DEVELOPMENT OF A MODELING FRAMEWORK FOR THE REGIONAL SPREAD OF PATHOGENS IN SWINE POPULATIONS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: ANIMAL HEALTH
• Reporting Frequency: Annual
• Accession No.: 1004145
• Project Start Date: Oct 1, 2014
• Project End Date: Sep 30, 2016
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIV OF MINNESOTA
(N/A)
ST PAUL,MN 55108

Performing Department
Veterinary Population Medicine

Non Technical Summary
The spread of pathogens in swine populations has negative effects on both animal and human health. For example, the introduction of porcine epidemic diarrhea virus (PEDV) in North America in April 2013 has caused significant economic losses to the US swine industry. PEDV is transmitted via the fecal-oral route and the nature and extent to which between-farm transmission is influenced by truck movements between farms, and between farms and feed plants, is yet to be determined. In addition, influenza A virus (IAV) not only negatively affects the health and productivity of domestic swine populations, but influenza has a major impact on human health. Influenza virus is transmitted via aerosol, is endemic in swine populations, and pork producers today perceive economic value in enhancing biosecurity for public health purposes. However, little is known about the effects of various interventions on IAV transmission. Mathematical models are powerful tools to understand transmission and develop control strategies for infectious diseases. Here we are in a unique situation to utilize cutting-edge modeling approaches on already collected (and emerging) data on pathogen transmission to help design effective mitigation strategies for the spread of swine pathogens. The main goal of this project is to stimulate collaboration between a new team of modelers and empiricists to reduce fecal-oral (PEDV) and airborne (IAV) transmission, which will ultimately benefit both animal and human health. The overall objective of this study is to construct a flexible modeling framework to simulate the spread of primarily fecal-oral and airborne infectious pathogens between swine herds, through the following specific aims:Utilize network approaches to formulate a between-farm transmission model.Create an integrated model of regional pathogen spread.Simulate PEDV and IAV transmission and test different control strategies to reduce pathogen spread.This model can be utilized to understand, mitigate, and prevent PEDV and IAV transmission as well as to quantify the effect of alternative strategies in the control of other food-borne and airborne pathogens. The ultimate focus of the proposed project is to give feedback to producers on ways to reduce transmission within and among swine herds.

Animal Health Component

50%

Research Effort Categories

Basic

50%

Applied

50%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3510	2080	100%

Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3510 - Swine, live animal;

Field Of Science
2080 - Mathematics and computer sciences;

Keywords

swine

influenza

mathematical model

modeling framework

pedv

iav

Goals / Objectives
The main goal of this project is to stimulate collaboration between a new team of modelers and empiricists to reduce fecal-oral (PEDV) and airborne (IAV) transmission, which will ultimately benefit both animal and human health. The overall objective of this study is to construct a flexible modeling framework to simulate the spread of primarily fecal-oral and airborne infectious pathogens between swine herds.

