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.
Graphical Abstract
[http://dx.doi.org/10.1016/j.tmaid.2005.06.009] [PMID: 16887738]
[http://dx.doi.org/10.1038/nature01097] [PMID: 12368864]
[http://dx.doi.org/10.3109/14756366.2015.1016513] [PMID: 25775094]
[http://dx.doi.org/10.1016/j.ijpddr.2017.07.001] [PMID: 28738214]
[http://dx.doi.org/10.1016/j.mib.2006.06.006] [PMID: 16814594]
[http://dx.doi.org/10.1172/JCI62182] [PMID: 22850879]
[PMID: 22973133]
[http://dx.doi.org/10.1586/erv.12.144] [PMID: 23414401]
[http://dx.doi.org/10.1016/S1474-4422(05)70247-7] [PMID: 16297841]
[http://dx.doi.org/10.7150/ijbs.7.1427] [PMID: 22110393]
[http://dx.doi.org/10.1016/j.ajpath.2012.08.010] [PMID: 23021981]
[http://dx.doi.org/10.1378/chest.11-2655] [PMID: 22871759]
[http://dx.doi.org/10.3389/fcimb.2014.00100] [PMID: 25120958]
[http://dx.doi.org/10.3389/fimmu.2019.00830] [PMID: 31057552]
[http://dx.doi.org/10.1038/nm0404-435c]
[http://dx.doi.org/10.1007/s11011-015-9787-5] [PMID: 26746434]
[http://dx.doi.org/10.1016/j.neurol.2019.07.008] [PMID: 31375284]
[http://dx.doi.org/10.1111/cmi.12270] [PMID: 24444337]
[http://dx.doi.org/10.1203/PDR.0b013e3181eee738] [PMID: 20606600]
[http://dx.doi.org/10.1038/415673a] [PMID: 11832955]
[http://dx.doi.org/10.1016/j.ajpath.2011.11.037] [PMID: 22260922]
[http://dx.doi.org/10.1371/journal.pone.0004912] [PMID: 19300530]
[PMID: 9626052]
[http://dx.doi.org/10.1111/j.1365-2141.2006.06067.x] [PMID: 16681646]
[http://dx.doi.org/10.1186/1475-2875-8-295] [PMID: 20003529]
[http://dx.doi.org/10.1186/1475-2875-10-383] [PMID: 22192385]
[http://dx.doi.org/10.1186/1475-2875-12-50] [PMID: 23383853]
[http://dx.doi.org/10.1128/CMR.14.4.810-820.2001] [PMID: 11585786]
[http://dx.doi.org/10.1586/eri.11.96] [PMID: 21905788]
[http://dx.doi.org/10.1371/journal.pmed.0020204] [PMID: 16104831]
[http://dx.doi.org/10.1016/S0968-0896(02)00161-X] [PMID: 12110308]
[http://dx.doi.org/10.1002/cmdc.200900342] [PMID: 19844934]
[http://dx.doi.org/10.2174/1871526513666131129155708] [PMID: 24304352]
[http://dx.doi.org/10.1021/np9605495] [PMID: 9134741]
[http://dx.doi.org/10.1021/jm900672t] [PMID: 20017491]
[http://dx.doi.org/10.1016/j.drudis.2014.06.010] [PMID: 24953707]
[http://dx.doi.org/10.4314/ahs.v12i2.3] [PMID: 23056012]
[http://dx.doi.org/10.1093/infdis/jit410] [PMID: 23943850]
[http://dx.doi.org/10.1016/j.jcrc.2013.09.001] [PMID: 24135012]
[http://dx.doi.org/10.1016/j.intimp.2019.105882] [PMID: 31520991]
[PMID: 30200698]
[http://dx.doi.org/10.1371/journal.ppat.1003099] [PMID: 23300448]
[http://dx.doi.org/10.1016/j.intimp.2018.08.041] [PMID: 30243072]
[http://dx.doi.org/10.1007/s00436-018-6016-2] [PMID: 30030625]
[http://dx.doi.org/10.1073/pnas.1801737115] [PMID: 29954866]
[http://dx.doi.org/10.1371/journal.pone.0213428] [PMID: 30849122]
[http://dx.doi.org/10.1371/journal.pone.0192717] [PMID: 29438386]
[http://dx.doi.org/10.1038/s41598-018-19840-x] [PMID: 29367729]
[http://dx.doi.org/10.1186/s12936-017-2109-0] [PMID: 29137631]
[http://dx.doi.org/10.1186/s12936-017-2092-5] [PMID: 29121917]
[http://dx.doi.org/10.1038/s41598-017-10672-9] [PMID: 28855623]
[http://dx.doi.org/10.1016/j.ijantimicag.2017.08.025] [PMID: 28843818]