Jajosky, R.P.; Jajosky, A.N.; Jajosky, P. Cerebral Malaria: Clinicians, Extracellular Vesicles, and Therapeutically-Rational Exchange (T-REX). Preprints2024, 2024040280. https://doi.org/10.20944/preprints202404.0280.v1
APA Style
Jajosky, R.P., Jajosky, A.N., & Jajosky, P. (2024). Cerebral Malaria: Clinicians, Extracellular Vesicles, and Therapeutically-Rational Exchange (T-REX). Preprints. https://doi.org/10.20944/preprints202404.0280.v1
Chicago/Turabian Style
Jajosky, R.P., Audrey Nadine Jajosky and Philip Jajosky. 2024 "Cerebral Malaria: Clinicians, Extracellular Vesicles, and Therapeutically-Rational Exchange (T-REX)" Preprints. https://doi.org/10.20944/preprints202404.0280.v1
Abstract
As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”
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