Babesiosis

[Section Outline]

Description
Etiology

Author:

Jonathan A.Edlow

Description

Tick-borne, infectious disease caused by intraerythrocytic protozoa of the genus Babesia, infects wide array of vertebrate animals, causes lysis of host RBCs
Asymptomatic to severe, life-threatening infection depending on the species of Babesia and the immune status of the patient
- Asymptomatic infection:
  - 50% of children and 25% of adults with infection have no symptoms
- Mild-moderate disease:
  - Usually immune-competent patients
  - Infections typically self-limited or resolve with antibiotic therapy
  - Mortality usually <5%
- Severe disease:
  - Defined as hospitalization >2 wk, ICU stay >2 d, or ending in death
  - Typically associated with immune compromise: Splenectomy; cancer; HIV; hemoglobinopathy; chronic heart, lung, or liver disease
  - Other groups at higher risk for severe disease: Neonates, >50 yr old, on immune-suppressive drugs (e.g., rituximab or anticytokine therapy [etanercept, infliximab])
  - Mortality can be as high as 21% among immune-suppressed patients
Complications develop in approximately one-half of the hospitalized patients:
- ARDS, DIC most common
- Can also see CHF, coma, liver failure, renal failure, splenic rupture
Co-occurrence with other tick-borne diseases should be considered in endemic regions under the following conditions:
- Lyme disease (Borrelia burgdorferi) - associated rash
- Human granulocytic anaplasmosis (Anaplasma phagocytophilum) - protracted symptoms with leukopenia
Risk factors for developing severe disease:
- Asplenia
- Malignancy
- HIV infection
- Immunosuppressive drugs
- Age>50
- Elevated alkaline phosphatase
- Elevated WBC counts
- Male gender

Etiology

Babesia:
- Species causing human disease:
  - Babesia microti - Northern and Midwestern U.S. (most common cause of disease in the U.S.)
  - Babesia divergens - Europe
  - Babesia duncani - Northern U.S. Pacific coast
- Case reports of babesiosis in Asia, Africa, Australia, and South America
- Animal reservoirs:
  - B. microti - white-footed mouse, white-tailed deer
  - B. divergens - cattle, rats
Transmission via Ixodes tick vector:
- Most common vector for transmission of babesiosis to humans
- Ixodes requires blood meal from a vertebrate host to pass through each stage of life cycle (larva, nymph, adult):
  - Most cases result from nymphal tick bites in late spring through summer, adult ticks can also transmit disease
Pathogen life cycle, pathogenesis:
- Protozoa pass from tick salivary gland s to mammalian bloodstream where they penetrate erythrocytes, mature and divide
- Mature protozoa exit from RBC resulting in membrane damage, lysis, hemolytic anemia, and hemoglobinuria
- Damaged RBCs become less deformable, enhancing removal by spleen; however, asplenic patients less able to clear infected RBCs, leading to more severe disease
- Damaged RBCs may result in microvascular stasis with secondary ischemic organ injury to liver, spleen, heart, kidney, or brain
Transmission via transfusion of RBCs, platelets:
- >150 cases since 1979, 75% of these since 2000
- Although not common, the incidence of transfusion-transmitted babesiosis is increasing
- B. microti is the most common pathogen
- Low-level parasitemia may not be visible on donor blood smears, yet can still transmit disease
- Often results in severe cases as recipients of blood products are often immune compromised or have significant comorbidities

Pediatric Considerations
Transmission can occur in utero and during delivery; youngest reported case was a 4-wk-old infant

Diagnosis ⬆ ⬇

[Section Outline]

Signs and Symptoms
Essential Workup
Diagnostic Tests & Interpretation
Differential Diagnosis

Signs and Symptoms

Gradual onset of malaise and fatigue, associated with fever as high as 105°F (40.6°C), 1-4 wk after tick bite, or 1-9 wk after transfusion with contaminated blood products

Common symptoms include chills and sweats, headache, anorexia, nonproductive cough, arthralgia, and nausea
Less common symptoms include vomiting, sore throat, abdominal pain, conjunctival injection, photophobia, weight loss, emotional lability, depression, and hyperesthesia

