key: cord-0008756-t5bxqd43
authors: Heuschele, Werner P.
title: Preventive Medicine for Some Economically Important Bovine Viral Diseases
date: 2017-07-20
journal: Vet Clin North Am Large Anim Pract
DOI: 10.1016/s0196-9846(17)30136-2
sha: 9001b914a0f375d8c4a114e5f24469ffe732e8e2
doc_id: 8756
cord_uid: t5bxqd43

nan

watery and sometimes bloody diarrhea, profuse salivation, emaciation, dehydration, depression, a mucopurulent nasal exudate, and erosions and ulcerations of the nostrils, muzzle, lips, gums, tongue, and oral cavity. Both diseases have since been shown to be due to the same virus, referred to as the bovine diarrhea-mucosal disease virus or, more commonly, the bovine virus diarrhea virus (BVDV).

The virus that causes BVD is a member of the family Togaviridae, genus Pestivirus, which also includes the viruses of hog cholera and Border disease of sheep. The latter two viruses are antigenically closely related to BVDV, based on studies by cross-neutralization, immunoprecipitation, and immunofluorescence . There is strong evidence that Border disease virus (BDV) of sheep is, in fact, BVDV, based on cross-infectivity and clinical responses of cattle to BDV and sheep to BVDV.

Bovine viral diarrhea is one of the most prevalent infections of cattle in the United States and appears to be so worldwide. Serologic surveys of unvaccinated cattle in the United States have indicated that 60 to 80 per cent have antibodies to BVD. A majority of BVD infections in cattle are subclinical but may persist and exacerbate as overt clinical disease in association with stress and concurrent acute infections with other agents. Grunder et al. have listed six clinical categories of BVDV infection in cattle that reflect their experiences in Germany with 117 cases over eight years. 8 These categories reasonably reflect the forms ofBVD manifested in North America as well:

(1) peracute fibrinohemorrhagic enteritis (in calves three to four months old), (2) acute respiratory or pneumoenteritis syndrome (in calves over three months old; in the United States, often one to three weeks old), (3) subclinical form (all age groups), (4) acute, subacute and chronic mucosal disease (in calves from six months to two years of age), (5) abortion, premature birth, stillbirth, congenital anomalies, and weak neonatal calves (in pregnant cows), and (6) acute catarrhal enteritis (mostly in cattle under two years of age). These categories would be representative of the forms of BVD we have encountered, but with less confinement to specific age categories for some. For example, peracute hemorrhagic enteritis, which they indicate as most common in calves three to four months of age, has been seen fairly frequently by us in adult heifers and cows just after parturition.

Recent interest in bovine embryo transplantation brings up another potential hazard of BVDV. A large percentage of commercial lots of fetal bovine serum, which is used as part of the fluid medium for bovine embryos, contains BVDV, usually noncytopathic strains. Bovine virus diarrhea virus has been demonstrated to be lethal for bovine embryos and hence may be responsible for a significant reduction in successful embryo transplants. Obviously, procedures that will inactivate BVDV in fetal bovine serum, such as gamma irradiation (cobalt or othe r source), should therefore be used b efore any lots of fetal bovine serum are used in embryo transplantation media.

Differentiation of BVD from other diseases causing abortion, erosions of the alimentary tract, diarrhea, and respiratory distress is difficult. Bovine viral diarrhea must be differentiated from rinderpest, malignant catarrhal fever, blue tongue, vesicular diseases, salmonellosis, coccidiosis, infectious bovine rhinotracheitis, and papular and ulcerative stomatitis. The severe mucosal disease form of BVD with alimentary tract erosions, bloody diarrhea, dehydration, and peracute to acute death occurs relatively infrequently in an outbreak. Differentiation from other diseases can to some extent therefore be based on the clinical history, morbidity, and mortality in a herd, and pathologic lesions. Definitive diagnosis, however, requires laboratory procedures such as virus isolation, demonstration of viral antigens in tissue sections by immunofluorescence, and demonstration of rising antibody titers between acute and convalescent serum samples. Serologic methods for assaying serum antibodies include virus neutralization, complement fixation, enzyme-linked immunoabsorbent assay (ELISA), immunodiffusion precipitation, and fluorescence inhibition.