Project Methods
Overall approach: We plan to use the approach outlined in a 2012 manuscript in Ecology Letters by Restif et al. emphasizing collaborative feedback loops between empiricists and modelers (Restif et al., 2012). The collaborative process is iterative, where fieldwork informs the models, and models inform the data collection. The concurrent stream of new PEDV information coming in from Co-PI, Morrison as well as new influenza transmission data from Co-PI Torremorell, will be used to refine the model. Morrison and Torremorell are in a position to collect additional data if deemed necessary for the modeling.Year 1. Specific aims 1 & 2: construction of between-farm and regional modelsModel formulation: A metapopulation network model would be an appropriate overarching framework for a regional model. We have recently developed a metapopulation within-farm transmission model, which has been used to study influenza dynamics within breeding farms and wean-to-finish facilities (Reynolds et al., in review). For the breeding farm, we included the typical components of a standard commercial farm, including the spatial separation of swine into different subpopulations. Each swine type (e.g. gilts, sows and piglets) in all locations (e.g. gilt development units, farrowing rooms and gestation areas) is thus explicitly modeled. This model framework allows for heterogeneities in pathogen transmission rate across the population. The logical and challenging next step is to build a regional model where the within-farm metapopulation models are nested within a network of between-farm contacts. We are in a unique and timely situation where Craft and Perez are hiring a new postdoc (Aditya Khanna) for a recently funded USDA grant. Khanna is an expert in mathematical modeling who specializes in building data-driven network models and simulating infectious diseases on these networks. His expertise with model development will produce exciting advances for both the applied and theoretical aspects of this proposed project. Khanna will develop the regional model, which would include within-farm and between-farm transmission, where between-farm transmission would occur via swine movement, transport of feed or fomites, and/or via aerosol. The model will be programmed in standard programming language (e.g. MATLAB, R, C++).Movement data procurement: We have access to movement data from two regions: the Midwest and North Carolina. Data on pig movements in the Midwest will be extracted from the MetaFarms software, which tracks swine production data. In MetaFarms different batches of pigs will be linked by premise ID; farm locations will be determined using Sows Tracking maps. In addition, if this project was funded, movement data could be sourced from the Pipestone System or a subset of the 372 farms enrolled in the ongoing National PRRS Incidence Project. [The PRRS study was started in 2011 and currently includes 14 production systems and veterinary clinics reporting PRRS incidence on a weekly basis for 372 sow farms (representing approximately 20% of the U.S. sow population) located across the country. Of these 14 systems, 11 also share site location with other participants.] In North Carolina (NC), three companies that account for approximately 90% of the pig farms in NC have agreed to share their data (frequency and destination of movements, farm location and other relevant epidemiological information) for this study. We are working with a fourth contact that accounts for an additional 5% of the sites. We will choose a few datasets for fitting the model, and the others for validating the model.Year 2. Specific aim 3: simulate PEDV and IAV spread & test different control strategiesModel parameterization: PEDV. In May 2013, we initiated an epidemiologic research project to determine the risk of lateral spread of PEDV to adjacent swine herds. As part of that project, we have enlisted the support of: National Pork Board; American Association of Swine Veterinarians; National Animal Health Laboratory Network; 4 major swine diagnostic laboratories; USDA Center for Epidemiology and Animal Health; 5 state veterinarians; 16 producers in 7 states and accounting for 294 locations with shared PEDv status and premises ID; and an additional 6 producers. In agreeing to participate, producers sign a release of confidentiality with University of Minnesota VDL. This release gives us access to the PEDV status and corresponding premises ID.IAV. Torremorell and collaborators have already collected extensive data on influenza transmission in swine in experimental and field populations. Data consist of temporal IAV infection rates in breeding herds and growing pig populations (Allerson et al., 2013a; Corzo et al., 2013). Additionally, data from vaccinated and non-vaccinated pigs under experimental conditions is available, including from studies on populations with maternal immunity, which is central to IAV control in pigs (Romagosa et al., 2011; Allerson et al., 2012). New information on IAV aerosol transmission is available in regards to load and duration of IAVs in aerosols in swine farms.Model simulation & validation: We will parameterize the models with the incubation and infectious period distributions appropriate to the disease of interest, and will run 1000 simulations, varying the parameters that we are least certain about, in order to estimate the spatiotemporal spread and likely (mean, median, 95% CI) incidence of hypothetical PEDV or IAV outbreaks in a typical region. We will conduct a sensitivity analysis to determine if incidence is particularly sensitive to certain parameter estimates. We have agreements from three major companies in NC to share their PEDV data with us; we will use data from one company to fit the model to the data and will use data from another other company to validate it. The third company is a back up plan in case that one of them fails, or if data do not have sufficient quality. If we receive the three of them and data are of good quality, we can always validate in 2 systems rather than just one.Test control strategies: Once the dynamic modeling framework is refined for each pathogen, it will be possible to test control strategies on the model, to see which control strategies reduce the incidence and speed of spread regionally. These interventions could be focused on within-farm activities (such as vaccination) or between-farm measures (e.g. biosecurity, such as movements), or combinations of different strategies. We will run 1000 simulations for each scenario.

