NC_OLD229: Porcine Reproductive and Respiratory Disease: Methods for the integrated control, prevention and elimination of PRRS in United States Swine Herds
Statement of Issues and Justification
The need as indicated by stakeholders. According to the National Pork Board (NPB), Porcine Reproductive and Respiratory Syndrome (PRRS) is the most economically significant disease facing the industry today, costing U.S. pork producers at least $600 million annually. The NAHMS 2000 report (Part II: Reference of Swine Health & Health Management in the United States, 2000) found that PRRS affected 21.4% of all breeding herd operations and, importantly, 58.3% of operations with greater than 500 sows. Similarly, 16.6% of all grow/finish operations had PRRS during the previous months, including 50.7% of large sites with 10,000 or more pigs. The estimated monetary losses due to PRRS virus outbreaks range from $100 to $510 per inventoried female (209). Thus a small sow or gilt herd of 250 animals would loose approximately $25,000 to $127,500, whereas, a herd of 1000 sows or gilts suffers a monetary loss of $100,000 to $500,000. Losses are not only due to reduced reproduction capacity in gilts or sows, but to other aspects of production. Typically, PRRS appears prior to breeding and continues to exert its negative economic impact through the farrowing, nursery, and finishing phases of production. For example, Dee and Joo (210) estimated that PRRS virus infection delayed marketability for 14 to 30 days at an additional cost of $7.50 to 15.00 per pig marketed.Swine producers have been extremely frustrated by the economic losses resulting from PRRSV infections and the lack of effective protocols for the control and/or prevention of this disease in herds. In July 2002, the NPB, through the Pork Checkoff Swine Health Committee, recommended an increased sense of urgency among those activities involved in control, elimination, vaccine development, and PRRS basic science research. In June 2003, the NPB, in collaboration with a broad-based stakeholder panel that included university researchers and extension personnel, biopharmaceutical companies, state and federal government agencies, and swine veterinarians, outlined a national initiative with broad objectives to create tools and strategies for the successful management of PRRS on U.S. swine farms (see the June 5, 2003, news release, Pork Checkoff Coordinating National PRRS Initiative, at www.porkboard.org/News/default.asp and the supplemental information therein; also Journal of Swine Health and Production 11(5):253-254). This panel identified at least 11 critical needs for research, technology transfer, and communication of research on PRRS:
1. Understanding the persistently infected pig, specifically, the mechanisms for persistence and testing strategies for identifying persistently infected pigs.
2. Cooperative vaccine development, including new and novel candidate vaccines.
3. Investigation of immune and antiviral therapies.
4. Implementation of PRRS virus typing systems for the purposes of vaccine development and diagnosis.
5. Creation of a national PRRS virus genomic sequence database for the purpose of cataloging old strains and tracking new strains during outbreaks.
6. Design and implementation of a national epidemiologic survey for the purpose of performing risk factor analyses to provide a fundamental understanding of the measures necessary for successful on-farm and regional PRRS elimination programs.
7. Understanding mechanisms of inter-farm virus transmission.
8. Design and implementation of regional PRRS virus elimination demonstration projects.
9. Engagement of international PRRS researchers into problems faced by U.S. producers.
10. Collaboration with researchers of related (non-swine) viruses for the purpose of developing model systems for understanding the disease.
11. Creation of real-time PRRS information/education systems for disseminating updates and information to producers and veterinarians.
These stakeholders' recommendations provide the relevance for this new NC-229 proposal. No other multistate project specifically addresses PRRS. Producers have indicated the need for research that enhances our knowledge to eliminate PRRS as the highest research priority of the NPB and NC-229 has embraced these stakeholder suggestions in the present proposal.
The importance of the work and the consequences of failing to respond. The United States swine industry is at a crucial economic crossroads. Increased production costs and declining prices have severely impacted many swine operations. In addition to market and price factors, pork producers are hampered by infectious disease problems that increase production costs. When the pseudorabies eradication programs were implemented in 1989, it was thought that one of the most devastating diseases in the U.S. swine industry would be quickly eradicated. In fact, our scientific and organizational abilities were affirmed when pseudorabies was declared eliminated from U.S. domestic swine herds on January 14, 2002. However, the expectation of reducing economic losses in swine due to viral diseases was shattered with the appearance in 1987 of PRRS, then known as mystery swine disease (190). Since 1991, when the viral etiology of PRRS was established by investigators in Europe (192) and then in the U.S.,(193) research has progressed towards understanding the disease and the associated virus. The release of the first live-attenuated commercial vaccine 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. A proportion of producers have reported satisfactory results using modified live vaccines, but several deficiencies in performance have been noted. In particular, virus shedding, transmission, and persistent infection of vaccine virus have been documented in the field and in controlled experiments (25; 193; 211). There are also efficacy issues related to the failure of vaccines to provide protective immunity against heterologous virus isolates and reversion to virulence has been alleged from off-label use (202). These issues have highlighted the adaptability of the virus, the difficulty in achieving progress in control of the disease and the frustration of producers and veterinarians, who cannot prevent, moderate or eliminate the disease. From the perspective of the level of scientific understanding and after 14 years of study, the name Mystery Disease is still an appropriate description of PRRS. An unfortunate consequence of our gaps in knowledge is the increasing use of alternative, but scientifically untested and potentially hazardous methods (such as using live field virus to vaccinate pigs) to control this disease.
