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PARASITOLOGY EXPERTISE FROM THE NCVP Peer Reviewed

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Infections transmitted by ticks are increasingly recognized as important causes of disease in North American dogs.

Veterinarians have been combatting canine bacterial and protozoal tick-borne diseases for decades (Table 1, page 56). In recent years, however, the geographic range of many of these pathogens has expanded, and several novel infections have been identifi ed, suggesting that the full complement of pathogens transmitted by ticks is more extensive than currently recognized in many regions of North America.

All of these infections share a common link: tick transmission. As a result, tick control for dogs is more important than ever. Following is a brief review of diagnosis and treatment of the more common tick-borne infections in dogs, and a description of some newly recognized infections that may become important for canine health in the future.

TICK-BORNE BACTERIAL DISEASESLyme DiseaseTransmission. Borrelia burgdorferi is the causative agent of Lyme disease in dogs and humans in the United States. Transmitted by Ixodes ticks, infection is most common in the Northeast,

Midwest, and West Coast states. In recent years, geographic expansion of the I scapularis/B burgdorferi maintenance cycle has resulted in increasing reports of disease in new regions, including the Great Lakes states, Mid-Atlantic states, southern Appalachia, and southern Canada.1

Presentation. Clinical signs develop in a minority of infected dogs and include fever, lethargy, and shifting polyarthritis. In some cases, potentially fatal glomerulonephritis can develop.2

Diagnosis. Clinical disease, when present, usually develops several months after infection, and serologic testing is the preferred means of diagnosis. However, most seropositive dogs do not appear to develop clinical signs. Some serologic targets are highly specifi c for B burgdorferi, such as the C6 assay (SNAP 4Dx Plus and Lyme Quant C6 tests, idexx.com), while others, such as immunofl uorescence antibody assays, may indicate past or current infection with several Borrelia species, complicating interpretation.3

Prevention. A combination of vaccination and diligent attention to tick control, with risk awareness supported by routine testing, can prevent Lyme disease, particularly in areas where infections are newly endemic.4

Parasitology Expertise from the NCVP

CANINE TICK-BORNE DISEASESLindsay A. Starkey, DVM, PhD, and Susan E. Little, DVM, PhD, Diplomate ACVM (Parasitology)Oklahoma State University

The Parasitology Expertise from the NCVP column is brought to you in partnership between the National Center for Veterinary Parasitology (ncvetp.org) and Today’s Veterinary Practice. The mission of the NCVP is to further the discipline of parasitology by bringing together partners from academia and industry to address emerging issues, serve the veterinary profession by developing future leaders in veterinary parasitology, and provide diagnostic and consulting services worldwide. Its goals include:

• Training graduate veterinarians and other scientists in clinical, applied veterinary parasitology• Promoting outstanding, clinically relevant veterinary parasitology research• Providing diagnostic veterinary services in clinical parasitology to practicing veterinarians• Offering balanced, science-based consulting expertise on parasite treatment and prevention

strategies.

How the C6 Peptide Detects AntibodyWhen B burgdorferi is transmitted to dogs in nature, the VlsE protein is expressed, resulting in production of antibodies that react to the C6 peptide. However, antibodies reactive to the C6 peptide are not produced following vaccination for Lyme disease, which provides a way to identify past or current infection in dogs. It is important to note that, even with this specifi c assay, a positive result indicates past or current infection with B burgdorferi but does not prove clinical disease.

How the

TODAY’S VETERINARY PRACTICE | July/August 2015 | tvpjournal.com

PARASITOLOGY EXPERTISE FROM THE NCVPPeer Reviewed

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AnaplasmosisTransmission. Two Anaplasma species are known to cause disease in North American dogs:5,6 • A phagocytophilum: Ixodes ticks (I scapularis and I

pacificus) are responsible for transmission, and A phagocytophilum infections are most prevalent in the Northeast and upper Midwest.

