Equine infectious anemia (EIA) is geographically widespread throughout the world. Few countries can claim disease freedom, with the exception of Japan and Iceland. EIA continues to pose a threat to equine industries globally because of the potential risk of spread of the virus through international movement of horses. Of the equid species known to be susceptible to the virus, horses and ponies are more likely to develop severe clinical manifestations of the disease than are donkeys or mules, in which infection is most frequently subclinical. However, many horses also experience asymptomatic infection after initial exposure to the virus.
Etiology and Pathogenesis
The causal agent of equine infectious anemia is an RNA virus, classified in the Lentivirus genus, family Retroviridae. The virus is readily inactivated by most common disinfectants, such as bleach, ethanol, iodophore disinfectants, phenolic compounds, glutaraldehyde, and formalin. Because bleach-based and ethanol disinfectants are readily inactivated in the presence of organic material, for example manure or soil, contaminated surfaces must first be cleaned thoroughly of such matter using soap and water before treating with a disinfectant. Pressure washing of a soiled surface is contraindicated because of the risk of aerosolization of potentially infectious blood or other body fluids on wall or floor surfaces.
In equids infected with EIA virus, there is a very close relationship between the development of overt signs of disease and the amount of virus present. Virus is found free in plasma or associated with monocytes and macrophages in infected animals. Virus burdens reach their highest levels during febrile episodes, after which they decline. It has been shown that the concentration of EIA virus in tissues must reach a threshold level to trigger a clinical response. The potential of a viral strain to induce disease is largely due to its replicative capacity or pathogenicity in the infected host.
The pathology of EIA-mediated disease is a consequence of macrophage infection that in turn interferes with host-cell gene expression; this leads to increased production of pro-inflammatory mediators or cytokines, in particular TNF-alpha, IL-1, IL-6, and transforming growth factor beta. Aside from the latter activating the arachidonic pathway that results in increased production of prostaglandin E2 and the induction of a febrile response, these cytokines may also cause thrombocytopenia. Increased production of TNF-alpha may also be partly responsible for the anemia that develops in EIA virus-infected equids by virtue of its ability to inhibit erythropoiesis.
Aside from the foregoing role that pro-inflammatory cytokines play in the pathogenesis of EIA, adaptive immune responses are also involved in the pathology of the disease. Platelets from infected horses have significant amounts of bound IgG or IgM, which result in their immune-mediated destruction, contributing to both splenomegaly and hepatomegaly.
There is reason to believe that cell-mediated and not humoral immune responses are responsible for initial control of EIA virus infection. Once acute viral infection has been controlled, the infected individual will remain free of overt signs of disease until a variant virus emerges that can evade the host’s immune system.
Epidemiology and Transmission
All equids infected with EIA virus remain lifelong carriers. Such individuals constitute the natural reservoir of the virus and ensure its perpetuation in equid populations over time. The combination of frequent carriers and mechanical transmission by blood-feeding insects explains why EIA is found in equine populations in a wide range of climatic zones and countries around the world.
Although EIA is usually considered a blood-borne infection, all body fluids and tissues should be regarded as potentially infectious, especially during febrile episodes when viral levels are high. Evidence of EIA virus has even been found in nasal swabs and in swabs taken from the buccal cavity and genitalia. There are limited data to suggest that infectious virus can be present in milk. EIA virus can also be passed to foals in utero. Evidence in support of venereal transmission is questionable; it is unlikely to occur unless semen is contaminated with blood in the case of an infected stallion.
There is circumstantial evidence suggesting that EIA virus may, under exceptional circumstances, also be transmitted via the respiratory route through aerosolization of blood when an infected horse is bleeding from the nostrils.
Transmission of EIA by biting flies is purely mechanical; the virus does not replicate in the insect. The chances of transmission of EIA among horses in close proximity to one another has been shown to be directly proportional to the volume of blood retained on the mouthparts of an insect after feeding. Based on this, horse flies Horse Flies and Deer Flies Tabanus spp (horse flies) and Chrysops spp (deer flies) are large (up to 3.5 cm long), heavy bodied, robust dipterans with powerful wings and very large eyes. They are swift fliers... read more , deer flies, and to a lesser extent, stable flies Stable Flies The stable fly, Stomoxys calcitrans, is often called the biting house fly. It is about the same in size and general appearance as Musca domestica, the house fly. It is brownish... read more , are the most efficient vectors of the virus. It is also because the bites are irritating and trigger host defensive behavior that interrupts the flies' feeding routine and results in their seeking out another susceptible host to complete their blood meal.
EIA transmission is influenced by the number and species of flies, density of the horse population, level of viremia in the host, and quantity of blood transferred. Infections are especially common in hot, humid countries of the world with very large biting fly populations. Symptomatic, febrile horses are more likely to transmit the disease than animals with inapparent infections.
Aside from the natural transmission of EIA by blood-feeding insects, the disease can also be readily transmitted iatrogenically through the re-use of blood-contaminated syringes and needles, surgical instruments, dental equipment, and IV sets and by the transfusion of infective blood or blood products. The virus is purported to persist for up to 96 hours on contaminated hypodermic needles. The importance of iatrogenic spread of EIA cannot be overstated. It has become increasingly common in some countries among a certain element of the equine industry that is indifferent to the inherent risks involved and the potential for dissemination of the virus.
