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https://www.readbyqxmd.com/read/28342669/extended-protection-capabilities-of-an-immature-dendritic-cell-targeting-malaria-sporozoite-vaccine
#1
Kun Luo, Fidel Zavala, James Gordy, Hong Zhang, Richard B Markham
Mouse studies evaluating candidate malaria vaccines have typically examined protective efficacy over the relatively short time frames of several weeks after the final of multiple immunizations. The current study examines the protective ability in a mouse model system of a novel protein vaccine construct in which the adjuvant polyinosinic polycytidilic acid (poly(I:C)) is used in combination with a vaccine in which the immature dendritic cell targeting chemokine, macrophage inflammatory protein 3 alpha (MIP3α), is fused to the circumsporozoite protein (CSP) of Plasmodium falciparum (P...
March 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28338744/understanding-the-molecular-mechanism-of-substrate-channeling-and-domain-communication-in-protozoal-bifunctional-ts-dhfr
#2
Karen S Anderson
Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. In contrast, several parasitic protozoa, including Leishmania majorg(Lm), Plasmodium falciparum (Pf), Toxoplasma gondii (Tg) and Cryptosporidium hominis(Ch), contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) having the two sequential catalytic activities contained on a single polypeptide chain...
February 4, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28337387/pro-and-anti-inflammatory-cytokines-in-children-with-malaria-in-franceville-gabon
#3
Sandrine Lydie Oyegue-Liabagui, Aline Gaëlle Bouopda-Tuedom, Lady Charlène Kouna, Sydney Maghendji-Nzondo, Herman Nzoughe, Nina Tchitoula-Makaya, Irene Pegha-Moukandja, Jean-Bernard Lekana-Douki
Severe Plasmodium falciparum malaria anemia (SMA) is a major cause of mortality in pediatric wards. Variations in inflammatory mediator production play an essential role in disease outcomes. Indeed, several studies have shown the involvement of pro- and anti-inflammatory cytokines such as IFN-γ, IL-6, TNF-α and IL-10 in malaria immunopathology. In other hand the exact role of Th17 cytokines such as IL-17, IL-22 and IL-21 in malaria remains poorly documented. Here, we investigated IFN-γ, TNF-α, IL-6, IL-12, IL-10, IL-4, IL-13, IL-17, IL-22 and IL-21 circulating levels and their association with malaria anemia and parasitemia in Gabonese children...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28337330/antimalarial-properties-of-simplified-kalihinol-analogues
#4
Mary Elisabeth Daub, Jacques Prudhomme, Choukri Ben Mamoun, Karine G Le Roch, Christopher D Vanderwal
Several kalihinol natural products, members of the broader isocyanoterpene family of antimalarial agents, are potent inhibitors of Plasmodium falciparum, the agent of the most severe form of human malaria. Our previous total synthesis of kalihinol B provided a blueprint to generate many analogues within this family, some as complex as the natural product and some much simplified and easier to access. Each analogue was tested for blood-stage antimalarial activity using both drug-sensitive and -resistant P. falciparum strains...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337195/nk-cells-uncertain-allies-against-malaria
#5
REVIEW
Asia-Sophia Wolf, Samuel Sherratt, Eleanor M Riley
Until recently, studies of natural killer (NK) cells in infection have focused almost entirely on their role in viral infections. However, there is an increasing awareness of the potential for NK cells to contribute to the control of a wider range of pathogens, including intracellular parasites such as Plasmodium spp. Given the high prevalence of parasitic diseases in the developing world and the devastating effects these pathogens have on large numbers of vulnerable people, investigating interactions between NK cells and parasitized host cells presents the opportunity to reveal novel immunological mechanisms with the potential to aid efforts to eradicate these diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28337184/the-maternally-inheritable-wolbachia-walbb-induces-refractoriness-to-plasmodium-berghei-in-anopheles-stephensi
#6
Deepak Joshi, Xiaoling Pan, Michael J McFadden, David Bevins, Xiao Liang, Peng Lu, Suzanne Thiem, Zhiyong Xi
The endosymbiont Wolbachia wAlbB induces refractoriness to Plasmodium falciparum in Anopheles stephensi, the primary mosquito vector of human malaria in the Middle East and South Asia. However, it remains unknown whether such refractoriness can be extended to other malaria species. In particular, it was reported that under very specific conditions, wAlbB can enhance Plasmodium infection in some hosts. Here, we measured the impact of wAlbB on the rodent malaria parasite Plasmodium berghei in A. stephensi by comparing the load of oocysts and sporozoites in midguts and salivary glands, respectively, between wAlbB-infected and -uninfected mosquitoes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28336871/magnetic-nanovectors-for-the-development-of-dna-blood-stage-malaria-vaccines
#7
Fatin M Nawwab Al-Deen, Sue D Xiang, Charles Ma, Kirsty Wilson, Ross L Coppel, Cordelia Selomulya, Magdalena Plebanski
DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs), polyethylenimine (PEI), and hyaluronic acid (HA) to deliver malaria DNA encoding Plasmodium yoelii (Py) merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex) to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice...
