II. Epidemiology

  1. Region affected
    1. Sporadic cases worldwide
    2. Endemic areas predominately in United States (Northeastern and Midwest U.S.)
      1. Massachusetts Islands: Nantucket, Martha's Vineyard
      2. New York Islands (Long Island, Shelter Island)
      3. Connecticut
      4. Cases also noted in California and southern states
  2. Peak transmission: May to September
  3. Incidence: 1000 to 2000 cases per year in U.S.
  4. Transmission
    1. Reservoir
      1. Multiple hosts including the white-footed mouse
    2. Tick-borne infection (Ixodid ticks)
      1. Ixodes dammini or Ixodes Scapularis
      2. Ixodes ricinus
      3. Tick must attach for 24 hours before transmission
    3. Less common transmission
      1. Red Blood Cell Transfusion
        1. Risk 0.17% in endemic regions
      2. Transplacental and perinatal transmission
  5. Incubation
    1. After Tick Bite: 5 to 33 days (may be as long as 9 weeks in some cases)
    2. After Blood Transfusion: over 60 days
  6. Ages affected: 40 to 50 years old

III. Pathophysiology

  1. Protozoans
    1. United States (mostly in Northeastern U.S.)
      1. Babesia Microti (small mammal and primate hosts)
    2. Europe
      1. Babesia divergens (rat, gerbil, cow hosts)
      2. Babesia bovis
  2. Infection
    1. Invades and replicates within Red Blood Cells
    2. Similar to Malaria

IV. Risk factors: Severe infection

  1. Older age (>60 years old)
  2. Asplenic patient
  3. Immunodeficiency (e.g. AIDS)
  4. Rituximab

VI. Symptoms

  1. Onset 1-9 weeks after exposure (Tick Bite)
  2. Similar to Malaria symptoms
  3. Generalized symptoms (Influenza-like symptoms)
    1. Fever, chills and diaphoresis (drenching sweats)
    2. Weakness
    3. Weight loss
    4. Arthralgia
    5. Myalgia
    6. Fatigue
    7. Diaphoresis
  4. Gastrointestinal symptoms
    1. Anorexia
    2. Nausea
    3. Abdominal Pain
    4. Vomiting
    5. Diarrhea
  5. Respiratory symptoms
    1. Cough
    2. Shortness of Breath
  6. Genitourinary symptoms
    1. Dark Urine
  7. Neurologic symptoms
    1. Headache
    2. Photophobia
    3. Neck and back stiffness
    4. Altered Level of Consciousness

VII. Signs

VIII. Differential Diagnosis

  1. Falciparum Malaria
    1. Both cause Hemolytic Anemia and Renal Failure
    2. Both cause high fever, Jaundice and Hemoglobinuria
  2. Other tick-borne illness
    1. Deer Tick (Ixodes tick) is also the vector for Lyme Disease and Anaplasmosis

IX. Labs

  1. Complete Blood Count
    1. Hemolytic Anemia (unique to Babesia compared with Lymes and Anaplasmosis)
    2. Decreased Leukocyte count
    3. Thrombocytopenia may be present
  2. Renal Function
    1. Increased Serum Creatinine and Blood Urea Nitrogen
  3. Liver Function Tests
    1. Increased transaminases (AST, ALT)
    2. Increased Lactate Dehydrogenase (LDH)
    3. Increased Serum Bilirubin
  4. Urinalysis
    1. Proteinuria

X. Diagnosis

  1. Peripheral Smear (Wright stain or Giemsa stain)
    1. Intraerythrocytic Parasites
    2. Similar to plasmodium (Malaria) except
      1. Babesia form tetrads (Maltese cross) within the RBCs
      2. No hemozoin pigments in RBCs
      3. Extracellular merozoites
    3. Contrast with intracellular Monocyte inclusions in Ehrlichiosis (morulae)
    4. Low Test Sensitivity (repeat samples may be needed)
  2. Serologic Detection
    1. Immunofluorescent Antibody titer >1:64
    2. Polymerase chain reaction
  3. Babesia PCR
  4. Consider co-transmission of other tick-borne infection
    1. Borrelia Burgdorferi (Lyme Disease)
    2. Anaplasmosis

XI. Management: Antibiotics

  1. Babesia is among a couple of Tick Borne Illnesses that do not respond to Doxycycline (Tularemia is the other)
  2. Mild to Moderate Disease: Combination Atovaquone and Azithromycin (preferred regimen)
    1. Antibiotic Course: 7 to 10 days (extend to 6 weeks for relapsing or persistent infection)
    2. Atovaquone (Mepron) 750 mg orally twice daily AND
    3. Azithromycin (Zithromax)
      1. First day: 500 mg orally
      2. Subsequent days: 250 mg orally daily
  3. Severe Disease: Combination Quinine and Clindamycin
    1. Antibiotic Course: 10 days
    2. Quinine (dosing is for salt component)
      1. Adult: 650 mg orally three times daily
      2. Child: 8 mg/kg (up to 650 mg) orally every 8 hours
    3. Clindamycin
      1. Adult: 300-600 mg IV q6 hours or 600 mg orally tid daily (or 1.2 g orally twice daily)
      2. Child: 7-10 mg/kg (up to 600 mg) IV or oral every 6-8 hours
  4. Exchange Transfusion
    1. Indicated in Critical Illness
    2. Blood Parasitemia exceeding 10%
    3. Massive Hemolysis
    4. Asplenic patient

XII. Course

  1. Variable
  2. Carried asymptomatically for years in some patients
  3. Mortality: 6-10% in severe cases (esp. Immunocompromised, Asplenia)

XIV. References

  1. Della-Giustina, Fox and Siegel (2021) Crit Dec Emerg Med 35(4): 17-23
  2. (2016) Sanford Guide to Antibiotics App, accessed 4/12/2016
  3. Green and Millsap (2016) Crit Dec Emerg Med 30(1): 4
  4. Boustani (1996) Clin Infect Dis 22:611-5 [PubMed]
  5. Krause (2000) N Engl J Med 343:1454-8 [PubMed]
  6. Mylonakis (2001) Am Fam Physician 63(10):1969-74 [PubMed]
  7. Pace (2020) Am Fam Physician 101(9): 530-40 [PubMed]
  8. Pruthi (1995) Mayo Clin Proc 70:853-62 [PubMed]

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