Optimizing exchange transfusion for patients with severe Babesia divergens babesiosis: Therapeutically-Rational Exchange (T-REX) of M antigen-negative and/or S antigen-negative red blood cells should be evaluated now.

Babesia divergens is an intraerythrocytic parasite, which is the major cause of babesiosis in Europe. For years, clinicians have been publishing stunning case reports that describe how some - but not all - conventional red blood cell (RBC) exchange transfusions have saved the lives of severely ill babesiosis patients. Due to markedly different patient outcomes, clinicians agree that new treatments and additional studies are needed. Here we argue that we should evaluate "therapeutically-rational exchange" (T-REX) in which the RBCs used to replace Babesia-parasitized RBCs are special disease-resistant RBC genetic variants (instead of the nondescript, "standard issue" RBCs used in conventional exchanges). T-REX seems prudent because with conventional exchange only some units of "standard issue" RBCs may be disease-resistant, while other units may not protect or may even promote disease. The random selection of RBCs for conventional RBC exchange may explain why clinical outcomes can vary dramatically. Fortunately, researchers have found that M antigen-negative (M-) and S antigen-negative (S-) RBCs resist invasion by B. divergens. Thus, we recommend evaluating T-REX of RBC variants that are B. divergens invasion-resistant: RBCs that are (1) M-, (2) S-, or (3) both M- and S-. By using only Babesia-resistant RBCs, T-REX eliminates the risk of unintentionally infusing Babesia-susceptible RBCs that might increase the severity of babesiosis. Because the T-REX variation of the conventional RBC exchange procedure is feasible, safe, and biologically plausible, we feel T-REX of Babesia-resistant RBCs should now be evaluated.