Cerebral malaria induced by plasmodium falciparum: clinical features, pathogenesis, diagnosis, and treatment

Song, Xiaonan; Wei, Wei; Cheng, Weijia; Zhu, Huiyin; Wang, Wei; Dong, Haifeng; Li, Jian

doi:10.3389/fcimb.2022.939532

Cited by 43 publications

(32 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[29][30] Several studies showed that malaria infection triggers long-term neurological deficits such as neurobehavioral disorders, motor skills, visual acuity, and seizures. [31][32] This study demonstrated that the administration of curcumin and kaempferol could suppress the development of ECM in mice by reducing the breakdown of the BBB and the neurobehavioral disorders associated with the disease. Several studies also reported strong antioxidant and anti-inflammatory activities that can produce a protective effect in the brains of PbA-infected mice.…”

Section: Groupsmentioning

confidence: 88%

Evaluation of Experimental Cerebral Malaria of Curcumin and Kaempferol in Plasmodium berghei ANKA-Infected Mice

Alkandahri¹,

Berbudi²,

Subarnas³

2023

Pharmacogn J.

View full text Add to dashboard Cite

Background: Cerebral malaria (CM) is one of the most severe complications of Plasmodium falciparum infection and the leading cause of death from malaria in endemic areas. Natural products with antioxidant and anti-inflammatory activities have become valuable alternative therapeutic options in CM treatment. Therefore, this study aimed to investigate the neuroprotective effects of curcumin and kaempferol in experimental cerebral malaria (ECM) in mice infected with Plasmodium berghei ANKA (PbA). Methods: After PbA infection, mice were divided into 9 groups, namely Group I (negative control (NC)) with 0.5% HPMC, Group II received chloroquine 20 mg/kg, Group III (normal) with aquadest, Groups IV, V, and VI received curcumin at doses of 20, 40, and 80 mg/kg, respectively, Groups VII, VIII, and IX received kaempferol at doses of 20, 40, and 80 mg/kg, respectively. The antimalarial activity was evaluated using Peter's four-day suppressive test. This was conducted to determine the % parasitemia, survival rate, AST and ALT, blood-brain barrier (BBB) leakage, and neurobehavioral disorders in mice with CM. Results: The results showed that all treatments had significant antimalarial activity, with the % suppression depending on the dose. It also indicates that PbA-infected mice had a survival rate of 11-19 days after infection, which was higher than those in the NC group. This suggested that curcumin and kaempferol have a protective effect on the survival of PbA-infected mice. Furthermore, they significantly reduced the AST and ALT concentrations in the sample compared to the NC group. The same was observed in cerebral vessel extravasation, where the Evans Blue stain assay showed significantly less dye extravasation in the brains of PbA-infected mice treated with curcumin and kaempferol. This indicated better-protected integrity of the BBB. Additionally, the results also demonstrated a decrease in neurological disorders arising during ECM in the group treated with curcumin and kaempferol. Conclusion: Considering these results, it is concluded that treatments with curcumin and kaempferol could improve animal survival, prevent AST and ALT elevations, as well as protect the BBB and neurobehavioral disorders associated with CM in PbA-infected mice.

show abstract

Section: Groupsmentioning

confidence: 88%

Evaluation of Experimental Cerebral Malaria of Curcumin and Kaempferol in Plasmodium berghei ANKA-Infected Mice

Alkandahri¹,

Berbudi²,

Subarnas³

2023

Pharmacogn J.

View full text Add to dashboard Cite

show abstract

“…A more pronounced coma was previously described as a risk factor for death during severe malaria in children [ 28 ], in adults presenting with CM [ 29 ], and in children presenting with CM [ 30 , 31 ]. Splenomegaly is also a clinical manifestation classically described in cerebral malaria [ 32 , 33 ], although rarely identified as a risk factor for death during CM. Through the analysis of haematologic factors, we observed higher numbers of leukocytes, among which lymphocytes and monocytes were associated with CM death, indicating an increased immune response related to the infection.…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria

Royo

Vianou²,

Kinkpé³

et al. 2023

Infect Dis Poverty

View full text Add to dashboard Cite

Background Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. Methods Children presenting with CM (n = 70) due to P. falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysed by univariate analysis using the nonparametric Mann‒Whitney U test and Pearson’s Chi2 test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. Results Univariate analysis revealed higher plasma levels of tumour necrosis factor (TNF), interleukin-1beta (IL-1β), IL-10, IL-8, C-X-C motif chemokine ligand 9 (CXCL9), granzyme B, and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite (PGEM) in children who died compared to those who survived CM (Mann–Whitney U-test, P-values between 0.03 and < 0.0001). The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM (adjusted odd ratio = 14.2, P-value = 0.002). Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, C–C motif chemokine ligand 17 (CCL17), CCL22, and urinary 15-F2t-isoprostane. Conclusions The main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion. Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation, endothelium activation and damage, inflammatory and oxidative response. These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications. Graphical Abstract

show abstract

“…[28], in adults presenting with CM [29], and in children presenting with CM [30,31]. Splenomegaly is also a clinical manifestation classically described in cerebral malaria [32,33], although rarely identi ed as a risk factor for death during CM. Through the analysis of haematologic factors, we observed higher numbers of leukocytes, among which lymphocytes and monocytes were associated with CM death, indicating an increased immune response related to the infection.…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma IL-8 as a risk factor for mortality in children presenting with cerebral malaria (NeuroCM study)

Royo

Vianou

Kinkpé

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. Methods: Children presenting with CM (n = 70) due to P. falciparuminfection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examinationwas complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysedby univariate analysis using the nonparametric Mann‒Whitney U test and Chi2 Pearson test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. Results: Univariate analysis revealed that higher plasma levels of TNF, IL-1β, IL-10, IL-8, CXCL9, granzyme B, and angiopoietin-2 and lower urinary levels of PGEM were associated with CM mortality. The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM. Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, CCL17, CCL22, and urinary 15-F2t-isoprostane. Conclusions: These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

show abstract

Cerebral malaria induced by plasmodium falciparum: clinical features, pathogenesis, diagnosis, and treatment

Cited by 43 publications

References 145 publications

Evaluation of Experimental Cerebral Malaria of Curcumin and Kaempferol in Plasmodium berghei ANKA-Infected Mice

Evaluation of Experimental Cerebral Malaria of Curcumin and Kaempferol in Plasmodium berghei ANKA-Infected Mice

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria

Elevated plasma IL-8 as a risk factor for mortality in children presenting with cerebral malaria (NeuroCM study)

Contact Info

Product

Resources

About