CONTROL ID: 2067192

TITLE: Veterinary Molecular Pathology

Bridging the Gap Between Clinical Disease and Molecular Pathogenesis

ABSTRACT BODY:

Narrative (400 words): The term “pathology” originates from the Greek words “pathos” and “logos” and is therefore best translated as the “study of disease”. Pathology was established as an essential part of modern medicine that studies the etiology, pathogenesis and outcome of diseases by the Italian physician Giovanni Battista Morgagni in 1761. Utilizing postmortem examinations, he based his studies on empiric data that identified and localized causes of diseases in different organ systems rather than explaining disease processes by an imbalance  of bodily fluids (humoral pathology) as proposed by the ancient Greeks. Rudolf Virchow revolutionized pathology and created the foundation of modern scientific medicine by introducing the concept of cellular pathology, which evaluates cell and tissue architecture to identify and classify morphologic alterations that form the basis of disease. These principles of cellular pathology are still relevant today. By identifying morphologic alterations, both gross and microscopically, pathologists have been able to determine disease processes, their cause and also predict the clinical outcome, thereby establishing pathology as the central science in modern medicine and especially disease investigations, with modern microbiology underscoring its importance. By being able to associate an infectious agent with a specific microscopic alteration, pathology became essential in both diagnostics and pathogenesis research of infectious diseases. Classical gross and microscopic evaluations of tissues, however, are insufficient to provide a precise prognosis for an individual patient or determine the proper therapeutic approach, and also fail to show causality of lesions with infectious agents that are not microscopically identifiable. This has led to a shift in the paradigm of how pathologists analyze tissues for diagnostic purposes or pathogenesis research, now also using molecular methods to visualize targets of interest within microscopic lesions or extract target cells for further molecular analysis. The evolution of cellular pathology into molecular pathology has already allowed us to link tissue alterations more precisely to the clinical course of disease and to molecular mechanisms of disease processes. Modern molecular veterinary pathology has altered the way we perform daily diagnostic testing and contribute to our understanding of pathogenesis. Embracing molecular pathology as the future of our profession requires a shift in our training methods of young pathologists, a close collaboration with scientists across medical disciplines, and education of the public on the benefits of integrating such new technologies into routine diagnostics, despite the higher costs.

Speaker Biography (300 words): Dr. med. vet. habil. Matti Kiupel, BS, MS, PhD, DACVP, Fachtierarzt für Veterinär Pathologie, is a Professor in the Department of Pathobiology and Diagnostic Investigation at Michigan State University in the College of Veterinary Medicine where he serves as the Section Chief of Anatomic Pathology in the Diagnostic Center for Population and Animal Health. He is also the head of the histology and immunohistochemistry laboratory, the largest veterinary diagnostic molecular pathology laboratory in the country.

Dr. Kiupel received his veterinary degree from the Freie University of Berlin, Germany in 1996. He completed his doctoral thesis research in 1999 on canine malignant lymphomas in a collaborative study between the University of Cambridge, UK, the University of Utrecht, Netherlands and the Freie University, Berlin, Germany. He completed a residency in anatomic pathology from 1996 until 1999 and a PhD on the pathogenesis on porcine circovirus in 2001 at Purdue University.

Dr. Kiupel has received many honors and awards in Germany, The United Kingdom, and the United States. He has served on 30 PhD and MS graduate student committees (11 as chair), and been the primary advisor of 7 residents in anatomic pathology. His work focuses on incorporating education in veterinary medicine and pathology with training in human biomedical research designed to address translation of research findings from animal models to the clinical setting. He has published more than 200 peer-reviewed scientific manuscripts and numerous book chapters in the field of veterinary and comparative pathology and specifically tumorpathology, and has been the lead author on the WHO fascicle of

neuroendocrine tumors of domestic animals. He also has maintained a strong interest in infectious, especially viral, diseases and has discovered numerous novel infectious diseases. He has an interest in ferret diseases and just finished an update of the chapter on viral diseases of ferrets for the next edition of "Ferret Biology and Diseases." Recently Dr. Kiupel has been invited to lead research into coral diseases for the Khalid Bin Sultan Living Oceans Foundation, exploring new frontiers in pathology and disease mechanisms.

