In an adult treated for Babesiosis, can the infection cause a persistently elevated white blood cell count after therapy?

Can Babesiosis Cause Persistently Elevated WBC After Treatment?

Yes, babesiosis can result in continued elevated white blood cell counts after therapy, and this finding warrants careful clinical evaluation to distinguish between persistent infection, coinfection, or underlying immunodeficiency rather than assuming treatment failure alone.

Understanding the Clinical Context

The Infectious Diseases Society of America guidelines explicitly state that some patients may have persistence of low-grade parasitemia for months after specific antimicrobial therapy 1. This persistent parasitemia can drive ongoing inflammatory responses, including leukocytosis. However, the guidelines emphasize that parasitemia persistence alone does not automatically indicate treatment failure—it represents a recognized phenomenon in babesiosis management 1.

When Elevated WBC Suggests Active Bacterial Infection

An elevated WBC count (≥14,000 cells/mm³) combined with a left shift (≥16% band neutrophils or absolute band count ≥1,500 cells/mm³) has high predictive value for bacterial infection requiring antimicrobial therapy 1, 2. Specifically:

• Absolute band count ≥1,500 cells/mm³ has a likelihood ratio of 14.5 for bacterial infection 1, 2
• Neutrophil percentage >90% has a likelihood ratio of 7.5 1
• Left shift ≥16% bands has a likelihood ratio of 4.7 1
• Total WBC ≥14,000 cells/mm³ has a likelihood ratio of 3.7 1, 2

In the context of treated babesiosis with persistent leukocytosis, you must obtain a manual differential count to assess for left shift and bands, as this distinguishes between ongoing parasitic inflammation versus superimposed bacterial infection 1, 2.

Prognostic Significance of Leukocytosis in Babesiosis

Research demonstrates that WBC counts >5 × 10⁹/L (5,000 cells/mm³) are strong predictors of severe disease outcome in hospitalized babesiosis patients, including prolonged hospitalization, ICU admission, and mortality 3. This finding was confirmed through multivariate analysis alongside male sex and alkaline phosphatase >125 U/L 3.

This means that persistent leukocytosis after treatment may indicate:

• Ongoing severe disease requiring more aggressive therapy 3
• Persistent parasitemia that has not cleared 1
• Coinfection with tick-borne pathogens 1
• Underlying immunodeficiency 1

Critical Evaluation Algorithm for Persistent Leukocytosis Post-Treatment

Step 1: Assess Parasitemia Status

• Obtain blood smear and PCR immediately to determine if parasitemia persists 4
• If parasitemia is present, monitor daily or every other day until it decreases to <5% 1
• Some patients have persistence of low-grade parasitemia for months despite appropriate therapy—this is recognized but requires close monitoring 1

Step 2: Evaluate for Coinfection

The IDSA guidelines explicitly recommend considering coinfection with Borrelia burgdorferi (Lyme disease) or Anaplasma phagocytophilum (HGA) in patients with especially severe or persistent symptoms despite appropriate antibabesial therapy 1. These coinfections can cause:

• Persistent fever beyond 48 hours of appropriate therapy 1
• Ongoing leukocytosis 1, 2
• Failure to improve clinically within expected timeframes 1

If coinfection is identified, add appropriate antimicrobial therapy (doxycycline for Lyme disease or HGA) 1.

Step 3: Screen for Underlying Immunodeficiency

An underlying immunodeficiency (including asplenia or prior splenectomy, malignancy, and HIV infection) should be considered in patients with severe or prolonged episodes of babesiosis 1. These patients may require:

• Higher doses of azithromycin (600–1,000 mg per day) 1
• Prolonged duration of therapy until parasitemia clears 1
• Consideration for red blood cell exchange if parasitemia remains high 1

Step 4: Determine if Continued Treatment is Needed

• In mild-to-moderate babesiosis, clinical improvement should occur within 48 hours after antiprotozoal therapy is begun, and symptoms should completely resolve within 3 months 1
• If the patient remains symptomatic with persistent parasitemia beyond standard 7–10 day therapy, longer duration of antimicrobial therapy may be necessary until parasitemia is cleared 1
• Asymptomatic patients with persistent low-grade parasitemia do not require treatment unless parasitemia persists for ≥3 months on repeat testing 4

Common Pitfalls to Avoid

Do not assume persistent leukocytosis automatically means treatment failure—some patients have recognized persistence of low-grade parasitemia for months after therapy 1. The key is whether the patient is clinically improving and whether parasitemia is decreasing 1.

Do not ignore the possibility of coinfection—tick-borne coinfections are common and can cause persistent symptoms and laboratory abnormalities despite appropriate antibabesial therapy 1.

Do not rely on total WBC count alone—always obtain a manual differential to assess for left shift, as this distinguishes parasitic inflammation from bacterial superinfection 1, 2.

Do not delay evaluation for underlying immunodeficiency in patients with severe or prolonged disease, as these patients require more aggressive and prolonged therapy 1.

When to Consider Red Blood Cell Exchange

Although not directly related to leukocytosis management, partial or complete RBC exchange transfusion is indicated for severe babesiosis with high-grade parasitemia (≥10%), significant hemolysis, or renal, hepatic, or pulmonary compromise 1. However, recent case series suggest that the 10% parasitemia threshold should not be applied arbitrarily—clinical state and evidence of end-organ failure should guide the decision 5. Notably, parasitemia can rebound rapidly after exchange transfusion, requiring close post-procedural monitoring 6.