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Cerebral malaria

Paul C Knox, Ian J C MacCormick, Emme Mbale, Macpherson Malewa, Gabriela Czanner, Simon P Harding
Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks. Therefore we investigated the impact of cerebral malaria on the development of reflexive pro-saccades and antisaccades. In a longitudinal study, 47 children previously admitted with retinopathy-confirmed cerebral malaria (mean age at admission 54 months), were compared with 37 local healthy controls (mean ages at first study visit 117 and 110 months respectively)...
2016: PloS One
Thummla Srinivas Redddy, Suresh Sr
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Sabrina Torre, Maria J Polyak, David Langlais, Nassima Fodil, James M Kennedy, Irena Radovanovic, Joanne Berghout, Gabriel A Leiva-Torres, Connie M Krawczyk, Subburaj Ilangumaran, Karen Mossman, Chen Liang, Klaus-Peter Knobeloch, Luke M Healy, Jack Antel, Nathalie Arbour, Alexandre Prat, Jacek Majewski, Mark Lathrop, Silvia M Vidal, Philippe Gros
Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15(L749R)) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15(L749R)-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ...
October 10, 2016: Nature Immunology
Saw Thu Wah, Hathairad Hananantachai, Usanee Kerdpin, Chotiros Plabplueng, Virapong Prachayasittikul, Pornlada Nuchnoi
Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention...
2016: Tropical Medicine and Health
Jai Shankar Singh, Vaibhav Kumar Shukla, Mansi Gujrati, Ram Kumar Mishra, Ashutosh Kumar
One of the most debilitating diseases Malaria, in its different forms, is caused by protozoan of Plasmodium species. Deadliest among these forms is the "cerebral malaria" which is afflicted upon by Plasmodium falciparum. Plasmodium adopts numerous strategies including various post-translational modifications (PTMs) to infect and survive in the human host. These PTMs have proven their critical requirement in the Plasmodium biology. Recently, sumoylation has been characterized as one of the important PTMs and many of its putative substrates have been identified in Plasmodium...
October 3, 2016: Biomolecular NMR Assignments
Sandeep K Shrivastava, Esther Dalko, Delphine Delcroix-Genete, Fabien Herbert, Pierre-André Cazenave, Sylviane Pied
Astrocytes and microglia are activated during cerebral malaria (CM) and contribute to the production and release of several mediators during neuroinflammatory processes. Whether these changes are the consequence of a direct crosstalk between glial cells and the malarial parasite and how these cells participate in the pathogenesis of CM is not yet clear. We therefore examined the interaction of astrocytes and microglia with Plasmodium berghei ANKA-infected red blood cells using primary cell cultures derived from newborn C57BL/6 mice...
October 3, 2016: Glia
Nathan R Brand, Robert O Opoka, Karen E S Hamre, Chandy C John
Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level)...
2016: PloS One
Sarah J Higgins, Lisa A Purcell, Karlee L Silver, Vanessa Tran, Valerie Crowley, Michael Hawkes, Andrea L Conroy, Robert O Opoka, John G Hay, Susan E Quaggin, Gavin Thurston, W Conrad Liles, Kevin C Kain
Cerebral malaria is a leading cause of global morbidity and mortality. Interventions targeting the underlying pathophysiology of cerebral malaria may improve outcomes compared to treatment with antimalarials alone. Microvascular leak plays an important role in the pathogenesis of cerebral malaria. The angiopoietin (Ang)-Tie-2 system is a critical regulator of vascular function. We show that Ang-1 expression and soluble Tie-2 expression were associated with disease severity and outcome in a prospective study of Ugandan children with severe malaria and in a preclinical murine model of experimental cerebral malaria...
September 28, 2016: Science Translational Medicine
Akshaya Kumar Mohanty, Praveen Kishore Sahu, Sanjib Mohanty
No abstract text is available yet for this article.
July 2016: Journal of Vector Borne Diseases
Brian DellaValle, Casper Hempel, Trine Staalsoe, Flemming Fryd Johansen, Jørgen Anders Lindholm Kurtzhals
No abstract text is available yet for this article.
September 27, 2016: Malaria Journal
Samuel Crocodile Wassmer, Georges Emile Raymond Grau
Plasmodium falciparum causes the most severe and fatal form of malaria in humans with over half a million deaths each year. Cerebral malaria, a complex neurological syndrome of severe falciparum malaria, is often fatal and represents a major public health burden. Despite vigorous efforts, the pathophysiology of cerebral malaria remains to be elucidated, thereby hindering the development of adjunctive therapies. In recent years, multidisciplinary and collaborative approaches have led to groundbreaking progress both in the laboratory and in the field...
September 23, 2016: International Journal for Parasitology
Julio Gallego-Delgado, Thomas Walther, Ana Rodriguez
RATIONALE: A recently proposed hypothesis states that malaria may contribute to hypertension in endemic areas1, but the role of angiotensin (Ang) II, a major regulator of blood pressure, was not considered. Elevated levels of Ang II may confer protection against malaria morbidity and/or mortality, providing an alternative explanation for hypertension in malaria endemic areas. OBJECTIVE: To discuss a possible alternative cause for hypertension in populations that have been under the selective pressure of malaria...
