Материал: Bovine Viral Diarrhea Virus Diagnosis, Management, and Control

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 causing embryonic loss or 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 (Singh et al., 1982). 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 (Singh, 1982; Singh et al., 1985). Vertical transmission from the recipient cow to the fetus can occur, resulting in embryonic/fetal death or the birth of a PI calf (Brock et al., 1991). 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 (Singh et al., 1985; Bielanski et al., 2000).

OTHER UNGULATE 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 (Carlsson and Belak, 1987). 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 (Liess and Moenning, 1990; Terpstra and Wensvoort, 1988). Deer seropositive to BVDV have been identified in North America and Europe (Davidson and Crow, 1983; Nielsen et al., 2000; Frolich et al., 2002). 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.

FOMITES

Fomites 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 (Gunn, 1993). 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 (Gunn, 1993).

No evidence has been presented that insects are a source of BVDV transmission in field outbreaks (Table 14.4). However, a role is possible: BVDV was isolated from nonbiting flies (Musca autumnalis) collected from the face of a PI animal, and experimental BVDV transmission between a PI animal and susceptible animals occurred when 50 biting flies fed on the PI animal for 5 minutes and 15 minutes later fed on susceptible animals (Gunn, 1993; Tarry et al., 1991).

VACCINATION TO CONTROL BVDV-INDUCED DISEASE AND PRODUCTION LOSSES

In addition to removal of PI reservoirs, BVDV transmission to and within the herd can be reduced with an appropriate vaccination program. Information from serological data and limited field trials can be used to make empirical recommendations regarding what constitutes an effective vaccination program to limit postnatal and gestational BVDV transmission.

IN VITRO EVIDENCE OF VACCINE EFFICACY

Although there were large variations in the vaccineinduced virus neutralizing antibody titers of individual colostrum-deprived calves vaccinated with two doses (21-day separation between doses) of an inactivated BVDV vaccine (Hamers et al., 2002) or with a modified live, temperature-sensitive BVDV vaccine (Hamers et al. 2000b), sera from all animals were capable of neutralizing a wide range of antigenically diverse European and American isolates of BVDV, including genotypes 1 and 2. In another study, administration of a single dose of a modified live BVDV vaccine in seronegative cows induced antibodies that were able to cross-neutralize 12 antigenically diverse strains of BVDV (Cortese et al., 1998c) and were detectable for at least 18 months.

COLOSTRAL IMMUNITY AND VACCINATION

OF YOUNG CALVES

Adequate intake of colostrum from BVDV seropositive dams provides protection from clinical disease in young calves (Cortese et al., 1998b; Ridpath et al., 2003). Vaccination of young calves has also been demonstrated to reduce clinical disease and mortality following experimental challenge (Cortese et al., 1998b). Calves that did or did not receive colostral antibodies and were vaccinated at 10–14 days of age with a single dose of modified live vaccine (MLV) containing type-1 BVDV were protected from clinical disease when experimentally challenged 21 days postvaccination with a virulent type-2 BVDV. In

contrast, calves that did not receive colostral antibodies to BVDV and did not receive the MLV vaccine suffered severe clinical disease and required euthanasia (Cortese et al., 1998b). Clinical scores, indicating severity of illness, were not significantly different between seropositive-vaccinated and seropositive-unvaccinated calves after experimental viral challenge in this trial (Cortese et al., 1998b). Most of the vaccinated calves that were seronegative prior to vaccination did not have measurable serum antibody response 21 days following vaccination at the time of experimental challenge, even though these calves were protected from clinical disease (Cortese et al., 1998b). Similarly, Ridpath et. al. (2003) demonstrated that an active protective response, not correlated to serum-neutralizing antibodies, was mounted in young calves in the presence of colostral-derived passive immunity. Thus serum antibody titers may represent an inadequate

measure of protection against disease (Cortese et al., 1998b; Ridpath et al., 2003).

