Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

An Update on Recent Advances for the Treatment of Cerebral Malaria

Author(s): Deepika Purohit, Sahil Kumar*, Rohit Dutt and Tilak Raj Bhardwaj

Volume 22, Issue 12, 2022

Published on: 17 January, 2022

Page: [1607 - 1618] Pages: 12

DOI: 10.2174/1389557521666211124143117

Price: $65

Open Access Journals Promotions 2
Abstract

Among all the parasitic diseases in humans, malaria is the most significant and malicious one. The widespread species are Plasmodium falciparum and Plasmodium vivax, but the infection caused by the former is the deadliest. According to the November 2018 report of the World Health Organization (WHO), a total of 219 million cases of malaria were reported globally in 2017, which led to an estimated 435,000 deaths. Mortality due to malaria is estimated at 1.5 - 2.7 million deaths each year. Among all the complications associated with Plasmodium falciparum infection, cerebral malaria (CM) is the most fretful, accounting for almost 13% of all malaria-related deaths. CM is a medical emergency that requires immediate clinical testing and treatment. A compromised microcirculation, with sequestration of parasitized erythrocytes, is central in the disease pathology. No effective therapeutic agents are available yet for the treatment of CM, and therefore, potential interventions are needed to be developed urgently. The currently available anti-malarial drugs lack lipophilicity and are thus not able to reach the brain tissues. Therefore, safe, cost-effective agents with improved lipophilicity possessing the potential to target brain tissues are needed to be searched in order to fight CM worldwide. The aim of present review is to systematically revise the published research work available concerning the development and evaluation of some potential drug targets in the management of CM.

Keywords: Cerebral malaria, lipophilic, parasite, Plasmodium falciparum, sequestration, pathogenesis.