September 22, 2016: Circulation Research
Chloé Latour, Myriam F Wlodarczyk, Grace Jung, Aurélie Gineste, Nicolas Blanchard, Tomas Ganz, Marie-Paule Roth, Hélène Coppin, Léon Kautz
Malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. Iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. We examined the regulation of hepcidin during malarial infection in mice using the rodent parasite Plasmodium berghei K173 (PbK). Mice infected with PbK develop a severe anemia and die after 18 to 22 days without cerebral malaria...
September 22, 2016: Haematologica
Fikregabrail Aberra Kassa, Kristin Van Den Ham, Anthony Rainone, Sylvie Fournier, Eric Boilard, Martin Olivier
Cerebral malaria claims the life of millions of people each year, particularly those of children, and is a major global public health problem. Thus, the identification of novel malaria biomarkers that could be utilized as diagnostic or therapeutic targets is becoming increasingly important. Using a proteomic approach, we previously identified unique biomarkers in the sera of malaria-infected individuals, including apolipoprotein E (ApoE). ApoE is the dominant apolipoprotein in the brain and has been implicated in several neurological disorders; therefore, we were interested in the potential role of ApoE in cerebral malaria...
2016: Scientific Reports
Julio Gallego-Delgado, Upal Basu-Roy, Maureen Ty, Matilde Alique, Cristina Fernandez-Arias, Alexandru Movila, Pollyanna Gomes, Ada Weinstock, Wenyue Xu, Innocent Edagha, Samuel C Wassmer, Thomas Walther, Marta Ruiz-Ortega, Ana Rodriguez
Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum-infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter-endothelial cell junctions in human brain microvascular endothelial cells (HBMECs)...
October 3, 2016: Journal of Clinical Investigation
Jens E V Petersen, Thomas Lavstsen, Alister Craig
Recent findings have linked brain swelling to death in cerebral malaria (CM). These observations have prompted a number of investigations into the mechanisms of this pathology with the goal of identifying potential therapeutic targets. In this issue of the JCI, Gallego-Delgado and colleagues present evidence that implicates angiotensin receptors and the relocation of β-catenin to the endothelial cell nucleus in CM. This study provides a renewed focus on infected erythrocyte debris as the cause of endothelial damage and challenges previous work implicating direct effects of infected erythrocyte sequestration in the brain as the major driver of disease...
October 3, 2016: Journal of Clinical Investigation
Yuri C Martins, Brandi D Freeman, Oscar B Akide-Ndunge, Louis M Weiss, Herbert B Tanowitz, Mahalia S Desruisseaux
Plasmodium berghei ANKA infection of C57BL/6 mice is a widely used model of experimental cerebral malaria (ECM). By contrast, the nonneurotropic P. berghei NK65 (PbN) causes severe malarial disease in C57BL/6 mice but does not cause ECM. Previous studies suggest that endothelin-1 (ET-1) contributes to the pathogenesis of ECM. In this study, we characterize the role of ET-1 on ECM vascular dysfunction. Mice infected with 10(6) PbN-parasitized red blood cells were treated with either ET-1 or saline from 2 to 8 days postinfection (dpi)...
September 15, 2016: American Journal of Pathology
Nan Hou, Yang Zou, Xianyu Piao, Shuai Liu, Lei Wang, Shanshan Li, Qijun Chen
Cell-mediated immune responses play important roles in immune protection against Plasmodium infection. However, impaired immunity, such as lymphocyte exhaustion, is a common phenomenon in malaria. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is an important regulatory molecule in cell-mediated immunity and has been implicated in malaria. In this study, it was found that the expression of Tim-3 expression on key populations of lymphocytes was significantly increased in both Plasmodium falciparum-infected patients and Plasmodium berghei ANKA (PbANKA)-infected C57BL/6 mice...
September 16, 2016: Journal of Infectious Diseases
Pedro Pallangyo, Frederick Lyimo, Paulina Nicholaus, Ulimbakisya Kain, Mohamed Janabi
Malaria remains a significant public health problem of the tropical world. Falciparum malaria is most prevalent in the sub-Saharan African region, which harbors about 90% of all malaria cases and fatalities globally. Infection by the falciparum species often manifests with a spectrum of multi-organ complications (eg, cerebral malaria), some of which are life-threatening. Spontaneous subdural empyema is a very rare complication of cerebral malaria that portends a very poor prognosis unless diagnosed and treated promptly...
July 2016: Journal of Investigative Medicine High Impact Case Reports
Tarun Keswani, Samrat Sarkar, Anirban Sengupta, Arindam Bhattacharyya
The role of cytokines in Plasmodium infection have been extensively investigated, but pro and anti inflammatory cytokines mediated imbalance during malaria immune-pathogenesis is still unrevealed. Malaria is associated with the circulating levels of Interleukin-6 (IL-6) and transforming growth factor β (TGF-β), but association between these two cytokines in immune response remains largely obscured. Using mouse model, we proposed that IL-6 and TGF-β are involved in immune regulation of dendritic cells (DC), regulatory T cells (Treg), T-helper cells (Th17) during P...
December 2016: Cytokine
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