Babesia spp.

Synopsis

CAPC Recommends

• Reduce risk of infection through year-round host-targeted tick control, avoiding areas with ticks, and limiting contact between dogs, especially when bite wounds may result.
• Diagnose babesiosis based on clinical signs, identification of intraerythrocytic organisms in stained blood smears, serology, or PCR.
• Treat babesiosis with either imidocarb diproprionate (large Babesia spp.) or a combination of atovaquone and azithromycin (small Babesia spp.)

Species

Canine

Babesia canis vogeli

Babesia sp. (Coco; also known as large Babesia sp.)

Babesia vulpes (also known as B. microti-like, Babesia cf. microti, B. annae, and Theileria annae)

Babesia gibsoni

Babesia conradae

• Babesia infections in domestic dogs include larger piroplasms collectively described as B. canis and smaller piroplasma that are often described as B. gibsoni-like. Three B. canis subspecies, B. canis canis, B. canis vogeli and B. canis rossi, are differentiated based on pathology, antigenic properties, tick vectors and genetic characterization, and these parasites are increasingly recognized as distinct species in current literature. Babesia canis vogeli (or B. vogeli) is enzootic to the United States. Babesia sp. (Coco) is a large species associated with case reports in Illinois, North Carolina, New Jersey, New York, Texas and Oklahoma, USA. Babesia vulpes is a small species originally described in northern Spain that is observed in wild canids and rarely domestic dogs. It is present in other European countries and in North America. Babesia conradae is a small species that has only been recovered dogs in California with a history of immunosuppression.

Feline

Babesia spp. infection has not been reported in domestic cats in the United States.

Overview of Life Cycle

• Dogs become infected with Babesia spp. when they are inoculated with sporozoites in tick saliva. After inoculation, Babesia sporozoites invade erythrocytes where they multiply asexually by binary fission. The resultant merozoites rupture the red blood cell and go on to invade additional erythrocytes. The genus Babesia is distinguished from other hemosporidian genera by the presence of intra-erythrocytic piroplasms only in the vertebrate host.
• Following ingestion by the tick, Babesia undergoes asexual division followed by development of gametes (gamogony). Gamogony is followed by asexual reproduction resulting in numerous sporozoites in the tick salivary glands. Sporozoites are the stages that are infective to vertebrate hosts. Below are stages in the life cycle. The piroplasms are in the vertebrate host. All other stages are in the tick.

Intra-erythorocytic piroplasms (replication) --> gametes --> fuse to form zygote --> migrates to hemocoel (undergo meiosis) --> ookinete --> sporokinete --> sporozoite

• Babesia canis vogeli is thought to cycle primarily between domestic dogs and Rhipicephalus sanguineus, the brown dog tick.
• Babesia gibsoni and other small species are also thought to be transmitted by R. sanguineus; although their life cycles have not yet been confirmed.
• Iatrogenic transmission is also possible through blood transfusion or blood-contaminated fomites.
• Fighting between dogs is a likely mode of mechanical transmission of B. gibsoni that may account, in part, for the relatively high prevalence of infection reported among American Staffordshire and American pit bull terriers.
• Vectors for other species of Babesia are unknown at this time.

Stages

• Piroplasms of Babesia spp. can be found within erythrocytes on stained blood smears.

• Babesia spp. in dogs may be differentiated to some degree by their size and general morphology. Babesia canis vogeli piroplasms are larger and often found in pairs, whereas those of B. gibsoni, B. conradae and Babesia vulpes are small, pleomorphic, ring-shaped organisms.

Babesia canis (arrow) within a red blood cell

Disease

• Dogs with babesiosis often present with moderate to severe hemolytic anemia and clinical illness characterized by fever, anorexia, depression, pallor, splenomegaly, and a bounding pulse. However, disease is considered uncommon in healthy, spleen-intact adult dogs in the United States.
• In general, disease is less severe with B. canis vogeli infection than with B. gibsoni and other small Babesia. Disease associated with Babesia sp. (Coco) has only been observed in immunocompromised dogs. Disease associated with Babesia conradae to date has only been observed in California. Babesia conradae was observed in closely-related dogs and/or dogs harboring Ornithodoros coriaceus suggesting that it may transmitted maternally or by this unique and regionally important soft tick. Little is known regarding disease (if any) in dogs harboring Babesia vulpes.
• Coinfection with Babesia spp. and other tick-borne pathogens has been documented and when present, may complicate interpretation of the clinical presentation and diagnostic assays.

