Pathology of Viral Diseases in Ruminants

Rinderpest (Cattle Plague)

Rinderpest, historically known as cattle plague, is a highly contagious viral disease that primarily affects cloven-hoofed animals, specifically cattle and buffalo. It also impacts sheep, goats, pigs, giraffes, and various wild ruminants. The disease holds significant historical importance as the first modern veterinary school in Lyon, France, established in $1762$, was founded specifically to combat Rinderpest. The World Organisation for Animal Health (OIE) was created in $1924$ to assist in its eradication, which was successfully achieved globally in $2011$. It remains a notifiable disease.

The aetiology of Rinderpest involves the Paramyxoviridae family, specifically the genus Morbillivirus. It is closely related to viruses causing PPR (Peste des Petits Ruminants), canine distemper, and measles, with various strains exhibiting variable virulence. Transmission occurs through aerosols and direct contact with ocular and nasal secretions. The pathogenesis follows an incubation period of $3-15$ days. The virus first replicates in lymphocytes and macrophages, leading to lymphoid necrosis, followed by replication in the epithelial cells of the gastrointestinal tract (GIT) and respiratory tract.

Typical gross lesions include areas of necrosis, erosions, congestion, and haemorrhage in the GIT and upper respiratory tracts. Epithelial necrosis of the abomasal mucous membrane results in a highly engorged or grey discoloured appearance. The pyloric region is often severely affected, showing congestion, petechiation, and submucosal oedema. While the rumen, reticulum, and omasum are usually unaffected, necrotic plaques may occasionally be found on the rumen pillars. Lymph nodes become enlarged and oedematous. A hallmark lesion is the presence of white necrotic foci in Peyer’s patches, where lymphoid necrosis and sloughing leave the architecture engorged or blackened. Linear engorgement and haemorrhages of the longitudinal folds in the large intestine are known as "Zebra striping." Carcasses are typically dehydrated, emaciated, and soiled with purulent discharges and fibronecrotic exudate.

Milder forms of Rinderpest in domestic animals may lack erosions, presenting only with slight congestion or white, pin-head-sized focal necrotic areas on the gum. In wild animals, such as African buffaloes, milder strains (lineage $2$) cause enlarged peripheral lymph nodes, plaque-like keratinised skin lesions, and keratoconjunctivitis. Lesser kudus may suffer blindness from severe keratoconjunctivitis without diarrhoea, while elands exhibit buccal mucosa necrosis and emaciation. Histopathologically, the disease is characterized by lymphoid and epithelial necrosis, viral-associated syncytia, and the presence of both intracytoplasmic and intranuclear inclusions.

Bovine Viral Diarrhoea and Mucosal Disease Complex

Bovine Viral Diarrhoea (BVDV) is caused by a virus in the family Flaviviridae, genus Pestivirus, which is the same genus as the Classical Swine Fever virus. Cattle of all ages are susceptible. The virus is classified into two genotypes, BVDV type $1$ and BVDV type $2$, further divided into cytopathogenic (cp) and noncytopathogenic (ncp) biotypes based on in vitro cell culture characteristics. Pathogenesis is heavily influenced by the timing of infection during pregnancy: infection before day $18$ results in no infection as the embryo is not yet attached; infection between days $29-41$ leads to embryonic death; infection between day $30$ and the end of the first trimester results in persistently infected (PI) calves; infection between $80$ and $150$ days causes teratogenic effects; and late-gestation infection leads to foetal seroconversion.

In acute infections of immunocompetent, non-pregnant animals, the virus infects lymphocytes and macrophages, causing a transient viraemia lasting $10-14$ days. This results in short-term leukopenia, lymphopenia, thrombocytopenia, and apoptosis in the thymus and Gut-Associated Lymphoid Tissue (GALT). Immunosuppression allows for secondary infections, such as those caused by Neospora caninum. Virus clearance usually occurs via T cell-mediated destruction of infected lymphocytes by day $9-13$, though some cattle may carry the virus for $98$ days or more. Gross lesions include erosions or ulcers along the GIT, catarrhal enteritis, and multifocal lymphoid depletion leaving karyorrhectic debris in germinal centers.

Persistent Infection (PI) occurs when a dam is infected with ncp BVDV during the first trimester (approximately $25-90$ days of gestation). The virus inhibits the induction of type I interferon in the fetus, allowing it to survive without an antibody response. PI animals shed large volumes of virus in all secretions including milk, semen, saliva, urine, and blood. While some PI animals appear healthy, many are stunted, prone to secondary infections, and typically die before $2$ years of age. Crucially, PI cows always give birth to PI calves.

