1. General Considerations

   1. Herpesviruses are widely distributed in nature and infect a variety of vertebrates. Most animal species harbor at least one member of the herpes virus group.
   2. We will discuss the diseases caused by herpesviruses that are of economic importance in cattle, sheep, pigs and horses including bovine herpes mammilitis, pseudo-lumpy skin disease, bovine herpes mammary pustular dermatitis, bovine malignant catarrhal fever and pseudorabies.
   3. Bovine herpes mammillitis
      1. It is caused by bovine herpesvirus 2, a dermatotropic herpesvirus.
      2. In temperate climates, the disease typically coincides with the presence of flies.
      3. Transmission is generally via direct contact between infected and susceptible animals during animal transportation. It is presumed that transmission may also occur via insect bites and that some cattle become carriers of the virus, which could result in virus shedding during stressful situations.
      4. The incubation period ranges from 5 to 10 days.
      5. Heifers are more susceptive and tend to be more severely affected. Outbreaks can occur in milking cows with about 30% morbidity.
      6. Two epidemiologic patterns have been described including a rapid disease spreading to the majority of the herd and a disease confined to calved heifers introduced in the milking herd for the first time.
      7. Clinical signs:
         1. Most cattle show no systemic illness but occasionally heifers may develop fever.
         2. Skin lesions are characterized initially by a painful and edematous teat.
         3. Initial lesions are followed by the development of an irregularly shaped vesicle. Within 24 hours, the vesicles rupture, leaving an ulcerated surface that exudes copious serum. Upon drying, this exudate forms a thick, dark, reddish brown scab.
         4. One or more teat can be affected and the disease can spread to the udder. Lesions on the udder may coalesce with those of the teat and extend to the perineum, which may result in vulvovaginitis.
         5. In the absence of secondary infection, healing is complete in 3 weeks but it may take as long as 10 weeks in severe cases.
         6. Economic loss can be significant because severely affected cows do not allow milking and cannot feed their calves.
      8. Differential diagnoses:
         1. Peracute staphylococcal mastitis
         2. Photosensitive dermatitis.
      9. Preliminary diagnosis is based on a detailed history, characteristic clinical signs and histopathological findings. For viral identification, viral isolation, serology, immunofluorescence and/or molecular tests are needed.
         1. Histopathology reveals epidermal keratinocyte syncytial formation and prominent eosinophilic intranuclear inclusion bodies (Cowdry’s Type A). The inclusion bodies are numerous for only about 5 days after the lesions develop because relatively soon thereafter the epidermis becomes necrotic and ulcerated.
         2. Molecular diagnostic methods, including quantitative PCR and next-generation sequencing, have high sensitivity and specificity and enable the detection of herpesvirus DNA or RNA in clinical samples. A non-nested PCR assay was successfully used to detect a wide range of herpesviruses.
      10. Treatment:
          1. Treatment is symptomatic and should focus on allowing the lesions to heal uneventfully without the development of secondary infections.
          2. Prevent milking of severely affected cows.
          3. Dip teats with iodine-based or crystal violet solution.
          4. Institute measures to stop the spreading of infection such as, isolation of affected animals, milking affected cows last, udder washing and teat disinfection, hand washing and disinfection of the milking machine between and after milking.

1. 4. Bovine pseudo-lumpy skin disease
      1. Similar to bovine herpes mamillitis, it is caused by bovine herpesvirus 2, a dermatotropic herpesvirus.
      2. The disease has a worldwide distribution but occurs primarily in southern Africa.
      3. It can affect dairy and beef cattle.
      4. Clinical signs:
         1. Transient moderate fever and mild lymphadenopathy occur initially but may not been noted.
         2. Cutaneous lesions are located much more superficially in the skin than those of true lumpy skin disease.
         3. Lesions are characterized by slightly raised circular to oval firm plaques with a central depression and superficial necrosis. Lesions range from 1-5 cm in diameter.
         4. Lesions start healing within 2 weeks and complete resolution and hair growth can occur within 2 months.
      5. Preliminary diagnosis is based on a detailed history, characteristic clinical signs and histopathological findings. For viral identification, viral isolation, serology, immunofluorescence and/or molecular tests are needed.
         1. Histopathology shows eosinophilic intranuclear inclusion bodies within keratinocytes of the stratum spinosum. In addition, hydropic interface dermatitis with epidermal keratinocyte syncytial formation is also a characteristic histopathological finding.
         2. Molecular diagnostic methods, including quantitative PCR and next-generation sequencing, have high sensitivity and specificity and enable the detection of herpesvirus DNA or RNA in clinical samples. A non-nested PCR assay was successfully used to detect a wide range of herpesviruses.
      6. Differential diagnosis:
         1. Lumpy-skin disease
      7. Treatment:
         1. No treatment is needed in most cases.

