Diagnosing and Managing Anaplasma Infection in Dogs

Signs of canine anaplasmosis may manifest following infection with either Anaplasma phagocytophilum or Anaplasma platys. However, many dogs with circulating antibodies to Anaplasma species do not exhibit obvious signs of disease. Both agents of anaplasmosis are transmitted by ticks, and their distribution corresponds with the range of their vector.

As tick-borne diseases continue to spread and vector-borne disease diagnostics continue to improve, veterinarians are diagnosing more dogs with Anaplasma infections. In managing seropositive dogs, consistent messaging for clinic staff and pet owners regarding diagnostic and control recommendations is critical for widespread awareness and success of preventive measures.

Anaplasmosis in Dogs

A phagocytophilum and A platys are well-known agents of anaplasmosis in dogs (TABLE 1). Both are obligate intracellular bacteria found globally and transmitted by ticks commonly found on dogs in North America. Prior infection with Anaplasma species does not appear to offer full protective immunity, meaning dogs are susceptible to reinfection.²

A phagocytophilum resides and multiplies primarily in neutrophils before disseminating throughout the body. Seropositive dogs are found in the northeastern, upper midwestern, and western United States. Ixodes scapularis (FIGURE 1A) is the primary vector in the Northeast and Midwest, while Ixodes pacificus is the primary vector in the West. The majority of I scapularis adults seek hosts in the cooler months of the year, and this unique characteristic is worth mentioning to pet owners.³ In nature, A phagocytophilum is maintained in various vertebrate hosts, such as rodents, and after feeding on a reservoir host, ticks remain infected after each molt.²

Figure 1A. Ixodes species are the vector for Anaplasma phagocytophilum. Courtesy National Center for Veterinary Parasitology (ncvetp.org)

A platys resides and multiplies in platelets, from which it disseminates. In the United States, most infections are diagnosed in southern regions where the suspected tick vector, the brown dog tick (Rhipicephalus sanguineus), thrives.² This tick species (FIGURE 1B) feeds on dogs at every life stage, and high tick burdens are not uncommon. Because this tick can infest kennels and homes, year-round activity and pathogen transmission is possible. Dogs are the primary reservoir for A platys, and brown dog ticks, once infected, can maintain infection between molts, allowing efficient pathogen transmission between dogs.¹

Figure 1B. Rhipicephalus sanguineus is the suspected vector for Anaplasma platys. Courtesy National Center for Veterinary Parasitology (ncvetp.org)

Subclinical infections are common, with up to 60% of seropositive dogs not showing obvious signs of infection.¹ If present, disease occurs soon after infection with A phagocytophilum; however, persistent manifestations were noted experimentally and chronic infection with A platys is not uncommon.² With A platys, disease is often mild with recurrent thrombocytopenia every 10 to 14 days, which is attributed to phagocytosis of infected platelets. Other signs may include bleeding tendencies (e.g., epistaxis). Dogs with A phagocytophilum infection might be lethargic, anorexic, or feverish. Thrombocytopenia can be seen in > 90% of patients and signs suggestive of polyarthritis, such as reluctance to move, could be present.^1,2

Trends in Diagnostic Testing

Canine seropositivity to tick-transmitted Anaplasma species has increased over the past few years, and some veterinarians in endemic areas may be detecting Anaplasma antibodies more often than any other tick-borne disease agent. When reviewing canine test results from IDEXX between 2013 and 2019, researchers demonstrated the continued expansion of A phagocytophilum across the United States.⁴ More recently in 2021, the Companion Animal Parasite Council documented that 1 out of every 50 tested dogs was seropositive to Anaplasma species, whereas in 2022, 1 in 30 dogs tested positive.^5,6 These escalating trends continued through 2023, and the reports may be explained, in part, by improved diagnostics and awareness. Several point-of-care enzyme-linked immunosorbent assays (ELISAs) exist, with a range of documented sensitivities and specificities; 1 ELISA reports sensitivity and specificity as high as 94.1% (95% confidence interval [CI]: 86.8% to 98.1%) and 98.4% (95% CI: 96.6% to 99.3%), respectively.⁷

Serology remains a popular method of detecting infections with Anaplasma species. Generally, it takes 1 to 2 weeks after infection before antibodies can be detected, and because there are varying levels of cross-reactivity, a positive result is reported at the genus level.⁸ Other diagnostics to consider include blood smears for visualization of morulae in neutrophils (A phagocytophilum) or platelets (A platys) (FIGURE 2). Neutrophils infected with A phagocytophilum are more likely to be seen during the acute phase in sick dogs, and the evaluation of blood smears yields moderate to high sensitivity in those cases.² However, the lack of morulae on a blood film should not rule out an infection as parasitemia may be low in chronic phases.