Submission of specimens for laboratory examination for any viral diseases requires special considerations: (1) selecting the appropriate tissues and specimens, (2) collecting and handling the specimens as aseptically as possible to prevent extraneous microorganisms from contaminating the specimens, (3) keeping specimens chilled to minimize growth of possible extraneous contaminants, and (4) getting the specimens to the laboratory as quickly as possible. Blood samples for serology should have the serum separated. When this is not possible, the clotted whole blood must not be frozen and must be sent as quickly as possible.

In the case ofBVD, appropriate specimens from living animals for submission to the laboratory include acute and convalescent serum (the latter taken two to four weeks after the acute sample); swabs of nasal secretions in Stewart's transport medium or in phosphate buffered saline containing 10 per cent glycerol, gentamicin (100 p,g/ml) and amphotericin B (50 p,g/ml); fecal swab in similar transport medium as for nasal swab; and heparinized unclotted blood. Tissues suitable for attempted isolation of the virus post mortem include tonsil, spleen, kidney, liver, mesenteric lymph node, lung, and a section of ileum containing Peyer's patches (tied-off and unopened) .

The demonstration of an antibody titer increase fourfold or greater between acute and convalescent serum samples is diagnostic. A single serum sample from several animals in a herd in which BVD vaccines have never been used provides evidence that BVD infection has been present in that herd. It also alerts one to the possibility that BVD infection may still be likely in the herd, as latent persistent infection is becoming a recognized phenomenon with BVD. 406 WERNER P. HEUSCHELE Animals with chronic BVD infection have been found in many instances to have no demonstrable serum antibodies to BVD. In such cases it has usually been possible to isolate or demonstrate BVD virus from leukocytes in the buffy coat, from feces, or from nasal secretions.

Infection and lesions of the alimentary tract resulting in profuse diarrhea and dehydration have generally been considered the principal pathogenetic basis for severe illness and deaths associated with BVD. More recent studies suggest that the effect of BVD infection on the immune system and on nonspecific cellular defense mechanisms may be the more important pathogenetic basis for disease that results. Impaired function of phagocytic cells (both macrophages and neutrophils) and of B-Iymphocytes and T-Iymphocytes has been well documented. Animals infected with BVDV are thus more susceptible to and suffer more severe pathogenetic effects from other infectious agents that may concurrently be present, such as: Pasteurella spp., coronavirus, adenoviruses, and toxigenic strains of Escherichia coli.

Shortly after the first modified live virus (MLV) vaccines against BVD were developed and used, many episodes of postvaccinal mucosal disease were reported, most usually in feedlot cattle that had been vaccinated upon arrival at the feedlot. Several workers have reviewed this problem of BVD vaccine-associated mucosal disease and presented the following possible explanations for this phenomenon: (1) vaccines were contaminated with virulent field strains of BVDV; (2) the vaccine strain of BVDV used were insufficiently attenuated, especially for use in highly stressed cattle; (3) cattle were already infected with BVDV and were in incubative stage at the time of vaccination; and (4) cattle that developed postvaccinal mucosal disease had preexisting immunodeficiency, possibly genetic in nature. Any or all of these explanations are plausible and may have been applicable singly or in combination in different episodes.

Improvements in vaccines and quality assurance standards have reduced some of the hazards of postvaccinal problems with BVD vaccines. However there is still a potential hazard in feedlot cattle that have just been weaned, moved through one or more sale barns, transported, crowded, dehydrated, or traumatized by castration, dehorning, and rough handling. These highly stressed animals are hardly ideal candidates for modified live virus vaccine or for any vaccine. There is ample evidence that administering various vaccines and performing the various other usual necessary procedures on beef calves before weaning, or several weeks before shipment from the farm of origin, result in far less disease morbidity, mortality, and production loss.

The use of BVD vaccines in dairy cattle or beef cow/calf units involves an entirely different set of circumstances than are associated with feedlot calves. One must be particularly concerned that any vaccines used in pregnant cows, or in other animals in contact with pregnant cows, are safe for and will not cause adverse effects upon the fetus (death, anomalies, abortion, stillbirth). Current modified live virus BVD vaccines are not approved for use in pregnant cows because of these risks . There are stituations, however, where the author and others have found a porcine cell line origin, modified live virus, NADL strain, BVD vaccine to be safe when used in pregnant dairy cows during the last trimester of gestation, that is, during the dry period. The indication for such use of this vaccine has been a persisting herd problem of weakness and pneumoenteritis with high mortality of neonatal calves involving BVDV and other complicating agents. A licensed vaccine containing the Singer strain of BVDV has been used in a similar way by many veterinarians . Results of such use, i.e., vaccinating pregnant cows and heifers with these BVD vaccines at seven to eight months' gestation, have been very gratifying. In most instances, there has followed a dramatic reduction in neonatal calf morbidity and mortality.

