Cerebral Malaria: Current Clinical and Immunological Aspects

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 May 6

PMID 35514965

Authors

Karin Albrecht-Schgoer

Peter Lackner

Erich Schmutzhard

Gottfried Baier

Affiliations

Soon will be listed here.

Abstract

This review focuses on current clinical and immunological aspects of cerebral malaria induced by infection. Albeit many issues concerning the inflammatory responses remain unresolved and need further investigations, current knowledge of the underlying molecular mechanisms is highlighted. Furthermore, and in the light of significant limitations in preventative diagnosis and treatment of cerebral malaria, this review mainly discusses our understanding of immune mechanisms in the light of the most recent research findings. Remarkably, the newly proposed CD8+ T cell-driven pathophysiological aspects within the central nervous system are summarized, giving first rational insights into encouraging studies with immune-modulating adjunctive therapies that protect from symptomatic cerebral participation of infection.

Citing Articles

Contribution of Magnetic Resonance Imaging Studies to the Understanding of Cerebral Malaria Pathogenesis.

Comino Garcia-Munoz A, Varlet I, Grau G, Perles-Barbacaru T, Viola A Pathogens. 2025; 13(12.

PMID: 39770302 PMC: 11728472. DOI: 10.3390/pathogens13121042.

Mouse NOD/Shi and NSY/Hos strains infected with Plasmodium berghei ANKA are models for experimental cerebral malaria.

Ohno T, Iwatake N, Miyasaka Y Exp Anim. 2024; 74(1):31-38.

PMID: 39069480 PMC: 11742482. DOI: 10.1538/expanim.24-0023.

Transcriptional responses of brain endothelium to patient-derived isolates .

Askonas C, Storm J, Camarda G, Craig A, Pain A Microbiol Spectr. 2024; 12(7):e0072724.

PMID: 38864616 PMC: 11218514. DOI: 10.1128/spectrum.00727-24.

Neurons upregulate PD-L1 via IFN/STAT1/IRF1 to alleviate damage by CD8 T cells in cerebral malaria.

Wang Y, Shen Y, Liang J, Wang S, Huang Y, Zhu Q J Neuroinflammation. 2024; 21(1):119.

PMID: 38715061 PMC: 11077882. DOI: 10.1186/s12974-024-03114-7.

Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges.

Li J, Docile H, Fisher D, Pronyuk K, Zhao L J Epidemiol Glob Health. 2024; 14(3):561-579.

PMID: 38656731 PMC: 11442732. DOI: 10.1007/s44197-024-00228-2.

References

de Azevedo-Quintanilha I, Vieira-de-Abreu A, Ferreira A, Reis P, Silva T, Nascimento D . Integrin αDβ2 influences cerebral edema, leukocyte accumulation and neurologic outcomes in experimental severe malaria. PLoS One. 2019; 14(12):e0224610. PMC: 6927624. DOI: 10.1371/journal.pone.0224610. View

Wu X, Brombacher F, Chroneos Z, Norbury C, Gowda D . IL-4Rα signaling by CD8α dendritic cells contributes to cerebral malaria by enhancing inflammatory, Th1, and cytotoxic CD8 T cell responses. J Biol Chem. 2021; 296:100615. PMC: 8100064. DOI: 10.1016/j.jbc.2021.100615. View

Taylor S, Parobek C, Fairhurst R . Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis. 2012; 12(6):457-68. PMC: 3404513. DOI: 10.1016/S1473-3099(12)70055-5. View

Hviid L, Jensen A . PfEMP1 - A Parasite Protein Family of Key Importance in Plasmodium falciparum Malaria Immunity and Pathogenesis. Adv Parasitol. 2015; 88:51-84. DOI: 10.1016/bs.apar.2015.02.004. View

Luzzatto L . Sickle cell anaemia and malaria. Mediterr J Hematol Infect Dis. 2012; 4(1):e2012065. PMC: 3499995. DOI: 10.4084/MJHID.2012.065. View

