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https://www.readbyqxmd.com/read/29353010/modulation-of-immune-responses-by-plasmodium-falciparum-infection-in-asymptomatic-children-living-in-the-endemic-region-of-mbita-western-kenya
#1
Caroline Kijogi, Daisuke Kimura, Lam Quoc Bao, Risa Nakamura, Evans Asena Chadeka, Ngetich Benard Cheruiyot, Felix Bahati, Kazuhide Yahata, Osamu Kaneko, Sammy M Njenga, Yoshio Ichinose, Shinjiro Hamano, Katsuyuki Yui
Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4-16years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya...
January 15, 2018: Parasitology International
https://www.readbyqxmd.com/read/29352039/disrupting-cd147-rap2-interaction-abrogates-erythrocyte-invasion-by-plasmodium-falciparum
#2
Meng-Yao Zhang, Yang Zhang, Xiao-Dong Wu, Kun Zhang, Peng Lin, Hui-Jie Bian, Min-Min Qin, Wan Huang, Ding Wei, Zhao Zhang, Jiao Wu, Ruo Chen, Fei Feng, Bin Wang, Gang Nan, Ping Zhu, Zhi-Nan Chen
Effective vaccines against Plasmodium falciparum malaria are still lacking and the molecular mechanism of the host-parasite interaction is not fully understood. Here we demonstrate that the interaction of RAP2, a parasite secreted rhoptry protein functioning in the parasitophorous vacuole formation stage of the invasion, and CD147 on host erythrocyte is essential for erythrocyte invasion by Plasmodium falciparum and is independent from all previously identified interactions involved. Importantly, the blockade of the CD147-RAP2 interaction by HP6H8, a humanized CD147 antibody, completely abolished the parasite invasion with both cure and preventative functions in a humanized mouse model...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29351800/drug-resistance-genes-pvcrt-o-and-pvmdr-1-polymorphism-in-patients-from-malaria-endemic-south-western-coastal-region-of-india
#3
Shiny Joy, Benudhar Mukhi, Susanta K Ghosh, Rajeshwara N Achur, D Channe Gowda, Namita Surolia
BACKGROUND: Malaria is highly prevalent in many parts of India and is mostly caused by the parasite species Plasmodium vivax followed by Plasmodium falciparum. Chloroquine (CQ) is the first-line treatment for blood stage P. vivax parasites, but cases of drug resistance to CQ have been reported from India. One of the surveillance strategies which is used to monitor CQ drug resistance, is the analysis of single nucleotide polymorphisms (SNPs) of the associated gene markers. Susceptibility to CQ can also be determined by copy number assessment of multidrug resistant gene (mdr-1)...
January 19, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29349926/extracellular-vesicles-from-early-stage-p-falciparum-infected-red-blood-cells-contain-pfemp1-and-induce-transcriptional-changes-in-human-monocytes
#4
Natália G Sampaio, Samantha Emery, Alexandra Garnham, Qiao Y Tan, Xavier Sisquella, Matthew A Pimentel, Neta Regev-Rudzki, Louis Schofield, Emily M Eriksson
Pathogens can release extracellular vesicles (EVs) for cell-cell communication and host modulation. EVs from Plasmodium falciparum, the deadliest malaria parasite species, can transfer drug resistance genes between parasites. EVs from late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect endothelial cell permeability, but little is known about EVs from early-stage iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for iRBC adherence and a major contributor to disease severity, in EVs only up to 12 hours-post RBC invasion...
