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

of BVDV in cattle populations. Current surveillance programs, designed to detect classic persistently infected animals, will invariably miss these types of infections. In addition, the true cost of BVDV must factor in the problems in production that occur after the virus has been shed. This is difficult to track because onset of acute infection and its repercussions on animal production may be months apart.

LOW-VIRULENCE STRAINS OF BVDV

It is easy to determine the impact of infection with highly virulent strains of BVDV. The impact of lowvirulence strains, on the other hand, is difficult to ascertain. However, infection with these strains should not be considered a benign event even though their effects may not be immediately apparent. Infection with low-virulence strains of animals that are actively laying down bone and muscle tissues may have long-term effects on their growth potential. In addition, low-virulence strains may lead to immunosuppression, setting up the animal for more severe secondary infections.

The impact of low-virulence strains on vulnerable populations of cattle should also be studied in detail. Examples of vulnerable animals include the fetus, weaned animals from which passive antibodies have disappeared or are waning, animals newly introduced into the herd, and stressed animals. Biosecurity to prevent the introduction of BVDV in animal herds and adequate vaccination programs are particularly important to limit infection in vulnerable animals. The significance of BVDV isolates from giraffe, antelope, and reindeer also need to be studied.

REFOCUSING CONTROL EFFORTS

Historically, BVDV control efforts have been based on vaccination. However, 40+ years of vaccination have not resulted in a significant decrease in BVDV losses nationwide. Although vaccination can be an effective component of a BVDV control plan, it is not a stand-alone answer to the problem. For a control effort to be effective, proactive management plans must be in place, and the development of such plans requires a complete understanding of BVDV transmission within populations, surveillance strategies, biosecurity on the farm, and the role of vaccination.

TRUE IMPACT OF BVDV

The compelling reason for a BVDV control program is that reducing BVDV infections is cost-effective. This premise assumes that the expenses incurred in

preventing BVDV infections are offset by savings realized by more efficient animal production. Although most producers agree that BVDV infections are detrimental, the full extent of BVDV’s impact on production is frequently underestimated. In a layman’s mind, BVDV-associated reproductive disease presents as the birth of PI animals. However, the birth of PI animals following the introduction of BVDV into a group of dams may represent just the tip of the iceberg. Clinical presentation of BVDVassociated reproductive disease also includes failure to conceive (repeat breeding), abortion, mummification, congenital abnormalities, and the birth of neonates that appear normal but fail to thrive. In order to determine the true impact of BVDV reproductive disease, animal producers and clinicians need to be alert to the many different forms of BVDV-induced reproductive problems.

BIOSECURITY ON THE FARM

Vaccination is a component of the control plan rather than an end unto itself and vaccines should not be considered “silver bullets” in the eradication of BVDV. In the absence of a good management program, which by definition would include a biosecurity plan, protection via vaccination will eventually fail. Preventing longand short-term exposures to BVDV by limiting the introduction of BVDV into a herd is as important as protecting the animals by vaccination. Thus, PI animals must be removed and new additions to the herd should be isolated until their BVDV-free status has been established. In the case of bred heifers, BVDV-free status cannot be assured until the calf has been tested. Care should be taken to assure that a good BVDV management program is in place for all parties when facilities and equipment are shared between production units. A producer’s biosecurity program is only as good as that of the neighbor he shares a fence with or the fellow exhibitor with whom he shares a show ring.

DISEASE SURVEILLANCE

The present testing for BVDV is sporadic and is usually done in response to an outbreak of the disease and focuses on the detection of PI animals. However, exposure to BVDV may result in subclinical disease that may impact profitability but is not immediately apparent from casual observation of the herd. Routine BVDV surveillance programs would be more effective at detecting and controlling BVDV outbreaks. Further, not all outbreaks of BVDV-related disease can be traced to contact with a PI animal. PI animals are certainly a major factor

in keeping BVDV in circulation, but acute BVDV infections cannot be ignored for surveillance programs to be effective. As discussed above, non-PI animals may experience prolonged viremia or may have localized infections that are not cleared. Further, aborted or stillborn fetuses may serve as sources of BVDV infection for a herd. Effective control programs must include the use of reliable tests for the detection of both acute and persistent infections and examination of aborted and stillborn fetuses.

VACCINE DESIGN

When developing vaccines, one of the questions that should be asked is whether the strains used in the vaccine reflect and protect against viruses the animal will be exposed to in the field. The first BVDV vaccines were produced in the 1960s. Viral strains used in these vaccines—e.g., Singer, NADC, NY-1, and C24V (Oregon strain), are still found in vaccines 40 years later. Retrospective analysis of these strains has shown that all of them belong to a single branch of the pestivirus family tree—e.g., BVDV genotype 1. In the early 1990s, a newly recognized group of BVDV field isolates, eventually termed BVDV genotype 2, was found to break through BVDV vaccination programs. A second generation of BVDV vaccines that contain the old vaccine strains plus strains from the BVDV 2 genotype are now becoming available. Time will tell whether these vaccines are more efficacious than the old ones.

