Economic and Production Effects of BVD
R.L. Larson, DVM, PhD, ACT

Introduction
Management and control of bovine viral diarrhea virus (BVDV) infection in cattle herds must consider two methods of transmission. The first is transmission of the virus from one animal to another (horizontal transmission), and the second is the transmission of the virus from an infected dam to her fetus (vertical transmission). Horizontal transmission of BVDV to calves or adult cattle results in a transient infection that is usually mild, but can result in severe disease in susceptible cattle exposed to a virulent strain of the virus. In addition, horizontal infection can lead to vertical transmission of BVDV, in that horizontal infection is the primary method by which a pregnant dam becomes infected with the virus and subsequently infects her fetus. 
The primary reservoir for and source of BVDV is cattle persistently infected (PI) with BVDV; with transiently infected cattle considered a less important source. Persistently infected animals are a much more efficient transmitter of BVDV than transiently infected animals because they secrete higher concentrations of virus for a longer period of time. Transiently infected animals experience a short period (7 to 10 days) where virus is shed in body secretions and excretions. In contrast, PI animals usually have a very high and persistent amount of virus circulating in their blood and other fluids, and BVDV is shed continually from virtually all secretions and excretions including nasal discharge, saliva, semen, urine, tears, milk, and to a lesser extent, feces. Horizontal transmission of BVDV to susceptible cattle has been shown to occur after only one hour direct contact with a single PI animal. Over-the-fence contact with a PI animal from a neighboring herd can also introduce BVDV into a susceptible herd. Horizontal transmission of the virus from either persistently or transiently BVDV-infected animals to susceptible cattle in direct contact may be via inhalation or ingestion of virus-containing body fluids. In addition, air transmission over short distances seems likely. 

Reproductive Effects of BVDV Infection
Even mild BVDV infections of breeding females can cause conception failure and may cause abortion or vertical fetal infection in pregnant, seronegative females. The immune status of the dam, the stage of gestation, and the characteristics of the virus itself are important factors in determining the result of vertical infection. Transplacental infection occurs with high efficiency during the pregnancy of susceptible dams. Fetal infection can lead to early embryonic death, abortion, birth defects, stunting, the birth of PI calves, or the birth of normal calves. Persistently infected cattle are the result of fetal exposure to the noncytopathic biotype of BVDV prior to the development of a competent immune system at about 125 days of gestation 
In addition to BVDV causing conception failure and abortion, reproductive efficiency can be decreased due to fatal birth defects following fetal infection between 100 and 150 days of gestation. The lesions associated with fetal infection with BVDV include brain malformations, spinal cord defects, cataracts and other eye abnormalities, sparse haircoats, a short lower jaw, growth retardation and lung immaturity.

Exposure of Beef Herds to Persistently Infected (PI) Cattle
Suckling calves are commonly in contact with the breeding herd during early gestation, prior to the time the bovine fetus develops a competent immune system. As a result, PI suckling calves are considered to be the primary source of BVDV infection in breeding herds. The result of an introduction of a PI animal into a beef herd depends on the timing of the introduction relative to the breeding season and the resulting immunologic status of the herd during early gestation.
Even in the absence of vaccination, the number of PI animals and the amount of BVDV infection in a herd seems to be self-limiting. A likely scenario for a BVDV-exposed herd is to experience an initial peak of disease and then in subsequent months and years, to experience low-level chronic reproductive losses. If a PI animal enters the herd either by birth or by purchase near the start of the breeding season, a high percentage of the herd may not be immunologically protected to the degree necessary to prevent infection, conception failure, abortion, or fetal infection. Once the PI animal is in contact with the breeding herd for a long enough period of time, the majority of the herd should become infected and seroconvert. Seropositive animals are less likely to have conception failures, abortions, or infected fetuses compared to seronegative animals. If no intervention is applied to the herd, the following year, the number of susceptible females should be greatly decreased and the number of abortions and infected fetuses should decrease. 
Estimates of the prevalence of PI animals in the general cattle population has been reported to range between 0.13% and 2.0%. And about 4% of U.S. beef herds are expected to have at least one PI animal (95% confidence interval 1-11%). Persistent infection has a clustered distribution, which means a few herds may contain several persistently infected cattle but most herds contain only normal cattle. Clustering of multiple PI animals in a herd is primarily due to exposure of numerous susceptible dams to a PI or transiently infected source of noncytopathic BVDV prior to day 125 of gestation. Although a high percentage of PI calves die at or near birth or at least by weaning, in some situations 17% to 50% of PI calves may survive so that they reach the age to enter the breeding pool or to enter a feedlot. Persistently infected females of breeding age not only are a source of horizontal transfer of BVDV, but will always produce a PI calf themselves.