The clinical findings and course of infection with equine infectious anemia virus 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 have been described as progressing 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 or misdiagnosed. Typically, this initial phase is followed by a prolonged period associated with:
recurring episodes of fever
increased heart and respiration rates
petechiation on mucous membranes
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. However, some chronically infected horses may continue to experience recurrent episodes varying from fever and thrombocytopenia to many of the extensive range of clinical signs that have been described. Such episodes are frequently associated with intercurrent infections and other sources of stress.
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 infrequently acute depression and epistaxis 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.
Although clinical signs can differ in range and severity between individuals, cases of EIA can present with many or most of the following:
low platelet count
increased heart and respiration rates
hemorrhages on mucous membranes
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 on internal organs, especially spleen and kidney, enlargement of the spleen and abdominal lymph nodes, and dependent edema of the limbs and ventral abdominal wall. Thrombosis of blood vessels has also been reported.
Histopathologically, there is a nonsuppurative hepatitis and, in some cases, a glomerulonephritis, periventricular leukoencephalitis, meningitis, or encephalitis. Ocular lesions may be seen in chronically infected animals. Proliferation of reticuloendothelial cells is evident in many organs, especially in the liver, where there is also accumulation of hemosiderin in Kupffer cells. Perivascular accumulation of lymphocytes can be found in various organs.
Diagnosis is based on serologic tests
The clinical signs of acute equine infectious anemia are often nonspecific and not definitive of the disease. Accordingly, a provisional clinical diagnosis must be confirmed by demonstration of antibodies to the virus in blood. Laboratory confirmation of a suspect case of EIA needs to be pursued without delay. A wide range of infectious and noninfectious diseases can clinically resemble and be confused with EIA. These include:
phenothiazine toxicity Tranquilizers, Antidepressants, Sleep Aids, and Anticonvulsants (Toxicity) Also see Overview of Systemic Pharmacotherapeutics of the Nervous System. Benzodiazepines bind γ-aminobutyric acid (inhibitory neurotransmitter) receptors and are used for seizure control and... read more
autoimmune hemolytic anemia
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 positive ELISA 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 reverse transcription PCR 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 logistic and economic reasons, it is no longer in vogue as a means of diagnosis of EIA.
No treatment is available
There is no antiviral treatment or cure for equine infectious anemia. Because confirmed cases of the disease are lifelong carriers of the virus, they are usually euthanized. The alternative to euthanasia is permanent isolation and quarantine of the infected animal at a distance of at least 200 yards from all other equids on a premises. Advocating supportive care under such circumstances is irrelevant.
Prevention and Control
No safe and effective vaccine is available for equine infectious anemia. Without the benefit of prophylactic vaccination, it is recommended that horse owners implement an EIA control plan for their premises. An integral part of such a program should be annual testing of all horses. More frequent testing may be indicated in areas that previously experienced a high incidence of EIA. All equines introduced to a herd should have a negative EIA test before arrival or be isolated while tests are pending. Horses competing in shows or performance events should be accompanied by proof that they have been tested for EIA within a specific period of time.
Vector control practices should be a part of any EIA prevention and control program. These should include routine application of insecticides and repellants as well as the implementation of insect control measures.
Any control program for EIA must emphasize awareness of how readily the causal virus can be transmitted indirectly from an infected individual to other equids on a premises through the re-use of contaminated needles, syringes, surgical or dental instruments, or other equipment. Strict observance of the principles of good hygiene and disinfection is essential if iatrogenic transmission of EIA is to be prevented.
Specific measures to prevent/control EIA can be summarized as follows:
Infected horses become lifelong carriers and pose a risk of infection to other horses. Management options for an EIA-positive horse are euthanasia or lifetime quarantine, with permanent isolation at least 200 yards away from noninfected horses.
Prevention is key to stopping the spread of EIA.
Use a sterile needle, syringe, and IV set for all injections or treatments.
Disinfect dental, tattoo, surgical equipment, lip chains, and bits thoroughly between horses. Remove all debris and blood with soap and water before disinfection.
Only administer commercially licensed blood or blood products.
Keep open wounds clean and covered, if possible.
Use a sterile needle and syringe each time when puncturing a multidose medication bottle.
Use sterile technique when drawing up and administering medications.
Require proof of a recent negative EIA test upon introduction of a horse onto a premises for the first time.
Practice good fly control by regular mucking out of stalls, proper disposal of manure away from horse stabling areas, and using fly sprays or natural predators to minimize fly presence.
There is no evidence that EIA virus is a zoonotic agent and transmissible to humans.
Equine infectious anemia (EIA) is a noncontagious infectious disease of equids caused by a virus of the same name. It is not known to be transmissible to humans.
The principal mode of natural transmission of EIA is on the mouth-parts of blood-feeding insects, especially horse flies and deer flies.
Diagnosis of EIA is based on serologic testing and demonstration of antibodies to the virus in blood.
No treatments or vaccines for EIA are available.
Prevention and control of EIA is based on identification and euthanasia or lifelong isolation of infected equids, avoidance of iatrogenic transmission of the virus, and implementation of vector control practices.
For More Information
Equine Infectious Anemia Technical Factsheet from The Center for Food Security & Public Health, Iowa State University