As more BVDV strains are characterized, subgenotypes of BVDV are being recognized within both BVDV 1 and BVDV 2 genotypes. Thus, BVDV 1 has been subdivided into BVDV 1a and BVDV 1b. Recent surveys in the U.S. have shown that BVDV 1b is found most frequently in association with clinical disease and that most BVDV 1 strains isolated from the field belong to the BVDV 1b subgenotype. However, when BVDV 1 strains used in vaccines were characterized, it was found that they predominantly belonged to the BVDV 1a subgenotype. The practical significance of this finding is not clear and it is also not known whether the inclusion of BVDV 1b in vaccines would offer better protection. Further research is needed to answer these questions.

The observation of incomplete fetal protection following prebreeding vaccination should also be examined. Currently used vaccines are evaluated by determining whether they protect against BVDVinduced respiratory disease. Although some vaccine manufacturers have started to evaluate their vaccines for fetal protection, more needs to be done in this

area. Current vaccines with fetal protection label claims were licensed based on a one-time challenge of BVDV. Animals in contact with PI animals will be challenged by virus shed by the PI on a daily basis. It is not known how well vaccination stands up to such repeated challenges. Further, fetal protection appears to be dependent upon the prevention of viremia, not reduction of viremia or clinical disease. Thus the “perfect” BVDV vaccine would prevent infection rather than disease and induce both cellular and humoral immune responses.

EFFECTS OF STRESS ON VACCINE EFFICACY

Vaccines are commonly administered when animals are gathered for weaning, sorting, branding, and shipping. Unfortunately, the animal is under stress from a number of different factors at these times and its immune response is not functioning at its peak. Vaccination at these times may not result in an optimum immune response and may even cause transient losses in production. Thus, management practices may impact on the efficacy of the vaccine and should be taken into account when implementing a control program with vaccination.

OTHER QUESTIONS

The recognition of severe acute BVD in the early 1990s changed our perception of BVDV-induced disease severity. It is important to continue to monitor the role of newly emerging strains of BVDV on disease severity and on acute and persistent infections. The role of vaccination in the emergence of new BVDV strains should be monitored, and the current methods for the detection of BVDV in semen samples need improvement. The development of a prenatal test to determine the existence of PI animals would also be useful.

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Note: Italicized page numbers indicate table or figure.

Abattoirs

genital tracts obtained from, 198 sampling from, 38

Abortions, 5, 8, 53, 57, 59, 93, 107 causes of, 114, 223, 224, 241 fetal infection and, 128–129 initial reports on, 147

Academy of Veterinary Consultants, BVDV position statement by, 25–26

AC-ELISA. See Antigen capture ELISA Active humoral immune response, 158 Active immunity, 105

Acute, prolonged infections, 240–241 Acute BVDV infections, 121, 123–126 bovine respiratory disease and, 105

esophageal ulcers in cattle suffering from, 112 horizontal transmission of BVDV and, 94 immune suppression in, 105, 125–126

role of viral and host factors in pathogenesis of, 121, 123

spread of BVD of low and high virulence in, 124 viral shedding and, 130–131

virus spread and development of lesions in, 123–125 comparing strains of high and low virulence, 125 strains of high virulence, 124–125

strains of low virulence, 123–124

Acutely infected animals, BVDV transmission from, 97–98

Acute mucosal disease, clinical signs of, 112 Adequate contact, herd immunity and, 93 Adequate contacts per time period, number of, 91 Aerosols, role of, in acquiring BVDV, 106

Agar gel-diffusion precipitin tests, 6

Agarose gel electrophoresis, PCR product identified by, 202

Akkina, R.K., 20, 203 Alopecia, 150, 224 Alpacas, 116

Alveolar macrophages, 157, 161 American Bison, 173

American Type Culture Collection, 23 Antelocapridae family, serologic surveys of ruminant

species within, 173

Antibodies against BVDV, epidemiological studies for estimation of prevalence of animals with, 39–42

Antibody carriers, prevalence of, 51

Antibody decay rate, calves susceptibility of infection and, 98

Antibody detection, 200

Antibody status, of individual animals, 50 Anticoagulant toxicity, 111

Antigen capture ELISA, 199 Antigenic diversity, 209, 210, 239

Antigenic variation, among BVDV 1 and BVDV 2 strains, 66

Antigen nucleic acid, detection of, 198 Antigen-presenting cells, 158, 164 Anti-idiopathic Mabs, 178