The question of duration of immunity following BVD vaccination or recovery from clinical disease remains controversial. It is believed by some that immunity to BVD is long, from three to five or more years. In the past several years, however, I have encountered several episodes of BVD in cattle vaccinated within one year, but involving a strain of BVD with significant antigenic variance from the vaccine strain.

Several workers have reported an antigenic variation among BVDV strains, reflected in significant differences in virus-neutralizing antibody titers, depending on whether strain-specific antisera were tested against homologous or heterologous BVDV strains . In crossprotection studies in calves, all strains appeared to cross-protect against challenge of immunity done 30 to 50 days after immunization. Longer term cross-protective immunity studies have not, however, been done. It is our belief, based on field experience, that homologous strain BVDV immunity is probably of relatively long duration but that heterologous strain immunity wanes by six months to one year. We therefore advocate annual vaccination of dairy cattle, during the open period, about two to three weeks after pa rturition. As indicated earlier, in herds where BVD has been identified as a significant disease problem in young calves and recently freshened cows and heifers, vaccination during the last trimester of pregnancy is recommended.

Vaccination of young calves has generally been considered ineffective owing to interference of passive colostral antibodies with an active immune response. The situation is not, however, black and white. The presence of maternal BVD antibodies in young calves does not totally block a primary active immune response to BVD vaccination. Evide nce from several studies suggests that an active immune response will occur under such circumstances, resulting in establishment of immunologic memory. The magnitude of the active immune response in this case appears to be inversely proportional to the titer of passive antibodies present. Therefore, in areas where BVD is endemic, BVD vaccination of calves two to four weeks old has been of value in reducing calf morbidity due to BVDV. Repeat vaccination four to eight months later and then annually is recommended when calfhood BVD vaccination is done.

In conclusion, BVD is considered a major cause of disease of young and adult cattle, ofte n reflected as severe respiratory, enteric, or other infection due to secondary agents that are enhanced in their pathogenicity by the suppressive effects of BVDV on cellular and immune defense mechanisms. A herd health program for dairy cattle should therefore include annual vaccination agains BVD, preferably during the open period. In herds with proven BVD in young calves and postparturient cows and heifers, vaccination of pregnant cows and heifers during the last trimester of pregnancy has been found to be safe and efficacious in reducing BVDV-related morbidity. In this latter situation, combination modified live virus intramuscular vaccines containing IBR and other agents besides BVDV should not be used, since intramuscular IBR modified live virus vaccine strains are abortigenic.

Infectious bovine rhinotracheitis (IBR) was first described in the western United States in feedlot cattle in 1955. An excellent review and update of IBR has been provided in 1977 by KahrsY It is seen most frequently as a respiratory disease characterized by rhinitis, conjunctivitis, tracheitis, and fever. Some strains have a high tropism for the genital tract and are responsible for infectious pustular vulvovaginitis in cows and heifers and balanoposthitis in bulls. Infection of susceptible pregnant cattle with IBR virus frequently results in abortion. Episodes of encephalitis due to IBR virus in calves have also been infrequently reported, and IBR virus has been isolated from the intestines of calves with enteritis and diarrhea on a few occasions.

Etiology IBR-IPV virus is classified as a member of the family Herpesviridae-that is, it is a herpesvirus. While there is some evidence of minor antigenic variation among strains ofIBR-IPV virus, the general evidence indicates that all strains belong to a single serotype. Being a herpesvirus, IBR virus has a proven predilection for establishing latent infections that may recrudesce upon stress.

The infectious bovine rhinotracheitis virus is considered ubiquitous in the United States and elsewhere in the world. The fact that it frequently occurs as a latent infection makes the probability of eventual exposure to IBR very high for cattle in the United States. Infection usually is transmitted by the respiratory route, but nose-to-genital contact and venereal transmission are associated with the genital (IPV) form. Abortions due to IBR virus are usually associated with infection via the respiratory tract with hematogenous spread of virus to the uterus, placenta, and fetus.

Genital infections with IBR virus have not usually been associated with abortion but may be responsible for reduced breeding performance.

Infectious bovine rhinotracheitis occurs in all breeds, sexes, and ages of cattle, but fatality rates are highest in young calves, especially neonates. Highly stressed feedlot calves tend to have higher rates of attack, more severe disease, and higher fatality rates than do dairy cattle or range cattle.

