Bovine leukosis virus: A new look at an old problem (Proceedings)

The stuff you were taught in vet school

Bovine leukosis virus is an oncogenic retrovirus of cattle. Once cattle are infected, the virus incorporates itself into the genome of the cow's lymphocytes. As such, the lymphocyte is the infectious unit in the transmission of BLV from cow to cow. Anything that allows for blood to move from animal to animal has the potential to move the virus. Some more common methods include dehorning using cutting methods, tattooing, rectal examination using multi-use sleeves, and blood sampling with the same needle and syringe. Transmission may also occur in utero, at calving, though colostrum ingestion in the neonate, and potentially by biting flies and natural service. Not all methods are equal in their ability to transmit the virus and not all cows are equally infectious. These variables may dramatically affect results in control and eradication programs.

Bovine leukosis virus is endemic in the United States cattle population. While this is well known, there is very little data regarding prevalence and scope of the disease within the US. A 1996 survey estimated that 89% of US dairy herds were infected with BLV and greater than 40% of all US dairy cattle were infected. In 2007, a follow up NAHMS study found 83% of tested bulk tanks to have antibody present with prevalence increasing as herd size increased. Less than 12% of the herds tested had a known case of lymphosarcoma in the year prior to testing. Although BLV is less prevalent in beef cattle, a 1997 survey of US beef cattle estimated that 38% of US beef herds and 10% of US beef cattle are infected with BLV.

Less than 5% of BLV infected cows will develop BLV-associated multicentric lymphosarcoma, a uniformly fatal neoplastic disease. Approximately 30 % of cattle infected with BLV will develop persistent lymphocytosis, a benign lymphoproliferative condition associated with infection with the virus. The magnitude of the lymphocytosis can vary from cow to cow, but typically ranges from 15,000 cells/μL – 20,000 cells/μL. The remainder of the animals will be subclinical with no apparent signs associated with BLV infection.

Economic losses associated with BLV are difficult to enumerate. Cattle with lymphosarcoma will incur clear losses due to decreased production, increased veterinary costs, premature culling, and potentially death. Losses in virally infected cattle without cancer are more difficult to discern. Studies are divided on whether loss exists in this group at all. Purebred herds that rely on domestic and foreign seedstock sales may incur substantial losses as many countries, particularly those in the European Economic Community, will not accept cattle, semen, or embryos from positive individuals or herds.

Control and eradication programs focus on limiting blood transfer from infected to naïve animals. In adult herds single use rectal sleeves, single use needles, disinfection of instruments between cows, and fly control are the major areas of focus. In calves recommendations include the applicable strategies for cattle, but also include cautery methods for dehorning. Segregation and selective culling are also advocated. Culling and natural attrition are responsible for the eventual removal of infected animals from the herd.

Testing for BLV status may be done for one of a number of reasons. A negative test may be required for some shows, sales, and for movement purposes depending on the destination requirements. If lymphosarcoma is suspected in a sick adult, a BLV test may help clarify the possibility of this diagnosis. It is important to remember that a positive test result is not confirmatory for lymphosarcoma. Whole herd tests may be performed for herd status information or may be a requirement for state regulated BLV control programs.

Serologic tests are the most commonly used tests for determining BLV status. Both ELISA and AGID methodologies are available. The AGID is still required by most countries as an export test. However, the ELISA is most commonly run for routine purposes. Turnaround time for serology is quick and the test is relatively inexpensive at $3-$6/test. Serologic tests rely on the detection of antibody to the virus. After viral exposure it typically takes 6 weeks – 14 weeks to develop a detectable antibody response. All test kits rely on the detection of GP51 and/or P24 antibodies. Positive serology results are consistently present in cattle infected with BLV and cattle not infected with BLV are nearly uniformly negative with regard to their serologic status. However, false positive and false negative tests do occur under predictable situations. False positive tests are most commonly seen in calves that receive colostrum from infected dams. The maternal origin antibody may be detectable for up to 6 months. False negative test results are seen most commonly in periparturient cows.