« Previous Next »
Graphical Abstract

[1]
WHO World Malaria Report. ; World Health Organization: Geneva, 2010.
[2]
WHO https://www.who.int/news-room/fact-sheets/detail/malaria
[3]
Kaur, B. India fourth in number of global malaria cases: Lancet report. Available from: https://www.downtoearth.org.in/news/health/india-fourth-in-number-of-global-malaria-cases-lancet-report-66595 (Accessed December 30, 2020).
[4]
World Malaria Report; World Health Organization: Geneva, 2008.
[5]
Ashley, E.; McGready, R.; Proux, S.; Nosten, F. Malaria. Travel Med. Infect. Dis., 2006, 4(3-4), 159-173.
[http://dx.doi.org/10.1016/j.tmaid.2005.06.009] [PMID: 16887738]
[6]
Gardner, M.J.; Hall, N.; Fung, E.; White, O.; Berriman, M.; Hyman, R.W.; Carlton, J.M.; Pain, A.; Nelson, K.E.; Bowman, S.; Paulsen, I.T.; James, K.; Eisen, J.A.; Rutherford, K.; Salzberg, S.L.; Craig, A.; Kyes, S.; Chan, M.S.; Nene, V.; Shallom, S.J.; Suh, B.; Peterson, J.; An-giuoli, S.; Pertea, M.; Allen, J.; Selengut, J.; Haft, D.; Mather, M.W.; Vaidya, A.B.; Martin, D.M.; Fairlamb, A.H.; Fraunholz, M.J.; Roos, D.S.; Ralph, S.A.; McFadden, G.I.; Cummings, L.M.; Subramanian, G.M.; Mungall, C.; Venter, J.C.; Carucci, D.J.; Hoffman, S.L.; Newbold, C.; Davis, R.W.; Fraser, C.M.; Barrell, B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 2002, 419(6906), 498-511.
[http://dx.doi.org/10.1038/nature01097] [PMID: 12368864]
[7]
Kumar, S.; Singh, R.K.; Patial, B.; Goyal, S.; Bhardwaj, T.R. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria. J. Enzyme Inhib. Med. Chem., 2016, 31(2), 173-186.
[http://dx.doi.org/10.3109/14756366.2015.1016513] [PMID: 25775094]
[8]
Duffy, S.; Avery, V.M. Plasmodium falciparum in vitro continuous culture conditions: A comparison of parasite susceptibility and tole-rance to anti-malarial drugs throughout the asexual intra-erythrocytic life cycle. Int. J. Parasitol. Drugs Drug Resist., 2017, 7(3), 295-302.
[http://dx.doi.org/10.1016/j.ijpddr.2017.07.001] [PMID: 28738214]
[9]
Kraemer, S.M.; Smith, J.D. A family affair: var genes, PfEMP1 binding, and malaria disease. Curr. Opin. Microbiol., 2006, 9(4), 374-380.
[http://dx.doi.org/10.1016/j.mib.2006.06.006] [PMID: 16814594]
[10]
Chan, J.A.; Howell, K.B.; Reiling, L.; Ataide, R.; Mackintosh, C.L.; Fowkes, F.J.I.; Petter, M.; Chesson, J.M.; Langer, C.; Warimwe, G.M.; Duffy, M.F.; Rogerson, S.J.; Bull, P.C.; Cowman, A.F.; Marsh, K.; Beeson, J.G. Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity. J. Clin. Invest., 2012, 122(9), 3227-3238.
[http://dx.doi.org/10.1172/JCI62182] [PMID: 22850879]
[11]
Craig, A.G.; Khairul, M.F.; Patil, P.R. Cytoadherence and severe malaria. Malays. J. Med. Sci., 2012, 19(2), 5-18.
[PMID: 22973133]
[12]
Beeson, J.G.; Chan, J.A.; Fowkes, F.J. PfEMP1 as a target of human immunity and a vaccine candidate against malaria. Expert Rev. Vaccines, 2013, 12(2), 105-108.
[http://dx.doi.org/10.1586/erv.12.144] [PMID: 23414401]
[13]
Idro, R.; Jenkins, N.E.; Newton, C.R. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol., 2005, 4(12), 827-840.
[http://dx.doi.org/10.1016/S1474-4422(05)70247-7] [PMID: 16297841]
[14]
Perkins, D.J.; Were, T.; Davenport, G.C.; Kempaiah, P.; Hittner, J.B.; Ong’echa, J.M. Severe malarial anemia: Innate immunity and patho-genesis. Int. J. Biol. Sci., 2011, 7(9), 1427-1442.
[http://dx.doi.org/10.7150/ijbs.7.1427] [PMID: 22110393]
[15]