February 10, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28336326/oxidative-stress-and-genes-regulation-of-cerebral-malaria-upon-zizyphus-spina-christi-treatment-in-a-murine-model
#8
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/28336173/effects-of-artesunate-on-some-biochemical-parameters-in-pregnant-albino-wistar-rats-challenged-with-lethal-strain-plasmodium-berghei-nk65-appreciating-the-activities-of-artemisinin-drugs-on-key-pregnancy-hormone-balance
#9
Chinaka O Nwaehujor, Onyeka V Asuzu, Daniel D Nwibo, Obichukwu C Nwobi, Ihechiluru I Ezeigbo
In humans, malaria in pregnancy can cause serious maternal and foetal morbidity and in extreme untreated cases, foetal mortality occurs. The therapeutic approach to curbing this malaise is the administration of an effective and/or combinations of anti-malaria medicaments. Acute or chronic administration of some of these drugs, however, gives rise to some adverse medical conditions including reproductive dysfunction, especially in pregnancy. Studies aimed at the hormonal interplays following administration of these drugs in pregnancy have been limited due to too few appropriate animal models...
March 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28335576/genome-wide-identification-and-evolutionary-analysis-of-sarcocystis-neurona-protein-kinases
#10
Edwin K Murungi, Henry M Kariithi
The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM), a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans...
March 21, 2017: Pathogens
https://www.readbyqxmd.com/read/28335490/monitoring-of-selected-health-indicators-in-children-living-in-a-copper-mine-development-area-in-northwestern-zambia
#11
Astrid M Knoblauch, Mark J Divall, Milka Owuor, Colleen Archer, Kennedy Nduna, Harrison Ng'uni, Gertrude Musunka, Anna Pascall, Jürg Utzinger, Mirko S Winkler
The epidemiology of malaria, anaemia and malnutrition in children is potentially altered in mining development areas. In a copper extraction project in northwestern Zambia, a health impact assessment (HIA) was commissioned to predict, manage and monitor health impacts. Two cross-sectional surveys were conducted: at baseline prior to project development (2011) and at four years into development (2015). Prevalence of Plasmodium falciparum, anaemia and stunting were assessed in under-five-year-old children, while hookworm infection was assessed in children aged 9-14 years in communities impacted and comparison communities not impacted by the project...
March 19, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#12
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28332319/piperazine-linked-4-aminoquinoline-chalcone-ferrocenyl-chalcone-conjugates-synthesis-and-anti-plasmodial-evaluation
#13
Amandeep Singh, Anu Rani, Jiri Gut, Philip J Rosenthal, Vipan Kumar
A series of piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates were prepared with a view to evaluate their activities against Plasmodium falciparum. The synthesized conjugates had in vitro IC50 values from 0.41-2.38 μM against chloroquine-resistant and mefloquine sensitive W2 strain of P. falciparum. The sub-micromolar activities of most of the synthesized conjugates suggest that such molecular frameworks can act as therapeutic templates for the design and synthesis of new antimalarials...
