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 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.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

“…The effect of plasma transfusion was also assessed. The results show that adjunctive treatment with whole blood via the intravenous route achieved survival rates of 90%, compared to 76% via the intraperitoneal route as previously described; 15 furthermore, the intravenous route was associated with improved recovery of clinical indicators of hematological and vascular health.…”

“…Prior work has demonstrated the therapeutic efficacy of whole blood transfusion in PbA-infected C57BL/6 mice with ECM, using intraperitoneal route for blood administration, resulting in 76% survival compared to 51% survival in ECM mice receiving artemether only. 15 In the previous study, the intraperitoneal route of transfusion was chosen as a proof of concept due to the difficulties of performing intravenous injection of large volumes in mice with ECM. However, clinically, blood transfusion is normally given via the intravenous route, and thus a solution was achieved by means of intrajugular injection.…”

“…The volume transfused (200 μL, approximately equivalent to 10 mL/kg) was previously defined. 15 Artemether 20 mg/mL (Dafra Pharma GmbH, Basel, Switzerland) was injected intraperitoneally at 20 mg/kg. 25 Healthy uninfected mice as well as untreated mice with ECM were studied for comparison.…”

“… 13 , 14 A similar association was reported in artemether-treated murine experimental cerebral malaria (ECM) in which intraperitoneal whole blood administered in the symptomatic late stages of the infection restored hematocrit, preserved vascular integrity, and increased survival. 15 The beneficial effects of intraperitoneal whole blood transfusion in ECM go hand-in-hand with prior evidence indicating that adjunctive therapies that restore vascular function are beneficial as adjunctive therapy in ECM. 16 , 17 , 18 , 19 …”

Malaria Related Neurocognitive Deficits and Behavioral Alterations

“…Several in vivo experimental studies have performed interventions before infection or associated with antimalarial treatmentin an attempt to improve clinical response, increase survival and reduce neurocognitive and behavioral impairments (Varo et al, 2018;Gul et al, 2021). Serghides et al (2014) got compelling effects of rosiglitazone, a PPARɣ agonist, as an adjuvant treatment of ECM.…”