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An update on cerebral malaria for therapeutic intervention

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Abstract

Background

Cerebral malaria is often pronounced as a major life-threatening neurological complication of Plasmodium falciparum infection. The complex pathogenic landscape of the parasite and the associated neurological complications are still not elucidated properly. The growing concerns of drugresistant parasite strains along with the failure of anti-malarial drugs to subdue post-recovery neuro-cognitive dysfunctions in cerebral malaria patients have called for a demand to explore novel biomarkers and therapeutic avenues. Due course of the brain infection journey of the parasite, events such as sequestration of infected RBCs, cytoadherence, inflammation, endothelial activation, and blood–brain barrier disruption are considered critical.

Methods

In this review, we briefly summarize the diverse pathogenesis of the brain-invading parasite associated with loss of the blood-brain barrier integrity. In addition, we also discuss proteomics, transcriptomics, and bioinformatics strategies to identify an array of new biomarkers and drug candidates.

Conclusion

A proper understanding of the parasite biology and mechanism of barrier disruption coupled with emerging state-of-art therapeutic approaches could be helpful to tackle cerebral malaria.

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References

  1. Idro R, Jenkins NE, Newton CRJ (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 4:827–840. https://doi.org/10.1016/S1474-4422(05)70247-7

    Article  PubMed  Google Scholar 

  2. Idro R, Ndiritu M, Ogutu B et al (2007) Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children. JAMA 297:2232–2240. https://doi.org/10.1001/jama.297.20.2232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Snow RW, Guerra CA, Noor AM et al (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434:214–217. https://doi.org/10.1038/nature03342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. World Health Organization (2000) Severe falciparum malaria. Trans R Soc Trop Med Hyg 94:1–90. https://doi.org/10.1016/S0035-9203(00)90300-6

    Article  Google Scholar 

  5. Hawkes M, Elphinstone RE, Conroy AL, Kain KC (2013) Contrasting pediatric and adult cerebral malaria. Virulence 4:543–555. https://doi.org/10.4161/viru.25949

    Article  PubMed  PubMed Central  Google Scholar 

  6. Storm J, Jespersen JS, Seydel KB et al (2019) Cerebral malaria is associated with differential cytoadherence to brain endothelial cells. EMBO Mol Med 11(2):e9164

    Article  PubMed  PubMed Central  Google Scholar 

  7. Storm J, Craig AG (2014) Pathogenesis of cerebral malaria—inflammation and cytoadherence. Front Cell Infect Microbiol 4:100

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nishanth G, Schlüter D (2019) Blood–brain barrier in cerebral malaria: pathogenesis and therapeutic intervention. Trend Parasitol 35:516–528. https://doi.org/10.1016/j.pt.2019.04.010

    Article  CAS  Google Scholar 

  9. van der Heyde HC, Nolan J, Combes V et al (2006) A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trend Parasitol 22:503–508. https://doi.org/10.1016/j.pt.2006.09.002

    Article  CAS  Google Scholar 

  10. Kadry H, Noorani B, Cucullo L (2020) A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barrier CNS 17:69. https://doi.org/10.1186/s12987-020-00230-3

    Article  Google Scholar 

  11. Adams Y, Olsen RW, Bengtsson A et al (2021) Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood–brain barrier in cerebral malaria. J Exp Med 218:e20201266. https://doi.org/10.1084/jem.20201266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tunon-Ortiz A, Lamb TJ (2019) Blood brain barrier disruption in cerebral malaria: beyond endothelial cell activation. PLoS Pathog 15:e1007786. https://doi.org/10.1371/journal.ppat.1007786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ponsford MJ, Medana IM, Prapansilp P et al (2012) Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis 205:663–671. https://doi.org/10.1093/infdis/jir812

    Article  PubMed  Google Scholar 

  14. Brown A, Turner L, Christoffersen S et al (2013) Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1. J Biol Chem 288:5992–6003. https://doi.org/10.1074/jbc.M112.416347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hsieh F-L, Turner L, Bolla JR et al (2016) The structural basis for CD36 binding by the malaria parasite. Nat Commun 7:12837. https://doi.org/10.1038/ncomms12837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lennartz F, Adams Y, Bengtsson A et al (2017) Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria. Cell Host Microbe 21:403–414. https://doi.org/10.1016/j.chom.2017.02.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Marion A, Maria B, Maxwell B et al (2016) Interaction between endothelial protein c receptor and intercellular adhesion molecule 1 to mediate binding of Plasmodium falciparum-infected erythrocytes to endothelial cells. MBio 7:e00615-e616. https://doi.org/10.1128/mBio.00615-16