Mucosal disease is a fatal condition that only develops in PI cattle. It occurs when the ncp BVDV in a PI animal undergoes mutation into a cp BVDV biotype. This biotype localizes in the germinal centers of lymph nodes, tonsils, and Peyer's patches. It promotes monocyte activation while inhibiting antigen presentation to T cells, causing uncontrolled inflammation. This leads to severe lymphoid depletion, atrophy of Peyer's patches, and disappearance of microvilli. Necrosis of keratinocytes in the stratum spinosum results in weakened epithelial surfaces that erode and ulcerate upon normal wear, leading to severe diarrhoea, dehydration, and secondary septicaemia. Lesions include ulcerative epidermitis of the planum nasale, mucosal ulceration of the larynx, oesophageal ulcers, and myocardial degeneration.

Bovine Ephemeral Fever (Three-Day Sickness)

Bovine Ephemeral Fever (BEF) is caused by an arbovirus in the family Rhabdoviridae, genus Ephemerovirus. It is characterized by a sudden fever lasting $1-2$ days, accompanied by stiffness and shifting lameness. Some animals may become recumbent for up to a week. Clinical signs include subcutaneous swelling in the sub-mandibular area or limb joints, elevated respiratory rate, dyspnoea, nasal and ocular discharges, hypersalivation, periorbital swelling, and increased excitability.

The pathogenesis involves the virus inducing neutrophilia $24$ hours post-infection. The virus infects endothelial cells, leading to inflammation and toxaemia in blood vessels, joints, and mucosa. Massive interferon production is associated with the accumulation of plasma fibrinogen in joints and body cavities (peritoneal, pleural, and cardiac). A sharp fall in blood calcium levels (hypocalcaemia) is responsible for signs of nerve paralysis.

Pathological findings include serofibrinous polyserositis in articular synovial membranes and body cavities, yielding yellow or brown gelatinous periarticular fluid. Other lesions include oedema of lymph nodes, pulmonary oedema, pericarditis (particularly at the heart base), skeletal muscle necrosis, and emphysematous lesions in the lungs and subcutaneous connective tissue. Differential diagnoses include Rift Valley fever, heartwater, botulism, babesiosis, and various poisonings such as Diplodia maydis.

Infectious Bovine Rhinotracheitis (IBR)

Infectious Bovine Rhinotracheitis (IBR), also known as Infectious Pustular Vulvovaginitis (IPV), is caused by Bovine Herpesvirus-1. The disease presentation depends on the viral strain and route of entry. While it primarily infects the upper respiratory tract, it can rarely cause reproductive disease (venereal form) or severe enteric and nervous disease in neonatal calves. A key feature is that the virus establishes a latent infection in the nervous system for life, reactivating during periods of stress.

Pathology is generally restricted to the upper respiratory tract, manifesting as mucosal swelling and congestion, necrotic foci, petechiae, and profuse fibrinopurulent exudate. In some cases, ruminal ulcers are observed in calves. While individual differential diagnoses include pneumonia or Mucosal Disease, outbreaks in groups must be distinguished from Bluetongue, Foot and Mouth Disease, and other respiratory pathogens like Bovine Parainfluenza virus or Bovine Respiratory Syncytial Virus.

Rift Valley Fever (RVF)

Rift Valley Fever is caused by a virus in the family Bunyaviridae, genus Phlebovirus. It is a major zoonosis and a significant disease for cattle, sheep, goats, and camels. The virus targets the liver and adrenal glands, where it replicates in hepatocytes and adrenal cortical cells. Hepatic damage significantly reduces prothrombin synthesis, impairing blood coagulation and leading to widespread haemorrhaging. In pregnant animals, infection almost invariably results in abortion at any gestation stage, with the fetuses often undergoing autolysis.

Newborn lambs and kids are the most susceptible, with mortality rates reaching $90\%$ or higher within $36$ hours of infection. They exhibit high fever, listlessness, and rapid respiration. Older or mature animals can have inapparent to acute disease, characterized by anorexia, weakness, and sometimes blood-stained nasal discharge or fetid diarrhoea (melaena). In adult cattle, the mortality rate is usually below $10\%$, and abortion may be the only clinical sign. A hallmark of RVF epizootics is the simultaneous occurrence of influenza-like illness in humans working with the livestock.

