The U.S. National Antimicrobial Resistance Monitoring System:
Transcription
The U.S. National Antimicrobial Resistance Monitoring System:
The U.S. National Antimicrobial Resistance Monitoring System: Achievements and Challenges Patrick McDermott, Ph.D. Director, NARMS U.S. Food & Drug Administration Center for Veterinary Medicine Office of Research Laurel, MD USA The “Golden Age” of Antibiotics Began in 1933, when an antibiotic called sulfanilamide cured a 10-month old German infant dying of a bloodstream staphylococcal infection. Gerhard Domagk, sulfa drug pioneer. Nobel Prize, 1939 The “Golden Age” of Antibiotics “For most of the infectious diseases on the wards of Boston City Hospital in 1937, there was nothing that could be done beyond bed rest and good nursing care. Then came the explosive news of sulfanilamide, and the start of the real revolution in medicine. I remember the astonishment when the first cases of pneumococcal and streptococcal septicemia were treated in Boston in 1937. The phenomenon was almost beyond belief. Here were moribund patients, who would surely have died without treatment, improving…within a matter of hours…and feeling entirely well within the next day…we became convinced, overnight, that nothing lay beyond reach for the future.” Lewis Thomas. Notes of a Medicine Watcher. ‘83. Viking Press •Albert Lasker Award •Member of the NAS •National Book Award The “Golden Age” of Antibiotics 1952 Words of Caution The Nobel Prize in Physiology or Medicine 1945 "for the discovery of penicillin and its curative effect in various infectious diseases" Sir Alexander Fleming Sir Howard Florey Ernst Chain Sir Alexander Fleming Nobel Lecture, December 11, 1945 “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.” Impact of Resistance 1. More expensive/toxic drugs 2. Additional diagnostic testing 3. Extended length of stay in the hospital 4. Costs to patient/family-time from work, increased mortality 5. Resistance genes remain a problem for the future – the hospital/farm as reservoir Summary of International Activities • TATFAR – created in 2009 to promote cooperation and info exchange between US and EU on human and animal aspects of AMR • GHSA AMR action package – Surveillance, one health, and R&D working groups • WHO GAP 2015 requests the Member States to effectively address the problem by strengthening their national systems – Surveillance – GLASS – PAHO – addressing AMR • G7 - under the 2015 German Presidency suggested convening an experts group – includes Japan • G20 – China plans to make AMR a subject for their presidency in 2016 7 The US National Action Plan March 2015 Outlines steps for implementing the National Strategy on Combating AntibioticResistant Bacteria and addressing the policy recommendations of the President’s Council of Advisors on Science and Technology (PCAST) report on Combating Antibiotic Resistance. Five goals: 1. Slow the emergence of resistant bacteria and prevent the spread of resistant infections. 2. Strengthen national one-health surveillance efforts to combat resistance. 3. Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria. 4. Accelerate basic and applied research and development for new antibiotics, other therapeutics, and vaccines. 5. Improve international collaboration and capacities for antibiotic-resistance prevention, surveillance, control, and antibiotic research and development. Includes information sharing, surveillance (drug use and resistance), stewardship 8 initiatives, risk assessments, and more. Level of concern depends on pathogen and type of resistance Urgent Threats Clostridium difficile Carbapenem-resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae Serious Threats Multidrug-resistant Acinetobacter Fluconazole-resistant Candida (a fungus) Vancomycin-resistant Enterococcus (VRE) Multidrug-resistant Pseudomonas aeruginosa Drug-resistant Salmonella Typhi Drug-resistant Shigella Methicillin-resistant S. aureus Drug-resistant Streptococcus pneumoniae Drug-resistant tuberculosis Drug-resistant Campylobacter Drug-resistant Non-typhoidal Salmonella ESBL+ Enterobacteriaceae Concerning Threats Vancomycin-resistant S. aureus (VRSA) Erythromycin-resistant Group A Streptococcus Clindamycin-resistant Group B Streptococcus FDA Center for Veterinary Medicine Strategy to Limit Resistance Multipronged strategy