Approach Considerations
Suspicion of babesiosis in a patient with a history of exposure in an endemic area, tick bite, fever, chills, and fatigue is crucial. Peripheral blood smear or PCR is necessary to make the diagnosis. [3] A complete blood count (CBC) count with differential may be helpful for determining the severity of infection.
Patients with congenital or acquired asplenia can have severe or fulminant babesiosis. In patients with fever of unknown origin (FUO), consider babesiosis as a diagnosis if the patient lives in an endemic area, has traveled to an endemic area, or received a blood transfusion in the past. [41]
If a patient is otherwise healthy and asymptomatic, no treatment is required. [3] Most of the otherwise healthy patients infected by B. microti appear to have a mild illness and recover without specific chemotherapy. Asymptomatic, immunocompetent patients do not require monitoring for clearance of parasitemia.
The IDSA recommends starting symptomatic patients on a combination treatment regimen of atovaquone and azithromycin (first line) or a combination of clindamycin and quinine (alternative therapy).
Immunocompromised patients should be monitored for parasitemia on blood smears until the blood smears are negative, regardless of symptoms. Symptomatic immunocompetent patients should have blood smears monitored for parasitemia during acute illness. Once symptoms have resolved, the IDSA recommends against monitoring blood smears for parasitemia. [3]
Intubation and mechanical ventilation may be required for patients who develop respiratory distress or failure. Other supportive care may be necessary in some patients; this could include vasopressors for hypotensive patients, blood transfusions, and dialysis. [7]
Pharmacologic Therapy
In asymptomatic, immunocompetent patients with positive results from peripheral smears or polymerase chain reaction (PCR) testing, treatment is not recommended. If a patient is diagnosed after symptoms have resolved, they should not receive treatment unless organisms are seen on peripheral smear for more than one month from the time of acute illness. PCR assays are not recommended for monitoring parasitemia in this patient group since relapse rarely occurs. [3]
In symptomatic, immunocompetent patients, antimicrobial therapy should be started after confirmed diagnosis to reduce the level of parasitemia. A drug regimen consisting of atovaquone and azithromycin is now first-line treatment and has been shown to be effective. [3] Clindamycin plus quinine is an alternative regimen, but it results in far more adverse effects.
Per the IDSA, the recommended regimens in adults are as follows [3] :
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Ambulatory adults with mild-moderate disease:
- First line: atovaquone 750 mg PO q12h plus azithromycin 500 mg PO on day one, followed by 250 mg PO q24h for 7-10 days
- Alternative treatment: clindamycin 600 mg PO q8h plus quinine sulfate 542 mg base (equal to 650 mg salt) PO q6-8h for 7-10 days
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Hospitalized adults with acute severe disease:
- First line: atovaquone 750 mg PO q12h plus azithromycin 500-1000 mg IV q24h until symptoms improve, then convert to step-down therapy
- Alternative treatment: Clindamycin 600 mg IV q6h plus quinine sulfate 542 mg base (equal to 650 mg salt) PO q6-8h until symptoms improve, then convert to step-down therapy
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Hospitalized adults, step-down therapy:
- First line: atovaquone 750 mg PO q12h plus azithromycin 250-500 mg PO q24h; total course of therapy is usually 7-10 days. Consider using a higher dose of azithromycin (500-1000 mg) in immunocompromised patients.
- Alternative treatment: clindamycin 600 mg PO q8h plus quinine sulfate 542 mg base (equal to 650 mg salt) PO q6-8h; total course of therapy is usually 7-10 days.
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Highly immunocompromised adults:
- Highly immunocompromised patients include the following:
- Patients who are receiving or have received rituximab for B-cell lymphoma or autoimmune disease
- Patients on immunosuppressive regimens for solid organ or bone marrow transplantations or malignancy
- Patients who have malignancy and are asplenic
- Patients who have HIV with a CD4 count of less than 200 (AIDS)
- These patients should receive the regimen for hospitalized adults with acute severe disease, followed by step-down therapy, but treatment must be continued for at least 6 consecutive weeks, and peripheral blood smears should be free of parasites for the 2 final weeks of this period.
- As previously stated, higher doses of oral azithromycin (500-1000 mg daily) should be considered in these patients when oral azithromycin is appropriate.
