We know a lot about bovine viral diarrhea virus (BVDV) in cattle, but we still have a lot to learn about persistent BVDV infection. Cattle persistently infected (PI) with BVDV are lifelong carriers and shedders of BVDV. A PI animal is defined as one that was infected at 40-150 days of gestation. The developing immune system of the fetus actually recognizes the virus as part of itself, which is referred to as immunotolerance.
“Because the virus is recognized as part of the fetus, it is not cleared and therefore is allowed to replicate as long as the fetus is alive or, more importantly, as long as the animal is alive once it is born,” explains Dan Grooms, DVM, PhD, Michigan State University.
Both Type 1 and Type 2 BVDV can cause PI animals, and only non-cytopathic (NCP) strains will cause persistent infection. NCP strains of BVDV can also cause death and abortion.
In the general population of cattle, about one out of every 1,000 cattle are likely PIs; however, on individual farms this prevalence can be much higher. “Bunching” of PI cases is related to BVDV actively circulating on a farm and among a group of pregnant females that are at the correct stage of gestation for PIs to be created, says Grooms.
The exact mechanism of transference of infection from dam to calf is not known. “Some evidence suggests a vasculitis occurs with BVDV infection, which may lead to a breakdown of the maternal-fetal blood barrier, allowing the virus to cross to the fetus, and other studies suggest that trophoblasts may become infected and lead to direct transmission across the placenta,” says Grooms.
Does a PI dam always have a PI calf? Most likely. “Since a PI cow is viremic, virus crosses the placenta via the bloodstream, so there is virtually constant exposure of the fetus to BVDV virus in a PI cow,” says Bruce Brodersen, DVM, PhD, University of Nebraska Veterinary Diagnostic Center.
PI is a PI is a PI?
But, are all PIs the same? “Aside from being persistently infected, it is not known if PI calves are significantly different from one another,” says Broder-sen. Chris Chase, DVM, PhD,
PI animals are approximately 10 times more likely to become chronically ill and realized than non-PI animals, and they are approximately 10 times more likely to die.
Some PI animals are poor performers, and some are essentially normal, says Grooms. “Although we don’t know for sure, the differences are likely due to strain of virus and timing of fetal infection.”
Once a PI always a PI? Yes, based on current knowledge. There may be different levels of virus shedding and clinical manifestations, but virus can always be found somewhere in the PI and they are at high risk of transmitting the disease to susceptible cattle. However, some PIs can mount an immune response against heterologous BVDV that may cross react against the persistent virus and partially clear it, notes Grooms. “Typically, in these animals, we cannot find virus in serum, but we can find it in white blood cells and nasal swabs.”
“There is evidence that suggests animals can clear themselves of persistent infection,” says Brodersen. “If it actually occurs, it is extremely rare.” However, says Grooms, “The bottom line is that people should not think that PIs can potentially get better. They should be destroyed, plain and simple.”
Persistent infection can also lead to mucosal disease, a fatal manifestation that, by definition, only occurs in PIs. Brodersen says the classical definition of mucosal disease is when a PI animal is superinfected with a strain of cytopathic BVDV that is antigenically similar to the persistently infecting virus, mucosal disease can develop. Grooms adds that the most common way that mucosal disease occurs is when the persistent virus that is replicating in the PI animal acquires a specific mutation that turns the virus from an NCP to a cytopathic biotype. This then starts a cascade of events that leads to the animal’s death.
Dan Grooms, DVM, PhD, says some PI animals are poor performers and some are essentially normal.
Typical signs of mucosal disease are bloody diarrhea and acute death. On necropsy, there are generally ulcers and erosions involving much of the gastrointestinal tract. However, adds Chase, 40-50% of PI animals that have sudden death have no lesions; they just die.
A necropsy may not always tell you grossly if you are looking at a PI calf, but there are some effects being a PI has on organs. Brodersen says the organs virus in a persistently infected animal attacks first tend to be lymphoid organs such as thymus and Peyer’s patches. Brodersen explains that these are areas of T-lymphocyte and B-lymphocyte proliferation. One of the main lesions seen in a PI animal is thymic atrophy. “I have seen calves that have died from some other cause, such as pneumonia, where their Peyer’s patches are depleted of lymphocytes or are necrotic,” notes Brodersen. Aside from the necrosis, the Peyer’s patches can be overlayed with intestinal mucosa and ulcerated and/or hemor-rhagic. “Pneumonia is another common finding in PI animals that have died.”
Overall, PI animals shed even more than an animal that is acutely infected and is in its peak of infection, explains Bruce Brodersen, DVM, PhD.
Because of its susceptibility to infection, the PI animal can, on occasion, display unusual infections and lesions such as abscessing gingivitis, notes Brodersen.
Shedding and viremia
Shedding levels may vary depending on concurrent BVDV immune response against other strains of BVDV and immunosuppression (induced by stress, metabolic state, etc.). Typically, PIs shed between 1,000 to one million virus particles per mL of secretions or serum. Virus can be shed through feces, semen, nasal secretions, coughing, orally, blood transferred on needles, colostrum, milk and placenta to the calf. Grooms says that the most likely source of transmission is respiratory secretions.
Brodersen adds that there can be a variation in the amount of virus shed, but overall, PI animals shed even more than an animal that is acutely infected and is in its peak of infection.
Many believe vaccination of a PI animal with a modified-live virus vaccine will cause it to die of mucosal disease. This, says Grooms, is very unlikely. “The only way this would occur is if the vaccine virus and persistent virus are antigenically similar. The chances of this occurring are extremely rare. PIs are vaccinated with an MLV BVDV vaccine every day with no major detrimental effects.”
