1. What Is New With BVDV Dan Grooms DVM, Ph.D Michigan State University
College of Veterinary Medicine
Department of Large Animal Clinical Sciences

2. Topics To Be Covered Information From NAHMS Dairy 2007 BVDV and Deer
Vaccines and Fetal Protection
Programmed Approach to BVDV Control

3. Only 31 % of producers were “fairly” knowledgeable = opportunity to educate

6. Summary BVDV knowledge - Room for improvement
High percentage of farms vaccinate
Higher prevalence of BVDV in larger herds

7. Dave Richey: Detroit Free Press
BVDV and Deer
Dave Richey: Detroit Free Press

8. Other states: 2-41% serological prevalence
BVDV and Deer
Serological evidence of BVDV infection in white tailed deer 0%
10%
Other states: 2-41% serological prevalence

9. BVDV and Deer IMPORTANCE? South Dakota
BVDV infected deer with all the characteristics of PI’s
Experimental Creation of PI Fawns
Intranasal with “deer” strain
Exposure to PI cattle
Survivability appears low
IMPORTANCE?

10. Wildlife as a Source of Infectious Diseases
White tailed deer - cattle
Bovine TB
Johne’s disease
Leptospirosis
Salmonella
Litchfield, Infantis, and Enteritidis (Nebraska)
Enzootic hemorrhagic disease (EHD)
IBR
BVDV

11. Need to be more aware of and manage wildlife – production animal interface

12. Effectiveness of BVDV Vaccines in Preventing Fetal Infection

14. Fetal Protection Against BVDV
Study
Vaccine
Virus
Challenge
Vaccinates*
Controls*
Percent Protected
Mclurkin et al 1975
Killed 1
CP 1
12/14
0/5
86%
Harkness et al 1985
Killed
9 CP 1
7/11
0/11
64%
Meyling et al 1987
3 NCP 1
2/8
25%
Cortese et al 1998
MLV 1
NCP 1
10/12
0/10
83%
Brock et al 2001
NCP 2
11/19
0/6
58%
Zimmer et al 2002
Killed CP and NCP
7/9
0/15
78%
5/15
33%
Patel et al 2002
Killed CP1
9/11
0/7
81%
Dean et al 2003
25/27
0/13
92%
Fairbanks et al 2004
MLV 1/2
18/18
100%
18/19
0/8
95%
Grooms 2004
Killed 1/2
NCP 1/2
11/15
0/14
73%
Experimental Infections.
What About Natural Exposure via PI’s?
Again, several studies have attempted to answer this question and peer reviewed studies using commercial vaccines are outlined above In general, it is apparent that fetal protection is not 100%. To date, only one study has has a used a type 2 challenge following a type 1 vaccine (Brock et al) and protection in this study was ~58%.

15. Study Objective
Evaluate the ability of an inactivated BVDV vaccine to provide fetal protection in the face of continuous BVDV challenge in the form of cattle persistently infected with BVDV
Our objective of this study was to evaluate the ability of an inactivated BVDV vaccine to provide fetal protection in the face of continuous BVDV challenge in the form of cattle persistently infected with BVDV, thus replicating what is more likely to occur in a real world situation.

16. Methods 60 Cross Bred Heifers Vaccinated 21 days apart (days 0 and 21)
BVD Virus and Type Seronegative
Randomly assigned to one of two groups
Vaccinated 21 days apart (days 0 and 21)
TO1 = Saline
TO2 = CattleMaster® GOLD™ FP™ 5-L5
Inactivated type1/2 BVDV antigen
Given prostaglandin on days 24 and 35
Bred by AI on days 35-44
From pregnant heifers, 15 randomly selected from from TO1 and TO2
To do this, 60 cross bred heifers were sourced. All heifers were free of BVD virus and neutralizing antibodies to both type 1 and 2 BVDV.
The heifers were randomly allotted to two groups, a control group designated as T01 and a vaccinated group, designated as T02. At day 0 and 21 of the study, the control group was injected with saline while the vaccinated group was immunized with a commercially available 4-way virus vaccine containing inactivated type 1 and 2 BVDV.
The heifers were then estrous synchronized using two injections of Lutalyse 11 days apart.
Starting on day 35 after the second Lutalyse shot and continuing until day 44, all heifers were then bred artificially.
Heifers were confirmed pregnant at day 40 at which point 15 controls and 15 vaccinated heifers were randomly selected to continue in the study.

17. Methods Vaccination Breeding PI Introduced Fetal Harvest
Day of Gestation ~1 ~50 ~150
100 day exposure
To review the time line….

