Source: MICHIGAN STATE UNIV submitted to
DIAGNOSIS AND PREVENTION OF BOVINE VIRAL DIARRHEA VIRUS (BVDV)
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0180731
Grant No.
(N/A)
Project No.
MICL01916
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Apr 1, 2009
Project End Date
Mar 31, 2014
Grant Year
(N/A)
Project Director
Grooms, D.
Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
Large Animal Clinical Sciences
Non Technical Summary
This project will provide important information necessary for the development of sound and economical BVDV control and prevention strategies. Not only will producers benefit by reducing economic loss associated with BVDV morbidity and mortality, but consumers will also benefit because of the reduced disease incidence which has both food safety and quality implications. For objective 1, we expect to develop and demonstrate new strategies for detecting herds infected with BVDV and cattle peristently infected with BVDV. These strategies would aid veterinarians and producers in economically detecting BVDV infected herds and could be used in large scale BVDV control and eradication efforts. For objective 2, we expect to further define the role that vaccination plays in fetal protection and preventiong bovine respiratory disease and discover ways to optimize this protection.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310110150%
3113410110150%
Goals / Objectives
Bovine viral diarrhea virus (BVDV) is one of the most important infectious agent of cattle which is of worldwide concern. Because of the extremely complex disease pathogenesis, it is difficult to establish the economic cost associated with BVDV. This project will provide important information necessary for the development of sound and economical BVDV control and prevention strategies. Not only will producers benefit by reducing economic loss associated with BVDV morbidity and mortality, but consumers will also benefit because of the reduced disease incidence which has both food safety and quality implications. This project will focus on two aspects which are critical to controlling BVDV; 1) Diagnosis of BVDV and 2) BVDV prevention strategies.
Project Methods
Objective 1a: Development of low cost strategies to screen herds for infection with BVDV is needed. To meet this objective, we will compare the use of sentinel animals as a method to screen herds for BVDV infection to individual animal testing. In cooperating herds, a subset of unvaccinated 6 month old calves (sentinels) will be tested for serum virus neutralization antibodies to both genotype 1 and 2 BVDV. At the same time, testing of all individual cattle on the farm will be conducted using pooled rtPCR on skin samples. The presence of VN titers in sentinel animals will be compared to test results from all individual animals. We plan to test this strategy on a minimum of 40 cow-calf herds in the Up[per Peninsula of Michigan. Objective 1b: The identification of cattle persistently infected with BVDV is a key component in the control and prevention of BVDV. Available screening assays are very good at detecting PI cattle; however their cost can be prohibitive and are all are laboratory based. The continued development and evaluation of effective and economical BVDV detection assays is critical to the widespread acceptance of BVDV testing. Current and future research will be aimed at refining and optimizing biosensors for real time and multiplex BVDV detection systems. Testing will continue to emphasize the development of biosensors that can work with a variety of different test substances (whole blood, serum, nasal swabs, and skin samples). These systems have the potential of being deployed patient side and presenting real time results. Objectiv 2a: In past research, we have developed a natural infection model for testing BVDV vaccines effectiveness in preventing fetal infection. Our plans are to extend this model to look at different vaccine strategies in preventing fetal BVDV infections. Variables we intend to examine include types of vaccines (live -vs- killed), timing of vaccines (prebreeding -vs- during pregnancy), and type of viral exposure (different genotypes with different pathogenicity). Objective 2b: Bovine viral diarrhea virus is known to be a part of the bovine respiratory disease complex (BRD), better known as shipping fever. The role that cattle persistently infected with BVDV may play in BRD is unknown. Using a model developed previously, we will continue to study the effect that PI calves have on non-PI cattle in feedlot settings after different intervention strategies are used. Variables that we will look at include types of vaccines used (killed -vs- live or different antigenic make-ups), timing of vaccine administration (pre-arrival -vs- on-arrival in feedlots), and preconditioning programs. Parameters to be measured include morbidity, mortality, growth performance and economic performance. The goal is to establish the importance of PI calves in BRD and the best management schemes to reduce the role that BVDV may play in BRD.

Progress 04/01/09 to 03/31/14

Outputs
Target Audience: The research conducted as part of this umbrella project is primarily directed at cattle producers. Indirectly, the research impacts the entire cattle industry and ultimately consumers thru improved food safety. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? During the reporting period, 1 MS studnet was trained in clonjuction with this project. In additon, 2 DVM summer sudents and 1 undergraduate students were involved with the project. How have the results been disseminated to communities of interest? Work supported by this project has been reported over the past 5 years at state, regional, and national meetings and published in peer reviewed journals. National meeting where reports were made related to this project in include the American Association of Bovine Practitioners, Conference of Researcher Workers in Animal Diseases, US Animal Health Association, National Cattlemen’s Association, and the USDA NC 1192 Regional Research Project. In addition, 5 peer reviewed manuscripts have been published on work originating from this project. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? This project has led to several positive outcomes beneficial to the cattle industry. The MI UP BVDV eradication project successfully led to the development of a BVDV eradication model that could be implemented on a local or regional basis. This project has led to behavioral changes that continued to be sustained among cattle producers involved in the project. The most important change that has occurred is the attention paid to biosecurity. In on-going informal conversations with producers involved in the program and based on results of survey work, bisoecurity practices continue to be emphasized and implemented. Increased attention is also being paid to the development and implementation of effective vaccine programs. Producers have developed a better appreciation for proper vaccine program development and implementation. Additionally, we added significant knowledge to the understanding of the inpact of BVDV in feedlots. Studies were conducted to further evaluate the effect of constant exposure to BVDV on feedlot animal health and performance. The specific objective was to determine if different pre-weaning BVDV exposures mitigated adverse consequences of constant BVDV exposure in a feedlot setting. Results of the trials indicated that PI cattle adversely affect the health and performance of feedlot cattle. The magnitude of that adverse effect varied and was likely influenced by many factors such as the age, breed, nutritional status, and immune status of individual calves; environmental factors such as shipping, stocking density, and ventilation; and viral factors such as genotype and pathogenicity. The effect of exposure of feedlot calves to PI cattle was mitigated by exposure of those calves to BVDV before feedlot entry, either by natural exposure or vaccination. Although exposure of calves to BVDV prior to feedlot entry did not guarantee complete protection of those calves against BVDV infection or development of BRD, it did reduce the risk and severity of disease. These findings support the practice of vaccinating feedlot calves against BVDV as a method to mitigate the negative effects should those calves be exposed to PI cattle in the feedlot. Vaccination of feedlot calves against BVDV in combination with identification and removal of PI cattle from the population should minimize the effect of BVDV on the health and performance of feedlot cattle.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Grooms DL, Brock KV, Bolin SR, Grotelueschen DM, Cortese VS. Effect of constant exposure to cattle persistently infected with bovine viral diarrhea virus on morbidity, mortality, and performance in feedlot cattle: summary of three studies. J Am Vet Med Assoc. 2014;244(2):212-224. doi: 10.2460/javma.244.2.212.


