**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ANTIMICROBIAL RESISTANCE (AMR) IS A CRITICAL GLOBAL ONE HEALTH PROBLEM IMPACTING ANIMAL, HUMAN AND ENVIRONMENTAL HEALTH. THE WORLD HEALTH ORGANIZATION DECLARES ANTIMICROBIAL RESISTANCE ONE OF THE TOP 10 GLOBAL PUBLIC HEALTH THREATS FACING HUMANITY (WHO, 2021). THE US DEPARTMENT OF AGRICULTURE (USDA) HAS DEVELOPED AN ANTIMICROBIAL RESISTANCE ACTION PLAN AND RECOGNIZES CONTROLLING ANTIBIOTIC RESISTANCE REQUIRES THE ADOPTION OF A ONE-HEALTH APPROACH TO DISEASE SURVEILLANCE THAT RECOGNIZES THAT RESISTANCE CAN ARISE IN HUMANS, ANIMALS, AND THE ENVIRONMENT (USDA). EMERGENCE OF RESISTANT BACTERIAL PATHOGENS CAUSING DISEASE IN ANIMALS, INCLUDING DAIRY CATTLE RESULTS IN DECREASED ANIMAL WELL-BEING AND INCREASED PRODUCTION COSTS. ANTIMICROBIAL RESISTANCE IS AN ANIMAL HEALTH ISSUE, AND INCREASED DISEASE SURVEILLANCE IS NEEDED BECAUSE WE DO NOT KNOW THE EXTENT OF THE PROBLEM. A CHALLENGE IS THE COSTLY AND TIME-CONSUMING NATURE OF COMPREHENSIVE ANTIMICROBIAL RESISTANCE SURVEILLANCE. THIS LIMITS OUR ABILITY TO UNDERSTAND THE EXTENT OF THE PROBLEM AND THE IMPACT OF INTERVENTIONS. PATHOGEN SURVEILLANCE HAS ADVANCED IN THE GENOMIC ERA. RECENT ADVANCES IN MOLECULAR BIOLOGY TECHNIQUES SUCH AS HIGH-THROUGHPUT OR NEXT GENERATION NUCLEIC ACID SEQUENCING HAVE REVOLUTIONIZED STRAIN TYPING, INFECTIOUS DISEASE EPIDEMIOLOGICAL SURVEILLANCE, AND EPIDEMIOLOGIC STUDIES OF PATHOGEN DYNAMICS WITHIN AND BETWEEN POPULATIONS. THESE MOLECULAR METHODS HAVE BEEN APPLIED TO ANTIMICROBIAL RESISTANCE SURVEILLANCE, WHICH DIFFERS FROM PATHOGEN DETECTION SURVEILLANCE, AS THE GOAL IS TO IDENTIFY ANTIMICROBIAL RESISTANCE DRIVERS TO MITIGATE ANTIMICROBIAL RESISTANCE DEVELOPMENT AND SPREAD. THERE ARE GAPS IN OUR KNOWLEDGE AND UNDERSTANDING OF HOW AMR SURVEILLANCE USING HIGH THROUGHPUT METAGENOMIC METHODS (I.E., CHARACTERIZING THE FARM RESISTOME) CAN INFORM FARMER AND VETERINARIAN KNOWLEDGE, OPINION AND ACTIONS RELATED TO ANTIMICROBIAL RESISTANCE AND ANTIMICROBIAL USE. THIS SABBATICAL PROJECT ADDRESSES THOSE GAPSWITH THREE OBJECTIVES.DURING MY SABBATICAL YEAR, FOR THE FIRST OBJECTIVE, I WILL COMPLETE A FIELD STUDY ON DAIRY FARMS WHERE I WILL COLLECT DATA ON ANTIMICROBIAL USE PRACTICES FOR TREATMENT OF CALF HEALTH ISSUES AND COLLECT SAMPLES FROM CALVES AND HUMANS ON THE PARTICIPATING FARMS. I WILL FOCUS ON DAIRY CALF HEALTH MANAGEMENT BECAUSE THIS IS ONE OF THE MOST FREQUENT REASONS FOR ANTIBIOTIC USE ON DAIRY FARMS AND AN AGE GROUP WHERE HUMAN CONTACT WITH SICK CALVES HAS PREVIOUSLY BEEN DEMONSTRATED TO RESULT IN TRANSMISSION OF ANTIBIOTIC RESISTANT PATHOGENS. MULTIPLE SAMPLES WILL BE COLLECTED OVER TIME TO QUANTIFY ANTIMICROBIAL RESISTANT PATHOGEN PREVALENCE, POSSIBLE CHANGES IN PREVALENCE OVER TIME AND POSSIBLE SPREAD OF ANTIMICROBIAL RESISTANT PATHOGENS BETWEEN HUMANS AND CALVES ON THE FARMS. THERE ARE TWO GENERAL METHODS TO IDENTIFY ANTIMICROBIAL RESISTANCE AMONG POTENTIAL BACTERIAL PATHOGENS FROM ANIMALS, HUMANS, AND THE ENVIRONMENT. THE FIRST IS TRADITIONAL CULTURE-BASED METHODS, WHERE T,HE BACTERIA ARE ISOLATED FROM THE SAMPLES AND THEN TESTED FOR SUSCEPTIBILITY TO A PANEL OF ANTIBIOTICS. THIS