BOVINE RESPIRATORY DISEASE

Bovine Respiratory Disease Complex: BVDV

Bovine Viral Diahrrea Virus

Introduction

Bovine viral diarrhea virus (BVDV) is a pathogen effecting cattle in almost every country in the world where these animals are raised (Radostits et al. 2007). The emergence of seemingly more virulent forms of the virus in the past few decades have made this a pathogen of increasing economic importance (Goens 2002).  The bovine viral diarrhea (BVD) disease complex is one of four diseases know as production limiting diseases in the Canadian dairy industry (Radostits etal. 2007) and is arguably one of the most economically important infectious diseases in the feedlot industry (Campbell 2004).  The virus’ high prevalence rate, resultant abortions, persistent infections, and manifestations, and untreatable nature make prevention and active management of BVD essential for cattle producers.  BVDV has been shown to infect a variety of hosts including sheep, goats, water buffalo, and wild ruminants, but cattle are the primary hosts and for that reason will be the only species discussed.

Etiology

BVDV is a member of the family Flaviviridae and genus Pestivirus, characterized by single sense stranded RNA viruses of two biotypes.  The rare cytopathic (CP) biotype will damage tissue cultures and the much more common non-cytopathic (NCP) will not.  The disease syndromes caused by the two biotypes differ mainly in the severity of disease that they cause upon infection. Both biotypes can cause disease in cattle, however, greater than 95% of BVDV infections, all of the persistent infections, and the more severe forms of the disease are caused by the non-cytopathic biotype (Kelling 2004).

The BVDV can be divided into two genotypes (BVDV-1 and BVDV-2) on the basis of antigenic and genetic differences, with each genotype containing both the CP and NCP forms.  Furthermore, both genotypes are divided into subtypes.  Both BVDV-1 and BVDV-2 have similar consequences if infection occurs prenatal but their effects vary with postnatal infection (Van den Hurk, 2000).  Severe cases of clinical disease are most commonly seen with the non-cytopathic BVDV-2 genotype (Kelling 2004).

 

Distribution, Prevalence and Transmision

BVDV occurs world wide with an estimated 60-80% of cattle over the age of 1 year having serum-neutralizing antibodies to the virus.  This number is attributable to both persistently infected animals and vaccination programs, with persistently infected (PI) cattle representing about 1-2% of all animals (Radostits et al 1997).  However this number can vary greatly depending on geographical location and vaccination programs.

Regardless of their prevalence, PI animals are typically the largest source of infection in any given herd (Radostits 2007) and represent a major challenge for the management of the BVDV and its associated diseases.  In close confinement housing operation a PI animal can infect up to 90% of the herd before it has reached 3-4 months of age (Houe 1999).  Despite the relatively low prevalence of persistently infected calves in randomly selected western Canadian (< 0.1) (Taylor et al. 1995) and American (4%)(Wittum et al. 2001) feedlots they remain a major source of the virus (Campbell 2004).  In general, the incidence of persistent infection in calves less than one year of age is 1-2% in most countries (Merk 2005).

BVDV can spread via direct or indirect contact and can be isolated in and is widely disseminated by nasal discharge, saliva, feces, semen, urine, tears and milk of persistently infected animals (Radostits 2007). Viremic PI animals are the major source of transmission of the BVDV and can remain clinically normal for years during which time they can transmit the disease through the aforementioned bodily fluids.  Transplacental transmission from dam to fetus is possible whether the dam is persistently or transiently infected.   Persistent infection in cattle can only be established via transplacental transmission in the first half of fetal life (Radostits 2007).  While primary infected animals (transiently viremic cattle) can be a source of the virus, transmission to naïve animals is slow, not as effective, and not possible via close contact (Radostits 2007).  Indirect transmission can occur via fomites, flies,  and aerosolization of the virus.  In general, young and unvaccinated cattle are the most likely to contract the virus.

Pathogenesis

As with any other disease the pathogenesis of the BVDV virus depends on the interaction between host, pathogen, and the environment.  There exists a wide range of clinical findings based on the host factors and the virulence of the particular form of BVDV involved.  In general, the BVDV complex can result in subclinical benign bovine viral diarrhea, fatal mucosal disease, peracute fatal diarrhea, immune suppression, thrombocytopenia and hemorrhagic disease, reproductive failure, and congenital abnormailities in calves (Radostits 2007).  For simplicity sake there will be no mention of environmental factors except to say that in intensive agricultural settings the health status of an animal is tied to its environment and for this reason sound housing and sanitation practices should be adhered to.  The clinical outcome of a BVDV infection is dependent upon host factors such as age of the animal at time in infection, age of fetus at time of transplacental infection, immune status (passive (colostrum) vs. actively (vaccination or previous exposure) derived), and the presence of stressors (Radostits 2007).   Pathogenesis is easily discussed in two categories of animals, immunocompentent non-pregnant cattle and immunocompetent pregnant cattle.