Progress 10/01/14 to 09/30/16

Outputs
Target Audience:We have published 9 peer-reviewed papers (the majority are in open access journals) and have presented our results to the swine industry (Leman Swine Conference 2016) and to swine veterinarians (American Association of Swine Veterinarians). We have held two preconference workshops at the Leman Swine Conference that have focused on foot-and-mouth disease in swine and applications of epidemiological modeling. Changes/Problems:No major changes/problems during this reporting period. What opportunities for training and professional development has the project provided?Students, postdocs, and research associates have been trained in quantitative methods, specifically disease modeling and simulation. A postdoc trained in wildlife disease ecology is now an expert on constructing mathematical models for production animals. This model is now being adapted for a FMD model for a PhD student's thesis and for a cattle movement network. The project has also provided training for another PhD student to construct a within-farm model of influenza dynamics; this has formed a chapter of her dissertation. All PhD students and the postdoc have gained experience presenting their results in oral, poster, and manuscript form. How have the results been disseminated to communities of interest?We have disseminated results via published conference proceedings, and in both oral and poster formats at national and international meetings (see lists below). Notable communities of interest include: the swine industry (Leman Swine Conference), swine veterinarians (American Association of Swine Veterinarians), and veterinary epidemiologists (International Symposium on Veterinary Epidemiology and Economics). We have published 9 manuscripts in peer reviewed journals (the majority of which are open access), which have explicitly acknowledged this grant. Oral presentations: White, L.A., M. Torremorell & M.E. Craft. Implications of management interventions on a model of influenza A virus persistence within swine breeding herds. Leman Swine Conference, St. Paul, MN (Sept 2016). This oral presentation was one of the top four student abstracts and was based on scientific merit and originality. White, L.A., M. Torremorell & M.E. Craft. Modeling influenza virus in swine farms. Preconference workshop, Leman Swine Conference, St. Paul, MN (Sept 2016). Kinsley, A., K. VanderWaal, M.E. Craft & A. Perez. Within- and Between-farm model of foot-and-mouth disease. Leman Swine Conference. St. Paul, MN (Sept 2016). Craft M.E., L.A. White, J.J.H. Reynolds & M. Torremorell. "Mathematical modeling of influenza A virus dynamics within swine farms and the effects of vaccination." 14th International Symposium on Veterinary Epidemiology and Economics, Merida, Yucatan, Mexico (Nov 2015). VanderWaal, K.L., Enns, E.A, Picasso, C., Alvarez, J., Perez, A., Fernandez, F., Gil, A., Craft, M. Wells, S.J. Modeling within- and between-farm transmission of bovine tuberculosis using dynamic cattle movement networks in Uruguay. Oral presentation at: 14th International Symposium on Veterinary Epidemiology and Economics. Nov 3-7, 2015. Merida, Mexico. Craft M.E., Reynolds, J.J.H. & M. Torremorell. "Mathematical modeling of influenza A virus dynamics within swine farms and the effects of vaccination," International Symposium on Neglected Influenza Viruses, University of Georgia, Athens, GA (April 2015). VanderWaal, K. Between-farm modeling of Porcine Epidemic Diarrhea virus spread. Invited oral presentation at: From geeks to geeks: Principles and applications of epidemiological modeling, Allen D. Leman Conference. 2016 Sept 17, St. Paul, MN. VanderWaal, K., Modeling spread of outbreaks - What can we learn to control them? Swine Disease Eradication Center Symposium. September 18, 2016. Allen D. Leman Swine Conference, St. Paul, MN. Iglesias I, VanderWaal K, Sampedro F, Kinsley A, Goldsmith T, Perez A.. Effectiveness of alternative control measures for foot-and-mouth disease in swine farms in the USA. International Meeting on Emerging Diseases and Surveillance (IMED). Vienna, Austria, November 2016. Perez AM. Keynote presentation: Swine Health Monitoring Program in the US. GEOVET, Valdivia, Chile, November 2016 Iglesias I, VanderWaal K, Sampedro F, Kinsley A, Goldsmith TJ, Perez AM. Control measures for foot-and-mouth disease in swine farms in the USA estimated using simulation modeling. Leman Conference, St Paul, MN, September 2016. Kinsley A, Craft M, Perez A. Modeling FMD in swine farms. CEEZAD meeting, Nebraska city, June 2015. Perez A. Keynote presentation, Principles of