Figure 2A. Neutrophils infected with morulae of Anaplasma phagocytophilum (black arrow). Courtesy National Center for Veterinary Parasitology (ncvetp.org)

Figure 2B. Platelets infected with morulae of Anaplasma platys (white arrow). Courtesy National Center for Veterinary Parasitology (ncvetp.org)

Sending blood or tissue samples to a laboratory for polymerase chain reaction (PCR) testing can also be considered. In chronic cases, PCR testing of biopsy samples from spleen, lymph node, or bone marrow may yield a greater sensitivity than peripheral blood; however, whole blood collected during acute illness appears to have acceptably high sensitivity.² PCR results can take several days to return to the clinic, and, as with blood films, a negative result does not rule out infection with low parasitemia, particularly in chronic cases. For these reasons, a multimodal approach to diagnosing anaplasmosis is recommended and samples should be collected as soon as clinical illness presents.

Managing Anaplasmosis Serologic Results

To assist veterinarians with managing seropositive dogs, some diagnostic companies have collaborated with veterinary specialists to develop clinical reference guides.⁹ These guides can help veterinarians develop diagnostic and management plans and aid client communication.

Positive Result With Clinical Signs

If a dog is exhibiting clinical signs of anaplasmosis and a serologic test result is positive, next considerations should include a complete blood count (CBC) and blood film evaluation of fresh whole blood. If thrombocytopenia or anemia—with or without neutrophilia and monocytosis—is present, the results agree with a diagnosis of anaplasmosis. Appropriate treatment with doxycycline, or other tetracycline, should be strongly considered, particularly if no other cause for these abnormalities is found.² The diagnosis would be strengthened if morulae are found in neutrophils (A phagocytophilum) or platelets (A platys).

In diagnosed cases, a recheck CBC should be considered approximately 7 days later to assess progression of disease or response to treatment. Alternatively, if no morulae are detected on blood film and the CBC is within normal limits, the positive serologic test may be an incidental finding and the noticeable clinical signs could be due to another cause; therefore, other testing (e.g., PCR) should be considered. In these situations, it is important to remember that many dogs can be seropositive without obvious clinical signs. Additionally, the signs suggestive of tick-borne diseases (e.g., lethargy, fever) overlap with those of many other infectious diseases.

Negative Result With Clinical Signs

If a dog is exhibiting clinical signs suggestive of anaplasmosis but a serologic test result is negative, the dog may be displaying acute disease prior to development of antibodies. When disease is recognized in dogs, it is shortly (approximately 1 to 2 weeks) after infection and may slightly precede production of antibodies, which can become detectable as early as 8 days after infection.^1,8 In these cases, a second serologic test may be warranted in 2 to 4 weeks, and PCR testing should be strongly considered since it is more likely to detect acute infections.^2,8

Since the window between clinical disease and antibody production is small, another cause may be responsible for the clinical signs observed. Performing additional diagnostic tests, such as a CBC, serum chemistry panel, blood film, urinalysis with urine protein to creatinine ratio, or tick-borne PCR panel, should be considered to explore other possibilities for the clinical signs.

Positive Result Without Clinical Signs

If a dog is not exhibiting clinical signs of anaplasmosis but a serologic test result is positive, a CBC and blood film are warranted. If morulae are seen on a blood film or thrombocytopenia is present on the CBC, then the dog may have anaplasmosis and treatment should be considered along with recheck testing of the CBC a week later. If no improvement is noted on recheck, other causes for the abnormalities should be investigated.

If a clinically normal, seropositive dog has a CBC within normal limits, the positive serologic result likely indicates a prior infection that remained undiagnosed or subclinical. In these cases, a recheck CBC can be performed in 7 days to ensure no clinical abnormalities develop, and treatment is not warranted if the CBC stays within normal limits.² Antibodies to Anaplasma species can be long-lived (i.e., several months or years), and chronically infected dogs may have high titers; however, if the pathogen is actively evading the immune system, a chronically infected dog may be seronegative at times.^2,8

Owners of seropositive but apparently healthy dogs should be advised on the signs of anaplasmosis and educated on proper tick control and removal and the value of annual tick-borne disease testing.

Negative Result Without Clinical Signs

If no clinical signs of anaplasmosis are present and an annual serologic test result is negative, infection with Anaplasma species is unlikely. However, the many benefits of tick prevention and annual testing for common tick-borne diseases should be reviewed with the pet owner. There is enough convincing evidence to suggest that tick-borne diseases will continue to spread to new areas; thus, the infection risk is rarely zero.¹⁰

Summary

Current trends in canine tick-borne diseases suggest anaplasmosis is a growing threat to dogs. As diagnostics improve and awareness of routine tick-borne disease testing increases, more dogs will be identified as seropositive to Anaplasma species. Not all seropositive dogs will display clinical signs, and the need for treatment is likely unnecessary in most cases. However, performing a CBC to assess platelet counts in seropositive dogs is necessary given the potential severity of disease; when thrombocytopenia is present, treatment should be considered. Additionally, PCR tests may provide more diagnostic evidence, but the results should be combined with serology and clinical history for treatment decisions. Evidence of infection by detection of antibodies presents the opportunity to educate clients on the need for annual tick-borne disease screening and strict tick control.