March 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28329730/synthesis-of-novel-quinoline-based-4-5-dihydro-1h-pyrazoles-as-potential-anticancer-antifungal-antibacterial-and-antiprotozoal-agents
#14
Jonathan Ramírez-Prada, Sara M Robledo, Iván D Vélez, María Del Pilar Crespo, Jairo Quiroga, Rodrigo Abonia, Alba Montoya, Laura Svetaz, Susana Zacchino, Braulio Insuasty
A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC50 values ranging from 2...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28329141/frequent-spread-of-plasmodium-vivax-malaria-maintains-high-genetic-diversity-at-the-myanmar-china-border-without-distance-and-landscape-barriers
#15
Eugenia Lo, Nancy Lam, Elizabeth Hemming-Schroeder, Jennifer Nguyen, Guofa Zhou, Ming-Chieh Lee, Zhaoqing Yang, Liwang Cui, Guiyun Yan
Background.: In Myanmar, civil unrest and the establishment of internally displaced persons (IDP) settlements along the Myanmar-China border have impacted malaria transmission. Methods.: Microsatellite markers were used to examine source-sink dynamics for Plasmodium vivax between IDP and surrounding villages in the border region. Genotypic structure and diversity were compared across the three years following the establishment of IDP in order to infer demographic history...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329101/naturally-acquired-antibodies-target-the-glutamate-rich-protein-on-intact-merozoites-and-predict-protection-against-febrile-malaria
#16
Ikhlaq Hussain Kana, Bright Adu, Régis Wendpayangde Tiendrebeogo, Susheel Kumar Singh, Daniel Dodoo, Michael Theisen
Background.: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies. Methods.: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay...
February 21, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329034/use-of-pfhrp2-only-rdts-rapidly-select-for-pfhrp2-negative-parasites-with-serious-implications-for-malaria-case-management-and-control
#17
Michelle L Gatton, Jessica Dunn, Alisha Chaudhry, Sadmir Ciketic, Jane Cunningham, Qin Cheng
Background: Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most utilising antibodies against histidine-rich protein 2 (PfHRP2). Reports of Plasmodium falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality microscopy. Methods: An agent-based stochastic simulation model of P.falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases...
March 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28327793/insights-into-cytochrome-bc1-complex-binding-mode-of-antimalarial-2-hydroxy-1-4-naphthoquinones-through-molecular-modelling
#18
Ana Carolina Rennó Sodero, Bárbara Abrahim-Vieira, Pedro Henrique Monteiro Torres, Pedro Geraldo Pascutti, Célia Rs Garcia, Vitor Francisco Ferreira, David Rodrigues da Rocha, Sabrina Baptista Ferreira, Floriano Paes Silva
BACKGROUND: Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES: The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28327148/drug-resistance-mediating-plasmodium-falciparum-polymorphisms-and-clinical-presentations-of-parasitaemic-children-in-uganda
#19
Stephen Tukwasibwe, Patrick Tumwebaze, Melissa Conrad, Emmanuel Arinaitwe, Moses R Kamya, Grant Dorsey, Samuel L Nsobya, Bryan Greenhouse, Philip J Rosenthal
BACKGROUND: Plasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles...
March 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28327145/diagnostic-challenges-and-case-management-of-the-first-imported-case-of-plasmodium-knowlesi-in-sri-lanka
#20
A Dewanee Ranaweera, Manjula N Danansuriya, Kusumawathie Pahalagedera, W M Kumudunayana T de A W Gunasekera, Priyani Dharmawardena, Keng Wai Mak, Pei-Sze Jeslyn Wong, Mei-Zhi Irene Li, Cheong Huat Tan, Hapuarachchige C Hapuarachchi, Hema D B Herath, Deepika Fernando
BACKGROUND: Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. CASE PRESENTATION: An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider...
March 21, 2017: Malaria Journal
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