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https://www.readbyqxmd.com/read/28934959/selective-inhibition-of-pfa-m1-over-pfa-m17-by-an-amino-benzosuberone-derivative-blocks-malaria-parasites-development-in-vitro-and-in-vivo
#1
Lotfi Bounaadja, Marjorie Schmitt, Sébastien Albrecht, Elisabeth Mouray, Céline Tarnus, Isabelle Florent
BACKGROUND: Plasmodium falciparum M1 family aminopeptidase is currently considered as a promising target for anti-malarial chemotherapy. Several series of inhibitors developed by various research groups display IC50/Ki values down to nM range on native PfA-M1 or recombinant forms and block the parasite development in culture at µM to sub-µM concentrations. A handful of these inhibitors has been tested on murine models of malaria and has shown anti plasmodial in vivo activity. However, most of these inhibitors do also target the other neutral malarial aminopeptidase, PfA-M17, often with lower Ki values, which questions the relative involvement and importance of each enzyme in the parasite biology...
September 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28931399/principles-practices-and-knowledge-of-clinicians-when-assessing-febrile-children-a-qualitative-study-in-kenya
#2
Anneka M Hooft, Kelsey Ripp, Bryson Ndenga, Francis Mutuku, David Vu, Kimberly Baltzell, Linnet N Masese, John Vulule, Dunstan Mukoko, A Desiree LaBeaud
BACKGROUND: Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment...
September 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28930265/a-review-on-ethno-medicinal-and-pharmacological-activities-of-sphenocentrum-jollyanum-pierre
#3
REVIEW
Olubukola Sinbad Olorunnisola, Olumide Samuel Fadahunsi, Peter Adegbola
Sphenocentrum jollyanum Pierre is a member of a diverse family of plants known as Menispermaceae. They are famous for a plethora of important biological functions. S. jollyanum is a shrub native to the tropical forest zones of West Africa and thrives in deep shade. It is widely cultivated in Cameroun, Sierra Leone, Nigeria, Ghana, and Côte d'Ivoire. S. jollyanum is employed in folk medicine as a cure for wounds, fever, coughs, high blood pressure, breast tumor, constipation, and as an aphrodisiac. Phytochemical investigations revealed that the plant is a rich source of secondary metabolites such as annin, alkaloids, saponins, and flavonoids...
July 3, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#4
Ching Hoong Chew, Yvonne Ai Lian Lim, Kek Heng Chua
BACKGROUND: Plasmodium is an obligate intracellular parasite. Apical membrane antigen 1 (AMA1) is the most prominent and well characterized malarial surface antigen that is essential for parasite-host cell invasion, i.e., for sporozoite to invade and replicate within hepatocytes in the liver stage and merozoite to penetrate and replicate within erythrocytes in the blood stage. AMA1 has long served as a potent antimalarial drug target and is a pivotal vaccine candidate. A good understanding of the structure and molecular function of this Plasmodium protein, particularly its involvement in host-cell adhesion and invasion, is of great interest and hence it offers an attractive target for the development of novel therapeutics...
2017: PeerJ
https://www.readbyqxmd.com/read/28928948/virtual-screening-workflow-tutorials-and-prospective-results-from-the-teach-discover-treat-competition-2014-against-malaria
#5
Sereina Riniker, Gregory A Landrum, Floriane Montanari, Santiago D Villalba, Julie Maier, Johanna M Jansen, W Patrick Walters, Anang A Shelat
The first challenge in the 2014 competition launched by the Teach-Discover-Treat (TDT) initiative asked for the development of a tutorial for ligand-based virtual screening, based on data from a primary phenotypic high-throughput screen (HTS) against malaria. The resulting Workflows were applied to select compounds from a commercial database, and a subset of those were purchased and tested experimentally for anti-malaria activity. Here, we present the two most successful Workflows, both using machine-learning approaches, and report the results for the 114 compounds tested in the follow-up screen...
