Caprine Arthritis Encephalitis Virus

Kevin Washburn

■ Definition and Etiology Caprine arthritis encephalitis virus (CAEV) is an RNA-enveloped lentivirus from the Ret- roviridae family that infects cells of the monocyte-macrophage lineage, with clinical manifestations ranging from subclinical disease to severe encephalitis.

■ Clinical Signs and Differential Diagnoses Only about 20% of CAEV-infected goats display clinical signs of disease during their lifetime, but recognized forms of disease include a leukoencephalomyelitis, interstitial pneumonia, chronic mastitis, and debilitating polysynovitis-arthritis.¹ Leukoencephalomalacia is observed primarily in kids 2 to 6 months of age, but reports have been noted in adults.¹ This form is characterized by an ascending paresis leading to paralysis, beginning in the rear limbs and sometimes involving the forelimbs. These signs may or may not be accompanied by a mild interstitial pneumonia. Goat kids may continue to be bright, alert, and appetent. The most severe manifestation of this form of CAEV infection is progressive paresis to paralysis to urinary retention and bloating. Differentials for this form of CAEV include meningitis, meningeal worm, and trauma. Chronic interstitial pneumonia with progressive weight loss and dyspnea is another recognized form of CAEV infection. Primary ruleouts for this form include lung worms, internal caseous lymphadenitis, pulmonary abscessation, and chronic bronchopneumonia.

The most common form of CAEV infection is polysynovitis­arthritis, which is most frequently recognized in mature goats but has been reported in goats as young as 6 months of age. Lameness caused by this form is intermittent and insidious in onset, but eventually affected joints become painful and enlarged. Enlargement of the joints is most typically due to hyperplasia of the synovial tissues and their associated sheaths rather than increased volume of joint fluid. The carpus is most frequently involved, but the stifle, coxofemoral, atlantooccipital, and hock joints are also potential locations. Affected goats have a stiff, stilted gait and progress to walking on their carpus or recumbency. Range of motion is greatly affected, contributing to chronic soft tissue contracture. The polysynovitis-arthritis form can be accompanied by a chronic interstitial pneumonia and weight loss, as well as some degree of mammary involve­ment.¹ Ruleouts for this common form of CAEV include septic arthritis and chronic degenerative joint disease.

■ Clinical Pathology and Laboratory Diagnosis Arthrocentesis to confirm suspicion of the polysynovitis-arthritis form of CAEV infection usually yields a brown to red-tinged fluid with an increased cell count and protein. Joint fluid cell counts in affected joints are dominated by mononuclear cells, differing from bacterial synovitis, where cells consist predomi­nantly of neutrophils. This predominance of mononuclear cells in CAEV infection is also seen in the cerebrospinal fluid (CSF) of goats affected with the leukoencephalomyelitis form. Radiographs may be a useful diagnostic tool for CAEV polysynovitis-arthritis; early cases display soft tissue swelling dorsal to the carpus.

The U.S. Department of Agriculture (USDA) recognizes an agar gel immunodiffusion (AGID) test using ovine progres­sive pneumonia virus antigen as the official test for CAEV. However, an enzyme-linked immunosorbent assay (ELISA) has been developed for detection of whole virus, core, or envelope proteins. Both AGID and ELISA are considered reliable enough to be incorporated into prevention and control programs. The AGID test is reportedly more specific but less sensitive than the ELISA.³ Polymerase chain reaction techniques have been developed for detection of antigen in milk, tissue, and blood. A study evaluating the performance of PCR and ELISA against viral culture for the detection of CAEV in goat kids found that PCR tended to have a lower sensitivity and higher specificity than ELISA, but combining these two tests in series or parallel may optimize the advantages and disad­vantages of each technique, thereby maximizing detection.⁴ Surveillance measures on goat dairies have included the use of ELISA tests on bulk milk samples that appear to be applicable for early detection of CAEV infection.⁵

A positive AGID test or ELISA in adults is synonymous with lifelong viral infection. Generally, time from infection to seroconversion ranges from 4 to 16 weeks, but some infected goats shed virus for long periods of time without seroconver­sion.⁶ Goat kids may be transiently positive for the presence of antibodies during the first 8 to 16 weeks of life after consum­ing CAEV antibody-containing colostrum, but because of the nonprotective nature of maternal antibodies, such kids may seroconvert to true viral infection shed from the infected dam.

