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2024年6月2日发(作者：)

CHAPTER 2.4.8

BOVINE VIRAL DIARRHOEA

SUMMARY

Cattle of all ages are susceptible to infection with bovine viral diarrhoea virus (BVDV) (see also

Chapter 4.3 in the Terrestrial Animal Health Code). Distribution of the virus is world-wide. The

clinical signs range from subclinical to the fulminating fatal condition called mucosal disease. Acute

infections may result in transient diarrhoea or pneumonia, usually in the form of group outbreaks.

Acute forms of the disease associated with high mortality have also been described, often, but not

always, associated with a haemorrhagic syndrome. However, most infections in the young calf are

mild and go unrecognised clinically. The virus spreads mainly by contact between cattle. Vertical

transmission plays an important role in its epidemiology and pathogenesis.

Infections of the bovine fetus may result in abortions, stillbirths, teratogenic effects or persistent

infection in the neonatal calf. Persistently viraemic animals may be born as weak, unthrifty calves or

may appear as normal healthy calves and be unrecognised clinically. Some of these animals may

later develop mucosal disease with anorexia, gastrointestinal erosions, and profuse diarrhoea,

leading invariably to death. Mucosal disease can arise only in persistently infected animals.

It is important to avoid the trade of viraemic animals. It is generally considered that serologically

positive, nonviraemic cattle are ‘safe’, providing that they are not pregnant. Antibody-positive

pregnant cattle carrying persistently infected fetuses are important transmitters of the virus between

herds. About 15% of persistently viraemic animals have antibody to the NS/2 protein and a lower

percentage to the E2 glycoprotein. Therefore, seropositivity cannot be equated with ‘safety’. Latent

infections are not generally thought to occur following recovery from acute infection, though semen

from acutely infected animals and, very rarely, recovered animals may be suspect.

Identification of the agent: BVDV is a pestivirus in the Flaviviridae and is closely related to

classical swine fever and ovine Border disease viruses. BVDV occurs in two forms:

noncytopathogenic and cytopathogenic. There are two antigenically distinct genotypes (types 1 and

2), and virus isolates within these groups exhibit considerable biological and antigenic diversity.

Persistently viraemic healthy animals resulting from congenital infection can be readily identified by

isolation of noncytopathogenic virus in cell cultures from blood or serum. It is necessary to use an

immune-labelling method to detect the growth of virus in the cultures. Alternative methods based on

direct detection of viral antigen or viral RNA in leukocytes are also available. Persistence of virus

should be confirmed by resampling after an interval of at least 3 weeks. These animals will usually

have no or low levels of antibodies to BVDV.

Viraemia in acute cases is transient and can be difficult to detect. In fatal cases of haemorrhagic

disease, virus can be isolated from tissues post-mortem. Confirmation of mucosal disease can be

made by isolation of the cytopathogenic biotype of BVDV, particularly from intestinal tissues.

Noncytopathogenic virus may also be detected, especially in blood.

Serological tests: Acute infection with BVDV is best confirmed by demonstrating seroconversion

using sequential paired samples from several animals in the group. The testing of paired (acute and

convalescent samples) should be done a minimum of 21 days apart and samples should be tested

side by side. The enzyme-linked immunosorbent assay for antibody and the virus neutralisation test

are the most widely used.

Requirements for vaccines and diagnostic biologicals: There is no standard vaccine for BVD,

but a number of commercial preparations are available. Modified live virus vaccine should not be

administered to pregnant cattle (or to their sucking calves) due to the risk of transplacental infection.

There is also a risk of inducing mucosal disease in persistently infected animals. Killed virus

698 OIE Terrestrial Manual 2008

Chapter 2.4.8. -- Bovine viral diarrhoea

vaccines generally require booster vaccinations. An ideal vaccine should be able to prevent

transplacental infection in pregnant cows.

BVDV is a particularly important hazard to embryo transfer and the manufacture of biological

products for other diseases due to the high frequency of contamination of batches of fetal calf

serum used as a culture medium supplement dams subject to embryo transfer, which makes use of

this material, may be at risk of infection.