Progress 01/01/13 to 09/30/13

Outputs
Target Audience: The research conducted as part of this umbrella project is primarily directed at cattle producers. Indirectly, the research impacts the entire cattle industry and ultimately consumers thru improved food safety. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Work supported by this project has been reported over the past 12 months at state, regional, and national meetings and published in peer reviewed journals. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? During this reporting period, outputs on this project primarily occurred in conjunction with the Michigan Upper peninsula BVDV Eradication Project. In 2013, we published a special report o this project outlining what has been done and the potential impacts.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Grooms DL, Barlett BB, Bolin SR, Corbett EM, Grotelueschen DM, Cortese VS. Special Report: A Review of the Michigan Upper Peninsula Bovine Viral Diarrhea Virus Eradication Project. J Am Vet Med Assoc. 2013 Aug 15;243(4):548-54. doi:10.2460/javma.243.4.548.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2013 Citation: Grooms DL, Brock KV, Bolin SR, Grotelueschen DM, Cortese VS. Effect of constant exposure to cattle persistently infected with bovine viral diarrhea virus on morbidity, mortality, and performance in feedlot cattle: summary of three studies. J Am Vet Med Assoc. Accepted for Publication, 2013.


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: During this reporting period, outputs on this project primarily occurred in conjunction with the ongoing Michigan Upper peninsula BVDV Eradication Project. 2012 marks the 6th year of the program. To date, over 60% of the UP cattle farms have enrolled in the project. Results of this project continue to be reported at national, regional and local meetings. In 2012, we reported out the results of a study looking at the potential for detecting BVDV virus by PCR in skin samples taken from calves following vaccination with a modified-live BVDV vaccine. Results of this study indicate the likelihood of detecting vaccine virus is small. The potential association of persistent infection with BVDV on colonization and shedding of shiga-toxin producing E. coli (STEC) was incorporated into a large STEC Ecology project. The hypothesis is that cattle that arte BVDV PI's may be at higher risk for colonization and shedding of STEC and may be also have unique characteristics (e.g. "super-shedding", persistent infection, etc) that are important to STEC epidemiology. PARTICIPANTS: Project personnel involved in the BVDV eradication project include faculty from the MSU College of Veterinary Medicine and MSU Extension educators. Roles are primarily in planning and implementing activities around the BVDV eradication project. In addition personnel from the Michigan Department of Agriculture and United States Department of Agriculture have also been involved in the project. The BVDV exposure field trial was conducted at MSU and was funded by Pfizer Animal Health. TARGET AUDIENCES: The research conducted as part of this umbrella project is primarily directed at cattle producers. Indirectly, the research impacts the entire cattle industry and ultimately consumers thru improved food safety. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The MI UP BVDV eradication project has led to behavioral changes that continued to be sustained. The most important change that has occurred is the attention paid to biosecurity. In on-going informal conversations with producers involved in the program and based on results of survey work, bisoecurity practices continue to be emphasized and implemented. Increased attention is also being paid to the development and implementation of effective vaccine programs. Producers have developed a better appreciation for proper vaccine program development and implementation.

Publications

  • Corbett EM, Grooms DL, Bolin SR. Evaluation of Skin Samples by RT-PCR Following Immunization with a Modified-Live Bovine Viral Diarrhea Virus Vaccine. Am J Vet Res. 2012;73(2):319-324.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: During this reporting period, outputs on this project primarily occurred in conjunction with the ongoing Michigan Upper peninsula BVDV Eradication Project. The UP BVDV Eradication Program is now entering its 5th year. To date, over 60% of the UP cattle farms are enrolled in the project. Results of this project were reported at national, regional and local meetings and monthly reports of activities related to the BVDV Eradication Project are presented in newsletters to stakeholders in the Upper Peninsula of Michigan. Additionally, a study was conducted to further evaluate the effect of constant exposure to BVDV on feedlot animal health and performance. The specific objective was to determine if different pre-weaning BVDV exposures mitigated adverse consequences of constant BVDV exposure in a feedlot setting. This field study was conducted with calves that originated from two farms. Two weeks prior to weaning, all calves were blocked by date of birth and assigned to one of two vaccination groups 1) vaccinated with Bovi-Shield GOLD FP 5 or 2) NOT vaccinated with Bovi-Shield GOLD FP 5 . At weaning, calves were moved to the Michigan State University Beef Cattle Research and Teaching Center where they were all comingled and housed in one pen. Upon arrival, 4 BVDV PI calves were immediately introduced into the group. Calves were housed with PI's and fed for 220 days. Morbidity and mortality parameters were calculated. Although there was a trend of decreased overall morbidity, retreatment and repull rates, there was no statistical difference between the vaccinated and unvaccinated groups (p=0.25). There was no difference between the pre-vaccinated and non-vaccinated groups in terms of weight or ADG over the course of the observation period. PARTICIPANTS: Project personnel involved in the BVDV eradication project include faculty from the MSU College of Veterinary Medicine and MSU Extension educators. Roles are primarily in planning and implementing activities around the BVDV eradication project. In addition personnel from the Michigan Department of Agriculture and United States Department of Agriculture have also been involved in the project. The BVDV exposure field trial was conducted at MSU and was funded by Pfizer Animal Health. TARGET AUDIENCES: The research conducted as part of this umbrella project is primarily directed at cattle producers. Indirectly, the research impacts the entire cattle industry and ultimately consumers thru improved food safety. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The UP BVDV eradication project has led to several noticeable changes in behaviors. The most important behavioral change that has occurred is the attention now being paid to biosecurity as it relates not only to BVDV but also other infectious disease that affect cattle. In addition, many livestock exhibitions in the UP of Michigan now are engaged in the BVDV control program by requiring that cattle be tested free of BVDV before coming to the exhibit. In the BVDV exposure study, no statistically significant differences between treatment groups were found in any of the parameters evaluated, however a trend in increased morbidity and decreased performance were observed in the non-vaccinated group. Previous studies have both supported and refuted a significant impact of BVDV PI's on feedlot performance. The trend of a negative impact of constant BVDV exposure supports findings from earlier studies and builds upon the evidence that constant exposure to BVDV is deleterious. These findings, as well as others, are moving the cattle industry towards more aggressive BVDV control practices.

