Causative agent
Equine piroplasmosis (EP) is caused by the protozoan parasites Theileria equi (formerly Babesia equi) and Babesia caballi. Babesia equi was renamed Theileria equi in 1998 following clarification of the parasite's life cycle and DNA structure. The B. caballi organism is approximately twice the size of T. equi.

Natural distribution
EP affects horses, donkeys, mules, and zebras. The wild zebra population is an important reservoir for the disease in Africa.

The causative organisms are endemic in 90% of the world, with only Canada, the United States, Australia, Japan, England, and Ireland not considered endemically affected. Antibody titers against T. equi and B. caballi are more prevalent in equids in tropical and subtropical areas.

An EP epidemic occurred in Florida in the 1960s following importation of infected horses from Cuba. Approximately 20% of horses on the Brighton Indian Reservation died from EP. After an aggressive eradication and tick control campaign, the United States was again considered free of the disease in 1982.

EP substantially impacts the international transport of horses, because horses having positive results of a serologic examination for antibodies to EP agents are generally not permitted to enter EP-free countries. During the 1996 Olympic Games in Atlanta, horses with detectable antibodies to EP agents that were from endemic areas were only allowed to compete in the stadium jumping and dressage events; competition in the cross-country phase was not permitted because of concerns about ticks in wooded areas (see role of ticks under "Transmission"). These horses were housed in isolation, and strict tick control was implemented. Similar measures were taken at the 2000 Olympic Games in Sydney, Australia.

Transmission
The agents of EP are transmitted by ticks and other biting insects, but may also be transmitted when needles and hypodermic syringes or blood are transferred between horses. Intrauterine infection of foals can occur, and is more likely in the case of T. equi infection.

Adult and nymphal ticks are capable of transmitting the disease. While obtaining a blood meal from an infected horse, the tick ingests infected equine erythrocytes (red blood cells). As the erythrocytes are digested in the tick's digestive tract, parasite trophozoites are released and undergo sexual reproduction, resulting in the production of zygotes. Zygotes develop into sporozoites, which undergo division and spread via the tick's hemolymph to its salivary glands. The causative agents are then transmitted when the infected tick bites a susceptible horse.

Once introduced into a susceptible horse, B. caballi sporozoites enter erythrocytes and begin asexual reproduction. The resulting merozoites can infect other erythrocytes. Affected cells begin to aggregate in smaller vessels and capillaries and an immune response is stimulated, resulting in the destruction of affected erythrocytes.

Theileria equi demonstrates a more complex life cycle once it infects the host. The organism enters the lymphoid tissue or circulating lymphocytes (a type of white blood cell) and undergoes asexual reproduction to produce macroschizonts and microschizonts. Macroschizonts produce macromerozoites, which enter the lymphoid cells and undergo sexual reproduction to produce additional macroschizonts and microschizonts. Micromerozoites produced by microschizonts infect erythrocytes and cause aggregation and destruction of affected erythrocytes.

Genera of ticks that transmit EP agents include Dermacentor, Hyalomma, Rhipicephalus, and Boophilus. Approximately 15 species of ticks are capable of transmitting EP agents. Dermacentor variabilis, the American dog tick, is a widely distributed tick species that can transmit EP agents. Transovarial transmission (the female tick transfers the infection to its developing ova and the hatched larvae are infected without ingesting a blood meal) occurs for B. caballi, but apparently not for T. equi. As a result of transovarial transmission, the tick can become an important reservoir for B. caballi.

The incubation period for EP is 10 to 30 days when associated with B. caballi, and 12 to 19 days when associated with T. equi. Coinfection can occur in endemic areas.

Clinical signs
Clinical signs of acute EP are nonspecific, and mimic many other diseases and conditions. Signs observed are the result of red blood cell destruction, complement activation, and release of inflammatory mediators (including bradykinin, histamine, and 5-hydroxytryptamine). The severity of clinical signs reflects the number of cells destroyed and the degree of activation of the complement and inflammatory cascades. Infection in some horses can be inapparent for many years. Sudden death may be observed in peracute cases, but is rare.

Infections with B. caballi are generally less severe, because a smaller number of erythrocytes are infected and destroyed. Clinical signs are nonspecific, and include poor appetite, reduced or poor performance, and weight loss. Infection can persist for 1 to 4 years. Horses infected with B. caballi may spontaneously clear the organism after 12 to 42 months.

Theileria equi results in more severe infection and disease, resulting in the destruction of up to 20% of the horse's erythrocytes. Some affected horses die within 24 to 48 hours of onset of clinical signs. Affected horses may be febrile. Anemia, increased respiratory rate, and increased heart rate are related to the decrease in the number of circulating red blood cells and the associated reduction in oxygen-carrying capacity of the blood. Icterus (jaundice) and red-tinged urine develop due to release of free hemoglobin into the blood from ruptured red blood cells. If sufficient amounts of free hemoglobin are present in the bloodstream or if a sufficient number of erythrocyte aggregates accumulate, kidney damage and subsequent failure can result. Because it is the primary organ involved in removing damaged red blood cells, the spleen is usually enlarged. Colic associated with impaction or diarrhea may be observed. Edema of the limbs may develop as a result of leakage of fluid into tissue spaces. Petechial hemorrhages on the mucous membranes and hind end weakness may also be observed. Spontaneous clearance of T. equi organisms does not appear to occur.

