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https://www.readbyqxmd.com/read/30315162/epistasis-studies-reveal-redundancy-among-calcium-dependent-protein-kinases-in-motility-and-invasion-of-malaria-parasites
#1
Hanwei Fang, Ana Rita Gomes, Natacha Klages, Paco Pino, Bohumil Maco, Eloise M Walker, Zenon A Zenonos, Fiona Angrisano, Jake Baum, Christian Doerig, David A Baker, Oliver Billker, Mathieu Brochet
In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members of a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 genetic interactions among protein kinases in Plasmodium berghei. This reveals a synthetic negative interaction between a hypomorphic allele of the protein kinase G (PKG) and CDPK4 to control erythrocyte invasion which is conserved in P...
October 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/30314489/prevalence-of-plasmodium-falciparum-infection-among-pregnant-women-at-first-antenatal-visit-in-post-ebola-monrovia-liberia
#2
Guillermo Martínez-Pérez, Dawoh Peter Lansana, Senga Omeonga, Himanshu Gupta, Bondey Breeze-Barry, Raquel González, Azucena Bardají, Adelaida Sarukhan, James D K Goteh, Edith Tody, Pau Cisteró, Benard Benda, Juwe D Kercula, Fanta D Kibungu, Ana Meyer García-Sípido, Quique Bassat, Christine K Tarr-Attia, Alfredo Mayor
BACKGROUND: Disruption of malaria control strategies during the West African 2014-2016 Ebola epidemic led to an increase in malaria-attributable mortality. However, recent data on malaria infection in vulnerable groups, such as pregnant women, are lacking in this post-Ebola scenario. This cross-sectional study aimed to assess the prevalence of Plasmodium falciparum infection and of molecular markers of drug resistance among pregnant women attending antenatal care in Monrovia, capital of Liberia...
October 11, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30314440/genetic-polymorphism-and-natural-selection-of-circumsporozoite-surface-protein-in-plasmodium-falciparum-field-isolates-from-myanmar
#3
Hương Giang Lê, Jung-Mi Kang, Mya Moe, Hojong Jun, Thị Lam Thái, Jinyoung Lee, Moe Kyaw Myint, Khin Lin, Woon-Mok Sohn, Ho-Joon Shin, Tong-Soo Kim, Byoung-Kuk Na
BACKGROUND: Plasmodium falciparum circumsporozoite protein (PfCSP) is one of the most extensively studied malaria vaccine candidates, but the genetic polymorphism of PfCSP within and among the global P. falciparum population raises concerns regarding the efficacy of a PfCSP-based vaccine efficacy. In this study, genetic diversity and natural selection of PfCSP in Myanmar as well as global P. falciparum were comprehensively analysed. METHODS: Blood samples were collected from 51 P...
October 12, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30308208/in-silico-modeling-of-plasmodium-falciparum-chloroquine-resistance-transporter-protein-and-biochemical-studies-suggest-its-key-contribution-to-chloroquine-resistance
#4
Hiasindh Ashmi Antony, Nishith Saurav Topno, Sathyanarayana N Gummadi, Devanarayanan Siva Sankar, Ramadas Krishna, Subhash Chandra Parija
Chloroquine (CQ) has been used for decades as the primary chemotherapeutic drug for the treatment of malaria. The emergence of drug resistance in Plasmodium falciparum has been considered to be because of the excessive use of antimalarial drugs worldwide. Moreover, the intense distribution and prevalence of chloroquine-resistant strains in endemic regions has aided the incidence of more complications to malaria treatment and control. Due to the lack of literature that portrays evident molecular mechanisms of drug resistance, it has been difficult to understand the drug resistance conferred by Plasmodium species...
October 8, 2018: Acta Tropica
https://www.readbyqxmd.com/read/30305101/dynamics-of-plasmodium-falciparum-gametocyte-carriage-in-pregnant-women-under-intermittent-preventive-treatment-with-sulfadoxine-pyrimethamine-in-benin
#5
Sayeh Jafari-Guemouri, Jamila Dhiab, Achille Massougbodji, Philippe Deloron, Ndam N Tuikue
BACKGROUND: In sub-Saharan Africa, malaria is a major cause of morbidity and mortality, in particular in children and pregnant women. During pregnancy, Plasmodium falciparum infected red blood cells expressing VAR2CSA are selected from circulation by selective cytoadherence to chondroitin sulfate proteoglycan receptors expressed in the placenta, leading to an increased susceptibility to malaria, long-lasting infections and poor pregnancy outcome. Partly because of these long-lasting infections, women were reported to have a higher density of gametocytes in their peripheral blood, and are considered as a potential reservoir for malaria transmission...