Publications

  • Corbett E, Grooms D, Bolin S. Detection of bovine viral diarrhea virus in skin samples by RT-PCR following immunization with a modified-live bovine viral diarrhea virus vaccine. Proceedings of the 20th Annual Phi Zeta Research Day, Michigan State University, October 1, 2010. p20.
  • Corbett E, Grooms D, Bolin S. Evaluation of skin samples by RT-PCR following immunization with a modified-live Bovine Viral Diarrhea Virus vaccine. Proceedings of the 2010 Conference of Research Workers in Animal Diseases, Chicago, IL, December 5-7, 2010, Abstract # 157.
  • Corbet EM. Serological Evaluation of Sentinel Calves in A BVDV Eradication Program. Masters Degree Thesis, Completed December 2010.
  • Corbett EM, Grooms DL, Bolin SR. Serological Evaluation of Sentinel Calves in a BVDV Eradication Program. J Vet Diagn Invest. 2011;23(3):511-515.
  • Grooms D, Bolin S, Bartlett B, Grotelueschen D, Cortese V. The Michigan Upper Peninsula BVDV Eradication Project. Proceedings of the 5th US BVDV Symposium, San Diego, CA, November 17-18, 2011.
  • Grooms D, Bolin S, Brock K, Grotelueschen D, Cortese V. Effect of constant BVDV PI exposure on morbidity, mortality and performance in Feedlot cattle: summary of three studies. Proceedings of the 5th US BVDV Symposium, San Diego, CA, November 17-18, 2011.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: During this reporting period, outputs on this project primarily occurred in conjunction with the ongoing Michigan Upper peninsula BVDV Eradication Project. Specific outputs include the following: 1) Implementation of the UP BVDV Eradication Program is now entering its 4th year. To date, over 50% of the UP cattle farms are enrolled in the project 2) A research project examining the implementation of a surveillance strategy using sentinel cattle to monitor BVDV free farm was completed. Results from this project are being reported out 3) A research project examining the probability that BVDV could be detected in skin samples used for BVDV diagnosis following vaccination with a commercially available BVDV vaccine, 4) Dr. Erik Corbett completed his MS degree using the BVDV eradication project has his primary source of data, 5) Three educational meetings were held in the UP focused BVDV control. Results of these activities have been reported at national, regional and local meetings and monthly reports of activities related to the BVDV Eradication Project are presented in newsletters to stakeholders in the Upper Peninsula of Michigan. PARTICIPANTS: Project personnel involved in this project include faculty form the MSU College of Veterinary Medicine and MSU Extension educators. Roles are primarily in planning and implementing activities around the BVDV eradication project. In addition personnel form the Michigan Department of Agriculture and United States Department of Agriculture have also been involved in the project. Finally, one graduate student has been involved in the project. A series of three outreach meetings were held in the Upper Peninsula of MI related to the BVDV eradication project. These meetings were targeted at producers, veterinarians, and other allied industry personnel. The focus of the meetings was biosecurity. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The UP BVDV eradication project has led to several noticeable changes in behaviors. The most important behavioral change that has occurred is the attention now being paid to biosecurity as it relates not only to BVDV but also other infectious disease that affect cattle. In addition, many livestock exhibitions in the UP of Michigan now are engaged in the BVDV control program by requiring that cattle be tested free of BVDV before coming to the exhibit.

Publications

  • Corbett E, Grooms D, Bolin S, Bartlett B. Application of Sentinel Serology in a BVDV Eradication Program. Proceedings of the 43rd Annual AABP Conference in Albuquerque NM, August 19-22, 2010.
  • Corbett E, Grooms D, Bolin S. Detection of bovine viral diarrhea virus in skin samples by RT-PCR following immunization with a modified-live bovine viral diarrhea virus vaccine. Proceedings of the 20th Annual Phi Zeta Research Day, Michigan State University, October 1, 2010.