    Article  Google Scholar 

  18. Faille D, Combes V, Mitchell AJ et al (2009) Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. FASEB J 23:3449–3458. https://doi.org/10.1096/fj.09-135822

    Article  CAS  PubMed  Google Scholar 

  19. Wassmer SC, Combes V, Grau GER (2011) Platelets and microparticles in cerebral malaria: the unusual suspects. Drug Discov Today Dis Mech 8:e15–e23. https://doi.org/10.1016/j.ddmec.2011.11.004

    Article  CAS  Google Scholar 

  20. Hochman SE, Madaline TF, Wassmer SC et al (2015) Fatal pediatric cerebral malaria is associated with intravascular monocytes and platelets that are increased with HIV coinfection. MBio 6(5):e01390-e1415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gramaglia I, Velez J, Combes V et al (2017) Platelets activate a pathogenic response to blood-stage Plasmodium infection but not a protective immune response. Blood 129:1669–1679. https://doi.org/10.1182/blood-2016-08-733519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sierro F, Grau GER (2019) The ins and outs of cerebral malaria pathogenesis: immunopathology, extracellular vesicles, immunometabolism, and trained immunity. Front Immunol 10:830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Burns AL, Dans MG, Balbin JM et al (2019) Targeting malaria parasite invasion of red blood cells as an antimalarial strategy. FEMS Microbiol Rev 43:223–238. https://doi.org/10.1093/femsre/fuz005

    Article  CAS  PubMed  Google Scholar 

  24. Mejia P, Treviño-Villarreal JH, Reynolds JS et al (2017) A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration. Malar J 16:455. https://doi.org/10.1186/s12936-017-2092-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cariaco Y, Lima WR, Sousa R et al (2018) Ethanolic extract of the fungus Trichoderma stromaticum decreases inflammation and ameliorates experimental cerebral malaria in C57BL/6 mice. Sci Rep 8:1547. https://doi.org/10.1038/s41598-018-19840-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Saiwaew S, Sritabal J, Piaraksa N et al (2017) Effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum infected erythrocytes. PLoS ONE 12:e0172718. https://doi.org/10.1371/journal.pone.0172718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Leitgeb AM, Charunwatthana P, Rueangveerayut R et al (2017) Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria. PLoS ONE 12:e0188754. https://doi.org/10.1371/journal.pone.0188754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Taoufiq Z, Pino P, N’dilimabaka N et al (2011) Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage. Malar J 10:52. https://doi.org/10.1186/1475-2875-10-52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Franke-Fayard B, Janse CJ, Cunha-Rodrigues M et al (2005) Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci USA 102:11468–11473. https://doi.org/10.1073/pnas.0503386102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bernabeu M, Smith JD (2017) EPCR and malaria severity: the center of a perfect storm. Trend Parasitol 33:295–308. https://doi.org/10.1016/j.pt.2016.11.004

    Article  Google Scholar 

  31. Kessler A, Dankwa S, Bernabeu M et al (2017) Linking EPCR-binding PfEMP1 to brain swelling in pediatric cerebral malaria. Cell Host Microbe 22:601-614.e5. https://doi.org/10.1016/j.chom.2017.09.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mandala WL, Msefula CL, Gondwe EN et al (2017) Cytokine profiles in malawian children presenting with uncomplicated malaria, severe malarial anemia, and cerebral malaria. Clin Vaccine Immunol 24:e00533-e616. https://doi.org/10.1128/CVI.00533-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dunst J, Kamena F, Matuschewski K (2017) Cytokines and chemokines in cerebral malaria pathogenesis. Front Cell Infect Microbiol 7:324

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sorensen EW, Lian J, Ozga AJ et al (2018) CXCL10 stabilizes T cell–brain endothelial cell adhesion leading to the induction of cerebral malaria. JCI Insight. https://doi.org/10.1172/jci.insight.98911

