Ryan Philip Jajosky1, Audrey N Jajosky2, Philip G Jajosky3. 1. Emory University, Department of Pathology and Laboratory Medicine, Atlanta, GA, USA; Biconcavity Inc., Retired USPHS Officer at Centers for Disease Control and Prevention,1106 Spring Mill Dr. SW, Lilburn, GA 30047, USA. Electronic address: rjajosk@emory.edu. 2. Case Western Reserve University, University Hospitals Cleveland Medical Center, Department of Pathology, 11100 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: ajajosky@gmail.com. 3. Biconcavity Inc., Retired USPHS Officer at Centers for Disease Control and Prevention,1106 Spring Mill Dr. SW, Lilburn, GA 30047, USA. Electronic address: jajosky@gmail.com.
Abstract
BACKGROUND: Using indicators of disease severity, clinicians can predict which Plasmodium falciparum (Pf) malaria patients being treated with artesunate or quinine are likely to die despite these drugs. Effective "rescue adjuncts" are needed when drugs alone are inadequate. "Therapeutically-rational exchange" (T-REX) of special malaria-resistant red blood cells (RBCs) has been proposed to optimize adjunctive exchange transfusion. METHODS: Studies were reviewed that (1) quantified how group-O status and "sickle-trait" (HbAS) and "C-trait" (HbAC) hemoglobins affect Pf mortality, risk of thrombosis, or birth outcomes for women with pregnancy associated malaria (PAM), (2) reported prevalences of "dual-gene" malaria-resistant RBCs, or (3) reflected the level of exchange-transfusion and malaria-related expertise in Benin and Nigeria. RESULTS: Data show that the malaria- and thrombosis-resistance of RBCs depend on specific genes and the patient's clinical status and medical history. In malaria-endemic Benin and Nigeria, prevalences of "dual-gene" malaria-resistant group-O HbAS and group-O HbAC RBCs are substantial, and both malaria- and exchange-related expertise are outstanding. CONCLUSIONS: T-REX of "dual-gene" malaria-resistant RBCs is feasible in Benin and Nigeria and warrants evaluation as a rescue adjunct for 3 subsets of Pf-malaria patients. For therapeutic use, group-O HbAS RBCs are likely to be more effective than non-O HbAS RBCs for Pf-infected patients who (1) have a history of thrombosis or (2) are taking birth-control hormones while group-O HbAC RBCs may substantially improve birth outcomes for women with PAM. Studies suggest it is prudent to assume - until proven otherwise - that T-REX of "dual-gene" malaria-resistant RBCs can improve ("personalize") rescue of these patient subsets.
BACKGROUND: Using indicators of disease severity, clinicians can predict which Plasmodium falciparum (Pf) malaria patients being treated with artesunate or quinine are likely to die despite these drugs. Effective "rescue adjuncts" are needed when drugs alone are inadequate. "Therapeutically-rational exchange" (T-REX) of special malaria-resistant red blood cells (RBCs) has been proposed to optimize adjunctive exchange transfusion. METHODS: Studies were reviewed that (1) quantified how group-O status and "sickle-trait" (HbAS) and "C-trait" (HbAC) hemoglobins affect Pf mortality, risk of thrombosis, or birth outcomes for women with pregnancy associated malaria (PAM), (2) reported prevalences of "dual-gene" malaria-resistant RBCs, or (3) reflected the level of exchange-transfusion and malaria-related expertise in Benin and Nigeria. RESULTS: Data show that the malaria- and thrombosis-resistance of RBCs depend on specific genes and the patient's clinical status and medical history. In malaria-endemic Benin and Nigeria, prevalences of "dual-gene" malaria-resistant group-O HbAS and group-O HbAC RBCs are substantial, and both malaria- and exchange-related expertise are outstanding. CONCLUSIONS: T-REX of "dual-gene" malaria-resistant RBCs is feasible in Benin and Nigeria and warrants evaluation as a rescue adjunct for 3 subsets of Pf-malaria patients. For therapeutic use, group-O HbAS RBCs are likely to be more effective than non-O HbAS RBCs for Pf-infected patients who (1) have a history of thrombosis or (2) are taking birth-control hormones while group-O HbAC RBCs may substantially improve birth outcomes for women with PAM. Studies suggest it is prudent to assume - until proven otherwise - that T-REX of "dual-gene" malaria-resistant RBCs can improve ("personalize") rescue of these patient subsets.