BVDV in calves can present in a number of ways. Immune suppression is probably the most costly manifestation. “All strains of BVDV have some type of immune suppression,” says Vic Cortese, DVM, PhD, Dipl. ABVP, Pfizer Animal Health. “Even the mild strains will cause immune suppression that can last approximately three weeks.”
Cortese notes that work has shown that when BVDV is circulating through a dairy, other diseases become more prominent. “You may be trying to fight these other diseases, but the underlying immune suppression caused by a BVDV infection is to blame.”
“If you have multiple PI calves along with inadequate management, you have the potential for a lot of clinical disease,” says Scott Smith, DVM, The Dairy Authority, LLC, Greeley, Colo. “Cattle are much more susceptible to other viral and bacterial infections. You may see a higher incidence of general scours and pneumonia and an increase in death loss. Salmonellosis, coccidiosis and other opportunistic diseases can often be found in populations with circulating BVDV.”
Clinical signs and PIs
Acute BVDV can also cause “bleeder syndrome” due to platelet destruction. Bleeder syndrome is only caused by the Type II BVDV strains, and not all of the Type IIs will cause this syndrome. Depletion and destruction of throm-bocytes causes a lack of clotting. “In young calves, you see hemorrhaging in the sclera and petecchial hemorrhages in the mouth,” says Cortese. “In adults, you’ll see nosebleeds.” Hematomas at injection sites, dripping blood from injections, severe blood loss from dehorning or castration and free blood in the thoracic cavity upon necropsy are also signs of bleeder syndrome.
One way to begin eliminating persistently infected (PI) BVDV animals from the dairy is to identify PI calves and then identify and test (and cull) any of their PI dams.
Cortese adds that BVDV is the only cause of severe platelet losses in North America, and a platelet count in a bleeder case can tip you off to a BVDV infection. Numbers will often drop below 100,000, and usually hemorrhaging will occur when below 50,000. Platelet numbers this low are a good indication of bleeder syndrome. Often, a lab may report too few platelets to count.
Persistently infected (PI) calves may or may not be visually evident. PI calves may be weak and runted and 10-15 pounds lighter than normal. However, on a dairy especially, PI calves often look normal though they are immunologically frail. “They tend to be the first to die in a respiratory outbreak,” says Cortese. “They can’t clear infections and are the primary source of BVDV spread on dairies.”
Smith adds that a calf with BVDV can present in a number of ways, especially if there is a secondary infection involved. “Respiratory symptoms are seen the most frequently, but you may also see diarrhea and lameness. Treatment is based mostly on supportive care and treatment of secondary bacterial infections.”
Cortese notes that 50 percent of PI calves will die within the first year of life. Another 40 percent will die before two years of age and only 10 percent make it to two years. PI animals tend to die near birth and later can die of mucosal disease, chronic BVDV and lameness.
The older the animal is, the less likely it is to be a PI animal because of this immunologic frailty of PI animals.
Creating a PI in utero
BVDV can affect the unborn calf in a variety of ways, mostly dependent upon the timing of exposure (see sidebar). If a nonimmune pregnant cow – this does not necessarily mean an unvaccinated cow – is exposed early in the first trimester, stillbirths, early embryonic death and mummification can occur. Later in the first trimester, between days 60-100, BVDV exposure can result in PI calves. In the second trimester, exposure to BVDV is likely to cause abortions and birth defects.
PI calves may be weak, runted and 10-15 pounds lighter than normal. However, on a dairy especially, PI calves often look normal though they are immunologically frail and prone to disease.
The birth of a persistently infected calf only occurs via in utero exposure. At birth, a calf is either PI or it isn’t. Persistent infection can only occur two ways: if the dam is PI or if a non-PI dam is exposed to BVDV and passes it on to the fetus during that critical 60-100-day-of-gestation window. The virus crosses the placenta before the calf’s immune system is developed – before MHC-1s have developed for self-recognition – and the immune system recognizes that strain of BVDV as part of itself and not as foreign protein.
It’s rare for PI bulls to create PI calves at breeding through infected semen because it’s too early in the trimester at conception to cause PI calves. Infection at this time, however, can create early embryonic death. The danger of PI bulls is when they are exposed later to pregnant cows and the shedding of virus through nose-to-nose contact at that critical time can create PI calves.
