NEEDS. The long-term goal of this collaborative project is to develop strategies to prevent and control enteric diseases of livestock and poultry, ultimately to decrease incidence of enteric diseases in food animals, and zoonotic gastroenteritis in humans.  Illnesses caused by enteric pathogens of animal origin (foodborne or zoonotic pathogens) continue to remain a prominent public health challenge in the USA (https://www.cdc.gov/ncezid/dfwed/edeb/). Despite many concerted efforts to control enteric pathogens as well as zoonotic pathogens in food animals at both on-farm (pre-harvest) and food processing (post-harvest) environments, the incidence of enteric diseases of animals and food and water-borne illnesses of humans remains high, and some are increasing. Nevertheless, a broad range of education and research-driven and practice-oriented control efforts have succeeded in controlling the incidence of key food-borne pathogens at low levels.  NC1202 originally started as NC62 in the 1960’s and has been an important contributor to research on the enteric diseases of swine. Over the last 20 years, our enteric diseases group has contributed significantly to an evolved and expanded effort to find evidence-based interventions to prevent enteric diseases in food animals and food-borne diseases in humans. In this renewal proposal, we remain committed to the prevention and control of animal and human diseases caused by enteric pathogens. A primary avenue for control is decreasing carriage and disease due to enteric pathogens in food animals. Our collaborative efforts harmonize with the recent government-wide initiative to better understand, characterize, and mitigate antimicrobial resistance (AMR) across the food chain. Our proactive and collaborative efforts will also contribute to national goals to further decrease the burden of foodborne illness by the year 2030 (https://www.healthypeople.gov/).

Diarrheal diseases account for multi-billion-dollar annual economic losses to the food animal industry due to reduced weight gain, mortality of young animals and treatment costs. Diarrheal infections in neonates, post-weaning period and adult animals are very important diseases in swine and other livestock and are caused by pathogenic bacteria and viruses including enterotoxigenic E. coli (ETEC), Clostridium perfringens, Salmonella, porcine epidemic diarrhea virus (PEDV), rotavirus (RV), calicivirus and emerging coronaviruses [porcine deltacoronavirus (PDCoV)]. Similarly, Brachyspira and Lawsonia species represent the most important causes of bacterial enteric diseases of grow/finish pigs in the US. L. intracellularis causes porcine proliferative enteropathy and B. hyodysenteriae/ B. hampsonii are the etiologic agents of swine dysentery. Therefore, effective prevention and control of enteric diseases are critical to maintain production efficiency, produce wholesome meat, enhance food security and safety, and animal well-being.

Foodborne illness is a major public health concern in the US. The CDC estimates that about 1 in 6 Americans get sick, 128,000 are hospitalized, and 3,000 die of foodborne diseases each year. Norovirus caused the most illnesses (5.5 million) whereas non-typhoidal Salmonella spp caused the most economic losses ($4.1 billion) followed by Toxoplasma gondii ($3.7 billion), Listeria monocytogenes ($3.2 billion), norovirus ($2.6 billion), and Campylobacter ($2.2 billion).

The Foodborne Diseases Active Surveillance Network (FoodNet) was established in 1995 and is a collaborative program among CDC, 10 state health departments, the USDA FSIS, and the FDA. FoodNet conducts surveillance for bacterial (Campylobacter, Listeria, Salmonella, enterohemorrhagic E. coli (EHEC) O157 and non-O157, Shigella, Vibrio, and Yersinia) and parasitic (Cryptosporidium, Cyclospora) infections diagnosed by laboratory testing of patient samples. It is not surprising that the US President, Congress, and USDA have made national food safety a high priority mission. Data from 2019 FoodNet report highlight three main points: 1) The number of infections diagnosed by culture-independent diagnostic tests (CIDTs) increased 32% compared with the previous 3 years; 2) Progress in controlling major foodborne pathogens in the United States has stalled; and 3) Incidence of some pathogen infections are decreasing, whereas others are increasing. These facts can be partially explained by the increased testing of samples and the increased use of more sensitive CIDTs in addition to the culture-based diagnostic tests compared with previous years. Importantly, most of the known bacterial, viral and parasitic food-borne disease agents are primarily zoonotic. Thus, investigation and control in animal reservoirs are required to understand their epidemiology and biology to maximize opportunities for control. For example, chickens are an important source of Salmonella and Campylobacter infections and S. Typhimurium infections in humans declined after widespread vaccination of chickens against this Salmonella serotype. In addition, several of these agents are also animal pathogens or have close relatives that are animal pathogens. Thus, investigating the host-microbe relationship in animal models or animal populations could solve these problems in humans.

