How is bovine virus diarrhea spread

In this time, the animal will be positive for virus antigen. In order to prevent misdiagnosing these animals as PIs, they can be re-tested twice after three to four weeks with an antigen ELISA the PCR stays positive for longer and both samples positive for viral antigen confirm a PI.

The main reservoir of infection is undoubtedly the persistently infected animal and, as such, the most critical part of the diagnosis and control program Brownlie, Persistently infected animals must be removed from the herd immediately Graham et al. For some time now special ear tags have been developed which take a small section of ear tissue into a small labeled container when applying the tags.

These tissue samples can then be tested for BVD antigen. The ear tissue test is not affected by colostrol antibodies and therefore can be done from birth. Main advantages are. Eradication alone leaves a herd vulnerable to BVD, and therefore vaccination should be considered to maintain the herd BVD-free if biosecurity failures are a possibility mainly due to neighboring cattle contact or buying in stock.

Vaccination does not modify the status of or eradicate PI animals. For optimal results, breeding animals should be vaccinated before the breeding season to ensure maximum protection is conferred for the first few months of gestation to prevent the creation of a PI Sexton, Vaccination to control and prevent BVD is now both possible and cost effective Brownlie et al.

However, vaccination can still mask underlying infection Brownlie, A new live vaccine contains type 1 and type 2 BVD antigen. BVD eradication leads to improved herd health and the ability to sell disease free stock, which may be important to some pedigree herds. There is no treatment for subclinical BVD or acute mucosal disease. Support therapy in the form of fluids and anti-inflammatory agents can be used for acutely infected animals.

There are no specific welfare considerations with regard to BVD, although control of disease should be considered as it impacts significantly on the health of the herd. Virus cell-to-cell transmission allows the virus to overcome barriers to free virus dissemination, such as antibodies or epithelial barriers. Here we show that BVDV exploits cell-cell contacts to propagate infection in a process that is resistant to antibody neutralization.

Our results provide new insights into the mechanisms underlying the pathogenesis of BVDV infection and can aid in the design of effective control strategies. So, even the best vaccination program is likely to fail in an environment with poor nutrition, stress overcrowding and without an isolation facility. Maintain a closed herd, if possible. Since BVD outbreaks are commonly associated with new animals entering the herd, maintaining a closed herd is the ideal approach to keep the virus out.

Unfortunately, this may not be possible. Today, many farms purchase all replacements, while others temporarily send heifers to contract raisers. And these raisers typically commingle heifers from many farms before they are returned home to the milking herd. Vaccinate with BVD vaccine two weeks prior to moving. When deciding which vaccine to use, consider the vaccine program of the herd of origin. If that herd is well vaccinated, one dose of killed BVD vaccine should be sufficient.

If it is not well vaccinated, or if the history is unknown, two doses of killed 2 weeks apart or one dose of modified live vaccine non pregnant animals only are be indicated. Since animals can only become carriers prior to birth, previously tested cattle do not need to be retested.

Do not allow carriers on the farm. Calves born to test negative pregnant replacements must also be tested. Move animals with your own truck, directly from farm to farm. Do not purchase them through an auction market or move them with unknown cattle due to the high risk of exposure to BVDV under these conditions. Isolate all new arrivals purchased or your own heifers for two to three weeks in a well-ventilated area, away from the rest of the herd, yet close enough to permit frequent checking for any signs of disease.

If any diseases are noted, remove the affected animals immediately, and call the veterinarian to establish a diagnosis and treatment regime. Continual exposure to BVDV from one or more persistently infected carriers may cause infection in vaccinated animals, so the herd may experience sporadic abortions and infertility.

Since exposure to BVDV from any source can result in a cow giving birth to a BVDV carrier, one can never be sure an animal is not a carrier until it tests negative. Therefore, it is recommended that all purchased cattle be tested before entering the herd, and all newborn calves be tested. Together, these veterinarians discuss with farm owners and managers the important aspects of BVD prevention.

In addition, they tour the farm to establish the level of risk for BVD, they develop a farm management plan to control and prevent the disease, and they establish a system to monitor the success of the program.