Polymerase chain reaction assays are relatively new to BLV diagnostics. It typically takes 1 day to run the test at a cost of $30-$50. This test has the advantage over serology because it detects BLV provirus. There are multiple methodologies using different primers yielding some differences in sensitivity (0.627 – 0.984) and specificity (0.89 - 1.0). The PCR is advocated for early detection of infection however, not all methodologies perform equally in this regard. The detection of provirus instead of antibody and the potential ability to detect small quantities of provirus makes this test viable in neonates, periparturient cows, and animals with recently acquired infections that have yet to seroconvert. The current cost of the PCR is too expensive for routine use of the test.

The stuff I hear most often

I work on several herds with a prevalence of >80% and no animals ever die of lymphosarcoma.

It is possible that no cows die of lymphosarcoma in this scenario, but it is highly unlikely. It is more likely that the cows are culled for poor production or poor response to therapy for disease that has not been definitively diagnosed. Each year from 1998-2002 lymphosarcoma is the #1 cause of adult cow carcass condemnations accounting for 12-19% of all condemnations in this carcass class. Lymphosarcoma condemnations almost double the next leading cause.

We never diagnose lymphosarcoma in my beef herds so they are not infected with BLV.

Since lymphosarcoma is the major negative outcome of infection with BLV, people often feel that infection does not exist in their herd because of the absence of cancer. As the carcass condemnation data would suggest, cases may be missed in cattle culled without a definitive diagnosis. In addition, since so few animals infected with the virus actually develop cancer it is possible to have virally infected cattle without actually seeing lymphosarcoma.

Control programs are tested tried and true.

The cornerstone of control programs is to limit the transfer of infected lymphocytes from infected to naïve cattle. As such, anything that can move blood from one animal to another is minimized. There is some conflicting data and some recommendations that are weakly supported in the veterinary literature, but overall the programs can be successful. One major problem is cost and dedication. Single use items (rectal sleeves, needles, ect), equipment disinfection, and testing have real associated costs. Segregation of purchased additions and test positive animals require facilities and manpower. For a disease with little perceived financial detriment, many producers are unwilling to take on the work and economic impact of control programs.

I am following all of the control and eradication protocols and I can't budge prevalence.

In the case of BLV infection not all cows or herds are created equal. Genetics and the development of persistent lymphocytosis both affect the appearance of BLV within a herd. There are definitely genetics associated with infection and outcome once infected. Infection and the development of cancer has been shown to run in family lines. As such, it is possible to increase the incidence of BLV-associated lymphosarcoma by selecting for prevalent genetics. It is unlikely that we will be able to test and cull based on cattle genetics anytime in the near future.

While considered to be a benign condition, persistent lymphocytosis has the potential to dramatically affect the viral reservoir present on a farm. Cattle with PL have an increased lymphocyte count, an increased proportion of virally infected cells, and more copies of integrated provirus than cattle without PL. As a result, these animals make a substantial contribution to the farm reservoir of virus. There is also data that would suggest that these cows are more efficient transmitters of the virus.

References/Suggested Reading

1. Brunner MA, Lein DH, Dubovi EJ. Experiences with the New York state bovine leukosis virus eradication and certification program. Vet Clin North Am 1997; 13(1):143-150.

2. DiGiacomo RF. The epidemiology and control of bovine leukemia virus infection. Vet Med 1992; 87(3):248-257.

3. Ferrer JF, Marshak RR, Abt DA, and Kenyon SJ. Relationship between lymphosarcoma and persistent lymphocytosis in cattle: A review. J Am Vet Med Assoc 1979; 175(7):705-708.

4. Hopkins SG and DiGiacomo RF. Natural transmission of bovine leukemia virus in dairy and beef cattle. Vet Clin North Am 1997; 13(1):107-128.

5. Johnson R and Kaneene JB. Bovine leukemia virus. Part II. Risk factors of transmission. Comp Cont Ed 1991; 13(4):681-691.

6. Johnson R and Kaneene JB. Bovine leukemia virus. Part IV. Economic impact and control measures. Comp Cont Ed 1991; 13(11):1727-1737.

7. USDA. High prevalence of BLV in U.S. dairy herds. USDA, APHIS, VS, NAHMS 228:197, 1997.

8. Juliarena MA, Gutierrez SE, Ceriani C. Determination of proviral load in bovine leukemia virus-infected cattle with and without lymphocytosis. Am J Vet Res 68(11):1220-1225.