Invited Commentary 

Exchange Transfusion for Severe Babesiosis—Insights From a Multicenter Retrospective Analysis

Eric A. Meyerowitz, Johanna P. Daily

JAMA Intern Med 2026;186;(5):607-608. doi:10.1001/jamainternmed.2026.0252

Babesia microti is a tickborne intraerythrocytic parasite reported in at least 24 states across the US, with 1827 cases reported in 2020.¹ Rising cases have been attributed to climate and weather changes across the country. Severe babesiosis, defined by high-grade parasitemia (>10%) and/or evidence of organ failure, is more common among older adults and individuals with comorbidities, immunosuppression, and asplenia.² Current guidelines^3,4strongly recommend combination antiparasitic therapy; however, only in certain severe cases do they recommend exchange red blood cell transfusion (ET) because evidence of its benefit has been limited to small case series and low-quality observational studies.

In this issue of JAMA Internal Medicine, The STOP-BABESIOSIS Investigators⁵ report a multicenter retrospective cohort study evaluating the effectiveness of ET initiated within 7 days of hospitalization among 629 patients with severe babesiosis. Eligible patients were adults (age ≥18 years) with parasitemia greater than 10%, or parasitemia of 5% to 10% with organ injury or severe hemolytic anemia; those with a Sequential Organ Failure Assessment (SOFA) score of 20 or higher were excluded. Using a composite primary outcome of in-hospital mortality or 30-day readmission, the authors found that ET was associated with improved outcomes. Mortality occurred in 2.2% of patients who received ET compared with 2.9% of those who did not (adjusted OR [aOR], 0.35; 95% CI, 0.12-0.98). Thirty-day readmission was also less frequent in the ET group (1.6% vs 7.1%; aOR, 0.22; 95% CI, 0.07-0.63), yielding an overall benefit for composite primary end point (aOR, 0.22; 95% CI, 0.09-0.51). Persistent or progressive organ injury occurred less often among patients treated with ET (aOR, 0.48; 95% CI, 0.27-0.84), while length of hospital stay did not differ significantly between groups. Together, these findings suggest that, in carefully selected adults with severe babesiosis, early ET was associated with lower mortality, fewer readmissions, and reduced progression of organ injury, providing the strongest clinical evidence to date supporting its targeted use despite long-standing uncertainty and limited prospective data.

The main limitation of this study⁵ was its retrospective design; however, to mitigate confounding and treatment timing, the investigators used multiple complementary approaches, including sequential target trial emulation, inverse probability of treatment weighting, and sensitivity analyses assessing the influence of year of admission and other covariates. Nevertheless, as acknowledged by the authors, residual unmeasured confounding remains an inherent concern in observational studies of treatment allocation, even with advanced analytic methods.

Clinically important questions in the management of severe babesiosis remain unresolved, particularly which patients are most likely to derive the greatest benefit from ET. In this study’s subgroup analysis,⁵ ET was associated with improved outcomes among patients 70 years or older (aOR, 0.16; 95% CI, 0.05-0.56), whereas no benefit was observed among those younger than 70 years (aOR, 0.33; 95% CI, 0.06-1.72). Similarly, patients with greater organ dysfunction (SOFA scores >12) appeared to benefit from ET (aOR, 0.08; 95% CI, 0.02-0.35), whereas those with SOFA scores of 12 or less did not (aOR, 0.34; 95% CI, 0.10-1.13). The use of the SOFA score to risk-stratify patients was an advance, providing more rigor to patient selection for ET; they should be incorporated in future studies and in clinical guidelines for severe babesiosis treatment.

In contrast, the association of ET with the primary outcome was similar, regardless of degree of admission parasitemia (5%-10% vs >10%).⁵ The 10% parasitemia cutoff has been traditionally used as an independent marker for severe disease; however, it is based on expert consensus opinion rather than on robust statistical evidence. These study’s⁵ findings suggest that patients with high parasitemia, but minimal organ dysfunction, experienced limited benefit from ET, whereas older patients or those with SOFA scores greater than 12 receive the greatest benefit. However, the small number of ET-treated patients within these subgroups precludes definitive conclusions, and further study is needed to better define which patients are most likely to benefit from ET.

Additional unanswered questions remain, including the optimal timing of ET initiation and indications for repeated ET sessions. In this study cohort,⁵ ET was initiated at a median (IQR) of 2 (1-3) days after hospitalization; 22% of patients underwent a second ET and 2.9% received a third. Those who received multiple ET treatments did so at the discretion of treating physicians, although the associated effects of multiple vs single ET treatments were not reported. Adverse events occurred in 5.7% of ET-treated patients, most commonly hypotension or shock (2.4%), while 1.4% had a transfusion reaction. These findings highlight the need for additional data to inform formal practice guidelines that address both the timing of initiation and indications for repeated ET sessions.

ET has not demonstrated efficacy in severe malaria, another intraerythrocytic parasitic infection caused by Plasmodium spp, which similarly can present with high parasite burden, hemolytic anemia, and severe organ dysfunction.⁶ Additionally, it is important to consider the mechanism of the potential benefit of ET. For example, standard blood transfusion in children with severe malaria was associated with increased survival.⁷ Whether blood transfusion could confer benefits comparable to those of ET in severe babesiosis is an important question for future study.

This large multicenter retrospective analysis by The STOP-BABESIOSIS Investigators⁵ provides further evidence to date supporting the consideration of ET in severe babesiosis, demonstrating an association with improved clinical outcomes despite low overall mortality. Although severe babesia incidence is low at a population level, randomized clinical trials remain feasible using efficient trial designs, including multicenter enrollment, adaptive Bayesian methods, enrolling highest-risk participants and measuring alternative end points, such as SOFA score changes.

Nevertheless, in the short term, given the feasibility constraints mentioned and the likelihood that a large-scale randomized clinical trial is not immediately forthcoming, this study⁵ provides important evidence supporting the current guidelines. Moreover, these findings lend support for a more targeted approach to patient selection for ET, prioritizing patients with substantial organ dysfunction—reflected by elevated SOFA scores—and older age groups.