NC229: Detection and Control of Porcine Reproductive and Respiratory Syndrome Virus and Emerging Viral Diseases of Swine

(Multistate Research Project)

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History of the groups activities and its outcomes: Rationale for renewing this project for the period 2014-2019


Started in 1999, the newly formed NC 229 Multistate Committee first addressed the topic Porcine Reproductive and Respiratory Disease Syndrome: Methods for the integrated control, prevention and elimination of PRRS in United States Swine Herds. Since its very onset, the group has used a novel "consortium" approach to pursue stakeholder-driven major scientific goals on the virology, immunology, epidemiology, diagnostics and control of PRRSV, combining National Pork Board (NPB), industry and USDA funds.


Close to a decade later (on November 2008, and just on the eve of its third and most recent renewal), the NC 229 Committee was awarded the first annual Experiment Station Award for Excellence in Multistate Research by the Experiment Station Committee On Organization And Policy, conferred by The Board on Agriculture Assembly, of the National Association of State Universities and Land-Grant Colleges. The NC229 committee was commended because (sic) it has been a model of multistate collaboration between institutions, working with stakeholders and providing leadership in partnering with private organizations such as swine breeding companies, diagnostic and vaccine companies and the National Pork Board. This committee is very connected to stakeholders in the swine industry and stakeholder concerns are addressed in the objectives of this project. The main reasons for such noteworthy distinction can be summarized as follows:


Throughout its existence, the NC-229 Multistate Committee has consisted of an important body of researchers that provides a forum for discussion and think-tank capabilities essential to coordinate strategies towards the control of PRRS and other major emerging diseases of swine, for example:


" The NC-229 group of researchers has been the main driving force for the preparation and successful award of an initial USDAs Coordinated Agricultural Project (CAP) in 2004-2008, which, following its renewal in 2010, led to the overall record achievement of almost $10 million dollars available for research, extension and education in PRRS and related diseases. The extraordinary significance of the NC-229-originated PRRS CAPs I and II , becomes clearly evident when it is taken into account that, combined with Check- off funding provided by swine industry (NPB), brought a total dedicated to PRRS research to more than $20 million dollars distributed for creative research and extension within the last ten years.


" The NC-229 scientific meetings offered the appropriate forum and the foundation for the organization of an Annual PRRS Scientific Symposium that, although initiated first at a national level, quickly became a yearly event of major international scope known as the International PRRSV Symposium. To this end, the basic scientific organizational capacity of NC-229 was energized and materialized thanks to the financial backing secured through the CAP funds and also through support received from the swine, pharmaceutical and biologics related industries.


" Since the initiation of this multistate committee, the NC-299 participants formed an important critical mass of collective expertise that nurtured numerous advisory cadres in charge of contributing knowledge for scientific panel reviews and policy-making recommendations on swine health to the NPB, USDA, academia in general and swine producers and veterinarians, both nationally and internationally .


Upon its most recent renewal in 2009, the NC-229 group expanded its goals beyond the topic of PRRSV to include other important swine emerging diseases. These additional important topics became an integral part of the program of annual symposiums of the NC-229 group, and proved to be of critical importance for those moments involving critical decisions or conclusions, such as the successful realization that porcine circovirus associated diseases (PCVAD) can be controlled by effective vaccination, the identification/characterization of swine influenza isolates of importance to public health, and most recently, the identification and quick adoption of diagnostic tools and appropriate disease management know-how to face the ongoing outbreak of porcine epidemic diarrhea virus (PEDV). The latter disease is now a reality faced by US swine producers, although it had been considered, until as recently as May 2013, just one more exotic disease to North America. Unfortunately, that is not the case anymore(3).


As we will exemplify in the following paragraphs, the overriding economic importance of PRRSV to North American agriculture, plus the significance of other emerging diseases represented for example by the permanent concern posed by swine influenza, the actual domestic threat presented by PEDV or the potentially very serious hazard represented by the presence of ASFV at the very doors of Europe and the Western Hemisphere(4), justify the continuation of this NC-229 multistate project. The intriguing and complex field of emerging viral diseases of swine surging and expanding in a planet with an ever-globalized economy does not allow us to let our guard down. Therefore, the title of Detection and Control of Porcine Reproductive and Respiratory Syndrome Virus and Emerging Viral Diseases of Swine for this multistate project, has been very appropriate.


The need as indicated by stakeholders:


PRRS continues to be the most devastating disease of swine in the USA. While important advances have been achieved in control of this disease, some important obstacles still exist due to the unique immuno-pathogenic characteristics of this virus. Successful completion of the NC-299 project aims will undoubtedly result in enhanced control of PRRS. Benefits will include reduced animal suffering, thus enhancing health and well-being. Swine producers will experience improved economic gain due to reduction in animal losses and more efficient pork production.