Immunocompetent non-pregnant cattle

Suclinical BVDV infections are by far the most common type of infection associated with BVDV.  It occurs in any class of cattle following the decline in maternal antibodies.  The infection rarely lasts more than a few days and is characterized by inappetence,  depression, mild diarrhea,  and transient leucopenia. 
Peracute BVD is a severe and highly fatal form of the disease caused by NCP BVDV-2, but it is much less common.  This form of the disease can result in thrombocytopenia (a decrease in the number of circulating platelets) and hemorrhagic syndrome, seen as hemorrhage from the sclera of the eyes, epistaxis (bleeding from the nose), and abnormal bleeding from injection sites.  The same form of the virus can cause meningoenchephalitis (inflammation of the brain and its protective lining), but so far only one such case has been reported (Radostits 2007)
Immunosuppression resulting from postnatal BVD infection and the subsequent potentiation of other diseases is an important issue when considering the pathogenesis of the BVDV.   Cattle with BVD have been shown to be more susceptible to infectious bovine rhinotracheitis, bovine respiratory disease,  and general enteritis.  BVDV functions as a potentiator for these other diseases by causing transient reductions in the number of circulating B and T lymphocytes (Radostits 2007).  Some modified live-BVDV vaccines have also been shown to elicit similar effects.
 
Immunocompetent pregnant cattle

The BVDV can cause fertilization failure, embryonic mortality, abortion, or the birth of persistently infected calves depending on the stage of gestation during which infection occurs.  If exposure occurs during the estrous cycle just prior to insemination a decrease in conception can occur due to a delay or reduction in ovulation (Radostits 2007).  Insemination of naïve cattle with BVDV positive semen can result in poor conception rates.  Infection between days 0-45 of gestation seems to have no effect on embryos.  Between 45-125 days of gestation infection of naïve animals can result in abortion, mummification, congenital defects, or the birth of persistently infected calves, a proportion of which will develop mucosal disease.  In general persistently infected calves will be ‘poor doers’.  Those that develop mucosal disease will do so because the NCP form of the virus with which they were infected undergoes a mutation to the CP form.  If infected between days 125-175 numerous congenital defects can occur.  Beyond day 175 of gestation the fetus is immunocompetent and the virus will likely be eliminated without having any effects.

 

Clinical Findings and Lesions

Subclinical infection is the predominant form of the disease featuring high morbidity but low mortality rates.  It is characterized by mild fever, mild diarrhea, leucopenia, and inappetence. This form of BVDV infection will often go undiagnosed because the signs are so mild and animals recover rapidly after a few days.
Acute mucosal disease can occur within BVDV positive herds in 5-25% of animals aged 6-24 months of age (Radostits 2007) with 45% morbidity and up to 100% mortality.  Infected animals are depressed, anorexic, drool profusely, have increased heart and respiration rates, may strain to defecate and the produce foul smelling watery diarrhea containing blood, mucous, and occasionally fibrinous tags.  Erosions or ulcers can be found in roughly 80% of cases within the oral cavity and on the muzzle of these animals and may progress to the point where the entire oral cavity appears grey and dead.   A pus-like nasal discharge associated with irritation of the nose is seen in most animals.   A small proportion of infected cattle may present with lameness.  Death due to dehydration typically occurs within 5-7days of the onset of signs.
Chronic mucosal disease can develop from the acute form of mucosal disease.  There will be transient appearance of diarrhea, inappetence, emaciation, bloat, hoof deformities, and erosive lesions of the oral cavity and skin.  Scabbing lesions of the skin in the genital and anal areas, as well as between the legs and around the dew claws can occur.  Failure of these lesions to heal is an important clinical finding for this disease.  Animals with chronic mucosal disease can survive for up to 18 months.
Peracute bovine viral diarrhea is a highly fatal disease reported as progressive outbreaks that can last for several weeks.  Animals suffer from severe depression, anorexia, high fever, profuse watery diarrhea, and a decrease or lack of milk production.   Abortion may also be common.  It can occur in all ages of cattle but mortality is highest in young animals, with death occurring a few days following the onset of symptoms.
Thrombocytopenia and hemorrhagic disease is characterized by bloody diarrhea, spotty or generalized hemorrhage  of visible mucosa and the eye, epistaxis(bleeding from the nose), and prolonged bleeding from injection or insect bite sites.   Cattle will also display fever, dehydration and rumen stasis.  Mortality is estimated to be 25%.
Reproductive consequences are seen as conception failure,  fetal abortion and mummification, premature births, still births, congenital defects, stunted weak calves, and the birth of persistently infected calves.   Fetal infection rates can reach as  high as 21% in beef herds (Radostits 2007).  PI calves are generally unthrifty, smaller in body size, and may have a curly hair coat.  Congenital defects typically include abnormalities of the head and its associated sensory structures.  Problems with mentation, gait, and general coordination are also common.