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: Two projects were conducted in 2009 that are in alignment with the goals and objectives of this program. The first project involves the continued implementations of the Michigan Upper Peninsula Bovine Viral Diarrhea Eradication Project. The objectives for this multidisciplinary, and multi-institutional, project are to devise, initiate, and complete a regional voluntary BVDV eradication program in the Upper Peninsula (UP) of MI. The purpose is to identify benefits of, and obstacles to, such a program and, ultimately, to demonstrate a feasible approach for regional disease eradication that may be adopted by other parts of the US. Accomplishments this past year included planning and carrying out of meetings across the UP aimed at educating and recruiting cattle producers to be part of the program. Regular updates on the project are disseminated through MSUE newsletters and presentations on the project have been made at both the state and national level. The second project involved developing further understanding about the impact of cattle persistently infected (PI's) with BVDV on the cattle industry and developing management strategies to mitigate these impacts. Specifically, we continue to study the potential for preconditioning programs in calves prior to entering a feedlot in mitigating the affects of constant exposure to BVDV PI's. Preliminary findings from this study show that prevaccination for BVDV can improve overall performance of calves constantly exposed to BVDV PI's. PARTICIPANTS: Collaborators in the BVDV eradication project include Pfizer Animal Health, Michigan Department of Agriculture, United States Department of Agriculture:APHIS:VS, and Michigan State University Extension. Personnel form these organizations have provided expertise in the project development, implementation and outreach activities. The MSU CVM Diagnostic Center for Population and Animal Health provides all the diagnostic services relative to this project. Pfizer Animal Health is a collaborator in the feedlot BVDV natural exposure program TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The projects included in this program add to the growing knowledge base and tool chest available to cattle producers to help manage and control bovine viral diarrhea virus. The Michigan Upper Peninsula BVDV Eradication program was initiated in the fall of 2007. To date, 2002 herds have enrolled in the project. These herds represent 18, 511 cattle in the UP. Approximately 9,180 have been tested for BVDV with 11 BVDV PI's from 5 farms having been detected. In addition to helping producers and the entire UP of Michigan eradicate this virus, the program is also increasing producer awareness about overall animal health and welfare. Finally, the program is being looked at from a national perspective as a positive step in the national control of BVDV. The development of new and innovative diagnostic assays, such as the biosensor being studied at MSU, will enhance industry efforts to identify and eliminated carriers of BVDV. Previous efforts in developing and validating new diagnostic tools have already substantially increased sample submission to animal diagnostic laboratories. Finally, understanding how to mitigate the health and performance effects of constant exposure to BVDV PI's is important from an animal health, welfare and food safety perspective. Results for the studies conducted in 2009 will further justify preconditioning programs as a way to protect the health of calves entering commingled feedlots.

Publications

  • Corbett E, Grooms D. Incidence of herds infected with bovine viral diarrhea virus in four Western counties enrolled in the Michigan Upper Peninsula BVDV eradication program. 42nd Annual Convention of the American Association of Bovine Practitioners, Omaha, NE, Sept. 10 - 212, 2009, p 203.
  • Bartlett B, Brunner M, Harms L, Bolin S, Cortese V, Grotelueschen D, Grooms, D. A programmed approach to BVDV eradication in the Upper Peninsula of Michigan beef and dairy herds. Proceedings of the 4th U.S. BVDV Symposium "BVDV Variability: Impact on Virulence, Host Range and Control", Phoenix, AZ, Jan. 25-27, 2009.


Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: Three projects were conducted in 2008 that are in alignment with the goals and objectives of this program. The first project involved the continued development of rapid and cost effective diagnostic assays for the detection of cattle persistently infected with bovine viral diarrhea virus. Specifically, we continued the development and testing of a polyanilene based conductometric biosensor as an inexpensive, rapid and field deployable assay. Currently, the biosensor is capable of reliably detecting 10-4 CCID/ml of virus in less than 2 minutes. This years focus was to test new ways to concentrate low titer viruses using polyanilene couple magnetic beads. We continue to work on improving sensitivity and reducing variability in this assay. The second project involves the initiation of the Michigan Upper Peninsula Bovine Viral Diarrhea Eradication Project. The objectives for this multidisciplinary, and multi-institutional, project are to devise, initiate, and complete a regional voluntary BVDV eradication program in the Upper Peninsula (UP) of MI. The purpose is to identify benefits of, and obstacles to, such a program and, ultimately, to demonstrate a feasible approach for regional disease eradication that may be adopted by other parts of the US. Accomplishments this past year included planning and carrying out of meetings across the UP aimed at educating and recruiting cattle producers to be part of the program. Regular updates on the project are disseminated through MSUE newsletters and presentations on the project have been made at both the state and national level. The final project involved developing further understanding about the impact of cattle persistently infected (PI's) with BVDV on the cattle industry and developing management strategies to mitigate these impacts. Specifically, we studied the potential for preconditioning programs in calves prior to entering a feedlot in mitigating the affects of constant exposure to BVDV PI's. Preliminary findings from this study show that prevaccination for BVDV can improve overall performance of calves constantly exposed to BVDV PI's. PARTICIPANTS: BVDV Eradication Project - Personel: Dr. Ben Bartlet (MSUE), Dr. Mike Brunner (MDA)and Dr. Lori Harms (USDA)are coordinating all local efforts in the UP including communications with producers, scheduling educational sessions and working with individual producers in setting up control programs. Dr. Steve Bolin (MSU CVM and Diagnostic Center for Population and Animal Health)is coordinating all the diagnostic efforts. Dr. Dan Grooms is providing educational support and coordinating reporting, outreach and marketing efforts. Partner organizations include the Michigan Department of Agriculture, United State Department of Agriculture APHIS:VS, and Pfizer Animal Health. In addition, private veterinary practitioners are important local partners who are helping to implement the program. Biosensor Project - Personnel: Dr. Vangie Alocilja coordinates all laboratory based research while Dr. Dan Grooms coordinates field activities related to this project. Feedlot Project - Personnel: Dr. Dan Grooms was the PI on this project. Drs. Steve Bolin and Roger Maes provided diagnostic support. Pfizer Animal Health funded the project and was an integral part of the project design. TARGET AUDIENCES: This project primarily targets the cattle industry of MI and the US. The primary target is cattle producers. However, educational efforts have also targeted veterinarians, industry support personnel such as livestock dealers, nutritionists and pharmaceutical salespeople. PROJECT MODIFICATIONS: Dr. Paul Coe retired form MSU on Dece 31, 2007 and is no longer active in the project.