Effects of BVDV Infection in Feeder Cattle
Infection with BVDV has been associated with respiratory disease outbreaks in feedlot situations. Persistently infected cattle are a primary source of BVDV transmission to in-contact susceptible cattle during marketing, trucking, and while in feeding pens and pastures and have been shown to have an impact on health performance of susceptible penmates and cattle in adjacent pens. Ongoing work is investigating the amount of disease in feedlot cattle that can be attributed to BVDV (both transiently and persistently infected cattle).

Economic Considerations for Diagnostic Testing
The cost of the presence of at least one PI animal in a beef herd has been reported to range from $14.85 per cow per year to $24.84 per cow per year. However, the cost of initiating a BVD PI screening protocol on a farm or ranch is significant. The likelihood of finding at least one PI animal in the herd, the negative production effects when PI animals are present, the cost of inputs and the value of animals sold (price cycle) all impact the economic value of annual screening for PI animals in cow-calf herds.
In order to quantify the economic benefit for removing BVDV persistently infected (PI) animals, a 10-year farm profitability simulation model was used to compare production scenarios with and without PI calves present. Differences in profitability between the scenarios estimates the value of diagnostic testing given expected prevalence in the herd. If the true prevalence of herds with at least one PI animal is 1% (low end of the 95% confidence interval for randomly selected herds), $0.60 is available for costs associated with each animal tested. If, however, the true prevalence of herds with at least one PI animal is 30% (high end of the 95% confidence interval for pre-screened herds), $18.40 is available for each animal tested. 
Because of the low prevalence of herds with at least one PI animal, not all producers are economically justified to initiate diagnostic screening protocols for PI BVDV cattle. However, if ranch history raises a suspicion of BVDV PI cattle being present in the herd, a protocol to screen the herd can be defended based on its likelihood to improve economic return.

Diagnostic Testing Strategies to Identify PI Calves
Because the persistently infected animal is an important reservoir and transmitter of BVDV, control programs must first identify and remove these animals from the breeding herd. Because of vertical transmission of the virus from viremic dams to their fetuses, PI animals should be removed prior to the start of the breeding season in beef herds with a controlled breeding season. In order to find and remove PI cattle prior to the start of the breeding season, all calves, all replacement heifers, all bulls, and all non-pregnant dams without calves due to not becoming pregnant, aborting, or calf death must be tested for PI status. Any female that is still pregnant at the time the herd is tested should be isolated from the breeding herd and kept isolated until her calf is tested and found to be negative. If a herd has had confirmed PI calves, or if the history strongly suggests the presence of PI calves, one assumes that the risk of PI cattle being present and a positive test may not need to be confirmed with a second test. In contrast, if there is no prior evidence of PI cattle being present in the herd, one should confirm all positive tests with a second confirmatory test. Once a calf is identified as PI, it should be euthanized and the dam should be tested. Most dams of PI calves are not PI themselves and if confirmed as non-PI, it can re-enter the breeding herd because naturally acquired immunity is considered to prevent any future fetal infections. If the dam is identified as a PI, it should be sold to slaughter immediately. 