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wilson NO, Solomon W, Anderson L et al (2013) Pharmacologic inhibition of CXCL10 in combination with anti-malarial therapy eliminates mortality associated with murine model of cerebral malaria. PLoS ONE 8:e60898. https://doi.org/10.1371/journal.pone.0060898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gun SY, Claser C, Teo TH et al (2018) Interferon regulatory factor 1 is essential for pathogenic CD8+ T cell migration and retention in the brain during experimental cerebral malaria. Cell Microbiol 20:e12819. https://doi.org/10.1111/cmi.12819

    Article  CAS  PubMed  Google Scholar 

  37. Schmidt KE, Kuepper JM, Schumak B et al (2018) Doxycycline inhibits experimental cerebral malaria by reducing inflammatory immune reactions and tissue-degrading mediators. PLoS ONE 13:e0192717. https://doi.org/10.1371/journal.pone.0192717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Crowley VM, Ayi K, Lu Z et al (2017) Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria. Malar J 16:463. https://doi.org/10.1186/s12936-017-2109-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Engwerda CR, Mynott TL, Sawhney S et al (2002) Locally up-regulated lymphotoxin α, not systemic tumor necrosis factor α, is the principle mediator of murine cerebral malaria. J Exp Med 195:1371–1377. https://doi.org/10.1084/jem.20020128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lell B, Köhler C, Wamola B et al (2010) Pentoxifylline as an adjunct therapy in children with cerebral malaria. Malar J 9:368. https://doi.org/10.1186/1475-2875-9-368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schmid U, Stenzel W, Koschel J et al (2017) The deubiquitinating enzyme cylindromatosis dampens CD8+ T cell responses and is a critical factor for experimental cerebral malaria and blood–brain barrier damage. Front Immunol 1(8):27

    Google Scholar 

  42. Swanson PA II, Hart GT, Russo MV et al (2016) CD8+ T cells induce fatal brainstem pathology during cerebral malaria via luminal antigen-specific engagement of brain vasculature. PLoS Pathog 12:e1006022. https://doi.org/10.1371/journal.ppat.1006022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Niewold P, Cohen A, van Vreden C et al (2018) Experimental severe malaria is resolved by targeting newly-identified monocyte subsets using immune-modifying particles combined with artesunate. Commun Biol 1:227. https://doi.org/10.1038/s42003-018-0216-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schumak B, Klocke K, Kuepper JM et al (2015) Specific depletion of Ly6Chi inflammatory monocytes prevents immunopathology in experimental cerebral malaria. PLoS ONE 10:e0124080. https://doi.org/10.1371/journal.pone.0124080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Besnard A-G, Guabiraba R, Niedbala W et al (2015) IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid Cells, M2 macrophages and regulatory T cells. PLoS Pathog 11:e1004607. https://doi.org/10.1371/journal.ppat.1004607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pankoui Mfonkeu JB, Gouado I, Fotso Kuaté H et al (2010) Elevated cell-specific microparticles are a biological marker for cerebral dysfunctions in human severe malaria. PLoS ONE 5:e13415. https://doi.org/10.1371/journal.pone.0013415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Piguet PF, Kan CD, Vesin C (2002) Thrombocytopenia in an animal model of malaria is associated with an increased caspase-mediated death of thrombocytes. Apoptosis 7:91–98. https://doi.org/10.1023/A:1014341611412

    Article  CAS  PubMed  Google Scholar 

  48. Combes V, Taylor TE, Juhan-Vague I et al (2004) Circulating endothelial microparticles in malawian children with severe falciparum malaria complicated with coma. JAMA 291:2542–2544. https://doi.org/10.1001/jama.291.21.2542-b

    Article  CAS  PubMed  Google Scholar 

  49. Dandewad V, Vindu A, Joseph J, Seshadri V (2019) Import of human miRNA-RISC complex into Plasmodium falciparum and regulation of the parasite gene expression. J Biosci 44:50. https://doi.org/10.1007/s12038-019-9870-x

    Article  CAS  PubMed  Google Scholar 

  50. Ye W, Chew M, Hou J et al (2018) Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLoS Pathog 14:e1007298. https://doi.org/10.1371/journal.ppat.1007298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wheway J, Latham SL, Combes V, Grau GER (2014) Endothelial microparticles interact with and support the proliferation of T cells. J Immunol 193:3378–3387. https://doi.org/10.4049/jimmunol.1303431