designed to limit or reverse resistance arising from the use of antibiotics in food-producing animals, while continuing to ensure the availability of safe and effective antibiotics for use in animals and humans • • • • • • • • • • The National Antimicrobial Resistance Monitoring System Extralabel use prohibition of fluoroquinolones and glycopeptides Revised safety assessment process (GFI #152) Withdrawal enrofloxacin in poultry Revised judicious use guidance (GFI #209) Cephalosporin extralabel use prohibition Industry guidance on eliminating production uses (GFI #213) Enhanced annual summary of antibiotic sales data Update on veterinary feed directive (GFI #120) Collaboration with international partners (WHO, OIE, Codex) 1996 1997 2003 2005 2012 2012 2013 2014 2015 What is integrated surveillance of antimicrobial resistance in foodborne bacteria? The coordinated sampling and testing of bacteria from food animals, foods, and clinically ill humans; and the subsequent evaluation of antimicrobial resistance trends throughout the food production and supply chain using harmonized methods. Source: WHO-AGISAR report Purpose of Integrated Surveillance 1. Baselines - Document resistance levels in different reservoirs 2. Spread - Describe the spread of resistant bacterial strains and resistance genes 3. Trends - Identify temporal and spatial trends in resistance 4. Attribution - Generate hypotheses about sources and reservoirs of resistant bacteria 5. Risk analysis - Understand links between use practices and resistance 6. BOI - Identify risk factors and clinical outcomes of infections caused by AMR bacteria 7. Education - Provide data for education on current and emerging hazards 8. Policy - Guide evidence-based policies and guidelines to control antimicrobial use in hospitals, communities, agriculture, aquaculture, and veterinary medicine 9. Regulations Pre-harvest - Support risk analysis of foodborne antimicrobial resistance hazards Post-harvest - Identify interventions to contain resistance and evaluate their effectiveness 10. Evaluate interventions 12 11. Go back to #1 Challenges of Integrated Surveillance for Antimicrobial Resistance 1. Gathering accurate information and bacterial isolates is expensive and laborious 2. Burden of illness and food consumption data are needed for design and prioritization of pathogens and commodities 3. Sound sampling scheme along the food chain is critical for valid trend analysis 4. Combining resistance and use data in a meaningful way 5. Cooperation, collaboration, good communication and data sharing between a. agriculture, industry and public health sectors b. microbiologists & epidemiologists within and across sectors Challenges of Integrated Surveillance for Antimicrobial Resistance 6. Political/financial support - Requires recognition of the public health issues and the need for ongoing risk assessments 7. Establish a process for review and enhancement 8. Remain flexible in order to stay current 9. Adapt to changing technologies 10. Understanding the implications of the data and the need for research 11. Publishing often very complex findings to different audiences in a timely manner 12. Using the data to formulate sound public health policy 13. International harmonization and cooperation Bacteria Tested Human - CDC Animal - USDA • • • • • • • • • • • • Non-Typhoidal Salmonella (1996) Campylobacter (1997) E. coli 0157:H7 (1996) Salmonella Typhi (1999) Shigella (1999) Vibrio Enterococcus (2001) E. coli (2004) Non-Typhoidal Salmonella (1997) Campylobacter (1998) E. coli (2000) Enterococcus (2003) Retail Meats - FDA (2002) • • • • Non-Typhoidal Salmonella Campylobacter Enterococcus E. coli NARMS Objectives 1. Monitor trends in antimicrobial resistance among foodborne bacteria from humans, retail meats, and animals 2. Disseminate timely information on antimicrobial resistance to promote interventions that reduce resistance among foodborne bacteria Conduct research to better understand the emergence, persistence, and spread of antimicrobial resistance 3. 