2017: F1000Research
https://www.readbyqxmd.com/read/28926409/effects-of-concurrent-exposure-to-antiretrovirals-and-cotrimoxazole-prophylaxis-among-hiv-exposed-uninfected-infants
#6
Alexander C Ewing, Caroline C King, Jeffrey B Wiener, Charles S Chasela, Michael G Hudgens, Debbie Kamwendo, Gerald Tegha, Mina C Hosseinipour, Denise J Jamieson, Charles Van der Horst, Athena P Kourtis
BACKGROUND: Given the potential of Cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with ARV agents that have overlapping toxicity profiles. METHODS: We used data from the Breastfeeding, Antiretrovirals and Nutrition-BAN study (2004-2010) to evaluate the association of CPT and ARV with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2,006 HEU infants in Lilongwe, Malawi...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28924231/population-genomics-of-virulence-genes-of-plasmodium-falciparum-in-clinical-isolates-from-uganda
#7
Shazia Ruybal-Pesántez, Kathryn E Tiedje, Gerry Tonkin-Hill, Thomas S Rask, Moses R Kamya, Bryan Greenhouse, Grant Dorsey, Michael F Duffy, Karen P Day
Plasmodium falciparum causes a spectrum of malarial disease from asymptomatic to uncomplicated through to severe. Investigations of parasite virulence have associated the expression of distinct variants of the major surface antigen of the blood stages known as Pf EMP1 encoded by up to 60 var genes per genome. Looking at the population genomics of var genes in cases of uncomplicated malaria, we set out to determine if there was any evidence of a selective sweep of specific var genes or clonal epidemic structure related to the incidence of uncomplicated disease in children...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923897/controlled-human-malaria-infection-applications-advances-and-challenges
#8
Danielle I Stanisic, James S McCarthy, Michael F Good
Controlled Human Malaria Infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or direct injection of sporozoites or parasitised erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of anti-malarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development where it is used to evaluate products in well-controlled early phase proof-of-concept clinical studies thus facilitating progression of only the most promising candidates for further evaluation in malaria-endemic areas...
September 18, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28914184/elements-of-effective-community-engagement-lessons-from-a-targeted-malaria-elimination-study-in-lao-pdr-laos
#9
Bipin Adhikari, Christopher Pell, Koukeo Phommasone, Xayaphone Soundala, Palingnaphone Kommarasy, Tiengkham Pongvongsa, Gisela Henriques, Nicholas P J Day, Mayfong Mayxay, Phaik Yeong Cheah
BACKGROUND: Mass drug (antimalarial) administration (MDA) is currently under study in Southeast Asia as part of a package of interventions referred to as targeted malaria elimination (TME). This intervention relies on effective community engagement that promotes uptake and adherence in target communities (above 80%). OBJECTIVE: Based on the experienced of designing and implementing the community engagement for TME in Laos, in this article we aim to present the elements of effective community engagement for mass antimalarial administration...
2017: Global Health Action
https://www.readbyqxmd.com/read/28902417/genetic-variants-related-to-disease-susceptibility-and-immunotolerance-in-the-duffy-antigen-receptor-for-chemokines-darc-fy-gene-in-the-black-lion-tamarin-leontopithecus-chrysopygus-primates
#10
Ashley Ansel, James D Lewis, Don J Melnick, Cristiana Martins, Claudio Valladares-Padua, Beatriz Perez-Sweeney
The DARC (Duffy antigen receptor for chemokines) gene encodes the DARC protein, which serves multiple roles in the immune system, as a binding site for the malarial parasites Plasmodium vivax and Plasmodium knowlesi, a promiscuous chemokine receptor and a blood group antigen. Variation in DARC may play particularly significant roles in innate immunity, immunotolerance and pathogen entry in callitrichines, such as the black lion tamarin (Leontopithecus chrysopygus). We compared amino acid sequences of DARC in the black lion tamarin (BLT) to non-human Haplorhine primates and Homo sapiens...
September 13, 2017: American Journal of Primatology
https://www.readbyqxmd.com/read/28901366/graphene-oxide-inhibits-malaria-parasite-invasion-and-delays-parasitic-growth-in-vitro
#11
Kenry, Ying Bena Lim, Mui Hoon Nai, Jianshu Cao, Kian Ping Loh, Chwee Teck Lim
The interactions between graphene oxide (GO) and various biological entities have been actively investigated in recent years, resulting in numerous potential bioapplications of these nanomaterials. Despite this, the biological interactions between GO and disease-causing protozoan parasites have not been well elucidated and remain relatively unexplored. Here, we investigate the in vitro interactions between GO nanosheets and a particular species of malaria parasites, Plasmodium falciparum (P. falciparum). We hypothesize that GO nanosheets may exhibit antimalarial characteristic via action mechanisms of physical obstruction of P...
September 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/28899381/ned-19-inhibition-of-parasite-growth-and-multiplication-suggests-a-role-for-naadp-mediated-signalling-in-the-asexual-development-of-plasmodium-falciparum
#12
Pablo Suárez-Cortés, Guido Gambara, Annarita Favia, Fioretta Palombi, Pietro Alano, Antonio Filippini
BACKGROUND: Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca(2+) signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. RESULTS: This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca(2+) release (Ned-19) on P...
