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Cerebral malaria

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https://www.readbyqxmd.com/read/28203236/the-deubiquitinating-enzyme-cylindromatosis-dampens-cd8-t-cell-responses-and-is-a-critical-factor-for-experimental-cerebral-malaria-and-blood-brain-barrier-damage
#1
Ursula Schmid, Werner Stenzel, Josephin Koschel, Maria Raptaki, Xu Wang, Michael Naumann, Kai Matuschewski, Dirk Schlüter, Gopala Nishanth
Cerebral malaria is a severe complication of human malaria and may lead to death of Plasmodium falciparum-infected individuals. Cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. Although CD8(+) T cells have been implicated in the development of murine experimental cerebral malaria (ECM), several other studies have shown that CD8(+) T cells confer protection against blood-stage infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28203097/cerebral-malaria-insight-into-pathogenesis-complications-and-molecular-biomarkers
#2
Farah Hafiz Yusuf, Muhammad Yusuf Hafiz, Maria Shoaib, Syed Ahsanuddin Ahmed
Cerebral malaria is a medical emergency. All patients with Plasmodium falciparum malaria with neurologic manifestations of any degree should be urgently treated as cases of cerebral malaria. Pathogenesis of cerebral malaria is due to damaged vascular endothelium by parasite sequestration, inflammatory cytokine production and vascular leakage, which result in brain hypoxia, as indicated by increased lactate and alanine concentrations. The levels of the biomarkers' histidine-rich protein II, angiopoietin-Tie-2 system and plasma osteoprotegrin serve as diagnostic and prognostic markers...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28198460/automated-detection-of-malarial-retinopathy-in-digital-fundus-images-for-improved-diagnosis-in-malawian-children-with-clinically-defined-cerebral-malaria
#3
Vinayak Joshi, Carla Agurto, Simon Barriga, Sheila Nemeth, Peter Soliz, Ian J MacCormick, Susan Lewallen, Terrie E Taylor, Simon P Harding
Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185296/a-report-of-cerebral-malaria-treated-with-automated-red-blood-cell-exchange
#4
Waseem Q Anani, Gerald P Smith, Mehraboon Irani, Kathleen E Puca
BACKGROUND: Adjunctive automated whole blood or red blood cell exchange (RBCEx) can rapidly decrease malarial hyperparasitemia. Several case reports and series suggest improvement in clinical symptomatology; however, recent Centers of Disease Control and Prevention (CDC) recommendations concluded that RBCEx has no efficacy as an adjunctive therapy. We present a case of mental status changes secondary to cerebral malaria treated with automated RBCEx resulting in rapid and dramatic neurologic improvement...
February 10, 2017: Transfusion
https://www.readbyqxmd.com/read/28182191/mir-155-modifies-inflammation-endothelial-activation-and-blood-brain-barrier-dysfunction-in-cerebral-malaria
#5
Kevin Richard Barker, Ziyue Lu, Hani Kim, Ying Zheng, Junmei Chen, Andrea L Conroy, Michael Hawkes, Henry S Cheng, Makon-Sébastien Njock, Jason E Fish, John M Harlan, Jose A López, W Conrad Liles, Kevin C Kain
miR-155 has been shown to participate in host response to infection and neuro-inflammation via negative regulation of blood-brain-barrier (BBB) integrity and T cell function. We hypothesized that miR-155 may contribute to the pathogenesis of cerebral malaria (CM). To test this hypothesis, we used a genetic approach to modulate miR-155 expression in an experimental model of cerebral malaria (ECM). In addition, an engineered endothelialized microvessel system and serum samples from Ugandan children with CM were used to examine an anti-miR-155 as a potential adjunctive therapeutic for severe malaria...
