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Plasmodium falciparum

Aditi A Sidhaye, Kanchan C Bhuran, Sneha Zambare, Munna Abubaker, Niroshini Nirmalan, Kamalinder K Singh
AIM: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. METHODS: Artemether-loaded nanoparticles (AANs) were designed and antimalarial activity evaluated in vitro/in vivo using Plasmodium falciparum/Plasmodium berghei species, respectively...
October 19, 2016: Nanomedicine
Kawsar R Talaat, Ruth D Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J MacDonald, Xiaowei Wang, Michael P Fay, Sara A Healy, Anna P Durbin, David L Narum, Yimin Wu, Patrick E Duffy
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®...
2016: PloS One
Claire Le Manach, Aloysius T Nchinda, Tanya Paquet, Diego Gonzalez Cabrera, Yassir Younis Adam, Ze Han, Sridevi Bashyam, Mohammed Zabiulla, Dale Taylor, Nina Lawrence, Karen L White, Susan A Charman, David Waterson, Michael J Witty, Sergio Wittlin, Mariette E Botha, Sindisiswe H Nondaba, Janette Reader, Lyn-Marie Birkholtz, Maria Belen Jimenez-Diaz, Maria S Martínez-Martínez, Santiago Ferrer-Bazaga, Iñigo Angulo-Barturen, Stephan Meister, Yevgeniya Antonova-Koch, Elizabeth A Winzeler, Leslie J Street, Kelly Chibale
Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics, and additionally, very potent activity against the liver and gametocyte parasite life-cycle stages...
October 17, 2016: Journal of Medicinal Chemistry
Neha Chaturvedi, Praveen K Bharti, Archana Tiwari, Neeru Singh
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses...
June 2016: Indian Journal of Medical Research
Luís Felipe S P Azeredo, Julia P Coutinho, Valquiria A P Jabor, Patricia R Feliciano, Maria Cristina Nonato, Carlos R Kaiser, Carla Maria S Menezes, Amanda S O Hammes, Ernesto Raul Caffarena, Lucas V B Hoelz, Nicolli B de Souza, Glaécia A N Pereira, Isabela P Cerávolo, Antoniana U Krettli, Nubia Boechat
Malaria remains one of the most serious global infectious diseases. An important target for antimalarial chemotherapy is the enzyme dihydroorotate dehydrogenase from Plasmodium falciparum (PfDHODH), which is responsible for the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthetic pathway. In this study, we have designed and synthesized fifteen 7-arylpyrazolo[1,5-a]pyrimidine derivatives using ring bioisosteric replacement and molecular hybridization of functional groups based on the highly active 5-methyl-N-(naphthalen-2-yl)-2-(trifluoromethyl)- [1,2,4]triazolo[1,5-a]pyrimidin-7-amine...
September 30, 2016: European Journal of Medicinal Chemistry
Dene R Littler, Hayley E Bullen, Katherine L Harvey, Travis Beddoe, Brendan S Crabb, Jamie Rossjohn, Paul R Gilson
The ubiquitous second messenger cAMP mediates signal transduction processes in the malarial parasite that regulate host erythrocyte invasion and the proliferation of merozoites. In Plasmodium falciparum the central receptor for cAMP is the single regulatory subunit (R) of Protein kinase A (PKA). To aid the development of compounds that can selectively dysregulate parasite PKA signalling we solved the structure of the PKA regulatory subunit in complex with cAMP and a related analog that displays antimalarial activity: Sp-2Cl-cAMPS...
October 13, 2016: Journal of Biological Chemistry
Praveen K Bharti, Man M Shukla, Pascal Ringwald, Sri Krishna, Pushpendra P Singh, Ajay Yadav, Sweta Mishra, Usha Gahlot, Jai P Malaiya, Amit Kumar, Shambhu Prasad, Pradeep Baghel, Mohan Singh, Jaiprakash Vadadi, Mrigendra P Singh, Maria Dorina G Bustos, Leonard I Ortega, Eva-Maria Christophel, Sher S Kashyotia, Gagan S Sonal, Neeru Singh
BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states...
