Babesiosis – MD Nexus

Epidemiology

Geography

Geographic Regions with High Endemicity

United States-New England
- Nantucket Island
- Southeastern Massachusetts/Cape Cod/Western Boston Suburbs
- Northeastern Massachusetts
- Southwest Rhode Island
- Eastern Connecticut
- Counties East of the Hudson River/Lower Hudson River Valley
- Southern/Central New Jersey Counties
- Southern New York
United States-Upper Midwest
- Minnesota
- Wisconsin

Geographic Regions with Low Endemicity

United States-New England
- Southern Coastal Maine/New Hampshire Counties
- Northern/Central Connecticut Counties
- Western Long Island
- Northern/Southern New Jersey Counties
- Delaware and Maryland Counties

Other Geographic Regions

Indiana: few reported cases

Risk Factors

Asplenia (see Asplenia, [[Asplenia]])
- Babesia is an Encapsulated Organism
Blood Transfusion (see Packed Red Blood Cells, [[Packed Red Blood Cells]])
Rituximab (see Rituximab, [[Rituximab]]): possible risk factor

Etiology/Microbiology

Routes of Transmission

Tick Bite (see Tick-Borne Illnesses, [[Tick-Borne Illnesses]]): main route of transmission
Transmission Via Blood Transfusion (see Packed Red Blood Cells, [[Packed Red Blood Cells]]): less common
- Platelet Transfusion (see Platelet Transfusion, [[Platelet Transfusion]]): few cases have been reported (platelets were contaminated with red blood cells)
Transplacental Transmission: case reports

Babesia Species

Babesia Microti

Geography
- Northeast US
- Upper Midwest US
Tick Vector: Ixodes Scapularis (see Ixodes Ticks, [[Ixodes Ticks]])
- Reservoir: white-tailed deer and mice
- Incubation Period: 5-33 days

Babesia Divergens

Geography
- Europe
Tick Vector: Ixodes Ricinus (this is also the presumed tick vector responsible for European cases of Human Granulocytic Anaplasmosis, HGA) (see Anaplasmosis)
- Reservoir: cattle

Other Babesia Species

Babesia Duncani
- Sporadic Outbreaks Along the Pacific Coast of the US (from California to Washington)
Babesia Divergens-Like Organisms: Midwestern US
- Midwest US (Kentucky, Missouri) and Northwest US (Washington)
Babesia Divergens-Like Organisms: Canary Islands
Babesia Venatorum: Europe
Babesia Venatorum: Northeastern China
Babesia Microti-Like Organisms: Japan
Babesia KO1: South Korea

Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

Mild-Moderate Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]]): may be seen
Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]]): may be seen

Blood Culture (see Blood Culture, [[Blood Culture]])

Useful

Peripheral (Thin) Blood Smear (see Peripheral Blood Smear, [[Peripheral Blood Smear]])

Thin Blood Smear is the Preferred Diagnostic Test
Technique
- Giemsa or Wright Stain
- Thick Blood Smears are Not Recommended, as Babesia are Small (<3 μm) and May Be Missed
Findings
- Trophozoites within Red Blood Cells
  - Rings with 1 Chromatin Dot: classic ring form
  - Maltese Cross (4 Merozoites Arranged in a Tetrad): seen with Babesia Microti, Babesia Duncani, and *Babesia Divergens

PCR for Babesia Microti DNA

Alternative Test
- More Sensitive Than Thin Blood Smear: may be useul early in the course of disease (when the organism burden is low)
- Do Not Amplify DNA from Plasmodium Species (Which Cause Malaria)
- Do Not Cross-React with Babesia Duncani
- Less Useful to Follow the Course of Disease, Since DNA May Be Detected for Weeks After Parasites are No Longer Visualized on the Thin Blood Smear

Serology

Indirect Immunofluorescence Assay (IFA)
- Serologic Testing for IgM/IgG Antibodies by IFA Can Be Performed, But Seropositivity Per Se Does Not Indicate Active Infection
- Antibodies May Be Absent Early in the Course of Disease

