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Cerebral malaria

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https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#1
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28934429/gene-expression-analysis-reveals-genes-common-to-cerebral-malaria-and-neurodegenerative-disorders
#2
Sandrine Cabantous, Ogobara Doumbo, Belco Poudiougou, Laurence Louis, Abdoulaye Barry, Aboubacar A Oumar, Abdoualye Traore, Sandrine Marquet, Alain Dessein
Cerebral malaria, a reversible encephalopathy affecting young children, is a medical emergency requiring urgent clinical assessment and treatment. We performed a whole-transcriptomic analysis of blood samples from Malian children with cerebral or uncomplicated malaria. We focused on transcripts from pathways for which dysfunction has been associated with neurodegenerative disorders. We found that SNCA, SIAH2, UBB, HSPA1A, TUBB2A, and PINK1 were upregulated (fold-increases, ≥2.6), whereas UBD and PSMC5 were downregulated (fold-decreases, ≤4...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28923378/malaria-parasites-in-a-hungry-host-kinases-and-host-caloric-restriction-brought-together
#3
Jose F Garcia-Bustos, Christian Doerig
A study recently published in Nature links reduced calorie nutritional intake of host mice with (i) reduced severity of cerebral malaria, (ii) decreased parasitemia, and (iii) activation of a nutrient-sensing pathway that regulates the parasite's proliferation rate. Here, we discuss these findings in the context of human malaria pathology and Plasmodium kinomics.
September 8, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28922459/therapeutic-plasma-exchange-in-the-treatment-of-complicated-plasmodium-falciparum-malaria-a-case-report
#4
Tsong-Yih Ou, Cheng-Yen Chuang, Chun-Da Chen, Chung-Yi Cheng
Severe falciparum malaria is associated with multiple organ dysfunction and a high rate of fatal outcome. Malaria is a world-wide disease in tropical areas through the bites of vector mosquitoes. Parasitic protozoans introduced by the mosquito's saliva to the blood travel to the liver then mature and reproduce. In humans, malaria is caused by Plasmodium falciparum, P. malariae, P. ovale, P. vivax, and P. knowlesi, and P. falciparum causes most deaths. Typical malaria symptoms include fever, chills, fatigue, headache, nausea, and vomiting...
September 18, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28874445/ifn-%C3%AE-mediates-experimental-cerebral-malaria-by-signalling-within-both-the-hematopoietic-and-non-hematopoietic-compartments
#5
Ana Villegas-Mendez, Patrick Strangward, Tovah N Shaw, Ivana Rajkovic, Vinko Tosevski, Ruth Forman, Werner Muller, Kevin N Couper
Experimental cerebral malaria (ECM) is an IFN-γ dependent syndrome. However, whether IFN-γ promotes ECM through direct and synergistic targeting of multiple cell populations or whether it causes ECM through acting primarily on a specific responsive cell type, is currently unknown. Here, using a panel of cell and compartment-specific IFN- γR2 deficient mice, we show that IFN-γ causes ECM by signalling within both the hematopoietic and non-haematopoietic compartments. Mechanistically, hematopoietic and non-haematopoietic compartment-specific IFN-γR signalling exerts additive effects in orchestrating intracerebral inflammation leading to ECM development...
September 5, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28863469/parasites-causing-cerebral-falciparum-malaria-bind-multiple-endothelial-receptors-and-express-epcr-and-icam-1-binding-pfemp1
#6
Nicaise Tuikue Ndam, Azizath Moussiliou, Thomas Lavstsen, Claire Kamaliddin, Anja T R Jensen, Atikatou Mama, Rachida Tahar, Christian W Wang, Jakob S Jespersen, Jules M Alao, Benoit Gamain, Thor G Theander, Philippe Deloron
Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the binding and accumulation of infected erythrocytes (IE) to blood vessels and tissues. Specific interactions have been described between PfEMP1 and human endothelial proteins CD36, intercellular adhesion molecule-1 (ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediatric malaria syndromes and the associated PfEMP1 members are still undefined. Methods: In a cohort of 94 hospitalized children with malaria, we characterized the binding properties of IE collected on admission, and var gene transcription using quantitative polymerase chain reaction...