Spatial and Risk Analysis Applied to Infectious Diseases in Swine, during the Brazilian Symposium on Saturday. Leman Conference, St Paul, MN, September 2015. Alvarez J, Valdes P, Tousignant S, Morrison R, Perez A. Novel analytic tools for surveillance, diagnosis, and control of PRRS in endemic settings. International Symposium on Emerging and Reemerging Pig Diseases. Kyoto, Japan, June 2015. Poster presentations: Kinsley, A., K. VanderWaal, G. Patterson, F. Sampedro, M. Craft & A. Perez. The impact of farm structure on foot-and-mouth disease in swine. Center of Excellence for Emerging and Zoonotic Animal Disease Annual Meeting. Nebraska City, NE (Nov 2016). Kinsley, A., K. VanderWaal, M. Craft & A. Perez. The impact of farm structure on foot-and-mouth disease in swine. College of Veterinary Medicine Points of Pride Research Day, University of Minnesota, St Paul, MN (Oct 2016). VanderWaal, K, E.A. Enns, C. Picasso, J. Alvarez, A. Perez, F. Fernandez, A. Gil, M.E. Craft & S. Wells. Design of optimal surveillance for bovine tuberculosis in Uruguay. College of Veterinary Medicine Points of Pride Research Day, University of Minnesota, St Paul, MN (Oct 2016). White, L.A., M. Torremorell & M.E. Craft. Implications of management interventions on a model of influenza A virus persistence within swine breeding herds. Leman Swine Conference, St. Paul, MN (Sept 2016). White, L.A., M. Torremorell & M.E. Craft. Implications of management interventions on a model of influenza A virus persistence within swine breeding herds. Options IX for the Control of Influenza, Chicago, IL (Aug 2016). VanderWaal, K, E.A. Enns, C. Picasso, J. Alvarez, A. Perez, F. Fernandez, A. Gil, M.E. Craft & S. Wells. Design of optimal surveillance for bovine tuberculosis in Uruguay. 14th Annual Ecology and Evolution of Infectious Diseases Conference. Ithaca, NY (June 2016). Kinsley, A.C., K. VanderWaal, M. Craft & A. Perez. "A model of foot-and-mouth disease in a farrow-to-finish swine herd," II International Conference on One Medicine One Science, University of Minnesota, Minneapolis, MN (April 2016). VanderWaal, K., E.A. Enns, C. Picasso, C. Packer & M.E. Craft. A novel approach for analyzing networks as potential pathways for disease transmission. II International Conference on One Medicine One Science, University of Minnesota, Minneapolis, MN (April 2016). White, L., M. Torremorell & M.E. Craft "A stochastic, mathematical model of influenza A virus within swine breeding herds: Implications of possible management interventions," American Association of Swine Veterinarians, New Orleans, LA (Feb 2016). Kinsley, A., K. VanderWaal, G. Patterson, J. Evanson, F. Sampedro, M. Craft & A. Perez. Development of parameter values for a within- and between-herd transmission model for foot and mouth disease in swine. Center of Excellence in Emerging and Zoonotic Animal Diseases Annual Meeting, Nebraska City, NE (Nov 2015). Kinsley, A., K. VanderWaal, G. Patterson, J. Evanson, F. Sampedro, M. Craft & A. Perez. "Development of parameter values for a within- and between-herd transmission model of foot and mouth disease in swine," Points of Pride Research Day, College of Veterinary Medicine, University of Minnesota (October 2015). Awarded Honorable Mention in the Poster Competition White, L., M. Torremorell & M.E. Craft "A stochastic, mathematical model of influenza A virus within swine breeding herds: Implications of possible management interventions," Leman Conference, St Paul, Minnesota (Sept 2015). VanderWaal, K.L., Enns, E.A, Picasso, C., Alvarez, J., Perez, A., Fernandez, F., Gil, A., Wells, S.J., Craft, M. Modeling transmission dynamics of bovine tuberculosis in Uruguay using dynamic cattle movement networks. Poster session at: 13th Annual Ecology and Evolution of Infectious Diseases Conference. Athens, GA. (2015) What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? We have completed two working mathematical models. The first model is a within-herd model for the transmission of an airborne pathogen (on which we spread influenza and test different intervention strategies). The second model is a between-farm model for a pathogen in which we know the spatio-temporal spread between farms, but are unsure of its exact routes of transmission between farms (PEDv). The influenza model has been published and the PEDv model publication is in preparation. Students, postdocs, and research associates have been trained in quantitative methods, specifically disease modeling and simulation, and results have been conveyed to stakeholders through oral and poster presentations at national and international meetings.

