Equine granulocytic anaplasmosis is a febrile disease of horses caused by the tick-transmitted bacterium Anaplasma phagocytophilum. The disease can produce a high fever, which is responsive to tetracyclines. Equine and canine infections serve as sentinels for human risk because the same tick species can transmit the pathogen to any of these host species. Definitive diagnosis is obtained by cytological evaluation or PCR assay.
Equine granulocytic anaplasmosis is an infectious, noncontagious, seasonal, tickborne disease. Originally observed in the US in northern California, it is now recognized in many states where the tick vectors occur. It is also present in Europe, Asia, Africa, and South America.
Etiology, Epidemiology, and Transmission of Equine Granulocytic Anaplasmosis
The causative rickettsial agent of equine granulocytic anaplasmosis (EGA) was initially termed Ehrlichia equi; however, after taxonomic reclassification based on DNA sequence relationships, it was renamed Anaplasma phagocytophilum. The organism has a wide host range; naturally occurring infections have been observed in horses, burros, dogs, llamas, rodents, a variety of wildlife species, and humans (in whom the disease is designated human granulocytic anaplasmosis).
The geographical range of anaplasmosis appears to be increasing, concurrent with longer tick vector seasons due to rising climatic temperatures. Infections in humans are most common in the upper midwestern and northeastern states of the US and occur in many other countries worldwide. A phagocytophilum frequently infects horses in geographical areas where the tick vectors (Ixodes spp) are present, and the geographical distribution of equine cases mirrors that of human cases; the highest reported seroprevalence is in the midwestern and northeastern US for both species. In California and areas at a similar latitude, the disease is seasonal, occurring in late autumn, winter, and spring.
A phagocytophilum is present in cytoplasmic vacuoles of neutrophils and occasionally eosinophils during the acute phase of infection, appearing 2−4 days after the onset of clinical signs. Blood smears treated with Wright-Giemsa stain reveal one or more loose aggregates (morulae) of blue-gray to dark blue coccoid, coccobacillary, or pleomorphic organisms within the cytoplasm of neutrophils (see cytological image). These morulae, also sometimes called inclusion bodies, are generally 1.5–5 mcm in diameter.
Courtesy of Dr. Francisco Conrado, DACVP.
The infection can be transmitted experimentally to susceptible horses by direct injection of whole blood from infected horses or from humans with granulocytic anaplasmosis. The incubation period is 1–3 weeks. Ixodes pacificus (the western black-legged tick), Ixodes scapularis, Ixodes ricinus, and Ixodes persulcatus can transmit A phagocytophilum to horses.
There is no zoonotic risk of EGA infection to humans via horses. Both humans and horses are exposed through tick bites, so equine cases in an area serve as sentinels for human risk.
Clinical Findings of Equine Granulocytic Anaplasmosis
Clinical signs of equine granulocytic anaplasmosis may be mild, and signs vary in severity with the horse's age as follows:
Horses < 1 year old may have a fever only.
Horses 1–3 years old may develop fever, depression, mild limb edema, and (rarely) ataxia.
Adults, and particularly geriatric horses, may exhibit fever, partial anorexia, depression, reluctance to move, limb edema, petechiation, and icterus.
Fever, which is highest after approximately 5 days of infection, is typically 39.5–40°C (103–104°F) but can be as high as 41.7–42.2°C (107–108°F). Fever can persist for 6–12 days. Clinical signs of EGA also vary with duration of illness, becoming more severe over several days.
Rarely, myocardial vasculitis causes transient ventricular arrhythmias. Other clinical presentations for acute infection include recumbency and severe myopathy. Any concurrent infection (eg, a leg wound or respiratory infection) can be exacerbated. Cytoplasmic inclusion bodies are few during the first 48 hours and increase to 5–40% of circulating neutrophils during peak bacteremia. Affected horses typically have leukocytopenia or pancytopenia with moderate to severe thrombocytopenia.