    Article  CAS  PubMed  Google Scholar 

  52. Sisquella X, Ofir-Birin Y, Pimentel MA et al (2017) Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors. Nat Commun 8:1985. https://doi.org/10.1038/s41467-017-02083-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. El-Assaad F, Wheway J, Hunt NH et al (2014) Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria. PLoS Pathog 10:e1003839. https://doi.org/10.1371/journal.ppat.1003839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Penet M-F, Abou-Hamdan M, Coltel N et al (2008) Protection against cerebral malaria by the low-molecular-weight thiol pantethine. Proc Natl Acad Sci USA 105(44):1321–1326. https://doi.org/10.1073/pnas.0706867105

    Article  PubMed  PubMed Central  Google Scholar 

  55. Nantakomol D, Dondorp AM, Krudsood S et al (2011) Circulating red cell-derived microparticles in human malaria. J Infect Dis 203:700–706. https://doi.org/10.1093/infdis/jiq104

    Article  PubMed  PubMed Central  Google Scholar 

  56. Combes V, Coltel N, Alibert M et al (2005) ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166:295–302. https://doi.org/10.1016/S0002-9440(10)62253-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cohen A, Zinger A, Tiberti N et al (2018) Differential plasma microvesicle and brain profiles of microRNA in experimental cerebral malaria. Malar J 17:192. https://doi.org/10.1186/s12936-018-2330-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ketprasit N, Cheng IS, Deutsch F et al (2020) The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients. Malar J 19:285. https://doi.org/10.1186/s12936-020-03360-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Barker KR, Lu Z, Kim H et al (2017) miR-155 modifies inflammation, endothelial activation and blood–brain barrier dysfunction in cerebral malaria. Mol Med 23:24–33. https://doi.org/10.2119/molmed.2016.00139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ghosh S, Sengupta A, Sharma S, Sonawat HM (2012) Metabolic fingerprints of serum, brain, and liver are distinct for mice with cerebral and noncerebral malaria: a 1H NMR spectroscopy-based metabonomic study. J Proteome Res 11:4992–5004. https://doi.org/10.1021/pr300562m

    Article  CAS  PubMed  Google Scholar 

  61. Hunt NH, Manduci N, Thumwood CM (1993) Amelioration of murine cerebral malaria by dietary restriction. Parasitology 107:471–476. https://doi.org/10.1017/S0031182000068049

    Article  PubMed  Google Scholar 

  62. Mejia P, Treviño-Villarreal JH, Hine C et al (2015) Dietary restriction protects against experimental cerebral malaria via leptin modulation and T-cell mTORC1 suppression. Nat Commun 6:6050. https://doi.org/10.1038/ncomms7050

    Article  PubMed  Google Scholar 

  63. Gordon EB, Hart GT, Tran TM et al (2015) Targeting glutamine metabolism rescues mice from late-stage cerebral malaria. Proc Natl Acad Sci USA 112:13075–13080. https://doi.org/10.1073/pnas.1516544112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang A, Huen SC, Luan HH et al (2018) Glucose metabolism mediates disease tolerance in cerebral malaria. Proc Natl Acad Sci USA 115:11042–11047. https://doi.org/10.1073/pnas.1806376115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zuzarte-Luís V, Mello-Vieira J, Marreiros IM et al (2017) Dietary alterations modulate susceptibility to Plasmodium infection. Nat Microbiol 2:1600–1607. https://doi.org/10.1038/s41564-017-0025-2

    Article  CAS  PubMed  Google Scholar 

  66. Holmberg D, Franzén-Röhl E, Idro R et al (2017) Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria. Malar J 16:303. https://doi.org/10.1186/s12936-017-1954-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Guillemin GJ (2012) Quinolinic acid, the inescapable neurotoxin. FEBS J 279:1356–1365. https://doi.org/10.1111/j.1742-4658.2012.08485.x

    Article  CAS  PubMed  Google Scholar 

  68. Bosco MC, Rapisarda A, Massazza S et al (2000) The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages. J Immunol 164:3283–3291. https://doi.org/10.4049/jimmunol.164.6.3283

