History

A 30-day-old male calf of undefined breed died and underwent necropsy at the Setor de Patologia Veterinária–Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, following a history of neurological signs with a clinical progression of 7 days. The bovine was part of a herd of 70 calves that were in an area of native pasture with their dams. In this herd, there was a history of anaplasmosis and bovine babesiosis (cattle tick fever); however, only this calf was affected by the neurological disease. The cows in this herd were vaccinated for reproductive diseases (bovine infectious rhinotracheitis, bovine viral diarrhea, and leptospirosis), bacillary hemoglobinuria, and rabies.

Clinical and Gross Findings

The calf had nasal and ocular discharge, weight loss, and fever for 7 days. During that time, the calf became less alert, developed motor incoordination, became comatose, and then died on day 7. Treatment was attempted with oxytetracycline (6 mg/kg, IM, q 24 h), penicillin (6.66 mg/kg, IM, q 24 h), and dipyrone (25 mg/kg, IM, q 8 h) for 5 days. However, despite the treatment, there was no clinical improvement and the calf died. During the necropsy, predominant findings were found in the brain, in which slightly depressed, friable (softening), and reddened areas were observed bilaterally in the rostral portion of the frontal lobes (Figure 1). Upon sectioning, these areas displayed a yellowish discoloration with reddish foci and a marked reduction of gray matter. Foci with similar lesions were also observed in the cortex of the right parietal lobe. No remarkable gross lesions were seen in the remaining organs.

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Postmortem images of the brain of a 30-day-old mixed-breed bull calf that died after 7 days of nasal and ocular discharge, weight loss, fever, and progressively deteriorating neurological signs (depression, motor incoordination, recumbency, then coma). A and B—There are friable, depressed, and hemorrhagic areas (asterisks) in the frontal telencephalic cortex. C—There are areas of rarefaction of the neuropil associated with pronounced malacia, marked infiltration of gitter cells, and perivascular cuffs (white arrow). H&E stain; bar = 100 µm. D—There is malacia associated with marked infiltration of gitter cells (green arrow), lymphocytes (blue arrow), plasma cells (red arrow), and macrophages surrounding blood vessels (perivascular cuffs). H&E stain; bar = 100 µm. Inset—An astrocyte with an amphophilic intranuclear viral inclusion body (black arrow). H&E stain, bar = 50 µm.

Citation: Journal of the American Veterinary Medical Association 262, 9; 10.2460/javma.24.04.0277

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Histopathologic Findings

Organ samples were collected, fixed in neutral-buffered 10% formalin, routinely processed for histopathology, sectioned at 3 µm, and stained with H&E. Segments of the CNS were collected and frozen for subsequent molecular analysis.

Histologically, the neurological lesions in the gray matter consisted of focally extensive areas of marked malacia associated with a moderate amount of necrotic neurons, infiltration of gitter cells, and hemorrhage. In the leptomeninges and surrounding blood vessels, a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells, and macrophages (perivascular cuffs) was observed (Figure 1). Furthermore, occasional neurons and astrocytes exhibited amphophilic intranuclear inclusion bodies.

Molecular Findings

Frozen samples of the brain were submitted for DNA extraction for further PCR assay. Primers forward (PF 5′ CGGCCACGACGCTGACGA 3) and reverse (PR 5′ CGCCGCCGAGTACTACCC 3) were designed to target a 575/572 bp fragment on bovine herpesvirus (BoHV) types 1 and 5 (nucleotides 873–1447 and 813–1384 from sequences accession) and were positive for the CNS samples.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: severe nonsuppurative and necrotizing meningoencephalitis with intranuclear inclusion bodies.

Etiological diagnosis: herpetic meningoencephalitis.

Case summary: herpetic meningoencephalitis (BHV-1 and BHV-5) in a 30-day-old mixed-breed calf.

