Babesiosis: what is it?

BABESIOSIS:

Basics

Description

• Tick-borne, malarialike disease caused by an intracellular parasite that invades the red blood cells.
• Protozoa pass from tick salivary glands to mammalian bloodstream.
• Erythrocytes are penetrated and infected by parasites that mature and divide.
• RBC membrane damage and lysis leads to hemolytic anemia and hemoglobinuria.
• Damaged RBCs become less deformable, enhancing removal by spleen.
• Asplenic patients are less able to clear infected RBCs, leading to more severe disease.
• Damaged RBCs may result in microvascular stasis with secondary ischemic organ injury.
• Subsequent complications can include renal failure secondary to acute tubular necrosis, shock, cardiac failure, hypotension, acute respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC)
• Babesiosis in Europe:
  • Often a fulminate disease in immunocompromised patients
  • 40% mortality in asplenic patients
  • Bovine strain (Babesia divergens)
• North America:
  • Usually presents as mild or subclinical disease in immunocompetent patients (5% mortality)
  • Rodent strain (Babesia microti) in the Northeastern United States
  • Canine strain (Babesia gibsoni) in the Northwestern United States
• Incubation period:
  • 1-4 weeks after tick bite
  • 6-9 weeks after transfusion
• Geographic distribution in the United States:
  • Coastal areas of Northeastern United States
  • Emerging clusters:
    • Midwest (Minnesota, Wisconsin, Missouri)
    • West coast (California, Washington)
    • Seasonal distribution: 80% of human cases occur between May and August when tick nymph populations and human outdoor activity are highest.
• Risk factors for severe disease:
  • Age >40 years
  • Splenectomy
  • Depressed cellular immunity (HIV, corticosteroid use, other immunosuppressive drugs)
  • Co-infection with Lyme disease
  • In immunosuppressed patients, up to 85% of RBCs may be infected.

Etiology

• Intraerythrocytic protozoa of the genus Babesia
• Transmitted to humans by the Ixodes tick:
  • Ixodes ricinus in Europe
  • Ixodes scapularis in the United States
  • Animal reservoirs:
    • Cattle in Europe
    • White-footed mouse in the United States
• I. scapularis:
  • Requires a blood meal to develop through each of it's three developmental stages.
  • Larvae:
    • Feed on white-footed mice
  • Nymphs:
    • Feed on humans
    • Nymph form is 1-2 mm in length
    • Tan color
    • Patients may not recall being bitten
  • Adult ticks:
    • Generally feed on white-tailed deer
  • Also the vector for Lyme disease and ehrlichiosis
• Transfusion-associated infections are possible:
  • Parasitemia not always visible on donor blood smear.
  • Risk of transmission in endemic areas reported to be 0.17%.

Pregnancy Considerations

Transmission can occur in utero and during delivery; youngest reported case was a 4-week old infant.

Diagnosis

Signs and Symptoms

Clinical spectrum ranges from mild to fulminate with symptoms lasting from weeks to months.

History

• Mild flulike illness
• Fatigue
• Anorexia
• Myalgias
• Arthralgias
• Cough
• Nausea
• Vomiting
• Headache
• Emotional lability

Physical Exam

• Conjunctival injection
• High-spiking fevers
• Shaking chills
• Drenching sweats
• Rash:
  • Uncommon
  • Petechial or purpuric rash caused by associated thrombocytopenia
  • Erythema migrans if concurrent Lyme disease
• Respiratory distress
• Dark urine
• Jaundice
• Hepatosplenomegaly
• Meningismus
• Altered sensorium
• Hypotension
• ARDS
• DIC

Essential Workup

• History of nonspecific febrile illness in any patient with recent outdoor activities or transfusion in an endemic area during warm weather should prompt consideration of diagnostic workup for babesiosis, especially if associated with hematuria, jaundice, anemia, splenomegaly, and lymphocytosis.
• Septic presentation in patients with above history and risk factors (asplenia, immunocompromised, age >40 years) should prompt consideration of diagnostic workup and empiric treatment for babesiosis

