Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria

Abstract Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In...

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Main Authors: Saba Gul, Flavia L. Ribeiro-Gomes, Aline S. Moreira, Guilherme S. Sanches, Fabiana G. Conceição, Cláudio Tadeu Daniel-Ribeiro, Hans C. Ackerman, Leonardo J. M. Carvalho
Format: Article
Language:English
Published: Nature Portfolio 2021-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-91499-3
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author Saba Gul
Flavia L. Ribeiro-Gomes
Aline S. Moreira
Guilherme S. Sanches
Fabiana G. Conceição
Cláudio Tadeu Daniel-Ribeiro
Hans C. Ackerman
Leonardo J. M. Carvalho
author_facet Saba Gul
Flavia L. Ribeiro-Gomes
Aline S. Moreira
Guilherme S. Sanches
Fabiana G. Conceição
Cláudio Tadeu Daniel-Ribeiro
Hans C. Ackerman
Leonardo J. M. Carvalho
author_sort Saba Gul
collection DOAJ
description Abstract Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 h. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 h after artemether treatment but returned to normal levels 24 h after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.
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spelling doaj.art-b8ef0055519d46e8a9563dd4cc95860d2022-12-21T21:27:05ZengNature PortfolioScientific Reports2045-23222021-06-0111111310.1038/s41598-021-91499-3Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malariaSaba Gul0Flavia L. Ribeiro-Gomes1Aline S. Moreira2Guilherme S. Sanches3Fabiana G. Conceição4Cláudio Tadeu Daniel-Ribeiro5Hans C. Ackerman6Leonardo J. M. Carvalho7Laboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria Research, Oswaldo Cruz InstituteLaboratory of Malaria and Vector Research, NIAID, NIHLaboratory of Malaria Research, Oswaldo Cruz InstituteAbstract Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 h. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 h after artemether treatment but returned to normal levels 24 h after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.https://doi.org/10.1038/s41598-021-91499-3
spellingShingle Saba Gul
Flavia L. Ribeiro-Gomes
Aline S. Moreira
Guilherme S. Sanches
Fabiana G. Conceição
Cláudio Tadeu Daniel-Ribeiro
Hans C. Ackerman
Leonardo J. M. Carvalho
Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
Scientific Reports
title Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
title_full Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
title_fullStr Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
title_full_unstemmed Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
title_short Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
title_sort whole blood transfusion improves vascular integrity and increases survival in artemether treated experimental cerebral malaria
url https://doi.org/10.1038/s41598-021-91499-3
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