Closing the PI loop
Closing the loop of persistent infection on the dairy involves identifying an infected calf and, when possible, her dam. “I like to test calves as early in life as possible to identify PIs and remove them to reduce the impact of BVDV in the herd, as well as the heifer-growing facility,” says Smith.
Many dairies or heifer growers are now ear-notch testing calves for persistent infection. The problem is when they find these calves and either euthanize or dispose of them, they often don’t go back to find that PI calf’s dam, which may or may not be PI itself. “Persistent infection is often along family lines,” says Cortese. “You must go back and test the dam to see if she’s a PI.”
Cortese notes that 7 percent of PI animals will be from PI dams. “If I just get rid of the PI calves, I still have infection through the cows on the dairy. If you’re going to spend money and time to find a PI calf, the dairy needs to know so they can test the dams.”
Smith says once a producer has an understanding of the dynamics of BVDV and how PI calves are produced, they are usually willing to test the dam. “Identification is rarely a problem when the calf is a heifer,” he says. “Bull calves are not identified on some dairies, and therefore, traceback is much tougher in that situation.”
Looking for BVDV in aborted fetuses can also identify problem dams. Any time Smith works up an abortion problem, he tests the fetus and dam for the presence of BVDV, and occasionally finds some positives.
Economics of PIs
In a 2002 study by Larson, et al, the economics of one PI animal in a beef herd were estimated. It was calculated that a reduced pregnancy rate of 5 percent, an increased pre-weaning mortality of 10 percent and a decreased weaning weight of 0.5 percent could have an economic effect of $14.85- $24.84 per year decreased return to fixed costs per beef cow exposed.
Bovine viral diarrhea virus was isolated from this calf with severe internal hydrocephalis. This calf had other congenital defects including scoliosis and pulmonary hypoplasia.
Photo credit: Bruce Brodersen, DVM, PhD
Cortese says because the death loss from BVDV is even greater in dairy herds, the economic losses are higher. “Assume on a dairy a prevalence rate of 4 percent PI animals in animals under 2 years of age. If I buy a group of 20 springing heifers, the risk of buying a PI animal is 66 percent. If I’m buying 10 yearling bulls, I have a 40 percent chance there will be one PI bull.”
BVDV biosecurity for calves
Vaccination alone won’t protect a dairy and its calves from BVDV. “A sound biosecurity plan is essential to obtain any amount of BVDVcontrol in our calf populations,” notes Smith. “Without proper biosecurity, we continue to allow BVDV a foothold in our calf populations that it will not yield.”
Cortese offers five areas of a BVDV control program:
Because of increased animal movement around the country and in and out of dairies, biosecurity is critical. It might be wise to encourage clients to close their dairies to outside visitors, limit visits to appointments only and hold meetings with suppliers, advisors, etc., off of the dairy premises.
2. Find if the herd currently has PIs
It’s important to know the current PI BVDV status of the herd. Cortese offers serological ways this can be accomplished.
Pre-colostral blood samples on calves. If a calf has antibody to BVDV, it indicates BVDV is circulating on the dairy because the calf is making antibodies and that the vaccination program is not preventing cross-placental transfer of BVDV. Five to six calves can be tested once every three or four months. Split the sample – send one to the lab and keep one. “If you get a high titer back, ask the lab to run IgG levels to tell if the calf has nursed,” says Cortese. “If the BVDV titer is higher than 1:16, you know in utero exposure has occurred if they have not nursed.”
Do serologic surveys at 6-8 months. This requires leaving some steers or heifers unvaccinated. Published work shows that if five calves are tested at 6-7 months and if three of the five calves run 1:16 or above, there has been exposure to a PI animal on the dairy.
Use sentinel animals, especially on larger dairies. This can be a slick tool to use if the dairy is having reproductive problems that might be associated with BVDV. It’s done by bleeding seronegative animals every three to four months to see what is circulating through the adult population, whether it’s BVDV, IBR or Neospora. Cortese says this is similar to what’s done in poultry and swine. “To do this, I recommend that the seronegative animals be home-raised,” he says. “If you purchase them, they might be PI but BVDV negative, and that will throw off the results. Make sure they are virus-isolated-negative, not just serology-negative.”
Polymerase chain reaction (PCR) tests on the milk can be useful, as they can pick up one PI out of 250 cows sampled. Cortese likes to narrow that number down and test in strings of 100. However, if you use PCR, keep in mind that if using modified-live BVDV vaccines in open cows or at preg-check, they can “pop” the PCR positive.