At the time the NC-229 2009 renewal was being submitted, the swine industry remained burdened with the staggering $560-million price tag for production losses associated with PRRS calculated in 2005(5). Since the previous economic study was released, and despite important advancements in research and production schemes, the cost of this disease continues to rise. A team led by Iowa State researchers recently completed a year-long study of the economic impact of the virus on the pork industry (7). The new study, which is in the process of being published by NPB and several industry web sites, estimates the total tab to the industry at $664 million annually, based on a review of production records from 80 breeding herds and grower pig closeout data on more than 600 groups of pigs over the past 3-5 years. Most importantly, the current analysis also includes expert opinions from more than 26 swine veterinarians who provide services to 2.4 million U.S. sows, which roughly represents 45% of the nations sow herd. In addition, based on these experts opinion survey, animal health costs tack on another $140 million annually due to PRRS. The annual biosecurity and other outbreak-related costs attributed to PRRS were estimated to be $191.86 million and $145.82 million, respectively. Biosecurity costs include installation of air filtration systems, truck washes and other changes to transportation, added showers, changes in pig flow, etc. Total additional costs were pegged at $477.79 million annually, putting the cumulative cost of the disease at more than $1 billion/year when added to production-related losses(7).


Since its discovery in 1991, the PRRS virus has proven itself as a significant pathogen of swine in nearly all production areas of the world(2). In 2006 it became apparent that strains of extraordinary virulence had surfaced in China, causing a major blow to the worlds largest swine herd(10). This threat and the general concern about virulence exacerbation by intense genome mutations in the field has reemphasized the need for effective PRRS control and the importance of finding predictably successful tools for managing or eliminating the virus from farms. The NPB, for the last 8 years, has been engaged in PRRSV area control and elimination efforts through research and education efforts that support and continue to develop tools and strategies to better manage the virus. In 2013, the Swine Health Committee of the NPB developed the following statement to help guide PRRS research and outreach efforts: The short-term objective (ideally to be accomplished in less than 3 years) is to reduce the impact PRRS has on producers, and to assess the feasibility and financial acceptability of PRRS area control and/or elimination for producers. To that end NPB has identified the following 4 major focus points, which are mirrored in and consist of the foundations of the objectives of this current NC229 proposal(8):


1) PRRSv Immunity and Vaccinology: centered at understanding correlates of immunity and mechanisms to broaden protection


2) PRRSv Epidemiology and Surveillance: with emphasis in understanding virus transmission and differential testing of animals(DIVA) and


3) Economic Impact of Interventions: with emphasis at determining the economic benefit of vaccination in positive herds


The national priorities for swine health research established by NPB and American association of swine Veterinarians (AASV) constitute an accurate gauge of the stakeholder needs in the area of other emerging diseases of swine of interest for the NC-229 committee. The NPB has announced, in its recent Spring 2013 call for proposals, that there is an extreme need to assess the interspecies transfer of influenza virus (human to pig and vice-versa) and to assess the impact of vaccine interventions, such as vaccine use in people and pigs on the curtailment of transmission of influenza in farms and in exhibition settings and other points of concentration(8). The current outbreaks of porcine epidemic diarrhea in the US have provided a dramatic and eloquent example of how industry can timely respond, on a real time basis, to a significant infectious disease emergency. The NPB, and the AASV, backed by USDA/ APHIS have been following up the PEDV epizootics literally since the emergence of the index case and substantial emergency funds to support the most immediate needs in research have already been made available(6). These include development and validation of diagnostic testing for PEDV, understanding tissue tropism, shedding characteristics, in vitro propagation of the agent and its environmental stability. Particularly remarkable are the initiative by NPB and USDA in 2012 and again in 2013 to respond to the threat posed by the extensive dissemination through Eastern Europe of African Swine Fever Virus (ASFV), the cause of a remerging disease that threatens to expand through Western Europe, since its introduction in the Caucasus and Russiain 2007. The ASFV is considered by the US swine industry a major threat, to the point that the NPB and the competitive programs of USDA-AFRI, in a remarkable turning point, are currently funding projects based in, besides the traditional USDA labs specialized in FAD (like PIADC) local universities and other US academic laboratories associated with NC-229 in order to conduct investigations in this foreign disease(9). In the case of ASFV, the priorities established by the US swine industry include research focused towards development of tools to detect, control, and limit adverse effects from ASFV in swine. The priorities include also the development of vaccine or other type of intervention to deal with a possible outbreak of ASFV in the continental US.