Shikani, H.J.; Freeman, B.D.; Lisanti, M.P.; Weiss, L.M.; Tanowitz, H.B.; Desruisseaux, M.S. Cerebral malaria: We have come a long way. Am. J. Pathol., 2012, 181(5), 1484-1492.
[http://dx.doi.org/10.1016/j.ajpath.2012.08.010] [PMID: 23021981]
[16]
Taylor, W.R.J.; Hanson, J.; Turner, G.D.H.; White, N.J.; Dondorp, A.M. Respiratory manifestations of malaria. Chest, 2012, 142(2), 492-505.
[http://dx.doi.org/10.1378/chest.11-2655] [PMID: 22871759]
[17]
Storm, J.; Craig, A.G. Pathogenesis of cerebral malaria-inflammation and cytoadherence. Front. Cell. Infect. Microbiol., 2014, 4, 100.
[http://dx.doi.org/10.3389/fcimb.2014.00100] [PMID: 25120958]
[18]
WHO. Definition of Cerebral Malaria. Available from: https://www.publichealth.com.ng/who-definition-of-cerebral-malaria/ (Accessed 21 June, 2021).
[19]
Sierro, F.; Grau, G.E.R. The ins and outs of cerebral malaria pathogenesis: Immunopathology, extracellular vesicles, immunometabolism, and trained immunity. Front. Immunol., 2019, 10, 830.
[http://dx.doi.org/10.3389/fimmu.2019.00830] [PMID: 31057552]
[20]
Taylor, T.E.; Fu, W.; Carr, R.A.; Whitten, R.O.; Mueller, J.G.; Fosiko, N.M. Corrigendum: Differentiating the pathologies of cerebral mala-ria by postmortem parasite counts. Nat. Med., 2004, 10(4), 435-435.
[http://dx.doi.org/10.1038/nm0404-435c]
[21]
Hora, R.; Kapoor, P.; Thind, K.K.; Mishra, P.C. Cerebral malaria--clinical manifestations and pathogenesis. Metab. Brain Dis., 2016, 31(2), 225-237.
[http://dx.doi.org/10.1007/s11011-015-9787-5] [PMID: 26746434]
[22]
Bruneel, F. Human cerebral malaria: 2019 mini review. Rev. Neurol. (Paris), 2019, 175(7-8), 445-450.
[http://dx.doi.org/10.1016/j.neurol.2019.07.008] [PMID: 31375284]
[23]
Esser, C.; Bachmann, A.; Kuhn, D.; Schuldt, K.; Förster, B.; Thiel, M.; May, J.; Koch-Nolte, F.; Yáñez-Mó, M.; Sánchez-Madrid, F.; Schinkel, A.H.; Jalkanen, S.; Craig, A.G.; Bruchhaus, I.; Horstmann, R.D. Evidence of promiscuous endothelial binding by Plasmodium falciparum-infected erythrocytes. Cell. Microbiol., 2014, 16(5), 701-708.
[http://dx.doi.org/10.1111/cmi.12270] [PMID: 24444337]
[24]
Idro, R.; Marsh, K.; John, C.C.; Newton, C.R. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr. Res., 2010, 68(4), 267-274.
[http://dx.doi.org/10.1203/PDR.0b013e3181eee738] [PMID: 20606600]
[25]
Miller, L.H.; Baruch, D.I.; Marsh, K.; Doumbo, O.K. The pathogenic basis of malaria. Nature, 2002, 415(6872), 673-679.
[http://dx.doi.org/10.1038/415673a] [PMID: 11832955]
[26]
Gillrie, M.R.; Lee, K.; Gowda, D.C.; Davis, S.P.; Monestier, M.; Cui, L.; Hien, T.T.; Day, N.P.J.; Ho, M. Plasmodium falciparum histones induce endothelial proinflammatory response and barrier dysfunction. Am. J. Pathol., 2012, 180(3), 1028-1039.
[http://dx.doi.org/10.1016/j.ajpath.2011.11.037] [PMID: 22260922]
[27]
Lovegrove, F.E.; Tangpukdee, N.; Opoka, R.O.; Lafferty, E.I.; Rajwans, N.; Hawkes, M.; Krudsood, S.; Looareesuwan, S.; John, C.C.; Liles, W.C.; Kain, K.C. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One, 2009, 4(3)e4912
[http://dx.doi.org/10.1371/journal.pone.0004912] [PMID: 19300530]
[28]
Turner, G.D.; Ly, V.C.; Nguyen, T.H.; Tran, T.H.; Nguyen, H.P.; Bethell, D.; Wyllie, S.; Louwrier, K.; Fox, S.B.; Gatter, K.C.; Day, N.P.; Tran, T.H.; White, N.J.; Berendt, A.R. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal micro-vascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am. J. Pathol., 1998, 152(6), 1477-1487.
[PMID: 9626052]
[29]