All participants will be recognized and identified by a certificate stating the level at which their herd is enrolled in the NYS Cattle Health Assurance Program. This certificate will serve as evidence to cattle buyers and consumers that animals, milk, and meat from this herd have a value-added component in the form of reduced risk for both cattle diseases and foodborne pathogens.

Phone: Fax: Email: diagcenter cornell. CoVs are the only known RNA viruses that evolved a mechanism for proofreading their genomes via activities of non-structural proteins 10—14 allowing them to escape lethal error catastrophe events 14 and to generate and maintain highly diverse and viable quasispecies pools. Bovine coronavirus BCoV is a pneumoenteric virus that belongs to the species Betacoronavirus 1 subgenus Embecovirus of the Betacoronavirus genus along with wild ruminant CoVs, porcine hemagglutinating encephalomyelitis virus, equine coronavirus, HCoV-OC43, HECoV, and canine respiratory coronavirus 1.

Due to their close antigenic and genetic relatedness, Betacoronavirus 1 species members appear to be host-range variants originating from the same parental virus as a result of multiple genetic recombination and interspecies transmission events 17 , 19 — Bovine CoV particles are enveloped and pleomorphic, 65— nm in diameter The latter consists of an S1 subunit that contains the dominant neutralizing epitopes and an S2 subunit that mediates viral membrane fusion.

The HE acts as a receptor-destroying enzyme esterase to reverse hemagglutination. The N protein lies internal to the virus envelope and is associated with the viral RNA, the M spans the viral envelope while the S and HE project from the envelope. Additionally, 16 non-structural proteins nsp have been identified in betacoronaviruses 23 , Like other enveloped viruses, BCoVs are sensitive to detergents and lipid solvents including ether, chloroform and are easily inactivated by most conventional disinfectants, formalin, and heat.

Bovine coronaviruses cause respiratory and enteric diseases in cattle and other ruminants but can be identified in the respiratory and intestinal tracts of healthy cattle 22 , 25 — BCoV is shed in feces and nasal secretions and is associated with 3 distinct clinical syndromes in cattle 27 : neonatal calf diarrhea [ N CD ] 22 , 28 , winter dysentery WD characterized by hemorrhagic diarrhea in adults 25 , 28 — 30 and respiratory infections in cattle of different ages commonly as a part of the bovine respiratory disease complex BRDC or shipping fever of feedlot cattle 22 , 26 , 31 , 32 Figure 1.

BRDC causes major economic losses to the beef and dairy cattle industries worldwide due to substantial morbidity and mortality. In North America, this complex represents the leading cause of morbidity and mortality in 6—month-old beef cattle after entry into feedlots Coronavirus image placed above animal represents potential carrier status. Rectangle boxes list unknown host and vaccine-associated factors that can result in suboptimal vaccine performance or lack of protection of cattle of different ages.

However, genotyping identified distinct sublineages and clusters based on the year and place of isolation but not on the disease type 19 , 35 — 38 Figure 2. Similarly, 2 to 3 subtypes of BCoV are recognized based on their biologic and antigenic characteristics identified in virus neutralization and ELISA [with monoclonal antibodies MAbs ] tests without association with the different disease types 22 , 26 — While some studies identified mutations potentially associated with respiratory and enteric phenotypes 40 — 42 ; these findings have not been consistently confirmed by other groups in observational or experimental studies Further, despite numerous genetic differences point mutations and deletions detected in the spike S gene between enteric and respiratory isolates or between BCoV and bovine-like CoVs from wild ruminants and humans, in vivo and in vitro experiments demonstrated high levels of cross-protection and cross-neutralization between such isolates 36 , 43 — Thus, no genetic or antigenic markers associated with the different disease manifestations have been identified, suggesting that the latter may result from the complex interplay between pathogens CoV and other viruses or bacteria , host and environmental factors.

Phylogenetic analysis of complete genomes of enteric and respiratory BCoVs and bovine-like CoVs from wild ruminants. The evolutionary history was inferred by using the Maximum Likelihood method and General Time Reversible model.

