Cerebral malaria

Neurosciences Unit, Institute of Child Health, London, United Kingdom.
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 6.81). 11/2000; 69(4):433-41.
Source: PubMed


Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogeneous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications-for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.

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Available from: Charles Newton, May 12, 2014
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    • "Involvement of extra-hippocampal damage during malaria infection was hypothesized in a previous study [6], although it was not possible to conclude whether the observed recall impairments were a marker of executive dysfunctioning because of the tool used. The diffuse pattern of involvement found in severe falciparum malaria [9], may damage the frontal lobe resulting in impairments in executive functioning. "
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    ABSTRACT: Background Persistent neurocognitive impairments occur in a fifth of children hospitalized with severe falciparum malaria. There is little data on the association between different neurological phenotypes of severe malaria (seizures, impaired consciousness and prostration) and impairments in executive function. Methods Executive functioning of children exposed to severe malaria with different neurological phenotypes (N = 58) and in those unexposed (N = 56) was examined using neuropsychological tests such as vigilance test, test for everyday attention test for children (TEA-Ch), contingency naming test (CNT) and self-ordered pointing test (SOPT). Linear regression was used to determine the association between neurological phenotypes of severe malaria and executive function performance scores, accounting for potential confounders. Results Children with complex seizures in severe malaria performed more poorly than unexposed controls in the vigilance (median efficiency scores (interquartile range) = 4.84 (1.28-5.68) vs. 5.84 (4.71-6.42), P = 0.030) and SOPT (mean errors (standard deviation) = 29.50 (8.82) vs. 24.80 (6.50), P = 0.029) tests, but no differences were observed in TEA-Ch and CNT tests. Performance scores for other neurological phenotypes of severe malaria were similar with those of unexposed controls. After accounting for potential confounders, such as child’s age, sex, schooling; maternal age, schooling and economic activity; perinatal factors and history of seizures, complex seizures remained associated with efficiency scores in the vigilance test (beta coefficient (β) (95% confidence interval (CI)) = -0.40 (-0.67, -0.13), P = 0.006) and everyday attention scores of the TEA-Ch test (β (95% CI) = -0.57 (-1.04, -0.10), P = 0.019); the association with SOPT error scores was weak (β (95% CI) = 4.57 (-0.73-9.89), P = 0.089). Combined neurological phenotypes were not significantly associated with executive function performance scores. Conclusion Executive function impairment in children with severe malaria is associated with specific neurological phenotypes, particularly complex seizures. Effective prophylaxis and management of malaria-associated acute seizures may improve executive functioning performance scores of children.
    Full-text · Article · Sep 2014 · Malaria Journal
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    • "It is 25 years since the first demonstration that the pro-inflammatory cytokine interferon-γ (IFN-γ) drives the pathogenesis of experimental cerebral malaria (Grau et al., 1989). It therefore seems appropriate to revisit this topic and evaluate progress in our understanding of the mechanisms involved, as well as their significance for the pathogenesis of this life-threatening (Molyneux et al., 1989; Newton et al., 2000) and disabling (Molyneux et al., 1989; Kihara et al., 2006; John et al., 2008) condition in human beings. "
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    ABSTRACT: There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-γ). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-γ in the pathogenesis of this often fatal and debilitating condition.
    Full-text · Article · Aug 2014 · Frontiers in Cellular and Infection Microbiology
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    • "The underlying factors that are hallmark of cerebral malaria are sequestration and cytoadherence of infected RBC, platelets, leukocytes; rosetting , auto-agglutination, release of inflammatory cytokines, hypoxia and cerebral oedema. As a result of these central nervous system (CNS) complications, the disease may progress to unarousable coma and death (Newton et al., 2000). Artemether (ARM) is oil soluble methyl ether of artemisinin effective against both chloroquine-resistant and chloroquine-sensitive strains of P. falciparum, as well as against Plasmodium vivax. "
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    ABSTRACT: The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of −34.4 mV. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that drug existed in amorphous form in NLC formulation. In vitro cytotoxicity assay using SVG p12 cell line and nasal histopathological studies on sheep nasal mucosa indicated the developed formulations were non-toxic and safe for intranasal administration. In vitro release studies revealed that NLC showed sustained release up to 96 h. Ex vivo diffusion studies using sheep nasal mucosa revealed that ARM-NLC had significantly lower flux compared to drug solution (ARM-SOL). Pharmacokinetic and brain uptake studies in Wistar rats showed significantly higher drug concentration in brain in animals treated intranasally (i.n.) with ARM-NLC. Brain to blood ratios for ARM-NLC (i.n.), ARM-SOL (i.n.) and ARM-SOL (i.v.) were 2.619, 1.642 and 0.260, respectively, at 0.5 h indicating direct nose to brain transport of ARM. ARM-NLC showed highest drug targeting efficiency and drug transport percentage of 278.16 and 64.02, respectively, which indicates NLC had better brain targeting efficiency compared to drug solution.
    Full-text · Article · Feb 2014 · Drug Delivery
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