Hollestelle, M.J.; Donkor, C.; Mantey, E.A.; Chakravorty, S.J.; Craig, A.; Akoto, A.O.; O’Donnell, J.; van Mourik, J.A.; Bunn, J. von Wi-llebrand factor propeptide in malaria: Evidence of acute endothelial cell activation. Br. J. Haematol., 2006, 133(5), 562-569.
[http://dx.doi.org/10.1111/j.1365-2141.2006.06067.x] [PMID: 16681646]
[30]
Conroy, A.L.; Lafferty, E.I.; Lovegrove, F.E.; Krudsood, S.; Tangpukdee, N.; Liles, W.C.; Kain, K.C. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar. J., 2009, 8, 295.
[http://dx.doi.org/10.1186/1475-2875-8-295] [PMID: 20003529]
[31]
Jain, V.; Lucchi, N.W.; Wilson, N.O.; Blackstock, A.J.; Nagpal, A.C.; Joel, P.K.; Singh, M.P.; Udhayakumar, V.; Stiles, J.K.; Singh, N. Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India. Malar. J., 2011, 10, 383.
[http://dx.doi.org/10.1186/1475-2875-10-383] [PMID: 22192385]
[32]
Prapansilp, P.; Medana, I.; Mai, N.T.; Day, N.P.J.; Phu, N.H.; Yeo, T.W.; Hien, T.T.; White, N.J.; Anstey, N.M.; Turner, G.D. A clinico-pathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria. Malar. J., 2013, 12, 50.
[http://dx.doi.org/10.1186/1475-2875-12-50] [PMID: 23383853]
[33]
Cerebral Malaria., https://www.malariasite.com/cerebral-malaria/
[34]
Lou, J.; Lucas, R.; Grau, G.E. Pathogenesis of cerebral malaria: Recent experimental data and possible applications for humans. Clin. Microbiol. Rev., 2001, 14(4), 810-820.
[http://dx.doi.org/10.1128/CMR.14.4.810-820.2001] [PMID: 11585786]
[35]
2020.
[36]
Singh, H.; Kapoor, V.K. Medicinal and Pharmaceutical Chemistry; Vallabh Prakashan, 2012, pp. 511-526.
[37]
Tripathi, K.D. Essentials of Medical Pharmacology; Jay Pee Brothers Medical Publishers, 2013, pp. 1-796.
[38]
Higgins, S.J.; Kain, K.C.; Liles, W.C. Immunopathogenesis of falciparum malaria: Implications for adjunctive therapy in the management of severe and cerebral malaria. Expert Rev. Anti Infect. Ther., 2011, 9(9), 803-819.
[http://dx.doi.org/10.1586/eri.11.96] [PMID: 21905788]
[39]
Dondorp, A.M.; Desakorn, V.; Pongtavornpinyo, W.; Sahassananda, D.; Silamut, K.; Chotivanich, K.; Newton, P.N.; Pitisuttithum, P.; Smithyman, A.M.; White, N.J.; Day, N.P. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med., 2005, 2(8)e204
[http://dx.doi.org/10.1371/journal.pmed.0020204] [PMID: 16104831]
[40]
Cheng, F.; Shen, J.; Luo, X.; Zhu, W.; Gu, J.; Ji, R.; Jiang, H.; Chen, K. Molecular docking and 3-D-QSAR studies on the possible antima-larial mechanism of artemisinin analogues. Bioorg. Med. Chem., 2002, 10(9), 2883-2891.
[http://dx.doi.org/10.1016/S0968-0896(02)00161-X] [PMID: 12110308]
[41]
Coghi, P.; Basilico, N.; Taramelli, D.; Chan, W.C.; Haynes, R.K.; Monti, D. Interaction of artemisinins with oxyhemoglobin Hb-FeII, Hb-FeII, carboxyHb-FeII, heme-FeII, and carboxyheme FeII: Significance for mode of action and implications for therapy of cerebral malaria. ChemMedChem, 2009, 4(12), 2045-2053.
[http://dx.doi.org/10.1002/cmdc.200900342] [PMID: 19844934]
[42]
Haynes, R.K.; Cheu, K.W.; N’Da, D.; Coghi, P.; Monti, D. Considerations on the mechanism of action of artemisinin antimalarials: Part 1--the ‘carbon radical’ and ‘heme’ hypotheses. Infect. Disord. Drug Targets, 2013, 13(4), 217-277.
[http://dx.doi.org/10.2174/1871526513666131129155708] [PMID: 24304352]
[43]
Beekman, A.C.; Barentsen, A.R.W.; Woerdenbag, H.J.; Van Uden, W.; Pras, N.; Konings, A.W.; el-Feraly, F.S.; Galal, A.M.; Wikström, H.V. Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J. Nat. Prod., 1997, 60(4), 325-330.
