Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body’s immune response result in clinical symptoms. Patients usually present with a flu-like illness and jaundice. In severe cases, organ damage may occur. The diagnosis is confirmed by the visual presence of parasites within RBCs, which are often noted to be in a “Maltese Cross” configuration. Serological testing and PCR are also used in the diagnosis. Azithromycin and atovaquone are often used in management. Coinfection with Borrelia and Anaplasma is common.

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General Characteristics of Babesia

Basic features of Babesia

  • Protozoan parasite
  • Intraerythrocytic
  • Oval or pear-shaped morphology (often called piroplasms)
  • Identified on Giemsa stain
  • > 100 species identified

Clinically relevant species

  • B. microti (most common species in North America)
  • B. duncani (North America)
  • B. divergens (Europe)

Epidemiology and Risk Factors


  • 94% of babesiosis cases in the United States occur in the following regions:
    • Northeast
    • Upper Midwest
  • Increasing incidence due to:
    • Rising deer population 
    • Deforestation
    • More humans living in wooded areas
  • 75% of cases are diagnosed between June and August.

Risk factors

For babesiosis:

  • Travel to an endemic area (within the previous 6 months)
  • Blood transfusion

For severe disease:

  • Age: 
    • Neonates 
    • > 50 years of age
  • Asplenia
  • Immunosuppression:
    • HIV/AIDS
    • Malignancy
    • Patients on immunosuppressive therapy



  • White-footed mouse (B. microti)
  • Cattle (B. divergens)


  • The primary vector for transmission to humans is the Ixodes tick.
  • Human-to-human transmission can rarely occur through:
    • Blood transfusion
    • Solid-organ transplantation
    • Transplacentally

Life cycle and pathophysiology

Outside a human host:

  • Tick carrying sporozoites → attaches to a mouse → transfers sporozoites
  • Sporozoites enter RBCs.
  • Once inside the RBC, sporozoites differentiate into trophozoites.
  • Trophozoites undergo asexual replication (binary fission) → merozoites
  • Merozoites produce gametocytes.
  • Tick takes a blood meal → gametes are transferred to the tick
  • Gametes are fertilized in the tick’s gut → sexual replication 
  • Invasion into the salivary gland of the tick → development into sporozoites

Inside a human host:

  • Tick carrying sporozoites → attaches to a host → transfer sporozoites into the dermis (typically the 2nd or 3rd day of attachment)
  • Sporozoites enter RBCs → differentiate into trophozoites (appear as multiple delicate rings)
  • Trophozoites undergo binary fission → merozoites (appear as tetrad structures or “Maltese Cross”)
  • Merozoites escape → rupture the RBCs (hemolysis) → invasion of other nearby RBCs → cycle repeats
  • Infected RBCs are recognized as abnormal in the spleen → targeted for destruction by macrophages
  • Hemolysis and host immune response → clinical manifestations
The life cycle and transmission of Babesia

Life cycle and transmission of Babesia

Image by Lecturio.

Clinical Presentation


The incubation period for babesiosis is 1–4 weeks.

Mild-to-moderate disease:

  • Flu-like symptoms:
    • Fatigue
    • Fever 
    • Chills
    • Diaphoresis
    • Malaise
    • Myalgia
    • Arthralgia
    • Headache
  • Evidence of hemolysis:
    • Yellow skin
    • Dark urine
  • Less common symptoms:
    • Anorexia
    • Nausea
    • Sore throat
    • Dry cough
    • Conjunctival infection

Severe disease:

  • Patients tend to have more intense symptoms.
  • In addition, patients may experience:
    • Altered mental status
    • Abdominal pain
    • Vomiting
    • Diarrhea
    • Shortness of breath
    • Neck stiffness
    • Photophobia
    • Hyperesthesia
  • Complications:
    • ARDS
    • Severe anemia
    • Congestive heart failure
    • Splenic rupture
    • Hepatitis
    • Renal failure
    • Disseminated intravascular coagulation
    • Coma
    • Shock
    • Death

Physical exam

  • General appearance:
    • Fever
    • Jaundice
  • ENT:
    • Scleral icterus
    • Pharyngeal erythema
    • Retinopathy with splinter hemorrhages
  • Abdominal exam:
    • Splenomegaly 
    • Hepatomegaly
  • Skin:
    • Petechiae may be present.
    • A rash may represent a concurrent Lyme disease infection.

Diagnosis and Management


  • Diagnostic testing:
    • Blood smear
      • “Maltese Cross” within RBCs
      • Ring forms within RBCs may also be present.
    • Indirect fluorescent antibody (IFA) testing for Babesia antibodies
    • PCR for Babesia DNA
  • Supporting evaluation:
    • CBC:
      • Hemolytic anemia (↓ hemoglobin, ↑ LDH, ↓ haptoglobin)
      • Neutropenia
      • Thrombocytopenia
    • Liver function tests:
      • ↑ ALT and AST
      • ↑ Total and indirect bilirubin
    • Basic metabolic panel:
      • ↑ BUN
      • ↑ Creatinine
  • Consider evaluating for coinfections:
    • Borrelia burgdorferi (Lyme disease)
    • Anaplasma phagocytophilum (anaplasmosis)


The mainstay of treatment is antibiotics and educating patients on preventive methods to avoid tick bites.