October 13, 2016: Malaria Journal
Kenn Foubert, Taposh Gorella, Ahmad Faizal, Paul Cos, Louis Maes, Sandra Apers, Danny Geelen, Luc Pieters
Within an ongoing research program on saponins with potential antileishmanial activity, four previously undescribed saponins were isolated from Maesa argentea leaves and identified by LC-MS/MS, GC-MS, and 1D and 2D NMR spectroscopy as 3β-O-{([β-D-glucopyranosyl-(1 → 2)-α-L-rhamnopyranosyl-(1 → 2)-β-D-galactopyranosyl-(1 → 3)]-[β-D-galactopyranosyl-(1 → 2)]-β-D-glucuronopyranosyl)}-21β-angeloyloxy-22α-butanoyloxy-13β,28-oxidoolean-16α,28α-diol (1), 3β-O-{([β-D-glucopyranosyl-(1 → 2)-α-L-rhamnopyranosyl-(1 → 2)-β-D-galactopyranosyl-(1 → 3)]-[β-D-galactopyranosyl-(1 → 2)]-β-D-glucuronopyranosyl)}-21β,22α-angeloyloxy-13β,28-oxidoolean-16α,28α-diol (2), 3β-O-{([β-D-glucopyranosyl-(1 → 2)-α-L-rhamnopyranosyl-(1 → 2)-β-D-galactopyranosyl-(1 → 3)]-[β-D-galactopyranosyl-(1 → 2)]-β-D-glucuronopyranosyl)}-21β-angeloyloxy-22α-(E)-cinnamoyloxy-13β,28-oxidoolean-16α,28α-diol (3), and 3β-O-{([α-L-rhamnopyranosyl-(1 → 2)-β-D-galactopyranosyl-(1 → 3)]-[β-D-galactopyranosyl-(1 → 2)]-β-D-glucuronopyranosyl)}-21β-angeloyloxy-22α-(E)-cinnamoyloxy-13β,28-oxidoolean-16α,28α-diol (4)...
October 13, 2016: Planta Medica
Thomas E Kraft, Monique R Heitmeier, Marina Putanko, Rachel L Edwards, Ma Xenia G Ilagan, Maria A Payne, Joseph M Autry, David D Thomas, Audrey R Odom, Paul W Hruz
The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose-sensor...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Karin Blomqvist, Christen DiPetrillo, Vincent A Streva, Stewart Pine, Jeffrey D Dvorin
Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm...
October 11, 2016: Molecular and Biochemical Parasitology
Alvaro Molina-Cruz, Martine M Zilversmit, Daniel E Neafsey, Daniel L Hartl, Carolina Barillas-Mury
Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P...
October 3, 2016: Annual Review of Genetics
Amuza Byaruhanga Lucky, Miako Sakaguchi, Yuko Katakai, Satoru Kawai, Kazuhide Yahata, Thomas J Templeton, Osamu Kaneko
The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts...
2016: PloS One
Yoann Duffier, Audrey Lorthiois, Pau Cisteró, Florian Dupuy, Grégory Jouvion, Laurence Fiette, Dominique Mazier, Alfredo Mayor, Catherine Lavazec, Alicia Moreno Sabater
The development of new drugs to disrupt malaria transmission requires the establishment of an in vivo model to address the biology of Plasmodium falciparum sexual stages (gametocytes). Herein we show that chemically immune-modulated NSG mice grafted with human erythrocytes support complete sexual development of P. falciparum parasites and generate high gametocytemia. Immunohistochemistry and RT-qPCR analyses indicate an enrichment of immature gametocytes in the bone marrow and the spleen, suggesting a sequestration mechanism reminiscent to that observed in humans...