September 12, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28893781/identification-of-heparin-modifications-and-polysaccharide-inhibitors-of-plasmodium-falciparum-merozoite-invasion-that-have-potential-for-novel-drug-development
#13
Michelle J Boyle, Mark Skidmore, Benjamin Dickerman, Lynsay Cooper, Antony Devlin, Edwin Yates, Paul Horrocks, Craig Freeman, Wengang Chai, James G Beeson
Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing, and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intra-erythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development. We have previously demonstrated that heparin-like-molecules, including those with low molecular weights and low anti-coagulant activities are potent and specific inhibitors of merozoite invasion and blood-stage replication...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893264/maximizing-research-study-effectiveness-in-malaria-elimination-settings-a-mixed-methods-study-to-capture-the-experiences-of-field-based-staff
#14
Sara E Canavati, Cesia E Quintero, Britt Haller, Dysoley Lek, Sovann Yok, Jack S Richards, Maxine Anne Whittaker
BACKGROUND: In a drug-resistant, malaria elimination setting like Western Cambodia, field research is essential for the development of novel anti-malarial regimens and the public health solutions necessary to monitor the spread of resistance and eliminate infection. Such field studies often face a variety of similar implementation challenges, but these are rarely captured in a systematic way or used to optimize future study designs that might overcome similar challenges. Field-based research staff often have extensive experience and can provide valuable insight regarding these issues, but their perspectives and experiences are rarely documented and seldom integrated into future research protocols...
September 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28893077/economic-burden-of-malaria-on-rural-households-in-gwanda-district-zimbabwe
#15
Resign Gunda, Shepherd Shamu, Moses J Chimbari, Samson Mukaratirwa
BACKGROUND: Malaria is a serious public health problem in sub-Saharan Africa and is a leading cause of morbidity and mortality. AIM: To estimate the economic burden of malaria in rural households. SETTING: The study was conducted in Gwanda district of Matabeleland South in Zimbabwe. A total of five malarious wards and all their households were selected for the study frame, out of which 80 households were chosen using clinic records. METHODS: A retrospective analysis of secondary data and a cross-sectional household survey were conducted to estimate the household economic burden of malaria...
August 28, 2017: African Journal of Primary Health Care & Family Medicine
https://www.readbyqxmd.com/read/28884826/an-experimental-test-of-the-physiological-consequences-of-avian-malaria-infection
#16
Laura A Schoenle, Meredith Kernbach, Mark F Haussmann, Frances Bonier, Ignacio T Moore
1.Chronic, low-intensity parasite infections can reduce host fitness through negative impacts on reproduction and survival, even if they produce few overt symptoms. As a result, these parasites can influence the evolution of host morphology, behavior, and physiology. The physiological consequences of chronic infection can provide insight into the processes underlying parasite-driven natural selection. 2.Here, we evaluate the physiological consequences of natural, low-intensity infection in an avian host-parasite system: adult male red-winged blackbirds (Agelaius phoeniceus) infected with haemosporidian parasites...
September 8, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28879213/dna-loaded-cationic-liposomes-efficiently-function-as-a-vaccine-against-malarial-proteins
#17
Wesley L Fotoran, Rachele Santangelo, Beatriz N M de Miranda, Darrell J Irvine, Gerhard Wunderlich
The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28875466/native-mass-spectrometry-ion-mobility-and-collision-induced-unfolding-categorize-malaria-antigen-antibody-binding
#18
Yining Huang, Nichole D Salinas, Edwin Chen, Niraj H Tolia, Michael L Gross
Plasmodium vivax Duffy Binding Protein (PvDBP) is a promising vaccine candidate for P. vivax malaria. Recently, we reported the epitopes on PvDBP region II (PvDBP-II) for three inhibitory monoclonal antibodies (2D10, 2H2, and 2C6). In this communication, we describe the combination of native mass spectrometry and ion mobility (IM) with collision induced unfolding (CIU) to study the conformation and stabilities of three malarial antigen-antibody complexes. These complexes, when collisionally activated, undergo conformational changes that depend on the location of the epitope...
September 5, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28874661/a-potent-series-targeting-the-malarial-cgmp-dependent-protein-kinase-clears-infection-and-blocks-transmission
#19
David A Baker, Lindsay B Stewart, Jonathan M Large, Paul W Bowyer, Keith H Ansell, María B Jiménez-Díaz, Majida El Bakkouri, Kristian Birchall, Koen J Dechering, Nathalie S Bouloc, Peter J Coombs, David Whalley, Denise J Harding, Ela Smiljanic-Hurley, Mary C Wheldon, Eloise M Walker, Johannes T Dessens, María José Lafuente, Laura M Sanz, Francisco-Javier Gamo, Santiago B Ferrer, Raymond Hui, Teun Bousema, Iñigo Angulo-Barturén, Andy T Merritt, Simon L Croft, Winston E Gutteridge, Catherine A Kettleborough, Simon A Osborne
To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874081/physicochemical-investigation-and-in-vivo-activity-of-anti-malarial-drugs-co-loaded-in-tween-80-niosomes
#20
Miloni Thakkar, Brijesh S
Drugs used for the treatment and prevention of malaria are often plagued by the problem of development of resistance. This has hampered their therapeutic efficiency and rendered them ineffective for monotherapy. However, if re-packaged and combined properly, many of these neglected anti-malarial drugs can possibly find their way back into the treatment regime. The present study evaluates the use of curcumin (CC) and primaquine (PRI) as an anti-malarial combination, packaged within niosomes, in comparison to their respective monotherapy options...
September 5, 2017: Journal of Liposome Research
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