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https://www.readbyqxmd.com/read/28732053/dysregulation-of-pulmonary-endothelial-protein-c-receptor-and-thrombomodulin-in-severe-falciparum-malaria-associated-ards-relevant-to-hemozoin
#1
Sitang Maknitikul, Natthanej Luplertlop, Georges E R Grau, Sumate Ampawong
To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution. A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined. Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging...
2017: PloS One
https://www.readbyqxmd.com/read/28732045/the-exported-chaperone-hsp70-x-supports-virulence-functions-for-plasmodium-falciparum-blood-stage-parasites
#2
Sarah C Charnaud, Matthew W A Dixon, Catherine Q Nie, Lia Chappell, Paul R Sanders, Thomas Nebl, Eric Hanssen, Matthew Berriman, Jo-Anne Chan, Adam J Blanch, James G Beeson, Julian C Rayner, Jude M Przyborski, Leann Tilley, Brendan S Crabb, Paul R Gilson
Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes of malaria, P. falciparum and P. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (IE) in the microvasculature. Cytoadhesion of P. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modify the erythrocyte cytoskeleton while others such as PfEMP1 project onto the erythrocyte surface where they bind to endothelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28731898/steady-progress-toward-a-malaria-vaccine
#3
Kirsten E Lyke
PURPOSE OF REVIEW: Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. RECENT FINDINGS: Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection...
July 20, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28729672/plasmodium-berghei-p47-is-essential-for-ookinete-protection-from-the-anopheles-gambiae-complement-like-response
#4
Chiamaka Valerie Ukegbu, Maria Giorgalli, Hassan Yassine, Jose Luis Ramirez, Chrysanthi Taxiarchi, Carolina Barillas-Mury, George K Christophides, Dina Vlachou
Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728995/a-mechanistic-model-quantifies-artemisinin-induced-parasite-growth-retardation-in-blood-stage-plasmodium-falciparum-infection
#5
Pengxing Cao, Nectarios Klonis, Sophie Zaloumis, David S Khoury, Deborah Cromer, Miles P Davenport, Leann Tilley, Julie A Simpson, James M McCaw
Falciparum malaria is a major parasitic disease causing widespread morbidity and mortality globally. Artemisinin derivatives-the most effective and widely-used antimalarials that have helped reduce the burden of malaria by 60% in some areas over the past decade-have recently been found to induce growth retardation of blood-stage Plasmodium falciparum when applied at clinically relevant concentrations. To date, no model has been designed to quantify the growth retardation effect and to predict the influence of this property on in vivo parasite killing...
July 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28728898/kbe009-an-antimalarial-bestatin-like-inhibitor-of-the-plasmodium-falciparum-m1-aminopeptidase-discovered-in-an-ugi-multicomponent-reaction-derived-peptidomimetic-library
#6
Jorge González-Bacerio, Sarah El Chamy Maluf, Yanira Méndez, Isel Pascual, Isabelle Florent, Pollyana M S Melo, Alexandre Budu, Juliana C Ferreira, Ernesto Moreno, Adriana K Carmona, Daniel G Rivera, Maday Alonso Del Rivero, Marcos L Gazarini
Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P...
July 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28724450/variation-in-species-composition-and-infection-rates-of-anopheles-mosquitoes-at-different-altitudinal-transects-and-the-risk-of-malaria-in-the-highland-of-dirashe-woreda-south-ethiopia
#7
Taye Yohannes Daygena, Fekadu Massebo, Bernt Lindtjørn
BACKGROUND: The transmission of malaria is heterogeneous, and varies due to altitude. The information on whether the transmission of malaria is indigenous or imported to highland areas is scarce. Therefore, this study aimed to assess the species composition and infection rates of Anopheles at different altitudinal transects, and the risk of malaria if any in the highland of Dirashe Woreda, South Ethiopia. METHODS: This study was conducted in Gato (low altitude; average elevation of 1273 m), Onota (mid-altitude; average elevation of 1707 m) and Layignaw-Arguba (high altitude; average elevation of 2337 m) from August 2015 to April 2016...
July 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#8
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28724402/a-dual-colour-fluorescence-in-situ-hybridization-fish-assay-for-identifying-the-zoonotic-malaria-parasite-plasmodium-knowlesi-with-a-potential-application-for-the-specific-diagnosis-of-knowlesi-malaria-in-peripheral-level-laboratories-of-southeast-asia
#9
Jyotsna Shah, Akhila Poruri, Olivia Mark, Urmila Khadilka, Franziska Mohring, Robert W Moon, Ranjan Ramasamy
BACKGROUND: Plasmodium knowlesi is primarily responsible for zoonotic malaria in several Southeast Asian countries. Precise identification of the parasite in the blood of patients presently relies on an expensive and elaborate PCR procedure because microscopic examination of blood and other available field identification techniques lack adequate specificity. Therefore, the use of a simple and inexpensive dual-colour fluorescence in situ hybridization (FISH) assay, analogous to FISH assays recently described for Plasmodium falciparum and Plasmodium vivax, was investigated as a potential tool for identifying P...
