"The Egg came first" Unravelling the Changing Epidemiology of Human Salmonellosis in the Netherlands and across Europe, with a focus on Salmonella Enteritidis

Salmonella is a zoonotic bacterial pathogen that significantly impacts food safety and public health in the Netherlands and across the European Union and European Economic Area (EU/EEA). Though extensive control measures in poultry have reduced its prevalence among poultry and human cases at the EU level, this decline has plateaued in recent years. This thesis investigates the evolving epidemiology of human salmonellosis, with a focus on Salmonella enterica serotype Enteritidis (SE), across the Netherlands and selected EU countries. It explores the disease’s drivers, including emerging sources of infection, antimicrobial resistance (AMR), and environmental factors. Finally, through expert elicitation, the thesis identifies key determinants behind the stagnating trend in SE incidence and proposes potential intervention strategies. Chapter 2: COVID-19 control measures led to a sharp, temporary drop in salmonellosis cases, especially travel-related SE cases. Changes in travel, dining habits, healthcare-seeking behavior, and testing policies likely contributed. Chapter 3: From 2006 to 2015, SE incidence declined in the Netherlands and Belgium, followed by stagnation or increases (particularly in the Netherlands). Factors such as age, travel, and AMR were linked to higher incidence, emphasizing the need to investigate upstream drivers in livestock. Chapter 4: Between 2015 and 2019, eggs were the leading source of Salmonella outbreaks across Europe, followed by pork. SE-related outbreaks were predominantly egg-associated. Outbreak frequency increased in Eastern Europe but declined in other regions. Chapter 5: Whole-genome sequencing showed that 65% of Dutch SE isolates (2019–2023) were clustered, with almost a third of these clusters persisting over time. Persistence lacked clear epidemiological or AMR explanations. Chapter 6: SE isolates showed a 13% annual AMR increase (2008–2019), especially to (fluoro)quinolones, ampicillin, and tetracycline. Resistance was significantly associated with travel outside the EU/EEA. Chapter 7: Despite reduced veterinary antimicrobial use (AMU) in the Netherlands, only limited correlations were found between livestock AMU and AMR in SE human isolates, with some associations observed (e.g., penicillin use in broilers). However, stronger correlations were found between AMU and AMR in another common serotype known for higher AMR levels than SE. Chapter 8: Weather factors such as temperature, humidity, and day length significantly affected salmonellosis incidence. A UK-developed model successfully predicted incidence trends in the Netherlands. Chapter 9: Experts identified flaws in poultry sampling and the premature relaxation of control measures as key contributors to the plateau in SE incidence. Priority interventions included enhanced biosecurity, improved sampling, and vaccination, especially targeting poultry. The final chapter discusses all findings and concludes that controlling Salmonella, like resolving the “chicken-or-egg” dilemma, requires addressing upstream factors in the farm-to-fork chain. SE control in poultry remains central. A One Health approach integrating human, animal, and environmental health is essential for sustainable Salmonella control in Europe.