  • Antimicrobial therapy:
    • 1st-line treatment: azithromycin and atovaquone 
    • Alternative: quinine and clindamycin
  • Exchange transfusion is indicated if:
    • Severe hemolysis (hemoglobin < 10 g/dL)
    • End-organ damage is present
    • High-grade parasitemia (> 10%)


Precautions should be taken in endemic areas, particularly in individuals at risk for severe disease and complications.

  • Tick prevention:
    • Protective clothing 
    • Use of tick repellents
    • Check for and remove ticks.
  • Screening of donated blood and organs
  • There is no prophylactic therapy or vaccination.

Comparison of Intraerythrocytic Parasites

The table below summarizes the characteristics of parasites that infect RBCs.

Table: Comparison of intraerythrocytic parasites
Microscopic appearance
  • Sporozoa
  • Pear shaped
  • Sporozoa
  • Thin, elongated
ReservoirWhite-footed mouse
  • Monkeys
  • Humans
TransmissionIxodes tickAnopheles mosquito
Common regions
  • North America
  • Europe
  • Africa
  • Asia
  • Central and South America
  • Flu-like symptoms
  • Abdominal symptoms
  • Hepatosplenomegaly
  • Hemolytic anemia
  • Renal failure
  • ARDS
  • CHF
  • DIC
  • Flu-like symptoms
  • Abdominal symptoms
  • Hepatosplenomegaly
  • Hemolytic anemia (more severe)
  • Renal failure
  • ARDS
  • DIC
  • Hypoglycemia
  • Blood smear
  • IFA
  • PCR
  • Blood smear
  • Antigen testing
  • PCR (not widely available)
  • Azithromycin and atovaquone
  • Clindamycin and quinine
Depends on species, severity, and resistance patterns, but may include a combination of:
  • Atovaquone
  • Proguanil
  • Quinine
  • Tetracyclines
  • Mefloquine
  • Chloroquine
CHF: congestive heart failure
DIC: disseminated intravascular coagulation
IFA: indirect fluorescent antibody

Differential Diagnosis

  • Malaria: a mosquito-borne infectious disease caused by Plasmodium species. Malaria often presents with fever, rigors, diaphoresis, jaundice, abdominal pain, hemolytic anemia, hepatosplenomegaly, and renal impairment. A blood smear in malaria shows a single pleomorphic ring. The “Maltese Cross” finding is not seen. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs.
  • Lyme disease: a tick-borne infection caused by the gram-negative spirochete, Borrelia burgdorferi. Lyme disease is also transmitted by the Ixodes tick. The presentation of Lyme disease can vary depending on the stage of the disease and may include the characteristic rash known as erythema migrans (not present in babesiosis). Neurological, cardiac, ocular, and joint manifestations are also common in later stages. Diagnosis of Lyme disease relies on clinical findings and tick exposure, and is supported by serological testing. Antibiotics are used for treatment. 
  • Viral hepatitis: liver inflammation due to infection with the hepatitis virus. Patients present with a prodromal flu-like illness, followed by jaundice, hepatosplenomegaly, and elevated transaminases. Hepatitis serologies are used in the diagnosis and help differentiate hepatitis from babesiosis. Management of acute hepatitis is supportive. 
  • Rocky Mountain spotted fever: a disease caused by Rickettsia rickettsii that presents with fever, fatigue, headache, and a rash following a tick bite. However, Rocky Mountain spotted fever is associated with the Dermacentor tick. Diagnosis is made based on the clinical features, biopsy of the rash, and serological testing. Treatment is with antibiotics including doxycycline.
  • Ehrlichiosis and anaplasmosis: tick-borne infections caused by Ehrlichia chaffeensis and Anaplasmosis phagocytophilum, respectively. Symptoms of ehrlichiosis and anaplasmosis include fever, headache, and malaise. Disseminated intravascular coagulation, multiorgan failure, and coma can also occur with severe disease. The diagnosis is made using PCR. Treatment of both diseases is with doxycycline.


  1. Krause, P., Vannier, E. (2019). Babesiosis: Microbiology, epidemiology, and pathogenesis. Retrieved on March 09, 2021, from
  2. Krause, P., Vannier, E. (2019). Babesiosis: Clinical manifestations and diagnosis. Retrieved on March 09, 2021, from
  3. Krause, P., Vannier, E. (2021). Babesiosis: Treatment and prevention. Retrieved on March 09, 2021, from

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