June 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28855623/nanocurcumin-is-superior-to-native-curcumin-in-preventing-degenerative-changes-in-experimental-cerebral-malaria
#7
Chaitanya Dende, Jairam Meena, Perumal Nagarajan, Viswanathan Arun Nagaraj, Amulya Kumar Panda, Govindarajan Padmanaban
Curcumin has many pharmacological activities despite its poor bioavailability and in vivo stability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843818/perillyl-alcohol-exhibits-in-vitro-inhibitory-activity-against-plasmodium-falciparum-and-protects-against-experimental-cerebral-malaria
#8
Adriana A Marin Rodriguez, Leonardo J M Carvalho, Emilia A Kimura, Alejandro M Katzin
The development of new drugs is one of the strategies to control malaria. Isoprenoid biosynthesis in Plasmodium falciparum is an essential pathway for parasite survival, and therefore a potential target for new antimalarial drugs. Indeed, plant-derived secondary metabolites such as terpenes exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in P. falciparum. In this study, the in vitro antiplasmodial activity of perillyl alcohol (POH) was evaluated, along with its in vitro toxicity and its effect on the isoprenylation process...
August 23, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28843047/dysregulation-of-limk-1-cofilin-1-pathway-a-possible-basis-for-alteration-of-neuronal-morphology-in-experimental-cerebral-malaria
#9
Praveen Kumar Simhadri, Ruchi Malwade, Ravisankar Vanka, Venkata Prasuja Nakka, Gowthamarajan Kuppusamy, Prakash Babu Phanithi
OBJECTIVE: Loss of cognition even after survival is the salient feature of cerebral malaria (CM). Currently, the fate of neuronal morphology is not studied at the ultra-structural level in CM. Recent studies suggest that maintenance of neuronal morphology and dendritic spine density (actin dynamics in particular) are essential for proper cognitive functions. LIMK-1/Cofilin-1signaling pathway is known to involve in the maintenance of actin dynamics through regulation of cofilin-1, in executing learning and memory functions...
August 26, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28840449/from-mitochondrial-function-to-neuroprotection-an-emerging-role-for-methylene-blue
#10
REVIEW
Donovan Tucker, Yujiao Lu, Quanguang Zhang
Methylene blue (MB) is a well-established drug with a long history of use, owing to its diverse range of use and its minimal side effect profile. MB has been used classically for the treatment of malaria, methemoglobinemia, and carbon monoxide poisoning, as well as a histological dye. Its role in the mitochondria, however, has elicited much of its renewed interest in recent years. MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28834130/lack-of-mortality-in-22-children-with-sickle-cell-anemia-and-severe-malarial-anemia
#11
Robert O Opoka, Paul Bangirana, Richard Idro, Estela Shabani, Ruth Namazzi, Chandy C John
Retrospective studies suggest that there is high mortality in children with sickle cell anemia (SCA) and severe malaria. We assessed mortality in Ugandan children with severe malarial anemia (SMA, n = 232) or cerebral malaria (CM, n = 267) by sickle cell hemoglobin genotype. Admission and 2-year follow-up mortality did not differ among children with SMA who had homozygous form of sickle cell hemoglobin (HbSS) versus normal form of adult hemoglobin (admission, 0/22, 0%, vs. 1/208, 0.5%; follow-up, 1/22, 4.5%; 7/207, 3...
August 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28803696/differential-modulation-of-glial-cell-mediated-neuroinflammation-in-plasmodium-berghei-anka-infection-by-tgf-%C3%AE-and-il-6
#12
Samrat Sarkar, Tarun Keswani, Anirban Sengupta, Soham Mitra, Arindam Bhattacharyya
Modulation of pro-inflammatory and anti-inflammatory axis and orientation of glial cell function towards neuroinflammation, were hallmark signs of cerebral malaria (CM). CM pathogenesis was concerned with the circulating levels of Interleukin 6 (IL 6) and Transforming growth factor β (TGF β). Definite roles of these two cytokines in brain related pathology remained largely unexplored. To study the effect of these two cytokines, we have examined changes in morphology and in activation profile of the glial cells after TGF β and IL 6 neutralization during CM in cortex and cerebellum of the Plasmodium berghei ANKA (PbA) infected male swiss albino mice...
August 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28792284/neurological-involvement-associated-with-plasmodium-vivax-malaria-from-pakistan
#13
Yousaf Abdullah Khan, Usman Hameed Mian, Najia Karim Ghanchi, Ali Bin Sarwar Zubairi, Mohammad Asim Beg
Plasmodium vivax is the most common specie causing malaria outside Africa with approximately 13.8 million reported cases worldwide. We report case of P. vivax infection with cerebral involvement. A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. After antimalarial therapy, patient made full recovery. Current case highlights increasing trend of cerebral complications caused by P...