[http://dx.doi.org/10.1021/np9605495] [PMID: 9134741]
[44]
Peng, J.; Kudrimoti, S.; Prasanna, S.; Odde, S.; Doerksen, R.J.; Pennaka, H.K.; Choo, Y.M.; Rao, K.V.; Tekwani, B.L.; Madgula, V.; Khan, S.I.; Wang, B.; Mayer, A.M.; Jacob, M.R.; Tu, L.C.; Gertsch, J.; Hamann, M.T. Structure-activity relationship and mechanism of action studies of manzamine analogues for the control of neuroinflammation and cerebral infections. J. Med. Chem., 2010, 53(1), 61-76.
[http://dx.doi.org/10.1021/jm900672t] [PMID: 20017491]
[45]
Ashok, P.; Ganguly, S.; Murugesan, S. Manzamine alkaloids: Isolation, cytotoxicity, antimalarial activity and SAR studies. Drug Discov. Today, 2014, 19(11), 1781-1791.
[http://dx.doi.org/10.1016/j.drudis.2014.06.010] [PMID: 24953707]
[46]
Mwanga-Amumpaire, J.; Ndeezi, G.; Tumwine, J.K. Effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mula-go Hospital: A randomized controlled trial. Afr. Health Sci., 2012, 12(2), 90-97.
[http://dx.doi.org/10.4314/ahs.v12i2.3] [PMID: 23056012]
[47]
Maude, R.J.; Silamut, K.; Plewes, K.; Charunwatthana, P.; Ho, M.; Abul Faiz, M.; Rahman, R.; Hossain, M.A.; Hassan, M.U.; Bin Yunus, E.; Hoque, G.; Islam, F.; Ghose, A.; Hanson, J.; Schlatter, J.; Lacey, R.; Eastaugh, A.; Tarning, J.; Lee, S.J.; White, N.J.; Chotivanich, K.; Day, N.P.; Dondorp, A.M. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia. J. Infect. Dis., 2014, 209(1), 120-129.
[http://dx.doi.org/10.1093/infdis/jit410] [PMID: 23943850]
[48]
Gwer, S.A.; Idro, R.I.; Fegan, G.; Chengo, E.M.; Mpoya, A.; Kivaya, E.; Crawley, J.; Muchohi, S.N.; Kihara, M.N.; Ogutu, B.R.; Kirkham, F.J.; Newton, C.R. Fosphenytoin for seizure prevention in childhood coma in Africa: A randomized clinical trial. J. Crit. Care, 2013, 28(6), 1086-1092.
[http://dx.doi.org/10.1016/j.jcrc.2013.09.001] [PMID: 24135012]
[49]
Chen, G.; Du, Y.T.; Liu, J.H.; Li, Y.; Zheng, L.; Qin, X.S.; Cao, Y.M. Modulation of anti-malaria immunity by vitamin A in C57BL/6J mice infected with heterogenic plasmodium. Int. Immunopharmacol., 2019, 76105882
[http://dx.doi.org/10.1016/j.intimp.2019.105882] [PMID: 31520991]
[50]
Jiang, X.H.; Chen, L.N.; Li, K.; Guo, Y.; Zheng, Z-Y.; Yang, T.; Zheng, X.J.; Li, Y.J.; Zhu, X.X. Protective effects of artesunate combina-tion on experimental cerebral malaria and nerve injury. Zhongguo Zhongyao Zazhi, 2018, 43(15), 3051-3057.
[PMID: 30200698]
[51]
Reis, P.A.; Estato, V.; da Silva, T.I.; d’Avila, J.C.; Siqueira, L.D.; Assis, E.F.; Bozza, P.T.; Bozza, F.A.; Tibiriça, E.V.; Zimmerman, G.A.; Castro-Faria-Neto, H.C. Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog., 2012, 8(12)e1003099
[http://dx.doi.org/10.1371/journal.ppat.1003099] [PMID: 23300448]
[52]
Wu, B.; Du, Y.; Feng, Y.; Wang, Q.; Pang, W.; Qi, Z.; Wang, J.; Yang, D.; Liu, Y.; Cao, Y. Oral administration of vitamin D and importance in prevention of cerebral malaria. Int. Immunopharmacol., 2018, 64, 356-363.
[http://dx.doi.org/10.1016/j.intimp.2018.08.041] [PMID: 30243072]
[53]
Kume, A. Kasai, S.; Furuya, H.; Suzuki, H. α-Tocopheryl succinate-suppressed development of cerebral malaria in mice. Parasitol. Res., 2018, 117(10), 3177-3182.
[http://dx.doi.org/10.1007/s00436-018-6016-2] [PMID: 30030625]
[54]
