Cerebral malaria – clinical manifestations and pathogenesis

Metabolic Brain Disease

Volumn 31, Issue 2, 2016, Pages 225-237

  Hora, Rachna ^a   Kapoor, Payal ^a   Thind, Kirandeep Kaur ^a   Mishra, Prakash Chandra ^a  

^a GURU NANAK DEV UNIVERSITY   (India)

Author keywords

Cerebral malaria; Cytoadherence; Neuroinflammation; Neurological deficits

Indexed keywords

NITRIC OXIDE;

APOPTOSIS; BIOAVAILABILITY; BLOOD BRAIN BARRIER; BRAIN MALARIA; CELL ACTIVATION; CLINICAL FEATURE; COGNITIVE DEFECT; COMA; ENDOTHELIUM CELL; EPILEPTIC STATE; HUMAN; IMMUNE RESPONSE; MOLECULAR PATHOLOGY; NERVOUS SYSTEM INFLAMMATION; NEUROLOGICAL COMPLICATION; NONHUMAN; PAPILLEDEMA; PATHOGENESIS; RETINOPATHY; REVIEW; SEIZURE; THROMBOCYTE ACTIVATION; ANIMAL; CEREBRAL MALARIA; DISEASE MODEL; INFLAMMATION; METABOLISM; PATHOLOGY; PLASMODIUM FALCIPARUM;

ANIMALS; BLOOD-BRAIN BARRIER; DISEASE MODELS, ANIMAL; HUMANS; INFLAMMATION; MALARIA, CEREBRAL; NITRIC OXIDE; PLASMODIUM FALCIPARUM;

EID: 84961172915     PISSN: 08857490     EISSN: 15737365     Source Type: Journal    
DOI: 10.1007/s11011-015-9787-5     Document Type: Review

References (138)