Impacts
The projects described in this report add to the growing knowledge base and tool chest available to cattle producers to help manage and control bovine viral diarrhea virus. The Michigan Upper Peninsula BVDV Eradication program was initiated in the fall of 2007. Progress to date has been substantial and acceptance of the program is very promising. To date, over 150 farms representing over 12,000 cattle have enrolled in the program. In addition to helping producers and the entire UP of Michigan eradicate this virus, the program is also increasing producer awareness about overall animal health and welfare. Finally, the program is being looked at from a national perspective as a positive step in the national control of BVDV. The development of new and innovative diagnostic assays, such as the biosensor being studied at MSU, will enhance industry efforts to identify and eliminated carriers of BVDV. Previous efforts in developing and validating new diagnostic tools have already substantially increased sample submission to animal diagnostic laboratories. Finally, understanding how to mitigate the health and performance effects of constant exposure to BVDV PI's is important from an animal health, welfare and food safety perspective. Results for the studies conducted in 2008 will further justify preconditioning programs as a way to protect the health of calves entering commingled feedlots.

Publications

  • Coe, P.H., Grooms, D.L., Metz, K., Holland, R.H.(2008). Changes in Antibiotic Susceptibility of Escherichia coli Isolated from Steers Exposed to Antibiotics during the Early Feeding Period. Veterinary Therapeutic, 9(3):241-247.
  • Bartlet, B., Brunner M., HArms, L., Bolin., Cortese, V., Groteluschen, D., Grooms, D.L., (2008). A programmed approach to BVD eradication in the Upper Peninsula of Michigan beef and dairy herds. Proceedings of the United State Animal Health Association, Greensboro, NC, October 25, 2008.
  • Grooms, D.L., BArtlet B. (2008). A programmed approach to BVD eradication in Upper Peninsula of Michigan beef and dairy herds. Proceedings of the Michigan State University Extension Fall Conference, Detroit, MI, October 14, 2008.
  • Bartlett, B., Grooms, D., Bolin, S.(2008). BVDV PI Eradication: Unintended Consequences Michigan Dairy Review, 13(2):15-16.
  • Bartlett, B., Grooms, D., Bolin, S.(2008). First-In-The Nation BVDV Eradication Program Launched in U.P. Michigan Dairy Review 2008;13(1):14-15.
  • Bartlett, B., Grooms, D., Bolin, S.(2008). Partnering in Animal Health - BVDV Eradication Project Begins. Cattle Call, 13(1):3.


Progress 01/01/07 to 12/31/07

Outputs
OUTPUTS: New to the project this year is the launching of the Michigan Upper Peninsula BVDV Eradication Project. Bovine viral diarrhea virus (BVDV) causes severe economic and productivity losses in cattle operations. Costs occur throughout the cattle industry and include reproductive, respiratory and immune suppressive related losses that occur in dairies, beef cow/calf operations, feedlots and other cattle enterprises. Because of the recognized effects of BVDV, many European countries are implementing BVDV eradication programs. In the US, recent efforts initiated by the Academy of Veterinary Consultants, National Cattlemen's Beef Associating and American Association of Bovine Practitioners have highlighted the importance of BVDV and the need for comprehensive control programs. Many individual producers have controlled BVDV in their cattle herds, but a state, regional or national control program has not been initiated or demonstrated. The objective of this project is to initiate a regional BVDV control program to control and eradicate BVDV. The purpose is to identify benefits and obstacles of such a program and demonstrate a feasible model that may be adopted by other parts of the US. In additon, this project has continued to work on developing new tools for the diagnosis of BVDV. Outputs from this project in 2007 have included further refinement of the conductometric biosensor used to detect BVDV and the exploration of new biosensor technology aimed at detecting pathogens important to animal and human health. This project has and continues to serve as the basis for training of students at various academic levels including undergraduate, graduate and post-graduate. It is also the basis of active collaboration between researchers that are expanding the knowledge learned in this project the to detection of other important animal and human pathogens. These inclulde Mycobacterium paratuberculosis in cattle, and important food pathogens including E. coli and Salmonella. Finally, this project has resulted in the application for a new patent on processes related to manufacturing of the biosensor. PARTICIPANTS: Dr. Steve Bolin, Michigan State University, College of Veterinary Medcine. Collaborative partner on the BVDV Eradication Project. Dr. Roger Maes, Michigan State University, College of Veterinary Medcine. Collaborative partner on the BVDV Eradication Project. Dr. Ben Bartlett, Michigan State University Extension, Collaborative partner on the BVDV Eradication Project. Michigan Departmetn of Agriculture and the United States Departmen of Agriculture, APHIS, VS. Collaborative partner on the BVDV Eradication Project. Pfizer Animal Health. Collaborative partner on the BVDV Eradication Project. Vangie Alocilja, Michigan Stte University, Department of Agriculture and Biosystems Engineering. Collaborative partner on the conductometric biosensor project. TARGET AUDIENCES: Cattle producers' are the primary target audience for this project. The goal is to positively impact the health and welfare of their cattle thus improving profitability, and product quality. In addition, other support personnel are also being targeted and include veterinarians, nutritionists, cattle markets, etc. By positively engaging the entire cattle industry, the potential impacts will be magnified.

Impacts
The Michigan regional BVDV Eradication program has been launched. The goal will be to involve and impact approximately 800 cattle producers in the UP of Michigan over the course of the project. This program has the potential to significantly impact cattle health and marketability on a regional basis. A rapid detection of BVDV in cell culture media using a biosensor has been demonstrated. Detection of cattle persistently infected with BVDV using ear notches was shown to be most consistent when compared to serum and nasal swabs Further development may make this a useful tool for the rapid and economical identification of BVDV PI cattle.