18. Laboratory Methods BVDV Type 1 and 2 serum virus neutralization
Dams (0, 21, 35, 63, 80, 90, 120, 150, and 190)
Fetus (Day 190)
BVDV virus isolation
Dams - WBC’s (Days 90, 97, 99 and 101)
PI’s – Nasal swabs (Days 90, 120, and 150)
Fetal tissues - Spleen, Liver, Lung, Brain (Day 190)
BVDV ELISA
Fetal Skin (Day 190)
Genotyping
Nested PCR
Laboratory methods that were used included the following. Type 1 and 2 BVDV serum virus neutralization was performed on the dams at days 0, 21, 35, 63, 80, 90, 120, 150, and 190 and the harvested fetuses.
Virus isolation was performed on WBC’s from dams at days 90, 97, 99 and 101 which corresponded to days 0, 7, 9 and 11 post PI introduction.
Virus isolation and titration was performed on nasal swabs taken from PI’s on days 90, 120, and 150.
At fetal harvest, virus isolation was attempted from fetal spleen, liver lung and brain and an antigen capture ELISA was performed on fetal skin
Finally, any virus that was isolated was genotyped as type one 1 or 2 using a nested PCR

19. Results

20. PI Characterization Nasal Secretions BVDV Titer (log10 CCID50)
Day of Study
PI #
Genotype 90
120
150
913
2 y Holstein Heifer 1b
4.1
1.7
4.5
405L
3 y Hereford Cow 2
4.3
163
1.9
2.7
3.5
P17
1 y Crossbred Steer
3.1 NA
First, I would like to describe the PI’s used in this study. First a note about these animals. Al were derived acquired from farms in the Midwest after being found on routine virus screening. So these animals closely represent virus that are actively circulating in the field at the time the study was conducted and 163 were both recently calved Holstein heifers from the same farm and their persistent BVDV was genotype L was a 3 year old Hereford cow from a seed stock operation and P17 was a yearling steer acquired from a feedlot which at the time was screening incoming cattle. Both of these animals were BVDV genotype 2. During the study tvirus titers in nasal secretions varied, but was always detectable. Also, P17 became ill 15 days after being commingled with the heifers and was humanely euthanized 17 days later.
*All PI’s sourced directly from farms

21. Clinical Findings All cows remained clinically healthy
1 control (T01) heifer was diagnosed day 171 (81 days post challenge or day 130 of gestation) - no fetus recovered
All other fetuses remained viable throughout study
One PI was euthanized 32 days after introduction to heifers (P17 – Type 2 steer)
One vaccinated heifer (T02) - Twins

22. BVDV Virus Neutralization
This chart depicts type 1 and 2 BVDV serum neutralization titers. Please note that what is being shown is the log to the base 2 titers. Some important notes. First, all animals were negative for BVDV antibodies prior to immunization. When the PI’s were introduced, the vaccinated heifers had significant titers to both type 1 and type 2 BVDV while the controls were still negative. Within 30 days of PI introduction, both the control and vaccinated animals had a significant increase in both type 1 and 2 titers, indicating virus exposure had occurred, and these increased titers were maintained to the conclusion of the study
1st Immunization
2nd Immunization
PI’s
Introduced
Day 80 Gestation
Day 150
Gestation

23. Virus Isolation - Dams Virus isolation from dam WBC’s
Day 0, 7, 9, 11 after PI introduction
8/15 control heifers (genotype 1 and 2)
3/15 vaccinated heifers (genotype 2 only)
After introduction of PI’s, virus was isolated from Dam buffy coats from 8/15 control heifers and 3 of 15 vaccinated heifers, which was significantly different. It is likely that if we had increased the frequency of our sampling schedule, the number of heifers which were positive would have increased. However, since the primary outcome we were interested in was fetal infection, more frequent sampling was felt to be unnecessary.
*Significant reduction in BVDV viremia in vaccinated heifers (P<0.05) based on sampling protocol

24. Virus Isolation - Fetus
Virus isolation from fetal tissues
14/14 controls
Genotype /14 (57%)
Genotype 2 – 11/14 (79%)
4/15 vaccinates
Genotype 1 - 4/4 (100%)
Genotype 2 - 2/4 (50%)
Skin ELISA
*Significant reduction in fetal BVDV infection in vaccinated heifers (P<0.05)
Finally, at fetal harvest, BVDV was isolated from fetuses derived from all control heifers and 4 of the 15 vaccinated heifers.. The same results were found with the antigen capture ELISA using fetal skin. Both genotypes of virus was isolated from fetus derived from the control and vaccinated heifers. Interestingly, in 6 of the control and 2 of the vaccinated heifers, both type 1 and 2 virus was isolated suggesting a dual infection
>Multiple viruses found in some fetuses

25. Conclusion
Vaccination significantly reduced fetal infection with BVDV in a continual exposure model
Protection WAS NOT 100% emphasizing the need for ID and removal of PI’s and biosecurity in addition to vaccination
Fetal infection with multiple viruses can occur = Risk of virus rearrangement
Our conclusions from this study –
Vaccination with a commercially available multivalent vaccine containing an inactivated BVDV fraction can significantly reduce fetal infection with BVDV
However, protection is not complete, emphasizing the need for biosecurity and PI detection as in conjunction with a sound vaccination program.