July 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#10
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28723116/integrated-magnetic-bead-quantum-dot-immunoassay-for-malaria-detection
#11
Chloe Kim, Gwendolyn Hoffmann, Peter C Searson
Malaria persists as a disease of high morbidity and mortality due to improper diagnosis, overuse of drugs, rapidly evolving drug resistant parasites, and poor disease monitoring. The two common tests used in developing countries, microscopic examination of Glemsa slides and rapid diagnostic tests (RDTs), have limitations associated with variability in specificity and sensitivity, and qualitative outcome. Here we report on an immunoassay using magnetic beads for capture and quantum dots for detection of histidine-rich protein 2 (HRP2)...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722611/phase-2a-open-label-4-escalating-dose-randomized-multicenter-study-evaluating-the-safety-and-activity-of-ferroquine-ssr97193-plus-artesunate-versus-amodiaquine-plus-artesunate-in-african-adult-men-with-uncomplicated-plasmodium-falciparum-malaria
#12
Christian Supan, Ghyslain Mombo-Ngoma, Maryvonne Kombila, Carmen L Ospina Salazar, Jana Held, Bertrand Lell, Cathy Cantalloube, Elhadj Djeriou, Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E Polhemus, Peter G Kremsner, Douglas S Walsh
Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722588/optimizing-direct-membrane-and-direct-skin-feeding-assays-for-plasmodium-falciparum-transmission-blocking-vaccine-trials-in-bancoumana-mali
#13
Mamadou B Coulibaly, Erin E Gabriel, Youssouf Sinaba, Daman Sylla, Adama Sacko, Lakamy Sylla, Boubacar Coulibaly, Jen C C Hume, Ibrahima Baber, Mahamadoun H Assadou, Issaka Sagara, Yimin Wu, Sara A Healy, Ogobara Doumbo, Sekou F Traore, Patrick E Duffy
Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali, since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA)...
June 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722587/lack-of-geospatial-population-structure-yet-significant-linkage-disequilibrium-in-the-reservoir-of-plasmodium-falciparum-in-bongo-district-ghana
#14
Shazia Ruybal-Pesántez, Kathryn E Tiedje, Mary M Rorick, Lucas Amenga-Etego, Anita Ghansah, Abraham Oduro, Kwadwo A Koram, Karen P Day
Malaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD...
July 3, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722583/a-direct-from-blood-reverse-transcriptase-polymerase-chain-reaction-assay-for-monitoring-falciparum-malaria-parasite-transmission-in-elimination-settings
#15
Brian J Taylor, Kjerstin Lanke, Shanna L Banman, Isabelle Morlais, Merribeth J Morin, Teun Bousema, Sanna R Rijpma, Stephanie K Yanow
We describe a novel one-step reverse transcriptase real-time PCR (direct RT-PCR) for Plasmodium falciparum malaria parasites that amplifies RNA targets directly from blood. We developed the assay to identify gametocyte-specific transcripts in parasites from patient blood samples, as a means of monitoring malaria parasite transmission in field settings. To perform the test, blood is added directly to a master mix in PCR tubes and analyzed by real-time PCR. The limit of detection of the assay on both conventional and portable real-time PCR instruments was 100 parasites/mL for 18S rRNA, and 1,000 parasites/mL for asexual (PFE0065W) and gametocyte (PF14_0367, PFGEXP5) mRNA targets...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722569/mass-azithromycin-and-malaria-parasitemia-in-niger-results-from-a-community-randomized-trial
#16
Kieran S O'Brien, Sun Y Cotter, Abdou Amza, Boubacar Kadri, Baido Nassirou, Nicole E Stoller, Zhaoxia Zhou, Chris Cotter, Sheila K West, Robin L Bailey, Philip J Rosenthal, Bruce D Gaynor, Travis C Porco, Thomas M Lietman
Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years...
June 19, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28720171/pacbio-assembly-of-a-plasmodium-knowlesi-genome-sequence-with-hi-c-correction-and-manual-annotation-of-the-sicavar-gene-family
#17
S A Lapp, J A Geraldo, J-T Chien, F Ay, S B Pakala, G Batugedara, J Humphrey, J D DeBARRY, K G Le Roch, M R Galinski, J C Kissinger
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features...
July 19, 2017: Parasitology
https://www.readbyqxmd.com/read/28720134/in-vitro-antioxidant-and-antimalarial-activities-of-leaves-pods-and-bark-extracts-of-acacia-nilotica-l-del
#18
Muhammad Bilal Sadiq, Pattamon Tharaphan, Kesinee Chotivanich, Joel Tarning, Anil Kumar Anal
BACKGROUND: The emergence of drug resistant malaria is threatening our ability to treat and control malaria in the Southeast Asian region. There is an urgent need to develop novel and chemically diverse antimalarial drugs. This study aimed at evaluating the antimalarial and antioxidant potentials of Acacia nilotica plant extracts. METHODS: The antioxidant activities of leaves, pods and bark extracts were determined by standard antioxidant assays; reducing power capacity, % lipid peroxidation inhibition and ferric reducing antioxidant power assay...
July 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28719950/isolation-and-characterization-of-vaccine-candidate-genes-including-csp-and-msp1-in-plasmodium-yoelii
#19
Seon-Hee Kim, Young-An Bae, Ju-Young Seoh, Hyun-Jong Yang
Malaria is an infectious disease affecting humans, which is transmitted by the bite of Anopheles mosquitoes harboring sporozoites of parasitic protozoans belonging to the genus Plasmodium. Despite past achievements to control the protozoan disease, malaria still remains a significant health threat up to now. In this study, we cloned and characterized the full-unit Plasmodium yoelii genes encoding merozoite surface protein 1 (MSP1), circumsporozoite protein (CSP), and Duffy-binding protein (DBP), each of which can be applied for investigations to obtain potent protective vaccines in the rodent malaria model, due to their specific expression patterns during the parasite life cycle...
June 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28719306/seasonal-variation-in-the-epidemiology-of-asymptomatic-plasmodium-falciparum-infections-across-two-catchment-areas-in-bongo-district-ghana
#20
Kathryn E Tiedje, Abraham R Oduro, Godfred Agongo, Thomas Anyorigiya, Daniel Azongo, Timothy Awine, Anita Ghansah, Mercedes Pascual, Kwadwo A Koram, Karen P Day
Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55...
July 2017: American Journal of Tropical Medicine and Hygiene
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