Of the PI animals, only 10 percent make it to the milking string,” says Cortese. “So all PI animals might exist in the youngstock, and PCR of milk won’t catch those.” It’s also important to remember that at any one time a percentage of the herd is not in the milking string, so PCRs will have to be done four to six months apart to catch those animals that were dry when the first animals were tested.
3. Cull PI animals
Vic Cortese, DVM, Dip. ABVP, notes that 50 percent of PI calves will die within the first year of life, another 40 percent will die before two years of age, and only 10 percent make it to two years.
Before implementing testing procedures, it’s important for the veterinarian to know the goals of the producer. If the producer will take action and cull the PI animals, put biosecurity programs in place and vaccinate, then it’s worthwhile to test and cull.
Especially for small, closed herds, testing all calves, culling PIs (and PI dams) and continuing to test all new calves will eventually lead to a negative herd over time. “A lot of calf ranches are doing this,” says Cortese. “They test incoming calves for PI, and if they find any positives, they snip off two teats so when they are sold it indicates they are PI. Ideally, we would like them euthanized, but many places will just cut off teats and send them out.”
4. Testing animals
There are different tests available to find PI animals. One of them, PCR, still has some false negative and false positive problems, notes Cortese.
The microplate virus isolation test uses serum that is incubated in wells then put in an ELISA. This test, however, can be blocked by maternal antibody, so it’s unreliable in an animal under 3 months of age and can give a lot of false negatives. It also requires a confirmation test three weeks later.
The immunohistochemistry (IHC) “ear-notch” test will identify PI animals because they will have BVDV in higher levels of the skin than will acutely infected or MLV-vaccinated animals. “A single sample can tell whether a calf is PI,” says Cortese. This test is also not blocked by maternal antibodies.
Another advantage is that any piece of skin will do, such as a piece of belly skin in show animals.
Scott Smith, DVM, says two keys to preventing PI calves are to optimize the immunity in the breeding herd with effective, timely vaccination and to reduce potential exposure by testing new herd additions.
Skin samples must be read within a week because the sample will break down. Samples can be sent in empty serum tubes with a small amount of formaldehyde. This test is also the only test that can be done on dead animal skin to determine persistent infection. “If an animal is worth posting, I send in some skin, too, fresh or fixed, within a week,” says Cortese.
Veterinarians and their clients have to be careful, however, when labs indicate they have done an “ear-notch test.” Some labs take fluid from a sample and do an ELISA on it, which will not differentiate PI from an acute or MLV-vaccinated animal. It is not the same as the immunohistochemistry test. “You need to find out what test the lab is doing, especially if you’re dealing with expensive animals,” says Cortese. “Know which skin test they are doing – IHC or ELISA on fluids.”
Smith adds that it’s important that veterinarians realize there are two different types of ear-notch tests, and they should weigh the advantages and disadvantages of each one.
Use a BVDV vaccine that has known protection for Type I and Type II BVDV and fetal protection. “The goal of vaccination has changed,” says Cortese. “We know we can protect the cow and stop her from dying, but the difficult goal now is to protect the calf.”
For open heifers, Smith recommends two doses of a modified-live vaccine with both Type I and Type II strains two to four weeks apart. For potentially pregnant heifers with unknown vaccine history, he recommends a product with a killed BVDV component. “In milking cows, all of the herds I work with use an MLV product with both Type I and Type II,” he says. “Cows get a dose when first confirmed pregnant to obtain fetal protection against BVDV. A second dose is given at or just prior to dry-off.”
Smith also makes sure all bulls are tested for PI BVDV prior to entering the herd, and they are given two doses of an MLV 4-way with both Type I and Type II BVDV two to four weeks apart. In addition, all bulls are given a dose of this vaccine every six months.
Cortese says that if there is a BVDV outbreak with much disease and death loss, two things are occurring: a virulent strain of BVDV and, regardless of the history, somewhere the vaccination program broke down. “They either didn’t vaccinate them, mishandled the vaccine or something happened in their vaccination program.”
Smith adds that the two keys to preventing PI calves are to optimize the immunity in the breeding herd with effective, timely vaccination and to reduce potential exposure by testing new herd additions for PI status. “The best way to prevent acute BVDV infections in calf populations is early testing, identification and removal of PI calves,” he says. “A sound vaccination program will also reduce the amount of clinical BVDV in a calf population with circulating virus.”