January 18, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29348637/plasmodium-dihydrofolate-reductase-is-a-second-enzyme-target-for-the-antimalarial-action-of-triclosan
#5
Elizabeth Bilsland, Liisa van Vliet, Kevin Williams, Jack Feltham, Marta P Carrasco, Wesley L Fotoran, Eliana F G Cubillos, Gerhard Wunderlich, Morten Grøtli, Florian Hollfelder, Victoria Jackson, Ross D King, Stephen G Oliver
Malaria, caused by parasites of the genus Plasmodium, leads to over half a million deaths per year, 90% of which are caused by Plasmodium falciparum. P. vivax usually causes milder forms of malaria; however, P. vivax can remain dormant in the livers of infected patients for weeks or years before re-emerging in a new bout of the disease. The only drugs available that target all stages of the parasite can lead to severe side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; hence, there is an urgent need to develop new drugs active against blood and liver stages of the parasite...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348479/prime-boost-vaccination-with-recombinant-protein-and-adenovirus-vector-expressing-plasmodium-vivax-circumsporozoite-protein-csp-partially-protects-mice-against-pb-pv-sporozoite-challenge
#6
Tarsila Mendes de Camargo, Elisângela Oliveira de Freitas, Alba Marina Gimenez, Luciana Chagas Lima, Karina de Almeida Caramico, Kátia Sanches Françoso, Oscar Bruna-Romero, Chiara Andolina, François Nosten, Laurent Rénia, Hildegund C J Ertl, Ruth S Nussenzweig, Victor Nussenzweig, Mauricio M Rodrigues, Arturo Reyes-Sandoval, Irene S Soares
Vaccine development against Plasmodium vivax malaria lags behind that for Plasmodium falciparum. To narrow this gap, we administered recombinant antigens based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia pastoris two chimeric proteins by merging the three central repeat regions of different CSP alleles (VK210, VK247, and P. vivax-like). The first construct (yPvCSP-AllFL) contained the fused repeat regions flanked by N- and C-terminal regions. The second construct (yPvCSP-AllCT) contained the fused repeat regions and the C-terminal domain, plus RI region...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347975/single-low-dose-primaquine-for-blocking-transmission-of-plasmodium-falciparum-malaria-a-proposed-model-derived-age-based-regimen-for-sub-saharan-africa
#7
W Robert Taylor, Htee Khu Naw, Kathryn Maitland, Thomas N Williams, Melissa Kapulu, Umberto D'Alessandro, James A Berkley, Philip Bejon, Joseph Okebe, Jane Achan, Alfred Ngwa Amambua, Muna Affara, Davis Nwakanma, Jean-Pierre van Geertruyden, Muhindo Mavoko, Pascal Lutumba, Junior Matangila, Philipe Brasseur, Patrice Piola, Rindra Randremanana, Estrella Lasry, Caterina Fanello, Marie Onyamboko, Birgit Schramm, Zolia Yah, Joel Jones, Rick M Fairhurst, Mahamadou Diakite, Grace Malenga, Malcolm Molyneux, Claude Rwagacondo, Charles Obonyo, Endalamaw Gadisa, Abraham Aseffa, Mores Loolpapit, Marie-Claire Henry, Grant Dorsey, Chandy John, Sodiomon B Sirima, Karen I Barnes, Peter Kremsner, Nicholas P Day, Nicholas J White, Mavuto Mukaka
BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0...
January 18, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29347942/infant-and-child-mortality-in-relation-to-malaria-transmission-in-kemri-cdc-hdss-western-kenya-validation-of-verbal-autopsy
#8
Nyaguara O Amek, Annemieke Van Eijk, Kim A Lindblade, Mary Hamel, Nabie Bayoh, John Gimnig, Kayla F Laserson, Laurence Slutsker, Thomas Smith, Penelope Vounatsou
BACKGROUND: Malaria transmission reduction is a goal of many malaria control programmes. Little is known of how much mortality can be reduced by specific reductions in transmission. Verbal autopsy (VA) is widely used for estimating malaria specific mortality rates, but does not reliably distinguish malaria from other febrile illnesses. Overall malaria attributable mortality includes both direct and indirect deaths. It is unclear what proportion of the deaths averted by reducing malaria transmission are classified as malaria in VA...