Lesions
Gross petechiation (see petechiation image), ecchymoses, and edema develop in the subcutis and fascia. Vasculitis is regional and likely gravity dependent; the subcutis and fascia of the legs are predominantly affected.
Courtesy of Dr. Gabriella K. Piquini.
Diagnosis of Equine Granulocytic Anaplasmosis
Cytological evaluation
Clinical evaluation
PCR assay
Serological testing
Horses should be considered suspect for equine granulocytic anaplasmosis if they live in or have traveled to an endemic area and present with acute fever and related clinical signs, particularly during seasons of high tick activity.
Differential diagnoses of EGA include the following:
purpura hemorrhagica
A blood sample should be taken for a CBC, and the buffy coat can be enriched for neutrophils. Cytological evaluation of the buffy coat demonstrating characteristic cytoplasmic inclusion bodies in neutrophils is diagnostic. Because the window for identification of morulae is short, absence of morulae should not be used to exclude a diagnosis of A phagocytophilum infection, particularly within the first few days of clinical signs.
PCR assay is the optimal test for EGA and can detect A phagocytophilum DNA in unclotted blood or buffy coat smears. Results may be positive 3−6 days after infection, generally approximately 2−3 days after clinical signs first appear. Positive results can continue for up to 4 months in the absence of persistent clinical signs.
Pearls & Pitfalls
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Immunofluorescence assay results may be negative early in the disease process, whereas many horses in endemic areas may test positive, indicating exposure but not necessarily active infection. Paired samples demonstrating a 4-fold increase in antibody titers against A phagocytophilum over 2–4 weeks can retrospectively confirm a diagnosis. The seroconversion timeline for A phagocytophilum infection can be unpredictable; patients that do not seroconvert within the expected time frame may have another antibody titer drawn later in the disease course to ensure later conversion has not occurred.
Commercial, point-of-care ELISAs marketed for canine samples perform favorably as an alternative to immunofluorescence assay; however, they still only detect antibodies and, therefore, confirm only exposure. Positive ELISA results can persist for up to 9 months. Thus, commercial ELISAs alone should not be used to confirm infection, particularly in the absence of clinical signs.
Treatment and Control of Equine Granulocytic Anaplasmosis
Antimicrobials
Supportive care
Tetracycline-class antimicrobials are extremely effective against A phagocytophilum. Oxytetracycline, doxycycline, and minocycline have all been used successfully to treat equine granulocytic anaplasmosis. Oxytetracycline should be administered slowly and/or diluted to decrease the likelihood of reactions such as hypotension, collapse, and renal tubular necrosis. Penicillin, chloramphenicol, and streptomycin have no inhibitory effect and, therefore, should not be used to treat EGA. Horses treated with tetracyclines early in infection for short durations may relapse within a few weeks. Some cases of EGA may be self-limiting.
Horses with severe edema or neurological signs may benefit from short-term corticosteroid treatment (dexamethasone, 0.1 mg/kg, IV, PO, or IM, every 24 hours for 2–3 days), as well as supportive care, including fluid therapy and pain management. The risk of laminitis appears to be very low; laminitis has not occurred in clinical cases or experimental infections of EGA.
Recovered horses are solidly immune for ≥ 2 years and are not believed to be carriers. Persistence of infection has been suggested with some European strains, but further verification is required. Tick control measures are mandatory for control of disease. There is no vaccine.
Key Points
Equine granulocytic anaplasmosis is a seasonal, tickborne, bacterial disease of horses. It is caused by Anaplasma phagocytophilum, which is transmissible to numerous host species, including humans, via ticks.
The disease is becoming more widespread, concurrent with climatic change and expansion of vector areas.
The causative bacterium targets horse neutrophils, and infection can produce severe fever, distal limb edema, and thrombocytopenia.
Antimicrobials and supportive care are highly effective treatments for affected horses.
For More Information
Oliver A, Conrado FO, Nolen-Walston R. Equine granulocytic anaplasmosis. Vet Clin North Am Equine Pract. 2023;39(1):133-145.
Also see pet owner content regarding anaplasmosis in horses.