Monitoring Herds for BVDV PI Risk 
The cost of initiating a BVDV PI whole-herd screening protocol on a farm or ranch is significant. In order to decide whether or not whole-herd screening is economically justified, several strategies can be employed to monitor herds for their risk of having PI cattle present.
Use of production records and laboratory evaluation of moribund and dead calves 
The minimal level of surveillance for every herd should include monitoring of herd fertility (early breeding season pregnancy proportion, pregnancy per insemination proportion, and total pregnancy proportion), neonatal calf morbidity and mortality proportions, and weaning proportions. Because of the negative effect of the presence of PI calves in a breeding herd on measures of reproductive efficiency, the presence of physical abnormalities at birth, and calf survivability to weaning, an unacceptable level of these symptoms increases the risk that BVDV is a problem in the herd and increases the likelihood that whole-herd screening for PI cattle will be economically rewarding. Although, in many situations, pregnancy rate drops significantly at the time of conception of the oldest PI animal, and about six months later, calf mortality increases; using production records alone lacks sensitivity for identifying herds with PI animals because the clinical indications of PI presence may be less noticeable in some outbreaks. The clinical signs and time sequence following introduction of BVDV infection into different herds varies considerably due to the different proportions of seronegative animals in the critical period of pregnancy and different virulence among BVDV strains.
In addition to monitoring production records, minimal surveillance should include the necropsy examination of as many aborted fetuses, stillborn calves, and calves that die pre-weaning as possible. In addition, sick calves from clusters of pneumonia, neonatal scours, or septicemia outbreaks that are not easily explained by sanitation or other problems should also be tested for BVDV exposure and PI status. If most pre-weaning deaths are examined for BVDV and found to be negative, it is not likely that PI animals are present in the herd. The presence of PI animals in the herd will be established by a single confirmed PI test. The presence of PI animals is not ruled out and may be considered likely if few sick or dead cattle are tested.
The advantage of utilizing production measures and necropsies to determine if herds have either a high or low risk for the presence of BVDV PI animals is that minimal expense is involved and these management tactics are inclusive for the monitoring of other disease and production problems. This level of monitoring is probably appropriate in herds with no evidence for the presence of PI animals and that are at low risk of PI introduction. The disadvantage is that at least one PI animal is allowed into the herd before production losses are identified, and production losses will continue for at least one year after intervention is initiated. 
Use of pooled samples of whole blood for PCR testing 
Herd monitoring for the introduction of PI animals can also be accomplished with pooled blood or serum samples for PCR testing. By pooling samples, the expense of screening herds with a low prevalence of PI animals is minimized. PCR testing is well suited to pooled-sample in that it is sensitive enough to detect minute amounts of virus. A single PI animal is detectable in pools of 200 to 250 negative samples. Animals contributing to negative samples are all assumed to be non-PI, whereas positive pools may contain samples from PI animals or transiently viremic animals.  If the initial pool is PCR-positive, it must be split and retested to differentiate viremic and non-viremic animals. The best size of the initial pool is determined by the balance between the cost savings of having large numbers of individuals represented in negative pools and few individuals represented in positive pools that require further diagnostics. If pool size is too large, there is an increased chance that any single pool will test positive, requiring additional testing to identify the few truly PI individuals in the pool. If the samples are grouped in unnecessarily small pools, the cost benefit of pooling samples is lost to the large number of negative pools tested for each positive pool identified. Researches have developed a model to determine that the economically optimum sample size depends on prevalence of true positives in the population and for a PI prevalence of 0.5% to 1.0%, the optimum number of samples in an initial pool is 20 to 30. 
If whole blood samples are collected for pooled PCR from all suckling calves prior to the start of the breeding season, PI cattle can be identified and removed prior to possible contact with pregnant females, thereby eliminating the opportunity for a PI animal within the herd to cause reproductive failure and the to create more PI animals in the next calf crop. If samples are taken at a later time, such as at weaning, although PI cattle can be removed from the herd, those continuously viremic animals were in contact with pregnant females throughout much of gestation and can cause reproduction and production losses including the creation of PI cattle in the next calf crop.
Use of serologic evaluation of sentinel animals 
Herd surveillance of dairy herds has been described using sentinel animals. Researchers found that serologic evaluation of unvaccinated six- to 12-month –old heifers for the presence of a high BVDV titer was a reasonable strategy for detecting herds that have PI cattle present. Herds that were identified as containing PI animals could then utilize other diagnostic tests to identify individual PI animals for removal. Because this monitoring occurs when potential PI animals are at least six months old, a positive herd test would indicate that the herd has been exposed to at least one continuously viremic animal for at least six months. Reproductive losses and the presence of PI calves in the next calf crop would be expected. 
Use of annual whole-herd testing 
Certain high biosecurity herds, such as herds selling or developing replacement breeding animals, may elect to undergo a high level of surveillance even in the absence of evidence that PI animals are present. This high level of biosecurity may be important to their marketing plan or may indicate a high value placed on avoiding the small, but real risk of introducing BVDV virus into the herd with subsequent negative reproductive, health, and marketing consequences. The first year that a beef herd adopts this strategy, all suckling calves, all females that were bred that failed to present a calf on test-day, all replacement heifers, and all bulls should be tested. If any calf is confirmed as a PI animal, his dam should be tested as well. In subsequent years, only suckling calves and any purchased animals need to be tested. If pregnant animals are purchased, the dam should be tested prior to or at arrival and the calf should be tested immediately after birth. In beef herds with a confined breeding season, this testing must occur before the start of the breeding season to ensure that no PI animals are in contact with pregnant females during gestation. Heifer development operations should test every heifer prior to or at arrival at the facility. Dairy operations should test every calf that stays on the same farm as the breeding herd, or is cared for by breeding herd employees, or if any equipment used on the calf-rearing farm is used on the breeding herd farm.