26. Sahiwal

27. A Programmed Approach To Controlling BVDV in Dairy Operations
Dan Grooms DVM, Ph.D
Michigan State University
College of Veterinary Medicine
Department of Large Animal Clinical Sciences

28. BVDV Control Program Biosecurity Vaccination
“Seek and Destroy” PI Cattle

29. Ohio Dairy March 95-May 96

30. Sources of BVDV Exposure
PI’s or Transient Infections
Replacements
Exhibition
Fence line
Shared pastures
Semen
Embryo’s/Recips
Other Species
Sheep/goats
Camelids
Cervidae
Insects
Inanimate Fomites
Vehicles
Equipment
People

31. BVDV Control Program Biosecurity “Seek and Destroy” PI Cattle
Vaccination

32. MOST WANTED
Known carrier of a virulent virus…Persistently infected with BVDV
CONSIDERED ARMED AND EXTREMELY DANGEROUS
IF YOU HAVE ANY INFORMATION CONCERNING THIS PERSON, PLEASE CONTACT YOUR VETERINARIAN
REWARD BJ

33. X Detection of PI’s Tests To Detect PI’s Virus Isolation IPMA Skin
IHC/FA/ELISA
PCR
Individual/Pooled
Blood ELISA X
Serology

35. Is BVDV A Problem?

36. BVDV is Suspected Is BVDV a Problem? BVDV is not Suspected
Poor reproductive performance despite good nutrition and fertility
High calf morbidity/mortality despite good sanitation and nutrition
Positive screening test
Laboratory confirmation of BVDV infection (virus detection or serology)
Is BVDV a Problem?
BVDV is not Suspected
Good reproductive performance
Good calf health
Screening tests have been negative
No laboratory evidence of BVDV infection (virus detection or serology)

37. BVDV Herd Screening

38. Continue Herd Screening Individual Testing
Herd Screening Tests
Necropsy
Serology on
Sentinels
Bulk Tank PCR
Pooled PCR
-Unvaccinated calves 6-12 m
-Target cohorts
-Both Type 1 and 2
-Looks only at lactating cows
-300 cows pools
-Groups of
-Cost effectiveness lost when
prevalence of PI’s is >10%
Negative
Positive
Continue Herd Screening
Individual Testing

39. Strategies For Testing Individual Cattle For BVD PI

40. Dairy Herds Multiple strategies for testing individual animals
Depending on strategy, testing will occur over a period of time

41. Potential Strategies Test everything at one time
Test new additions (expanding herd)
Test new born calves
Test replacements
Test pools followed by individuals

42. Test all Calves and Adults w/o offspring
Pregnant cows/heifers
may be carrying PI fetuses.
Must test newborn calves ASAP.
Test all Calves and Adults w/o offspring
Assumption: Calves most likely to be PI’s
Calves serve as sentinels for dams
VI/IPMA
Skin
IHC or ELISA
Pooled
PCR
Retain in Herd
Positive
If Calf
Positive
Negative
Individual
Test
Record Dam as Negative
If Calf
Options:
Isolate and Retest
Eliminate
Test Dams
Positive
Negative

45. BVDV Control Program Biosecurity Control Virus Exposure Vaccination
“Seek and Destroy” PI Cattle
Vaccination

46. BVDV-Reproduction- Vaccines
Many case/field studies suggest “vaccine failure/vaccine breaks” w/respect to reproductive disease caused by BVDV.
Experimental studies also show that BVDV vaccines are not 100% efficacious in preventing reproductive disease.

47. Vaccination is a Tool Not Silver Bullet

48. My Thoughts on BVDV Vaccines
Believe that MLV vaccines are more effective than killed vaccines
Research and biology supports this opinion
Killed vaccines are useful and certainly have a role in BVDV control

49. My Thoughts on BVDV Vaccines
Not a fan of giving MLV BVDV/IBR vaccines to pregnant cows
Two viruses known to cause fetal wastage
Ideal timing is prior to breeding
Maybe a better time is late in pregnancy
Dry off
Prebreeding
Low Stress
Improved colostral antibodies

50. My Thoughts on BVDV Vaccines
Conceptually, “rotating” vaccines makes sense, but no science to support benefits
Idea is to broaden antigenic exposure
Bovishield Gold = NADL (1) and ( )
Vista = Singer (1) and 125c (2)
Titanium = C24V (1) and 296 (2)