AP. See Apparent prevalence APAF-1, 186

APC. See Antigen-presenting cells Apoptosis, 22, 157, 158, 186, 187 Apparent prevalence, 36

AR. See Attributable risk

Arcanobacter pyogenes, 172 Archbald, L.F., 148

Arsenic poisoning, 110

Artificial insemination (AI) centers prevalence of PI at, 95

testing requirements for bulls in, 17

Artiodactyla order, occurrence in ungulates belonging to, 115–116

Ataxia, 129, 150 ATPase, 82 Attributable risk, 50

Atypical persistent infection, 16–17 Austria, prevalence in, 46

AVC. See Academy of Veterinary Consultants Axis deer, 116

Baigent, S.J., 188

Baker, J.C., 13, 14

246

Barlow, R.M., 10

Baule, C., 14, 22

BBMM. See Bovine bone marrow-derived macrophages B-cells, 164, 240

BCV. See Bovine respiratory coronavirus BDV. See Border disease virus Beaudeau, F., 201

Becher, P., 15

Beef calves, age-matched, from herd suffering from mucosal disease, 112

Beef cattle, control programs and, 233

Beef cow herds, control program for BVDV in, 234 Beer, M., 214

Belgium

BVDV genotypes identified in, 46 prevalence in, 52

Bennett, R.M., 58

BEV-3. See Bovine enterovirus-3 Bhudevi, B., 202

BHV-1. See Bovine herpes virus-1 Bielefeldt-Ohmann, H., 12

Biologics, possible BVDV contamination of, 171 Biosecurity

control programs and, 209 for dairy herds, 234, 235 on farm, 241

importance of, 152

inter-herd transmission and, 101

to prevent herd exposure to PI animals, 233 whole-herd testing and, 230

Biotypes BVDV, 73–74

practical significance of, 74 recurrent shedding and, 98 Bison, cell lines survey and, 173

Bitsch, V., 21

Bittle, J.L., 6

Blindness, in calves, 164 Blue tongue, 110 B-lymphocytes

decrease of, in acute BVDV infection, 125 lymphoid tissue lesions and, 134

Bolin, S.R., 9, 13, 15, 16, 203

Bone marrow, effect of BVDV on, 163 Border disease virus, 5, 65, 171, 198, 218 Bovidec (C-vet), 217

Bovine bone marrow-derived macrophages, 187 Bovine enterovirus-3, 177

Bovine herpes virus-1, 161, 210 Bovine papular stomatitis, 114

Bovine polyclonal antibody (Pab)-based IPMA, 198 Bovine respiratory coronavirus, 161

Bovine respiratory disease, 105, 106, 115, 161 Bovine respiratory syncytial virus, 110, 125, 161, 210 Bovine species, BVDV adaptation for replication in,

151

Bovine turbinate cells, 199

Bovine viral diarrhea-mucosal disease, 4

Index

Bovine viral diarrhea virus, xi, 3

acute and persistent infections in bull, 10 atypical persistent infection, 16–17 binding and entry of, 82

biotypes, 73–74

practical significance of, 74 characterizations of, 4–5

circulation of, in cattle populations, 122 clinical/subclinical manifestations of and sequelae to

congenital infection with, 106 control by vaccination, 20–21, 25 control strategies for, 12–14 control without vaccination, 21 detection of, 12

diagnosis and control 1960s, 5–6

1970s, 7–8

diagnosis by virus isolation, 18 economic impact of, 56–58, 59

effects/consequences of, on disease and production, 53–56

entry of into cells, translation, and replication, 68–71 epidemiological framework for description of occur-

rence of, 36 eradication programs, 25–26

experimental production of persistent infection and mucosal disease, 8–10

factors affecting transmission of, 91–92 forms of, 105

future research on, 165

genetic recombination and spontaneous and postvaccinal mucosal disease, 15

genotypes, 71–73

differences between BVDV 1 and BVDV 2, 73 prevalence of, 72

similarities between viruses from BVDV 1 and 2 genotype, 72–73

subgenotypes of BVDV 1 and BVDV 2, 73 heterogeneity of, 74

immune responses to, 157–159

isolates/analysis of genotype compared with clinical presentation, 110

late-onset mucosal disease, 15–16 measurable/quantifiable epidemiological variables,

35–38

molecular actions of cytopathic and noncytopathic BVDV, 22–23

molecular biology advances and, 11–12, 17–18 monoclonal antibody-based tests for, 18–19

normal calves from persistently infected cows and, 16 old cytopathic BVDV strains, 23–24

outcomes and factors influencing outcome of infections from, 122

overall view of infection from, 190

persistent infections in sick and apparently healthy cattle, 7

phylogenetic studies, 14–15 polymerase chain reaction, 19–20