A. INTRODUCTION

Bovine viral diarrhoea virus (BVDV) is a pestivirus in the family Flaviviridae and is closely related to classical

swine fever and ovine Border disease viruses (23). Two antigenically distinct genotypes of BVDV exist, types 1

and 2, with further subdivisions discernable by genetic analysis (74). The two genotypes may be differentiated

from each other, and from other pestiviruses, by monoclonal antibodies (MAbs) directed against the E2 and E

RNS

major glycoproteins, or by genetic analysis (65, 68). Multiplex polymerase chain reaction (PCR) enables virus

typing direct from blood samples (33). Type 1 virus is generally more common although the prevalence of type 2 is

reported to be almost as high as type 1 in North America. BVDV of both genotypes may occur in

noncytopathogenic and cytopathogenic forms (biotypes), classified according to whether or not it produces visible

change in cell cultures. Usually, it is the noncytopathogenic biotype that circulates in cattle populations. Each

biotype has a specific role in a variety of clinical syndromes – acute, congenital and chronic infections (5, 11).

Type 2 viruses are usually noncytopathogenic and have been associated with outbreaks of severe acute infection

and a haemorrhagic syndrome (16). However recent type 2 viruses isolated in the United Kingdom have been

associated with a disease indistinguishable from that seen with the more frequently isolated type 1 viruses. Some

type 1 isolates have been associated with particularly sever and fatal disease outbreaks in adult cattle (20)

clinically mild and inapparent infections are common with both genotypes.

Although ubiquitous, control of BVDV can be achieved at the herd level, and even at the national level, as

evidenced by the progress towards eradication made in many European countries (56).

B. DIAGNOSTIC TECHNIQUES

a) Acute infections

Acute infections of cattle occur particularly in young animals, and may be clinically inapparent or associated

with diarrhoea (1). Affected animals may be predisposed to secondary infections, for example those leading

to shipping disease, perhaps due to an immunosuppressive effect of the virus. Bulls may suffer a temporary

depression of fertility and can show transient shedding of virus in the semen (62). Cows may also suffer from

infertility, likely associated with changes in ovarian function (35) and secretions of gonadotrophin and

progesterone (30). During acute infections, a brief viraemia may be detectable and nasal shedding of virus

may occur. There may also be a transient leukopenia, thrombocytopenia or temperature response, but these

can vary greatly among animals. A serological response is the most certain means of diagnosing a previous

infection. The clinical picture is generally one of high morbidity and low mortality, though more severe

disease is sometimes seen (12). In particular, outbreaks of a severe form of acute disease with

haemorrhagic lesions, thrombocytopenia and high mortality have been reported sporadically from some

countries (1, 6) and infection with Type 2 viruses in particular has been demonstrated to cause altered

platelet function (76). Other acute outbreaks may show fever, pneumonia, diarrhoea and sudden death in

any age group, with haemorrhagic signs (16).

b) Congenital infection

If noncytopathogenic virus infects the bovine fetus, this may result in abortion, stillbirth, teratogenic effects or

a congenital infection that persists in the neonatal calf (1, 11, 26, 55). Confirmation that an abortion is

caused by BVDV is often difficult to establish (69), but virus may be isolated from fetal tissue in some cases,

or viral antigen or genome may be demonstrated. An attempt should also be made to detect specific

antibody in samples of fetal fluids or serum, or in the supernatant fluid from a tissue suspension. Stillbirths or

teratogenic effects may be associated with an active fetal immune response to the virus during mid-to-late

gestation. The dam will often have high antibody titres (>1/2000) to BVDV, which is suggestive of fetal

infection and is probably due to the fetus providing the dam an extended challenge of virus (47).

Although congenital infection with BVDV often leads to abortion, it is not always recognised in the field.

Infection during the first third of the gestation period can result in the abortion of a conceptus that is small

and goes unnoticed by the farmer. The cow would return to service and the failure to maintain pregnancy

would be classified as an example of early embryonic death. Another possible outcome of infection is the

death and subsequent resorption of fluids from the fetus that results in mummification. It is frequently

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