B: Babesiosis

Babesiosis

BASICS

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.

DIAGNOSIS

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—mild 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.
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.
Renal failure and metabolic acidosis 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 biological sample (usually EDTA anticoagulated whole blood); can differentiate subspecies and species; more sensitive than microscopy.

TREATMENT

May require inpatient or outpatient care, depending on the severity of disease.
Hypovolemic animals should receive aggressive fluid therapy.
Severely anemic animals may require blood transfusion.

MEDICATIONS

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.
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. Prolonged immune suppressive therapy BEFORE specific antiprotozoal therapy is contraindicated.
The use of a polymerized bovine hemoglobin solution may improve oxygen-carrying capacity in severely anemic animals but does not appear to be superior to packed red blood cells.
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.

FOLLOW-UP

Recheck the CBC and biochemistry as needed to monitor for resolution of anemia, thrombocytopenia, icterus, and other signs.
Most patients have a clinical response within 1–2 weeks of treatment.
2–3 consecutive negative PCR tests beginning 2 months post-treatment should be performed to rule out treatment failure and persistent parasitemia. IFA titers are not recommended for follow-up because may persist for years.
Long-term follow-up of B. conradae, B. annae, or B. felis after treatment has not been reported.
When a dog housed in a multi-dog kennel is diagnosed with babesiosis, all dogs in that kennel should be screened since there is a high percentage of carrier animals in kennel situations.
Co-infection with other vector-transmitted pathogens (e.g., Erhlichia, hemotropic Mycoplasma, Leishmania) should be considered, especially in animals that fail to respond to treatment.

PREVENTION/AVOIDANCE

Vaccines for B. canis canis and B. canis rossi are available in Europe, but these vaccines do 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 within 24 hours of attachment.

MISCELLANEOUS

All potential blood donors should test negative for the disease (preferably by 2–3 consecutive PCR tests) prior to use as a donor animal.

ZOONOTIC POTENTIAL

N/A

PREGNANCY/FERTILITY/BREEDING

Transplacental transmission

ABBREVIATIONS

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