Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
Large Animal Clinical Sciences
Non Technical Summary
NATURE AND IMPORTANCE OF THE PROBLEM AND RELEVANCE TO THE MISSIONOF AGBIORESEARCH: This proposal seeks to describe, measure, and model antimicrobial resistant bacteria transmission dynamics to determine potential means of retarding AMRB emergence. Antimicrobial resistance bacteria (AMRB) is increasing globally and poses a serious threat to human and animal health (Roca et al., 2015). AMRB is recognized as one of the greatest threats to human and animal health worldwide (Llor & Bjerrum, 2014). Just one organism, methicillin-resistant Staphylococcus aureus (MRSA), kills more Americans every year than emphysema, HIV/AIDS, Parkinson's disease and homicide combined (Infectious Diseases Society of America, 2011). Globally, 20% and 3.7% of new cases of previously treated cases of tuberculosis are estimated to be caused by strains that are resistant. For decades, these antituberculosis drugs were effective against tuberculosis, but today the effect is insufficient. Currently, only one-half of multidrug-resistant tuberculosis is effectively treated with the existing drugs (World Health Organization, 2014). Extensively drug-resistant tuberculosis has been identified in 84 countries globally. There is a striking lack of development of new drugs active against these multidrug-resistant Gram-negative bacteria, particularly those producing carbapenemases and none of the antibiotics currently available are now effective (Boucher et al., 2013). This increase in resistance is believed to be caused by a wide range factors (Ventola, 2015); however, the linkages between the hypothesized root causes and observed increase in AMRB is not well understood and the parameter space must be defined and measured (Martínez & Baquero, 2014). The lack of understanding is due to the highly complex nature of AMRB and is likely due to multiple interacting and synergistic factors:within the AMRB microbiome;within AMRB disease hosts;the selection pressure being applied to bacterial species by humans via the use various antimicrobials in humans and livestock;the environmental persistence of antimicrobial compounds in human engineered and natural environments (e.g., healthcare settings, farms, food processing facilities);the environmental persistence of AMRB in engineered environments and in nature;the persistence of AMRB in wildlife, humans, and livestock; and,the transmission dynamics between all living organisms.
Animal Health Component
33%
Research Effort Categories
Basic
33%
Applied
33%
Developmental
34%
Goals / Objectives
The long-term objective of this project is to advance understanding of AMRB ecology and epidemiology by operationally defining, measuring, and quantifying the relationships, transmission dynamics, and looking for causal mechanisms of AMRB.Project 1: Conducting surveillance on farms to identify AMRB species and describe the locations where they are present in the environmentThis project aims to understand what types of AMRB are present on dairy farms and where they are present. This project hypothesizes that the environment contains AMRB and serves as a reservoir for AMRB exposures to wildlife, humans, and dairy cattle, and that different locations of the environment pose different levels of risk to AMRB transmission between species. This project also aims to understand the levels of AMRB present spatially to determine if spatial proximity contributes to AMRB transmission in wildlife, humans, and livestock. Finally, this project aims to understand the types of resistance present and describe the threats to food production and human health.Activity 1: Collect environmental samples from spatially random locations.Activity 2: Collect environmental samples from locations thought to be high risk (convenience sampling) for transmission (e.g., effluent, animal waste collection areas, bird roosting locations, animal pens).Activity 3: Characterize and operationally define sample selection sites.Activity 4: Use information to narrow the scope of future transmission studies.Activity 5: Analyze and map results, and share risk characterization findings with stakeholders.Depending on interest from stakeholders and availability of data, the activities above will be repeated at additional animal production areas in Michigan.Project 2: Spatial correlation between AMRB environmental reservoirs and AMRB in Livestock and Wildlife HostsThis project aims to better understand the spatial risk of AMRB on farms and correlate this pattern with AMRB in wildlife and livestock hosts. Broadly, this effort will compare spatial AMRB to samples collected from wildlife and livestock longitudinally to determine if increased exposure spatially contributes to increased AMRB in livestock and the rate at which ARMB transmission occurs.Activity 1: Identify AMRB hot-spots and densities from Project 1.Activity 2: Collect longitudinal biological samples from wildlife and livestock.Activity 3: Test samples genetically and compare AMRB results to environmental AMRB samples.Activity 4: Produce maps of likely exposure locations, calculate the rate of transmission, and characterize AMRB transmission risks.Activity 5: Share findings with local producers and industry associations to improve understanding and ARMB transmission risk and AMRB transmission risk mitigation strategies.Depending on interest from stakeholders and availability of data, the activities above will be repeated at additional animal production areas in Michigan.Project 3: Measuring and quantifying human exposure to AMRB with GeoQuestionThis project will collect data from humans working on farms to quantify exposures spatially and to measure AMRB risk perception and risk mitigation behaviors in high fidelity.Activity 1: Participants at animal production facilities (farms) will be recruited to the study and will download an application to track and measure precise human trajectories and exposures, and to respond to survey questions on smartphones.Activity 2: Spatial and survey data related to AMRB risk perception and mitigation behavior will be analyzed and mapped to better understand exposures and risk perception related to potentially high risk AMRB locations.Activity 3: Share findings with local producers and industry associations to improve understanding and ARMB transmission risk and AMRB transmission risk mitigation strategies.Depending on interest from stakeholders and availability of data, the activities above will be repeated at additional animal production areas in Michigan.