ABILITY OF VACCINES TO PROVIDE FETAL

PROTECTION

Using vaccination strategies to prevent or reduce clinical disease caused by BVDV is important in the management of bovine respiratory disease in feedlot and other confined cattle situations. However, when controlling BVD in cowherds, controlling clinical disease is minimally important compared to preventing fetal infection that results in embryonic/fetal loss or creation of PI animals. Fetal protection is immunologically more difficult than protection from clinical disease; however, the majority of vaccines are licensed based on their ability to reduce clinical signs in acute infection, not to reduce reproductive loss or fetal infection. Fetal infection can be prevented if the immune system of an exposed herd is

primed so that it can effectively neutralize circulating virus before it has a chance to cross the placenta and cause fetal infection. Evidence from earlier as well as recently reported trials indicates that maternal vaccination provides some protection of the fetus, although protection does not extend to 100% of fetuses (Kelling et al., 2000). In fact, efficacy of maternal vaccination to provide fetal protection has been reported to range from 25–100% for inactivated vaccines (Meyling et al., 1987; Harkness et al., 1987; Brownlie et al., 1995) and from 58 to 88% for modified live vaccines (Cortese et al., 1998a; Brock and Cortese, 2001). The presence of measurable levels of BVDV antibody in dams following vaccination appears to provide fetal protection and is important in a planned vaccination program for BVDV control. It should be realized, however, that a sufficient amount of virus is able to escape neutralization inactivation by circulating antibodies in some dams to cause transplacental infection, abortion, and the development of persistent fetal infection. Thus, vaccination programs by themselves are inadequate in controlling BVDV (Cortese et al., 1998a; Brock and Cortese, 2001; Brownlie et al., 1995).

CONTROL PROGRAMS TO LIMIT LOSSES DUE TO BVDV

BEEF CATTLE

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 (Harkness, 1987). Cattle that have been infected with BVDV after birth and have recovered are considered to be protected from clinical disease following subsequent exposure to the virus even if they are seronegative (Ridpath et al., 2003). Animals that are seropositive in response to natural exposure are also considered to be protected from future transmission of the virus to a fetus. An immunocompetent animal that gives birth to a persistently infected animal will develop high antibody titers and is likely to eliminate future BVDV infections rather than pass them to the fetus. Thus, an immunocompetent dam (nonPI) could have, at most, one PI calf.

While vaccination does provide some protection from fetal infection, the herd level protection is not equal to that generated by natural exposure. As a result, 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 (Kelling, 1996).

Removal of PI animals

Herds should be routinely monitored to determine the presence of PI animals. If the presence of PI cattle is confirmed or strongly suspected, a whole-herd screening protocol, most likely utilizing IHC of skin samples or PCR as described earlier, 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 animal (BVDV) shedders, the numbers of naturally exposed seropositive animals in a herd decreases (Kelling, 1996). All replacement heifers and bulls that enter the breeding herd, whether raised or purchased, should be tested prior to the start of breeding to ensure that they are not PI animals. If a pregnant animal is purchased, it should be segregated from the breeding herd until both the dam and the calf are confirmed to be non-PI. Fenceline 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 virus-shedding animal. Modified live vaccines are believed to stimulate more complete protection against transplacental infection (Kelling, 1996). For that reason, one recommendation is to vaccinate unstressed, healthy heifers with MLV vaccines. Vaccine administration should be timed so that a protective immune response coincides with the first 4 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 PI calves. If heifers have not been previously vaccinated, the primary vaccination should be done

I.Monitor herd for risk of PI presence

a.If PI presence is confirmed or strongly suspected, a whole-herd screening to identify and remove PI individuals is undertaken

b.Monitoring options:

i.Monitor production (reproduction efficiency, neonatal and postnatal death loss), monitor ill neonates for BVDV viremia, and necropsy (with laboratory submissions) as many abortions, stillbirths, and neonatal deaths as possible

ii.Use pooled samples of whole blood taken from suckling calves prior to breeding for PCR testing

iii.Use serologic evaluation of sentinel animals

iv.Use annual whole-herd screening prior to breeding season (all suckling calves and purchased replacements)

II.Biosecurity for herd against BVDV entrance a. Isolate herd during breeding/gestation from

cattle of unknown BVD PI status

(avoid fence-line contact with stocker cattle, neighbors’ cattle, etc.)

b.Vaccinate to reduce virus circulation and to reduce production of PI calves in face of virus circulation

i.Use MLV vaccine two or more times between weaning and two months prior to first breeding as heifers

ii.Use vaccines according to label to booster cowherd annually

c.Biosecurity to prevent introduction of virus into herd

i.Test purchased bulls and heifers

ii.Test raised replacement heifers and bulls

iii.Monitor population for evidence of introduction of PI animals

d.Purchasing bred heifers

i.If heifers are tested prior to purchase, still need to test calf after birth.

ii.If heifers are not tested prior to purchase, can test heifer prior to entry into herd and then test calf after birth, or isolate heifer until calf is born and test the calf (only need to test heifer if calf is positive).

iii.Percutaneous collection of fetal fluids for detection of PI calf has been described – not recommended at this time

iv.Serology in late gestation to identify PI-carrying unvaccinated dams

(Good negative predictive value, poor positive predictive value)

e.Fomites

i.Maintain sanitation to prevent viral spread via nose tongs, injection needles, palpation sleeves, etc.

twice. The first dose should be given when the heifers are 6 months of age or older, and the second dose should be given 2 months before breeding. Beef cows should be revaccinated annually before breeding according to label directions (Kelling, 1996).

