribution studies would be helpful for hyper-endemic serotypes such as Salmonella Mississippi. In this thesis, I demonstrate that the burden of Salmonella enterica in Australia is high, and provide evidence for the formation of targeted policies and interventions to prevent infection. My findings on using phylogenomic data will be instrumental in implementing WGS for routine surveillance and outbreak investigations