Publications

• Type: Journal Articles Status: Published Year Published: 2016 Citation: Ezenwa, V.O., E.A. Archie, M.E. Craft, D.M. Hawley, L.B Martin, J. Moore & L. White. (2016) Host behavior-parasite feedback: an essential link between animal behavior and disease ecology. Proceedings of the Royal Society: B. 283(1828), 20153078. DOI:�10.1098/rspb.2015.3078
• Type: Journal Articles Status: Published Year Published: 2016 Citation: K. Manlove, J. Walker, M.E. Craft, K. Huyvaert, M. Joseph, R. Miller, P. Nol, K. Patyk, D. O'Brian, D. Walsh & P. Cross. (2016) One Health or Three? Publication silos among the One Health disciplines. PLOS Biology 14(4), e1002448.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Kinsley, A.C., G. Patterson, K.L. VanderWaal, M.E. Craft & A.M. Perez. (2016) Parameter values for epidemiological models of Foot-and-Mouth disease in swine. Frontiers in Veterinary Science. 3(44), doi.org/10.3389/fvets.2016.00044
• Type: Journal Articles Status: Published Year Published: 2016 Citation: White, L.A., M. Torremorell & M.E. Craft. (2016) Influenza A virus in swine breeding herds: Combination of vaccination and biosecurity practices can reduce likelihood of endemic piglet reservoir. Preventative Veterinary Medicine. doi: 10.1016/j.prevetmed.2016.12.013
• Type: Journal Articles Status: Published Year Published: 2016 Citation: VanderWaal, K.L., C. Picasso, E. Enns, M.E. Craft, J. Alvarez, F. Fernandez, A. Gil, A. Perez, & S. Wells. (2016) Network analysis of cattle movements in Uruguay: Quantifying heterogeneity for risk-based disease surveillance and control. Preventative Veterinary Medicine. 123, p 12-22. doi.org/10.1016/j.prevetmed.2015.12.003
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Craft, M.E. (2015) Infectious disease transmission and contact networks in wildlife and livestock. Philosophical Transactions of the Royal Society B- Biological Sciences. 370: 20140107. http://dx.doi.org/10.1098/rstb.2014.0107
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Escobar, L.E. & M.E. Craft. (2016) Advances and limitations of disease biogeography using ecological niche modeling. Frontiers in Microbiology. 7:1174. doi: 10.3389/fmicb.2016.01174
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Hirsch, B.T., J.J.H. Reynolds, S. D. Gehrt & M.E. Craft. (2016) Which mechanisms drive seasonal rabies outbreaks in raccoons? A test using dynamic social network models. Journal of Applied Ecology. 53(3), 804-813. doi: 10.1111/1365-2664.12628.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: VanderWaal, K. L., Ezenwa, V. O. (2016), Heterogeneity in pathogen transmission: mechanisms and methodology. Functional Ecology, 30:�16061622. doi:�10.1111/1365-2435.12645
• Type: Journal Articles Status: Under Review Year Published: 2017 Citation: VanderWaal, K., E.A. Enns, C. Picasso, J. Alvarez, A. Perez, F. Fernandez, A. Gil, M.E. Craft & S. Wells. Optimal surveillance strategies for bovine tuberculosis in a low-prevalence country. (SubmittedScientific Reports).
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: White, L.A., M. Torremorell & M.E. Craft. (2016) "Implications of management interventions on a model of influenza A virus persistence within swine breeding herds," Options IX for the Control of Influenza Conference, Abstract # P-357, Chicago, IL, USA, p. 207.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: White, L.A., M. Torremorell & M.E. Craft. (2016) "A stochastic, mathematical model of influenza A virus within swine breeding herds: Implications of possible management interventions," Proceedings of the American Association of Swine Veterinarians, New Orleans, LA, p. 310.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Alvarez J, Valdes-Donoso P, Tousignant S, Alkhamis M, Morrison R, Perez A, 2016. Novel analytic tools for the study of porcine reproductive and respiratory virus (PRRSv) in endemic settings. Porcine Health Management , 2:3 DOI: 10.1186/s40813-016-0019-0
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Alvarez J, Goede D, Morrison R, Perez A, 2016. Spatial and temporal epidemiology of porcine epidemic diarrhea (PED) in the Midwest and Southeast regions of the United States. Preventive Veterinary Medicine 123:155-160 DOI information: 10.1016/j.prevetmed.2015.11.003