Project Methods
RESEARCH METHODS/EXPERIMENTAL PROCEDURESProject 1: Conducting surveillance on farms to identify AMRB species and describe the locations where they are present in the environmentActivity 1: We will collect environmental samples from spatially random selected locations at 2 MSU animal agriculture facilities. These locations will be randomly selected spatially using GIS software. After locations are randomly selected at the farms, a GPS device will be used to determine the exact location on the ground and a point environmental sample will be collected (i.e., soil, water, feed, etc.). After collection, bacteria will be cultured from the sample and tested for resistance using the NARMS panel. Only resistant bacteria will be analyzed in this study.Activity 2: We will collect environmental samples from locations thought to be high risk (convenience sampling) for transmission (e.g., effluent, animal waste collection areas, bird roosting locations, wildlife feeding areas, animal pens). After collection, bacteria will be cultured from the sample and tested for resistance using the NARMS panel. Only resistant bacteria will be analyzed in this study.Activity 3: We will characterize and operationally define sample selection sites. The risk characterization will restate the scope of the assessment, express results clearly, articulate major assumptions and uncertainties, identify reasonable alternative interpretations, and separate scientific conclusions from policy judgments. The operational definitions of key terms (e.g., effluent, feed pile, runoff, holding pond, etc.) will be provided to enable replication and comparison of the study's results to different study sites.Activity 4: We will use the surveillance data and risk characterization information to narrow the scope of transmission studies (Project 2). AMRB identified in Activities 1 and 2 will be used to identify specific wildlife species and locations that will be sampled longitudinally in Project 2.Activity 5: We will analyze results to characterize and describe the types of AMRB present and will map the density of AMRB at sampled locations. Geographic interpolation techniques will be used to predict risk spatially. Lastly, these results will be communicated to farm managers, farm employees, scientific journals and to industry stakeholders.Project 2: Spatial correlation between AMRB environmental reservoirs and AMRB in Livestock and Wildlife HostsActivity 1: We will identify AMRB hot-spots and densities from Project 1 and use these hot spots to create a spatial case-control study (Activities 2, 3, & 4) to determine if AMRB cases in livestock and wildlife clusters with high risk locations. This will be used to determine the level of effect that environmental AMRB exposure risk has on wildlife and livestock.Activity 2: We will collect longitudinal biological samples from wildlife and livestock of species identified in Activity 1. Convenience sampling will be used to collect samples from wildlife and livestock located near high risk AMRB locations. Concurrently, we will use drones to create high precision spatial data to create digital elevation models and to measure land-cover and water precisely (e.g., associated environmental risk factor data).Activity 3: We will test samples genetically and compare AMRB results to environmental AMRB samples. Genetic testing will be performed and phylogenic trees will be constructed using whole genome sequencing to determine the directionality of transmission between the environment, wildlife, and livestock.Activity 4: We will produce maps of likely exposure locations, and calculate the rate of transmission (i.e., Rt, R0, Rts) between all permutations of transmission observed between species and the environment. This information will be used to characterize AMRB transmission risks and will be used to make objective and practical recommendations to increase on farm biosecurity.Activity 5: Lastly, we will share findings with local producers and industry associations to improve understanding and ARMB transmission risk and AMRB transmission risk mitigation strategies.Project 3: Measuring and quantifying human exposure to AMRB with GeoQuestionActivity 1: We will recruit participants at animal production facilities (farms) to this exposure and risk perception study. Participants will download a mobile application that tracks and measures precise human trajectories and exposures. This information will be used to identify the duration of potential high risk AMRB exposures.Activity 2: In addition to passively collected trajectory data, participants will respond to ecological momentary assessment survey questions on their smartphones related to risk perception and risk mitigation behaviors (e.g., hand washing, face touching, use of personal protective equipment (PPE) and the proper use of PPE. The spatial and survey data related to AMRB risk perception and mitigation behavior will be analyzed and mapped to better understand exposures and risk perception related to potentially high risk AMRB locations.Activity 3: Lastly, we will share findings with local producers and industry associations to improve understanding and ARMB transmission risk and AMRB transmission risk mitigation strategies.