DAIRY CATTLE

The management of U.S. dairies is vastly different than that of beef cows; dairy calves are removed from their dams soon after birth and are not in contact with the breeding herd during gestation. Hence, calf transmission of BVDV to pregnant females is eliminated or greatly reduced in dairy herds as compared to beef herds. However, because many pregnant replacement females are purchased or raised off-site on dairies, the risk of introduction of a PI replacement animal or pregnant non-PI an-

imal with a PI fetus is greater in dairy operations than in beef herds. Biosecurity for dairy herds should include screening of potential replacement heifers prior to the start of their first breeding season, biosecurity of heifer and adult cows during gestation to prevent exposure to PI or transiently infected animals, and a vaccination program to provide some level of protection in the face of exposure to viremic animals.

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 are not a concern. However, BVDV viremia or seroconversion has been associated with respiratory disease outbreaks in feedlot situations (Martin et al., 1989; Fulton et al., 2000; Fulton et al., 2002).

Table 14.6. Control program for BVDV in dairy herds.

I.Monitor herd for risk of PI presence

a.If PI presence is confirmed or strongly suspected, a whole-herd screening to identify and remove PI individuals is undertaken

b.Monitoring options:

i.Monitor production (reproduction efficiency, neonatal and postnatal death loss), monitor ill neonates for BVDV viremia, and necropsy (with laboratory submissions) as many abortions, stillbirths, and neonatal deaths as possible

ii.Use serologic evaluation of sentinel animals

iii.Test all heifer calves that may be saved as replacements

(IHC of skin samples or PCR of pooled whole blood samples)

II.Biosecurity to prevent introduction of BVDV into herd

a.Test all heifer calves that are potential replacements if raising own replacements

b.Test purchased replacement heifers and bulls prior to or at delivery

c.Obtain replacement heifers from source that has a strict biosecurity program in place

d.Use vaccines according to label to booster cowherd

e.Monitor population for evidence of introduction of PI animals

III.Biosecurity for heifer raisers

a.Test all heifers prior to or at arrival at development facility/farm

b.Isolate heifers during breeding/gestation from cattle of unknown BVD PI status

c.Vaccinate with MLV product two or more times between six months of age and start of breeding

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. 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.

Table 14.7. Control program for BVDV in stocker/feedlot operations.

I.Vaccination of incoming cattle with MLV product

II.Screening incoming cattle for BVDV PI animals

a.Low prevalence causes even a test with high specificity to have more false positive than true positives

b.Testing should be done prior to cattle being commingled and trucked. Transmission and

infection likely to occur during stress and crowding of commingling and trucking.

III.Purchasing PI-free certified cattle

a.All cattle in a group are test negative (IHC of skin sample or pooled PCR of whole blood)

b.Economic benefit is determined by multiplying the cost of having a PI feeder calf

present (increased pen morbidity, mortality, treatment failure, and performance) by the expected prevalence for similar cattle.

IV. Purchasing PI-low risk cattle

a.All cattle in the group originate from farm(s) with a complete vaccination program and BVDV PI screening protocol

V.Purchasing cattle of unknown PI risk

a.Cost of unknown status is determined by multiplying the cost of having a PI calf present by the expected prevalence for similar cattle

b.Cost of unknown PI risk is added to other costs for break-even calculation

REFERENCES

Baker JC: 1987, Bovine viral diarrhea virus: A review.

J Am Vet Med Assoc 190:1449–1458.

Barber DML, Nettleton PF, Herring JA: 1985, Disease in a dairy herd associated with the introduction and spread of bovine virus diarrhoea virus. Vet Rec 117:459–464.

Baszler TV, Evermann JF, Kaylor PS, et al.: 1995, Diagnosis of naturally occurring bovine viral diarrhea virus infections in ruminants using monoclonal antibody-based immunohistochemistry. Vet Pathol 32:609–618.