4. Assist the FDA in making decisions related to the approval of safe and effective antimicrobial drugs for animals NARMS Strategic Plan Goal 1: To develop, implement and optimize a shared database, with advanced data acquisition and reporting tools Goal 2: To make sampling more representative and more applicable to trend analysis Goal 3: To strengthen collaborative research projects to address high risk food safety issues 2012-2016 Goal 4: To support international activities which promote food safety, and mitigate the spread of antimicrobial resistance 1. Monitor Trends: Sampling Strategy 18 Human isolated testing - CDC • Bacteria isolated at the state laboratory and sent to CDC for susceptibility testing and additional analyses • Non-typhoidal Salmonella- all 50 states submit every 20th isolate • Campylobacter- 10 FoodNet sites submit every 2nd, 3rd, or 5th isolate • More details at www.cdc.gov/narms Retail meat testing - FDA • 14 sites total since 2013 • 2002- mid 2015 each site collected 40 meats/month (10 each of chicken parts, ground turkey, pork chop, and ground beef) • Beginning mid 2015 each site collects 80 meats/month (40 chicken parts, 20 ground turkey, 10 pork chop, and 10 ground beef) • All sites culture for Salmonella (all meat types) and Campylobacter (poultry) • Four sites culture for E. coli and Enterococcus • Isolates are sent to FDA for analysis • Sample total = 6,720 per annum 13,440 History of NARMS - USDA Old System (HACCP) 1. In Plant Pathogen Western Lab FSIS PR/HACCP samples Midwestern Lab ARS Eastern Lab received Salmonella isolates Eastern Lab Chicken carcasses Campylobacter, E coli, Enterococcus Swine Cattle Campylobacter Salmonella Chicken Turkeys x x x x E. coli x Enterococcus x x New System (Cecal) • • • • • Samples taken by FSIS veterinarians and inspectors at FSIS-regulated plants and establishments Cecal samples better reflect animal status and less confounded by plant events A randomized, nationally representative testing of slaughterhouses Ability to distinguish production classes Complete microbiology for all animal species Swine hogs, sows Cattle dairy, beef steers, heifers Chicken Turkeys Campylobacter x x x x Salmonella x x x x E. coli x x x x Enterococcus x x x x Pathogen History of NARMS – USDA 2. On-Farm • Collaboration with USDA- Agricultural Research Service (ARS) and University partners • Examining resistance on farm and differences between farm and slaughter • Looking for rare phenotypes (early detection) • Interventions • Drug use information 22 NARMS Highlights 2013 • • • • About 80% of human Salmonella isolates are not resistant to any of the tested antibiotics, a finding that has not changed in the past 10 years. Further, resistance to ceftriaxone, azithromycin, and quinolones, three important drugs used to treat human Salmonella isolates, remains below 3%. Salmonella multi-drug resistance (resistance to three or more classes of antibiotics) in human, cattle, and chicken isolates has not changed or declined in the last decade, CipR C. jejuni resistance was at its lowest level in retail chicken to date (11%). 23 NARMS Highlights 2013 Multidrug resistance (MDR) in human isolates of a common Salmonella serotype (l 4,[5],12:i:-) continues to rise. Resistance has more than doubled from 18% in 2011 to 46% in 2013. An increase in MDR and ceftriaxone resistance was also observed in Salmonella serotype Dublin isolated from cattle and human sources. 24 Resistance in Salmonella from Humans: 1948-1990s 25 Resistance in Salmonella from Humans: 1996-2011 26 Resistance in Salmonella from Humans: 1948-2011 27 1. Monitor Trends: Laboratory Methods 28 Antimicrobial Susceptibility Testing NCCLS Quality Control Organisms (ug/ml) Antimicrobial cefoxitin azithromycin chloramphenicol tetracycline ceftriaxone amoxicillin/clavulanate ciprofloxacin gentamicin nalidixic acid ceftiofur sulfamethoxazole trimethoprim/sulfa kanamycin ampicillin streptomycin positive control negative control Total # wells Resistant NARMS #wells Ranges breakpoint /plate S. aureus E. faecalis E. coli P. aeruginosa Within ug/ml 29213 29212 25922 27853 CLSI QC 1-4 0.25-2 2-8 0.12-1 1-8 0.12-0.5 0.12-0.5 0.12-1 >=32 >=16 >=32 >=16 >=4 >=32/16 >=4 >=16 >=32 >=8 >=512 >=4/76 >=64 >=32 7 8 5 4 8 6 9 7 7 7 6 6 4 6 0.5-32 0.125-16 2-32 4-32 0.5-64 1-32 0.015-4 0.25-16 0.5-32 0.12-8 16-512 0.12-4 8-64 1-32 none 2 3 1 96 32-64 0.25-1 32-128 <0.5/9.5 1-4 0.25-1 64-256 4-16 8-32 0.25-1 0.25-2 4-16 32-128 <0.5/9.5 16-64 0.5-2 1-4 0.5-4 2-8 0.5-2 0.03-0.12 2/1-8/4 0.004-0.015 0.25-1 1-4 0.25-1 8-32 <0.5/9.5 1-4 2-8 1-4 8-32 8-64 0.25-1 0.5-2 16-64 