METHOD IS THE STANDARD FOR IDENTIFICATION OF ANTIMICROBIAL RESISTANT ORGANISMS, PRESUMED TO MAXIMIZE DIAGNOSTIC ACCURACY (SENSITIVITY AND SPECIFICITY), YET CULTURE-BASED SUSCEPTIBILITY TESTING IS LABOR INTENSIVE, COSTLY AND REQUIRES DAYS TO COMPLETE. THE ALTERNATIVE IS GENETIC SEQUENCE-BASED DETECTION METHODS. ANTIMICROBIAL RESISTANCE IS GENETICALLY ENCODED, AND THE PRESENCE OF ANTIMICROBIAL RESISTANCE MARKERS CAN BE IDENTIFIED FROM SAMPLES BY IDENTIFICATION OF THE GENE SEQUENCES. THIS APPROACH HAS THE POTENTIAL ADVANTAGE FOR HIGH-THROUGHPUT, LARGE-SCALE SURVEILLANCE OF ANIMALS, HUMANS, AND THEIR ENVIRONMENT. THIS APPROACH ALSO ALLOWS DETERMINATION FROM BOTH CULTURABLE AND UNCULTURABLE BACTERIA IN SAMPLES. DURING THE SABBATICAL, I WILL APPLY BOTH APPROACHES TO THE SAMPLES COLLECTED FROM ANIMALS, HUMANS AND THE FARM ENVIRONMENT, WITH THE GOAL OF QUANTIFYING THE DIAGNOSTIC CHARACTERISTICS OF GENE SEQUENCE-BASED ANTIMICROBIAL RESISTANCE DETECTION METHODS. FOR THE SECOND OBJECTIVE, I WILL USE THE EMPIRICAL DATA COLLECTED FROM THE FIELD STUDY TO DEVELOP A MODEL OF ANTIMICROBIAL RESISTANCE SPILLOVER BETWEEN HUMANS AND ANIMALS ON DAIRY FARMS. THE INCORPORATION OF METAGENOMICS ANTIMICROBIAL RESISTANCE DATA INTO MODELS OF PATHOGEN SPREAD BETWEEN HUMANS AND ANIMALS ON FARMS IS A NOVEL ADVANCE OF EPIDEMIOLOGICAL MODELING AND MOLECULAR EPIDEMIOLOGY TOOLS. COMBINING MOLECULAR EPIDEMIOLOGY AND CONTACT OR SOCIAL NETWORK ANALYSIS INTO SOCIO-MOLECULAR EPIDEMIOLOGY HAS THE POTENTIAL TO ADVANCE ANTIBIOTIC RESISTANCE CONTROL PRACTICES. UNDER THIS OBJECTIVE, I WILL IMPROVE OUR UNDERSTANDING OF HOW MOLECULAR GENOMICS DATA CAN IMPROVE OUR UNDERSTANDING OF THE MAINTENANCE AND SPREAD OF ANTIMICROBIAL RESISTANT PATHOGENS ON DAIRY FARMS. FOR THE THIRD OBJECTIVE, I WILL DESCRIBE HOW MONITORING ANTIBIOTIC RESISTANCE ON DAIRY FARMS MAY INFLUENCE FARMER ATTITUDES AND BEHAVIORS RELATED TOTHE PROBLEM OF ANTIBIOTIC RESISTANCE. UNDER THIS OBJECTIVE I WILL IMPROVE OUR UNDERSTANDING OF HOW FARMERS AND VETERINARIANS MIGHT USE GENOMIC DATA THAT QUANTIFIES ANTIMICROBIAL RESISTANCE ON DAIRY FARMS. I WILL GENERATE QUALITATIVE DATA THAT WILL HELP INFORM BEST PRACTICES FOR REPORTING ANTIMICROBIAL RESISTANCE SURVEILLANCE DATA TO FARMERS AND VETERINARIANS AND DETERMINE HOW THESE DATA MAY INFLUENCE FARMER AND VETERINARIAN ATTITUDE AND BEHAVIOR REGARDING ANTIBIOTIC USE. THE EMERGING ADVANCED MOLECULAR GENETIC APPROACHES TO ANTIMICROBIAL RESISTANCE SURVEILLANCE HAVE THE POTENTIAL TO INCREASE OUR ABILITY MONITOR ANTIMICROBIAL RESISTANCE BECAUSE THE METHODS ARE FASTER AND LESS LABOR INTENSIVE. THIS WOULD ALLOW FOR MORE FREQUENT AND MORE COMPREHENSIVE SURVEILLANCE. IT IS UNCLEAR IF THE AVAILABILITY OF THESE TOOLS WOULD CHANGE FARMER AND VETERINARIAN ATTITUDES AND BEHAVIORS REGARDING ANTIMICROBIAL RESISTANCE AND ANTIBIOTIC USE. THIS PROJECT WILL ADDRESS THAT GAP IN KNOWLEDGE, AND WILL CONTR,BUTE TO OUR ABILITY TO MITIGATE ANTIMICROBIAL RESISTANCE IN AGRICULTURAL PRODUCTION SYSTEMS, WITH A FOCUS ON SMALL- TO MEDIUM-SIZED DAIRY FARMS.
$244,642FY2023National Institute of Food and AgricultureUSDA
University Of Vermont & State Agricultural College, Burlington VT