Prevalence

• Canine infection with Babesia spp. is common throughout the world. Infection is more common in areas where tick infestation pressure is high and when routine acaricide use is not practiced. Although B. canis vogeli is perhaps the most well known, infection with B. gibsoni occurs more commonly in some areas and in some canine breeds in the United States.
• Babesia spp. are reported from throughout the United States with certain species specific occurrences. Infections appear to be more common in the southern states.
• Babesia sp. (Coco) has been reported from Illinois, North Carolina, New Jersey, New York, Texas and Oklahoma, USA.
• Infection with B. gibsoni occurs more commonly in certain breeds, such as American Staffordshire and American pit bull terriers, a phenomenon that is thought to be attributable to direct dog-to-dog mechanical transmission via bite wounds.
• Babesia conradae has only been reported from California.
• Aside from its documented presence in North America, the detailed prevalence and distribution of Babesia vulpes is unknown.

Host Associations and Transmission Between Hosts

• Most Babesia spp. are transmitted to dogs via tick feeding. Ticks are not able to transmit infection immediately upon first attachment to a host; they require a period of approximately 24 to 48 hours of initial feeding before organisms are able to pass across the salivary glands and into the vertebrate host. However, tick removal should not be delayed regardless of the average time for transmission of these parasites.
• Rhipicephalus sanguineus is the most common vector of etiologic agents of canine babesiosis in the United States.
• Direct transmission of Babesia spp. from an infected to a naïve animal can also occur following blood transfusion or iatrogenic inoculation with contaminated needles or surgical instruments. Direct dog-to-dog transmission via dog bites is thought to be an important means of transmission for B. gibsoni and may account for the apparently high prevalence of this organism in American Staffordshire and American pit bull terriers.

Prepatent Period and Environmental Factors

• Sporozoites enter the blood during tick feeding. Piroplasms become evident within erythrocytes on blood smears in approximately 1 to 3 weeks.
• The reported incubation period from infection to first appearance of clinical signs is 10–28 days. It is important to note that clinical signs are likely to appear well after tick detachment. Thus it may be difficult to correlate appearance of clinical signs and presence of attached ticks.
• Although clinical disease may resolve, Babesia infections are often persistent in dogs. Even after appropriate therapy, infection can persist for the life of the dog. Splenectomy or other instances of immune-compromise of persistently infected dogs could result in recrudescence of latent infections and relapse of the clinical disease. The use of Babesia-positive dogs as blood donors is discouraged.
• Infection with additional strains and/or species of Babesia also may occur when tick exposure or bite wound transmission continues.
• Note that for those species of Babesia that are known to be transmitted by ticks, environmental factors such as wildlife, vegetation, and climate often determine the occurrence and prevalence of vector ticks.

Site of Infection and Pathogenesis

• Ticks inoculate sporozoites of Babesia spp. directly into the bite wound. Organisms invade circulating erythrocytes and begin multiplying asexually.
• Rupture of red blood cells during asexual replication leads to intravascular hemolysis and hemolytic anemia. Immune-mediated clearance of parasitized erythrocytes contributes to the anemia.
• Thrombocytopenia, hypoalbuminemia, and hyperglobulinemia also occur.
• Splenectomy can exacerbate both parasitemia and clinical disease from infection with Babesia spp.
• Similarly, splenectomy and immunosuppression (e.g., via corticosteroids) can result in recrudescent parasitemia and relapse clinical disease from latent Babesia.

Diagnosis

• Definitive diagnosis of Babesia spp. infection relies on identification of piroplasms in erythrocytes on stained blood smears. Although organisms may be numerous in blood smears from animals with acute babesiosis, parasitemias are often low, and organisms may rarely be found in samples collected from dogs with chronic babesiosis or asymptomatic carriers.
• Serology may be helpful in identifying the presence of antibodies to Babesia spp. Indirect fluorescent antibody (IFA) assays, enzyme-linked immunosorbent (ELISA) assays, and immunochromatographic tests (ICT) have been used successfully. However, since antibodies may cross-react to several species, it may be difficult to confirm the infections with individual Babesia species. Recent development of recombinant ELISA procedures has improved the specificity of some ELISA methods. It is important to remember that antibody detection methods are often not useful in detecting acute infections.
• Molecular diagnosis of Babesia spp. infection in dogs and cats via polymerase chain reaction (PCR) of whole blood has become readily available. Both standard and nested PCR procedures are in use. A positive PCR result indicates the presence of Babesia-specific DNA. However, negative results may be observed if the level of circulating organisms falls below the level of assay detection. This may occur because of a normal decrease in circulating organisms or temporary suppression of infection following treatment. To maximize the utility of molecular diagnostics, blood samples should be collected early in the course of clinical disease.