8/152-32/608 yes yes yes yes yes yes yes yes yes yes yes yes yes yes None in CLSI QC range 29 Drug selection • Important in veterinary medicine (e.g. tetracycline) • Important in human medicine (e.g. carbapenems) • Important in both human and veterinary medicine (e.g. cephalosporins, fluoroquinolones) • Epidemiologic markers (e.g. chloramphenicol) • Harmonized with CIPARS 30 Added Value of NARMS • • Understanding the sources of resistance also helps with strain attribution in BOI estimates Outbreak detection – PulseNet (NARMS PulseNet database has >12,000 data entries) • 8,380 Salmonella • 3,439 Campylobacter • 547 E. coli • 69 Vibrio • • • • • • • • Phylogenetics Evolution of MDR Virulence Trend analysis Method development Emerging trends Networked of trained and dedicated laboratory personnel and epidemiologists Infrastructure for targeted studies Opportunity to serve broader FDA food safety priorities Additional Analyses Source: CDC 32 2. Reporting: Disseminate timely information 33 Human Population Retail Meats Physician Visit Random stratified sampling in 14 States ORA Imported Foods Local Lab State Lab Grocery Stores Chicken Ground turkey Ground beef Pork chop Farm Pilots Farm to Slaughter Drug use data point Animals Random sampling of national production at slaughter Chickens, Turkeys, Cattle, Swine HACCP 2013-present HACCP 1997-2013 Chicken only Other pathogens surveyed Campylobacter Salmonella Enterococcus E. coli Data Integration Integrated Report Integrated NARMS Report 35 Integrated NARMS Report cont’d 36 Integrated NARMS Report cont’d 37 Antimicrobial Drugs Approved for Use in Food-Producing Animals: 2011 Sales and Distribution Data Reported by Drug Class Domestic Export Antimicrobial Class Aminoglycosides Annual Totals (kg) 214895 Cephalosporins Ionophores 26,611 4,123,259 Lincosamides Macrolides 190,101 582,836 Penicillins 880,163 Sulfas 371,020 Tetracyclines 5,642,573 NIR 1,510,572 Tetracyclines 15,321 NIRE 185,333 38 Conduct Research 39 Added Value of Integrated Surveillance • • • • • • • • • Source attribution is useful in burden of illness estimates Database of strain relatedness for outbreak detection Phylogenetics Evolution of MDR Virulence Method development Emerging trends Networked of trained and dedicated laboratory personnel and epidemiologists Infrastructure for targeted studies Opportunity to serve broader food safety priorities Welch TJ, Fricke WF, McDermott PF, et al. Multiple antimicrobial resistance in plague:an emerging public health risk. PLoS One. 2007 Mar 21;2(3):e309. NARMS Research: Filling the Gaps in Surveillance 1. Standardize and validate in vitro antimicrobial susceptibility testing methods 2. Measure the effects of veterinary antimicrobials on emergence of resistance in zoonotic foodborne bacteria in target animals 3. Examine the role of animal feeds (rendered products, dried commodities, complete feeds) in the ecology of resistance 4. Risk factors and clinical outcomes infections caused by AR pathogens 5. Characterize and compare molecular mechanisms of resistance 6. Develop rapid methods to identify/characterize resistant bacteria (WGS) Assist the FDA 42 Qualitative Risk Assessment: Components and Procedures Hazard Characterization Qualitative Risk Assessment Release Assessment probability that resistant bacteria are present in target animal as a consequence of drug use (rank as High, Medium, or Low ) Exposure Assessment probability for humans to ingest bacteria in question from the relevant food commodity (rank as High, Medium, or Low ) Consequence Assessment probability that human exposure to resistant bacteria results in an adverse health consequence (rank as High, Medium, or Low ) Overall Risk Estimate: Integration of release, exposure and consequence assessments. (rank as High, Medium, or Low ) Risk Estimation Where can we use NARMS Data? • Release Assessment – Parameters: • • • • • Mechanism of Activity – Class of Drug, targeted action Spectrum of Activity – Gram +/- activity, susceptibility data Resistance mechanisms – Structural, efflux, gene Resistance Transfer – chromosomal, mobile element Selection Pressure – co-selection • Exposure Assessment – Parameters: • Consumption of commodity • Prevalence of zoonotic pathogens in commodity • Prevalence of resistance in zoonotic pathogens 44 Consequence Assessment Describes