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.
In the final analysis, 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 an economic catastrophe. Even farms that survive a PRRS outbreak become re-infected despite all best efforts to protect the animals. Failing to solve the PRRS problem 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.
Continuous changes and refinements in food animal production techniques support the hypothesis that PRRS virus represents the tip of the iceberg of emerging disease threats to the food animal industry. This brings a sense of urgency to this proposed project, as it represents a new animal health paradigm to address future disease threats. Moreover, PRRS is a newly emergent disease, unknown 20 years ago. It is in the same taxonomic order (Nidovirales) as the SARS coronavirus. Currently, PRRS is not pathogenic for human beings. However, three characteristics of the ecology of this virus (its uncertain origin, rapid evolution rate and human-pig contact), increase its potential to become a human pathogen. Thus, perhaps another reason to work towards elimination of this virus.
The technical feasibility of the research. Successful realization of the study objectives will require basic and applied research studies, including functional genomics, immunology, 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 PRRS virus control and elimination. In working towards these goals, the NC-229 committee directed and coordinated the preparation and submission (July 30, 2003) of a $4 million grant proposal to the USDA National Research Initiative Integrated Program office on the Integrated Control and Elimination of PRRS virus in the U.S. This proposal describes collaborative research, education, and outreach plans via the coordinated efforts of the NPB and the NC-229 multi-state consortium of PRRS researchers, academic institutions, USDA, and private industry. This project has been recommended by the USDA for funding and will provide a financial resource for the NC-229 technical committee to work with the USDA-NRI project director to implement a coordinated multistate and multidisciplinary approach to the elimination of PRRS.
The advantages of a multi-state research effort. The NPB, NC-229 and other swine health experts have concluded that complete elimination of PRRS virus is the only viable long-term strategy for alleviating the economic impact of the virus. Successful elimination of the PRRS virus will not rely on a single technology or solution, but on multiple strategies applied to all levels in the swine production system. Within this framework, NC-229 will continue to build on the capacity it has developed to coordinate ideas and resources, focus on specific problems and projects, and respond quickly to new information related to PRRS virus elimination. While there is much expertise available from single entities, the best hope for the control and elimination of PRRS is a collaborative, multidisciplinary research program that focuses on specific aspects of the disease. The NC-229, composed of personnel from eleven stations (IA, IL, KS, MN, MO, MS, NC, NE, OH, SD and VA), plus USDA-BARC, USDA-NADC, and the University of Guelph (Canada), has a history of productive and collaborative PRRS virus research (see Related, Current, and Previous Work).
Likely impact of successfully completing the work. The greatest impact of the successful conclusion of this research will be a new paradigm for the control of PRRS virus infections. Progress toward this goal will proceed through the successful accomplishment of specific aims and milestones described later in this proposal. A principal milestone is the creation and operation of a virtual university environment where investigators share data and ideas. A second milestone is a regional PRRS demonstration project that will demonstrate new protocols and management techniques for the elimination of PRRS virus from herds. Other important research outcomes include;
1. The discovery and development of methods that prevent establishment of PRRS virus infection on a pig farm and facilitate elimination of ongoing infections.
2. The identification of factors involved in inter-farm transmission and the role of geography and viral genetics in regional spread between area farms.
3. The development and delivery of differential immunodiagnostics capable of determining animal infection status, rapidly identifying virus strains and detecting and differentiating animals exposed to field versus vaccine viruses, including newly developed marker vaccines.
4. The design and implementation of eradication protocols in relevant ecological settings.
5. The development of outreach and educational materials and real time delivery methods that provide biosecurity and compliance information and training to producers, veterinarians, and swine health specialists, including multi-lingual biosecurity manuals and protection protocols. This material will also be readily available through the internet.
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