CURRENT CATEGORY/DISCIPLINE: Plenary

AUTHORS/INSTITUTIONS: M. Kiupel, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, Michigan, UNITED STATES;

AWARDS:

Trainee Letter:

CONTROL ID: 2068885

TITLE: Veterinary Laboratory Knowledge Translation and Transfer

ABSTRACT BODY:

Narrative (400 words): Entry into the molecular age has presented exciting challenges and opportunities for veterinary laboratory medicine. Based on their incoming caseload and their ability to solicit submissions, diagnostic labs serve as resources in identifying emerging issues, and then also able to utilize the new knowledge for test development. To be useful to veterinary laboratories and their clients, test results must of course be relevant, credible, accurate, unambiguous, and timely, and available at minimal cost to users. A tall order!

In order to translate new knowledge into diagnostic applications offered to clients, the diagnostic lab must validate the test in-house, often based on a published peer-reviewed publication, and following the guidelines of the AAVLD Requirements for an Accredited Veterinary Medical Diagnostic Laboratory and the OIE (World Organization for Animal Health). When validating a new test for a common pathogen, diagnostic labs typically have a distinct advantage of incoming/archived case materials that can be used for test validation.

When dealing with a new condition or agent – be it new strains of Brachyspira, new immunohistochemistry targets, white nose syndrome in bats, or porcine epidemic diarrhea virus - a strength of the AAVLD is the network of accredited sister labs willing to share material. Primers and probes can be designed, ordered, and delivered promptly to facilitate rapid test development. Synthetic control material may also be available for purchase. Given the availability of partial and whole genome sequencing, variant microbes can be identified speedily, trends in disease spread tracked, and disease control implemented.

The desired outcome of this test development process is to fill a need and have a beneficial impact on client service. If sufficiently unique, the new test and its supporting documentation could be publishable in the Journal of Veterinary Diagnostic Investigation to be quickly and widely shared with the laboratory community.

Speaker Biography (300 words): After completing his DVM at WCVM, Saskatoon, in 1969, and PhD in Veterinary Clinical Pathology at the Ontario Veterinary College in Guelph in 1973, Dr. Maxie worked in Kenya investigating the pathology of trypanosomiasis and theileriosis (1974-77). He worked on faculty at the OVC (1977-82, tenured associate professor) and as a Veterinary Pathologist (1982-94), and then as Guelph Laboratory Head (1994-97), for Veterinary Laboratory Services of the Ontario Ministry of Agriculture, Food and Rural Affairs. He was board certified as an anatomic pathologist by the American College of Veterinary Pathologists in 1984. He is currently the Director of the Animal Health Laboratory (1997 - ) and co-Executive Director (2007 - ) of the Laboratory Services Division at the University of Guelph.

Dr. Maxie was the editor-in-chief of the Canadian Veterinary Journal (1986 - 1991), and chair of the editorial committee of the CVMA until 1998. His scientific publications include 10

book chapters and >50 peer-reviewed articles. He edited the 3 volumes, and co-authored 3 chapters, in the 5th edition of “Jubb, Kennedy and Palmer's, Pathology of Domestic Animals", published in 2007, and is currently editing the 6th edition of this work. He is a past-president of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) (2007-08), a long-time member of the AAVLD Accreditation Committee and past-chair of the Strategic Planning Committee. He was the 2011-12 president of the Canadian Animal Health Laboratorians Network (CAHLN). Effective November 1, 2014, he will succeed Dr. Jerry Saliki as editor-in-chief of JVDI.

CURRENT CATEGORY/DISCIPLINE: Plenary

AUTHORS/INSTITUTIONS: G. Maxie, H. Cai, D. Ojkic, D. Slavic, J. DeLay, University of Guelph, Guelph, Ontario, CANADA;

AWARDS:

Trainee Letter:

CONTROL ID: 2068973

TITLE: Leveraging Laboratory Data for Animal Health Surveillance

ABSTRACT BODY:

Narrative (400 words): Building comprehensive and integrated animal health surveillance systems requires identifying and then leveraging appropriate surveillance streams to meet the specific purpose of the surveillance. Those purposes or objectives may include: 1) claims of disease freedom, 2) emerging disease detection, documentation and characterization, 3) continuity of business, 4) identifying changes in disease prevalence, temporal or geographic distribution and, 5) identifying areas requiring more intensive surveillance. The flow of laboratory test data into surveillance systems has proven invaluable for many surveillance purposes and objectives.