October 12, 2016: Scientific Reports
Andrea K Boggild, Jennifer Geduld, Michael Libman, Cedric P Yansouni, Anne E McCarthy, Jan Hajek, Wayne Ghesquiere, Jean Vincelette, Susan Kuhn, David O Freedman, Kevin C Kain
BACKGROUND: Malaria remains the most common specific cause of fever in returned travellers and can be life-threatening. We examined demographic and travel correlates of malaria among Canadian travellers and immigrants to identify groups for targeted pretravel intervention. METHODS: Descriptive data on ill returned Canadian travellers and immigrants presenting to a CanTravNet site between 2004 and 2014 with a diagnosis of malaria were analyzed. Data were collected using the GeoSentinel data platform...
July 2016: CMAJ Open
Joshua M A Stough, Stephen P Dearth, Joshua E Denny, Gary R LeCleir, Nathan W Schmidt, Shawn R Campagna, Steven W Wilhelm
C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome...
2016: Frontiers in Microbiology
Kunal, P K Agrawal, M Ghosh, Vishal Parmar, Sankar Suman
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Peter W Gething, Daniel C Casey, Daniel J Weiss, Donal Bisanzio, Samir Bhatt, Ewan Cameron, Katherine E Battle, Ursula Dalrymple, Jennifer Rozier, Puja C Rao, Michael J Kutz, Ryan M Barber, Chantal Huynh, Katya A Shackelford, Matthew M Coates, Grant Nguyen, Maya S Fraser, Rachel Kulikoff, Haidong Wang, Mohsen Naghavi, David L Smith, Christopher J L Murray, Simon I Hay, Stephen S Lim
Background Malaria control has not been routinely informed by the assessment of subnational variation in malaria deaths. We combined data from the Malaria Atlas Project and the Global Burden of Disease Study to estimate malaria mortality across sub-Saharan Africa on a grid of 5 km(2) from 1990 through 2015. Methods We estimated malaria mortality using a spatiotemporal modeling framework of geolocated data (i.e., with known latitude and longitude) on the clinical incidence of malaria, coverage of antimalarial drug treatment, case fatality rate, and population distribution according to age...
October 10, 2016: New England Journal of Medicine
Gihoon Choi, Daniel Song, Sony Shrestha, Jun Miao, Liwang Cui, Weihua Guan
In response to the urgent need of a field-deployable and highly sensitive malaria diagnosis, we developed a standalone, "sample-in-answer-out" molecular diagnostic system (AnyMDx) to enable quantitative molecular analysis of blood-borne malaria in low resource areas. The system consists of a durable battery-powered analyzer and a disposable microfluidic compact disc loaded with reagents ready for use. A low power thermal module and a novel fluorescence-sensing module are integrated into the analyzer for real-time monitoring of loop-mediated isothermal nucleic acid amplification (LAMP) of target parasite DNA...
October 10, 2016: Lab on a Chip
Cheryl Sarah Philipose, T Umashankar
INTRODUCTION: Malaria is a mosquito borne disease which is a major public health problem and a leading cause of morbidity and mortality worldwide. Various haematological parameters have been studied to help predict malaria, such as alteration in the leucocyte count, platelet counts and erythrocyte counts. The neutrophil lymphocyte count ratio (NLCR) was found to have a good predictive value in systemic inflammation, particularly in critical care setting. AIMS AND OBJECTIVES: The present study aims to study the various haematological parameters and acertain the predictive value of NLCR and MLR in the detection of malaria...
July 2016: Tropical Parasitology
Hiasindh Ashmi Antony, Vrushali Pathak, Kanjaksha Ghosh, Subhash Chandra Parija
OBJECTIVE: The objective of this study was to compare the protein expression patterns of Plasmodium falciparum extracellular and intracellular proteins separated by two-dimensional electrophoresis (2-DE) from the chloroquine-sensitive (CQS) MRC2 strain and chloroquine-resistant (CQR) RKL9 strain. Materials and Methods: Both the extracellular protein (ECP) and intracellular protein (ICP) were extracted and solubilized. The proteins were separated by 2-DE, first based on their charges using isoelectric focusing and then their sizes by electrophoresis...
July 2016: Tropical Parasitology
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