Strangward, P.; Haley, M.J.; Albornoz, M.G.; Barrington, J.; Shaw, T.; Dookie, R.; Zeef, L.; Baker, S.M.; Winter, E.; Tzeng, T.C.; Golen-bock, D.T.; Cruickshank, S.M.; Allan, S.M.; Craig, A.; Liew, F.Y.; Brough, D.; Couper, K.N. Targeting the IL33-NLRP3 axis improves the-rapy for experimental cerebral malaria. Proc. Natl. Acad. Sci. USA, 2018, 115(28), 7404-7409.
[http://dx.doi.org/10.1073/pnas.1801737115] [PMID: 29954866]
[55]
Gramaglia, I.; Velez, J.; Chang, Y-S.; Caparros-Wanderley, W.; Combes, V.; Grau, G.; Stins, M.F.; van der Heyde, H.C. Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak. PLoS One, 2019, 14(3)e0213428
[http://dx.doi.org/10.1371/journal.pone.0213428] [PMID: 30849122]
[56]
Schmidt, K.E.; Kuepper, J.M.; Schumak, B.; Alferink, J.; Hofmann, A.; Howland, S.W.; Rénia, L.; Limmer, A.; Specht, S.; Hoerauf, A. Doxycycline inhibits experimental cerebral malaria by reducing inflammatory immune reactions and tissue-degrading mediators. PLoS One, 2018, 13(2)e0192717
[http://dx.doi.org/10.1371/journal.pone.0192717] [PMID: 29438386]
[57]
Cariaco, Y.; Lima, W.R.; Sousa, R.; Nascimento, L.A.C.; Briceño, M.P.; Fotoran, W.L.; Wunderlich, G.; Dos Santos, J.L.; Silva, N.M. Et-hanolic extract of the fungus Trichoderma stromaticum decreases inflammation and ameliorates experimental cerebral malaria in C57BL/6 mice. Sci. Rep., 2018, 8(1), 1547.
[http://dx.doi.org/10.1038/s41598-018-19840-x] [PMID: 29367729]
[58]
Crowley, V.M.; Ayi, K.; Lu, Z.; Liby, K.T.; Sporn, M.; Kain, K.C. Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria. Malar. J., 2017, 16(1), 463.
[http://dx.doi.org/10.1186/s12936-017-2109-0] [PMID: 29137631]
[59]
Mejia, P.; Treviño-Villarreal, J.H.; Reynolds, J.S.; De Niz, M.; Thompson, A.; Marti, M.; Mitchell, J.R. A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration. Malar. J., 2017, 16(1), 455.
[http://dx.doi.org/10.1186/s12936-017-2092-5] [PMID: 29121917]
[60]
Dende, C.; Meena, J.; Nagarajan, P.; Nagaraj, V.A.; Panda, A.K.; Padmanaban, G. Nanocurcumin is superior to native curcumin in preven-ting degenerative changes in experimental cerebral malaria. Sci. Rep., 2017, 7(1), 10062.
[http://dx.doi.org/10.1038/s41598-017-10672-9] [PMID: 28855623]
[61]
Rodriguez, A.A.M.; Carvalho, L.J.M.; Kimura, E.A.; Katzin, A.M. Perillyl alcohol exhibits in vitro inhibitory activity against Plasmodium falciparum and protects against experimental cerebral malaria. Int. J. Antimicrob. Agents, 2018, 51(3), 370-377.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.08.025] [PMID: 28843818]
[62]
https://www.epainassist.com/infections/what-is-cerebral-malaria-and-how-is-it-treated
[63]
https://www.cdc.gov/malaria/resources/pdf/Malaria_Treatment_Table_120419.pdf
[64]
FDA Approval of Artesunate for Injection for Treatment of Severe Malaria., https://www.cdc.gov/malaria/new_info/2020/artesunate_approval.html
[65]
Mannitol as Adjunct Therapy for Childhood Cerebral Malaria., https://ClinicalTrials.gov/show/NCT00113854
[66]
Efficacy of intrarectal versus intravenous quinine for the treatment of childhood cerebral malaria., https://ClinicalTrials.gov/show/NCT00124267
[67]
https://ClinicalTrials.gov/show/NCT00697164
[68]
https://ClinicalTrials.gov/show/NCT01660672
[69]
A Safety and Feasibility Study of Enteral LVT vs., https://ClinicalTrials.gov/show/NCT01982812
[70]
https://ClinicalTrials.gov/show/NCT01388842
[71]
Study of the safety of intravenous artesunate., https://ClinicalTrials.gov/show/NCT00292942

Rights & Permissions Print Cite
Article Metrics
49
1
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy