Source: UNIV OF WISCONSIN submitted to
MITIGATING TRANSMISSION OF ANTIMICROBIAL RESISTANCE ON LARGE DAIRY FARMS BY REDUCING BEHAVIORAL PATHWAYS OF EXPOSURE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
1011993
Grant No.
2017-68003-26500
Project No.
WIS01975
Proposal No.
2016-09585
Multistate No.
(N/A)
Program Code
A4171
Project Start Date
May 1, 2017
Project End Date
Feb 1, 2018
Grant Year
2017
Project Director
RUEGG, P. L.
Recipient Organization
UNIV OF WISCONSIN
21 N PARK ST STE 6401
MADISON,WI 53715-1218
Performing Department
DAIRY SCIENCE
Non Technical Summary
Antibiotics play an important role in maintaining human health and animal well-being but use of these important compounds must be balanced against the risk of developing resistance. The role of antibiotic usage on dairy farms in development and dissemination of bacteria (germs) that may be resistant to antibiotics is not well defined. While there is some concern among the general public about public health risks based on exposure to potentially resistant germs found on farms, farm workers have the greatest risks of exposure to bacteria shed by dairy cows. Farm workers have close contact with both healthy and ill cattle and have the greatest risk of exposure to potentially resistant bacteria. In this project, we will determine if work practices on dairy farms are associated with exposure to bacteria that may harbor resistance genes and evaluate if we can reduce exposure by changing farm worker practices. We will do so by first assessing usage of antibiotics on a number of large farms and comparing antibiotic usage among these farms. In the next step, we will enroll farms that have the greatest and least amount of use of antibiotics in further studies. After enrolling those farms, we will determine if the amount of antibiotic usage is associated with increased risks of exposure of farm workers to resistant bacteria. We will intensively study the way that work is performed on the enrolled farms with the goal of identifying critical control points where farm workers have the greatest risk of potential exposure to important bacteria that may be found in cattle manure. After collecting biological samples from both cows and farm workers, we will use sophisticated new laboratory techniques that allow us to detect very small amounts of pathogens and the genes that cause resistance to antibiotics. After performing the laboratory work, we will analyze relationships between farm work practices and risk of exposure to pathogens and resistance genes. Based on an analysis of the risks, we will develop a training program to educate and change farm worker practices to reduce exposure to these pathogens and ultimately to reduce the risk that resistant pathogens have the opportunity to infect people both on and off farms. We will evaluate the impact of the training program by comparing the risks before and after the training occurred. Finally, we will use extension networks and multimedia interactive materials to transfer our knowledge to the broader agricultural community. Overall, it is our goal to develop evidence-based, industry-wide workplace behavioral and educational programs that ensure the continued sustainability of our dairy farming communities.
Animal Health Component
25%
Research Effort Categories
Basic
25%
Applied
50%
Developmental
25%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7123499110025%
7123410117015%
3073410308025%
3073410302035%
Goals / Objectives
Antibiotics are essential for treatment of bacterial diseases and their use has improved welfare of both humans and animals but benefits of using antibiotics on farms must be balanced against the potential for development and spread of resistance. Reported associations between administration of antimicrobials to dairy cattle and development of resistance are weak but farm workers have frequent contact with cattle and are at high risk of exposure to bacterial pathogens that may harbor resistnace genes. These workers may be an important "entry point" for resistant genes to move from dairy cattle into the human population. Unfortunately, critical control points associated with exposure to pathogens and resistance genes by farm workers are not well understood. Our overarching hypothesis is that risks of transmission of potentially resistant pathogens from dairy cattle to farm workers are dependent on human behavior, and these risks can be reduced by changing farm worker behavior through evidence-based interventions.Work system analysis is an innovative approach used to better understand worker behavior and critical control points associated with transmission of pathogens that may contain resistance genes. Thus, our strategy is to apply a systems engineering approach to identify critical control points for transmission of pathogens and resistance genes that can be modified to reduce risk of exposure. In this project we will use the following aims to identify potential routes of exposure to pathogens that may harbor resistance genes and develop and evaluate interventions that result in decreased risk:Aim 1. Identify farm worker behaviors associated with increased risk of carriage of selected pathogens and resistance genes on farms with varying exposures of cows to antimicrobials. We will define relationships between antimicrobial usage and carriage of selected resistance genes in farm workers and dairy cattle and determine if the risk of carriage varies among farms with different levels of usage.Aim 2. Measure carriage of pathogens and resistance genes in biological specimens collected from farm workers and animals on farms with high and low antimicrobial usage and conduct an epidemiological risk factor analysis of behavioral predictors of carriage of pathogens and resistances genes.Aim 3. Develop, perform & evaluate an intervention to change worker behaviors that are associated with exposure to pathogens and resistance genes. We will design this intervention to be efficient and evidence-based, given the results of Aim 1 and Aim 2.Aim 4. Transfer knowledge to end-users using extension networks and innovative multimedia interactive materials. In so doing, we hope to lower the risk of transmission of pathogens that may harbor resistance genes from dairy cattle to the human population industry-wide.
Project Methods
Our first aim is to identify farm worker behaviors associated with increased risk of carriage of selected pathogens and resistance genes on farms with different exposures of cows to antimicrobials and to define relationships between antimicrobial usage and carriage of selected resistance genes in farm workers and dairy cattle. To do this, we will visit 40 large dairy farms and quantify antimicrobial usage by calculating the defined daily dosage of all antimicrobials used for all age groups of cattle. After quantifying usage, we will identify percentiles of DDD usage and enroll 8 farms which have the lowest (n = 4) and highest (n = 4) usage for further participation in the next aims. We will then perform a work systems analysis on the 8 enrolled farms to identify associations between work practices and risk of exposure to selected pathogens and resistance genes. This will be achieved by adapting a Systems Engineering in Patient Safety Approach that has been used in hospital settings for improved infection control to the farm setting. A mixed methods approach will be used to identify work system barriers that increase risk of exposures to pathogens and resistance genes.Our second aim is to measure carriage of pathogens and genes in biological specimens collected from farm workers and animals on farms with high and low AMU and conduct a risk factor analysis of behavioral predictors of carriage of pathogens and resistance genes. To achieve this aim we will collect fecal specimens from selected dairy cattle and stool samples from selected higher risk farm workers. Next generation laboratory approaches will be used to to measure carriage of pathogens and ARG in biological specimens collected from both farm workers and animals. qPCR will be used to detect three known pathogens including Campylobacter jejuni, Salmonella enterica, and enterohemorrhagic Escherichia coli and all manure samples will be subjected to a real-time qPCR analysis of 285 resistance genes using the Wafergen SmartChip nanowell real-time qPCR platform.We will perform a shotgun metagenomics analysis on the 25 manure samples that display the greatest diversity and relative abundance of resistance genes from our qPCR analysis and are positive for our resistance gene-carrying pathogen specific qPCR analysis. Shotgun sequence reads will be generated from gDNA using the Illumina Next-Seq 500 platform. Identification of resistance genes will be conduct via comparison with the Comprehensive Antibiotic Resistance Database.We will then use the data previously generated in aims 1 and 2 to conduct an epidemiological risk factor analysis of behavioral predictors of carriage of pathogens and ARG with the goal of quantifying the strength of association between behavioral predictors and microbiological outcomes. Our unit of analysis is the individual farm worker, and our outcome variables are binary (pathogen or resistance gene detected or not detected). Our study design is hierarchical, in that workers are nested within farms. We will also sample workers more than once. Our experimental design will inlcude a multi-level analytical approach, utilizing a hierarchical logistic regression analysis with repeated measures.Our third aim is to develop, perform & evaluate an intervention to change worker behaviors that are associated with exposure to pathogens and resistance genes. The intervention will be based on results of aim 1 and 2 and will be conducted on 4 of the 8 farms (4 will serve as controls). We will establish a unique, unified theoretical behavioral/condition change framework that will be used to develop and to evaluate the intervention and will identify specific, measurable, quantitative means to measure sustained adoption of recommended intervention behaviors and conditions. We will evaluate the impact of the intervention on both behaviors and on carriage of resistance genes. If the intervention results in successful reduction in risks, then it will be offered to all 8 farms and used in our fourth aim.Our fourth aim is to transfer knowledge to end-users using extension networks and innovative multimedia interactive materials. We will develop a centralized online resource center that will integrate extension resources with results of our applied research to increase awareness of usage of antimicrobial usage practices and reduce potential biological risks of exposure of dairy farm workers to resistant pathogens and genes. Initial emphasis will be on gaining input from our project advisory board and collaborating farmers about appropriate formats of our resources. Materials will be developed to equip trainers (extension agents, veterinarian and farm workers) to be able to multiply our efforts beyond the duration of the project funding and beyond our geographical region.Project staff will develop bilingual training programs that use a hybrid learning structure. Most modules will include online training, short "how-to" videos, problem based teaching scenarios and specific learning objectives. Each module will include materials directly targeted at farm workers as well as materials designed to equip managers with training resources. Users of the materials will be required to register (on-line) to gain access to the materials and follow-up evaluations will be performed via SurveyMonkey® to allow for appropriate revisions.

Progress 05/01/17 to 04/30/21

Outputs
Target Audience:During this reporting period, the target audience of this project was primarily dairy farmers who participated in the assessment of antimicrobial usage on their farms. Another target audience included our advisory board, which is composed of dairy farmers, dairy veterinarians, industry professionals, and extension agents. Changes/Problems:We have initiated the transfer of the primary grant from the administration of UW Madison to Michigan State University, as the PD has moved to MSU. No aims or disruptions of the project will result as a subcontract to UW Madison has been developed to continue the collaboration and complete the work exactly as proposed. Dr. Ruegg remains an Emeritus Professor at UW Madison and will continue to lead this project. Monthly conference calls and quarterly face to face meetings of project personnel are already scheduled. What opportunities for training and professional development has the project provided?Professional develop has occurred for 2 graduate students as they have worked one-on-one with their research mentors and have learned the necessary skills to visit dairy farms and collect information about AMU. Additional training has occurred for an undergraduate student who learned how to write recruitment letters for farm based research projects and how to collect and store confidential data. How have the results been disseminated to communities of interest?Initial letters describing the project goals and objectives were sent to >150 farms. These letters served to educate the recipients about the importance of responsible antimicrobial usage. What do you plan to do during the next reporting period to accomplish the goals?We will calculate the Defined Daily Doses for each farm and rank the farms from greatest to least users of antimicrobials. We will then enroll 4 higher and 4 lower users of antimicrobials in Aim 2, Obj. 2 which includes the use of work systems analysis to associate increased risk of exposure to selected pathogens and carriage of ARG on farms with farm worker behavior. During this period, we also intend to collect fecal samples and stool samples to achieve our goals and objectives for Aim 2. We are very close to being on schedule with our initial plan.

Impacts
What was accomplished under these goals? We have completed about 75% of Aim 1 and will complete the rest of Aim 1 and the subsequent aims after the project is administratively transferred to Michigan State University as the PD (Pamela Ruegg) has transferred to MSU. We are close to being on schedule and as proposed during this reporting period we were focused on completing Aim 1, Objective 1. To accomplish this, we enrolled 40 farms that contained at least 500 cows and utilized computerized records. On those farms we performed a survey and collected data about dairy illnesses and AMU. All farm visits were completed by the end of December 2017 and we are currently in the process of combining the data and calculating the Defined Daily Doses for each illness and each farm. We will then determine the total DDD used at farm level by dividing the reported total mg or IU of each antimicrobial used by the DDD of that antimicrobial. AMU will be summarized per 1000 cow or calf days and total AMU will be estimated. Low AMU herds will be defined based on the bottom 10th percentile of use while high AMU herds will be defined based on 90th percentile of DDD among the studied farms. The 4 low and 4 high AMU herds will be enrolled in Obj.2. of Aim 1.

Publications


    Progress 05/01/17 to 04/30/18

    Outputs
    Target Audience:During this reporting period, the target audience of this project was primarily dairy farmers who participated in the assessment of antimicrobial usage on their farms. Another target audience included our advisory board, which is composed of dairy farmers, dairy veterinarians, industry professionals, and extension agents. Changes/Problems:We have initiated the transfer of the primary grant from the administration of UW Madison to Michigan State University, as the PD has moved to MSU. No aims or disruptions of the project will result as a subcontract to UW Madison is being developed to continue the collaboration and complete the work. What opportunities for training and professional development has the project provided?Professional develop has occurred for 2 graduate students as they have worked one-on-one with their research mentors and have learned the necessary skills to visit dairy farms and collect information about AMU. Additional training has occurred for an undergraduate student who learned how to write recruitment letters for farm based research projects and how to collect and store confidential data. How have the results been disseminated to communities of interest?Initial letters describing the project goals and objectives were sent to >150 farms. These letters served to educate the recipients about the importance of responsible antimicrobial usage. What do you plan to do during the next reporting period to accomplish the goals?We will calculate the Defined Daily Doses for each farm and rank the farms from greatest to least users of antimicrobials. We will then enroll 4 higher and 4 lower users of antimicrobials in Aim 2, Obj. 2 which includes the use of work systems analysis to associate increased risk of exposure to selected pathogens and carriage of ARG on farms with farm worker behavior. During this period, we also intend to collect fecal samples and stool samples to achieve our goals and objectives for Aim 2.