• A platys: Rhipicephalus sanguineus is considered this agent’s vector, and A platys infection is seen throughout the U.S. but is most common in south central states, such as Texas and Oklahoma, likely due to higher populations of R sanguineus.1 Presentation. Clinical signs of anaplasmosis

include fever, lethargy, anorexia, and lameness. Dogs

with anaplasmosis often have thrombocytopenia, with low platelet counts more likely to be cyclical in A platys infections. However, as with B burgdorferi, many dogs may be clinically normal despite current infection.5-7

Diagnosis. In clinically affected dogs, anaplasmosis is best diagnosed through a combination of polymerase chain reaction (PCR), serologic testing, and careful examination of stained blood smears (Table 2):6,8 • PCR assays are most useful for identifying early,

active infections prior to antibiotic treatment.• Serologic testing is more likely to confirm

established infections.

TABLE 1. Common Canine Tick-Borne Disease Agents in North America DISEASE DISEASE AGENTS PRIMARY TICK VECTOR(S) GEOGRAPHIC

DISTRIBUTION

Bacterial Disease

Lyme borreliosis Borrelia burgdorferi Ixodes scapularisIxodes pacifi cus

Northeast, Midwest, and West Coast states; southern Canada; recent expansion in Mid-Atlantic states

Anaplasmosis Anaplasma phagocytophilum

Ixodes scapularisIxodes pacifi cus

Northeast, Midwest, West Coast states

Anaplasma platys Rhipicephalus sanguineus* South central, southwestern U.S.; reported nationwide

Ehrlichiosis Ehrlichia canis Rhipicephalus sanguineus South central, southwestern U.S.; reported nationwide

Ehrlichia ewingiiEhrlichia chaffeensisPanola Mountain

Ehrlichia species

Amblyomma americanum Central and southeastern U.S.; extending northward along the Atlantic coast

Ehrlichia muris Ixodes scapularis Upper Midwest (Minnesota and Wisconsin)

Rocky Mountain spotted fever

Rickettsia rickettsii Dermacentor variabilisRhipicephalus sanguineus

South central, southwestern, and eastern U.S.; western mountain states

Protozoal Disease

Babesiosis Babesia vogeli§ Rhipicephalus sanguineus South central, eastern U.S.; reported nationwide

Babesia gibsoni† Rhipicephalus sanguineus* Reported sporadically nationwide

Other Babesia species Various tick species worldwide Occasionally reported

Hepatozoonosis Hepatozoon americanum Amblyomma maculatum South central and southeastern U.S.

Hepatozoon canis Rhipicephalus sanguineus* Reported sporadically nationwide

* Transmission cycle not yet con� rmed in North America§ Also referred to as B canis vogeli† More commonly transmitted by dog bite in North America



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• Antibodies can be detected in many dogs during both early and established acute disease.

• Identification of morulae on blood smears can be readily achieved in many patients, particularly during acute infection.

EhrlichiosisTransmission. Several different Ehrlichia species can infect dogs in the U.S., including E canis (Figure 1), E ewingii, E chaffeensis, Panola Mountain Ehrlichia species, and E muris.6,9,10 Different tick species are responsible for transmitting these Ehrlichia species, resulting in widespread distribution of infection.

Presentation. Common clinical abnormalities associated with acute ehrlichiosis include fever, lethargy, myalgia, anorexia, and thrombocytopenia; epistaxis and petechial and ecchymotic hemorrhages may be seen in severe cases of E canis–induced ehrlichiosis, while lameness and polyarthritis are more commonly associated with E ewingii infection.6,9,10 Some animals that become chronically infected with E canis can develop pancytopenia, neurologic disease, bleeding

diatheses, or ocular abnormalities, and fatalities are often reported.6 Many dogs, however, exhibit subclinical Ehrlichia species infections.6,11

Diagnosis. As with anaplasmosis, diagnosis can be made through PCR, serologic testing, and examination of blood smears; concurrent use of 2 or more methods improves the likelihood of confi rming a diagnosis.8,11