January 18, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29346080/new-insight-into-the-action-of-tryptanthrins-against-plasmodium-falciparum-pharmacophore-identification-via-a-novel-submolecular-qsar-descriptor
#9
Joel A Olson, Raymond J Terryn, Elizabeth L Stewart, J Clayton Baum, Mark J Novak
A new submolecular quantitative structure activity relationship (QSAR) descriptor was applied toward elucidating the anti-malarial pharmacophore of tryptanthrins, a class of compounds known for their anti-parasitic activities. The new descriptor is based on experimental and computational measurements of the tunneling barriers of individual lobes of the molecular orbitals. Lobe-by-lobe QSAR correlation plots revealed a single lobe of the LUMO to be strongly associated with tryptanthrin's anti-malarial activity...
December 27, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29345221/therapeutic-response-to-dihydroartemisinin-piperaquine-for-p-falciparum-and-p-vivax-nine-years-after-its-introduction-in-southern-papua-indonesia
#10
Jeanne Rini Poespoprodjo, Enny Kenangalem, Johny Wafom, Freis Chandrawati, Agatha M Puspitasari, Benedikt Ley, Leily Trianti, Zoé Korten, Asik Surya, Din Syafruddin, Nicholas M Anstey, Jutta Marfurt, Rintis Noviyanti, Ric N Price
Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days...
January 15, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29345110/remarkable-similarity-in-plasmodium-falciparum-and-plasmodium-vivax-geranylgeranyl-diphosphate-synthase-ggpps-dynamics-and-its-implication-for-anti-malarial-drug-design
#11
Aishwarya Venkatramani, Clarisse G Ricci, Eric Oldfield, J Andrew McCammon
Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a growing cause of morbidity and mortality. P. falciparum is more lethal than is P. vivax, but there is a vital need for effective drugs against both species. Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the biosynthesis of quinones and in protein prenylation, and has been proposed to be a malaria drug target. However, the structure of P. falciparum GGPPS (PfGGPPS) has not been determined, due to difficulties in crystallization...
January 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29343745/malaria-infected-red-blood-cells-release-small-regulatory-rnas-through-extracellular-vesicles
#12
Kehinde Adebayo Babatunde, Smart Mbagwu, María Andrea Hernández-Castañeda, Swamy R Adapa, Michael Walch, Luis Filgueira, Laurent Falquet, Rays H Y Jiang, Ionita Ghiran, Pierre-Yves Mantel
The parasite Plasmodium falciparum causes the most severe form of malaria. Cell communication between parasites is an important mechanism to control population density and differentiation. The infected red blood cells (iRBCs) release small extracellular vesicles (EVs) that transfer cargoes between cells. The EVs synchronize the differentiation of the asexual parasites into gametocytes to initiate the transmission to the mosquito. Beside their role in parasite communication, EVs regulate vascular function. So far, the exact cargoes responsible for cellular communication remain unknown...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342401/matched-placental-and-circulating-plasmodium-falciparum-parasites-are-genetically-homologous-at-the-var2csa-id1-dbl2x-locus-by-deep-sequencing
#13
Andreea Waltmann, Jaymin C Patel, Kyaw L Thwai, Nicholas J Hathaway, Christian M Parobek, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Philippe Deloron, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
In pregnancy-associated malaria, infected erythrocytes accumulate in the placenta. It is unclear if in polyclonal infections this results in distinct peripheral and placental parasite populations. We used long amplicon deep sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral and placental samples collected at delivery from a high transmission area to determine genetic homology. Despite substantial sequence variation and detecting 23 haplotypes, the matched pairs mostly contained the same genetic variants, with 11 pairs sharing 100% of their variants, whereas others showed some heterogeneity...