History

Febrile, flu-like illness in patients who:
- Live in, or traveled to an endemic area within past 2 mo (especially during spring, summer)
- Have had blood product transfusions within past 6 mo
Shock or sepsis presentation in patients with above history, especially in presence of risk factors for severe disease (see above)

Physical Exam

Fever (most common finding)
Hepatosplenomegaly
Pharyngeal erythema
Jaundice
Retinopathy with splinter hemorrhages
Retinal infarcts
Rash may be seen:
- Petechiae, ecchymosis
- Erythema migrans suggests concurrent Lyme disease
Severe disease:
- Tachypnea
- Hypoxia
- Hypotension
- Altered mental status

Essential Workup

Microscopy of thin blood smear with Giemsa or Wright staining to demonstrate Babesia organisms
When smears are negative, polymerase chain reaction (PCR) assay can be used
Indirect immunofluorescent antibody testing can be used to recognize babesial antigens when microscopy and PCR assays are negative

Diagnostic Tests & Interpretation

Lab

Microscopy:
- Intraerythrocytic parasites can be round, oval, or pear shaped
- Parasites in budding tetrad formation (Maltese cross) are pathognomonic for babesiosis, but not commonly seen
- Most common finding is intraerythrocytic round or oval (pyriform) rings with pale blue cytoplasm and red-staining nucleus
- Extracellular parasites may be seen with high levels of parasitemia
- Parasitemia levels are generally between 1-10%, but can be as high as 80%; may be <1% in early stages of disease
- Ring forms may appear similar to Plasmodium falciparum (malaria); in babesiosis there are no pigment deposits (hemozoin) that are usually seen with malaria
PCR:
- Amplification of babesial 18s rRNA gene is more sensitive than microscopy
- Results can be available within 24 hr
- Useful in cases with low levels of parasitemia
Serology:
- Indirect immunofluorescent antibody testing may be useful when microscopy and PCR testing are negative
- IgM antibody usually detectable 2 wk after onset of illness
- IgG titers ≥1:256 suggest active or recent infections; IgM titers ≥1:64 suggest acute infection
Nonspecific lab abnormalities that may be seen in babesiosis:
- Mild-to-moderate hemolytic anemia (low hematocrit/hemoglobin, low haptoglobin, elevated reticulocyte count, elevated lactate dehydrogenase, elevated total bilirubin)
- Thrombocytopenia is common
- LFTs (elevated alkaline phosphatase, transaminases, lactate dehydrogenase, bilirubin)
- Urinalysis (hemoglobinuria, proteinuria)
- Elevated BUN, creatinine suggests renal insufficiency
- Hyperkalemia may result from massive hemolysis

Differential Diagnosis

Malaria
Other tick-borne diseases:
- Lyme disease
- Borrelia miyamotoi infection
- Human granulocytic anaplasmosis
- Ehrlichiosis
- Rocky Mountain spotted fever
- Colorado tick fever
- Q fever
- Tularemia
- Relapsing fever
Typhoid fever
Acute hemolytic anemia

Treatment ⬆ ⬇

[Section Outline]

Prehospital
Initial Stabilization/Therapy
ED Treatment/Procedures
Medication

Prehospital

Ensure a patent airway in patients with respiratory distress
Provide supplemental oxygen and ventilatory assistance as needed
If patient presents in shock, establish IV access and administer a fluid bolus of 0.9% NS 500 mL (peds: 20 mL/kg) IV

Initial Stabilization/Therapy

Airway management, ventilatory support for patients with acute respiratory distress
IV access should be established in patients with evidence or risk factors for severe disease
IV fluids, pressor support for patients in shock
Cardiac monitor: Patients with severe disease may develop cardiac ischemia, arrhythmias