    Impacts
    What was accomplished under these goals? During this reporting period, we were focused on AIM 1 and specifically objective 1 and have completed approximately 75% of the goals for that aim. To accomplish this, we enrolled 40 farms that contained at least 500 cows and utilized computerized records. On those farms we performed a survey and collected data about dairy illnesses and AMU. All farm visits were completed by the end of December 2017 and we are currently in the process of combining the data and calculating the Defined Daily Doses for each illness and each farm. We will then determine the total DDD used at farm level by dividing the reported total mg or IU of each antimicrobial used by the DDD of that antimicrobial. AMU will be summarized per 1000 cow or calf days and total AMU will be estimated. Low AMU herds will be defined based on the bottom 10th percentile of use while high AMU herds will be defined based on 90th percentile of DDD among the studied farms. The 4 low and 4 high AMU herds will be enrolled in Obj.2. of Aim 1.

    Publications


      Progress 05/01/17 to 02/01/18

      Outputs
      Target Audience:During this reporting period, the target audience of this project was primarily dairy farmers who participated in the assessment of antimicrobial usage on their farms. Another target audience included our advisory board, which is composed of dairy farmers, dairy veterinarians, industry professionals, and extension agents. Changes/Problems:We have initiated the transfer of the primary grant from the administration of UW Madison to Michigan State University, as the PD has moved to MSU. No aims or disruptions of the project will result as a subcontract to UW Madison has been developed to continue the collaboration and complete the work exactly as proposed. Dr. Ruegg remains an Emeritus Professor at UW Madison and will continue to lead this project. Monthly conference calls and quarterly face to face meetings of project personnel are already scheduled. What opportunities for training and professional development has the project provided?Professional develop has occurred for 2 graduate students as they have worked one-on-one with their research mentors and have learned the necessary skills to visit dairy farms and collect information about AMU. Additional training has occurred for an undergraduate student who learned how to write recruitment letters for farm based research projects and how to collect and store confidential data. How have the results been disseminated to communities of interest?Initial letters describing the project goals and objectives were sent to >150 farms. These letters served to educate the recipients about the importance of responsible antimicrobial usage. What do you plan to do during the next reporting period to accomplish the goals?We will calculate the Defined Daily Doses for each farm and rank the farms from greatest to least users of antimicrobials. We will then enroll 4 higher and 4 lower users of antimicrobials in Aim 2, Obj. 2 which includes the use of work systems analysis to associate increased risk of exposure to selected pathogens and carriage of ARG on farms with farm worker behavior. During this period, we also intend to collect fecal samples and stool samples to achieve our goals and objectives for Aim 2. We are very close to being on schedule with our initial plan.

      Impacts
      What was accomplished under these goals? We have completed about 75% of Aim 1 and will complete the rest of Aim 1 and the subsequent aims after the project is administratively transferred to Michigan State University as the PD (Pamela Ruegg) has transferred to MSU. We are close to being on schedule and as proposed during this reporting period we were focused on completing Aim 1, Objective 1. To accomplish this, we enrolled 40 farms that contained at least 500 cows and utilized computerized records. On those farms we performed a survey and collected data about dairy illnesses and AMU. All farm visits were completed by the end of December 2017 and we are currently in the process of combining the data and calculating the Defined Daily Doses for each illness and each farm. We will then determine the total DDD used at farm level by dividing the reported total mg or IU of each antimicrobial used by the DDD of that antimicrobial. AMU will be summarized per 1000 cow or calf days and total AMU will be estimated. Low AMU herds will be defined based on the bottom 10th percentile of use while high AMU herds will be defined based on 90th percentile of DDD among the studied farms. The 4 low and 4 high AMU herds will be enrolled in Obj.2. of Aim 1.

      Publications