Post-mortem findings include focal or generalized hepatic necrosis (white necrotic foci approximately $1\,mm$ in diameter), hepatomegaly, and subcapsular haemorrhages. In aborted fetuses, the liver may appear brown-yellowish. Further lesions include widespread cutaneous haemorrhages, petechial or ecchymotic haemorrhages on serosal membranes, haemorrhagic enteritis, and congestion of the kidneys and gallbladder. Jaundice is more frequently seen in calves than other groups.

Bovine Vesicular Stomatitis

Bovine Vesicular Stomatitis is caused by the Vesicular Stomatitis Virus (VSV), a member of the family Rhabdoviridae, genus Vesiculovirus. Two distinct immunological classes exist: New Jersey (NJ) and Indiana (IND). The Indiana group is further subdivided into IND-$1$ (Classical), IND-$2$ (Cocal), and IND-$3$ (Alagoas). The pathology is characterized by the formation of vesicles, ulcers, erosions, and crusting on the muzzle, lips, oral mucosa, nostrils, teats, and feet. These vesicles are prone to rupture, particularly on the hard palate and dental pad. Because its clinical presentation—severe salivation and oral/foot lesions—is indistinguishable from Foot and Mouth Disease, Swine Vesicular Disease, and Vesicular Exanthema of Swine, it is a high-priority differential diagnosis.

Bovine Spongiform Encephalopathy (BSE)

Bovine Spongiform Encephalopathy (BSE) is a transmissible, fatal central nervous system disease of cattle caused by prions, which are unconventional transmissible agents similar to those causing scrapie in sheep. It is a zoonotic disease, linked to the variant Creutzfeldt-Jakob disease in humans. BSE has a long incubation period of at least $4-5$ years. The clinical course is insidious, beginning with behavioral changes like apprehension, nervousness, or frenzy, and progressing to abnormalities in posture, ataxia, hypermetria, muscle fasciculations, tremors, and hyperaesthesia. Autonomic dysfunction, such as reduced rumination and bradycardia, is also noted.

Pathogenesis studies suggest that after oral exposure, the agent replicates in the Peyer’s patches of the ileum before migrating to the CNS via peripheral nerves. While there are no characteristic gross lesions, histopathology reveals a characteristic spongiform encephalopathy, defined by bilateral and symmetrical vacuolization of the gray matter neuropil. Its slow onset and progressive nature help differentiate it from nervous ketosis, lead poisoning, or rabies.

Rotavirus and Bovine Leucosis

Rotavirus (family Reoviridae) is a primary cause of diarrhoea in newborn calves aged $1$ to $2$ weeks. The virus infects enterocytes on the microvilli of the small intestine, leading to vacuolization and death of enterocytes, followed by crypt epithelium hyperplasia. The disease mechanism involves malabsorption, villus ischemia, the activity of the NSP4 viral enterotoxin, and activation of the enteric nervous system. This results in watery-brown to light green faeces, potentially containing blood and mucus.

Bovine Leucosis, or Bovine Lymphosarcoma, is caused by the Bovine Leukaemia Virus (BLV), a retrovirus. While most cattle remain persistently infected without signs, approximately $29\%$ develop persistent lymphocytosis (non-neoplastic), and less than $5\%$ develop malignant lymphosarcoma. Lymphosarcoma is most common in cattle aged $4-8$ years. Gross pathology includes clay-like enlargement of lymph nodes, splenomegaly, anaemia, and neoplastic masses in the heart, intestines, uterus, and abomasum. Ventral oedema and retrobulbar lymph node enlargement (causing exophthalmos) are also characteristic.

Orf and Bluetongue

Orf, also known as contagious ecthyma or scabby mouth, is caused by the Orf virus (genus Parapoxvirus, family Poxviridae). It is a zoonotic disease affecting sheep and goats, typically initiated by abrasions from pasture. Lesions progress through macule, papule, and vesicle stages, appearing at the commissures of the mouth, lips, oral mucosa, and feet. Histopathology reveals acanthosis, spongiosis, and rare eosinophilic intracytoplasmic inclusion bodies ($2-10\,\mu m$) in keratinocytes. In humans, it presents as "milker’s nodules."

Bluetongue is caused by an Orbivirus (family Reoviridae) with at least $24$ recognized serotypes, transmitted by Culicoides midges. The virus replicates in regional lymph nodes before disseminating to mononuclear phagocytic and endothelial cells. Notably, the virus infects erythrocytes, facilitating prolonged infection. Pathology in sheep includes severe bilateral secondary pneumonia, cardiac haemorrhages, muscle necrosis, and congestion of the spleen and liver. Histopathology highlights acute myonecrosis and pulmonary oedema, with protein-rich fluid accumulating in the airspaces.