Surveillance for classical swine fever, whose objective is to support the U.S. claim of disease freedom, includes a laboratory component. Similarly, current laboratory testing efforts to support the Swine Enteric Coronavirus reporting requirements are critical for emerging disease detection, documentation and characterization. Both of these laboratory streams have well-defined data requirements. Questions arise, however, about what surveillance data elements are best collected through the laboratory submission and testing process and which elements may be more appropriately collected outside of those processes. A minimum set of 15 animal health laboratory data elements to support surveillance was suggested by Kloeze et al. (Kloeze, J., Transboundary and Emerging Diseases, 2011). This data set was designed to support domestic and international disease reporting requirements, effective analysis and syndromic surveillance efforts. It was suggested that these 15 elements all be included on a laboratory submission form. The completeness and accuracy of the data on a submission form and subsequent accuracy of the data moved through the laboratory to the surveillance system thus relies primarily on the diligence and thoroughness of the submitter of the samples to the laboratory and secondarily on the laboratory’s ability to capture that submitted data

accurately. Is the laboratory sample submission and testing process the most appropriate place to collect surveillance data? Other potential options will be presented.

In addition to questions about the appropriateness of surveillance data collection at the time of sample submission are questions about the information technology structures necessary to make this surveillance stream efficient and effective. Examples will be presented of current data management and transfer processes, including the laboratory messaging service, Veterinary Services Processing Streamlining and what is needed to move these and other IT systems forward.

Speaker Biography (300 words): Dr. Brian McCluskey received a Doctorate in Veterinary Medicine from Washington State University in 1987, and, following graduation, was in large animal practice, primarily dairy, in western Washington state. He joined APHIS in 1990 and

was stationed in Charleston, West Virginia as a section veterinary medical officer. He was then sponsored by APHIS Cattle Diseases Staff in a graduate program at the University of Florida and after receiving his Masters degree in epidemiology, was stationed at the Colorado Area Office as the Area Epidemiology Officer. During this time he became a Diplomate in the American College of Veterinary Preventive Medicine. Brian then moved to the Center for Animal Health Monitoring in Fort Collins, CO as the Dairy Commodity Support Analyst. He received a PhD in Epidemiology at Colorado State University in 2003 and from 2003 to 2007 was the Director of the USDA’s National Surveillance Unit. He joined the Senior Executive Service in 2007 as the Director of Veterinary Services Western Region. Brian was named APHIS, Veterinary Services Chief Epidemiologist, a senior scientist level position, in 2011.

CURRENT CATEGORY/DISCIPLINE: Plenary

AUTHORS/INSTITUTIONS: B. McCluskey, USDA, APHIS, Fort Collins, Colorado, UNITED STATES;

AWARDS:

Trainee Letter:

CONTROL ID: 2073827

TITLE: Veterinary Pharmacovigilance and the Use of Diagnostic Laboratory Data and Services by the Animal Health Industry

ABSTRACT BODY:

Narrative (400 words): Animal health companies (AHC) utilize laboratory services during development, licensure and post licensing marketing of veterinary pharmaceutical, biological and diagnostic products. This discussion will focus on the use of laboratory data and services in monitoring the safety and efficacy of marketed veterinary products. The documentation, investigation, and assessment of reports of suspected adverse events associated with use of marketed veterinary medical products are collectively referred to as veterinary pharmacovigilance. Pharmacovigilance surveillance depends on spontaneous reporting from end users including pet owners, producers, distributors and veterinarians. Adverse events may include an unexpected effect, including adverse reactions, drug residue, or ecotoxicity, and/or a lack of efficacy relative to label indications. Human exposures, physical product defects and extra label use are also documented. The regulatory frameworks that define reporting requirements and timelines vary by type of product and licensing agency. Animal Health Companies typically use a pharmacovigilance database that allows recording of product incidents, has query capabilities for retrieving data to report trends and allows electronic submission to regulatory authorities.

Adverse event investigations often involve utilization of diagnostic testing by an attending veterinarian in consultation with a technical veterinarian from the AHC to investigate a reported product incident. The breed, sex, age, concomitant medications and concurrent or pre-existing health conditions are all recorded. In herds, the number of patients exposed, morbidity and mortality data is collected. The attending veterinarian’s clinical findings are entered using a standardized clinical sign dictionary (VEDDRA system). Pathology, microbiology, molecular biology, serology and toxicology tests may be used to investigate

reports in an attempt to determine the cause of the event reported; to assess if the experience is related to an adverse product event; and to trend such reports over time.

Beyond individual case investigations, examples of use of diagnostic laboratory services and data in pharmacovigilance include examination of bacterial isolates to monitor antimicrobial resistance patterns. Monitoring of vaccine efficacy and characterization of bacterial and viral isolates from ill but appropriately vaccinated animals allows identification of newly emerging strains or pathogens should efficacy fail. The goal of pharmacovigilance is to incorporate these findings in product profiles to provide safe and effective products for practical use, to extend claims and to quickly identify and resolve product issues not identified in pre-licensing clinical trials.