The incubation period of the genital and respiratory forms of IBR infection varies from two to six days. Abortions due to IBR virus may occur eight to 90 days following an apparent or inapparent respiratory tract infection.

To some extent clinical signs and lesions are helpful in the diagnosis of IBR. However, because differential diagnosis must also consider other diseases causing erosions in the nasal mucosa, respiratory signs, and abortion-such as BVD, blue tongue, malignant catarrhal fever, and vesicular diseases-laboratory confirmation by virus isolation or serology is essential to obtain a definitive diagnosis. Nasal swabs in transport medium are most valuable for virus isolation from acute respiratory cases, whereas vaginal or preputial swabs are appropriate for genital infections . In cases of abortion, the entire fetus and placenta should be submitted. Serologic diagnosis is based on demonstration of a rising titer between acute and convalescent sera. As previously mentioned, proper handling and prompt submission of specimens are essential.

Spread ofIBR takes place readily by the aerosol-respiratory route, contact, and fomites. Separation and isolation of clinically affected animals and hygienic measures aid in reducing the spread of infection.

Prevention ofIBR is most effectively accomplished by immunization. Several types of vaccine are available and the choice of which to use depends largely on the circumstances of the group of animals to be vaccinated, the preference and judgment of the consulting veterinarian, and the logistics of administration.

Modified Live Virus-Intramuscular. Vaccines in this category have the advantage of ease of administration and convenience for combination with other immunizing agents such as BVDV and leptospiral bacterins. Their efficacy in preventing IBR respiratory disease and abortion has been well documented. They have the disadvantage of being less attenuated than strains used in intranasal IBR vaccines, are abortigenic in susceptible pregnant cows, and hence are contraindicated for use in pregnant cows or in calves in close contact with pregnant cows. Intramuscular IBR vaccines induce satisfactory systemic immune responses but do not generally stimulate local immunity in the respiratory tract as do intranasal vaccines. Recent evidence indicates that they will confer protection as early as do intranasal vaccines, that is, within 48 hours after vaccination.

Modified Live Virus-Intranasal. Intranasal modified live virus IBR vaccines were first licensed in 1969. They have the advantage over intramuscular vaccines in that they may be safely used in pregnant cows at any stage of gestation. They also rapidly induce interferon in nasal secretions, which confers early protection (within 40 hours after vaccination) against IBR, bovine rhinovirus, and possibly other bovine viruses, directly within the upper respiratory tract. Local secretory immunity in the respiratory tract, mediated largely by immunoglobulin A, is another important benefit conferred by intranasal modified live virus IBR vaccines not obtained with intramuscular modified live virus vaccines. The systemic immune response is similar to that obtained with intramuscular modified live virus vaccines, or recovery from natural infection.

Intranasal MLV IBR vaccines have been successfully used in young calves to induce a primary immune response, even in the presence of significant titers of passive colostrum-derived IBR serum antibodies. When used in this manner, the vaccines should be given after five days of age, when corticosteroid blood levels of the calves, which are elevated at birth, have returned to normal levels. Vaccination should be repeated at four to six months of age.

The only apparent disadvantage of intranasal modified live virus IBR vaccines is the greater difficulty of administration as compared with intramuscular vaccines. This is outweighed, however, by the several advantages described.

Killed Virus-Intramuscular. Killed or inactivated IBR vaccines, usually in combination with other antigens have been available for some time. While they have been shown to induce protection, they have the disadvantage of requiring repeated dosages, which occasionally cause severe anaphylactic reactions. The duration of immunity conferred is probably short (6 to 12 months), although this is controversial. They have the advantage of safety, other than possible anaphylaxis, for pregnant cows or calves, and there is no shedding or latent viral persistence.

Because the advantages of the intranasal IBR vaccines considerably outweigh their disadvantages, I prefer these IBR vaccines over intramuscular ones for use in herd health programs . All intranasal vaccines currently available contain both IBR and parainfluenza-3 (PI-3) modified live virus and thus provide optimal protection against both agents.

Beginning with the neonatal calf at five to seven days of age, administer one dose divided between both nostrils. Early calfhood vaccination has been of considerable value in reducing respiratory disease commonly encountered during the first month of life in dairy calves. Administration of BVD vaccine should follow at about two to three weeks of age. Repeat the IBRlPI-3 and BVD vaccination at six months of age and annually thereafter during the open period in cows.