ED Treatment/Procedures

Antipyretics for fever
Start antibiotic therapy in symptomatic patients after confirming diagnosis on microscopy or PCR
Mild-moderate disease:
- Oral atovaquone + azithromycin for 7-10 d is the regimen of choice
- Clindamycin + quinine is an effective alternative, but associated with significant side effects (tinnitus, vertigo, gastroenteritis) that may require reduced dosing or stopping medication in up to one-third of patients
Severe disease:
- IV clindamycin + oral quinine for 7-10 d is regimen of choice (IV quinine may be used, but may cause ventricular arrhythmias and requires QT monitoring)
- RBC exchange transfusion is indicated in patients with parasitemia >10%; hemoglobin <10 g/dL; or pulmonary, renal, or hepatic complications
- Persistent or relapsing disease may be seen in immunocompromised patients; these patients should receive antibiotic therapy for at least 6 wk, continuing for 2 wk after the last positive blood smear; can use stand ard combinations (see above)
Asymptomatic infection:
- Antibiotics are not indicated unless parasitemia on blood smears persists >3 mo

Medication

Acetaminophen: 500 mg (peds: 10-15 mg/kg, do not exceed 5 doses/24 hr) PO q4-6h, do not exceed 4 g/24 hr
Atovaquone: 750 mg (peds: 20 mg/kg; max 750 mg/dose) PO b.i.d for 7 d
Azithromycin: 500 mg (peds: 10 mg/kg; max 500 mg) PO on day 1, followed by 250 mg (peds: 5 mg/kg; max 250 mg) PO per day: 6 d
Clindamycin: 300-600 mg (peds: 7-10 mg/kg q6-8h) IV q6h; 600 mg (peds: 7-10 mg/kg q6-8h) PO q8h for 7-10 d
Ibuprofen: 400 mg (peds: 20-40 mg/kg/d) PO q6-8h PRN
Quinine: 650 mg (peds: 25 mg/kg/d) PO q8h for 7-10 d

Follow-Up ⬆ ⬇

[Section Outline]

Disposition
Follow-up Recommendations

Disposition

Admission Criteria

Parasitemia >4%
Severe anemia (hemoglobin <10 g/dL)
- Significant symptoms or complications
- Respiratory distress
- Hypotension or shock
- New renal insufficiency or hepatic failure
- Altered mental status
- Severe hemolysis (jaundice, hematuria)
- Patients with post splenectomy
- Immunosuppression

Discharge Criteria

Patients with asymptomatic, mild, or moderate disease
Parasitemia <4%
Intact spleen, immune competent
Able to tolerate oral medications

Issues for Referral

Immunodeficient patients are more likely to have persistent or relapsing disease following initial treatment and should be referred for infectious disease consultation
Patients with an indication for RBC exchange transfusion may require transfer to a facility that can provide this

Follow-up Recommendations

Patients diagnosed with babesiosis should follow up with their primary care physician or infectious disease specialist for monitoring of parasitemia levels following completion of antibiotic course in symptomatic patients and at 3 mo in asymptomatic patients

Pearls and Pitfalls ⬆ ⬇

Babesiosis can be a life-threatening disease in asplenic patients
Consider babesiosis as a potential cause of respiratory distress/shock in patients with a travel history to an endemic area
Microscopy findings may not be present in early stages of disease when parasitemia levels are low
Coinfection with Lyme disease is quite common and has implications in terms of antimicrobial treatment

Additional Reading ⬆ ⬇

Gelfand JA, VannierEG. Clinical manifestations, diagnosis, treatment, and prevention of babesiosis . UpToDate. 2017.
LederK, WellerPF. Epidemiology and pathogenesis of babesiosis . UpToDate. 2017.
LindenJV, PrusinskiMA, CrowderLA, et al. Transfusion-transmitted and community acquired babesiosis in New York, 2004-2015 . Transfusion. 2018;58(3):660-668.
VannierE, GewurzBE, KrausePJ. Human babesiosis . Infect Dis Clin North Am. 2008;22(3):469-488, viii-ix.
VannierE, KrausePJ. Human babesiosis . N Engl J Med. 2012;366:2397-2407.

See Also (Topic, Algorithm, Electronic Media Element)

Lyme Disease

section name header

Basics ⬇

Pediatric Considerations

Diagnosis ⬆ ⬇

History

Physical Exam

Lab

Treatment ⬆ ⬇

Follow-Up ⬆ ⬇

Admission Criteria

Discharge Criteria

Issues for Referral

Pearls and Pitfalls ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