Original Investigation 

Red Blood Cell Exchange Transfusion for Severe Babesiosis

STOP-BABESIOSIS Investigators

JAMA Intern Med 2026;186;(5):597-607. doi:10.1001/jamainternmed.2026.0244

Key Points

Question  Is red blood cell exchange transfusion (ET) associated with improved clinical outcomes in patients hospitalized with severe babesiosis?

Findings  In this multicenter cohort study of 629 patients hospitalized with severe babesiosis at 82 US sites, 33% received ET within 7 days. The composite end point of in-hospital death or 30-day readmission occurred in 3.6% of ET-treated patients vs 9.8% of those not treated, a significant difference.

Meaning  These findings indicate that ET was associated with significantly improved clinical outcomes in patients with severe babesiosis.

Abstract

Importance  Babesiosis is a worldwide emerging tick-borne disease with an expanding geographic range in the US, Europe, and Asia. Red blood cell exchange transfusion (ET) is often used as an adjunctive treatment for severe illness from babesiosis, particularly in patients with high parasitemia, acute organ injury, or severe hemolytic anemia. Data supporting its clinical effectiveness, however, are lacking.

Objective  To test whether ET improves clinical outcomes among hospitalized adult patients with severe babesiosis.

Design, Settings, and Participants  This target trial emulation used data from a multicenter cohort study of 3233 consecutive adults hospitalized with babesiosis from 2010 to 2024 at 82 sites across the northeastern US. Patients were eligible if they had parasitemia greater than 10%, or 5% to 10% with either acute organ injury or severe hemolytic anemia. Data were analyzed from April to August 2025.

Exposure  Treatment with ET in the first 7 days of hospitalization.

Main Outcomes and Measures  A composite of in-hospital death or 30-day readmission. Outcomes were compared between patients who received ET within the first 7 days of admission and those who did not. The analysis used logistic regression, with inverse probability of treatment weighting (IPTW) to adjust for potential confounders.

Results  The analysis included 629 patients (median [IQR] age, 71 [63-79] years; 446 male [70.9%]), among whom 209 (33.2%) received ET in the first 7 days of hospitalization. Patients treated with ET were more severely ill at baseline than those not treated with ET (median parasitemia, 14.0% vs 7.2%); however, severity of illness characteristics were well balanced after applying IPTW. In the main analysis, the primary end point occurred in 3.6% of patients who received ET and in 9.8% who did not (adjusted odds ratio, 0.22; 95% CI, 0.09-0.51). The benefit of ET was confirmed in multiple sensitivity analyses.

Conclusions and Relevance  This multicenter cohort study found that among severely ill adults hospitalized with babesiosis, the adjusted risk of in-hospital death or 30-day readmission was nearly 5-fold lower in those treated with ET vs those not treated with ET. These data support ET for severely ill patients with babesiosis, although the findings may be susceptible to unmeasured confounding. Further research is needed to identify which patients are most likely to benefit.