The importance of the work and the consequences of failing to respond:


The US swine industry is at a crucial economic crossroads. Increased production costs and a strained economy have severely impacted many swine operations and pork producers are further hampered by infectious disease problems that increase production costs. When the viral etiology of PRRS was established by investigators in the Netherlands in 1991(11)and shortly thereafter, in the U.S. (1)research has progressed towards understanding the disease and the associated virus. The release of the first live-attenuated commercial vaccine (MLV) in June 1994 was hailed as a significant achievement and a hoped-for solution for an industry that was experiencing acute and chronic infections of PRRS virus. However, MLV have not fully met expectations; deficiencies including virus shedding, persistent infection, potential reversion to virulence and incomplete protection have been reported. Moreover, there is no method to distinguish infected from vaccinated pigs. Because of vaccine failures, many producers have sought controlled exposure or acclimation, i.e., the intentional infection of naive animals with wild-type live PRRSV either through contact with infected animals or exposure to infectious material . Thus, young pigs are exposed to farm-specific live virus in an attempt to induce immunity; however, this results in continuous spread of the virus and perhaps inadvertent spread of other diseases. There are several reasons why PRRS virus infections are difficult to control. First, mutation of the virus creates strains with unique antigenic profiles that result in poor cross-protective immunity . Second, PRRS virus elicits a rather complicated and unique immune response that subverts the immune system and results in persistently infected swine . Third, PRRSV synergizes with ubiquitous infectious agents of low virulence to produce clinically and economically significant disease syndromes, such as porcine respiratory disease complex (PRDC). Fourth, anecdotal evidence strongly suggests that the virus can efficiently move between farms, even those that utilize rigorous biosecurity and good production practices. Finally, relatively few tools, including effective vaccines and surveillance techniques, are available to producers and veterinarians for managing the disease. If ignored and left untreated, PRRS virus becomes entrenched in all phases of a production system, setting the stage for a biological "train wreck" and economic catastrophe. Even farms that survive a PRRS outbreak become re-infected despite all best efforts to protect the animals.


Porcine epidemic diarrhea virus has recently emerged and continues to spread across the country throughout many states. Initiation of research programs on PEDV was perceived by industry as an impending necessity that could not afford any delay. Herd loss may affect pork production as countless pigsmost suckling and early-weaned pigsdie from the gastrointestinal disease. Since the identification of the virus was confirmed in the United States on May 17, 2013, more than 400 cases have been reported. Cases in suckling and nursery pigs became prevalent in the middle of the summer 2013 with a high mortality rate of 30 percent to 100 percent in early-weaned pigs in naïve herds. Nursery pigs, grow/finish pigs and adult animals experience a high rate of morbidity but low mortality with the virus, any potential impact on pork supply could be expected within several months, mot ?likely towards December 2013. Typical of incipient outbreaks of an unknown disease, lack of data on pig PEDV cases makes it difficult to calculate its financial impact. How well the virus is controlled in upcoming months will be vital.
If not prevented a possible outbreak of African swine fever virus (FAD) can have a significant negative impact to producers. A recent study estimates the annual economic benefit of prevention of a FAD like ASFV just to the pork industry is worth $137million(8)


Worldwide there is great concern that the next pandemic will be caused by potential cross-species adaptation and spread of influenza viruses . Influenza viruses infect humans, swine, and avian species; they can exchange genetic sequences and produce new re-assortant viruses. Thus besides the respiratory problems caused in swine by flu viruses, swine are a potential source of new influenza viruses that can infect humans(12). This is particularly problematic given the potential for re-assortment of swine flu viruses with highly pathogenic avian influenza. Influenza is just one of numerous transboundary viral diseases of concern to the swine industry. Foot-and-mouth disease and classical swine fever virus are each major foreign animal disease threats to US producers.


Overall there is a sense of urgency and a very compelling justification for this proposed NC229 project. It presents an animal health paradigm to address future disease threats to swine and to humans. It provides new technologies to control newly emergent diseases. PRRSV was unknown just 20 years ago and PCV2b emerged in 2004 and PEDV as we speak!. Failing to solve these swine disease problems jeopardizes foreign trade in swine breeding animals, semen, and pork products; places a secure, nutritious, and wholesome food supply for the U.S. consumer at risk; and continues the downward economic spiral as farmers lose their livelihood. The new NC229 project will provide substantial opportunities to address important swine diseases based on inter-institutional cooperation at the national and international level.