Tests

Lab

• Nonspecific studies:
  • CBC (anemia, thrombocytopenia, mild leukopenia, atypical lymphocytosis)
  • Liver function studies (elevated alkaline phosphatase, transaminases, lactate dehydrogenase, bilirubin)
  • Urinalysis (hemoglobinuria, proteinuria)
  • Hemolysis profile (elevated reticulocyte count, decreased serum haptoglobin, hyperbilirubinemia, elevated lactate dehydrogenase, hemoglobinuria)
  • Elevated blood urea nitrogen, creatinine suggests renal insufficiency
  • Elevated serum potassium may result from massive hemolysis
• Specific diagnostic studies:
  • Peripheral blood smear:
    • Microscopy of Giemsa- or Wright-stained thin smears
    • Parasites within RBCs can be round, oval, or pear shaped
    • Most common appearance is round (ring forms) to oval (pyriform) rings with pale blue cytoplasm and red-staining nucleus; extracellular parasites may also be seen
    • Parasites in budding tetrad formation (Maltese cross) are a rare, but highly suggestive finding of babesiosis.
    • Level of parasitemia can range from <1->85%; higher levels more common in splenectomized patients
  • Polymerase chain reaction:
    • Available for both Babesia microti and B. divergens
    • Higher sensitivity, equal specificity to blood smear
    • Useful in cases with very low levels of parasitemia
    P.125
    
    
  • Serology:
    • Indirect immunofluorescent antibody assay
    • Serum antibody titer usually rises within a few weeks of infection; falls off slowly over months
    • Titers of 1:64 or higher considered positive (acute or prior infection); serology may remain positive for years
    • Titers of 1:256 or more are indicative of acute infections
• Blood and urine cultures if presentation consistent with sepsis
• Cerebrospinal fluid analysis if presentation suggestive of CNS infection

Imaging

• Chest radiograph indicated for respiratory complaints or evidence of hypoxia
• Head CT may be indicated in setting of altered mental status.
• Abdominal CT may be indicated in setting of splenomegaly and hypotension.
• ECG indicated for ischemic symptoms

Differential Diagnosis

• Malaria
• Other tickborne diseases:
  • Lyme disease
  • Ehrlichiosis
  • Rocky Mountain spotted fever
  • Colorado tick fever
  • Q fever
  • Tularemia
  • Relapsing fever
• Typhoid fever

Treatment

Alert

Acute respiratory failure, shock, and myocardial infarction have been reported as complications of babesiosis.

Pre Hospital

• Ensure a patent airway
• Provide supplemental oxygen and ventilatory assistance as needed
• If patient appears to be in shock, establish IV access and administer a fluid bolus of 0.9% normal saline 500 mL (peds: 20 mL/kg) IV

Initial Stabilization

• Airway management, ventilatory support for patients with acute respiratory failure
• Pulse oximetry: hypoxia may be present in patients with severe disease.
• IV access should be established in patients with evidence or risk factors for severe disease.
• IV fluids
• Pressor support for patients in shock

ED Treatment

• Start empiric antibiotic therapy with two drug regimen in patients at risk with significant symptoms and/or shock
• Clindamycin plus quinine:
  • Adverse effects (tinnitus, abdominal complaints) or treatment failure may limit use.
• Atovaquone plus
  • Comparable efficacy to clindamycin-quinine (65% versus 73%) with fewer adverse effects (12% versus 67%) and may be used as an alternative
• Exchange transfusion as adjunctive therapy in patients with severe symptoms or risk factors for severe disease:
  • Immunodeficiency
  • splenia
  • Severe hemolysis
  • B. divergens infection
  • High-level parasitemia (>10%)
• Antibiotic therapy in known mild or asymptomatic cases due to risk of transmission via blood transfusion or recrudescence, especially if risk factors for severe disease are present
• Hemodialysis may be indicated for patients with acute renal failure
• Treat fever with antipyretics

Medication (Drugs)

• Acetaminophen: 325-1,000 mg (peds: 40-60 mg/kg/24h) PO/PR q4h-q6h PRN
• Atovaquone: 750 mg (peds: 40 mg/kg/24h) PO b.i.d. × 7 days
• Azithromycin: 500 mg (peds: 10 mg/kg up to max. 500 mg) PO on day 1, followed by 250 mg (peds: 5 mg/kg up to max. 250 mg) PO per day: 6 days
• Clindamycin: 300-600 mg (peds: 20 mg/kg/24h in 3 div. doses) PO q8h 7-10 days
• Ibuprofen: 200-400 mg (peds: 20-40 mg/kg/24h) PO q6h-q8h PRN
• Quinine: 650 mg (peds: 25 mg/kg/24h) PO q8h × 7-10 days
  • Quinine is contraindicated in pregnancy

Follow-Up

Disposition

Admission Criteria

• Patients with severe disease:
  • Severe, symptomatic anemia
  • Jaundice
  • Renal insufficiency
  • Respiratory distress
  • DIC
  • Shock
• Patients at risk of developing severe disease:
  • Immunodeficiency, asplenia
  • Severe hemolysis
  • B. divergens infection
  • High-level parasitemia (>10%)
• Patients requiring exchange transfusion

Discharge Criteria

• Patients with asymptomatic or mild disease
• Intact spleen
• Able to tolerate oral medications