January 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29342267/safety-of-single-dose-primaquine-in-g6pd-deficient-and-g6pd-normal-males-in-mali-without-malaria-an-open-label-phase-1-dose-adjustment-trial
#14
Ingrid Chen, Halimatou Diawara, Almahamoudou Mahamar, Koualy Sanogo, Sekouba Keita, Daouda Kone, Kalifa Diarra, Moussa Djimde, Mohamed Keita, Joelle Brown, Michelle E Roh, Jimee Hwang, Helmi Pett, Maxwell Murphy, Mikko Niemi, Bryan Greenhouse, Teun Bousema, Roly Gosling, Alassane Dicko
Background: The World Health Organization recommendation on the use of single low-dose primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. Methods: We conducted an open-label, non-randomized, dose-adjustment trial of the safety of three single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys ages 11-17 years, and 5-10 years, including G6PD-normal control groups...
January 12, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29342212/sequence-variation-in-plasmodium-falciparum-merozoite-surface-protein-2-is-associated-with-virulence-causing-severe-and-cerebral-malaria
#15
Suwanna Chaorattanakawee, Pornlada Nuchnoi, Hathairad Hananantachai, Uranan Tumkosit, David Saunders, Izumi Naka, Jun Ohashi, Jintana Patarapotikul
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease...
2018: PloS One
https://www.readbyqxmd.com/read/29342187/induction-of-high-tolerance-to-artemisinin-by-sub-lethal-administration-a-new-in-vitro-model-of-p-falciparum
#16
Serena De Lucia, Ioannis Tsamesidis, Maria Carmina Pau, Kristina R Kesely, Antonella Pantaleo, Francesco Turrini
Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P...
2018: PloS One
https://www.readbyqxmd.com/read/29340263/diagnostic-delay-for-imported-malaria-a-case-of-plasmodium-falciparum-malaria-misdiagnosed-as-common-cold
#17
Ryota Hase
A 37-year-old Japanese man experienced fever and headache 8 days after returning to Japan following a 6-month stay in Nigeria. He visited two clinics but was sent home from each with a diagnosis of common cold. He was eventually brought to the emergency department with an altered mental status. Severe P. falciparum malaria was confirmed; his initial parasitemia index was 5.4%. He recovered fully with antimalarial treatment. This case suggests that primary care physicians should obtain recent travel history and consider malaria for any febrile patient who has returned from a malaria-endemic area...
January 2018: Journal of General and Family Medicine
https://www.readbyqxmd.com/read/29339517/infected-erythrocytes-expressing-dc13-pfemp1-differ-from-recombinant-proteins-in-epcr-binding-function
#18
Yvonne Azasi, Gabriella Lindergard, Ashfaq Ghumra, Jianbing Mu, Louis H Miller, J Alexandra Rowe
Recent advances have identified a new paradigm for cerebral malaria pathogenesis in which endothelial protein C receptor (EPCR) is a major host receptor for sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain and other vital organs. The parasite adhesins that bind EPCR are members of the IE variant surface antigen family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) containing specific adhesion domains called domain cassette (DC) 8 and DC13. The binding interaction site between PfEMP1 and EPCR has been mapped by biophysical and crystallography studies using recombinant proteins...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339390/identification-of-hsp90-inhibitors-with-anti-plasmodium-activity
#19
Dora Posfai, Amber L Eubanks, Allison I Keim, Kuan-Yi Lu, Grace Z Wang, Philip F Hughes, Nobutaka Kato, Timothy A Haystead, Emily R Derbyshire
Malaria remains a global health burden partly due to Plasmodium parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood stage Plasmodium parasites, but details about its function during malaria's elusive liver stage are unclear. We used target-based screens to identify compounds that bind to Plasmodium falciparum and human Hsp90, which revealed insights into chemotypes with species selective binding. Using cell-based malaria assays, we demonstrate that all identified Hsp90-binding compounds are liver and blood stage Plasmodium inhibitors...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29338786/a-systematic-review-of-transfusion-transmitted-malaria-in-non-endemic-areas
#20
Federica Verra, Andrea Angheben, Elisa Martello, Giovanni Giorli, Francesca Perandin, Zeno Bisoffi
BACKGROUND: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient's bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients...
January 16, 2018: Malaria Journal
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