human health consequence of exposure to resistant bacteria based on importance of drug (or related drugs) to humans (ranking of antimicrobials) Drug Ranking Examples • Critically Important 3rd Generation cephalosporins (Ceftriaxone), macrolides (Erythromycin), fluoroquinolones (Ciprofloxacin). • Highly Important 4th Generation cephalosporins, aminoglycosides, clindamycin • Important 1st & 2nd Generation cephalosporins, monobactams, quinolones Examples of Risk Management Tools Approval conditions Category 1 (H) Category 2 (M) Category 3 (L) Marketing status Rx Rx/VFD Rx/VFD/OTC Extra-label use ELU restriction Restricted in some cases ELU permitted Extent of use Low Low/Medium Low, Medium, High Advisory committee review YES In certain cases NO Post-approval monitoring NARMS NARMS NARMS GFI #152, Table 8, pp. 25 Withdrawal of Approval of Fluoroquinolones for Poultry • In 2000, CVM proposed the withdrawal of the approval of the new animal drug applications for fluoroquinolone use in poultry. • Abbott Laboratories withdrew their application for sarafloxacin. • Bayer Corp. requested a hearing to address the safety of Baytril™, the trade name for enrofloxacin. • CVM research validated a standardized AST method for Campylobacter to evaluate the resistance data being reported • CVM research conducted in vivo treatment studies with Campylobacter infected broilers • The Final Decision of the FDA Commissioner to withdraw the approval became effective September 12, 2005. 47 Extra-Label Use Prohibition of Certain Cephalosporins • Effective April 5, 2012 • FDA prohibits unapproved uses of 3rd gen. cephalosporins in cattle, swine, chickens and turkeys. The prohibited uses include: –using cephalosporin drugs at unapproved dose levels, frequencies, durations, or routes of administration; –using cephalosporin drugs in cattle, swine, chickens or turkeys that are not approved for use in that species (e.g., cephalosporin drugs intended for humans or companion animals); –using cephalosporin drugs for disease prevention. 48 Impact of GFI #209 • Removes production claims for medically important antimicrobials used in food-producing animals • Places other feed and water drugs under veterinary control • Begins in January 2017 • Sensitivity of NARMS to measure impact will be tested 49 The future of integrated antimicrobial resistance monitoring 50 Surveillance Today Humans • Isolate pure cultures from samples obtained from animals, foods & people • Ship them to central laboratories to conduct a small number of expensive and labor intensive assays in batch using specialized reagents 1 2 3 4 5 6 7 8 9 10 11 12 13 Typhimurium Enteritidis Newport Heidelberg I 4,[5],12:i:Javiana Muenchen Montevideo Tennessee Mississippi Oranienburg Braenderup Agona Chicken Breast Typhimurium Kentucky Heidelberg Enteritidis Montevideo I 4,[5],12:i:Hadar Mbandaka Oranienburg Other Ground Turkey Hadar Heidelberg Saintpaul Reading Schwarzengrund Senfternberg Agona Minnesota Albany I 4,5,12:r:Muenchen Other Cattle Montevideo Dublin Muenster Newport Mbandaka Typhimurium Cerro Anatum Agona Meleagridis Infantis Other Swine Typhimurium Derby Johannesburg Infantis Anatum Saintpaul Adelaide London Hadar Agona Muenchen Other – AST, PFGE, Serotyping • Present aggregated phenotype data over time in an integrated fashion • Perform research projects to more fully characterize and compare strains, and publish the results months-years later. – Phage typing, plasmid typing, MLST, CRISPR, virulence typing, R-gene sequencing, etc. 51 Surveillance tomorrow Next generation sequencing technology is changing the science of infectious disease. It has the potential to serve as the single assay of NARMS surveillance in the future and to supplant multiple methods, saving time and money. 1. 2. 3. 4. Classical serotyping PFGE and other strain typing methods In vivo antimicrobial susceptibility testing Piecemeal PCR gene detection and plasmid typing And to provide: 1. 2. 3. 4. 5. 6. 7. 8. 