ANOTHER VIRUS OF PUBLIC /CONSUMER HEALTH CONCERN: BOVINE LEUKEMIA. ENDEMIC IN AMERICA’S DAIRY COWS AND BEEF By Michael W. Fox BVetMed, PhD, DSc, MRCVS
The coronavrirus pandemic has put the world community on alert with regard to the animal-origins of many emerging diseases which cost human lives and the global economy. Advances in comparative medicine and a One Health approach to preventing diseases spread from other animals to humans, so-called zoonoses, are making some headway in national and international public health policies and priorities. There is a serious, chronic viral disease in America’s dairy and beef cattle that has public health consequences. Both beef and dairy cattle are the natural hosts for this oncogenic retrovirus, namely the Bovine leukemia virus (BLV).
In the U.S., a recent survey indicates that 89% of dairy operations and 38% of beef operations had cattle seropositive for BLV, also known as enzootic bovine leukosis. Currently, there are no Federal regulations specific to curbing spread of bovine leukemia virus in the U.S. cattle population. (1). Bovine leukemia virus (BLV) is an oncogenic retrovirus that infects lymphocytes (white blood cells). Proliferation of these virus-infected lymphocytes results in either a persistent lymphocytosis, a benign form of the disease, or neoplastic tumors that invade many different organ systems (referred to as enzootic bovine leucosis or lymphosarcoma.
Transmission of BLV is mainly horizontal. Iatrogenic procedures are an important route as they facilitate transfer of contaminated blood between individuals, e.g. vaccinations, dehorning, rectal examinations and surgical procedures. Natural transmission by direct contact requires contact with infected blood, exudates or tissues which enter through broken skin. Vertical transmission is most likely from colostrum/milk and is less important, although it does provide a method for control.
In the USDA report (1) it is noted: “Less than 5% of BLV-infected cattle develop lymphosarcoma. The remainder of BLV-infected cattle develop persistent lymphocytosis. Lymphosarcoma is most commonly observed in 4 to 8 -year-old animals; animals less than 2 years of age rarely show signs of disease. Clinical signs are highly variable because they depend largely on the organ system (e.g. alimentary, cutaneous, ophthalmic, neurologic, reproductive, reticuloendothelial, multicentric) invaded by these neoplastic lymphocytes. Consequently, signs of infection may include, but are not limited to, peripheral and/or internal lymph node enlargement (lymphadenopathy), labored breathing (dyspnea), bloat, jugular vein distention, increased heart rate (tachycardia), brisket edema, weight loss, decreased milk production, fever, loss of appetite, infertility, rear limb weakness or paralysis, protruding eyeball (exophthalmia), gastrointestinal obstructions and/or ulcers with digested blood (melena), and increased blood lymphocytes counts”.
The bovine leukosis or leukemia virus suppresses the immune system, (2) increasing the probability of bacterial infections especially of the udder, leading to high white cell counts in marketed milk and reliance on antibiotics to treat and prevent mastitis-infection of the udder and other diseases. This is a significant contributing factor in the public health issue of antibiotic-resistant strains of bacteria in our food and environment.
Additional stressors potentially leading to immunosuppression include lack of humane husbandry practices, with overcrowding, confinement, poor sanitation, high “concentrate’ diets lacking natural roughage and the use of anabolic steroids, ractopamine (a beta-agonist) and rBGH ( recombinant bovine growth hormone) to boost productivity. Also considerable is electropollution, stray voltage being an issue on many dairy farms and being identified as a possible contributor to the high incidence of canine lymphoma in dogs exposed to electromagnetic radiation, along with herbicides of which cattle are processors in their feed. (3).
Antibiotic use on U.S. dairy operations remained mostly unchanged from 2002 to 2007. Since 2002, just over half of operations have used medicated milk replacer. About 60 percent of operations used antibiotics to treat pre-weaned heifers for disease, primarily respiratory disorders and diarrhea or other digestive problems. Sulfonamide and tetracycline were the most common antibiotics used to treat pre-weaned heifers. The use of ionophores and other antibiotics in weaned heifer rations remained the same from 2002 to 2007. Respiratory disease was the most common condition treated with antibiotics among weaned heifers in 2002 and 2007. Mastitis was the most common disease in cows for which antibiotics were used. Cows with mastitis were treated with antibiotics by about 85 percent of operations, and approximately 90 percent of operations used intramammary antibiotics for cows at dry-off. Cephalosporin was the primary antibiotic used for treating mastitis in 2002 and 2007. Tetracycline was the primary antibiotic used to treat lameness for both study years. (4)
A new report published by the Natural Resources Defense Council documents the overuse of antibiotics in the beef industry. Cattle producers purchased 42% of all imported antibiotics sold for livestock in the United States in 2018. In 2018, 7.5 million pounds of antibiotics were sold for human use and 5.6 million pounds were sold for cattle. This is in stark contrast to the European Union, where the use of antibiotics in cattle is discouraged. (5).