1. Anstey NM et al (1996) Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med 184:557–567
2. Armah H, Wiredu EK, Dodoo AK, Adjei AA, Tettey Y, Gyasi R (2005) Cytokines and adhesion molecules expression in the brain in human cerebral malaria. Int J Environ Res Public Health 2:123–131
3. Bachmann J et al (2014) Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria. PLoS Pathog 10:e1004038
4. Bangirana P et al (2014) Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis:ciu293
5. Barbier M et al (2011) Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. PLoS One 6:e19651
6. Barfod A, Persson T, Lindh J (2009) In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1. Parasitol Res 105:1557–1566
7. Beare NA, Southern C, Chalira C, Taylor TE, Molyneux ME, Harding SP (2004) Prognostic significance and course of retinopathy in children with severe malaria. Arch Ophthalmol 122:1141–1147
8. Beare NA, Taylor TE, Harding SP, Lewallen S, Molyneux ME (2006) Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg 75:790–797
9. Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME (2009) Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 199:263–271
10. Beeson JG et al (2000) Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nat Med 6:86–90
11. Berendt A, Simmons D, Tansey J, Newbold C, Marsh K (1989) Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341:57–59
12. Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, John CC (2007) Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics 119:e360–e366
13. Boivin MJ, Vokhiwa M, Sikorskii A, Magen JG, Beare N (2014) Cerebral malaria retinopathy predictors of persisting neurocognitive outcomes in Malawian children. Pediatr Infect Dis J
14. Bridges DJ et al (2010) Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings. Blood 115:1472–1474
15. Brown GC (2001) Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta (BBA)-Bioenergetics 1504:46–57
16. Brown H, Rogerson S, Taylor T, Tembo M, Mwenechanya J, Molyneux M, Turner G (2001) Blood–brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg 64:207–213
17. Buchanan JE, Phillis JW (1993) The role of nitric oxide in the regulation of cerebral blood flow. Brain Res 610:248–255
18. Cabrales P, Zanini GM, Meays D, Frangos JA, Carvalho LJ (2011) Nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology. J Infect Dis:jir058
19. Carter J, Murira G, Ross A, Mung’ala-Odera V, Newton C (2003) Speech and language sequelae of severe malaria in Kenyan children. Brain Inj 17:217–224
20. Carter JA, Mung’ala-Odera V, Neville BG, Murira G, Mturi N, Musumba C, Newton CR (2005) Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry 76:476–481. doi:10.1136/jnnp.2004.043893
21. Carter JA, Lees JA, Gona JK, Murira G, Rimba K, Neville BG, Newton CR (2006) Severe falciparum malaria and acquired childhood language disorder. Dev Med Child Neurol 48:51–57
22. Charunwatthana P, Faiz MA, Ruangveerayut R, Maude R, Rahman MR, Roberts LJ (2009) N-acetylcysteine as adjunctive treatment in severe malaria: a randomized double blinded placebo controlled clinical trial. Crit Care Med 37:516
23. Combes V et al (2004) Circulating endothelial microparticles in malawian children with severe falciparum malaria complicated with coma. JAMA 291:2542–2544
24. Combes V et al (2005) ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166:295–302
25. Conroy AL et al (2010) Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case–control study. PLoS One 5:e15291
26. Cooke BM, Berendt AR, Craig AG, MacGregor J, Newbold CI, Nash GB (1994) Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin. Br J Haematol 87:162–170
27. Cramer JP et al (2005) Age dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria. Tropical Med Int Health 10:672–680
28. Crawley J, Smith S, Muthinji P, Marsh K, Kirkham F (2001) Electroencephalographic and clinical features of cerebral malaria. Arch Dis Child 84:247–253
29. de Miranda AS et al (2015) Evidence for the contribution of adult neurogenesis and hippocampal cell death in experimental cerebral malaria cognitive outcome. Neuroscience 284:920–933
30. Dondorp AM, Kager PA, Vreeken J, White NJ (2000) Abnormal blood flow and red blood cell deformability in severe malaria. Parasitol Today 16:228–232
31. Duraisingh MT et al (2005) Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in plasmodium falciparum. Cell 121:13–24
32. El-Assaad F, Wheway J, Hunt NH, Grau GER, Combes V (2014) Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria. PLoS Pathog 10:e1003839
33. English M, Waruiru C, Lightowler C, Murphy S, Kirigha G, Marsh K (1996) Hyponatraemia and dehydration in severe malaria. Arch Dis Child 74:201–205
34. English M, Sauerwein R, Waruiru C, Mosobo M, Obiero J, Lowe B, Marsh K (1997) Acidosis in severe childhood malaria. QJM 90:263–270