TABLE 2. Diagnostic Strategies for Tick-Borne Disease Agents DIAGNOSTIC METHOD

BENEFITS LIMITATIONS

Blood smear evaluation

• Rapid, in-clinic assay• Visualization of organisms (if present)

confi rms presence of Anaplasma species, Ehrlichia species, and protozoal agents

• Slide scanning can be time-consuming• Diagnosis to species level may be diffi cult• Useful only for identifying infection with

Anaplasma species, Ehrlichia species, and protozoal agents

Whole blood PCR

• Widely available through diagnostic laboratories

• Sensitive for acute infections with well-characterized Anaplasma and Ehrlichia species before initiation of antibiotic treatment

• Sensitive for identifying infection with Babesia and Hepatozoon species

• Depending on assay design, may be more specifi c than serologic testing`

• Some assays may provide quantitative results

• In-clinic testing with same-day results not usually available

• Some organisms (Borrelia burgdorferi, Rickettsia species) unlikely to be present in blood sample, despite presence of infection and clinical disease

• Less reliable when very low circulating rickettsemia present (chronic infection) and after initiation of antibiotic treatment

• May not identify presence of infection with novel disease agents

• May lead to false-positive results due to presence of closely related agents

Serologic testing

• In-clinic assays available for many agents• Depending on design, allows for detection

of antibodies to several different agents with one assay

• Panel assays often available from diagnostic laboratories

• Some assays may provide quantitative results• Paired (acute and convalescent) samples

collected 2–4 weeks apart can identify rising or falling titers and, thus, recent infection

• May be less useful in acute infections before seroconversion if only a single sample is evaluated

• Antibodies persist for months to years after infection, which can confuse interpretation

• Cross-reactivity common, particularly with immunofl uorescence-based assays, including to nonpathogenic organisms

FIGURE 1. Morulae of Ehrlichia canis (arrows) within monocytes. Wright-Giemsa stain, magnifi cation, 1000×. Courtesy National Center for Veterinary Parasitology



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Rocky Mountain Spotted FeverTransmission. Rocky Mountain spotted fever—caused by Rickettsia rickettsii—is considered one of the most serious tick-borne diseases in the Americas due to its high fatality rate and rapid onset. Infection with R rickettsii is most commonly transmitted by Dermacentor variabilis in eastern North America and D andersoni in the Rocky Mountain states, but other tick species, including R sanguineus and Amblyomma species, have been confi rmed to also transmit infections in North, Central, and South America.12

Presentation. Clinical signs include rapid onset of fever, lethargy, and anorexia. Thrombocytopenia is often present, and some dogs may develop bleeding diatheses. Neurologic complications occur frequently. Clinical disease, although relatively uncommon, is associated with high fatality rates in both humans and dogs, particularly when treatment is delayed or withheld.13 Prompt, aggressive treatment can result in a rapid response, with resolution of clinical signs within a few days.

Diagnosis. Diagnosis can be confi rmed with serologic testing, but treatment should be initiated upon suspicion of infection rather than upon diagnostic confi rmation because:8 • Many patients with acute infection and disease

have not yet seroconverted • PCR of whole blood is less likely to identify

infection with R rickettsii than with Anaplasma or Ehrlichia species. When presenting and convalescent titers are

compared, demonstration of a rising titer can be diagnostic. Serologic assays for R rickettsii are not specifi c, and when tick infestations are common, many dogs will have antibodies reactive to R rickettsii due to past infection with other, nonpathogenic Rickettsia species. Results of any

diagnostic tests should always be interpreted together with clinical presentation.14

TICK-BORNE PROTOZOAL DISEASESBabesiosisTransmission. Many Babesia species cause disease in dogs worldwide. However, the 2 most commonly identifi ed in North American dogs are: • B vogeli (formerly B canis vogeli), transmitted by

R sanguineus (Figure 2) • B gibsoni, usually transmitted between

dogs through contaminated blood during dog fighting; also transmitted by ticks (Haemaphysalis species) in other parts of the world, with R sanguineus suspected, but not confirmed, to be involved in transmission.15 Infection with B vogeli appears particularly

common in the southern U.S., where R sanguineus populations are intense; infections are often identifi ed in kennels harboring infestations with brown dog ticks.16

Presentation. Dogs with clinical babesiosis present with anorexia, fever, and depression; hemolytic anemia and pale mucous membranes are common. Disease is considered more common following splenectomy.17 Infection with B gibsoni is most commonly reported in American Staffordshire and American pit bull terriers.16

Diagnosis. Infection is usually diagnosed by careful examination of stained blood smears for characteristic large (B vogeli) or small (B gibsoni) piroplasms within red blood cells.15 Serologic testing and PCR are also widely available and can be helpful in identifying chronic and acute infections, respectively.