According to one determination of how many dairy cows are infected with BLV in the U.S. an average of 40 cows per herd was discovered to be infected. “94.2% of herds had at least one BLV antibody positive cow detected. The average within-herd standardized apparent prevalence (AP) was 46.5%. Lactation-specific AP increased with increasing lactation number, from 29.7% in first lactation cows to 58.9% in 4th and greater lactation cows. Significant differences were not observed based on region, state, breed, or herd size. These results are consistent with a historical trend of increasing prevalence of BLV among US dairy cattle.
Given the findings of other studies on the negative impacts of BLV infection on milk production and cow longevity, these findings are clinically relevant for veterinarians counseling dairy clients on the risks of BLV to their herds. (6).Making cow-calf separation less traumatic and allowing calves to suckle and spend some time with their mothers could help improve the immune systems of both. In a report discovering the Bovine leukemia virus in human blood, the investigators state: “Bovine leukemia virus (BLV) infection is widespread in cattle globally and is present in marketed beef and dairy products. Human infection with BLV has been reported in breast and lung cancer tissues and was significantly associated with breast cancer in 3 case-control studies. The purpose of this current research was to determine if BLV is present in human blood cells and if antibodies to BLV are related to blood cell infection”. Their research confirmed this possibility. (7). New data on the link between BLV and breast cancer in women was recently published. (8).
The only way to eradicate this virus is to test and kill infected animals, since there is no vaccine. Improved surveillance- testing and culling may not be economically feasible without government funding and compensation. The public could be at additional risk receiving COVID-19 antibodies derived from bovine plasma from cattle infected with the coronavirus for such antibody production if they are not tested and declared free of the BLV virus.
The mad cow prion disease infecting some 2,000 consumers of beef who developed CJ disease and risks of other zoonotic diseases from cattle all call for heightened vigilance. These include fifteen cattle diseases with zoonotic potential in the United States, some of which are more common than others: anthrax, brucellosis, cryptosporidiosis, dermatophilosis, Escherichia coli, giardiasis, leptospirosis, listeriosis, pseudo-cowpox, Q fever, rabies, ringworm, salmonellosis, tuberculosis, and vesicular stomatitis.(9). BLV now needs to be added to this list. The 24% incidence of hepatitis E virus in U.S. pigs is another emerging health concern. (10).
De-regulation of slaughtering standards in the spring of 2020 to allow faster processing puts consumers at risk because of compromised visual (so-called organoleptic) inspection of animals, and slaughterhouse workers from higher processing speeds increasing rates of injury, incidence of COVID-19 infections and the risk of contamination even from particles from stunned animals’ brains infecting workers’ brains. (11).
According to a review of BLV by Michigan State University: “At around the same time that North American dairy industries chose not to pursue BLV, many other countries opted to initiate BLV control programs, such that currently 21 countries have successfully eradicated BLV from all their cattle herds. Bovine leukemia virus was eradicated from all cattle in 12 European countries as of 2003, and from 8 additional European countries and New Zealand as of 2011. Additionally, BLV has been eradicated from most regions of Poland, Portugal, and Italy. In Western Australia, BLV has been successfully eradicated from dairy herds, but the government has decided to not attempt eradication of BLV from beef herds, which have a very low prevalence of infected cattle. In these countries, eradication was achieved mainly by testing and culling or segregating positive cattle.” (12).
It would seem that enzootic bovine leukemia (BLV) is essentially accepted in the U.S. with pasteurization of milk being the main preventive rather than mounting a concerted One Health initiative (13) of eradication which has been accomplished in other countries.
To be effective in reducing and preventing BLV and other zoonotic diseases, we must shift our diets and agriculture to a more sustainable, plant-based and microbial sourcing of nutritious foods; increase funding for disease surveillance (14); adopt humane and ecologically integrated farmed animal husbandry practices; keep free-ranging livestock and people out of the few remaining biodiversity hotspots left on Earth that are in urgent need of protection and restoration where various wild species are reservoirs for emerging diseases of pandemic potential.