The percentage of trees in which the associated taxa clustered together is shown next to the branches. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. This analysis involved 53 nucleotide sequences. Black triangle markers are used for bovine-like CoVs isolated from wild ruminants, and black round markers are used to mark respiratory BCoVs. The collapsed branch includes a cluster of recent BCoV strains from Japan BCoV attachment is blocked by acetylesterase or neuraminidase treatment and can be restored by resialylation.

It is further hypothesized that after the initial binding to sialic acid SA -containing receptors, the BCoV S protein may interact with a specific cellular receptor that leads to a conformational change and the viral-cell membrane fusion The receptor-binding lectin and receptor-destroying esterase domains of the HE protein also play important roles for viral entry 55 ; although, these interactions may be weaker than for the S protein because HE is a less efficient hemagglutinin.

Additionally, heparan sulfate was identified as an alternative attachment factor, but this may be related to the cell culture adaptation, not affecting the in vivo infection and pathogenesis Specifically, studies indicate that blood group A individuals are at higher risk of infection suggesting that HBGAs may serve as additional cellular receptors. Overall, the complex interactions between BCoVs, their cellular receptors and mucosal microbiota need to be comprehensively evaluated to improve our understanding of BCoV epidemiology, pathogenesis and interspecies transmission.

Bovine coronavirus is widespread in cattle of all ages, resulting in economic losses to the beef and dairy industry throughout the world. Moreover, BCoVs are commonly identified in the respiratory and intestinal tracts of healthy and diseased cattle Recent evidence suggests that BCoV can persist in colostrum-deprived calves or colostrum-fed calves with repeated nasal shedding 59 and detectable BCoV antibodies for up to 3 years suggesting that active immune response does not always result in viral clearance After its accidental discovery in by Mebus et al.

The virus plays a major role in the development of CD during the first 3 weeks of life in both dairy and beef cattle herds 27 , The disease results from the virus infecting both the small and large intestines, destroying villi and leading to severe, sometimes bloody, diarrhea and high mortality 65 — Virus replication initially occurs in different sections of the small intestine subsequently spreading throughout the large intestine and causing a malabsorptive diarrhea.

Stunted and fused small intestinal villi as well as atrophied colonic ridges are observed during pathological examination 65 , 66 , The compensatory crypt hyperplasia and increased fluid secretion further exacerbates diarrhea The loss of the mature IECs capable of absorption and digestive enzyme secretion greatly diminishes the absorptive, metabolic and secretory capacity of the intestinal tract 22 , Continual feeding often provides more nutrients than the damaged small intestinal epithelium can absorb This in turn leads to undigested nutrient fermentation in the large intestine, increased fluid accumulation, bacterial overgrowth and overproduction of organic acids, aggravating diarrhea 69 , Altogether, it leads to dehydration, metabolic acidosis and electrolyte imbalance due to sodium, chloride, potassium, and bicarbonate loss While these pathological changes and the ensuing disease are most severe in younger animals, BCoV infection also contributes to winter dysentery WD development in adult dairy cattle that causes a dramatic decrease in milk production and significant economic losses 25 , 27 , BCoV causes enteritis in both dairy and beef herds, with most cases occurring within the first 30 days of life 22 , 61 , 64 , CD may occur as early as 24 h of age in colostrum-deprived calves and as late as 5 months of age 59 , 68 , Thus, calves born to BCoV-positive cows have a significantly higher risk of developing diarrhea due to periparturient exposure to the contaminated perineum, teats, and the calving area It was confirmed that it can infect and cause diarrhea in gnotobiotic calves as well as induce complete cross-protective immunity against the virulent BCoV-DB2 enteric CD strain Based on complete genome analysis, it is hypothesized that porcine hemagglutinating encephalomyelitis virus and HCoV-OC43 have evolved from ancestral BCoV strains at some point in the past Enteric BCoVs bovine-like CoVs can also infect dogs experimentally and various domestic and wild ruminant species naturally and experimentally , causing clinical 82 or subclinical infections and seroconversion 83 , These data raise questions of whether dogs or wild ruminants could also be a reservoir for bovine-like CoVs transmissible to cattle, or conversely, if cattle can transmit CoVs to dogs, other ruminant species and humans.