HepatozoonosisTransmission. The most common and severe cause of canine hepatozoonosis in the U.S. is Hepatozoon americanum, transmitted by Amblyomma maculatum primarily in southern states.18 In recent years, H canis has also been identifi ed in the U.S., although this R sanguineus–transmitted pathogen is more common in dogs in South America, Europe, Africa, and Asia.

Rather than transmission by tick bite, hepatozoonosis agents infect dogs when they ingest a tick containing infective sporozoites during grooming, predation or, in the case of H americanum, when cystozoites are ingested from tissues of rodents or rabbits that have ingested infected ticks.19

FIGURE 2. Piroplasms of Babesia vogeli within erythrocytes. Wright-Giemsa stain, magnifi cation, 1000×. Courtesy National Center for Veterinary Parasitology



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Presentation. Dogs with disease due to H americanum usually present with fever, myalgia, muscle atrophy, and poor body condition. Profound neutrophilia is often present, and periosteal bone proliferation may occur.18 Without treatment, body condition continues to deteriorate and many affected dogs die or are euthanized.

Diagnosis. Disease is most commonly diagnosed by whole blood PCR, although gamonts are occasionally found on blood smears (Figure 3). Histologic examination of muscle biopsy specimens is more sensitive than whole blood PCR for diagnosing infection, but less commonly pursued due to the invasive nature of sample collection. Serologic assays to confi rm Hepatozoon infection are not available.

NOVEL TICK-BORNE DISEASE AGENTSA variety of novel pathogens transmitted by ticks have been described in North America in recent years:• Canine, human, and tick infections with novel

Ehrlichia species have been described9,10

• Canine and human infections with spotted fever group Rickettsia species other than R rickettsii have been reported14,20

• Canine infections with previously unrecognized Babesia and Hepatozoon species have been identified17,21

• Some data suggest that ticks may transmit other organisms, such as Bartonella species.22,23 In addition, viral tick-borne pathogens have

been increasingly identifi ed in humans.24,25 Heartland virus and Bourbon virus are 2 examples of recently identifi ed, apparently tick-transmitted pathogens in humans, although neither has yet been described in dogs.

TREATMENT OF TICK-BORNE DISEASESWhen treating dogs suspected of having tick-borne disease:1. Base the decision to treat primarily on your

clinical judgment. 2. Use diagnostic results as an adjunct to clinical

judgment, but not as the basis for administering or withholding treatment.

3. In dogs with moderate to severe clinical illness, do not: » Delay treatment while waiting for diagnostic

test results » Withhold treatment if fi ndings on serologic

testing or PCR are negative. 4. Do not delay treatment in dogs with clinical disease,

particularly rickettsial infections; these patients may be serologically negative at initial presentation and PCR may fail to identify a novel disease agent, but delaying treatment can result in death.

Bacterial DiseaseTreatment of choice for common bacterial tick-borne disease agents is doxycycline. Recommended regimens vary according to the specifi c target agents, but doxycycline at 10 mg/kg PO Q 24 H for 28 days is effective against B burgdorferi, Anaplasma species, Ehrlichia species, and R rickettsii.5,6,8

Clinical improvement is typically evident within the fi rst week of therapy.6,26 Dogs that do not respond to doxycycline should be carefully re-evaluated for additional etiologic agents. Co-infection with bacterial and protozoal agents is frequent and can be responsible for apparent doxycycline treatment failure in some patients.