    Article  CAS  PubMed  Google Scholar 

  69. Mathema VB, Na-Bangchang K (2015) A brief review on biomarkers and proteomic approach for malaria research. Asian Pac J Trop Med 8:253–262. https://doi.org/10.1016/S1995-7645(14)60327-8

    Article  CAS  PubMed  Google Scholar 

  70. Swearingen KE, Lindner SE (2018) Plasmodium parasites viewed through proteomics. Trend Parasitol 34:945–960. https://doi.org/10.1016/j.pt.2018.08.003

    Article  CAS  Google Scholar 

  71. Galassie AC, Link AJ (2015) Proteomic contributions to our understanding of vaccine and immune responses. Proteomics Clin Appl 9(11–12):972–989. https://doi.org/10.1002/prca.201500054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nilsson Bark SK, Ahmad R, Dantzler K et al (2018) Quantitative proteomic profiling reveals novel Plasmodium falciparum surface antigens and possible vaccine candidates. Mol Cell Proteomics 17:43–60. https://doi.org/10.1074/mcp.RA117.000076

    Article  CAS  PubMed  Google Scholar 

  73. Bachmann J, Burté F, Pramana S et al (2014) Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria. PLoS Pathog 10:e1004038. https://doi.org/10.1371/journal.ppat.1004038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gitau EN, Kokwaro GO, Karanja H et al (2013) Plasma and cerebrospinal proteomes from children with cerebral malaria differ from those of children with other encephalopathies. J Infect Dis 208:1494–1503. https://doi.org/10.1093/infdis/jit334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang Y, Huang C, Kim S et al (2015) Multiple stiffening effects of nanoscale knobs on human red blood cells infected with Plasmodium falciparum malaria parasite. Proc Natl Acad Sci USA 112:6068–6073. https://doi.org/10.1073/pnas.1505584112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Florens L, Liu X, Wang Y et al (2004) Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes. Mol Biochem Parasitol 135:1–11. https://doi.org/10.1016/j.molbiopara.2003.12.007

    Article  CAS  PubMed  Google Scholar 

  77. Bertin GI, Sabbagh A, Argy N et al (2016) Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria. Sci Rep 6:26773. https://doi.org/10.1038/srep26773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kumar M, Varun CN, Dey G et al (2018) Identification of host-response in cerebral malaria patients using quantitative proteomic analysis. Proteomics Clin Appl 12(4):1600187

    Article  Google Scholar 

  79. Abdi AI, Yu L, Goulding D et al (2017) Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome. Wellcome Open Res 2:50

    Article  PubMed  PubMed Central  Google Scholar 

  80. Mantel P-Y, Hoang AN, Goldowitz I et al (2013) Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 13:521–534. https://doi.org/10.1016/j.chom.2013.04.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Boldt ABW, van Tong H, Grobusch MP et al (2019) The blood transcriptome of childhood malaria. EBioMedicine 40:614–625. https://doi.org/10.1016/j.ebiom.2018.12.055

    Article  PubMed  PubMed Central  Google Scholar 

  82. Beri D, Ramdani G, Balan B et al (2019) Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria. Sci Rep 9:2875. https://doi.org/10.1038/s41598-018-37816-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Moussa E, Huang H, Ahras M et al (2018) Proteomic profiling of the brain of mice with experimental cerebral malaria. J Proteomics 180:61–69. https://doi.org/10.1016/j.jprot.2017.06.002

    Article  CAS  PubMed  Google Scholar 

  84. Moussa EM, Huang H, Thézénas ML et al (2018) Proteomic profiling of the plasma of Gambian children with cerebral malaria. Malar J 17:337. https://doi.org/10.1186/s12936-018-2487-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sampaio NG, Cheng L, Eriksson EM (2017) The role of extracellular vesicles in malaria biology and pathogenesis. Malar J 16:245. https://doi.org/10.1186/s12936-017-1891-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Thiam A, Sanka M, Ndiaye Diallo R et al (2019) Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in senegal. BMC Med Genomic 12:148. https://doi.org/10.1186/s12920-019-0599-z