Where it is desired to provide maximal colostrum-derived passive immunity to newborn calves, intranasal IBRlPI-3 and porcine cell origin NADL strain BVD vaccines may be safely given to cows during the dry period. When this practice is preferred to vaccination of neonatal calves, they should be given their first doses of IBRlPI-3 intranasal vaccine and BVD vaccine at four months of age, followed by repeat vaccination at one year and annually thereafter.

Parainfluenza-3 virus was first isolated from cattle in 1959, in association with cases of "shipping fever'" in feedlot cattle. While it was first considered the etiologic agent of "shipping fever" pneumonia, attempts to experimentally reproduce this syndrome with PI-3 virus alone were unsuccessful. It was soon found that shipping fever or bovine respiratory disease complex was the result of a combination of any of several viruses, including PI-3; bacteria, especially Pasteurella hemolytica; and predisposing stress factors such as weaning, castration, dehorning, shipment, and inclement weather.

Inapparent or subclinical infections ofPI-3 virus are common, but when environmental and management conditions are poor (such as through poor ventilation, crowding, heavy parasitism, and inadequate nutrition), PI-3 virus may become an important initiator of respiratory disease, especially in young dairy calves. It should be emphasized that PI-3 virus alone causes a mild infection of the respiratory tract, but one that is sufficiently damaging to the mucociliary and epithelial barrier to allow penetration by secondary invaders such as Pasteurella spp. or Mycoplasma spp.

Bovine parainfluenza-3 virus is a member of the family Paramyxoviridae, which is closely related but not identical to strains of human and ovine origin.

Infection with PI-3 virus is widespread among cattle throughout the world. Its clinical importance remains a matter of controversy. Under optimal environmental and management conditions it produces mild, usually subclinical infections. In situations of stress and poor environmental conditions especially poorly ventilated housing, and in association with other infectious agents, it undoubtedly contributes to development of calf pneumonia and so-called shipping fever, which is more aptly termed "the bovine respiratory disease complex."

As with IBR infections, diagnosis ofPI-3 infection can be made by virus isolation from respiratory secretions and serologically by demonstrating antibody titer elevations between acute and convalescent sera.

From the foregoing discussions it can be readily seen that good management and proper environment are important in minimizing potential adverse effects of PI-3 infection in cattle. Prophylactic immunization has value, as one seldom finds management and environment totally optimal in most intensive calf-rearing enterprises.

Parainfluenza-3 vaccines are almost always combined with other antigens, especially IBR virus, in currently available vaccines. Most evidence indicates that the quality of immunity to PI-3 conferred by intranasal vaccines is superior to that conferred by intramuscular vaccines, live or dead. The local immunity in the respiratory tract stimulated by intranasal vaccine is a definite advantage over solely systemic immunity provided by parenteral PI-3 vaccines. A schedule for use of combined IBRlPI-3 intranasal modified live virus vaccine has been presented in the foregoing section on IBR.

Several other viruses have been isolated from cattle in association with outbreaks of re spiratory disease. When these viruses have been used to experimentally infect susceptible calves, they have usually produced only mild clinical signs. Viruses included in this category, for which at present there are no available vaccines in the United States, are bovine rhinoviruses, bovine adenoviruses, bovine herpesvirus-type 4, bovine respiratory syncytial virus, and reoviruses I, II, and III. All of these viruses are apparently ubiquitous in the cattle population of the United States, based on serologic surveys. Many believe they are important components of the bovine respiratory disease complex, especially when associated with various stresS factors and combined with other infectious agents, such as other viruses, mycoplasmas, chlamydiae, and other bacteria. Undoubtedly mixed infections are more common than single agent infections, and it is these that are responsible for the larger proportion of respiratory and enteric disease problems in cattle, especially calves.

In addition to BVD viruses, other viruses associated in North America with enteritis, especially in calves, include bovine rotavirus, bovine coronavirus, and bovine parvovirus. Often severe diarrhea in calves associated with these viruses may also be associated with enterotoxigenic strains of Escherichia coli and/or bovine strains of Chlamydia psittaci.

While rotaviruses and coronaviruses have been strongly implicated in the etiology of neonatal bovine diarrhea, or calf scours, experimental reproduction of disease with these viruses has been difficult. They undoubtedly playa role in neonatal calf enteritis, but poor management may be the more important factor that provides the circumstances for these viruses to exert their fullest pathogenic potential. The mechanisms whereby bovine rotaviruses and coronaviruses produce enteritis and diarrhea in young calves have been well described elsewhere and will therefore not be discussed here.