■ Pathophysiology The characteristic granulomatous inflammatory pathology produced in affected tissues is thought to be due to immune complexes generated by the interaction of nonneutralizing antibodies produced by lymphocytes and associated virus-infected macrophages. Localization of such inflammatory lesions occurs where tissue-associated macro­phages are found. Tissues of importance for CAEV localization include the synovium, mammary gland, lung, and central nervous system (CNS), therefore the manner in which the disease manifests itself is to be expected.

■ Epidemiology Transmission involves the transfer of virus-laden cells from one animal to the next. Transfer of CAEV to neonates through colostrum and milk is a highly efficient natural mode of transmission.^7,8 Transmission has also been reported through direct contact, so herd owners who do not practice segregation of seropositive animals continually have difficulty controlling and eradicating the disease.^7-10 Complete separation of kids from dams immediately following parturition and during the periparturient period is necessary; evidence exists that even kids not allowed to nurse become infected. CAEV proviral DNA has been detected in the caprine genital tract, and experimental infection of goat embryos with CAEV has been reported. In addition, intramammary and in utero transmission have been described.^10,13 All of the described means of acquiring the virus are potential explanations for continued transmission in herds where segregation and sound colostrum and milk management are practiced.

Maedi-visna virus (MVV), also known as ovine progressive pneumonia, is another lentivirus that together with CAEV is commonly referred to as small ruminant lentivirus (SRLV). Although sheep are most likely to display clinical signs of MVV and goats signs of CAEV, studies have shown that these viruses can be transmitted from sheep to goats and vice versa.

A study examining the prevalence of antibody to CAEV in the United States found that 31% of all goats tested were seropositive, and 73% of herds had at least one seropositive member. Serum samples in this study were obtained from 28 states. Prevalence was highest in the western Pacific and northern plains regions on family-owned farms and increased with age. Prevalence in this study was lowest in the Angora breed.

■ Necropsy Findings Grossly, goats affected with the polysynovitis-arthritis form of CAEV have thickened, sometimes folded synovium consistent with synovial hyperplasia due to chronic inflammation. Microscopically, synovial hyperplasia is characterized by mononuclear infiltration of lymphocytes, plasma cells, and macrophages. Synovial spaces contain fibrin, and synovial villi and collagen are necrotic.¹

No gross lesions are apparent in the CNS of goats affected with the leukoencephalomyelitis form of CAEV, but microscopi­cally, perivascular infiltration of lymphocytes, macrophages, and plasma cells is observed. Perivascular infiltration is often accompanied by malacia of the brain and spinal cord, in addition to loss of myelin. Occasionally, degenerative lesions are seen in the gray matter.

■ Treatment and Prognosis Prognosis for CAEV infec­tion varies because most goats do not show clinical disease; once signs begin, however, rapid deterioration ensues. Arthritis and accompanying weight loss progress, and there is no treat­ment. Kids or mature goats affected with the leukoencepha­lomyelitis form do not survive and should be euthanized for humane reasons. Reportedly, a genetically determined predis­position for development of CAEV arthritis exists and can be identified with DNA fingerprinting.

■ Prevention and Control Prevention and control centers on colostrum and milk management, but kids should also be prevented from any contact with the dam following parturition.

Despite diligent prevention and control programs based on elimination of colostrum and milk transmission, isolation of seronegative goats, and serologic monitoring, obstacles to a CAEV-free herd are often encountered. Detection of virus has been reported in properly treated colostrum.⁷ Overheating colostrum denatures immunoglobulin, thereby preventing effective passive transfer of immunity, but not heating colostrum long enough or at high-enough temperatures fails to inactivate the virus. Feeding overheated colostrum may also cause diarrhea in kids. Attention to time and temperature details during heat treatment of colostrum and pasteurization of milk are of the utmost importance for effective colostrum and milk manage­ment. Some farms routinely feed cow colostrum, but neonatal isoerythrolysis has been reported in kids consuming cows' milk, and the lack of goat-specific immunoglobulin transfer is less than ideal.¹⁸ Serologic monitoring can be complicated by the fact that viral shedding precedes seroconversion, so all goats should be tested a minimum of twice yearly to ensure that any new cases are detected and managed accordingly. Unfortunately, no vaccine is currently available for CAEV.