Biosecurity - Other Potential Sources of BVDV
Bulls (PI and transiently infected)
Male PI calves will occasionally be selected for use as breeding bulls. The amount of BVDV excreted in the semen of persistently infected bulls is very high. BVDV-contaminated semen is an efficient horizontal transmitter of disease from bull to cow. If PI bulls are used, all or most seronegative females bred with the semen will become infected with BVDV although most will not produce a PI calf. Although PI bulls will shed BVDV in semen for prolonged periods of time, virus excretion in semen from transiently infected bulls was confined to days 10-14 post experimental infection and the virus titer in semen of transiently infected bulls was much lower than for PI bulls.
Embryo transfer
Embryo transfer is a potential route of transmission of BVDV. If the embryo recipient is PI, vertical transmission to the transferred embryo will occur with the creation of a PI fetus. Although there is no evidence to suggest that BVDV is present inside the embryos of viremic females, the virus can be present on the intact zona pellucida of PI and transiently infected females and the virus is present at high levels in the uterine environment of PI donors. Established washing procedures will remove contaminating virus, but if these procedures are not followed, BVDV from the collection fluids or virus present on the zona pellucida can be horizontally transferred to a susceptible recipient cow. Vertical transmission from the recipient cow to the fetus can occur resulting in fetal death or the birth of a PI calf. BVDV infection of the recipient cow and fetus can also occur when both the donor and recipient are free of BVDV if BVDV-contaminated fetal serum is used in the embryo transfer process or if contaminated liquid nitrogen is in direct contact with embryos.

Other species (domestic and wildlife)
Other ungulate species may be potential sources of BVDV to susceptible cattle herds. Transmission of BVDV between sheep and cattle has been demonstrated, but the importance of this transmission has not been established. BVDV has also been isolated from pigs, but again, the importance of pigs as a source of the virus to susceptible herds is not established. Deer seropositive to BVDV have been identified in North America and Europe. However, the existence of PI deer has not been demonstrated and cattle are assumed to be the source of BVDV infection for free-ranging ruminants.
Mechanical spread
Human activities may serve in the transmission of BVDV from PI cattle to susceptible animals. A 19-gauge needle was able to infect susceptible cattle with BVDV when used IV within 3 minutes of drawing blood from a PI animal. Nose tongs were able to infect susceptible cattle with BVDV when used for 90 seconds within 3 minutes of being used in a PI animal. And a palpation sleeve was able to transmit the virus from a PI heifer to susceptible heifers that were palpated after her.  
No evidence has been presented that insects are a source of BVDV transmission in field outbreaks. However, a role is possible in that BVDV was isolated from non-biting flies collected from the face of a PI animal, and experimental BVDV transmission between a PI animal and susceptible animals occurred when 50 biting flies were fed on the PI animal for 5 minutes and 15 minutes later fed on susceptible animals. 