Progress 10/01/14 to 09/30/15

Outputs
Target Audience:We are presenting our work to the global swine industry at the Allen D. Leman Swine Conference, Sept 19-22nd 2015. This venue will target hundreds of industry participants from over 20 countries. http://www.cvm.umn.edu/vetmedce/events/adl/home.html Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A postdoc trained in wildlife disease ecology is now an expert on constructing mathematical models for production animals. This model is now being adapted for a FMD model for a PhD student's thesis. The project has also provided training for another PhD student to construct a within-farm model of influenza dynamics; this will form a chapter of her dissertation. How have the results been disseminated to communities of interest?We will be presenting the between-farm model at a FMD workshop and the within-farm model on a poster at the upcoming Leman Swine conference. What do you plan to do during the next reporting period to accomplish the goals?For the between farm model, we will simulate PEDv on the movement network. We also have PEDv sequence data; if there is enough variation in the sequences, we will 'fit' the model to the data to obtain a realistic model of the main routes of PEDv spread between farms. For the within-farm influenza model, we will write up the results in the form of a manuscript.

Impacts
What was accomplished under these goals? The modeling framework has been constructed, the postdoc has partnered with a large swine company and has obtained (a) livestock movements and (b) pathogen status for the corresponding time period of a PEDv outbreak. The new team of modelers and empiricists is very happy with the flexible between-farm model. More work was conducted on a within-farm influenza model-- seeing if it was theoretically possible to eliminate influenza within a breeding farm after initial introduction of the virus.

Publications

• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: White, L.,* M. Torremorell & M.E. Craft "A stochastic, mathematical model of influenza A virus within swine breeding herds: Implications of possible management interventions," Leman Conference, St Paul, Minnesota (Sept 2015).
• Type: Journal Articles Status: Submitted Year Published: 2016 Citation: Alvarez J, Goede D, Morrison R, Perez A. Spatial and temporal epidemiology of porcine epidemic diarrhea (PED) in the Midwest and Southeast regions of the United States. Preventive Veterinary Medicine. Submitted.
• Type: Journal Articles Status: Submitted Year Published: 2016 Citation: Perez A, Wallin J, Alba A, Goede D, McCluskey B, Morrison R. Monitoring the spread of swine enterocoronavirus disease in the U.S. in the absence of a regulatory framework . Frontiers in Veterinary Science. Submitted.