BHV-4 Contributes to Udder Lesions

Gross photos- Severe, ulcerative, progressive mammary lesions

Histologic images- Udder skin- Normal dermal structures, including adnexal structures, are replaced by sheets of proliferating spindle cells. Note the scarcity of blood vessels. The higher power image shows a pure population of these spindle cells along with small blood vessels.

( Dr. Doug Lyman, University of Wisonsin )

Control measures for bovine herpesvirus 4 (BHV-4), which is relatively common in dairy herds, could reduce udder disease and protect milk quality.

In this case from the Wisconsin Veterinary Diagnostics Laboratory, a well-managed, highly productive, 1,700 cow dairy herd experienced, over the course of five or more years, an increasing incidence of severe, ulcerative, progressive mammary lesions, affecting 15% of cows. Lesions most often developed in the mammary clefts and spread to affect the majority of the ventral udder and medial teat surfaces, but also developed on the lateral udder and spread distally to affect the lateral teat surfaces. 

Lesions also developed on the ventral abdomen cranial to the udder itself and subsequently spread caudally to the udder.  The lesions start as areas of superficial dermatitis, before progressing to areas of deep, necrotizing, ulcerative dermatitis.  With progression, lesions often necrose and migrate into the udder glandular tissue itself, sometimes resulting in milk fistulas or hemorrhage.

A few animals developed pedunculated masses arising in the mammary cleft. Multiparous animals are affected more frequently, but primiparous animals also develop lesions throughout their lactation.  Lesions have not been identified in prepartum heifers.  The lesions typically improve throughout the dry period, but do not completely resolve and sometimes recrudesce after freshening. Tissue on the margins of the lesions is often thickened and firm with an ivory appearance on cut section.  See gross photos.    

A variety of topical disinfectants, topical antiparasitics, and drying agents have been applied without effect.  Parenteral administration of broad spectrum antibiotics in severe cases has also been unsuccessful.  The entire herd was on an annual topical antiparasitic pour on program since approximately 2002, with the exception of 2009 and continuing to the present.   Skin scrapings of lesions from multiple individuals were examined microscopically and no ectoparasites were identified. 

Punch biopsies from the margins of expanding lesions were obtained from 5 cows. Histopathology of these biopsies is described in the image legends. Ancillary testing of these samples included:

  • PCR testing: Five of five samples tested positive for bovine herpesvirus 4 (BHV-4) with CT levels ranging from 30 to 37.
  • Electron microscopy: Four of five samples had particles consistent with herpesviruses.
  • Virus isolation: Positive in only the sample with the lowest CT value.
  • Serology: Serum from 15 animals exhibiting the aforementioned udder lesions and from 10 unaffected lactating herdmates was submitted to the National Veterinary Services Laboratory in Ames, IA for BHV-4 indirect fluorescent antibody testing. Testing revealed an odds ratio of 26, indicating that test positive animals were 26 times more likely to have lesions or, vice versa, animals with lesions were 26 times more likely to test positive.

Several years have now passed since this testing and, though new cases continue to occur, the incidence is now less than 1% at any given time. Significant management changes to this end have included:

  • BLV/leucosis control: Testing identified a very high prevalence of BLV in the herd. A suspected BHV-4 and BLV synergism along with an increasing incidence of clinical lymphoma led to control measures of individual needle use for all injections and pasteurization of colostrum. Clinical incidence of lymphoma cows and BLV/Leucosis associated conditions (cancer eye, etc.) significantly decreased, however, incidence screening has not been repeated.
  • Bedding quality: The farm placed more emphasis on improving recycled sand quality, including decreased moisture content, decreased bacterial counts, and decreased organic matter.
  • Culling: The farm engaged in aggressive culling in 2017-2018 with excessive replacements and discontinued use of BST.
  • Udder health: Combined efforts greatly improved udder health, with somatic cell counts (SCC) now averaging 95 to 100.

A common “uncommon” disease

BHV-4 is a member of the gammaherpesvirus family and has been linked to numerous bovine health problems but has never been proven to be causative. Unlike members of the alphaherpesvirus family, such as IBR and mammillitis viruses, gammaherpesviruses circulate in infected macrophages and lymphocytes and can induce proliferations of mesenchymal cells such as seems to occur with udder lesions, though it has been suggested that BHV-4  s incapable of this. Vertical transmission of this virus has been documented along with postpartum seroconversion. 

The virus appears to be common in the Wisconsin dairy cattle population with limited testing suggesting an incidence of 25 to 50%. A possible synergism with BLV was mentioned above and is based on known occurrences of this phenomenon involving gammaherpesviruses and retroviruses in other species.  

Mesenchymal proliferations on the bovine heart and pericardium that have colloquially come to be known as “shaggy heart disease” often test positive for both BHV-4 virus and BLV, though BLV testing was, regrettably,  not performed on the biopsies in this case. Similar proliferations in the myocardium and liver have also been identified in cows from this herd.  

Interestingly, the equine lung disease termed  equine multinodular pulmonary fibrosis, which features a proliferation of mesenchymal cells  similar to those mentioned above,  has recently been shown to be associated with infection by equine herpesvirus 5, also a gammaherpesvirus , though a coinfectant has not been identified.

A flurry of inquiries and submissions subsequent to initial dissemination of this information suggests that this condition is relatively common but continues to run under the diagnostic radar. Histopathology suggests the possibility of an ischemia induced lesion which would go a long ways towards explaining the slowly progressive and slowly regressive nature of the condition as well as the refractoriness to the many treatments attempted. Unfortunately, association does not establish causation and much work needs to be done to better characterize this perplexing and consequential condition.

Many thanks to Dr. Kelly Peters of Appleton, Wis. for the initial and follow-up herd/clinical information and for the procurement of the necessary biopsies. Thanks also to my colleague, Dr. Phil Bochsler, for alerting me to infection by this virus.


 

 

 

 

 

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