January 1, 2017: Tropical Doctor
https://www.readbyqxmd.com/read/28757574/finding-a-balance-between-protection-and-pathology-the-dual-role-of-perforin-in-human-disease
#14
REVIEW
Robin C Willenbring, Aaron J Johnson
Perforin is critical for controlling viral infection and tumor surveillance. Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore-forming protein results in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region of PRF1 are not yet associated with disease. Animal models of viral-associated blood-brain barrier (BBB) disruption and experimental cerebral malaria (ECM) have identified perforin as critical for inducing pathologic central nervous system CNS vascular permeability...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28754152/cerebrospinal-fluid-kynurenine-and-kynurenic-acid-concentrations-are-associated-with-coma-duration-and-long-term-neurocognitive-impairment-in-ugandan-children-with-cerebral-malaria
#15
Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert O Opoka, Paul Bangirana, Carl M Sellgren, Ronny Wickström, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy C John
BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed...
July 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28748845/a-case-of-plasmodium-vivax-malaria-presenting-as-acute-cerebral-infarct
#16
Sanjay Kumar Kochar, Sneha Dayanand Kamath, Nitesh Toshan, Yamini Singhal, Anju Kochar
No abstract text is available yet for this article.
April 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/28742109/young-sprague-dawley-rats-infected-by-plasmodium-berghei-a-relevant-experimental-model-to-study-cerebral-malaria
#17
Sokhna Keita Alassane, Marie-Laure Nicolau-Travers, Sandie Menard, Olivier Andreoletti, Jean-Pierre Cambus, Noémie Gaudre, Myriam Wlodarczyk, Nicolas Blanchard, Antoine Berry, Sarah Abbes, David Colongo, Babacar Faye, Jean-Michel Augereau, Caroline Lacroux, Xavier Iriart, Françoise Benoit-Vical
Cerebral malaria (CM) is the most severe manifestation of human malaria yet is still poorly understood. Mouse models have been developed to address the subject. However, their relevance to mimic human pathogenesis is largely debated. Here we study an alternative cerebral malaria model with an experimental Plasmodium berghei Keyberg 173 (K173) infection in Sprague Dawley rats. As in Human, not all infected subjects showed cerebral malaria, with 45% of the rats exhibiting Experimental Cerebral Malaria (ECM) symptoms while the majority (55%) of the remaining rats developed severe anemia and hyperparasitemia (NoECM)...
2017: PloS One
https://www.readbyqxmd.com/read/28735651/the-effect-of-artesunate-on-short-term-memory-in-lyme-borreliosis
#18
B K Puri, J S Hakkarainen-Smith, J A Monro
Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria. We hypothesised that concomitant administration of artesunate in Lyme borreliosis patients would help alleviate the severity of self-reported short-term memory impairment...
August 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28719298/cognitive-outcomes-and-psychiatric-symptoms-of-retinopathy-positive-cerebral-malaria-cohort-description-and-baseline-results
#19
Rachel Brim, Sebastian Mboma, Margaret Semrud-Clikeman, Sam Kampondeni, Jed Magen, Terrie Taylor, John Langfitt
Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The Cognitive Outcomes and Psychiatric symptoms of retinopathy-positive CM (COPS) cohort is the first large (N = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures semi-annually for up to 5 years...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28710387/protein-tyrosine-phosphatase-inhibition-prevents-experimental-cerebral-malaria-by-precluding-cxcr3-expression-on-t-cells
#20
Kristin M Van Den Ham, Logan K Smith, Martin J Richer, Martin Olivier
Cerebral malaria induced by Plasmodium berghei ANKA infection is dependent on the sequestration of cytotoxic T cells within the brain and augmentation of the inflammatory response. Herein, we demonstrate that inhibition of protein tyrosine phosphatase (PTP) activity significantly attenuates T cell sequestration within the brain and prevents the development of neuropathology. Mechanistically, the initial upregulation of CXCR3 on splenic T cells upon T cell receptor stimulation was critically decreased through the reduction of T cell-intrinsic PTP activity...
July 14, 2017: Scientific Reports
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