    Article  CAS  Google Scholar 

  87. Almelli T, Nuel G, Bischoff E et al (2014) Differences in gene transcriptomic pattern of Plasmodium falciparum in children with cerebral malaria and asymptomatic carriers. PLoS ONE 9:e114401. https://doi.org/10.1371/journal.pone.0114401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nambou K, Nie X, Tong Y, Anakpa M (2021) Weighted gene co-expression network analysis and drug–gene interaction bioinformatics uncover key genes associated with various presentations of malaria infection in african children and major drug candidates. Infect Genet Evol 89:104723. https://doi.org/10.1016/j.meegid.2021.104723

    Article  CAS  PubMed  Google Scholar 

  89. Nallandhighal S, Park GS, Ho Y-Y et al (2019) Whole-blood transcriptional signatures composed of erythropoietic and NRF2-regulated genes differ between cerebral malaria and severe malarial anemia. J Infect Dis 219:154–164. https://doi.org/10.1093/infdis/jiy468

    Article  CAS  PubMed  Google Scholar 

  90. Oakley MS, Anantharaman V, Venancio TM et al (2011) Molecular correlates of experimental cerebral malaria detectable in whole blood. Infect Immun 79:1244–1253. https://doi.org/10.1128/IAI.00964-10

    Article  CAS  PubMed  Google Scholar 

  91. Malaria Genomic Epidemiology Network (2019) Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa. Asia Ocean Nat Commun 10:5732. https://doi.org/10.1038/s41467-019-13480-z

    Article  CAS  Google Scholar 

  92. Damena D, Denis A, Golassa L, Chimusa ER (2019) Genome-wide association studies of severe P. falciparum malaria susceptibility progress, pitfalls and prospects. BMC Med Genomics 12(1):120

    Article  PubMed  PubMed Central  Google Scholar 

  93. Tan QW, Mutwil M (2020) Malaria.tools—comparative genomic and transcriptomic database for Plasmodium species. Nucleic Acid Res 48:D768–D775. https://doi.org/10.1093/nar/gkz662

    Article  CAS  PubMed  Google Scholar 

  94. Aurrecoechea C, Brestelli J, Brunk BP et al (2009) PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acid Res 37:D539–D543. https://doi.org/10.1093/nar/gkn814

    Article  CAS  PubMed  Google Scholar 

  95. Rout S, Mahapatra RK (2019) In silico analysis of Plasmodium falciparum CDPK5 protein through molecular modeling, docking and dynamics. J Theor Biol 461:254–267. https://doi.org/10.1016/j.jtbi.2018.10.045

    Article  CAS  PubMed  Google Scholar 

  96. Rout S, Mahapatra RK (2019) In silico study of M18 aspartyl amino peptidase (M18AAP) of Plasmodium vivax as an antimalarial drug target. Bioorg Med Chem 27:2553–2571. https://doi.org/10.1016/j.bmc.2019.03.039

    Article  CAS  PubMed  Google Scholar 

  97. Rout S, Warhurst DC, Suar M, Mahapatra RK (2015) In silico comparative genomics analysis of Plasmodium falciparum for the identification of putative essential genes and therapeutic candidates. J Microbiol Method 109:1–8. https://doi.org/10.1016/j.mimet.2014.11.016

    Article  CAS  Google Scholar 

  98. Liu X, Wang Y, Liang J et al (2018) In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome. BMC Genomics 19:312. https://doi.org/10.1186/s12864-018-4654-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Liu X, Wu Y, Zhao Y et al (2021) Identification of Plasmodium falciparum-specific protein PIESP2 as a novel virulence factor related to cerebral malaria. Int J Biol Macromol 177:535–547. https://doi.org/10.1016/j.ijbiomac.2021.02.145

    Article  CAS  PubMed  Google Scholar 

  100. Talundzic E, Ravishankar S, Kelley J et al (2018) Next-generation sequencing and bioinformatics protocol for malaria drug resistance marker surveillance. Antimicrob Agent Chemother 62:e02474-e2517. https://doi.org/10.1128/AAC.02474-17

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, Odisha, 751024, India

    Chinmaya Panda & Rajani Kanta Mahapatra

  2. Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India

    Chinmaya Panda

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  1. Chinmaya Panda
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  2. Rajani Kanta Mahapatra
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Correspondence to Rajani Kanta Mahapatra.

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Panda, C., Mahapatra, R.K. An update on cerebral malaria for therapeutic intervention. Mol Biol Rep 49, 10579–10591 (2022). https://doi.org/10.1007/s11033-022-07625-5

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