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Cerebral malaria

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https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#1
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29137631/synthetic-oleanane-triterpenoids-enhance-blood-brain-barrier-integrity-and-improve-survival-in-experimental-cerebral-malaria
#2
Valerie M Crowley, Kodjo Ayi, Ziyue Lu, Karen T Liby, Michael Sporn, Kevin C Kain
BACKGROUND: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection associated with high mortality and neurocognitive impairment in survivors. New anti-malarials and host-based adjunctive therapy may improve clinical outcome in CM. Synthetic oleanane triterpenoid (SO) compounds have shown efficacy in the treatment of diseases where inflammation and oxidative stress contribute to pathogenesis. METHODS: A derivative of the SO 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), CDDO-ethyl amide (CDDO-EA) was investigated for the treatment of severe malaria in a pre-clinical model...
November 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29132978/intensive-care-in-severe-malaria-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#3
REVIEW
Dilip R Karnad, Mohd Basri Mat Nor, Guy A Richards, Tim Baker, Pravin Amin
Severe malaria is common in tropical countries in Africa, Asia, Oceania and South and Central America. It may also occur in travelers returning from endemic areas. Plasmodium falciparum accounts for most cases, although P vivax is increasingly found to cause severe malaria in Asia. Cerebral malaria is common in children in Africa, manifests as coma and seizures, and has a high morbidity and mortality. In other regions, adults may also develop cerebral malaria but neurological sequelae in survivors are rare...
November 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/29129674/cytotoxic-t-lymphocyte-granzyme-b-mediates-neuronal-cell-death-during-plasmodium-berghei-anka-induced-experimental-cerebral-malaria
#4
Prabhakar Eeka, Prakash Babu Phanithi
Cerebral malaria is a complex, acute, neurological disease characterised by a sudden onset of cerebral symptoms. This disease is manifested as initial arousable stage that is followed by an unarousable coma and eventually death. Parasite burden and CD8+ T cell count in the brain determines the disease outcome. Cytotoxic CD8+ T cell-derived Granzyme-b is required for the development of experimental cerebral malaria (ECM), but the mechanism of pathogenesis is not known. Here, we show that CD8+ T cells infiltrate in to the brain during ECM releasing Granzyme-b that is cytotoxic to neuronal cells...
November 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29127615/fungal-and-parasitic-cns-infections
#5
Pratibha Singhi, Arushi Gahlot Saini
Central nervous system fungal infections can be broadly divided into those that infect a healthy host such as Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Sporothrix spp., and those that cause opportunistic infections in an immunocompromised host such as Candida, Aspergillus, Zygomycetes, Trichosporon spp. The clinical manifestations of central nervous system fungal infections commonly seen in children in clinical practice include a chronic meningitis or meningoencephalitis syndrome, brain abscess, rhino-cerebral syndrome and rarely, a fungal ventriculitis...
November 11, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29121917/a-single-rapamycin-dose-protects-against-late-stage-experimental-cerebral-malaria-via-modulation-of-host-immunity-endothelial-activation-and-parasite-sequestration
#6
Pedro Mejia, J Humberto Treviño-Villarreal, Justin S Reynolds, Mariana De Niz, Andrew Thompson, Matthias Marti, James R Mitchell
BACKGROUND: Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy. Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host. However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM. RESULTS: The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection...
November 9, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29120741/getting-your-head-around-cerebral-malaria
#7
Jeffrey D Dvorin
Cerebral malaria is one of the most severe complications of human infection by the Plasmodium falciparum parasite. In this issue of Cell Host & Microbe, Kessler et al. (2017) provide valuable insights into the diagnosis and pathogenesis of this poorly understood manifestation of malaria.
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29117626/unravelling-the-roles-of-innate-lymphoid-cells-in-cerebral-malaria-pathogenesis
#8
J Palomo, Vfj Quesniaux, D Togbe, F Reverchon, B Ryffel
Cerebral malaria (CM) is due to Plasmodium parasite infection leading to inflammatory immune responses in the central nervous system (CNS), accompanied by lung inflammation and anemia. Here, we focus on the role of the innate immune response in experimental cerebral malaria (ECM) caused by blood-stage murine Plasmodium berghei ANKA-infection. While T cells are important for ECM pathogenesis, the role of innate lymphoid cells (ILC) is only emerging. The role of ILCs and non-lymphoid cells such as neutrophils and platelets contributing to the host immune response leading to ECM and human cerebral malaria (HCM) is reviewed...