Publications

  • Muhammad-Tahir, Z., Alocilja, E.C., Grooms, D.L. (2007). Indium Tin Oxide-Polyaniline Biosensor: Fabrication and Characterization. Sensors, 7:1123-1140.
  • Grooms, D.L. (2006). Persitently infected with BVDV? Now What? Cattle Call 11(4):1-2 and Michgian Dairy Review, 12(2):10-11.
  • Grooms, D.L., Maes R. (2007). Update on BVD Testing - Pooled Ear Notch PCR Now Avaialble. Cattle Call, 12(2):6


Progress 01/01/06 to 12/31/06

Outputs
The overall goal of this project was to develop a rapid, low cost, animal side biosensor for detecting cattle persistently infected with bovine viral diarrhea virus (BVDV). The developed conductometric biosensor consists of two parts: an immunosensor and an electronic data collection system. The immunosensor was comprised of four, one-time-use, disposable membranes: sample application membrane, conjugate membrane, capture membrane, and absorption membrane. Polyaniline conjugated to BVDV specific antibodies serve as the detection element. Polyaniline is a conductive polymer that serves as an electric wire between two electrodes. Silver electrodes were fabricated on the capture membrane to electrically connect the immunosensor to the electronic data acquisition system consisting of a copper wafer and an ohmmeter linked to a computer. To date, the biosensor has been tested using different sample types collected form known BVDV infected cattle. However, the ability to consistently detect BVDV has been variable. The objective of this study was to compare different preparations of polyaniline in their ability to reduce variability in the biosensor response. Water-soluble and non-water soluble polyaniline preparations were first investigated in the biosensor. Water-soluble polyaniline was found to provide the least variability in electrical response when used in the biosensor. Next, different manufacturers preparations of water-soluble polyaniline were studied. No difference was found in the electrical response of different polyaniline preparations when used in the biosensor. Currently, we are studying the process of fractionating the conjugation mixture of the water-soluble polyaniline and antibodies. Once the fractionation is successfully conducted, the performance of the biosensor with the purified conjugation mixture will be compared with non-fractionated preparations.

Impacts
Cattle persistently infected with bovine viral diarrhea virus (BVDV) are the major source of spread of this virus both within and between farms. Detecting and eliminating these animals is critical for the efficient control of this important virus. An inexpensive and rapid conductimetric biosensor platform for detecting BVDV has been developed and initially tested. Rapid and cost effective detection of cattle persistently infected with BVDV will significantly enhance BVDV control programs both national and globally. Additionally, the developed technology can potentially be adapted to many important pathogens such as foot and mouth disease (FMD).

Publications

  • Muhammad-Tahir Z., Alocilja E.C., Grooms D.L. 2005. Rapid detection of bovine viral diarrhea virus as surrogate of bioterrorism agents. IEEE Sensors Journal. 5(4):757-762.
  • Tahir, Z.M., Alocilja E.C., Grooms D.L. 2006. Polyaniline synthesis and its biosensor application. Biosensors and Bioelectronics, Selected Papers from the Eighth World Congress on Biosensors, Part I. 20(8):1690-1695.
  • Muhammad-Tahir Z., Alocilja E.C., Grooms D.L. 2006. Fabrication of an indium tin oxide-polyaniline biosensor. IEEE Sensors Journal. Submitted.
  • Muhammad-Tahir Z., Alocilja E.C., Grooms D.L. 2006. Performance analysis of an indium tin oxide-polyaniline biosensor for bovine viral diarrhea detection. Biosensors and Bioelectronics. Submitted.


Progress 01/01/05 to 12/31/05

Outputs
Development of a Conductometric Biosensor for Detection of BVDV - A virus biosensor was adapted from a previous conductometric biosensor used for bacterial detection. During the past year, testing of the modified biosensor has been conducted on different biological samples including serum, nasal swabs and ear notches collected from cattle known to be persistently infected with BVDV. Serum: Serum was collected from PI's and added undiluted to the biosensor. Using this method, the biosensor was unable to consistently detect virus from cattle persistently infected with BVDV. This may be related to a virus concentration issue or some type of interference related to serum matrix. Currently, we are studying methods to make serum a more useful sample in the biosensor including changing carriers and adding filtration systems. Nasal swabs: Nasal swabs were collected and placed in DMEM tissue culture media. After vortexing, the tissue culture media was used as the sample for the biosensor. Virus could not consistently be detected in nasal swabs. Nasal swabs typically have lower detectable levels of virus and sample cleanliness may interfere with the biosensor working correctly. Ear notches: Ear notches were placed in 0.1% PBS and allowed to set for 30 minutes, following vortexing, the PBS elute was used in the biosensor. Virus could consistently be detected in ear notch elute. Conclusion: Ear notch elute appears to be a good sample to use in the conductometric biosensor for detecting cattle persistently infected with BVDV.

Impacts
Rapid detection of BVDV by a conductometric biosensor has been demonstrated. Further development may make this technology useful for the rapid and economical detection of PI cattle as an aid in the control of BVDV.

Publications

  • Tahir, Z.M., Alocilja, E.C., and Grooms, DL. 2005. Polyaniline synthesis and its biosensor application. Biosens Bioelectron. 15;20(8):1690-1695.


