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Cerebral malaria

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28052109/defining-surrogate-endpoints-for-clinical-trials-in-severe-falciparum-malaria
#7
Atthanee Jeeyapant, Hugh W Kingston, Katherine Plewes, Richard J Maude, Josh Hanson, M Trent Herdman, Stije J Leopold, Thatsanun Ngernseng, Prakaykaew Charunwatthana, Nguyen Hoan Phu, Aniruddha Ghose, M Mahtab Uddin Hasan, Caterina I Fanello, Md Abul Faiz, Tran Tinh Hien, Nicholas P J Day, Nicholas J White, Arjen M Dondorp
BACKGROUND: Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. METHODS: Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine...
2017: PloS One
https://www.readbyqxmd.com/read/27991544/transcriptomic-profiling-of-microglia-reveals-signatures-of-cell-activation-and-immune-response-during-experimental-cerebral-malaria
#8
Barbara Capuccini, Jingwen Lin, Carlos Talavera-López, Shahid M Khan, Jan Sodenkamp, Roberta Spaccapelo, Jean Langhorne
Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the response of microglia, in this severe complication. We examined microglia by genome wide transcriptomic analysis in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Thousands of transcripts were differentially expressed in microglia at two different time points during infection...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27940786/long-term-behavioral-problems-in-children-with-severe-malaria
#9
John Mbaziira Ssenkusu, James Steven Hodges, Robert Opika Opoka, Richard Idro, Elsa Shapiro, Chandy Chiramukhathu John, Paul Bangirana
BACKGROUND: Severe malaria in children is associated with long-term neurocognitive impairment, but it is unclear whether it is associated with long-term behavioral problems. METHODS: Children <5 years old with cerebral malaria (CM) or severe malarial anemia (SMA) treated at Mulago Hospital, Kampala, Uganda were assessed for behavioral outcomes at 0, 6, 12, and 24 months using the Child Behavior Checklist. Sample sizes at 0, 12, and 24 months were 122, 100, and 80 in the CM group, 130, 98, and 81 in the SMA group, and 149, 123, and 90 in healthy community control (CC) children, respectively...
November 2016: Pediatrics
https://www.readbyqxmd.com/read/27923948/decreased-rate-of-plasma-arginine-appearance-in-murine-malaria-may-explain-hypoargininemia-in-children-with-cerebral-malaria
#10
Matthew S Alkaitis, Honghui Wang, Allison K Ikeda, Carol A Rowley, Ian J C MacCormick, Jessica H Chertow, Oliver Billker, Anthony F Suffredini, David J Roberts, Terrie E Taylor, Karl B Seydel, Hans C Ackerman
BACKGROUND:  Plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion. METHODS:  We used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27917875/exploring-experimental-cerebral-malaria-pathogenesis-through-the-characterisation-of-host-derived-plasma-microparticle-protein-content
#11
Natalia Tiberti, Sharissa L Latham, Stephen Bush, Amy Cohen, Robert O Opoka, Chandy C John, Annette Juillard, Georges E Grau, Valéry Combes
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection responsible for thousands of deaths in children in sub-Saharan Africa. CM pathogenesis remains incompletely understood but a number of effectors have been proposed, including plasma microparticles (MP). MP numbers are increased in CM patients' circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that this characterisation could help understand CM pathogenesis...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#12
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27887739/differences-in-the-modulation-of-reactive-species-lipid-bodies-cyclooxygenase-2-5-lipoxygenase-and-ppar-%C3%AE-in-cerebral-malaria-susceptible-and-resistant-mice
#13
Tatiana K S Borges, Érica A R Alves, Henda A R Vasconcelos, Fabiana P Carneiro, André M Nicola, Kelly G Magalhães, Maria Imaculada Muniz-Junqueira
Proinflammatory responses are associated with the severity of cerebral malaria. NO, H2O2, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and -resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H2O2, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages...
November 17, 2016: Immunobiology
https://www.readbyqxmd.com/read/27884751/a-systematic-review-of-the-effect-of-cannabidiol-on-cognitive-function-relevance-to-schizophrenia
#14
REVIEW
Ashleigh L Osborne, Nadia Solowij, Katrina Weston-Green
BACKGROUND AND OBJECTIVES: Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living. Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored...
January 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27865203/minocycline-prevents-cerebral-malaria-confers-neuroprotection-and-increases-survivability-of-mice-during-plasmodium-berghei-anka-infection
#15
Thittayil Suresh Apoorv, Phanithi Prakash Babu
Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study...