Foals infected in utero may be aborted or may be born anemic and weak. Differentiating EP from neonatal isoerythrolysis or sepsis may be difficult. Foals born to infected dams, but that are not infected in utero, will usually become carriers of the disease.

Horses infected with T. equi become lifelong carriers of this EP agent. When stressed, carriers may develop acute disease. Horses with chronic EP exhibit exercise intolerance, weight loss, transient fevers, reduced appetite, and an enlarged spleen.

Human infection with T. equi has been reported infrequently. Fever, hemolytic anemia, and hemoglobinuria may be observed.

Diagnosis
Organisms causing EP may be observed in Giemsa-stained blood or organ smears obtained from horses that are acutely affected, but are difficult to detect in horses that are carriers because the number of parasites harbored is lower. Blood samples collected during a febrile episode may yield better results. Several thin and thick blood smears (air dried and fixed with methanol) or an unclotted sample of blood (in a lavender EDTA tube) should be submitted for analysis. Horses infected with B. caballi carry low numbers of organisms in the blood; because infected erythrocytes tend to aggregate in smaller vessels, peripheral venipuncture may increase the chance of obtaining infected cells. Thick preparation of blood smears may also facilitate detection of organisms. Protozoa of B. caballi are paired and joined at their posterior ends, whereas four T. equi organisms combine in a tetrad or 'Maltese cross' configuration.

Complement fixation (CF) is the standard laboratory test for diagnosing infection with EP agents, but false negative and false positive results may occur. The indirect fluorescent antibody (IFA) test and competitive enzyme-linked immunosorbent assay (CELISA) are currently the preferred means of meeting requirements for international equine transport and trade as per the World Organization for Animal Health (OIE). Use of the CELISA was implemented in 2004 by the United States Department of Agriculture; however, due to conflicting results on pre-importation and post-importation tests (negative and positive, respectively), the USDA reversed its decision in late 2004 and now requires use of the CF test for detection of EP agents. The IFA test can distinguish between T. equi and B. caballi. A minimum of 20 ml of serum should be submitted for serologic examination. Submitted samples should be packed on wet ice or with frozen gel packs for transport to the diagnostic laboratory.

If results of serologic and microscopic testing are inconclusive, approximately 500 ml of whole blood is drawn from the suspect horse and transfused into a susceptible, splenectomized horse. The transfused horse is then closely monitored for signs of the disease, and a diagnosis is confirmed by microscopic observation of organisms in its erythrocytes. Alternatively, an uninfected tick is allowed to feed on the suspect animal, and parasites are then detected in the tick or by transmission of the disease to another susceptible animal. In vitro cultures and DNA probes are alternative methods of diagnosis.

Treatment
EP is a reportable disease. State or federal animal health officials should be immediately notified if EP is suspected.

In endemic regions, treatment via medication is instituted in affected horses. Diminazene diaceturate, phenamidine isethionate, and amicarbalide diisethionate are effective in eliminating clinical signs of B. caballi infection. Buparvaquone and other antitheilericidal drugs demonstrate some efficacy against T. equi, and may eliminate the parasite when combined with imidocarb. Theileria equi is more refractory to treatment than B. caballi, and higher dosages of imidocarb are required. The drug has a narrow range of safety, and dosages required for effective treatment of T. equi approach toxic dosages. Imidocarb appears to induce toxicosis and death more readily in donkeys.

Morbidity and mortality
The case fatality rate (the number of affected horses that die from the disease) may approach 50% for susceptible animals, and is highest for horses infected with T. equi.

Prevention and control
Because EP agents are transmitted by ticks, tick control is a vital preventive measure. Infected horses must be quarantined and isolated to reduce exposure to ticks. Pets and wildlife (including rodents) must be prevented from entering the isolation area, as they may carry ticks capable of transmitting EP agents.

No vaccine is available. The continued presence of organisms in an infected horse confers a level of active immunity from acute disease (premunition); however, once the organisms are eliminated, the horse can readily become reinfected.

Prevention in EP-free countries is by imposition of strict import regulations. Horses with antibodies to EP agents are only allowed into these countries under specific circumstances, and are strictly quarantined and isolated from susceptible animals. Strict tick control measures are instituted. Sentinel animals may be placed in isolation, and tested periodically for antibodies to EP agents. Under certain circumstances, horses for which positive results of testing are obtained after importation may be euthanatized in accord with federal law.

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