Necropsy findings
Acute mucosal disease and peracute BVD have similar presentation upon necropsy with the gross abnormalities being confined to the gastrointestinal tract.  Shallow erosions with little to no inflammation can be seen in the oral cavity, esophagus and various stomach compartments.  In the abomasum these can be accompanied by hemorrhages and edema.  In the small intestine patchy and diffuse congestion can occur but the more definitive lesions occur as 10-12cm long red-black ovals which represent damage to the Peyer’s patches.   The large intestine congestion takes on a ‘tiger stripe’ pattern following the normal folds of the internal surface of the colon.


Chronic mucosal disease can be distinguished from the above by the presence of elevated, yellow, friable(easily crumbled or pulverized) plaques, in the gastrointestinal tract, especially the tongue and the rumen.  Lesions of the Peyer’s patches may be more difficult to identify.

Diagnosis
BVD can be tentatively diagnosed from the history and clinical signs, but a definitive diagnosis may require laboratory support especially during outbreaks of mucosal disease or peracute bovine diarrhea which can appear similar to rinderpest and malignant catarrhal fever (Merk 2005).  Laboratories can confirm BVDV using PCR, immunohistochemistry, serology, virus isolation, and antibody ELISAs.  The testing strategy used and samples to be submitted will depend on the herd history, vaccination status, age of the animals, cost of the test, needs of the producer, and reason for doing the testing. 
The gold standard for diagnosing BVDV is virus isolation.  It can be attempted using nasal or ocular swabs, semen, intestinal tissues, spleen or most other tissues, and blood samples.  Blood samples are the best option in live animals.  The samples are used to inoculate cell cultures and in positive cultures the virus is then identified via immunoflourescence or immunoenzyme staining.

Treatment and Prevention

The most effective means of prevention and control of BVDV is the elimination of both PI individuals and the potential for the birth of PI calves (Radostits 2007).  To do this will require simultaneous implementation of sound vaccination, herd-monitoring, biosecurity and biocontainment programs.   As treatment infected animals is not a viable option (Radostits 2007), the control, prevention, and future eradication efforts for this disease must be implemented by the cow-calf industry (Campbell 2004) and by individual dairy barns (Brock 2004). 

BVDV biosecurity programs attempt to prevent introduction of the virus to a naïve herd and thus are the most important aspect of BVDV prevention and control.  Dr. Kenny Brock at Auburn University has initiated the Top 10 List to prevent BVD in a herd. It is as follows:

1.  Maintain a strict level of herd biosecurity.
2.  Purchase only open animals that are known to be BVD-negative before purchase.
3.  Isolate any new additions or animals re-entering the herd for a minimum of 30 days.
4.  Test any new additions for BVD, and vaccinate during the isolation period.
5.  Maintain good sanitation and routinely disinfect contaminated areas. Prevent          contamination from outside sources by disinfection.
6.  Prevent contact with neighboring cattle of unknown status.
7.  Protect pregnant animals from potential sources of exposure during the first trimester.
8.  Prevent mixing of animal groups immediately before breeding and during the first trimester.
9.  Conduct surveillance for BVD by performing necropsy on dead animals and collect blood samples on any calves that are poor-doers and calves that have respiratory disease.
10.  Vaccinate the cow herd yearly. Ensure that heifers are properly vaccinated at 6 months of age (two doses) and are booster vaccinated before breeding.
(University of Florida IFAS Extension)

Whether a farm/feedlot is free of the BVDV or has recovered from a BVDV infection/outbreak a strict biosecurity program should be maintained as recurrence is likely due to the endemic nature of the virus.  Ongoing biocontainment efforts, including vigilant vaccination programs, are essential for any herd with previous history of infection or any herd that imports animals or semen.