1. 5. Bovine herpes mammary pustular dermatitis
      1. It is caused by bovine herpesvirus 4.
      2. Lesions are seen in lactating cows and tend to be more numerous and severe in heifers.
      3. Lesions are characterized by vesicles and pustules and are typically localized to the udder.
      4. The disease appears to be generally mild and economic losses are minor.
      5. Differential diagnosis:
         1. Udder impetigo caused by Staphylococcus spp. is an important differential.
      6. Diagnosis:
         1. Preliminary diagnosis is based on a detailed history, characteristic clinical signs and histopathological findings. For viral identification, viral isolation, serology, immunofluorescence and/or molecular tests are needed.
            1. Histopathology shows intraepidermal pustules, necrotic keratinocytes, and a predominance of neutrophils in the dermis. Intranuclear inclusion bodies can be seen in keratinocytes adjacent to the necrotic epidermis.
            2. Molecular diagnostic methods, including quantitative PCR and next-generation sequencing, have high sensitivity and specificity and enable the detection of herpesvirus DNA or RNA in clinical samples. A non-nested PCR assay was successfully used to detect a wide range of herpesviruses
      7. Treatment:
         1. The disease is typically mild and no treatment is needed in most cases.

1. 6. Bovine malignant catarrhal fever
      1. It is an acute often fatal systemic disease of cattle and less frequently other ruminants and pigs.
      2. It has a wide distribution around the world.
      3. Several closely related gammaherpesviruses have been associated with the disease.
      4. The incubation period in natural infection varies from about 3 to 4 weeks but in experimentally infected animals it ranged from 7 days to 10 weeks.
      5. At least two distinct epidemiologic patterns of the disease have been reported:
         1. The “wildebeest”-associated form is caused by Alcelaphine herpesvirus 1 and is transmitted by wildebeest. It is seem primarily in Africa but it can also occur in wildlife facilities keeping wildebeest.
         2. The sheep-associated form is seen all over the world and is caused by ovine herpesvirus 2. Sheep transmit the virus to cattle and other susceptible hosts.
      6. Clinical signs:
         1. There are several different clinical forms.
            1. Nonspecific signs include fever, depression, leukopenia and generalized lymphadenopathy.
            2. The clinical presentation seen most frequently is the “head and eye” form. It is characterized by profuse nasal and ocular discharge, bilateral diffuse corneal edema, photophobia, conjunctivitis, and oral mucosal erosions. Erosions can also affect the oral cavity mucosa and gastrointestinal mucosa leading to melena.
            3. Cutaneous lesions can be seen in the “head and eye” form and are characterized by erythema, scaling, necrosis, and ulceration of the muzzle and face. Occasionally lesions are seen in the teats, udder, vulva and scrotum. Papules, crusts, thickening, oozing and necrosis may affect the skin in the perineal, axillary, inguinal and back regions.
            4. Less common clinical presentations include (i) fever up to 108°F followed by rapid death; (ii) neurologic signs, (iii) severe hemorrhagic diarrhea followed by death in about 1 to 2 days.
      7. Differential diagnoses:
         1. The clinical signs of malignant catarrhal fever probably most closely resemble Bluetongue in cattle, especially the oral and muzzle lesions.
         2. Vesicular diseases (e.g. foot-and-mouth disease, vesicular stomatitis) might also be differential diagnoses but can easily be excluded because these diseases elicit vesicles in the oral mucosae, teats, and coronary bands.
      8. Diagnosis:
         1. Preliminary diagnosis is based on a detailed history, characteristic clinical signs and histopathological findings. For viral identification, viral isolation, serology assays (i.e. viral neutralization, immunoperoxidase, immunofluorescence and ELISA) and/or molecular tests are needed. The monoclonal-based competitive ELISA is currently the most specific technique. PCR assay is the only test able to distinguish the different viruses.
      9. Treatment:
         1. It is nearly always fatal and usually does not respond to treatment. Considering the significant immunopathologic reaction, large doses of corticosteroids (dexamethasone at 55 mg per 50 kg) may help in symptomatic treatment of the disease.
         2. Antibiotics and/or sulfonamides should be administered simultaneously.

1. 7. Pseudorabies

      1. Pseudorabies (also known as Aujesky’s disease, mad itch, infectious bulbar paralysis) is a contagious infectious disease caused by Suid Herpesvirus 1 (SuHV-1), an alpha-herpesvirus with potent neurotropism.
      2. The reservoir hosts of the virus are feral and domestic pigs and wild boars.
      3. It is primarily a disease of pigs but it occurs incidentally in most species.
      4. There are reports of the disease also affecting humans including veterinarians and animal management personnel are at higher risk.
      5. Pseudorabies has a worldwide distribution.
      6. Clinical signs:
         1. It is acute and rapidly fatal (24-72 hours).
         2. In companion animals, viral transmission can occur by ingestion of infected pig offal and raw meat or via a bite wound of an infected pig.
         3. After inoculation, the pseudorabies virus is transported via sensory nerves to the spinal cord and the brain.
         4. Nerve irritation and inflammatory changes cause unrelenting pruritus that is not relieved by scratching. The pruritus typically starts between 1-10 days from exposure to the virus. Skin lesions are secondary to self-mutilation and the virus is not present in the skin.
         5. In ruminants and swine, pseudorabies causes an intense, localized, unilateral pruritus.
         6. The site of the itch is determined by the site of the infection in spinal ganglia, sensory neurons of dorsal horns, and brain stem.
         7. Any part of the body can be affected.
      7. Differential diagnosis:
         1. Rabies.
      8. Diagnosis:
         1. History, characteristic clinical signs, confirmation of pseudorabies infection by virus isolation on frozen brain tissue, and molecular techniques (PCR and real-time PCR). Serologic tests (i.e. seroneutralization and ELISA) are not used because typically the animals die before antibodies are formed
      9. Treatment:
         1. There is no treatment because affected animals die within 24-72 hours post-infection.

References

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