Strangward P, Haley M, Shaw T, Schwartz J, Greig R, Mironov A . A quantitative brain map of experimental cerebral malaria pathology. PLoS Pathog. 2017; 13(3):e1006267. PMC: 5358898. DOI: 10.1371/journal.ppat.1006267. View

Tanwar G, Khatri P, Sengar G, Kochar A, Kochar S, Middha S . Clinical profiles of 13 children with Plasmodium vivax cerebral malaria. Ann Trop Paediatr. 2011; 31(4):351-6. DOI: 10.1179/1465328111Y.0000000040. View

Pais T, Penha-Goncalves C . Brain Endothelium: The "Innate Immunity Response Hypothesis" in Cerebral Malaria Pathogenesis. Front Immunol. 2019; 9:3100. PMC: 6361776. DOI: 10.3389/fimmu.2018.03100. View

Ghazanfari N, Mueller S, Heath W . Cerebral Malaria in Mouse and Man. Front Immunol. 2018; 9:2016. PMC: 6139318. DOI: 10.3389/fimmu.2018.02016. View

10.

Timmann C, Thye T, Vens M, Evans J, May J, Ehmen C . Genome-wide association study indicates two novel resistance loci for severe malaria. Nature. 2012; 489(7416):443-6. DOI: 10.1038/nature11334. View

11.

Walk J, Stok J, Sauerwein R . Can Patrolling Liver-Resident T Cells Control Human Malaria Parasite Development?. Trends Immunol. 2019; 40(3):186-196. DOI: 10.1016/j.it.2019.01.002. View

12.

Ravenhall M, Campino S, Sepulveda N, Manjurano A, Nadjm B, Mtove G . Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania. PLoS Genet. 2018; 14(1):e1007172. PMC: 5806895. DOI: 10.1371/journal.pgen.1007172. View

13.

De Niz M, Ullrich A, Heiber A, Blancke Soares A, Pick C, Lyck R . The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites. Nat Commun. 2016; 7:11659. PMC: 4894950. DOI: 10.1038/ncomms11659. View

14.

Griffith J, Sokol C, Luster A . Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014; 32:659-702. DOI: 10.1146/annurev-immunol-032713-120145. View

15.

Wilson N, Jain V, Roberts C, Lucchi N, Joel P, Singh M . CXCL4 and CXCL10 predict risk of fatal cerebral malaria. Dis Markers. 2011; 30(1):39-49. PMC: 3260027. DOI: 10.3233/DMA-2011-0763. View

16.

Oquendo P, Hundt E, Lawler J, Seed B . CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989; 58(1):95-101. DOI: 10.1016/0092-8674(89)90406-6. View

17.

Karnad D, Mat Nor M, Richards G, Baker T, Amin P . Intensive care in severe malaria: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine. J Crit Care. 2017; 43:356-360. DOI: 10.1016/j.jcrc.2017.11.007. View

18.

Palomo J, Reverchon F, Piotet J, Besnard A, Couturier-Maillard A, Maillet I . Critical role of IL-33 receptor ST2 in experimental cerebral malaria development. Eur J Immunol. 2015; 45(5):1354-65. DOI: 10.1002/eji.201445206. View

19.

Spycher C, Klonis N, Spielmann T, Kump E, Steiger S, Tilley L . MAHRP-1, a novel Plasmodium falciparum histidine-rich protein, binds ferriprotoporphyrin IX and localizes to the Maurer's clefts. J Biol Chem. 2003; 278(37):35373-83. DOI: 10.1074/jbc.M305851200. View

20.

Seydel K, Kampondeni S, Valim C, Potchen M, Milner D, Muwalo F . Brain swelling and death in children with cerebral malaria. N Engl J Med. 2015; 372(12):1126-37. PMC: 4450675. DOI: 10.1056/NEJMoa1400116. View