51. Summary Important and Prevalent virus in the dairy industry
Many clinical manifestations
Control =
Vaccination
Biosecurity
Seek and destroy PI’s

52. Case Study 1000 head rapidly expanding dairy
Raises no replacements
Consulted because of high incidence of abortions – 10%
Vaccine program
Erratic
Killed type 1 vaccine

53. Case Study Step 1 – What is causing abortion? Submitted fetuses
Bulk tank milk PCR for BVDV
Results
6 fetuses submitted – 3 positive for type 2 BVDV. No other conclusive findings.
Bulk tank positive for BVDV

54. Case Study Step 2 – Find PI’s
Elected to screen entire adult herd for BVDV
1 PI found in adult herd
Started screening calves at birth
~0.5% incidence over next 12 months

55. Case Study Step 3 - Management
Screen all incoming heifers/cows and newborn calves
Incoming = 0.2% incidence
Calves = 0.5% incidence
Initially, vaccinated entire herd with type 1/2 killed vaccine
Switched to MLV type1/2 vaccine prebreeding and at dryoff

56. Case Study
Results
Abortion incidence has dropped to ~2%

58. Come on Dr. Grooms, get off the ivory tower kick
Come on Dr. Grooms, get off the ivory tower kick..give us some good take home stuff…How can we really tell if we’ve got BVDV?

59. Top 10 Reasons You Know You Have BVDV
When your carcass compost pile doubles as a sled riding hill for the kids!!

60. Top 10 Reasons You Know You Have BVDV
When your carcass compost pile doubles as a sled riding hill for the kids!!
When every animal is walking around with strange looking v-shaped notch in their ear.

61. Top 10 Reasons You Know You Have BVDV
When your carcass compost pile doubles as a sled riding hill for the kids!!
When every animal is walking around with strange looking v-shaped notch in their ear.
When your drug rep say “It can’t be BVDV, you used our vaccine”.

62. Top 10 Reasons You Know You Have BVDV
When your carcass compost pile doubles as a sled riding hill for the kids!!
When every animal is walking around with strange looking v-shaped notch in their ear.
When your drug rep say “It can’t be BVDV, you used my vaccine”.
When you walk into the calf barn and every calf looks like Michael Jackson!!!!.

63. Top 10 Reasons You Know You Have BVDV
When your carcass compost pile doubles as a sled riding hill for the kids!!
When every animal is walking around with strange looking v-shaped notch in their ear.
When your drug rep say “It can’t be BVDV, you used my vaccine”.
When you walk into the calf barn and every calf looks like Michael Jackson!!!!.
When you think BVD stands for “Bad Veterinary Disease”
Dr. Grooms DVM BVD

64. Top 10 Reasons You Know You Have BVDV
When your pregnancy rate is approaching the approval rating of George W.

65. Top 10 Reasons You Know You Have BVDV
When your pregnancy rate is approaching the approval rating of Dick Cheney.
When your nutritionist blames poor health on your previous nutritionist who blamed it on his/her predecessor who blamed it on

66. Top 10 Reasons You Know You Have BVDV
When your pregnancy rate is approaching the approval rating of Dick Cheney.
When your nutritionist blames poor health on your previous nutritionist who blamed it on his/her predecessor who blamed it on
When you have cattle on your farm named “Runt”, “Pipsqueak”, “Shorty”, “Wobbles”,“Tiny”, “Clutzo” and “Nubby”.
Will I ever grow up!!

67. Top 10 Reasons You Know You Have BVDV
When your pregnancy rate is approaching the approval rating of Dick Cheney.
When your nutritionist blames poor health on your previous nutritionist who blamed it on his/her predecessor who blamed it on
When you have cattle on your farm named “Runt”, “Pipsqueak”, “Shorty”, “Wobbles”,“Tiny”, “Clutzo” and “Nubby”.
When you’ve just won a million dollar law suit against the electric company because of “stray voltage”, but herd health still stinks.

68. Top 10 Reasons You Know You Have BVDV
When your pregnancy rate is approaching the approval rating of Dick Cheney.
When your nutritionist blames poor health on your previous nutritionist who blamed it on his/her predecessor who blamed it on
When you have cattle on your farm named “Runt”, “Pipsqueak”, “Shorty”, “Wobbles”,“Tiny”, “Clutzo” and “Nubby”.
When you’ve just won a million dollar law suit against the electric company because of “stray voltage”, but herd health still stinks.
You’ve lost everything but your

69. Michigan State University College of Veterinary Medicine
Dan Grooms DVM PhD
Michigan State University
College of Veterinary Medicine

71. Just call me typhoid Bubba!