Discerning Environmental Pathways of Campylobacter Transmission (DEPiCT): An interdisciplinary framework for understanding the origins and spread of non-foodborne campylobacteriosis

Campylobacteriosis is the primary zoonosis in Europe, causing over 1.6 M cases and €76 M costs annually in the Netherlands alone (~17 M people). Most cases are caused by Campylobacter jejuni and C. coli, which are widespread in livestock and wildlife, providing many ways for human exposure beyond just food. Despite all the research and control efforts in the food chain, there is no significant decrease in human campylobacteriosis. Up to 80% of human campylobacteriosis cases can be attributed to the poultry reservoir, but only ~40% of poultry-borne cases are attributable to poultry consumption; thus, many poultry-borne Campylobacter strains infect humans via other routes. Campylobacter is often found in environmental sources like surface water, indicating recent contamination with (animal) fecal material, but its environmental routes are still largely unexplored. While Campylobacter survives poorly outside the host, there are some environmentally adapted strains that play a key role in the transmission between animals and humans via the environment. Surface water is a ‘sink’ that collects Campylobacter strains from different hosts whose relative contributions are largely unknown, though wild birds are thought to play a major role. However, the devastating H7N7 bird flu epidemic hitting the Netherlands in 2003 showed that even without a huge drop in poultry consumption, the massive poultry culling and closure of poultry abattoirs to contain the epidemic was associated with a 44-50% drop in human campylobacteriosis where these measures were enforced, suggesting a major role of the environment in human exposure to poultry-borne strains. Moreover, while studies show that poultry and wild birds are the most important contributors to Campylobacter surface water pollution, their contributions vary with the size of the poultry production. The environment may also act as a source of Campylobacter (re)colonization in livestock. As the environment seems to be a key player in Campylobacter epidemiology and the non-foodborne side of campylobacteriosis receives little attention despite its potential to provide new targets for Campylobacter control and research, this project will discern the origins and spread of Campylobacter strains contaminating the environment and will determine their contribution to human campylobacteriosis morbidity, as well as the underlying (non-foodborne) transmission routes. As a collaboration of 4 leading institutes in public, animal and environmental health in the Netherlands (RIVM, CVI, UU and Alterra WUR), we will collect and type with a gene-by-gene approach (whole-genome multilocus sequence typing, wg-MLST) over 1200 C. jejuni/coli isolates representative of the Dutch eco-epidemiological situation from human cases, surface water (agricultural ditches, recreational waters, wastewater outlets), animals (broilers, layers, beef/dairy cattle, sheep/goats, pigs, pets), and wild birds (Anseriformers, Charadriformes, Columbiformes, Suliformes) using both well-established surveillance systems and ad hoc sampling schemes. We will: (i) characterize genotypically the strains circulating in surface water, animals and humans; (ii) quantify the contribution of different wild bird, farm and companion animals to Campylobacter pollution in different surface water types, seasons and areas with varying human, livestock and wild bird densities; (iii) quantify the contribution of different animal reservoirs and surface water to human campylobacteriosis in different seasons and areas with varying human, livestock and wild bird densities to estimate both the fraction of human cases attributable to the environment and the relation between human cases and reservoir density; (iv) determine the evolutionary history and relations of Campylobacter strains in the environment, humans and animals to understand their diversity and ecology, identify source-specific genetic markers, examine the role of the environment in the emergence of pathogenic strains, and perform source attribution at a high resolution; (v) conduct combined source attribution and case-control analyses to identify risk exposures for human campylobacteriosis of environmental origin and its underlying transmission routes. By depicting the epidemiology of non-foodborne campylobacteriosis, this project will allow for the delineation of more holistic control strategies, including those preventing Campylobacter dissemination into the environment. Besides standard scientific outputs, the results of this project will be translated into practical action points and advices for regulatory authorities on how to tackle environmental campylobacteriosis. The project members host national/international Campylobacter reference labs and participate since many years in advisory groups for the Dutch Ministries of Health and Economic Affairs, as well as the poultry industry, so through these forums knowledge gained in this project will be translated into interventions.