Bovine viral diarrhea

Following viral entry and contact with the mucosal lining of the mouth or nose, replication occurs in epithelial cells. BVDV replication has a predilection for the palatine tonsils, lymphoid tissues and epithelium of the oropharynx.

Phagocytes take up BVDV or virus-infected cells and transport them to peripheral lymphoid tissues; the virus can also spread systemically through the bloodstream. Viraemia occurs 2–4 days after exposure and virus isolation from serum or leukocytes is generally possible between 3–10 days post infection.[20]

During systemic spread the virus is able to gain entry into most tissues with a preference for lymphoid tissues. Neutralising antibodies can be detected from 10 to 14 days post infection with titres continuing to increase slowly for 8–10 weeks. After 2–3 weeks, antibodies effectively neutralise viral particles, promote clearance of virus and prevent seeding of target organs.[21]

Fetal infection is of most consequence as this can result in the birth of a persistently infected neonate. The effects of fetal infection with BVDV are dependent upon the stage of gestation at which the dam suffers acute infection.

BVDV infection of the dam prior to conception, and during the first 18 days of gestation, results in delayed conception and an increased calving to conception interval. Once the embryo is attached, infection from days 29–41 can result in embryonic infection and resultant embryonic death.

Infection of the dam from approximately day 30 of gestation until day 120 can result in immunotolerance and the birth of calves persistently infected with the virus.

BVDV infection between 80 and 150 days of gestation may be teratogenic, with the type of birth defect dependent upon the stage of fetal development at infection. Abortion may occur at any time during gestation. Infection after approximately day 120 can result in the birth of a normal fetus which is BVD antigen-negative and BVD antibody-positive. This occurs because the fetal immune system has developed, by this stage of gestation, and has the ability to recognise and fight off the invading virus, producing anti-BVD antibodies.

BVD virus can be maintained as a chronic infection within some immunoprivileged sites following transient infection. These sites include ovarian follicles, testicular tissues, central nervous system and white blood cells. Cattle with chronic infections elicit a significant immune response, exhibited by extremely high antibody titres.

Persistently infected animals did not have a competent immune system at the time of BVDV transplacental infection. The virus, therefore, entered the fetal cells and, during immune system development, was accepted as self. In PIs the virus remains present in a large number of the animal's body cells throughout its life and is continuously shed. PIs are often ill-thrifty and smaller than their peers, however, they can appear normal. PIs are more susceptible to disease, with only 20% of PIs surviving to two years of age.[22] If a PI dam is able to reproduce they always give birth to PI calves.[23]

The PI cattle that do survive ill-thrift are susceptible to mucosal disease. Mucosal disease only develops in PI animals and is invariably fatal.[5] Disease results when a PI animal is superinfected with a cytopathic biotype arising from mutation of the non-cytopathic strain of BVDV already circulating in that animal.[24] The cp BVDV spreads to the gastro-intestinal epithelium, and necrosis of keratinocytes results in erosion and ulceration. Fluid leaks from the epithelial surface of the gastro-intestinal tract causing diarrhoea and dehydration. In addition, bacterial infection of the damaged epithelium results in secondary septicaemia. Death occurs in the ensuing days or weeks.

Antigen ELISA and rtPCR are currently the most frequently performed tests to detect virus or viral antigen. Individual testing of ear tissue tag samples or serum samples is performed. It is vital that repeat testing is performed on positive samples to distinguish between acute, transiently infected cattle and PIs. A second positive result, acquired at least three weeks after the primary result, indicates a PI animal. rtPCR can also be used on bulk tank milk (BTM) samples to detect any PI cows contributing to the tank. It is reported that the maximum number of contributing cows from which a PI can be detected is 300.

Antibody (Ig) ELISAs are used to detect historical BVDV infection; these tests have been validated in serum, milk and bulk milk samples. Ig ELISAs do not diagnose active infection but detect the presence of antibodies produced by the animal in response to viral infection. Vaccination also induces an antibody response, which can result in false positive results, therefore it is important to know the vaccination status of the herd or individual when interpreting results. A standard test to assess whether virus has been circulating recently is to perform an Ig ELISA on blood from 5–10 young stock that have not been vaccinated, aged between 9 and 18 months. A positive result indicates exposure to BVDV, but also that any positive animals are very unlikely to be PI animals themselves. A positive result in a pregnant female indicates that she has previously been either vaccinated or infected with BVDV and could possibly be carrying a PI fetus, so antigen testing of the newborn is vital to rule this out.[5] A negative antibody result, at the discretion of the responsible veterinarian, may require further confirmation that the animal is not in fact a PI.

At a herd level, a positive Ig result suggests that BVD virus has been circulating or the herd is vaccinated. Negative results suggest that a PI is unlikely however this naïve herd is in danger of severe consequences should an infected animal be introduced. Antibodies from wild infection or vaccination persist for several years therefore Ig ELISA testing is more valuable when used as a surveillance tool in seronegative herds.