November 16, 2016: Cytokine
https://www.readbyqxmd.com/read/27853090/steroid-pulse-therapy-may-mitigate-prolonged-neurological-manifestations-after-eradication-of-severe-plasmodium-falciparum-parasitemia
#16
Chihiro Hasegawa, Akiko Inagaki, Gohei Yamada, Koji Morita, Isamu Kitamura, Koya Ariyoshi
A 58-year-old Japanese man with a high parasitemia of Plasmodium falciparum, returning from Uganda, was admitted to our hospital since his consciousness level rapidly deteriorated after the initial dose of mefloquine. Despite the parasitemia was cleared by quinine by day 7, the coma remained unchanged and diffuse leukoencephalopathy was detected on magnetic resonance image. Steroid pulse therapy was initiated on day 8. Subsequently, the neurological manifestations improved and he was discharged on day 73 without any sequelae...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27824335/oxidative-insult-can-induce-malaria-protective-trait-of-sickle-and-fetal-erythrocytes
#17
Marek Cyrklaff, Sirikamol Srismith, Britta Nyboer, Kvetoslava Burda, Angelika Hoffmann, Felix Lasitschka, Sophie Adjalley, Cyrille Bisseye, Jacques Simpore, Ann-Kristin Mueller, Cecilia P Sanchez, Friedrich Frischknecht, Michael Lanzer
Plasmodium falciparum infections can cause severe malaria, but not every infected person develops life-threatening complications. In particular, carriers of the structural haemoglobinopathies S and C and infants are protected from severe disease. Protection is associated with impaired parasite-induced host actin reorganization, required for vesicular trafficking of parasite-encoded adhesins, and reduced cytoadherence of parasitized erythrocytes in the microvasculature. Here we show that aberrant host actin remodelling and the ensuing reduced cytoadherence result from a redox imbalance inherent to haemoglobinopathic and fetal erythrocytes...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27808089/splenic-differentiation-and-emergence-of-ccr5-cxcl9-cxcl10-monocyte-derived-dendritic-cells-in-the-brain-during-cerebral-malaria
#18
Isabella C Hirako, Marco A Ataide, Lucas Faustino, Patricia A Assis, Elizabeth W Sorensen, Hisashi Ueta, Natalia M Araújo, Gustavo B Menezes, Andrew D Luster, Ricardo T Gazzinelli
Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b(+)F4/80(+)CD11c(+)MHCII(high)DC-SIGN(high)Ly6c(+) and express high levels of CCR5, CXCL9 and CXCL10 (CCR5(+)CXCL9/10(+) MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route...
November 3, 2016: Nature Communications
https://www.readbyqxmd.com/read/27798544/brain-derived-neurotrophic-factor-is-associated-with-disease-severity-and-clinical-outcome-in-ugandan-children-admitted-to-hospital-with-severe-malaria
#19
Chloe R McDonald, Andrea L Conroy, Michael Hawkes, Robyn E Elphinstone, Joel L Gamble, Kyla Hayford, Sophie Namasopo, Robert O Opoka, W Conrad Liles, Kevin C Kain
BACKGROUND: Malaria remains a leading cause of childhood death and neurological disability in sub-Saharan Africa. Here we test the hypothesis that malaria-induced alterations to circulating brain-derived neurotrophic factor (BDNF) are associated with poor clinical outcomes in children with severe malaria. METHODS: We quantified BDNF (by ELISA) in plasma samples collected (at presentation [day1], day 3, and day 14), during a prospective study of Ugandan children admitted to hospital with severe malaria (n=179)...
October 25, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27796746/a-neuroprotective-effect-of-the-glutamate-receptor-antagonist-mk801-on-long-term-cognitive-and-behavioral-outcomes-secondary-to-experimental-cerebral-malaria
#20
Aline Silva de Miranda, Fátima Brant, Luciene Bruno Vieira, Natália Pessoa Rocha, Érica Leandro Marciano Vieira, Gustavo Henrique Souza Rezende, Pollyana Maria de Oliveira Pimentel, Marcio F D Moraes, Fabíola Mara Ribeiro, Richard M Ransohoff, Mauro Martins Teixeira, Fabiana Simão Machado, Milene Alvarenga Rachid, Antônio Lúcio Teixeira
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes...
October 28, 2016: Molecular Neurobiology
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