BVDV Biocontaiment strategies attempt to control already existing disease in a herd by minimizing the occurrence or severity of BVDV infection, or to completely eliminate the virus from a herd. The goals of BVDV biocontainment are to increase host immunity, remove PI cattle from the herd, and to prevent contact between infected and susceptible animals (Radostits 2007).  As with any other aspect of cattle management, herd monitoring is essential for the timely identification and response to potential sources of BVDV infections, the most pertinent being PI cattle.  Along with the culling of these animals, immunization programs to prevent further dissemination of the virus are needed.  Some basic vaccination principles outlined by the Dr. E.J. Richey of the  University of Florida follow:

1.  Initiate vaccination of calves after 4-6 months of age to avoid interference from maternal antibodies passed to the calf during colostral feeding. When using killed BVD vaccine, re-vaccination in 30-60 days will be required to stimulate an adequate level of protection. The BVD vaccinations should be completed in the calves at least 30 days before weaning.
2.  Properly vaccinate all unvaccinated heifers and cows before breeding to ensure protection for the fetus.
3.  Properly vaccinate all bulls before putting them out with the cows or heifers.
4.  Properly vaccinate all new additions before adding them to the herd.
5.  When using killed BVD vaccine, annual boosters are required to maintain an adequate resistance level when dealing with Type 1 BVD. If dealing with Type 2 BVD, vaccinate using a killed BVD vaccine containing Type 1 and Type 2 viruses or booster at three month intervals using different company products. Breeding stock should be booster vaccinated immediately before the breeding season to provide maximum protection to the fetus. Even if MLV-BVD vaccine was used as the initial vaccination agent, a booster vaccination using either MLV or killed BVD vaccine is recommended every few years. Remember, do not booster vaccinate pregnant cows with replicating BVD vaccine.
(University of Florida IFAS Extension)

The continued prevalence of the BVDV and seeming failure of current widespread vaccination efforts against BVDV may be attributable in part to the difficulty of vaccinating for all the various genotypes of the virus, but also to the mixing of cattle at market, during transport, and at the feedlot prior to and immediately following vaccination (Campbell 2004).  
A detailed discussion on the types of vaccines currently available to producers can be found at http://edis.ifas.ufl.edu/VM023.

References
Baker, JC.  (1995)  The clinical manifestations of bovine viral diarrhea infection.  Vet Clin North Am Food Anim Pract. 13(3):425-54.
Brook, K.V. (2004)  Strategies for the control and prevention of bovine viral diarrhea virus.  Vet Clin Food Anim. 20:171-180.
Campbell, J.R. (2004)  Effect of bovine diarrhea virus in the feedlot.  Vet. Clin. North. Am. Food Anim. Pract.  20(1):39-50.
Goens, D.S. (2002).  The evolution of bovine viral diarrhea: a review.  Can. Vet. J. 43(12): 946-954.
Houe, H. (1999) Epidemiological features and economical importance of bovine viral diarrhea virus (BVDV) infections.  Vet. Micro.  64:89-107.
Richey, E.J.  Bovine Viral Diarrhea.  University of Florida IFAS Extension.  Accessed on line at http://edis.ifas.ufl.edu/VM023
Kelling C.L. (2004). Evolution of Bovine Viral Diarrhea Virus Vaccines. Veterinary Clinics    Food Animal Practice. 20: 115-129. 
Merck Veterinary Manual.  Acessed on-line at http://www.merckvetmanual.com/mvm/index.jsp
Taylor, L.F., Van Donkersgoed, J., Dubovi, E.J, Harland, R.J, van der Hurk, J.V., Ribble, C.S, Janzen, E.D. (1995)  The prevalence of bovine viral diarrhea virus infection is a population of feedlot calves in western Canada.  Can. J. Vet. Res.  59:87-93.
Wittum, T.E., Grotelueschen, D.M., Brock, K.V., Kvasnicka, W.G., Floyd, J.G, Kelling, C.L.  (2001). Persistent bovine viral diarrhoea virus infection in US beef herds. Prev Vet Med.  49:83–94.
Van den Hurk, J.  (2000).  Health Management: Bovine Viral Diarrhea.  Accessed on line at http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/beef11736

Produced by Chase Wendorff, Tim Ritson-Bennett, Adam Schierman, Troy Gowan, Justin Rosing for WCVM class project