What the tests say
Using immunohistochemistry (IHC), a PI animal should be positive at any age, including at birth and in the face of colostrum. The gold standard confirmatory test for PI BVDV cattle is the virus isolation (VI) test, taken three weeks apart. It’s important to wait three weeks to allow acute infections to be cleared by a normally functioning immune system. If the animal is persistently infected, the infection will not be cleared. Other tests may not detect a PI animal, particularly a calf that has significant amounts of maternal antibodies. “Antibodies can bind with the virus to inhibit ELISA tests,” says Brodersen. “
Virus isolation from white blood cells and lymphatic tissue of PI animals should always be positive. PIs may be negative on virus isolation during two scenarios. The first is from serum if taken after colostrum ingestion. This false negative result can last one to four months. The second is if cross-reacting neutralizing antibodies are present that pull out virus from the serum.
While IHC is very accurate at identifying PI animals, Brodersen says, in rare situations, IHC can be positive on an acutely infected animal. “When that happens, the viral antigen can remain in the skin for months, so a follow-up or confirmatory IHC would mistakenly identify the animal as PI.” When that is suspected, a second type of test (
PIs are immunotolerant only to the specific strain the fetus was exposed to in utero. Exposure to other antigenically dissimilar strains can lead to detectable BVDV titers. “For example,” explains Grooms, “if the persistent virus is a Type I virus, exposure to a Type II virus will likely lead to an immune response against that virus that can be detected by serology. Exposure can take place by natural infection or vaccination. Therefore, serology, or more specifically a lack of BVDV antibodies, should not be used as an indicator of persistent infection.”
Persistent BVDV infection has a variety of detrimental performance factors. Work by Grooms indicates that female PI cattle can have decreased ovarian function that may lead to decreased fertility. Chase adds that congenital infection can result in delayed estrus and that he has seen many PI heifers that would not breed. Brodersen recalls a case in which a 6-year-old bull was persistently infected and had no signs of reduced fertility.
Most PIs do not thrive and will fall behind their cohorts, though this is not universally true. More importantly, the presence of PIs has a detrimental effect on non-PI cohorts. Based on the Texas A&M Ranch To Rail program, cattle that become sick during the feeding phase never fully recover the cost of the medicine and loss of performance, and it is not known if being a PI animal has any effect on meat quality.
There is also documented immune dysfunction in PIs that makes them more susceptible to other diseases such as pneumonia, diarrhea, etc. PIs often die before adulthood because of these common calfhood maladies. The virus affects different populations of lymphocytes in terms of numbers and their functions, explains Brodersen. “This effect on the immune system exacerbates other infections such as bovine respiratory syncytial virus, infectious bovine rhinotracheitis virus and Mannheimia haemolytica.”
Guy Loneragan, BVSc, PhD, West Texas A&M University, says based on his data, PI animals are approximately 10 times more likely to become chron-ically ill and realized than non-PI animals, and that PI animals are approximately 10 times more likely to die than non-PI animals.
“We generated some rough estimates that indicate approximately 50% of PI animals that arrive at the feedlot cannot be accounted for in either the dead pile or the realizer pen,” notes Loneragan. “Therefore, they must make it to slaughter with the rest of their cohorts.”
Since they survive to slaughter, they provide long-term exposure to penmates. “In other words,” says Loneragan, “to reduce exposure time, we would ideally have all PIs die on day 1, but about 50% seem to survive to normal slaughter providing tremendous exposure time for non-PI cohorts.”
What to do with PIs?
PIs are lifelong carriers and shedders of BVDV. They serve as the major reservoir for virus transmission on and between farms. Therefore, they need to be managed to stop possible transmission. Organizations, such as the
To prevent BVDV transmission between herds by PIs, PI cattle should be immediately sent to slaughter, isolated from non-PI cattle until they reach slaughter weight or humanely euthanized. Selling PI cattle on the open market is not an acceptable solution. BVDV is not a zoonotic pathogen and no threat to human food.
CI versus PI -- What's the difference?
In recent years, researchers have been examining a different aspect of BVDV called congenital infection. Julia Ridpath, PhD,
1. No calf (early embryonic death and reabsorbtion, abortion or stillbirth)
2. Persistently infected (PI) BVDV calf
3. Congenitally infected (CI) animal born with antibodies
According to theory, the CI animal is a late-gestation fetus that becomes infected with BVDV and develops some immune response. “It appears they are infected as a fetus, develop antibodies and ‘shake’ the infection off before birth,” says Ridpath.
Mark Thurmond, DVM, PhD, University of California-Davis, adds that CI animals are infected in utero, probably after 140 days of gestation. PI fetuses are infected before about 120-140 days in gestation.
“CI animals are antibody-positive precolostrally, whereas PI calves are antibody-negative precolostrally,” explains Thurmond.
After colostrum consumption, CI calves have significantly higher colostral BVDV titers and longer decay than non-CI calves. Some CI calves maintain high titers (>1:1024) for several months after birth (Munoz-Zanzi et al AJVR, 2003). “If the calf had an infection, that means the dam also did, so the dam should have a really nice titer against BVDV in the colostrum,” says Ridpath. “Dams of CI calves are negative for BVDV but have high titers. If it was a PI dam, it would have a PI calf, not a CI calf.”
Thurmond notes that CI animals experience a higher morbidity in the first 8-9 months, compared with non-CI calves. Munoz-Zanzi et al found that calves with CI BVDV were 2.3 times more likely to have a severe morbid episode compared with calves without CI. Ridpath agrees. “Producers have told me they have ‘crap-out’ calves -- they just don’t tolerate vaccination, shipment stress and breeding,” she says. “They just don’t do as well as they should.”
Thurmond adds that CI heifers also experience lower fertility than normal animals.