Clinical Manifestations

General Comments

Variable Severity of Disease: ranges from asymptomatic disease to rapidly fatal disease
- Most Immunocompetent Patients Have Mild-Subclinical Disease
Risk Factors for Severe Babesiosis
- Age >50 y/o
- Anti-CD20 Therapy (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]])
  - Rituximab (Rituxan) (see Rituximab, [[Rituximab]])
- Anti-Tumor Necrosis Factor-α (TNFα) Therapy (see Anti-Tumor Necrosis Factor-α Therapy, [[Anti-Tumor Necrosis Factor-α Therapy]])
  - Etanercept (Enbrel) (see Etanercept, [[Etanercept]])
  - Infliximab (Remicade) (see Infliximab, [[Infliximab]])
- Asplenia/Splenectomy (see Asplenia, [[Asplenia]])
- Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
- Immunosuppression
- Male Gender
- Malignancy
Coinfection: may occur in some cases
- Lyme Disease and Babesiosis (see Lyme Disease, [[Lyme Disease]])
- Lyme Disease and Anaplasmosis (see Lyme Disease, [[Lyme Disease]] and Anaplasmosis, [[Anaplasmosis]])

Constitutional Manifestations

Chills/Sweats (see Chills, [[Chills]])
High Fever (see Fever, [[Fever]])
Malaise

Gastrointestinal Manifestations

Anorexia (see Anorexia, [[Anorexia]])
Elevated Liver Function Tests (LFT’s) (see Elevated Liver Function Tests, [[Elevated Liver Function Tests]])

Hematologic Manifestations

Mild-Moderate Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]])
Splenic Infarction (see Splenic Infarction, [[Splenic Infarction]])
Splenic Rupture (see Splenic Rupture, [[Splenic Rupture]])
Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

Neurologic Manifestations

Headache (see Headache, [[Headache]])

Rheumatologic Manifestations

Arthralgias (see Arthralgias, [[Arthralgias]])
Myalgias (see Myalgias, [[Myalgias]])

Treatment

General Comments

Therapy is Recommended for Symptomatic Infection Only

Clindamycin + Quinine (see Clindamycin, [[Clindamycin]] and Quinine, [[Quinine]])

Clindamycin (IV) + Quinine (PO) is the Classical Regimen for Babesiosis: recommended by the Infectious Diseases Society of America (IDSA) for severe disease
Administration
- Usual Course: 7-10 days
- Course for Highly Immunocompromised Patients: at least 6 wks (with negative thin blood smears for at least 2 wks prior to discontinuation of therapy)
Clindamycin + Quinine Regimen Has a High Incidence of Adverse Effects: adverse effects occur in 72% of cases
- Hearing Loss (see Hearing Loss, [[Hearing Loss]])
- Diarrhea (see Diarrhea, [[Diarrhea]])
- Tinnitus (see Tinnitus, [[Tinnitus]])
- Vertigo (see Vertigo, [[Vertigo]])

Atovaquone + Azithromycin (see Atovaquone, [[Atovaquone]] and Azithromycin, [[Azithromycin]])

Indications
- Mild-Moderate Disease
Administration: oral atovaquone + oral azithromycin
- Usual Course: 7-10 days
- Course for Highly Immunocompromised Patients: at least 6 wks (with negative thin blood smears for at least 2 wks prior to discontinuation of therapy)
Adverse Effects: lower incidence of adverse effects (only 15% of cases) than with the classical clindamycin + quinine regimen
Clinical Efficacy
- Atovaquone + Azithromycin is as Effective Clindamycin + Quinine Regimen in Mild-Moderate Babesiosis (N Engl J Med, 2000) [MEDLINE]
- Resistance: has been reported in immunocompromised hosts (Clin Infect Dis, 2010) [MEDLINE]

Exchange Transfusion (see Exchange Transfusion, [[Exchange Transfusion]])

Indications
- High-Grade Parasitemia (≥10%)
- Severe Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]]): most common indication for exchange transfusion
- Pulmonary/Renal/Hepatic Compromise
Technique
- Unclear Superiority of Red Blood Cell vs Whole Blood vs Plasma Exchange

Prognosis

Risk Factors for Persistent/Relapsing Babesiosis
- B-Cell Lymphoma Treated with Rituximab (Rituxan) Therapy (see Rituximab, [[Rituximab]])
- HIV with Low CD4 Count (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
- Immunosuppression for Solid Organ/Hematopoietic Stem Cell Transplant

References

Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000 Nov 16;343(20):1454-8 [MEDLINE]
Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection. Clin Infect Dis. 2010 Feb 1;50(3):381-6. doi: 10.1086/649859 [MEDLINE]
Human babesiosis. N Engl J Med. 2012;366:2397–2407 [MEDLINE]
Diagnosis, treatment and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis. JAMA. 2016;315:1767–1777 [MEDLINE]
CDC Tickborne Diseases of the United States (Accessed 7/17) [LINK]