Bovine viral diarrhoea

What it is

Bovine viral diarrhoea (BVD) is caused by bovine viral diarrhoea virus (BVDV), a Pestivirus of the family Flaviviridae with two main species, BVDV-1 and BVDV-2. Each has two biotypes according to their effect in cell culture: non-cytopathic, the one that usually circulates in the field, and cytopathic. The virus is transmitted by direct contact with secretions, transplacentally and, to a lesser extent, by semen, fomites and contaminated vaccines.

The outcome of infection depends on the immune status of the animal and, in the pregnant female, on the stage of gestation:

• Acute or transient infection in non-pregnant animals: often subclinical or mild, with fever, leukopenia and diarrhoea. It causes immunosuppression, which favours other infections, above all bovine respiratory disease. Some BVDV-2 strains cause a severe acute disease with thrombocytopenia and haemorrhages.
• Fetal infection: early in gestation it can cause embryonic death and return to oestrus; later, abortion, mummification or congenital malformations.
• Persistently infected (PI) calves: when a non-cytopathic virus infects the fetus before its immune system is competent, roughly between days 40 and 125 of gestation, the calf is born immunotolerant to the virus. It sheds large amounts of virus throughout its life, without producing antibodies against it, and is the main source of infection for the herd. Many grow poorly and die young, but others look normal. A PI female always produces PI calves.
• Mucosal disease: develops in PI animals, usually between 6 months and 2 years of age, when a cytopathic virus antigenically very similar to their own is added, often arising by mutation of the animal's own virus. It is almost always fatal.

It is not a zoonosis.

Who it affects

Cattle of any age and type. Reproductive losses affect non-immune pregnant females, mucosal disease affects young PI animals, and immunosuppression with respiratory disease mainly affects calves and feedlot groups. The risk of introducing the virus increases with buying animals (especially pregnant females, which may carry a PI fetus), attending shows and markets and contact with other herds at pasture. Other ruminants, such as sheep, goats and deer, can be infected.

Anatomy involved

• Small intestine: in mucosal disease there are erosions and ulcers of the mucosa and necrosis and haemorrhage of the Peyer's patches, especially in the ileum, visible from the serosa as elongated dark areas. They cause the profuse diarrhoea.
• Oesophagus: linear erosions of the oesophageal mucosa, together with those of the mouth, forestomachs and abomasum, are a characteristic lesion of mucosal disease.
• Uterus: the virus crosses the placenta and infects the embryo or fetus. Depending on timing it causes embryonic death, abortion, mummification, malformations or the birth of PI calves, weak calves or apparently healthy calves.
• Brain: fetal infection during development of the nervous system, around mid-gestation, causes cerebellar hypoplasia, hydranencephaly or hydrocephalus. Affected calves are born with ataxia, tremors and inability to stand; ocular defects such as cataracts and retinal atrophy are also common.

Clinical signs

• Acute infection: often inapparent; fever, depression, drop in milk yield, mild diarrhoea and, in calves, respiratory disease or diarrhoea caused by other pathogens. Severe BVDV-2 forms present with haemorrhages and high mortality.
• Reproductive problems: poor fertility, return to oestrus, abortions, mummies, weak or malformed calves.
• PI animals: ill-thrift and recurrent disease, although some show no signs.
• Mucosal disease: fever, anorexia, profuse diarrhoea, salivation, erosions in the mouth, muzzle and interdigital spaces, dehydration and death within days to weeks; a chronic form with progressive weight loss also exists.

Diagnosis

• Detection of PI animals: the basis of control programmes. Viral antigen (antigen ELISA or immunohistochemistry) or RNA (RT-PCR) is detected in an ear notch sample taken at birth, often with the official ear tag, or in blood. A positive is confirmed with another sample at least 3 weeks later to distinguish a PI animal from a transient infection. In the blood of young calves colostral antibodies can interfere with the antigen ELISA, but not with the ear notch sample.
• Herd surveillance: RT-PCR on bulk-tank milk detects lactating cows shedding virus, and antibodies in bulk-tank milk or in serum from a small group of unvaccinated young stock show whether the virus is circulating in the herd.
• Mucosal disease and abortions: typical necropsy lesions, histopathology, virus isolation or PCR on fetal tissues and placenta.

Treatment and control

There is no antiviral treatment. In acute infection supportive treatment is given and, if there are secondary bacterial infections, antimicrobials; drug use in food-producing animals is subject to national regulations and meat and milk withdrawal periods. Mucosal disease has no treatment and PI animals should be removed from the herd.

Control rests on three pillars:

• Biosecurity: buying animals from free or tested herds, quarantine, testing calves born to purchased pregnant females and avoiding contact with other herds.
• Identification and removal of PI animals as early as possible.
• Vaccination (inactivated or modified-live vaccines) to protect females before breeding; it reduces, but does not completely prevent, fetal infection.

Several countries have run national eradication programmes, some without vaccination (the Scandinavian countries, Switzerland) and others based on ear notch testing of all calves (Ireland, Germany and others), with good results (see Key studies).

Key studies

• Newcomer et al. (2015), meta-analysis of 46 controlled studies published in 41 articles on the efficacy of vaccination against reproductive disease, with homologous, heterologous or field challenge. Vaccinated cows had nearly 45% fewer abortions and nearly 85% less fetal infection than unvaccinated cows, and in field trials pregnancy risk increased by about 5%. Protection against fetal infection is high but not complete, so vaccination does not replace detection of PI animals.
• Scharnböck et al. (2018), meta-analysis of 325 studies in 73 countries (1961–2016), with 6.5 million animals tested. Prevalence of PI animals was low (≤0.8%) in Europe, North America and Australia, medium (0.8–1.6%) in East Asia and high (more than 1.6%) in West Asia. In Europe prevalences fell over time and in North America they increased; the highest were found in countries without any control or eradication programme, including vaccination. The original studies were very heterogeneous.
• Hay et al. (2016), prospective cohort study of 35,160 cattle in Australian feedlots followed for their first 50 days. Only 85 (0.24%) were PI, but BVDV-1 was detected in 59% of pens. PI animals had a higher risk of respiratory disease (OR 1.9; 95% credible interval 1.0–3.2), and exposure to the virus in the pen also increased it (OR 1.7; 1.1–2.5). It is a study from a single country and a single production system.
• van Roon et al. (2020), meta-analysis of 18 European observational studies on risk factors for herd infection. Risk was higher in dairy than in beef herds (OR 1.63), with herd size (OR 1.04 for every 10 additional animals), participation in shows or markets (OR 1.45), introduction of animals (OR 1.41) and contact with other herds at pasture (OR 1.32). Heterogeneity between studies was high.
• Graham et al. (2021), description of the mandatory Irish eradication programme, started in 2013 and based on ear notch sampling of all newborn calves. Prevalence of PI calves fell from 0.66% in 2013, present in 11.3% of herds, to 0.03% and 0.55% of herds at the end of 2020. Early on, a key problem was that some farmers retained PI calves. These are descriptive programme data, without a control group.
• Schweizer et al. (2021), review of the mandatory Swiss programme, started in 2008 without vaccination. The proportion of calves born PI fell from around 1.4% to less than 0.02%, which allowed a switch to serological surveillance, and by the end of 2020 more than 99.5% of farms were free. Eliminating the last foci proved difficult, partly because of border disease virus in sheep. It is a narrative review by the programme's own officials, with descriptive data.