Comments

The gross and microscopic findings in this calf were consistent with meningoencephalitis caused by BoHV infection (herpetic meningoencephalitis). The etiological diagnosis was established through PCR analysis for the bovine herpesvirus C glycoprotein (types 1 and 5), detected from frozen samples of the brain. Bovine herpesvirus is a large, enveloped DNA virus belonging to the family Herpesviridae, subfamily Alphaherpesvirinae, and genus Varicellovirus.¹

Cases of necrotizing meningoencephalitis in cattle have been classically associated with BoHV-5 infection. Bovine herpesvirus type 1 infection is typically related to abortion, respiratory diseases (infectious bovine rhinotracheitis), and genital diseases (infectious bovine vulvovaginitis and balanoposthitis) in cattle. However, it is known that both BoHV-1 and BoHV-5 cause identical neurological diseases in endemic areas. In the present case, both herpesviruses (BoHV-1 and BoHV-5) were detected, which is already described in the literature.² Therefore, it is suggested that cases of necrotizing meningoencephalitis caused by BoHV-1 infection are not uncommon and could have coinfection with both types in the development of neurological lesions in cattle.

Meningoencephalitis due to BoHV-1 or BoHV-5 shares many similarities regarding epidemiological and clinicopathological findings. The disease mainly affects calves and young adults submitted to environmental or management-related stressors, including weaning, high number of cattle in a restricted area, transportation, and introduction of new animals into the herd.^1–3 This report describes an unusual presentation of the disease, involving the isolated case of a 30-day-old calf. Cases of cattle infected by BoHV-1 and BoHV-5 generally involve animals older than the age reported here.^2,3 Furthermore, stressful factors frequently related to the development of the disease (weaning, transport, high density) were not identified in this case. It is suggested that failure in colostrum intake favored viral infection. Adequate colostral intake contributes to immunological strengthening, preventing the development of clinical disease in cattle.^3,4 The disease has an average clinical duration of 6 days, consistent with the present case, although cases with both acute and chronic progression have been reported.² The clinical signs of the present case indicate a classical clinical course, with initial clinical signs characterized by fever, profound depression, and nasal and ocular discharge.^3,4 The progression of the disease is characterized by blindness, excessive salivation, nystagmus, opisthotonus, incoordination, and recumbency.^1,3

Grossly, as seen in this case, there is hyperemia of the leptomeninges, hemorrhages, and softening of the frontal cortex. In more advanced cases, there may be areas of absence of the telencephalic cortex. Similar to what is documented in the literature, brain lesions were predominant in the rostral portions of the telencephalon, which reinforce the diagnostic suspicion of herpesvirus infection. This morphological aspect, combined with the absence of lesions in the trigeminal nerve, reinforces the evidence that the olfactory pathway is the main route of viral invasion into the nervous system in natural cases of the disease.²

Histologically, the cattle in this report showed necrotizing nonsuppurative meningoencephalitis, similar to other cases described for BoHV-1 and BoHV-5 infection. The lesions are commonly observed in the gray matter in the rostral portions of the telencephalon and are characterized mainly by mononuclear perivascular cuffs, leptomeningitis, neuronal necrosis, gliosis, and gitter cell infiltration. These histological changes vary in terms of location and progression.² The occurrence of intranuclear astrocytic or neuronal viral inclusions, like in this case, may vary among cases, especially in the early lesions, but when present they play a crucial role in the presumptive diagnosis of bovine herpesvirus infection.^1,3

Herpetic meningoencephalitis does not have a specific treatment, and prevention measures are based on disease control. Cross protection between BoHV-1 and BoHV-5 has been experimentally demonstrated in cattle through immunization; however, these results do not yet allow us to conclude that the vaccine provides cross protection in field challenges.¹ In this case, the recommendation of identifying persistently infected animals and eliminating them from the herd can be an alternative for disease control.

One of the medications used for the treatment of the animal, dipyrone, was commercially available in the area where the herd was affected. It is emphasized that this medication is not approved by the FDA and therefore is not commercially available in the US. On the basis of the epidemiological aspects and gross and microscopic findings in this calf, the main differential diagnoses at the time of necropsy included rabies, bacterial meningitis, cerebral babesiosis, listeriosis, and polioencephalomalacia.^1,2 The areas of cortical malacia visible macroscopically in the frontal regions of the brain in this case are lesions frequently observed in herpetic meningoencephalitis in cattle and assist in the suspicion and diagnosis of the condition. Furthermore, molecular analysis of the nervous system confirmed the infectious agent involved.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

ORCID

P. Sônego https://orcid.org/0009-0001-1719-9373