9. Genome/nucleotide surveillance Virulence profiles Molecular phage typing Markers for source attribution Better understanding of emerging trends Costs savings - $20 - $60 per isolates Resistance to drugs not tested Integration with drug use information Metagenomic surveillance and CIDT 34/P aph(2’)-Ig tetO aad9* aadE sat4 53 Surveillance tomorrow • Separate microbial surveillance systems based on and limited by methodology (PulseNet, NARMS, HACCP, NSS, hospital programs) will eventually contribute to and share a common, mobile, database. • New opportunities for additional sample sources as costs continue to drop ($20-60/isolate) resulting in better trend analysis and greater sensitivity to changing patterns. • Ability to address resistance in other ecosystems involving zoonotic and environmental spread – Companion animals, other (minor) food animal sources, imported products, environmental, produce, etc. • Other pathogens and bacteria • Real time data collection and analysis • Better informed and more rapid public health response 54 NARMS Objectives with WGS 1. Monitor trends in antimicrobial resistance among foodborne bacteria from humans, retail meats, and animals 2. Disseminate timely information on antimicrobial resistance to promote interventions that reduce resistance among foodborne bacteria Conduct research to better understand the emergence, persistence, and spread of antimicrobial resistance 3. 4. 1. Monitor genomes in antimicrobial resistant foodborne bacteria from humans, retail meats, food animals, companion animals, feral animals and the environment. 2. Disseminate timely information on changes in the resistome to promote interventions that reduce resistance among foodborne bacteria and to prevent emerging resistances from becoming widespread 3. Assist the FDA in making decisions related to the approval of safe and effective antimicrobial drugs for animals 4. Conduct in vivo research to better understand the emergence, persistence, and spread of antimicrobial resistance under different conditions Assist the FDA in making decisions related to the approval of safe and effective antimicrobial drugs for animals Strengths of NARMS • Comprehensive susceptibility data for managing risks associated with food animal antibiotic use, including pre-approval review of new animal antibiotics and post-approval safety monitoring of adverse events • Most extensive program of its kind in the word, suitable to the large US food productions systems • Excellent example of federal collaboration and federal-state partnership – • • • • • • CDC-FoodNet, CDC-PulseNet, USDA-FSIS, USDA-ARS, USDA-APHIS, FDA-ORA,FDA-CFSAN, NIH, Universities, Industry. Is a recognized model for international capacity building and technical standards Robust and targeted research programs Well characterized isolates are a rich source of information on FBP Infrastructure in place for ad hoc food hazard analyses Exceptional staff of well-trained and dedicated microbiologists, epidemiologists, veterinarians, database managers, molecular biologists, bioinformaticians, statisticians. NARMS assists FDA in decision making on approving safe and effective antimicrobial drugs, and supports the Agency’s mission as a science-based regulatory agency Challenges • • Detailed drug use information in food producing animals • Additional retail food isolates for better trend analysis • Examining other pathogens and commodities as needed without compromising core functions. Continued progress on linking databases on food safety • Exploiting other sources of data on AR (e.g., hospitals and clinics) • Professional development and training on emerging technologies • Collecting and incorporating import data into NARMS as needed • Resources for research • IT and computing infrastructure for WGS • • Communication of complex data sets in a clear way to different audiences Future Needs Providing timelier data generation, analysis and reporting Acknowledgements USDA-ARS FDA/CVM CDC Eileen Thacker Paula Fedorka-Cray Jovita Haro Jason Abbott Sherry Ayers Sonya Bodeis-Jones Emily Crarey Sharon Friedman Stuart Gaines Michael Grabenstein David Heller Claudine Kabera Claudia Lam Melissa Warren Crystal Rice-Trujillo Jonathan Sabo Heather Tate Thu Thuy-Tran Shenia Young Shaohua Zhao Cindy Friedman Jean Whichard Beth Karp Jason Folster Allison O’Donnell Jared Reynolds Julian Grass Felicita Medalla USDA-APHIS Dave Dargatz Bruce Wagner USDA-FSIS Uday Dessai Emilio Esteban Alice Thayer Bill Cray Jodie Plumblee FDA/CFSAN Eric Brown Mark Allard Ruth Timme Errol Strain Mary Torrence Non-federal partners Public health and veterinary diagnostic laboratories FoodNet EIP funded sites Thank you 59