Maged Muhammed

Isaac I. Bogoch

Eleftherios Mylonakis

DESCRIPTION

• Babesia is a protozoa with affinity for human red blood cells. It is a common cause of hemolytic disease in endemic areas.
• The main mechanism for transmission of Babesia microti is through deer tick bites (Ixodid species). Other less common routes of transmission include blood transfusions and maternally transmitted babesiosis.
• Northeastern and Midwestern US is where most B. microti is found. Other Babesia species exist in western US and Europe (1).

EPIDEMIOLOGY

• Babesia is considered an emerging infectious disease as there are an increasing number of reported cases in the last decade (2).
• Increases in deer populations, tick density, and greater human activity in endemic areas are thought to contribute to the rise in Babesia infections.
• Many cases of Babesia are subclinical in younger individuals so the prevalence of this infection is likely underestimated. Data from blood donors demonstrate that 0.5–15% of individuals have been exposed in highly endemic areas.

RISK FACTORS

• Living in/or traveling to endemic regions.
• Asplenic patients.
• Immunosuppression (e.g., HIV, chemotherapy).

GENERAL PREVENTION

• Endemic areas can be avoided in seasons of high transmission (May through October) especially by asplenic and immunocompromised persons who are at risk of severe illness (3).
• Insect repellant is helpful for the prevention of tick bite, specifically products with N-diethyl-meta-toluamide (DEET).
• Early removal of ticks is important; the tick must remain attached for at least 24 hours before the transmission occurs. Daily self-examination is recommended for persons who engage in outdoor activities in endemic areas.
• Examining pets for ticks is recommended in endemic areas.
• Clothes can be treated with permethrin to prevent infection.

PATHOPHYSIOLOGY

The life cycle involves transmission of Babesia between vertebrate hosts and Ixodes ticks. Humans are "dead end" and "accidental" hosts as the primary contact points for B. microti are between white-footed mice and ticks. Although humans may become ill when infected, humans do not play a role in the transmission of infection. Ixodes ticks transmit the sporozoite to host blood. The sporozoites invade the erythrocytes and become trophozoites. The trophozoites replicate asexually by budding, yielding 2–4 merozoites. The merozoites disrupt RBCs and invade other RBCs leading to hemolysis and anemia.

ETIOLOGY

• The most common cause of Babesia in the US is B. microti found in New England, coastal New York, and Midwest regions.
• Other common Babesia species that cause disease in humans include Babesia divergens in Europe and Babesia duncani in Western US.

COMMONLY ASSOCIATED CONDITIONS

• Co-infection with Lyme disease and human granulocytic anaplasmosis is common as both are transmitted by Ixodes ticks in endemic regions (4).
• In the endemic areas, up to 10% of patients with Lyme disease are co-infected with Babesia.

[Outline]

• Information
• Description
• Epidemiology
• Risk Factors
• General Prevention
• Pathophysiology
• Etiology
• Commonly Associated Conditions

HISTORY

Patients may be asymptomatic or report the following symptoms:

• Fever
• Chills
• Weakness
• Headache
• Nausea/vomiting
• Abdominal pain
• Diarrhea
• Joint pain
• Shortness of breath/chest pain
• Dark urine
• Also ask about recent Lyme infection, travel/living in endemic areas, outdoor exposures, pets, recent tick bites

PHYSICAL EXAM

• Fever
• Splenomegaly
• Hepatomegaly
• Pallor
• Jaundice
• Absence of lymphadenopathy
• Look for a rash consistent with erythema chronicum migrans in cases of Lyme co-infection

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

• Thin blood smears to assess for intra-erythrocytic parasites and evidence of hemolysis. Multiple blood smears may be necessary over several days in cases of low parasitemia and in early onset of infection.
• Complete blood count: Anemia and thrombocytopenia.
• Evidence of hemolysis: Elevated reticulocyte count, LDH, and indirect bilirubin. Also low haptoglobin.
• Liver function tests.

Follow Up & Special Considerations

• If the organism is not detected by blood smear, PCR amplification of 18 srRNA is recommended.
• In patients with a high probability of infection, indirect immunofluorescent antibody testing is recommended when both blood smear and PCR are negative.

Imaging

Usually imaging is not necessary in mild cases. Abdominal ultrasonography will confirm hepatomegaly or splenomegaly.

Pathological Findings

Like malaria, Babesia appears as an intra-erythrocytic parasite. Babesia parasites can be visualized outside of red blood cells in heavy infection – this is not seen in malarial infections. Occasionally, Babesia parasites (in the intracellular merozoite phase) appear in tetrads, known as the "Maltese cross."

DIFFERENTIAL DIAGNOSIS

• Sepsis
• Lyme
• Human granulocytic anaplasmosis
• Hepatitis
• Malaria
• Lymphoma

[Outline]

• History
• Physical Exam
• Diagnostic Tests & Interpretation
  • Lab
    • Initial Lab Tests
    • Follow Up & Special Considerations
  • Imaging
  • Pathological Findings
• Differential Diagnosis

MEDICATION

First Line

For B. microti infection: 7–10 days of oral atovaquone 750 mg 2 times per day plus oral azithromycin 500–1,000 mg/day on day 1, followed by 250 mg/day afterwards.

Second Line

For B. microti infection: Oral quinine 650 mg, 3 or 4 times a day plus oral clindamycin 600 mg 3 times a day for 7–10 days. Intravenous formulations can be used. Quinine and clindamycin are used in severe cases.

ADDITIONAL TREATMENT

General Measures

• Asymptomatic individuals who are immunocompetent and have detectable parasites on blood smear for less than 3 months do not require treatment (5).
• Longer treatment courses may be necessary in immunocompromised hosts or in cases of high parasite burden. Treatment should continue for at least 6 weeks, including 2 weeks of therapy after parasites are no longer detectable in blood smears.

Issues for Referral

An infectious disease specialist should be involved if there are signs or symptoms of severe infection or infection in an immunocompromised host.

Additional Therapies

Red blood cell exchange transfusions may be necessary in severe cases where parasitemia is high (>10%) or there are symptoms of shock/ARDS.

[Outline]

• Medication
  • First Line
  • Second Line
• Additional Treatment
  • General Measures
  • Issues for Referral
  • Additional Therapies

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Hospitalized patients should have a CBC and blood smear checked daily to monitor hemolysis, anemia, and parasite burden.

PATIENT EDUCATION

Inform patients about risk factors for acquiring Babesia and take precautions to avoid re-infection.

COMPLICATIONS

• DIC
• Anemia
• CHF
• ARDS
• Renal dysfunction
• Hypotension

[Outline]

• Follow Up Recommendations
  • Patient Monitoring
• Patient Education
• Complications

ICD9

088.82 Babesiosis

• Red blood cell exchange transfusion is recommended in case of severe disease with end organ failure.
• Unless the parasitemia has persisted for more than 3 months, there is no need to treat asymptomatic cases of babesiosis in immunocompetent hosts.

1. Vannier E, Gewurz BE, Krause PJ. Human babesiosis. Infect Dis Clin North Am 2008;22:469–488.
2. Krause PJ, McKay K, Gadbaw J, et al. Increasing health burden of human babesiosis in endemic sites. Am J Trop Med Hyg 2003;68:431–436.
3. Mylonakis E. When to suspect and how to monitor babesiosis. Am Fam Physician 2001;63:1969–1974.
4. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43(9):1089–1134.
5. Krause PJ, Gewurz BE, Hill D, et al. Persistent and relapsing babesiosis in immunocompromised patients. Clin Infect Dis 2008;46(3):370–376.