Although most food-borne pathogens cause acute disease, many of them can cause severe complications or chronic diseases. Severe manifestations include hemorrhagic colitis, septicemia, meningitis, joint infection, hemolytic uremic syndrome with complicating brain damage, paralysis and miscarriage, inflammatory diseases, among other diseases. The incidence of autoimmune disorders is rapidly increasing, and a number of these syndromes are triggered by enteric pathogens. For example, C. jejuni is a leading cause of bacterial food-borne gastroenteritis that can trigger serious autoimmune diseases. The acute neuropathies such as Guillain Barré Syndrome (GBS), Miller Fisher Syndrome (MFS), Inflammatory Bowel Disease (IBD) and Reiter’s Arthritis (RA) have all been associated with Campylobacter infection. It has now been demonstrated that specific antibiotic resistance carriage by enteric pathogens can further exacerbate these autoimmune manifestations when antibiotics are used.

Unique dynamic interactions between enteric pathogens, animals, humans, and their gut microbiota (microbiome), sharing the same environment, are considered within the “One Health” concept. This new NC1202 project will develop and employ interdisciplinary approaches to address critical areas that will enhance animal health, food safety and food security by maintaining efficient livestock and poultry production and reducing reliance on antibiotic use through the development of alternative approaches for sustainable food animal agriculture.

IMPORTANCE & CONSEQUENCES.  The USDA Economic Research Service (ERS) estimated that the total cost of foodborne illness for the 15 leading foodborne pathogens in the USA in 2018 imposed over $17.6 billion in the economic burden on economy, due to medical costs, productivity losses, and costs associated with premature deaths due to diseases. Besides human health risks, animal diarrheal disease due to food-safety-related pathogens and other animal-specific pathogens remain an economically important cause of production loss to livestock producers. Diarrheal diseases account for multi-billion-dollar annual economic losses to the food animal industry due to reduced weight gain, mortality of young animals and treatment costs. Neonatal diarrhea and post-weaning diarrhea and diarrhea in grow/finish pigs are among the most important swine diseases and are caused by pathogenic bacteria and viruses including ETEC, Lawsonia, Brachyspira, PEDV, PDCoV and RV. Foodborne illness incidence can be reduced with new knowledge and new detection procedures that have been and will be developed through this collaborative research. Production systems for food animals have evolved toward large size and complexity. At the same time, there is a new initiative to withdraw the use of growth promoting and prophylactic antibiotics. Due to the recent ban on use of antibiotics for growth promotion in food animals, there is a new emphasis towards natural, grass-fed, and organic production systems. These new animal systems pose new challenges associated with food-borne pathogens as animals encounter diversely contaminated water and soil. Continued research in support of food safety and control of diarrheal diseases of livestock is needed to optimize animal health and welfare and to produce safe foods. The consequences of inaction are increases in disease incidence and costs accompanied by burgeoning chronic disease rates.

FEASIBILITY. Based on recent data by FoodNet, foodborne illness is still common and costly, yet a preventable-public health problem. The significant foodborne pathogens include but are not limited to norovirus, Salmonella, Campylobacter, STEC, Listeria, Clostridium perfringens, and Staphylococcus aureus. Progress has been made in preventing and controlling foodborne illness; the incidence of several high impact pathogens has declined based on targeting them for control and prevention, such as the widespread vaccination of chickens against Salmonella Typhimurium was strongly associated with the decreased incidence of the related foodborne illness in humans due to this pathogen. CDC believes this success demonstrates the feasibility of preventing foodborne illnesses; research, collaboration and dissemination of successful innovations will be essential to continue this trend.

MULTISTATE EFFORTS. The magnitude of this problem dictates a team-based approach to devising and implementing preventative strategies. Individuals with markedly varied areas of expertise are needed to devise scientific strategies for pathogen control, educate agricultural experts and producers, and apply new strategies on farms. The complexity and range of these enteric pathogens and of the food animal production systems in which they occur require collaborative research involving scientists with a wide range of expertise to work together in pursuit of solutions. No individual institution can match the range of scientific expertise we offer. The NC1202 group has bacteriologists, virologists, parasitologists, molecular biologists, epidemiologists, pathologists, systems biologists and immunologists with a long history of successful collaboration and productivity in developing innovative strategies.

IMPACTS, INNOVATION, OUTCOMES. 1) Emerging diseases. We expect to identify, characterize and develop improved detection and prevention methods related to newly recognized, novel or emerging causes of zoonotic enteric disease and enteric pathogens of food animals. 2) Developing preventions & interventions. We expect to develop and improve preventative measures and interventions to reduce the incidence of enteric and foodborne pathogen infections in food animals. We also expect to develop effective and sustainable approaches to mitigate AMR. 3) Disseminating knowledge. We will provide training or continuing education to disseminate new information to students, producers, veterinarians, diagnostic labs, and others to implement interventions and preventative measures. Expected outcomes will be increased understanding of mechanisms of initiation of acute and chronic enteric infections for known and emerging enteric pathogens. This will provide science-based best practices and implementation strategies for preventive measures and interventions for the major enteric diseases of food animals. The new NC1202 project addresses critical, timely, cross-cutting research areas and objectives (e.g., antimicrobial resistance, intestinal microbiome) that will enhance food safety while maintaining efficient pork, beef, and poultry production.