- Highly immunocompromised patients include the following:
Relapse is more common in immunocompromised patients. If a patient experiences relapse, the IDSA notes that the following regimens have been used with limited evidence:
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Atovaquone + azithromycin + clindamycin
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Atovaquone + clindamycin
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Atovaquone/proguanil + azithromycin
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Atovaquone + azithromycin + clindamycin + quinine
With relapse, higher doses of azithromycin (500 or 1000 mg daily) have been used. [3]
In children, the following regimens are recommended [3] :
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Ambulatory children with mild-moderate disease:
- First line: Atovaquone 20 mg/kg/dose (up to 750 mg) q12h PO plus azithromycin 10 mg/kg/dose (up to 500 mg) PO on day one, followed by 5 mg/kg/dose q24h for 7-10 days
- Alternative treatment: Clindamycin 7-10 mg/kg/dose (up to 600 mg/dose) PO q8h plus quinine sulfate 6 mg base/kg/dose (equivalent to 8 mg salt/kg/dose; up to 542 mg base or 650 mg salt/dose) PO q6-8h for 7-10 days
-
Hospitalized children with acute severe disease:
- First line: Atovaquone 20 mg/kg/dose (up to 750 mg) q12h PO plus azithromycin 10 mg/kg/dose (up to 500 mg) q24h IV until symptoms improve, then convert to step-down therapy
- Alternative treatment: Clindamycin 7-10 mg/kg/dose (up to 600 mg/dose) IV q8h plus quinine sulfate 6 mg base/kg/dose (equivalent to 8 mg salt/kg/dose; up to 542 mg base or 650 mg salt/dose) PO q6-8h until symptoms improve, then convert to step-down therapy
-
Hospitalized children, step-down therapy
- Atovaquone 20 mg/kg/dose (up to 750 mg) q12h PO plus azithromycin 10 mg/kg/dose (up to 500 mg) PO; total therapy is usually 7-10 days.
- Clindamycin 7-10 mg/kg/dose (up to 600 mg/dose) PO q8h plus quinine sulfate 6 mg base/kg/dose (equivalent to 8 mg salt/kg/dose; up to 542 mg base or 650 mg salt/dose) PO q6-8h; total therapy is usually 7-10 days.
-
Highly immunocompromised children:
- Include the same group of highly immunocompromised patients described above in the adult regimens section.
- These patients should receive the regimen for hospitalized children with acute severe disease, followed by step-down therapy, but treatment must be continued for at least 6 consecutive weeks, and peripheral blood smears should be free of parasites for the 2 final weeks of this period.
-
Relapse regimens in children are similar to the relapse regimens listed above for adults.
A prospective, non-blinded, randomized study found that a seven-day course of atovaquone (750 mg every 12 hours) plus azithromycin (500 mg on day 1 and 250 mg/day thereafter) was as effective as clindamycin (600 mg every 8 hours) plus quinine (650 mg salt every 8 hours) in producing a clinical response and clearing parasitemia [42] ; however, the risk of adverse effects in the clindamycin-quinine group was substantially greater at 72% when compared to the atovaquone-azithromycin group at 15%.
The combination of clindamycin, doxycycline, and azithromycin was successfully used in a patient who was allergic to quinine.
Another case report described a patient with acquired immune deficiency syndrome (AIDS) and babesiosis who failed treatment with azithromycin and atovaquone followed by quinine and clindamycin. The addition of atovaquone-proguanil to the treatment regimen led to cure. [43]
One report listed 3 highly immunocompromised patients who received a subcurative course of azithromycin-atovaquone, which led to the development of resistance to this regimen. [44]
Parasitemia may persist despite treatment with either of the drug regimens described above. In areas endemic for Lyme disease, physicians should consider coinfection with Lyme disease as a possibility and treat accordingly. [3]
Immunocompromised individuals who are infected by B. microti are at risk for persistent relapsing illness. As previously described, such patients generally require antibabesial treatment for 6 weeks or longer to achieve cure, including a final 2 weeks during which parasites are no longer detected on blood smears. [45]
Atovaquone is a pregnancy category C drug, azithromycin and clindamycin are both in category B, and quinine has no US FDA pregnancy category as of this writing. Quinine does cross the placenta, but it is sometimes used in patients where the benefit outweighs the risk.
Exchange Transfusion and Supportive Care
Exchange transfusion is employed in patients who are profoundly ill with high levels of parasitemia and hemolysis. In severe cases of babesiosis—as demonstrated by high parasitemia (>10%), significant hemolysis, or renal, hepatic, or pulmonary dysfunction—it may be lifesaving. [3] When used concurrently with chemotherapy, exchange transfusion reduces the level of parasitemia and may remove toxic erythrocyte, babesial, or macrophage-produced factors.
Patients with severe babesiosis need to be hospitalized. In addition to receiving anti-Babesia treatment, they may require supportive care. Critically ill patients should be transferred to the intensive care unit (ICU). Patients with mild-to-moderate babesiosis who are discharged from the hospital should undergo the same laboratory tests as hospitalized patients.
Patients being treated for babesiosis should be monitored clinically, and serial blood smears should be obtained to document the degree of parasitemia and the effectiveness of therapy. Serial CBC counts may be obtained to assess the reticulocyte response and evaluate decrease in the hemolytic process. Be alert for the possibility of hemophagocytic syndrome.
Monitor the level of oxygenation, and watch for the development of respiratory complications after the initiation of treatment in patients who present with respiratory complaints. Respiratory distress may be due to endotoxin sensitivity; endotoxin release often results from medication-induced intraerythrocytic death of the parasites. Mechanical ventilation may be necessary in patients with severe disease.
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Peripheral smear showing babesiosis.
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Ixodes scapularis, tick vector for babesiosis. Image courtesy of Centers for Disease Control and Prevention.
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Blood smear showing Babesia species in erythrocytes. Image courtesy of Centers for Disease Control and Prevention.
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Babesia species, tetrad formation. Image courtesy of Centers for Disease Control and Prevention.