October 11, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30304836/specific-targeting-of-plant-and-apicomplexa-parasite-tubulin-through-differential-screening-using-in-silico-and-assay-based-approaches
#6
Emmanuelle Soleilhac, Loraine Brillet-Guéguen, Véronique Roussel, Renaud Prudent, Bastien Touquet, Sheena Dass, Samia Aci-Sèche, Vinod Kasam, Caroline Barette, Anne Imberty, Vincent Breton, Marylin Vantard, Dragos Horvath, Cyrille Botté, Isabelle Tardieux, Sylvaine Roy, Eric Maréchal, Laurence Lafanechère
Dinitroanilines are chemical compounds with high selectivity for plant cell α-tubulin in which they promote microtubule depolymerization. They target α-tubulin regions that have diverged over evolution and show no effect on non-photosynthetic eukaryotes. Hence, they have been used as herbicides over decades. Interestingly, dinitroanilines proved active on microtubules of eukaryotes deriving from photosynthetic ancestors such as Toxoplasma gondii and Plasmodium falciparum , which are responsible for toxoplasmosis and malaria, respectively...
October 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30303245/antiplasmodial-activity-and-cytotoxicity-isolation-of-active-alkaloids-and-dereplication-of-xylopia-sericea-leaves-ethanol-extract-by-uplc-dad-esi-ms-ms
#7
Douglas Costa Gontijo, Geraldo Célio Brandão, Maria Fernanda Alves do Nascimento, Alaíde Braga de Oliveira
OBJECTIVES: To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. METHODS: Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively...
October 10, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/30302277/basal-and-starvation-induced-autophagy-mediates-parasite-survival-during-intraerythrocytic-stages-of-plasmodium-falciparum
#8
Shiny Joy, Lavanya Thirunavukkarasu, Palak Agrawal, Archana Singh, B K Chandrasekhar Sagar, Ravi Manjithaya, Namita Surolia
The precise role of autophagy in P. falciparum remains largely unknown. Although a limited number of autophagy genes have been identified in this apicomplexan, only Pf Atg8 has been characterized to a certain extent. On the basis of the expression levels of Pf Atg8 and the putative Pf Atg5, we report that the basal autophagy in this parasite is quite robust and mediates not only the intraerythrocytic development but also fresh invasion of red blood cells (RBCs) in the subsequent cycles. We demonstrate that the basal autophagy responds to both inducers and inhibitors of autophagy...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/30302009/febrile-temperature-elevates-the-expression-of-phosphatidylserine-on-plasmodium-falciparum-fcr3csa-infected-red-blood-cell-surface-leading-to-increased-cytoadhesion
#9
Rou Zhang, Rajesh Chandramohanadas, Chwee Teck Lim, Ming Dao
During the asexual intra-erythrocytic cycle, Plasmodium (P.) falciparum exports parasitic proteins to the surface of infected red blood cells (iRBCs) facilitating its cytoadhesion to various endothelial host receptors. This adhesive behavior is a critical contributor towards disease manifestation. However, little is known about the influence of recurring elevated temperature - a common symptom of the malaria infection - on the adhesive properties of iRBCs to endothelial receptors. To address this, we performed dual-micropipette step-pressure technique between P...
October 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30301933/development-of-a-molecular-adjuvant-to-enhance-antigen-specific-cd8-t-cell-responses
#10
Benedict R Halbroth, Sarah Sebastian, Hazel C Poyntz, Migena Bregu, Matthew G Cottingham, Adrian V S Hill, Alexandra J Spencer
Despite promising progress in malaria vaccine development, an efficacious subunit vaccine against P. falciparum remains to be licensed and deployed. This study aimed to improve on the immunogenicity of the leading liver-stage vaccine candidate (ChAd63-MVA ME-TRAP), known to confer protection by eliciting high levels of antigen-specific CD8+ T cells. We previously showed fusion of ME-TRAP to the human MHC class II invariant chain (Ii) could enhance CD8+ T cell responses in non-human primates, but did not progress to clinical testing due to potential risk of auto-immunity by vaccination of humans with a self-antigen...
October 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30300360/blood-outgrowth-endothelial-cells-boecs-as-a-novel-tool-for-studying-adhesion-of-plasmodium-falciparum-infected-erythrocytes
#11
Gertrude Ecklu-Mensah, Rebecca W Olsen, Anja Bengtsson, Michael F Ofori, Lars Hviid, Anja T R Jensen, Yvonne Adams
The lack of suitable animal models for the study of cytoadhesion of P. falciparum-infected erythrocytes (IEs) has necessitated in vitro studies employing a range of cell lines of either human tumour origin (e.g., BeWo and C32 cells) or non-human origin (e.g., CHO cells). Of the human cells available, many were isolated from adults, or derived from a pool of donors (e.g., HBEC-5i). Here we demonstrate, for the first time, the successful isolation of blood outgrowth endothelial cells (BOECs) from frozen stabilates of peripheral blood mononuclear cells obtained from small-volume peripheral blood samples from paediatric malaria patients...
2018: PloS One
https://www.readbyqxmd.com/read/30297791/a-reference-document-on-permissible-limits-for-solvents-and-buffers-during-in-vitro-antimalarial-screening
#12
Renugah Naidu, Gowtham Subramanian, Ying Bena Lim, Chwee Teck Lim, Rajesh Chandramohanadas
Antimalarial drug discovery expands on targeted and phenotype-based screening of potential inhibitory molecules to ascertain overall efficacy, phenotypic characteristics and toxicity, prior to exploring pharmacological optimizations. Candidate inhibitors may have varying chemical properties, thereby requiring specific reconstitution conditions to ensure solubility, stability or bioavailability. Hence, a variety of solvents, buffers, detergents and stabilizers become part of antimalarial efficacy assays, all of which, above certain threshold could interfere with parasite viability, invasion or red blood cell properties leading to misinterpretation of the results...