DAIRY AND BEEF CARCINOGENICITY
Questions are also being raised concerning the contribution of consuming cow’s milk and meat to various health issues. The review by Willett and Ludwig (15) summarizes the evidence for the benefits and possible risks associated with consumption of cow’s milk. The authors describe the relationship of milk consumption to the risks of fracture, obesity, cardiovascular disease, allergies, and various cancers.
This is not the first study to demonstrate a positive association between dairy and increased breast cancer risk. In one survey of breast cancer cases across 40 countries and five continents, cows’ milk ranked second (only under meat) on a list of foods most correlated with breast cancer. (16). The authors state: ”When we name cows’ milk as one of the important routes of human exposure to estrogens, the general response of Western people is that “man has been drinking cows’ milk for around 2000 years without apparent harm.” However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751).”
Researchers believe the natural hormones found in all cows’ milk—including estrogen and IGF-1—may be the cause for this increased risk of specific cancers. Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer. (17).
Consumption of beef and processed meats has been linked in several studies with colorectal cancer. (18). Individual genetic susceptibility has been recently indicated (19). Clearly, it is time for consumers and healthcare advisors to recognize the risks of consuming beef, dairy and other foods of animal origin which could be a source of zoonotic diseases or result in cancer and other health problems which may be minimized by reduced consumption, improved disease surveillance and sourcing essential nutrients of plant origin.
2. Frie MC, Coussens PM. Bovine leukemia virus: a major silent threat to proper immune responses in cattle. Vet Immunol Immunopathol. 2015 Feb 15;163(3-4):103-14
3. Canine Lymphoma. https://www.acvim.org/Animal-Owners/Animal-Education/Health-Fact-Sheets/Oncology/Canine-Lymphoma
6. Prevalence of Bovine Leukemia Virus Antibodies in US Dairy Cattle. Rebecca M. LaDronka et al , Veterinary Medicine International Volume 2018, Article ID 5831278, 8 pages https://doi.org/10.1155/2018/5831278).
7. Bovine leukemia virus discovered in human blood. Gertrude C. Buchring et al BMC Infectious Diseases volume 19, Article number: 297 (2019)
8. Bovine leukemia virus DNA associated with breast cancer in women from South Brazil. Schwingel, D., Andreolla, A.P., Erpen, L.M.S. et al. Sci Rep 9, 2949 (2019). https://doi.org/10.1038/s41598-019-39834-7
10. Hepatitis E Virus in Pigs from Slaughterhouses, United States, Sooryanarain H, Heffron CL, Hill DE, Fredericks J, Rosenthal BM, Werre SR, et al. 2017–2019. Emerg Infect Dis. 2020;26(2):354-357. https://dx.doi.org/10.3201/eid2602.191348
11.Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain Stacy M. Holzbauer, Aaron S. DeVries, James J. Sejvar, PLoS One. 2010; 5(3): e9782.
12. http://blv.msu.edu/basics/prevalence.html 13. https://www.onehealthinitiative.com 14. Bartlett PC, Sordillo LM, Byrem TM, et al. Options for the control of bovine leukemia virus in dairy cattle. J Am Vet Med Assoc 2014;244:914–922. See also: http://blv.msu.edu/resources/USAHA-Oct-16-2017.pdf 15. Walter C. Willett and David S. Ludwig, Milk and Health N Engl J Med 2020; 382:644-654 DOI: 10.1056/NEJMra1903547 https://www.nejm.org/doi/full/10.1056/NEJMra1903547 16. Davaasambuu Ganmaa and, Akio Sato The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers. Med Hypotheses. 2005;65(6):1028-37. doi: 10.1016/j.mehy.2005.06.026. Epub 2005 Aug 24. 17. Johanna E. Torfadottir, Laufey Steingrimsdottir, Lorelei Mucci,et al. Milk Intake in Early Life and Risk of Advanced Prostate Cancer. Am J Epidemiol. 2012 Jan 15; 175(2): 144–153. 18. Kathryn E Bradbury, Neil Murphy, Timothy J Key Diet and colorectal cancer in UK Biobank: a prospective study International Journal of Epidemiology, Volume 49, Issue 1, February 2020, Pages 246–258, https://doi.org/10.1093/ije/dyz064 19. Justyna Klusek, Anna Nasierowska-Guttmejer, Artur Kowalik et al The Influence of Red Meat on Colorectal Cancer Occurrence Is Dependent on the Genetic Polymorphisms of S-Glutathione Transferase Genes Nutrients. 2019 Jul; 11(7): 1682. Published online 2019 Jul 22. doi: 10.3390/nu11071682