The technical feasibility of the research:


Successful realization of the study objectives requires basic and applied research studies, including immunology, functional genomics, epidemiology, genetics, and molecular biology. Within this framework, NC-229 has the capacity to coordinate ideas and resources, focus on specific problems and projects, and respond immediately to new information related to virus control and elimination. It has also provided a method of dissemination through coordinated national and international meeting forums. A well documented record of such capacity of the group is represented by having attained and successfully managed two major CAP grants in PRRS during the last 10 years. This achievement attests to the expert technical know-how of the group. A remarkable spin off of the seminal funding obtained through the CAPs is represented by the continuous utilization by the group of CAP-generated results to amplify and leverage further funding through USDA NIFA competitive grants, NPB research grant program and industry funds.


The advantages of a multi-state research effort:


The NPB, NC-229 and other swine health experts have concluded that effective control of swine viruses will not rely on a single technology or solution, but on multiple strategies applied to all levels in the swine production system. While there is much expertise available from single entities, the best hope for the control and elimination of PRRSV and swineviral infections is a collaborative, multidisciplinary research program that focuses on specific aspects of the diseases. Since 2008, the NC-229 has been expanded to 14 stations (CT, GA, IA, IL, KS, MD, MO, MN, NC, NE, OH, IN, SD, and VA), 3 ARS labs (USDA-BARC, USDA-MARC, USDA-NADC), and importantly, international groups in China, Mexico and Spain.


Likely impact of successfully completing the work. The greatest impact of the successful conclusion of this research will be new paradigms for the control of PRRS and other swine viral emerging diseases. Progress toward this goal will proceed through the successful accomplishment of specific aims and milestones described later in this proposal. The creation and operation of a virtual university environment where investigators share data and ideas has been effected by the previous PRRS CAP programs. A major milestone for this NC229 renewal will be to expand this network to address the real industry problem of complex swine viral diseases. A second milestone will be risk assessment projects that will demonstrate new protocols and management techniques for the control and elimination from & Having multiple stations and researchers involved, will provide expertise in the vast array of viral diseases where knowledge in one area may translate to control in another. Therefore, not only is the NC229 consortium a multi-state multi-country multi-university group, but also a multi-pathogen related group. Communication across these collaborations will help in not only helping solve the current infectious disease problems, but also in being ready for the next emerging disease.


1. Benfield, D. A., E. Nelson, J. E. Collins, L. Harris, S. M. Goyal, D. Robison, W. T. Christianson, R. B. Morrison, D. Gorcyca, and D. Chladek. 1992. Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). J Vet Diagn Invest 4:127-33.


2. Meulenberg, J. J. 2000. PRRSV, the virus. Vet Res 31:11-21.


3. Mole, B. Deadly pig virus slips through US borders. Nature 499:388.


4. Mur, L., B. Martinez-Lopez, and J. M. Sanchez-Vizcaino. Risk of African swine fever introduction into the European Union through transport-associated routes: returning trucks and waste from international ships and planes. BMC Vet Res 8:149.


5. Neumann, E. J., J. B. Kliebenstein, C. D. Johnson, J. W. Mabry, E. J. Bush, A. H. Seitzinger, A. L. Green, and J. J. Zimmerman. 2005. Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227:385-92.


6. NPB. 2013. PEDV Research & Resources. http://www.pork.org/Research/2641/ResearchLatestNews.aspx.


7. NPB. 2011. Pork Checkoff Study: PRRS Costs Industry $664 Million Annually
http://www.pork.org/News/1265/PRRSCostsIndustry664Million.aspx#.Uin3i7xcRSc


8. NPB. 2013. Spring 2013 Call for Proposals. http://www.pork.org/filelibrary/RFPs/2013/2013SpringCall.pdf.


9. PorkCheckoff. 2013. Funded research through general call http://www.pork.org/filelibrary/ResearchGrants/2013%20-%20thru%20General%20Call.pdf.


10. Tian, K., X. Yu, T. Zhao, Y. Feng, Z. Cao, C. Wang, Y. Hu, X. Chen, D. Hu, X. Tian, D. Liu, S. Zhang, X. Deng, Y. Ding, L. Yang, Y. Zhang, H. Xiao, M. Qiao, B. Wang, L. Hou, X. Wang, X. Yang, L. Kang, M. Sun, P. Jin, S. Wang, Y. Kitamura, J. Yan, and G. F. Gao. 2007. Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS One 2:e526.


11. Wensvoort, G., C. Terpstra, J. M. Pol, E. A. ter Laak, M. Bloemraad, E. P. de Kluyver, C. Kragten, L. van Buiten, A. den Besten, F. Wagenaar, and et al. 1991. Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 13:121-30.


12. York, I., and R. O. Donis. The 2009 pandemic influenza virus: where did it come from, where is it now, and where is it going? Curr Top Microbiol Immunol 370:241-57.
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