35. English M, Wale S, Binns G, Mwangi I, Sauerwein H, Marsh K (1998) Hypoglycaemia on and after admission in Kenyan children with severe malaria. QJM 91:191–197
36. Epp C, Li F, Howitt CA, Chookajorn T, Deitsch KW (2009) Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum. RNA 15:116–127
37. Favre N et al (1999) Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect 1:961–968
38. Fiedler U et al (2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12:235–239
39. Freitas-Junior LH et al (2000) Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407:1018–1022
40. Freitas-Junior LH et al (2005) Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 121:25–36
41. Fried M, Duffy PE (1996) Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:1502–1504
42. Furlan M, Robles R, Lamie B (1996) Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 87:4223–4234
43. Gallo EF, Iadecola C (2011) Neuronal nitric oxide contributes to neuroplasticity-associated protein expression through cGMP, protein kinase G, and extracellular signal-regulated kinase. J Neurosci 31:6947–6955
44. Gramaglia I et al (2006) Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 12:1417–1422
45. Grau GE, Piguet PF, Gretener D, Vesin C, Lambert PH (1988) Immunopathology of thrombocytopenia in experimental malaria. Immunology 65:501
46. Grau GE, Tacchini-Cottier F, Vesin C, Milon G, Lou JN, Piguet PF, Juillard P (1992) TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction. Eur Cytokine Netw 4:415–419
47. Grau GE et al (2003) Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 187:461–466
48. Guha SK et al (2014) Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior. Brain Behav Immun 42:123–137
49. Gyan B et al (2009) Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children. AmJTrop Med Hyg 80:541–546
50. Havlik I et al (2005) Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 99:333–340
51. Hemmer CJ, Kern P, Holst FG, Nawroth PP, Dietrich M (1991) Neither heparin nor acetylsalicylic acid influence the clinical course in human Plasmodium falciparum malaria: a prospective randomized study. Am J Trop Med Hyg 45:608–612
52. Hempel C, Hyttel P, Staalso T, Nyengaard JR, Kurtzhals JAL (2012) Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria. Malar J 11:216
53. Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano C, Haldar K (2004) A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306:1934–1937
54. Hiratsuka M, Katayama T, Uematsu K, Kiyomura M, Ito M (2009) In vivo visualization of nitric oxide and interactions among platelets, leukocytes, and endothelium following hemorrhagic shock and reperfusion. Inflamm Res 58:463–471
55. Hossain M, Qadri SM, Liu L (2012) Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature. J Inflamm 9:28–35
56. Idro R, Karamagi C, Tumwine J (2004) Immediate outcome and prognostic factors for cerebral malaria among children admitted to Mulago Hospital Uganda. Ann Trop Paediatr: Int Child Health 24:17–24
57. Idro R, Jenkins NE, Newton CR (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 4:827–840
58. Idro R, Carter JA, Fegan G, Neville BGR, Newton CRJC (2006) Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Arch Dis Child 91:142–148
59. Idro R, Kakooza-Mwesige A, Balyejjussa S, Mirembe G, Mugasha C, Tugumisirize J, Byarugaba J (2010) Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res Notes 3:104
60. Jain K, Sood S, Gowthamarajan K (2013) Modulation of cerebral malaria by curcumin as an adjunctive therapy. Braz J Infect Dis 17:579–591
61. John CC et al (2008) Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122:e92–e99
62. John CC, Kutamba E, Mugarura K, Opoka RO (2010) Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium falciparum malaria 8(9):997–1008
63. Kawachi S, Leffer DJ, Van Der Heyde HC, Laroux S, Gray L, Bharwani SS, Grisham MB (2000) Role of different nitric oxide synthese (NOS) isoforms in the regulation of endothelial cell adhesion molecule (ECAM) expression in vivo. Gastroenterology 118:A827
64. Kim H, Higgins S, Liles WC, Kain KC (2011) Endothelial activation and dysregulation in malaria: a potential target for novel therapeutics. Curr Opin Hematol 18:177–185
65. Kochar D, Kumawat B, Kochar S (1997) Seizures in cerebral malaria. QJM 90:605–607
66. Kochar DK, Kumawat BL, Vyas SP (2000) Prognostic significance of eye changes in cerebral malaria. J Assoc Physicians India 48:473–477
67. Kochar D, Kumawat B, Kochar S, Halwai M, Makkar R, Joshi A, Thanvi I (2002) Cerebral malaria in Indian adults: a prospective study of 441 patients from Bikaner, north-west India. J Assoc Physicians India 50:234–241
68. Kraisin S et al (2011) Association of ADAMTS13 polymorphism with cerebral malaria. Malar J 10:366
69. Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci 88:4651–4655