Overall, the existing evidence indicates that BCoVs are associated with serious and economically significant disease. In Thomas et al. Subsequently, numerous investigators have confirmed that enteric and respiratory BCoVs are members of the same quasispecies 86 , despite genotypic and antigenic differences between individual isolates Since , the role of respiratory BCoV in BRDC development and reduced growth performance in feedlot cattle has been increasingly recognized 26 , 27 , 31 , 87 — Currently, respiratory tract infections in growing and feedlot calves are frequently attributed to BCoV 26 , 27 , 91 , 92 and can manifest as mild respiratory disease coughing, rhinitis or pneumonia in 2—6-month-old calves 26 , In another study, testing cattle 3-day pre-arrival demonstrated that nasal shedding consistently preceded fecal shedding Fifty-eight to ninety-five percent of feedlot cattle seroconverted to BCoV by 3 weeks after arrival 87 , 90 , 94 , The widespread distribution of BCoV could be explained by two main factors: 1 shedding of high titers of the virus from respiratory and intestinal tracts 59 , 92 , and 2 existence of asymptomatic carrier animals within most herds.

These carrier animals shed the virus in nasal secretions and feces and serve as a source of infection to neonates and other susceptible animals on the farm 59 , BCoV seroprevalence studies that surveyed Norwegian dairy herds have demonstrated that calves in BCoV-seropositive herds had an increased risk of respiratory disease development compared with BCoV-seronegative herds In two subsequent studies, calves shedding respiratory BCoV nasally were 2.

Further, in 3 of 4 outbreaks in Italy, the classic signs of BRDC dyspnea, fever, respiratory distress were evident in 2—3-month-old calves positive for BCoV and negative for other respiratory viral pathogens, while presence of common bacterial pathogens of cattle Staphylococcus spp. Despite this abundant circumstantial evidence derived from epidemiological studies and routine diagnostic testing for respiratory pathogens, the role of BCoV in the bovine respiratory disease complex BRDC has been debated for several decades This is because attempts to experimentally reproduce clinical respiratory disease are often unsuccessful 45 , — Table 1.

Of interest one out of the 4 studies that failed to reproduce clinical disease Table 1 reported somewhat extensive pathological changes in the respiratory tract of the colostrum-deprived calves inoculated with KWD3 strain Table 1. In two studies, investigators were able to reproduce some features of respiratory disease of variable severity Table 1 78 , , In the first one, 7 colostrum-deprived or colostrum-fed calves received tracheal-organ culture supernatant containing BCoV from a field case and developed cough, nasal discharge, and diarrhea with a few scattered areas of atelectasis observed in lungs of 3 calves at post-mortem Table 1.

The consensus opinion is that the respiratory disease and pathology may vary with BCoV strain, animal age, co-infections with other pathogens from BRDC complex , weather and additional environmental stress factors Table 2 26 , The list of other viral and bacterial pathogens identified in association with BRDC is rather extensive and includes: parainfluenza virus, type 3, bovine respiratory syncytial virus, adenovirus, enterovirus, reovirus, influenza D virus, bovine viral diarrhea virus, bovine herpesvirus 1 and 4, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis , and Trueperella pyogenes Multiagent experiments evaluated interactions between the respiratory pathogens and stress and emphasized their synergistic effects in the BRDC, but no such experiments have been reported for BCoV 32 , , A recent study has concurrently identified BCoV, H.

The multifactorial nature of BRDC makes treating it extremely challenging. For example, antibiotic treatment of animals with BRDC may lead to massive release of bacterial lipopolysaccharides LPS inducing proinflammatory cytokine response and further enhancing lung damage 27 , while treatment with corticosteroids can reduce the numbers of CD4 and CD8 T cells and certain cytokine levels compromising protective immunity and exacerbating disease , In the last several decades, numerous CoV strains sharing extensive biologic, antigenic and genetic similarities with BCoV named therefore bovine-like CoVs have been identified in the feces, intestinal contents or respiratory secretions of a diverse group of domestic and wild captive or free-range ruminant species Table 3.