November 8, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/29117196/validity-of-a-minimally-invasive-autopsy-for-cause-of-death-determination-in-maternal-deaths-in-mozambique-an-observational-study
#9
Paola Castillo, Juan Carlos Hurtado, Miguel J Martínez, Dercio Jordao, Lucilia Lovane, Mamudo R Ismail, Carla Carrilho, Cesaltina Lorenzoni, Fabiola Fernandes, Sibone Mocumbi, Zara Onila Jaze, Flora Mabota, Anelsio Cossa, Inacio Mandomando, Pau Cisteró, Alfredo Mayor, Mireia Navarro, Isaac Casas, Jordi Vila, Maria Maixenchs, Khátia Munguambe, Ariadna Sanz, Llorenç Quintó, Eusebio Macete, Pedro Alonso, Quique Bassat, Jaume Ordi, Clara Menéndez
BACKGROUND: Despite global health efforts to reduce maternal mortality, rates continue to be unacceptably high in large parts of the world. Feasible, acceptable, and accurate postmortem sampling methods could provide the necessary evidence to improve the understanding of the real causes of maternal mortality, guiding the design of interventions to reduce this burden. METHODS AND FINDINGS: The validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in an observational study in 57 maternal deaths by comparing the results of the MIA with those of the gold standard (complete diagnostic autopsy [CDA], which includes any available clinical information)...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29113976/co-infection-with-chikungunya-virus-alters-trafficking-of-pathogenic-cd8-t-cells-into-the-brain-and-prevents-plasmodium-induced-neuropathology
#10
Teck-Hui Teo, Shanshan W Howland, Carla Claser, Sin Yee Gun, Chek Meng Poh, Wendy Wl Lee, Fok-Moon Lum, Lisa Fp Ng, Laurent Rénia
Arboviral diseases have risen significantly over the last 40 years, increasing the risk of co-infection with other endemic disease such as malaria. However, nothing is known about the impact arboviruses have on the host response toward heterologous pathogens during co-infection. Here, we investigate the effects of Chikungunya virus (CHIKV) co-infection on the susceptibility and severity of malaria infection. Using the Plasmodium berghei ANKA (PbA) experimental cerebral malaria (ECM) model, we show that concurrent co-infection induced the most prominent changes in ECM manifestation...
November 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29113928/cerebral-malaria-causes-enduring-behavioral-and-molecular-changes-in-mice-brain-without-causing-gross-histopathological-damage
#11
Thaíze Lopes de Souza, Ana Claudia Beck Grauncke, Leandro Rodrigo Ribeiro, Fernanda Kulinski Mello, Sara Marchesan Oliveira, Fátima Brant, Fabiana S Machado, Mauro Schneider Oliveira
Malaria, parasitic disease considered a major health public problem, is caused by Plasmodium protozoan genus and transmitted by the bite of infected female Anopheles mosquito genus. Cerebral malaria (CM) is the most severe presentation of malaria, caused by P. falciparum and responsible for high mortality and enduring development of cognitive deficits which may persist even after cure and cessation of therapy. In the present study we evaluated selected behavioral, neurochemical and neuropathologic parameters after rescue from experimental cerebral malaria caused by P...
November 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/29111495/dual-modal-ultra-bright-nanodots-with-aggregation-induced-emission-and-gadolinium-chelation-for-vascular-integrity-and-leakage-detection
#12
Guangxue Feng, Jackson Liang Yao Li, Carla Claser, Akhila Balachander, Yingrou Tan, Chi Ching Goh, Immanuel Weng Han Kwok, Laurent Rénia, Ben Zhong Tang, Lai Guan Ng, Bin Liu
The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS)...
October 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29107705/amp-activated-protein-kinase-ampk-is-decreased-in-the-mouse-brain-during-experimental-cerebral-malaria
#13
Thittayil Suresh Apoorv, Chintanuri Karthik, Phanithi Prakash Babu
Cerebral malaria (CM) is a severe form of malaria caused by Plasmodium falciparum and P.vivax. CM affects the brain leading to coma and is the leading cause of death in malaria patients. The enzyme, adenosine 5'-monophosphate-activated protein kinase (AMPK), is an important metabolic sensor that helps in maintaining energy homeostasis during normal physiological as well as pathological conditions. In the present study, we studied the status of AMPK in the mouse model of CM. The C57BL/6 mice infected by rodent-specific P...
