Overview of Equine Infectious Anemia
Equine infectious anemia (EIA) is a noncontagious, infectious disease of horses and other Equidae. It is caused by an RNA virus classified in the Lentivirus genus, family Retroviridae. EIA can present as an acute, subacute, or chronic infection. On occasion, the virus can be a cause of significant morbidity and mortality. The most frequently encountered form of the disease is the inapparent, chronically infected carrier.
Under natural conditions, the most important mode of transmission of EIA is by the transfer of virus-infective blood by blood-feeding insects between horses in close proximity. Virus is found free in the plasma or cell associated, principally in monocytes and macrophages of infected animals. Although infection is considered primarily blood borne, all tissues and body fluids are potentially infectious, especially during episodes of clinical disease when viral burdens are high. Transmission of EIA by biting flies is purely mechanical; the virus does not replicate in the vector. The chance of transmission of EIA is directly proportional to the volume of blood retained on the mouthparts of the insect after feeding. In that respect, horse flies, deer flies, and to a lesser extent, stable flies are likely the most efficient vectors. It is also because they are capable of triggering host defensive behavior that interrupts feeding and results in their seeking a new susceptible host to complete their blood meal.
Additionally, EIA can be readily transmitted iatrogenically through use of blood-contaminated syringes, needles, or surgical equipment, or by transfusion of infective blood or blood products. Infrequently, transplacental transmission can occur in infected mares that experience one or more clinical episodes during pregnancy. There is evidence, although circumstantial, from a significant outbreak of EIA in an equine hospital in Ireland, of probable spread of the virus by direct or indirect transfer between horses in stalls sharing the same barn.
A very close relationship exists between presence and severity of clinical signs of EIA and the amount of virus present in infected animals. Viral burdens are highest during febrile episodes of the disease. Many of the clinical signs associated with the acute form of EIA result from infection of macrophages and the release of pro-inflammatory mediators or cytokines, specifically tumor necrosis factor α, IL-1, IL-6, and transforming growth factor ß. This response together with suppression of platelet production are believed to be the factors responsible for the thrombocytopenia that is a characteristic feature of EIA. In addition, immune responses play a major role in the pathogenesis of EIA. Platelets from infected horses have significant amounts of bound IgG or IgM, which leads to their immune-mediated destruction, contributing to both splenomegaly and hepatomegaly.
The clinical findings and course of EIA are variable, depending on the virulence of the virus strain, viral dose, and susceptibility of the horse. After an incubation period of 15–45 days or longer in naturally acquired cases of infection, classic cases of the disease progress through three clinical phases. An initial or acute episode lasting 1–3 days is characterized by fever, depression, and thrombocytopenia. Because these signs can be mild and transitory, they are often overlooked. Typically, this initial phase is followed by a prolonged period associated with recurring episodes of fever, thrombocytopenia, anemia, petechiation on mucous membranes, dependent edema, muscle weakness, and loss of condition. The interval between episodes can range from days to weeks or months. In most cases, the episodes of clinical disease subside within a year, and infected horses become inapparent carriers and reservoirs of EIA virus. Many of these horses remain clinically normal.
Although the foregoing represents the most commonly described clinical course of the disease, some outbreaks of EIA can be associated with peracute infection in which the primary viral infection is uncontrolled; this can result in a very high fever, severely reduced platelet counts, and acute depression, leading to death. In view of the wide variation in response seen in natural cases of infection, it is not possible to confirm a diagnosis of EIA based solely on clinical grounds.
Gross lesions frequently seen in acute cases of EIA include enlargement of the spleen, liver, and abdominal lymph nodes; dependent edema; and mucosal hemorrhages. Chronic cases of infection are characterized by emaciation, pale mucous membranes, petechial hemorrhages, enlargement of the spleen and abdominal lymph nodes, and dependent edema. Histopathologically, there is a nonsuppurative hepatitis and, in some cases, a glomerulonephritis, periventricular leukoencephalitis, meningitis, or encephalitis. Proliferation of reticuloenthelial cells is evident in many organs, especially in the liver, where there is also accumulation of hemosiderin in Küpffer cells. Perivascular accumulation of lymphocytes can be found in various organs.