Protozoal DiseaseTreatment recommendations for canine babesiosis and hepatozoonosis vary depending on the specifi c agent responsible. • Infections with large Babesia species, such

as B vogeli, can be treated with imidocarb dipropionate, 6 mg/kg IM, with the dose repeated in 14 days.

• Infections with small Babesia species, such as B gibsoni, are generally more difficult to treat; a combination of atovaquone, 13 mg/kg PO Q 8 H for 10 days, and azithromycin, 10 mg/kg PO Q 24 H for 10 days, is recommended.27 Hepatozoonosis due to H americanum is

particularly challenging to treat and requires either:18 • Ponazuril, 10 mg/kg PO Q 12 H for 14 days or

FIGURE 3. Gamont of Hepatozoon americanum (arrow) within a leukocyte. Wright-Giemsa stain, magnifi cation, 1000×. Courtesy National Center for Veterinary Parasitology



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• Triple therapy for 14 days with (1) trimethoprim sulfamethoxazole, 15 mg/kg PO Q 12 H; (2) clindamycin, 10 mg/kg PO Q 8 H; and (3) pyrimethamine, 0.25 mg/kg PO Q 24 H.Regardless of initial therapy choice, dogs

with American canine hepatozoonosis should be maintained long-term (2 years or more) on suppressive therapy with decoquinate, 10 to 20 mg/kg PO Q 12 H. Nonsteroidal anti-infl ammatory drugs are also useful to improve clinical condition.

PCR = polymerase chain reaction

References1. Little SE, Beall MJ, Bowman DD, et al. Canine infection with

Dirofi laria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp., in the United States, 2010–2012. Parasit Vectors 2014; 7:257.

2. Littman MP, Goldstein RE, Labato MA, et al. ACVIM small animal consensus statement on Lyme disease in dogs: Diagnosis, treatment, and prevention. J Vet Intern Med 2006; 2:422-434.

3. Little SE, Heise SR, Blagburn BL, et al. Lyme borreliosis in dogs and humans in the USA. Trends Parasitol 2010; 26:213-218.

4. Krupka I, Straubinger RK. Lyme borreliosis in dogs and cats: Background, diagnosis, treatment and prevention of infections with Borrelia burgdorferi sensu stricto. Vet Clin North Am Small Anim Pract 2010; 40:1103-1119.

5. Carrade DD, Foley JE, Borjesson DL, et al. Canine granulocytic anaplasmosis: A review. J Vet Intern Med 2009; 23(6):1129-1141.

6. Little SE. Ehrlichiosis and anaplasmosis in dogs and cats. Vet Clin North Am Small Anim Pract 2010; 40(6):1121-1140.

7. Gaunt SD, Beall MJ, Stillman BA, et al. Experimental infection and co-infection of dogs with Anaplasma platys and Ehrlichia canis: Hematologic, serologic, and molecular fi ndings. Parasit Vectors 2010; 3:33.

8. Allison RW, Little SE. Diagnosis of rickettsial diseases in dogs and cats. Vet Clin Pathol 2013; 42(2):127-144.

9. Hegarty BC, Maggi RG, Koskinen P, et al. Ehrlichia muris infection in a dog from Minnesota. J Vet Intern Med 2012; 26(5):1217-1220.

10. Qurollo BA, Davenport AC, Sherbert BM, et al. Infection with Panola Mountain Ehrlichia sp. in a dog with atypical lymphocytes and clonal T-cell expansion. J Vet Intern Med 2013; 27(5):1251-1255.

11. Starkey LA, Barrett AW, Beall MJ, et al. Persistent Ehrlichia ewingii infection in dogs after natural tick infestation. J Vet Intern Med 2015; 29(2):552-555.

12. Dahlgren FS, Holman RC, Paddock CD, et al. Fatal Rocky Mountain spotted fever in the United States, 1999-2007. Am J Trop Med Hyg 2012; 86(4):713-719.

13. Nicholson WL, Allen KE, McQuiston JH, et al. The increasing recognition of rickettsial pathogens in dogs and people. Trends Parasitol 2010; 26(4):205-212.