70. Lacerda MVG, Mourão MPG, Coelho HCC, Santos JB (2011) Thrombocytopenia in malaria: who cares? Mem Inst Oswaldo Cruz 106:52–63
71. Larkin D et al (2009) Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition. PLoS Pathog 5:e1000349
72. Looareesuwan S et al (1983) Retinal hemorrhage, a common sign of significance in cerebral malaria Am J Trop Med Hyg September 1983 32: 911–915. Am J Trop Med Hyg 32:1002–1012
73. Lopansri BK et al (2003) Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production. Lancet 361:676–678
74. Lopez-Rubio JJ, Gontijo AM, Nunes MC, Issar N, Hernandez Rivas R, Scherf A (2007) 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites. Mol Microbiol 66:1296–1305
75. Marchi N, Tierney W, Alexopoulos AV, Puvenna V, Granata T, Janigro D (2011) The etiological role of blood–brain barrier dysfunction in seizure disorders Cardiovascular psychiatry and neurology 2011
76. Matsushita K, Yamakuchi M, Morrell CN, Ozaki M, O’Rourke B, Irani K, Lowenstein CJ (2004) Vascular endothelial growth factor regulation of Weibel-Palade body exocytosis. Blood
77. Maude RJ et al (2009) The spectrum of retinopathy in adults with Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 103:665–671
78. Maude RJ et al. (2014) Magnetic resonance imaging of the brain in adults with severe falciparum malaria Renal failure (creatinine > 3 g/dL or anuria) 5:12
79. Mayer C, Slater L, Erat MC, Konrat R, Vakonakis I (2012) Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. J Biol Chem 287:7182–7189
80. Medana IM, Turner GDH (2006) Human cerebral malaria and the blood brain barrier. Int J Parasitol 36:555–568
81. Medana IM et al (2002) Axonal injury in cerebral malaria. Am J Pathol 160:655–666
82. Miranda AS et al (2013) Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria. Malar J 12:1–13
83. Mohanty S, Mishra SK, Pati SS, Pattnaik J, Das BS (2003) Complications and mortality patterns due to Plasmodium falciparum malaria in hospitalized adults and children, Rourkela, Orissa, India. Trans R Soc Trop Med Hyg 97:69–70
84. Molyneux M, Taylor T, Wirima J, Borgsteinj A (1989) Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. QJM 71:441–459
85. Morel O et al. (2005) [The significance of circulating microparticles in physiology, inflammatory and thrombotic diseases] La Revue de medecine interne/fondee par la Societe nationale francaise de medecine interne 26:791–801
86. Mwanga-Amumpaire J et al (2015) Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial. In: Open forum infectious diseases. Oxford University Press, p ofv111
87. Nacer A, Movila A, Baer K, Mikolajczak SA, Kappe SHI, Frevert U (2012) Neuroimmunological blood brain barrier opening in experimental cerebral malaria. PLoS Pathog 8:e1002982
88. N’Dilimabaka N et al (2014) P. Falciparum isolate-specific distinct patterns of induced apoptosis in pulmonary and brain endothelial cells. PLoS One 9:e90692
89. Newton C et al (1997) Intracranial hypertension in Africans with cerebral malaria. Arch Dis Child 76:219–226
90. Newton CR, Hien TT, White N (2000) Cerebral malaria. J Neurol Neurosurg Psychiatry 69:433–441
91. Ockenhouse CF et al (1992) Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med 176:1183–1189
92. Okoromah C, Afolabi BB, Wall E (2011) Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria. Cochrane Database Syst Rev 4
93. Olliaro P (2008) Mortality associated with severe Plasmodium falciparum malaria increases with age. Clin Infect Dis 47:158–160
94. Olumese P, Adeyemo A, Gbadegesin R, Walker O (1997) Retinal haemorrhage in cerebral malaria. East Afr Med J 74:285–287
95. Oluwayemi IO, Brown BJ, Oyedeji OA, Oluwayemi MA (2014) Neurological sequelae in survivors of cerebral malaria. Pan Afr Med J 15(1)
96. Organisation W (2013) World malaria report 2013. WHO, Geneva
97. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424
98. Penet M-F, Abou-Hamdan M, Coltel N, Cornille E, Grau GE, De Reggi M, Gharib B (2008) Protection against cerebral malaria by the low-molecular-weight thiol pantethine. Proc Natl Acad Sci 105:1321–1326
99. Percãrio S et al (2012) Oxidative stress in malaria. Int J Mol Sci 13:16346–16372
100. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1:223–236
101. Petter M et al (2011) Expression of P. falciparum var genes involves exchange of the histone variant H2A. Z at the promoter. PLoS Pathog 7:e1001292
102. Phiri HT et al (2011) Elevated plasma von Willebrand factor and propeptide levels in Malawian children with malaria. PLoS One 6:e25626
103. 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
104. Piguet PF, Da Laperrousaz C, Vesin C, Tacchini-Cottier F, Senaldi G, Grau GE (2000) Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase-and urokinase receptor-deficient mice. Infect Immun 68:3822–3829
105. Pino P et al (2003) Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 187:1283–1290