February 2, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28181563/the-antimicrobial-molecule-trappin-2-elafin-has-anti-parasitic-properties-and-is-protective-in-vivo-in-a-murine-model-of-cerebral-malaria
#6
Christian Roussilhon, Gilles Bang, Fabien Bastaert, Brigitte Solhonne, Ignacio Garcia-Verdugo, Roger Peronet, Pierre Druilhe, Anavaj Sakuntabhai, Salaheddine Mecheri, Jean-Michel Sallenave
According to the WHO, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. Therefore new antimalarials capable of limiting organ damage are still required. We show that systemic and lung adenovirus (Ad)-mediated over-expression of trappin-2 (T-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing Plasmodium berghei ANKA (PbANKA) strain. Systemically, T-2 reduced PbANKA sequestration in spleen, lung, liver and brain, associated with a decrease in pro-inflammatory cytokines (eg TNF-α in spleen and lung) and an increase in IL-10 production in the lung...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143519/severe-malaria-in-europe-an-8-year-multi-centre-observational-study
#7
Florian Kurth, Michel Develoux, Matthieu Mechain, Denis Malvy, Jan Clerinx, Spinello Antinori, Ida E Gjørup, Joaquím Gascon, Kristine Mørch, Emanuele Nicastri, Michael Ramharter, Alessandro Bartoloni, Leo Visser, Thierry Rolling, Philipp Zanger, Guido Calleri, Joaquín Salas-Coronas, Henrik Nielsen, Gudrun Just-Nübling, Andreas Neumayr, Anna Hachfeld, Matthias L Schmid, Pietro Antonini, Tilman Lingscheid, Peter Kern, Annette Kapaun, José Saraiva da Cunha, Peter Pongratz, Antoni Soriano-Arandes, Mirjam Schunk, Norbert Suttorp, Christoph Hatz, Thomas Zoller
BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe...
January 31, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28139719/a-functional-il22-polymorphism-rs2227473-is-associated-with-predisposition-to-childhood-cerebral-malaria
#8
Sandrine Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Hélia Dessein, Charlène Couturier, Florence Burté, Aboubacar A Oumar, Biobele J Brown, Abdoualye Traore, Nathaniel K Afolabi, Abdoulaye Barry, Samuel Omokhodion, Wuraola A Shokunbi, Olugbemiro Sodeinde, Ogobara Doumbo, Delmiro Fernandez-Reyes, Alain J Dessein
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138045/clinical-comparison-of-retinopathy-positive-and-retinopathy-negative-cerebral-malaria
#9
Chandler Villaverde, Ruth Namazzi, Estela Shabani, Robert O Opoka, Chandy C John
Cerebral malaria (CM) is a severe and often lethal complication of falciparum malaria. A classic malaria retinopathy is seen in some (retinopathy-positive [RP]) children but not others (retinopathy-negative [RN]), and is associated with increased parasite sequestration. It is unclear whether RN CM is a severe nonmalarial illness with incidental parasitemia or a less severe form of the same malarial illness as RP CM. Understanding the clinical differences between RP and RN CM may help shed light on the pathophysiology of malarial retinopathy...
January 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28129766/severe-plasmodium-vivax-infection-in-korea
#10
Jae Hyoung Im, Hea Yoon Kwon, JiHyeon Baek, Seong Wook Park, Areum Durey, Kyung Hee Lee, Moon-Hyun Chung, Jin-Soo Lee
BACKGROUND: Although severe malaria by Plasmodium vivax has been increasingly reported, there are marked variations in the type and rate of the complications by geographic area. This is possibly because of the presence of concurrent falciparum malaria or bacteraemia, and of differences in underlying immune status among the infected subjects. Furthermore, published studies on P. vivax in temperate regions are limited. The present study investigated severe vivax malaria in Korea, where only vivax malaria occurs...
January 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28127335/increased-cd11b-and-hypoxia-inducible-factors-1alpha-expressions-in-the-lung-tissue-and-surfactant-protein-d-levels-in-serum-are-related-with-acute-lung-injury-in-severe-malaria-of-c57bl-6-mice
#11
Wike Astrid Cahayani, Eviana Norahmawati, Niniek Budiarti, Loeki Enggar Fitri
BACKGROUND: We aimed to reveal the role of CD11b and hypoxia-inducible factors-1alpha (HIF-1α) expressions on monocytes and alveolar macrophages of lung tissue, and the levels of serum surfactant protein-D (SP-D) in severe malaria-associated acute lung injury (ALI). METHODS: The C57BL/6 mice were divided into control group, renal malaria group (inoculated with 10(6)Plasmodium berghei ANKA), and cerebral malaria group (inoculated with 10(7)P. berghei ANKA). The expressions of CD11b and HIF-1α in lung tissue were observed by immunohistochemistry, and serum SP-D levels were measured by ELISA...