Progress 01/01/04 to 12/31/04

Outputs
A key to controlling BVDV is identifying and eliminating carriers of virus, better known as cattle persistently infected (PI) with BVDV. PIs shed large amounts of virus and serve as the major source of virus transmission within and between farms. The development of a rapid and cost effective field based system to detect PIs would be beneficial for more practical implementation of BVDV control strategies. In this study, a conductometric biosensor previously developed for use in detecting foodborne pathogens was adapted to detect BVDV in cell culture media. The biosensor uses antibodies as the biological sensing element and polyaniline as the transducer and molecular switch. The principle of detection can be described briefly as follows: A liquid sample containing the antigen (Ag) is dropped on the sample application membrane. The sample containing the antigen flows to the conjugate membrane by capillary action and binds to the primary antibody (Ab) that is conjugated to the conductive polyaniline molecules (Pan). The bound Ag forms a soluble Pan-Ab-Ag complex that is transported by capillary flow to the electrical capture membrane that is coated with the secondary antibody and with silver electrodes fabricated on both sides. The Pan-Ab-Ag binds to the secondary antibody, forming a Pan-Ab-Ag-Ab sandwich and which creates a molecular bridge between the two electrodes. This molecular bridge reduces the resistance between the electrodes and resistance measurement is taken using a multimeter. In phase I of the study the biosensor was constructed and initially tested using BVDV grown in cell culture and diluted to different concentrations. Concentrations of the various capture antibodies and polyaniline was optimized and the detection limit of the sensor determined. The biosensor was capable of detecting both a type 1 and type 2 BVDV viruses grown in cell culture. The minimum virus concentration in cell culture that was detectible using the current architecture was 10(-3) cell culture infective doses per milliliter (CCID/ml). When applied to BVDV spiked serum, the biosensor was capable of detecting virus at the same concentration of 10 (-3) CCID/ml. The amount of time between sample application in the biosensor to stabilization of the electrical current averaged 2 minutes. Results of this preliminary study provide proof of concept that a rapid field based biosensor can be developed that is capable of detecting BVDV in both cell culture media and blood at a concentration that is biologically relevant for identifying PI's. This biosensor architecture has the capability of being miniaturized and automated to facilitate large scale field-testing if necessary. With mass production, the cost of the biosensor has the capability of being very low. Extension of this biosensor architecture to other disease agents is of great interest including agents of bioterrorism and foreign animal diseases.

Impacts
The development of rapid and efficient detection methods and strategies for BVDV wil allow for timely elimination of cattle persistently infected with BVDV, thus elimination virus reservoirs and stopping virus transmission. These strategies may have added value in feedlot enterprices where the presence of cattle persistenly infected with BVDV was shown to impact performance

Publications

  • Tahir ZM, Alocilja EC, Grooms DL. 2005. Polyaniline Synthesis And Its Biosensor Application. Biosens Bioelectron. 20(8):1690-5.
  • Grooms DL, Muhamammad-Tahir Z, Alocilja EC. 2004 Rapid Detection Of Bovine Viral Diarrhea Virus Using A Conductometric Biosensor. Proceedings of 37th Annual Meeting of the American Association of Bovine Practitioners, Ft. Worth TX, Sept 22-24, p 172.


Progress 01/01/03 to 12/31/03

Outputs
Detection and elimination of cattle persistently infected (PI) with BVDV is a key method of control for this disease. In this project, two approaches were taken to meet the objectives of the project. The first approach was to develop new diagnostic strategies and tests necessary to identify cattle infected with BVDV. By doing this, cattle persistently infected with BVDV can be identified and eliminated as a source of viral transmission. The second approach was to study important avenues of virus transmission and how to prevent them in a economical and strategic manner. In support of the first objective, three different testing stratgies were studied. Each has its advantages in diagnosing BVDV at both the individual and herd level. Skin biopsy of neonatal calves was shown to be an accurate test for early detection of cattle persisitently infected with BVDV. Use of serology on sentinal calves was shown to be an efficient way of screening herds for evidence of BVDV infection at the herd level. In support of the second objective, the importance of cattle persitently infected with BVDV in a feedlot setting was demonstrated. Feedlot calves constantly exposed to BVDV persistently infected cattle were more likely to get sick and require treatment when compared to calves unexposed to BVDV. Growth performance was affected early, but no diference in overall performance was seen at the end of the study.

Impacts
The development of rapid and efficient detection methods and strategies for BVDV wil allow for timely elimination of cattle persistently infected with BVDV, thus elimination virus reservoirs and stopping virus transmission. These strategies may have added value in feedlot enterprices where the presence of cattle persistenly infected with BVDV was shown to impact performance

Publications

  • Grooms, D.L., Keilan, E. 2002. Screening of neonatal calves for bovine viral diarrhea virus by immunohistochemistry on skin samples. Clin. Diagn. Lab. Immun. 9(4):898-900.
  • Pillars RA, Grooms DL. Serological evaluation of five unvaccinated heifers for detecting herds persistently infected with bovine viral diarrhea virus, Am J Vet Res, 2002;63(4):499-5.
  • Grooms DL, Brock KV, Norby B. Performance Of Feedlot Cattle Exposed To Animals Persistently Infected With Bovine Viral Diarrhea Virus. Proceedings of the 83th Annual Meeting of The Conference of Research Workers in Animal Diseases, St. Louis, MO, November 11, 2002. Abstract # 186.
  • Grooms DL, Kaiser L, Walz PH, Baker JC. Study of cattle persistently infected with bovine viral diarrhea virus that lack detectable virus in their serum. J Am Vet Res, 2001;219(5):629-631


Progress 01/01/02 to 12/31/02

Outputs
Detection and elimination of cattle persistently infected (PI) with BVDV is a key method of control for this disease. Use of immunohistochemistry (IHC) for detection of BVDV antigen in skin samples has shown promise as a tool for detecting PI cattle. One strategic advantage of IHC would be detection of neonatal calves that are PI with BVDV. To determine if IHC in neonatal calves is comparable to traditional methods of detecting persistent BVDV infections, we compared IPMA on buffy coats to immunohistochemistry on skin biopsies in 2-week-old Holstein calves as part of a large dairy herd-screening program. Three hundred thirty two calves were tested from three different dairy farms. The sensitivity of IHC relative to IPMA for detecting PI calves was 100% while the specificity was 99.7%. The positive predictive value of IHC in neonatal calves was 85.7% while the negative predictive value was 100%. The kappa value of IHC and IPMA on buffy coats was 0.92.