October 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29107642/linking-epcr-binding-pfemp1-to-brain-swelling-in-pediatric-cerebral-malaria
#14
Anne Kessler, Selasi Dankwa, Maria Bernabeu, Visopo Harawa, Samuel A Danziger, Fergal Duffy, Sam D Kampondeni, Michael J Potchen, Nicholas Dambrauskas, Vladimir Vigdorovich, Brian G Oliver, Sarah E Hochman, Wenzhu B Mowrey, Ian J C MacCormick, Wilson L Mandala, Stephen J Rogerson, D Noah Sather, John D Aitchison, Terrie E Taylor, Karl B Seydel, Joseph D Smith, Kami Kim
Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29102350/prevalence-of-cerebral-palsy-in-uganda-a-population-based-study
#15
Angelina Kakooza-Mwesige, Carin Andrews, Stefan Peterson, Fred Wabwire Mangen, Ann Christin Eliasson, Hans Forssberg
BACKGROUND: Few population-based studies of cerebral palsy have been done in low-income and middle-income countries. We aimed to examine cerebral palsy prevalence and subtypes, functional impairments, and presumed time of injury in children in Uganda. METHODS: In this population-based study, we used a nested, three-stage, cross-sectional method (Iganga-Mayuge Health and Demographic Surveillance System [HDSS]) to screen for cerebral palsy in children aged 2-17 years in a rural eastern Uganda district...
October 25, 2017: Lancet Global Health
https://www.readbyqxmd.com/read/29096633/cerebral-malaria-induces-electrophysiological-and-neurochemical-impairment-in-mice-retinal-tissue-possible-effect-on-glutathione-and-glutamatergic-system
#16
Karen R H M Oliveira, Nayara Kauffmann, Luana K R Leão, Adelaide C F Passos, Fernando A F Rocha, Anderson M Herculano, José L M do Nascimento
BACKGROUND: Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome...
November 2, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29034214/pathogenic-cd8-t-cells-cause-increased-levels-of-vegf-a-in-experimental-malaria-associated-acute-respiratory-distress-syndrome-but-therapeutic-vegfr-inhibition-is-not-effective
#17
Thao-Thy Pham, Melissa Verheijen, Leen Vandermosten, Katrien Deroost, Sofie Knoops, Kathleen Van den Eynde, Louis Boon, Chris J Janse, Ghislain Opdenakker, Philippe E Van den Steen
Malaria is a severe disease and kills over 400,000 people each year. Malarial complications are the main cause of death and include cerebral malaria and malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite antimalarial treatment, lethality rates of MA-ARDS are still between 20 and 80%. Patients develop pulmonary edema with hemorrhages and leukocyte extravasation in the lungs. The vascular endothelial growth factor-A (VEGF-A) and the placental growth factor (PlGF) are vascular permeability factors and may be involved in the disruption of the alveolar-capillary membrane, leading to alveolar edema...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29025399/plasmodium-falciparum-epcr-binding-pfemp1-expression-increases-with-malaria-disease-severity-and-is-elevated-in-retinopathy-negative-cerebral-malaria
#18
Estela Shabani, Benjamin Hanisch, Robert O Opoka, Thomas Lavstsen, Chandy C John
BACKGROUND: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM)...
October 13, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28987173/parasitic-and-fungal-infections
#19
Nikolaus Deigendesch, Jean Costa Nunez, Werner Stenzel
Parasitic infections of the central nervous system (CNS) comprise a plethora of infectious agents leading to a multitude of different disease courses and thus diagnostic and therapeutic challenges. The prevalence of different pathogens is basically dependent on geographic and ethnic backgrounds, its infectious route frequently involving a third party, such as flies or domestic animals. The present review focuses on cerebral malaria due to Plasmodium falciparum infection, and Toxoplasma gondii encephalitis. Fungi produce a large variety of inflammatory conditions of the CNS with a variegated spectrum of signs and symptoms, which may involve the meninges and the brain parenchyma, where they produce cerebritis or abscesses and granulomatous lesions, respectively...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28970738/genetic-diversity-of-cd14-promoter-gene-polymorphism-rs2569190-is-associated-with-regulation-of-malaria-parasitemia-and-susceptibility-to-plasmodium-falciparum-infection
#20
Olusola Ojurongbe, Roland I Funwei, Tara J Snyder, Najihah Aziz, Yi Li, Catherine O Falade, Bolaji N Thomas
CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp -159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease...
2017: Infectious Diseases
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