July 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28122790/cytokine-profiles-in-malawian-children-presenting-with-uncomplicated-malaria-severe-malarial-anemia-and-cerebral-malaria
#12
Wilson L Mandala, Chisomo L Msefula, Esther N Gondwe, Mark T Drayson, Malcolm E Molyneux, Calman A MacLennan
Pro-inflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anaemia (SMA) and uncomplicated malaria (UCM), and healthy controls. We analysed serum cytokine concentrations in acute infection, and in convalescence. With the exception of IL-5, cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM...
January 25, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28107860/the-role-of-heme-oxygenase-1-in-pathogenesis-of-cerebral-malaria-in-the-co-culture-model-of-human-brain-microvascular-endothelial-cell-and-itg-plasmodium-falciparum-infected-red-blood-cells
#13
Pimwan Thongdee, Kesara Na-Bangchang
OBJECTIVE: To investigate the role of human host heme-oxygenase-1 (HO-1) in pathogenesis of cerebral malaria in the in vitro model. METHODS: The effect of human host HO-1 [human brain microvascular endothelial cell (HBMEC)] on hemoglobin degradation in the co-culture model of HBMEC and ITG Plasmodium falciparum-infected red cells (iRBC) through measurement of the enzymatic products iron and bilirubin. RESULTS: Following exposure to the HO-1 inducer CoPPIX at all concentrations, the HBMEC cells apoptosis occurred, which could be prominently observed at 15 μM of 3 h exposure...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28103875/effects-of-plasmodium-falciparum-infection-on-umbilical-artery-resistance-and-intrafetal-blood-flow-distribution-a-doppler-ultrasound-study-from-papua-new-guinea
#14
Maria Ome-Kaius, Stephan Karl, Regina Alice Wangnapi, John Walpe Bolnga, Glen Mola, Jane Walker, Ivo Mueller, Holger Werner Unger, Stephen John Rogerson
BACKGROUND: Doppler velocimetry studies of umbilical artery (UA) and middle cerebral artery (MCA) flow help to determine the presence and severity of fetal growth restriction. Increased UA resistance and reduced MCA pulsatility may indicate increased placental resistance and intrafetal blood flow redistribution. Malaria causes low birth weight and fetal growth restriction, but few studies have assessed its effects on uteroplacental and fetoplacental blood flow. METHODS: Colour-pulsed Doppler ultrasound was used to assess UA and MCA flow in 396 Papua New Guinean singleton fetuses...
January 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28101311/a-hospital-based-retrospective-comparative-study-of-complications-outcomes-clinical-and-laboratory-parameters-of-malaria-with-and-without-neurological-involvement
#15
Sohaib Ahmad, Nadia Shirazi, Nowneet K Bhat, Minakshi Dhar, Garima Mittal, Manish Mittal, Nidhi Kaeley, Manoj Kumar
BACKGROUND & OBJECTIVES: Classically associated with Plasmodium (P.) falciparum, neurological complications in severe malaria is associated with increased morbidity and mortality. However, reports implicate the long considered benign P. vivax for causing severe malaria as well. We aimed to analyse the cerebral complications in malaria, and study if there is a species-related difference in the presentation and outcomes. METHODS: We retrospectively compared patients with malaria hospitalised from 2009-15, with (n=105) and without (n=1155) neurological involvement regarding outcomes, complications, demographic attributes, clinical features, and laboratory parameters...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28096086/platelets-activate-a-pathogenic-response-to-blood-stage-plasmodium-infection-but-not-a-protective-immune-response
#16
Irene Gramaglia, Joyce Velez, Valery Combes, Georges E R Grau, Melanie Wree, Henri C van der Heyde
Clinical studies indicate that thrombocytopenia correlates with the development of severe falciparum malaria, suggesting that platelets either contribute to control of parasite replication possibly as innate parasite killer cells or function in eliciting pathogenesis. Removal of platelets by anti-CD41 mAb treatment, platelet inhibition by aspirin, and adoptive transfer of WT platelets to CD40-KO mice, which do not control parasite replication, resulted in similar parasitemia compared with control mice. Human platelets at a physiological ratio of 1 platelet to 9 RBCs did not inhibit the in vitro development or replication of blood-stage P...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28073351/exploring-neurodevelopmental-outcome-measures-used-in-children-with-cerebral-malaria-the-perspectives-of-caregivers-and-health-workers-in-malawi
#17
Emmie W Mbale, Terrie Taylor, Bernard Brabin, Macpherson Mallewa, Melissa Gladstone
BACKGROUND: Progress has been made in tackling malaria however there are still over 207 million cases worldwide, the majority in children. As survival rates improve, numbers of children with long-term neurodisabling sequelae are likely to increase. Most outcome studies in cerebral malaria (CM) have focused only on body function and structure and less on outcomes within the broader framework of the International Classification of Functioning and Disability (ICF). The aim of this study was to utilise qualitative methods to identify relevant clinical outcomes in CM to support formulation of a core outcome set relevant to CM and other acquired brain injuries for use in future clinical trials...