There is a great deal of controversy over the best approach to the prevention of neonatal calf diarrhea associated with rotaviruses and coronaviruses. As with bovine respiratory diseases, it is likely that single agent infections are the exception rather than the rule. Particularly in situations of poor management, housing, and nutrition of baby calves, the situation is optimal for E. coli, rotaviruses, and coronaviruses to inflict their severest effect. Well-ventilated, dry, uncrowded housing, good sanitation, and adequate nutrition are important ingredients of good management to prevent both respiratory and enteric diseases. It is my opinion that late-term vaccination of pregnant cows with recently available E. coli, K-99 bacterins, and rotavirus/coronavirus combination vaccines, combined with a program assuring early and continuous feeding of colostrum from vaccinated cows to neonatal calves through one month of age, provides the best approach to prevention of calf enteritis. This, of course, assumes that the above other management factors are optimized. The more or less continuous presence of passive antibodies in the gut of young calves, provided by the feeding of colostrum, appears to be the most rational approach for this problem.

Administration of modified live virus rotavirus/coronavirus vaccines orally to the neonatal calf in principle appears to be sound as a means of inducing active local secretory immunity in the gut of the calf against these agents. But proponents of this approach to prophylaxis often overlook the fact that the calf is exposed to these agents plus E . coli and probably other agents with enteropathogenic potential within minutes of birth into a heavily contaminated environment. A vaccine virus would probably be too late to successfully compete with the virulent field viruses that are already present.

Another argument against the value of oral vaccine in the neonatal calf is the fact that many calves will have already ingested colostrum at the time of oral vaccination. The presence of passive antibodies in the gut would logically neutralize and interfere with the absorption of vaccine virus in the gut, thereby precluding development of the active local secretory immune response that is sought as the means of protecting the calf against enteric disease due to these viruses.

The provision of passive antibodies by colostrum on a continuous basis during the critical first 30 days of the life of the calf would, therefore, be a more suitable approach to prevention of calf enteritis.

Several viruses responsible for respiratory, generalized, reproductive, and enteric diseases have been discussed. The vaccination recommendations provided for those for which vaccines are currently available are the programs which in our experience have provided the best results, where good management practices also prevailed. In no case can vaccines be expected to provide adequate protection when there are flagrant violations of good management, which includes suitable dry, sanitary, well-ventilated shelter, and adequate nutrition.

Another aspect important to a herd health program to prevent viral diseases is the proper storage and handling of viral vaccines being used in a health program. Modified live virus vaccines are particularly vulnerable to loss of potency and effectiveness through mishandling and improper storage. Freeze-dried modified live virus vaccines must be stored at normal refrigerator temperatures (4°C, 40°F) until used. After freeze-dried modified live virus vaccines are rehydrated with the diluents provided they should be used within a few minutes, as viral titer will decline rapidly at ambient temperature, particularly if it is high.

Exposure of vaccines to sunlight, heat, or radiation for extended periods of time may significantly reduce the antigenicity and protective value in both live and killed virus vaccines. The use of antiseptics on the skin at the site of intended vaccine inoculation may also adversely affect the viral content of modified live virus vaccines. Although these factors may seem self-evident as contributory to the failure of vaccination programs, they are often overlooked and violated and must therefore be kept in mind.

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Maternal immunity to infectious bovine rhinotracheitis and bovine viral diarrhea viruses: Duration and effect on vaccination in young calves

The ruminant immune system

Colloquium on selected diarrheal diseases of the young: Part 2

Duration of active and colostrum derived passive antibodies to bovine viral diarrhea virus in calves

Hagan and Bruner's Infectious Diseases of Domestic Animals

Disease outbreak in calves caused by a mixed infection with infectious bovine rhinotracheitis virus and bovine virus diarrhoea virus

Diagnosis of bovine virus diarrhoea/mucosal disease (BVD) under consideration of the present epizootic situation

New perspectives on the epidem iology of bovine virus diarrhea-mucosal disease (BVD-MD)

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Infectious bovine rhinotracheitis: A review and update

Depression of bovine monocyte chemotactic responses by bovine viral diarrhea virus

Bovine viral diarrhea in the neonatal calf

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Detection of bacteremia in cattle inoculated with bovine viral diarrhea virus

Effects of bovine viral diarrhea infection on bovine polymorphonuclear leukocyte function

Isolation, characterization and pathogenicity studies of a bovine respiratory syncytial virus