October 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30297725/the-plasmodium-falciparum-male-gametocyte-protein-p230p-a-paralog-of-p230-is-vital-for-ookinete-formation-and-mosquito-transmission
#13
Catherin Marin-Mogollon, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Fiona J A van Pul, Jai Ramesar, Ahmad Syibli Othman, Hans Kroeze, Jun Miao, Liwang Cui, Kim C Williamson, Robert W Sauerwein, Chris J Janse, Shahid M Khan
Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown...
October 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30297570/severe-falciparum-malaria-in-children-in-enugu-south-east-nigeria
#14
B O Edelu, I K Ndu, O O Igbokwe, O N Iloh
Introduction: Severe malaria remains one of the leading causes of morbidity and mortality in sub-Saharan Africa and parts of Asia despite several efforts in prevention and management. The prevalence and pattern of presentation may vary from one location to another and from one age group to another. Objectives: This study was undertaken to review the prevalence and pattern of severe malaria among children presenting in the two tertiary hospitals in Enugu, south-east Nigeria...
October 2018: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/30296683/hemozoin-inhibiting-2-phenylbenzimidazoles-active-against-malaria-parasites
#15
Fabrizio P L'abbate, Ronel Müller, Roxanne Openshaw, Jill M Combrinck, Katherine A de Villiers, Roger Hunter, Timothy J Egan
The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation <100 μM and 50% parasite growth <2 μM...
September 28, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30295650/crispr-cas9-gene-editing-to-make-conditional-mutants-of-human-malaria-parasite-p-falciparum
#16
Heather M Kudyba, David W Cobb, Anat Florentin, Michelle Krakowiak, Vasant Muralidharan
Malaria is a significant cause of morbidity and mortality worldwide. This disease, which primarily affects those living in tropical and subtropical regions, is caused by infection with Plasmodium parasites. The development of more effective drugs to combat malaria can be accelerated by improving our understanding of the biology of this complex parasite. Genetic manipulation of these parasites is key to understanding their biology; however, historically the genome of P. falciparum has been difficult to manipulate...
September 18, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/30290825/efficacy-of-artemether-lumefantrine-and-dihydroartemisinin-piperaquine-for-the-treatment-of-uncomplicated-malaria-in-papua-new-guinea
#17
Livingstone Tavul, Manuel W Hetzel, Albina Teliki, Dorish Walsh, Benson Kiniboro, Lawrence Rare, Justin Pulford, Peter M Siba, Stephan Karl, Leo Makita, Leanne Robinson, Johanna H Kattenberg, Moses Laman, Gilchrist Oswyn, Ivo Mueller
BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy. METHODS: Between June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance of anti-malarial drug efficacy...
October 5, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30290808/a-randomized-trial-of-dihydroartemisinin-piperaquine-versus-artemether-lumefantrine-for-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-mali
#18
Souleymane Dama, Hamidou Niangaly, Moussa Djimde, Issaka Sagara, Cheick Oumar Guindo, Amatigue Zeguime, Antoine Dara, Abdoulaye A Djimde, Ogobara K Doumbo
BACKGROUND: Artemether-lumefantrine (AL) and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in many endemic countries, including Mali. Dihydroartemisinin-piperaquine (DHA-PQ) is also an alternative first-line artemisinin-based combination therapy, but only few data are available on DHA-PQ efficacy in sub-Saharan Africa. The main aim of this study was to compare clinical efficacy of DHA-PQ versus AL, using the World Health Organization (WHO) 42-day in vivo protocol...
October 5, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30287688/role-of-phospholipid-synthesis-in-the-development-and-differentiation-of-malaria-parasites-in-the-blood
#19
Nicole Kilian, Jae-Yeon Choi, Dennis R Voelker, Choukri Ben Mamoun
The lifecycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine...
October 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30286076/community-based-prevalence-of-typhoid-fever-typhus-brucellosis-and-malaria-among-symptomatic-individuals-in-afar-region-ethiopia
#20
Biruk Zerfu, Girmay Medhin, Gezahegne Mamo, Gezahegn Getahun, Rea Tschopp, Mengistu Legesse
BACKGROUND: In sub-Saharan Africa, where there is the scarcity of proper diagnostic tools, febrile illness related symptoms are often misdiagnosed as malaria. Information on causative agents of febrile illness related symptoms among pastoral communities in Ethiopia have rarely been described. METHODS: In this a community based cross-sectional survey, we assessed the prevalence of typhoid fever, typhus, brucellosis and malaria among individuals with a set of given symptoms in Amibara district, Afar Region, Ethiopia...
October 4, 2018: PLoS Neglected Tropical Diseases
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