Treatment

• Dogs infected with B. canis vogeli and other large Babesia spp. usually respond to treatment with imidocarb diproprionate at a dose of 6.6 mg/kg IM or SC administered twice at 14-day intervals.. Imidocarb diproprionate should not be administered intravenously to dogs.
• Babesia gibsoni and small Babesia spp are considered more difficult to treat than B. canis vogeli and large Babesia. Recommended treatment protocols for B. gibsoni and other small Babesia involve combining atovaquone (13.3 mg/kg PO q8h for 10 days) with azithromycin (10 mg/kg PO q 24 h for 10 days). Buparvaquone (5 mg/kg IM twice with 48 hr intervening) and azithromycin (10 mg/kg PO q24 h for 10 days) in combination have also been used successfully for treatment of small Babesia spp. Babesia spp. infections can also be treated with diminazene aceturate (3.5 mg/kg IM once) and pentamidine isethionate (16 mg/kg IM q24h for 2 doses).
• Other antiprotozoal drugs or antibiotics such as phenamidine, parvaquone, artemisinin derivatives, doxycycline, minocycline, clindamycin, enrofloxacin and metronidazole have been used with variable success (see Baneth, 2018).
• Treatment for babesiosis reduces parasitemia and supports resolution of clinical signs, but it is important to remember that the infection itself may not be eliminated. Dogs diagnosed with Babesia spp. should be considered permanent carriers of the infection

Control and Prevention

• Stringent adherence to routine application of effective acaricides is essential for preventing infection with Babesia spp.
• Vaccines are not available to prevent Babesia spp. infection of pets in North America.
• Babesia spp. are primarily transmitted by R. sanguineus, a tick that can survive indoors and thus year-round as established long-term infestations in homes and kennels. Although more common in warmer months and milder climates, when/where outdoor survival of R. sanguineus is optimal, this tick can occur anywhere there are dogs. CAPC recommends that all pets be maintained on tick-control products year-round.
• Attached ticks found on pets should be removed promptly to prevent transmission of any pathogens they may harbor. To avoid potential exposure to zoonotic pathogens and accidental inoculation of agents into the pet during the removal process, ticks should be retracted using forceps or a commercial tick-removal device, and care should be taken to avoid contact with tick contents, ideally by wearing gloves. Careful attention to handwashing following tick removal is also recommended.
• Blood donors should be screened for infection with Babesia spp. by serology, PCR, and blood smear, and any dogs testing positive excluded.
• Splenectomy or corticosteroid treatments of Babesia-positive dogs should be avoided as much as possible.
• Discourage dog fighting to prevent direct dog-to-dog transmission of B. gibsoni.

Public Health Considerations

• Babesia spp. infecting canine hosts are not known to infect people.
• People can become infected with Babesia microti (and other related Babesia spp. that normally infect rodents). Note that the previous reference to Babesia vulpes (Babesia microti-like) is not Babesia microti. In North America, Ixodes spp. ticks are the only known vectors of human infections with zoonotic Babesia spp.; dogs are not implicated in the maintenance or transmission of these zoonotic infections.

Selected References

• Uilenberg, 2006. Babesia--a historical overview. Vet Parasitol. 138(1-2):3-10. PubMed PMID: 16513280.
• Irwin, 2010. Canine babesiosis. Vet Clin North Am Small Anim Pract. 40(6):1141-56. PubMed PMID: 20933141.
• Sikorski et al., 2010. Babesiosis caused by a large Babesia species in 7 immunocompromised dogs. J Vet Intern Med. 24(1):127-31. PubMed PMID: 20002547.
• Di Cicco et al., 2012. Re-emergence of Babesia conradae and effective treatment of infected dogs with atovaquone and azithromycin. Vet Parasitol. 8;187(1-2):23-7. PubMed PMID: 22305297.
• Kȍster LS et al., 2015. Canine babesiosis: a perspective on clinical complications, biomarkers, and treatment. Vet Med Res Reports. 6:119-128 (http://dx.doi.org/10.2147.VMRR.560431).
• Baneth G. 2018. Antiprotozoal treatment of canine babesiosis. Vet Parasitol. 254:58-63.
• Annoscia G et al., 2017, A new PCR for the detection and differentiation of Babesia canis and Babesia vogeli. Ticks Tick Borne Dis. 8:862-855.
• Eichenberger RM et al., 2017. An ELISA for the early diagnosis of acute babesiosis detecting circulation antigen of large Babesia spp. Vet Parasitol. 243:162-168.