Vaccination to Control BVDV-Induced Disease and Production Loss
In addition to removal of PI reservoirs, BVDV transmission to and within the herd can be reduced with an appropriate vaccination program. To date, using laboratory information and limited field trials, one can only make empirical recommendations regarding what constitutes an effective vaccination programs to limit postnatal and gestational BVDV transmission. 
Laboratory evidence of vaccine efficacy
Laboratory work has indicated that although there were large variations in the vaccine-induced virus neutralizing titers of individual colostrum-deprived calves vaccinated with two doses (21 day separation between doses) of an killed BVDV vaccine or a modified live BVDV vaccine, serum from each animal was capable of neutralizing a wide range of antigenically diverse European and American isolates of BVDV, including genotypes I and II. Other work has shown that administration of a single dose of a modified live vaccine against BVDV stimulated an antibody response in seronegative cows that was detectable for at least 18 months. These antibodies were able to cross neutralize 12 antigenically diverse strains of BVDV. 
Ability of vaccines to provide fetal protection
The benefit of preventing clinical disease in vaccinated cattle exposed to BVDV is minimal when considering the management and control of the disease. Cowherd vaccination programs are primarily designed to prevent fetal infection, which is immunologically more difficult than protection from clinical disease. In order to prevent fetal infection, vaccination of an exposed herd would have to prime the immune system to effectively neutralize circulating virus before they can cross the placenta and cause fetal infection. Evidence from earlier as well as recently reported trials indicate the vaccination provides some protection of the fetus when the dam is experimentally challenged, but that protection does not extend to 100% of fetuses of exposed dams. 

Control Programs to Limit Losses Due to BVDV
Control program for BVDV in beef cowherds
The primary goals of BVDV control in breeding herds are to prevent fetal infection in order to eliminate BVDV-associated reproductive losses (thereby preventing the birth of PI calves) and to reduce losses from transient BVDV infections. Cattle that have been infected with BVDV after birth and recovered are considered to be protected from clinical disease following subsequent exposure but protection may not be 100%. While vaccination does provide some protection from fetal infection, BVDV control is generally achieved by a combination of: removal of PI cattle, vaccination, and a biosecurity system that prevents the introduction of PI animals into the herd and minimizes the contact with potentially viremic cattle or wildlife. 
Removal of PI animals
Herds should be monitored to determine the risk that one or more PI cattle are present. If the presence of PI cattle is confirmed or strongly suspected, a whole-herd screening protocol, should be undertaken to identify and remove PI individuals. A second whole-herd screening the following year may be advisable in some herds where risk of continued fence-line or other exposure to PI animals is high.  
Biosecurity to prevent herd exposure to PI animals
Biosecurity to prevent herd exposure to PI or transiently infected animals is important, especially after the removal of PI cattle, because with the removal of PI BVDV shedders, the percentage of naturally protected seropositive animals in a herd decreases. All replacement heifers and bulls that enter the breeding herd, whether raised or purchased, should be tested and confirmed to not be PI prior to the start of breeding. If a pregnant animal is purchased, it should be segregated from the breeding herd until both the dam and the calf is confirmed to not be PI. Fence line contact with neighboring cattle should be managed so that stocker cattle are not adjacent to the breeding herd during early gestation, and other cowherds are not adjacent unless they also have a strict biosecurity and vaccination program in place. 
Vaccination as a component of biosecurity
Biosecurity also involves application of a vaccination protocol to reduce the risk of fetal infection in the event of cowherd exposure to a viremic and shedding animal. Live, replicating vaccines (MLV) have inherent properties that may enable them to stimulate more complete protection against transplacental infection. For that reason, one recommendation is to vaccinate unstressed, healthy heifers with MLV vaccine. Vaccine administration should be timed so that a protective immune response coincides with the first four months of gestation. This is done to maximize the potential for adequate immunity to protect against fetal infection and reproductive failure or the birth of persistently infected calves. In heifers not previously vaccinated, the primary series should consist of two administrations. The first dose should be given when the heifers are 6 months of age or older, and the second dose should be given two months before breeding. Beef cows should be revaccinated annually before breeding according to label directions.
Control program for BVDV in stocker/feedlot operations
	Because pregnancy is not a common or desirable component of stocker and feedlot operations, vertical transmission and reproductive losses due to BVDV is not a concern. Vaccination is currently the primary control intervention for BVDV in stocker and feedlot operations. Screening cattle for the presence of PI individuals prior to purchase or at arrival has not been adequately evaluated for economic return. The economic return will depend on the prevalence of PI cattle, the sensitivity and specificity of the test used, and the economic cost of the disease to the operation.

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