Experimental inoculation of gnotobiotic Gn or colostrum-deprived calves demonstrated that many of the bovine-like CoVs were capable of efficient replication in these calves, produced enteric disease and generated cross-protective immune responses 48 , Additionally, 6.

Similar to the lack of genetic markers for discriminating between enteric and respiratory BCoVs, no reliable genetic markers were identified to distinguish between BCoVs and ruminant bovine-like CoVs Finally, no consistent changes were observed in the genomes of bovine-like CoVs after passage in gnotobiotic calves.

These data suggest that wild ruminants may represent a natural reservoir for bovine-like CoVs and transmit them to cattle or vice versa; these BCoVs represent a single host-range CoV species Such interspecies infections may result in generation of more genetically divergent, potentially recombinant strains that escape immune responses and could potentially spread to other species including humans based on an historical precedent Of interest, while bovine-like CoVs are frequently detected in diarrheic or healthy wild ruminants, there are no reports of occurrence of CoV-related respiratory disease outbreaks in the wild ruminants.

This once again emphasizes the multifactorial nature of BRDC in cattle and suggests that its development is likely related to existing herd management practices including crowded housing, transportation, constant influx of new animals, production-associated stresses in cows, etc.

An enteropathogenic BCoV strain caused a subclinical infection and seroconversion in experimentally infected dogs A recent report demonstrated that the HECoV strain infects upper respiratory and intestinal tracts causing diarrhea and intestinal lesions and conferring complete cross-protection against the virulent BCoV DB2 strain in gnotobiotic calves Finally, while the most common ancestor has not been identified, it is assumed that HCoV-OC43 has emerged in the human population at the end of the 19th century likely originating form a BCoV ancestral strain via recombination events Thus, detailed investigation of the endemic and emerging BCoV strains in the context of the host glycobiology is needed to identify and control potential pre-pandemic variants.

Pneumoenteric BCoVs replicate in the upper respiratory and the intestinal tracts and are detected in nasal secretions and feces, with nasal often preceding fecal shedding 27 , 90 , 95 , , , BCoV has also been detected or isolated from lung in animals with respiratory disease The complete list of post-mortem diagnostic samples from animals with suspected respiratory or enteric BCoV disease includes tissues from the respiratory tract e.

For live animals, nasal secretions collected with sterile polyester swabs and feces collected in sterile fecal cups should be chilled and transported to the diagnostic lab 95 , From live calves with acute respiratory disease, tracheobronchial lavage fluids that were previously shown to be positive for BCoV antigen by ELISA can be aspirated The acute transient nature of enteric BCoV infections in younger calves and seronegative cattle necessitates sample collection at disease onset or shortly thereafter.

However, persistent or long-term intermittent shedding has been reported in recovered or healthy cattle, respectively 59 , 60 , Due to the stress of shipping and comingling of animals from different sources, the peak of BCoV nasal or fecal shedding associated with BRDC infections occurs within 1 week after arrival to the feedlot 89 — 91 , Detection of BCoV in nasal secretions or feces can be done using immune electron microscopy, which has the advantage of detecting other viruses, but its sensitivity is relatively low 59 , For fecal samples, internal controls or additional sample dilution may be needed to detect interference by PCR inhibitors Because BCoV antibodies are widespread in cattle, paired acute and convalescent serum samples are needed for serologic diagnosis of BCoV infections The correlates of immune protection against BCoV infections remain poorly defined.

In multiple studies the BCoV-binding, neutralizing and HI antibody levels in serum of naturally infected calves or cattle on arrival in feedlots were correlated with protection against enteric or respiratory disease including pneumonia , or BCoV shedding 27 , 91 , 94 , 95 , 98 , — Inoculation of gnotobiotic or colostrum-deprived calves with CD, WD, or respiratory BCoV strains induced complete protection against diarrhea following challenge with a CD strain 43 , However, whether the serum antibodies themselves confer protection against BCoV or they only reflect previous BCoV exposure is uncertain and requires further investigation.