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Cerebral malaria

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https://www.readbyqxmd.com/read/28339598/high-postdischarge-morbidity-in-ugandan-children-with-severe-malarial-anemia-or-cerebral-malaria
#1
Robert O Opoka, Karen E S Hamre, Nathan Brand, Paul Bangirana, Richard Idro, Chandy C John
Summary: Postdischarge readmission and outpatient illnesses are frequent in children with severe malarial anemia or cerebral malaria. Trials of postdischarge malaria prophylaxis in children with severe malaria should be considered. Background: Cerebral malaria (CM) and severe malarial anemia (SMA) account for a substantial proportion of malaria-related deaths in sub-Saharan Africa. However, postdischarge morbidity in children with CM or SMA has not been well established...
October 7, 2016: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28336326/oxidative-stress-and-genes-regulation-of-cerebral-malaria-upon-zizyphus-spina-christi-treatment-in-a-murine-model
#2
Murad A Mubaraki, Taghreed A Hafiz, Saleh Al-Quraishy, Mohamed A Dkhil
The development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. The urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. Interestingly, the Zizyphus spina Cristi leaf extract (ZLE) has been found to exhibit antiplasmodial activity. This study evaluated the protective effect of ZLE against Plasmodium berghei-induced cerebral tissue injuries in mice...
March 21, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28318894/synthesis-and-human-bacterial-carbonic-anhydrase-inhibition-with-a-series-of-sulfonamides-incorporating-phthalimido-moieties
#3
Menshawy A Mohamed, Alaa A-M Abdel-Aziz, Helmy M Sakr, Adel S El-Azab, Silvia Bua, Claudiu T Supuran
A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I and II, and the α- and β-class CAs from the pathogenic bacterium Vibrio cholerae, VchCAα and VhcCAβ. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4...
March 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28279348/structure-guided-identification-of-a-family-of-dual-receptor-binding-pfemp1-that-is-associated-with-cerebral-malaria
#4
Frank Lennartz, Yvonne Adams, Anja Bengtsson, Rebecca W Olsen, Louise Turner, Nicaise T Ndam, Gertrude Ecklu-Mensah, Azizath Moussiliou, Michael F Ofori, Benoit Gamain, John P Lusingu, Jens E V Petersen, Christian W Wang, Sofia Nunes-Silva, Jakob S Jespersen, Clinton K Y Lau, Thor G Theander, Thomas Lavstsen, Lars Hviid, Matthew K Higgins, Anja T R Jensen
Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone...
March 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28273147/a-quantitative-brain-map-of-experimental-cerebral-malaria-pathology
#5
Patrick Strangward, Michael J Haley, Tovah N Shaw, Jean-Marc Schwartz, Rachel Greig, Aleksandr Mironov, J Brian de Souza, Sheena M Cruickshank, Alister G Craig, Danny A Milner, Stuart M Allan, Kevin N Couper
The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28272506/a-murine-model-to-study-epilepsy-and-sudep-induced-by-malaria-infection
#6
Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff
One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264905/perforin-expression-by-cd8-t-cells-is-sufficient-to-cause-fatal-brain-edema-during-experimental-cerebral-malaria
#7
Matthew Huggins, Holly L Johnson, Fang Jin, Aurelie N'Songo, Lisa M Hanson, Stephanie J LaFrance, Noah S Butler, John T Harty, Aaron J Johnson
Human cerebral malaria (HCM) is a serious complication of Plasmodium falciparum infection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, a large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the most prominent predictor of fatal HCM. Therefore, in this study we sought to define the mechanism controlling brain edema through the use of the murine experimental cerebral malaria (ECM) model. Specifically, we investigated the ability of CD8 T cells to initiate brain edema during ECM...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28261571/targeting-angiotensin-ii-type-1-receptor-at1r-inhibits-the-harmful-phenotype-of-plasmodium-specific-cd8-t-cells-during-blood-stage-malaria
#8
João L Silva-Filho, Celso Caruso-Neves, Ana A S Pinheiro
CD8(+) T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28249591/controlled-release-of-artemisone-for-the-treatment-of-experimental-cerebral-malaria
#9
Jacob Golenser, Viola Buchholz, Amir Bagheri, Abed Nasereddin, Ron Dzikowski, Jintao Guo, Nicholas H Hunt, Sara Eyal, Natalia Vakruk, Andreas Greiner
BACKGROUND: Cerebral malaria (CM) is a leading cause of malarial mortality resulting from infection by Plasmodium falciparum. Treatment commonly involves adjunctive care and injections or transfusion of artemisinins. All artemisinins that are in current use are metabolized to dihydroxyartemisinin (DHA), to which there is already some parasite resistance. We used artemisone, a derivative that does not convert to DHA, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an advantage given the immunopathological nature of CM)...
March 1, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28217817/a-high-pct-level-correlates-with-disease-severity-in-plasmodium-falciparum-malaria-in-children
#10
Novella Carannante, Marco Rossi, Fiorentino Fraganza, Grazia Coppola, Daniela Chiesa, Vittorio Attanasio, Francesco Sbrana, Antonio Corcione, Carlo Tascini
Most clinicians in developed countries have limited experience in making clinical assessments of malaria disease severity and/or monitoring high-level parasitemia in febrile patients with imported malaria. Hyperparasitemia is a risk factor for severe P. falciparum malaria, and procalcitonin (PCT) has recently been related to the severity of malaria. In developed countries, where not all hospital have skilled personnel to count parasitemia, a rapid test might be useful for the prompt diagnosis of malaria but unfortunately these tests are not able to count the number of parasites...
January 2017: New Microbiologica
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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