January 10, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28067620/characterisation-of-the-opposing-effects-of-g6pd-deficiency-on-cerebral-malaria-and-severe-malarial-anaemia
#18
Geraldine M Clarke, Kirk Rockett, Katja Kivinen, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Muminatou Jallow, David J Conway, Kalifa A Bojang, Margaret Pinder, Stanley Usen, Fatoumatta Sisay-Joof, Giorgio Sirugo, Ousmane Toure, Mahamadou A Thera, Salimata Konate, Sibiry Sissoko, Amadou Niangaly, Belco Poudiougou, Valentina D Mangano, Edith C Bougouma, Sodiomon B Sirima, David Modiano, Lucas N Amenga-Etego, Anita Ghansah, Kwadwo A Koram, Michael D Wilson, Anthony Enimil, Jennifer Evans, Olukemi K Amodu, Subulade Olaniyan, Tobias Apinjoh, Regina Mugri, Andre Ndi, Carolyne M Ndila, Sophie Uyoga, Alexander Macharia, Norbert Peshu, Thomas N Williams, Alphaxard Manjurano, Nuno Sepúlveda, Taane G Clark, Eleanor Riley, Chris Drakeley, Hugh Reyburn, Vysaul Nyirongo, David Kachala, Malcolm Molyneux, Sarah J Dunstan, Nguyen Hoan Phu, Nguyen Ngoc Quyen, Cao Quang Thai, Tran Tinh Hien, Laurens Manning, Moses Laman, Peter Siba, Harin Karunajeewa, Steve Allen, Angela Allen, Timothy Me Davis, Pascal Michon, Ivo Mueller, Síle F Molloy, Susana Campino, Angeliki Kerasidou, Victoria J Cornelius, Lee Hart, Shivang S Shah, Gavin Band, Chris Ca Spencer, Tsiri Agbenyega, Eric Achidi, Ogobara K Doumbo, Jeremy Farrar, Kevin Marsh, Terrie Taylor, Dominic P Kwiatkowski
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype...
January 9, 2017: ELife
https://www.readbyqxmd.com/read/28066899/a-role-for-the-histone-h2a-deubiquitinase-mysm1-in-maintenance-of-cd8-t-cells
#19
Michael Förster, Rupinder K Boora, Jessica C Petrov, Nassima Fodil, Isabella Albanese, Jamie Kim, Philippe Gros, Anastasia Nijnik
Several previous studies outlined the importance of the histone H2A deubiquitinase (H2A-DUB) MYSM1 in the regulation of stem cell quiescence and hematopoiesis. In this study we investigated the role of MYSM1 in T cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM1 is intricately involved in the maintenance, activation, and survival of CD8+ T cells. Mysm1 ablation resulted in a 2-fold reduction in CD8+ T cell numbers, and also led to a hyperactivated CD8+ T cell state accompanied by impaired proliferation and increased proinflammatory cytokine production after ex vivo stimulation...
January 9, 2017: Immunology
https://www.readbyqxmd.com/read/28065475/could-the-rts-s-as01-meningitis-safety-signal-really-be-a-protective-effect-of-rabies-vaccine
#20
REVIEW
Bradford D Gessner, Darryn L Knobel, Anne Conan, Adam Finn
The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5-17month but not the 6-12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5-17month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates...
February 1, 2017: Vaccine
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