What is BVDV?
BVDV belongs to the pestivirus group that includes Type I and II BVDV, hog cholera and border disease. Pesti-viruses, as a group, have the ability to cross-infect and cause disease in cloven-hoofed animals. “Fortunately, it has not learned how to jump to humans,” says Vic Cortese, DVM, PhD, Dipl. ABVP, “because BVDV has been one of the most common contaminants in human vaccines.”
All BVDVs are not alike. There are strains that are entirely respiratory in nature or reproductive in nature. Some strains are virulent, others less so. In the wild, normally all BVDV exists in a noncytopathic (NCP) state, meaning they leave surrounding cells intact. All cytopathic (CP) strains, which punch holes in other cells, arise from mutations of NCP BVDV.
It’s a common misperception that cytopathicity is related to virulence, but Cortese says that’s not the case. “Many virulent strains are NCP, and the CP strains usually occur in PI animals. Cytopathicity is not related to virulence.”
CP and NCP strains can only be differentiated in a lab – they cannot be distinguished by clinical signs.
Brachygnathic calf: Because of the shortened mandible, the tongue appears abnormally long.
Photo credit: Bruce Brodersen, DVM, PhD
BVDV infections during gestation
Paul Walz, DVM, PhD, Auburn University, says transplacental infection is a common event in pregnant cattle exposed to BVDV. Most acute, postnatal infections are subclinical, yet infection in pregnant cattle may result in significant disease. The outcome of fetal infection with BVDV is dependent upon time of infection (i.e. gestational age of the fetus), organ system involved in the infection and properties of the virus (i.e. biotype, virulence and target cell range).
Days 0-45 of gestation
Infection of cattle prior to insemination results in impaired conception rates due in part to ovarian infection and dysfunction as a result of BVDV viremia. Viral antigen and ovaritis have been described in acutely infected cattle with BVDV. Conception and pregnancy rates are lower if the animals are viremic at the time of insemination. Retrospective determination of serologic status has indicated that cows that seroconvert during the early gestation period have significantly lower conceptions rates than cows that were immune. Additional work has demonstrated that overall conception rates were lower for herds defined by having a persistently infected (PI) carrier present.
Days 45-125 of gestation
The development of the fetal immune system occurs during this period of fetal development. The most outstanding feature or outcome of infection during this period is the development of persistent infection. By definition, cattle that are persistently infected with BVDV are immunotolerant to BVDV. Biotype is important during this period – infection with either biotype is capable of causing fetal death, however, only the noncytopathic (NCP) biotype is capable of causing persistent infection. Persistent infection occurs from an in utero exposure to NCP BVDV. The PI calf cannot recognize the infecting BVDV as foreign and never mounts an immune response to it.
Congenital malformations may be produced by BVDV infection during this period as well. The period of organogenesis occurs approximately between days 100-150 of gestation. Central nervous system malformation and defects in myelination have been reproduced in experimental infections prior to 125 days.
Days 125-175 of gestation
Abortion may be observed at any time during gestation as a result of BVDV infection, but most abortions attributed to BVDV seem to be reported during this time. Part of this may be bias as fetuses of this gestational age may be more likely to be submitted for a diagnostic workup. Following BVDV infection, expulsion of the fetus may occur shortly or may be delayed for several months after infection. Following experimental infection at around days 100-120 of gestation, abortion was observed 30-50 days after infection.
Congenital malformations may also be observed during this period as well, including cerebellar hypoplasia, hypomyelinogenesis, hydranencephaly, alopecia, cataracts, optic neuritis, brachygnathism, hydrocephalus, microencephaly, thymic aplasia, hypothrichosis, pulmonary hypoplasia and growth retardation. However, it has not been determined if congenital malformations are the direct result of viral infection on developing cells, or the host immune response in destroying virally infected cells.
Days 175 to term
Beyond day 175 of gestation, the fetus is determined immunocompetent. Infection during this period usually results in the birth of a calf that is clinically normal and seropositive on a pre-colostral blood sample. Detrimental effects of BVDV infection in late gestation seem to be less common, however, weak calves and abortions have been reported. In addition, recent data suggest that calves exposed to BVDV in utero that appear normal at birth may be predisposed to postnatal disease such as scours and pneumonia.
This information excerpted from the proceedings of Kansas State University’s Bovine Conference on Investigating Pregnancy Wastage in Cattle Herds, May 2003.