A provisional clinical diagnosis of EIA must be confirmed by demonstration of antibodies to the virus in blood. Although the internationally accepted serologic test is the agar gel immunodiffusion or Coggins test, there is increasing acceptance of a variety of ELISA tests, either competitive or synthetic antigen–based, because they can provide rapid results. Because ELISA tests can give a higher rate of false positives, all ELISA positive results must be confirmed by the Coggins test. When used in combination, ELISA and agar gel immunodiffusion tests provide the highest level of sensitivity combined with specificity. The Western blot is a supplemental test that can be resorted to in cases of conflicting results with other diagnostic tests. A problem with available serologic tests is that they can give negative results when testing sera collected within the first 10–14 days of infection. Whereas the vast majority of horses infected with EIA virus will have seroconverted by 45 days, there have been exceptional cases in which the interval has been ≥90 days. Virus detection assays such as the reverse transcription PCR assay are not routinely used to diagnose EIA. Notwithstanding their sensitivity, they may not detect virus in carrier horses with very low viral loads. Although the animal inoculation test is highly sensitive for detection of EIA virus, for logistical and economic reasons, it is no longer in vogue as a means of diagnosis of EIA.
No specific treatment or safe and effective vaccine is available. Because equids infected with EIA virus present the only known source of infection, antibody-positive animals should be kept at a safe distance (~200 m) from other equids. The only recognized exception to this rule is the progeny of seropositive mares, which may possess maternal antibodies to the virus after ingesting colostrum. In most cases, passive antibody against EIA virus wanes and is no longer detectable in the Coggins test by 6–8 mo of age; detectable antibody may persist up to 12 mo, however, if ELISA testing is used.
The risk associated with maintaining infected breeding stock varies. Field studies have indicated excellent success in raising test-negative foals from inapparent carriers of EIA virus. The risks of infection in utero increase dramatically if clinical signs of EIA are seen in the mare before parturition. Unfortunately, it is not possible to accurately determine the risk posed by any equid infected by EIA virus. Inapparent carrier horses maintain low-level viremias that may increase under stressful circumstances. As compared with seronegative healthy horses, inapparent carriers have increased serum globulin concentrations and lymphocyte subset changes that are consistent with immune activation or chronic inflammation. Because EIA virus persists in infected equids for life, most regulatory agencies assume all equids seropositive for EIA virus pose the same high risk.
In the USA, seropositive horses must be placed under quarantine within 24 hr after the positive test results are known. The quarantine area must provide separation of at least 200 yd from all other equids. After a confirmatory test is performed, seropositive horses must be permanently identified using the National Uniform Tag code number assigned by the USDA to the state in which the reactor was tested, followed by the letter “A.” This identification may take the form of a hot brand, chemical brand, freezemark, or lip tattoo, and it must be applied by a USDA representative. Reactor horses must be removed from the herd by euthanasia, slaughter, or quarantine at the premises of origin. They may move interstate only under official permit to a federally inspected slaughter facility or a federally approved diagnostic or research facility, or to return to the premises of origin. After a reactor is detected in a herd, testing for EIA must be performed on all horses on the premises and repeated until all remaining equids on the premises test negative. These horses must be retested at 30- to 60-day intervals until no new cases are found. Quarantine on the premises is released when tests on the entire herd have been negative for at least 60 days after the reactor equids have been removed.
All equids shipped across state lines in the USA must be tested for EIA with a negative result within 12 mo before transport. All equids sold, traded, or donated within a state must have tested negative for EIA no more than 12 mo before change in ownership and, preferably, no more than 60–90 days. All equids entering horse auctions or sales markets are required to have a negative test before sale, or the horse must be held in quarantine within the state until the test results are known.
It is recommended that horse owners implement an EIA control plan for their premises. All horses should be tested every 12 mo as part of a routine health program. More frequent testing may be indicated in areas that perennially have a high incidence of EIA. Owners of equids entering shows or competitive events should present proof to event officials of a negative EIA test. All new equids introduced to a herd should have a negative EIA test before entry or be isolated while tests are pending. Vector control practices, including application of insecticides and repellents and environmental insect control, should be implemented. Good hygiene and disinfection principles should be maintained to prevent iatrogenic infection of horses with contaminated needles, syringes, or equipment.