Overview

• Babesiosis is the disease caused by the protozoal parasites of the genus Babesia. Merozoites or piroplasms are the stage that infects mammalian red blood cells.
• B. canis-a large (4–7 µm) piroplasm that infects dogs; B. canis is distributed worldwide, and there are three subspecies based on genetic, biologic, and geographic data. B. canis vogeli has been reported in the United States, Africa, Asia, and Australia. B. canis rossi is the most virulent and is present in Africa. B. canis canis has been reported in Europe.
• Some have proposed that these organism are indeed three distinct species: B. vogeli, B. rossi, and B. canis.
• Recent studies have identified at least three genetically distinct small (2–5 µm) piroplasms that can infect dogs:
  • B. gibsoni (a.k.a. B. gibsoni [Asia])-small piroplasm that infects dogs; worldwide distribution; emerging disease in the United States.
  • B. conradae (a.k.a. B. gibsoni [United States/California])-small piroplasm that infects dogs; only reported in California.
  • Babesia (Theileria) annae (a.k.a. Spanish dog piroplasm and B. microti-like parasite)-small piroplasm that infects dogs; reported in Spain, other parts of Europe, and most recently in the United States.
• Babesia sp. (Coco)-large piroplasm identified in splenectomized and immune-suppressed dogs in the United States.
• Several other single-case reports of novel Babesia sp. and other piroplasms (i.e., T. equi) have been published.
• B. felis-small (2–5 µm) piroplasm that infects cats; reported in Africa.
• Cytauxzoon felis-small piroplasm that infects cats; reported in the United States.
• Infection may occur either by tick transmission, direct transmission via blood transfer during dog bites, blood transfusions, or transplacental transmission.
• Incubation period averages about 2 weeks, but some cases are not clinically diagnosed for months to years.
• Piroplasms infect and replicate in red blood cells, resulting in both direct and immune-mediated hemolytic anemia.
• Immune-mediated hemolytic anemia is likely to be more clinically important than parasite-induced RBC destruction, since the severity of signs does not depend on the degree of parasitemia.

Systems Affected

• Hemic/Lymphatic/Immune-anemia, thrombocytopenia (bleeding tendencies appear rare), fever, splenomegaly, lymphadenomegaly, vasculitis (experimental only).
• Hepatobiliary-increased liver enzymes (mild-moderate, not the sole abnormality detected).
• Nervous-cerebral babesiosis, weakness, disorientation, collapse (most common with B. canis rossi).
• Renal/Urologic-renal failure (B. canis rossi and B. annae).

Signalment

• Any age or breed of dog can be infected.
• B. canis infections are more prevalent in greyhounds.
• B. gibsoni (Asia) infections are more prevalent in American pit bull terriers.
• Any age or breed of cat can be infected, but to date, only C. felis has been reported in the United States.

Signs

• Signs are similar in dogs and cats.
• Signs can be peracute, acute, or chronic.
• Some carrier animals have no detectable clinical signs.
• Dogs-lethargy, anorexia, pale mucous membranes, fever, splenomegaly, lymphadenomegaly, pigmenturia, icterus, weight loss, discolored stool.
• Cats-lethargy, anorexia, pale mucous membranes, icterus.

Causes & Risk Factors

• History of tick attachment.
• Splenectomized animals develop more severe clinical disease.
• History of splenectomy or chemotherapy appear to be risk factors for Babesia sp. (Coco).
• Immune suppression may cause clinical signs and increased parasitemia in chronically infected dogs.
• History of a recent dog-bite wound is a risk for B. gibsoni (Asia) infection.
• Recent blood transfusion from a subclinically infected donor.

Differential Diagnosis

• Any cause of immune-mediated hemolytic anemia or thrombocytopenia, including idiopathic immune-mediated hemolytic anemia or thrombocytopenia, ehrlichiosis, Rocky Mountain spotted fever, systemic lupus erythematosus, neoplasia, endocarditis, hemotrophic mycoplasmosis (haemobartonellosis), and cytauxzoonosis
• A positive Coombs' test does not rule out babesiosis since many animals with babesiosis are also Coombs' positive.
• Non-immune-mediated hemolytic anemia, including microangiopathic anemia, caval syndrome, splenic torsion, DIC, Heinz body anemia, pyruvate kinase deficiency, phosphofructokinase deficiency.
• Hepatic and post-hepatic jaundice.