Impacts
Immunohistochemistry for the detection of neonatal calves persistently infected with BVDV is accurate and can be a useful tool for the control and prevention of BVDV in cattle operations.

Publications

  • Grooms, D.L., Keilan, E. 2002. Screening of neonatal calves for bovine viral diarrhea virus by immunohistochemistry on skin samples. Clin. Diagn. Lab. Immun. 9(4):898-900.


Progress 01/01/01 to 12/31/01

Outputs
Cattle persistently infected (PI) with bovine viral diarrhea virus(BVDV) are the major reservoir of infection within and between herds. The key to eradicating BVDV is the identification and removal of all PI cattle. The objective of this study was to determine if the evaluation of BVDV antibody titers in 5 randomly selected unvaccinated heifers (sentinel heifers) was an accurate way to predict if a herd was infected with the virus. Blood samples were collected from all cattle in fourteen Michigan dairy herds. To identify cattle infected with BVDV, virus isolation was performed on all samples using the immunoperoxidase monolayer assay (IPMA). Serum virus neutralizing antibody titers to both type I and type II BVDV were determined on 5 randomly selected unvaccinated heifers 6-12 months of age. A positive serological evaluation was defined as a herd with at least 3 of 5 heifers with BVDV titers greater than 1:128 (SN positive) to either type I or type II BVDV. Conversely, a negative serological evaluation was defined as a herd with at least 3 of 5 heifers with BVDV titers less than 1:64 (SN negative). The genotype of all isolated viruses was determined by reverse transcriptase PCR.Four herds were classified as infected with BVDV based on serological evaluation of 5 sentinel heifers. Virus was isolated from at least 1 animal in each of these herds. BVDV was isolated from 2 herds that were classified as not infected with BVDV by serological evaluation of 5 sentinel heifers. These data are summarized in the table below. Based on this data, a sensitivity of 66% and a specificity of 100% was obtained when using BVDV titers in 5 sentinel heifers for predicting the presence of BVDV in a herd. In the BVDV-positive herds, the genotype of the virus isolated from the herd corresponded to the type of antibody titers that were highest in the sentinel heifers from that same herd. The two herds in which BVDV was isolated in spite of a negative serological evaluation were unique cases. In one herd, a single PI was identified that was only 3 months of age and had not had contact with the sentinel group. In the other herd, an age cohort of PI calves (who did not have BVDV titers) was identified and 3 of those were randomly selected for serological analysis. To avoid this problem, IPMA can be run in parallel with the serum neutralization test in the sentinel heifers to identify PI cattle in this group. Using serological analysis of sentinel heifers 6-12 months of age is a quick, accurate, and inexpensive method for identifying herds infected with BVDV prior to whole herd screening. The sensitivity of this method can be further improved by running IPMA in parallel with virus neutralization to avoid possible false negatives from the inclusion of PI calves in the sentinel group. Moreover, the genotype of the virus infecting the herd can also be determined using this method and may be valuable in developing vaccination protocols.

Impacts
Identification of cattle persistently infected with BVDV is an essential management strategy for the control and prevention of this virus. Serological analysis of sentinel heifers 6-12 months of age was shown to be a quick, accurate, and inexpensive method for identifying herds infected with BVDV prior to whole herd screening. In addition, this screening method was shown to be a useful way to make prliminary identification of the virus genotype that may be circulating on a farm.

Publications

  • Grooms DL, Kaiser L, Walz PH, Baker JC. Cattle persistently infected with BVDV with no detectable virus in their serum: Are they important? J Am Vet Res, 2001;219(5):629-631.
  • Pillars R, Grooms D. Serological evaluation of five unvaccinated heifers for detecting herds persistently infected with bovine viral diarrhea virus. Proceedings of The 34th Annual Convention of The American Association of Bovine Practitioners, Vancouver, British ColumbiaSept 13-15, 2001, p 134.


Progress 01/01/00 to 12/31/00

Outputs
The goal of this project is to determine the potential clinical use of passive immunization of dairy cattle with purified anti-coliform antibodies for the treatment and prevention of coliform mastitis and other endotoxin-induced shock diseases. We have successfully achieved our goals of this project. We hyperimmunized steers with a core antigen anti-J5 E. coli bacterin, and determined by ELISA the presence of high concentrations of anti-J5 antibodies in serum. By salt fractionation, and a two-step affinity chromatography purification, we were able to isolate and purify in mg quantities anti-J5 IgG2 antibodoes. This isotype has been determined in vitro to enhance neutrophil phagocytosis because of strong opsonization characteristics. We plan to continue this research by testing the efficacy of these purified anti-J5 antibodies to prevent an experimental E. coli mastitis by passively immunizing dairy cattle directly into the mammary gland.

Impacts
(N/A)

Publications

  • No publications reported this period


Progress 01/01/99 to 12/31/99

Outputs
Cattle persistently infected with BVDV typically have high levels of virus in their serum that is easily detectable by virus isolation, IPMA. However, it is evident that some PI cows may have undetectable levels of BVDV in serum while virus can still be isolated from buffy coats and nasal swabs. In an effort to determine how commonly this may occur, cows 2 years of age and older were screened for BVDV by IPMA using both serum and buffy coats. To date, a total of 1,952 cows have been tested from 11 dairy farms and 2 beef farms. A total of 5, .26 percent PI animals have been detected. In all 5 PI animal, both serum and buffy coat samples were positive for BVDV by IPMA. Based on this information, the prevalence of PI cattle that are BVDV negative by IPMA testing of serum is less than 0.04 percent.

Impacts
(N/A)

Publications

  • No publications reported this period