106. Pino P, Taoufiq Z, Nitcheu J, Vouldoukis I, Mazier D (2005) Blood–brain barrier breakdown during cerebral malaria: suicide or murder? THROMBOSIS AND HAEMOSTASIS-STUTTGART- 94:336
107. Pino P et al (2004) Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum infected erythrocytes. Cell Microbiol 6:839–848
108. Pongponratn E, Riganti M, Harinasuta T, Bunnag D (1985) Electron microscopy of the human brain in cerebral malaria. Southeast Asian J Trop Med Public Health 16:219–227
109. Ralph SA, Scheidig-Benatar C, Scherf A (2005) Antigenic variation in Plasmodium falciparum is associated with movement of var loci between subnuclear locations. Proc Natl Acad Sci U S A 102:5414–5419
110. Reis PA et al (2010) Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. PLoS Pathog 6:e1000963
111. Reis PA et al (2012) Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog 8:e1003099
112. Rockett KA, Awburn MM, Cowden WB, Clark IA (1991) Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun 59:3280–3283
113. Rowe JA, Claessens A, Corrigan RA, Arman M (2009) Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications. Expert Rev Mol Med 11:e16
114. Sattar MA, Hoque HW, Amin MR, Faiz MA, Rahman MR (2009) Neurological findings and outcome in adult cerebral malaria. Bangladesh Med Res Counc Bull 35:15–17
115. Schindler SM, Little JP, Klegeris A (2014) Microparticles: a New perspective in central nervous system disorders. BioMed Res Int 2014:756327
116. Senczuk AM, Reeder JC, Kosmala MM, Ho M (2001) Plasmodium falciparum erythrocyte membrane protein 1 functions as a ligand for P-selectin. Blood 98:3132–3135
117. Serirom S, Raharjo WH, Chotivanich K, Loareesuwan S, Kubes P, Ho M (2003) Anti-adhesive effect of nitric oxide on plasmodium falciparum cytoadherence under flow. Am J Pathol 162:1651–1660
118. Smith JD et al (1995) Switches in expression of plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82:101–110
119. Su X-z et al (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytes. Cell 82:89–100
120. Susomboon P et al (2006) Down-regulation of tight junction mRNAs in human endothelial cells co-cultured with Plasmodium falciparum infected erythrocytes. Parasitol Int 55:107–112
121. Toure FS et al (2008) Apoptosis: a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria. Parasite Immunol 30:47–51
122. Turner GD et al (1994) An immunohistochemical study of the pathology of fatal malaria: evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 145:1057
123. Turner GD et al (1998) Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 152:1477
124. van der Heyde HC, Nolan J, Combes V, Gramaglia I, Grau GE (2006) A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 22:503–508
125. van Hensbroek MB et al (1996) The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 174:1091–1097
126. Waller KL, Cooke BM, Nunomura W, Mohandas N, Coppel RL (1999) Mapping the binding domains involved in the interaction between the plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and the cytoadherence ligand P. FalciparumErythrocyte membrane protein 1 (PfEMP1). J Biol Chem 274:23808–23813
127. Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, Harinasuta T (1982) Dexamethasone proves deleterious in cerebral malaria: a double-blind trial in 100 comatose patients. N Engl J Med 306:313–319
128. Wassmer SC, Combes V, Candal FJ, Juhan-Vague I, Grau GE (2006a) Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect Immun 74:645–653
129. Wassmer SC, Lépolard C, Traoré B, Pouvelle B, Gysin J, Grau GE (2004) Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis 189:180–189
130. Wassmer SC, de Souza JB, Frère C, Candal FJ, Juhan-Vague I, Grau GE (2006b) TGF-beta-1 released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. J Immunol 176:1180–1184
131. Weatherall DJ, Miller LH, Baruch DI, Marsh K, Doumbo OK, Casals-Pascual C, Roberts DJ (2002) Malaria and the red cell ASH Education Program Book 2002:35–57
132. Weinberg JB, et al. (2014) Dimethylarginines: endogenous inhibitors of nitric oxide synthesis in children with falciparum malaria. J Infect Dis:jiu156
133. White NJ, Phillips RE, Looareesuwan S, Chanthavanich P, Warrell DA (1988) Single dose phenobarbitone prevents convulsions in cerebral malaria. Lancet 332:64–66
134. White VA, Lewallen S, Beare N, Kayira K, Carr RA, Taylor TE (2001) Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 95:618–621
135. World Health O (2000) Severe falciparum malaria. Trans R Soc Trop Med Hyg 94:1–90
136. Yeo TW et al (2008a) Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. J Infect Dis 198:602–608
137. Yeo TW et al (2008b) Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci 105:17097–17102
138. Zanini GM, Cabrales P, Barkho W, Frangos JA, Carvalho L (2011) Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice. J Neuroinflammation 8:66