CBC/Biochemistry/Urinalysis

• Anemia-absent to severe; usually regenerative (reticulocytosis) unless signs are very acute; anemia can be severe in some cases (PCV <10%), anemia is not present in all cases.
• Thrombocytopenia-usually moderate to severe; some animals have thrombocytopenia without anemia. Thrombocytopenia is the most common hematologic abnormality.
• Leukocyte responses are variable, with both leukocytosis and leukopenia reported.
• Hyperbilirubinemia may be present depending on the rate of hemolysis.
• Hyperglobulinemia is common in chronic infections and may be the only biochemical abnormality in some animals.
• Mildly elevated liver enzymes from anemia/hypoxia.
• Proteinuria and hypoalbuminemia (protein-losing nephropathy) may occur
• Azotemia and metabolic acidosis secondary to renal failure have been reported with B. canis rossi and B. annae.
• Bilirubinuria is common.
• Hemoglobinuria is detected less commonly in the United States than in Africa.

Other Laboratory Tests

• Microscopic examination of stained thin or thick blood smears-can provide a definitive diagnosis; sensitivity depends on microscopist experience and staining technique; most success using a quick modified Wright stain; capillary blood may enhance sensitivity; microscopy may not accurately differentiate the species or subspecies.
• IFA-tests for antibodies in serum that react with Babesia organisms; cross-reactive antibodies can prevent the differentiation of species and subspecies; some infected animals, particularly young dogs, may have no detectable antibodies.
• PCR-tests for the presence of Babesia DNA in a biologic sample (usually EDTA anticoagulated whole blood); can differentiate subspecies and species; more sensitive than microscopy.

Drug(s) Of Choice

• Imidocarb dipropionate (FDA approved; 6.6 mg/kg SC or IM every 1–2 weeks) and diminazine aceturate (not FDA approved; 3.5–7 mg/kg SC or IM every 1–2 weeks) decrease morbidity and mortality in affected animals. They may completely clear B. canis infections but not B. gibsoni (Asia).
• Combination therapy of azithromycin (10 mg/kg PO q24h for 10 days) and atovaquone (13.5 mg/kg PO q8h for 10 days) is the treatment of choice and the only treatment that can potentially clear B. gibsoni (Asia) infections in dogs. In a controlled study, 85% of dogs cleared the infection after treatment.
• A combination of clindamycin (25 mg/kg PO q12h), metronidazole (15 mg/kg PO q12h), and doxycycline (5 mg/kg PO q12h) had been associated with elimination or reduction of the parasite below the limit of detection of PCR testing. Unfortunately a well-defined treatment course has not been established, with treatment times ranging from 24 to 92 days.
• A combination of doxycycline (7–10 mg/kg PO q24h), enrofloxacin (2–2.5 mg/kg PO q12h) and metronidazole (5–15 mg/kg PO q12h) for 6 weeks was associated with clinical remission in 85% of dogs but PCR was not performed to assess its effect on parasitemia.
• Metronidazole (25–50 mg/kg PO q24h for 7 days), clindamycin (12.5–25 mg/kg PO q12h for 7–10 days), or doxycycline (10 mg/kg PO q12h for 7–10 days) alone each have been reported to decrease clinical signs but not to clear infections.
• Primaquine phosphate (1 mg/kg IM, single injection) is the treatment of choice for B. felis.
• Since the anemia and thrombocytopenia are often immune mediated, immunosuppressive agents, such as prednisone (2.2 mg/kg/day PO), may be indicated in some cases that are not responding to anti-protozoal treatments alone. Prolonged immune suppressive therapy BEFORE specific antiprotozoal therapy is contraindicated.
• Antibabesial drugs (imidocarb and diminazene) can cause cholinergic signs that can be minimized by administering atropine (0.02 mg/kg SC, 30 minutes prior to imidocarb or diminazine administration).

Contraindications

High doses of antibabesial drugs (imidocarb and diminazene) have resulted in liver and kidney failure.

Prevention/Avoidance

Vaccines for B. canis canis and B. canis rossi are available in Europe, but these vaccines may not confer protection against other Babesia spp.

Tick control is important for disease prevention. Some recent studies suggest that using acaracides can prevent infection with Babesia spp. All attached ticks should be removed as soon as possible.

Zoonotic Potential

N/A

Pregnancy/Fertility/Breeding

Transplacental transmission

Abbreviations

• DIC = disseminated intravascular coagulation
• EDTA = ethylenediaminetetra-acetic acid
• FDA = US Food and Drug Administration
• IFA = indirect fluorescent antibody
• PCR = polymerase chain reaction
• PCV = packed cell volume
• RBC = red blood cell