14. Barrett A, Little SE, Shaw E. “Rickettsia amblyommii” and R montanensis infection in dogs following natural exposure to ticks. Vector Borne Zoonotic Dis 2014; 14(1):20-25.

15. Irwin PJ. Canine babesiosis. Vet Clin North Am Small Anim Pract 2010; 40(6):1141-1156.

16. Birkenheuer AJ, Correa MT, Levy MG, et al. Geographic distribution of babesiosis among dogs in the United States and association with dog bites: 150 cases (2000-2003). JAVMA 2005; 227(6):942-947.

17. Sikorski LE, Birkenheuer AJ, Holowaychuk MK, et al. Babesiosis caused by a large Babesia species in 7 immunocompromised dogs. J Vet Intern Med 2010; 24(1):127-131.

18. Allen KE, Johnson EM, Little SE. Hepatozoon spp. infection in the United States. Vet Clin North Am Small Anim Pract 2011; 41:1221-1238.

19. Johnson EM, Panciera RJ, Allen KE, et al. Alternate pathway of infection with Hepatozoon americanum and the epidemiologic importance of predation. J Vet Intern Med 2010; 23:1315-1318.

20. Paddock CD, Finley RW, Wright CS, et al. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin Infect Dis 2008; 47:1188-1196.

21. Allen KE, Li Y, Kaltenboeck B, et al. Diversity of Hepatozoon species in naturally infected dogs in the southern United States. Vet Parasitol 2008; 154(3-4):220-225.

22. Cotte V, Bonnet S, Le Rhun D, et al. Transmission of Bartonella henselae by Ixodes ricinus. Emerg Infect Dis 2008; 14(7):1074-1080.

23. Reis C, Cote M, Le Rhun D, et al. Vector competence of the tick Ixodes ricinus for transmission of Bartonella birtlesii. PLoS Negl Trop Dis 2011; 5(5):e1186. doi:10.1371/journal.pntd.0001186. [PMC free article] [PubMed] [Cross Ref].

24. Pastula DM, Turabelidze G, Yates KF, et al. Notes from the fi eld: Heartland virus disease—United States, 2012-2013. MMWR Morb Mortal Wkly Rep 2014; 63(12):270-271.

25. Kosoy OI, Lambert AJ, Hawkinson DJ, et al. Novel thogotovirus associated with febrile illness and death, United States, 2014. Emerg Infect Dis 2015. doi:10.3201/eid2105.150150.

26. Neer TM, Breitschwerdt EB, Greene RT, Lappin MR. Consensus statement on ehrlichial disease of small animals from the infectious disease study group of the ACVIM, American College of Veterinary Internal Medicine. J Vet Intern Med 2002; 16(3):309-315.

27. Birkenheuer AJ, Levy MG, Breitschwerdt EB. Effi cacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs. J Vet Intern Med 2004; 18(4):494-498.

SUSAN E. LITTLESusan E. Little, DVM, PhD, Diplomate ACVM (Parasitology), is a veterinarian, par-asitologist, and co-director of the National Center for Veterinary Parasitology at Okla-homa State University, where she serves as Regents Professor and the Krull-Ewing Chair in Veterinary Parasitology. She has been recognized for teaching excellence through the Pfi zer (Norden) Distinguished Teaching Award and National Student AVMA Excel-lence in Teaching Award, and for outstand-ing research through the Pfi zer Award for Research Excellence. She received her DVM from Virginia–Maryland College of Veteri-nary Medicine (Virginia Institute of Technol-ogy) and PhD from University of Georgia.

LINDSAY A. STARKEYLindsay A. Starkey, DVM, PhD, is a vet-erinarian, parasitologist, and currently the Bayer Resident in Veterinary Para-sitology through the National Center for Veterinary Parasitology at Oklaho-ma State University. She received the AAVP/Merck Outstanding Graduate Student Award and the AAVP/CAPC Graduate Student Award in Zoonotic Disease from the American Association of Veterinary Parasitologists for her dis-sertational research, which focused on ticks and tick-borne diseases. Dr. Star-key received her DVM and PhD from Oklahoma State University.

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