Equine Infectious Anemia

Johanna L. Watson • Brett A. Sponseller

Equine infectious anemia virus (EIAV) is an RNA virus, a member of the Retroviridae family, belonging to the lentivirus genus. It has a structure and genome organization similar to other animal and human lentiviruses and uses virally encoded reverse transcriptase to convert the RNA genome to a DNA intermediate that is integrated into the host's genome by another virally encoded enzyme, integrase.

Identification of Equids Seropositive for EIAV

EIA is a USDA-regulated disease. In 2003, the USDA estimated that serosurveillance of nearly 2 million samples cost U.S. horse owners in excess of $48 million. USDA-accredited labo­ratories use a testing scheme that detects the presence of serum antibody to the virus. The Coggins test, developed by Dr. Leroy Coggins in 1970, provided the first efficient serologic test for detection of EIAV-infected animals and remains a USDA-accepted test.^3,4 There are also four licensed ELISAs, one of which is a cELISA. These ELISAs detect antibody directed at the transmembrane glycoprotein (gp45) and/or the p26 antigen.⁵ All U.S. states, Canada, and Mexico accept either the Coggins test or one of the licensed ELISAs when EIA testing is required for entry. Equids that cross state lines or attend many equestrian events (e.g., shows, races) have to be seronegative for EIA.

Serosurveillance can lead to detection of horses infected with EIAV that otherwise appear healthy. Indeed, most horses infected with the virus are inapparent carriers. However, blood transferred from an inapparent carrier to another horse, either through instruments (needles, nasogastric tubes, dental equip­ment, etc.), blood products, or by insect vectors (primarily tabanids) can lead to infection and a fatal outcome.

Equine Infectious Anemia

The clinical form of the disease is characterized by three defined temporal stages: acute, chronic, and inapparent. The acute stage occurs with the initial burst of viremia and is characterized by high fever, thrombocytopenia, and nonspecific signs of malaise including lethargy and inappetence. In experimentally infected horses, thrombocytopenia inversely correlates with virus load and occurs slightly in advance of onset of fever. Ecchymoses and petechiae may also be detected on mucous membranes. During the chronic stage, similar clinical features occur during recurrent episodes of viremia, which are inter­spersed with periods of clinical quiescence and low viremia. Throughout the chronic stage, clinical episodes tend to gradually diminish in severity and duration. The inapparent stage occurs once levels of viremia are immunologically contained and no clinical signs are detected. Horses experiencing clinical disease at any point may develop DIC and die. In addition, episodes of stress (e.g., transportation, racing, extreme temperatures) may precipitate clinical disease. Corticosteroids have been experimentally used to induce recrudescence of clinical disease.⁷ Other chronic manifestations of EIA include development of dependent edema, weight loss, anemia, and other signs of ill thrift.

Lentiviruses have a DNA-dependent RNA polymerase (reverse transcriptase) that misincorporates nucleotides, resulting in changes in the viral genome.⁹ This mechanism allows for generation of viral variants that differ genetically from preexist­ing ones. As a result, genetic and antigenic variation of epitopes for neutralizing antibody and cytotoxic T lymphocytes allows viral escape from adaptive immune responses.^10,11 Antigenic variation plays a central role in clinical disease recurrence throughout the chronic stage of infection and thwarts attempts to develop an effective vaccine.⁹

EIAV can replicate effectively in monocytes, dendritic cells, and tissue macrophages^12-14 and has been shown to replicate in endothelial cells. EIAV replication in endothelial cells may play a role in the development of DIC by viral damage to endothelial cells, with subsequent exposure of subendothelium.¹⁵ This in turn could lead to platelet aggregation and formation of thrombi.¹⁶ In addition, damaged endothelium may lead to development of dependent tissue edema by transudation of fluid through compromised small vessels.¹⁵

Pathology and Clinical Pathology

Necropsy examination of horses that die of EIA may demon­strate splenomegaly, lymphadenopathy, hepatomegaly, pro­nounced hepatic lobular architecture, ecchymoses of the mucosa and viscera, dependent subcutaneous edema, and thrombotic disease of small vessels.

Clinicopathologic abnormalities will vary depending on the stage and severity of infection. During clinical disease, a fre­quently profound thrombocytopenia develops concurrently with each successive episode of fever. Platelet dysfunction in EIAV-infected horses has been demonstrated, possibly exacerbat­ing bleeding tendencies and the progression to DIC in clinically affected equids.¹⁷ Anemia due to intravascular hemolysis, extravascular hemolysis, and depression of bone marrow erythropoiesis may progressively develop during the chronic stage of infection.¹⁸ During the inapparent stage of infection, horses typically have increased plasma total solids and globulin concentrations, mild anemia, and decreased albumin concentra- tion.¹⁹ Polyclonal B-cell activation is also evident, suggesting chronic antigenic stimulation despite clinical quiescence.¹⁹ Concomitant fever and thrombocytopenia should prompt immediate consideration of EIA. A history of recurring fever is also suggestive of EIA, particularly when other causes of fever have been ruled out.

Prevention, Control, and Regulatory Considerations

It is well recognized that seroprevalence varies with the region of the United States.¹⁸ States considered at high risk include Texas, Oklahoma, Louisiana, and Arkansas, whereas the mid­Atlantic area, New England, Alaska, and Hawaii are considered low-risk regions. The remaining states are classified as being at intermediate risk. Despite regional differences in risk to noninfected horses, sporadic outbreaks do occur. Veterinarians should encourage all horse owners to test for EIAV, test new arrivals, and maintain good fly control.

Once a seroreactor is identified, all contact horses are quarantined and undergo testing until two negative test results at 30- to 60-day intervals are obtained for all individuals in the quarantined herd.¹⁶ The required interval is based on the need to allow recently infected horses to seroconvert. Seroreac- tors may be either quarantined or euthanized, depending on state regulations. Quarantined horses must be at least 200 yards from seronegative animals, the distance shown to be sufficient to obviate viral spread by insect vectors. In addi­tion, seroreactors remaining in permanent quarantine must be permanently identified. A USDA code number followed by the letter A is assigned to the quarantined horse and permanently applied to the horse in the form of a brand or lip tattoo.

Because an EIA eradication program has never been implemented in the United States, persistence of EIAV-infected horses can be expected. The vast majority of horses in the United States are not tested annually, so to encourage horse owners to voluntarily maintain vigorous surveillance testing, the veterinary community must educate them about the consequences of EIAV infection. Horse owners are often unprepared to deal with the financial and emotional losses associated with detection of a horse seropositive for EIAV.

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