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Malaria drug resistance

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https://www.readbyqxmd.com/read/29463745/rocaglates-as-dual-targeting-agents-for-experimental-cerebral-malaria
#1
David Langlais, Regina Cencic, Neda Moradin, James M Kennedy, Kodjo Ayi, Lauren E Brown, Ian Crandall, Michael J Tarry, Martin Schmeing, Kevin C Kain, John A Porco, Jerry Pelletier, Philippe Gros
Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29454844/the-epidemiology-of-febrile-illness-in-sub-saharan-africa-implications-for-diagnosis-and-management
#2
REVIEW
Michael J Maze, Quique Bassat, Nicholas A Feasey, Inácio Mandomando, Patrick Musicha, John A Crump
BACKGROUND: Fever is among the most common symptoms of people living in Africa, and clinicians are challenged by the similar clinical features of a wide spectrum of potential aetiologies. AIM: To summarise recent studies of fever aetiology in sub-Saharan Africa focusing on causes other than malaria. SOURCES: A narrative literature review by searching the MEDLINE database, and recent conference abstracts. CONTENT: Studies of multiple potential causes of fever are scarce, and for many participants the infecting organism remains unidentified, or multiple co-infecting microorganisms are identified, and establishing causation is challenging...
February 15, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29454237/liposomes-of-dimeric-artesunate-phospholipid-a-combination-of-dimerization-and-self-assembly-to-combat-malaria
#3
Muhammad Ismail, Longbing Ling, Yawei Du, Chen Yao, Xinsong Li
Artemisinin and its derivatives are highly effective drugs in the treatment of P. falciparum malaria. However, their clinical applications face challenges because of short half-life, poor bioavailability and growing drug resistance. In this article, novel dimeric artesunate phospholipid (Di-ART-GPC) based liposomes were developed by combination of dimerization and self-assembly to address these shortcomings. Firstly, Di-ART-GPC conjugate was synthesized by a facile esterification of artesunate (ART) and glycerophosphorylcholine (GPC) and confirmed by MS, 1 H NMR and 13 C NMR...
February 10, 2018: Biomaterials
https://www.readbyqxmd.com/read/29444080/promising-approach-to-reducing-malaria-transmission-by-ivermectin-sporontocidal-effect-against-plasmodium-vivax-in-the-south-american-vectors-anopheles-aquasalis-and-anopheles-darlingi
#4
Yudi T Pinilla, Stefanie C P Lopes, Vanderson S Sampaio, Francys S Andrade, Gisely C Melo, Alessandra S Orfanó, Nágila F C Secundino, Maria G V B Guerra, Marcus V G Lacerda, Kevin C Kobylinski, Karin S Escobedo-Vargas, Victor M López-Sifuentes, Craig A Stoops, G Christian Baldeviano, Joel Tarning, Gissella M Vasquez, Paulo F P Pimenta, Wuelton M Monteiro
BACKGROUND: The mosquito resistance to the insecticides threatens malaria control efforts, potentially becoming a major public health issue. Alternative methods like ivermectin (IVM) administration to humans has been suggested as a possible vector control to reduce Plasmodium transmission. Anopheles aquasalis and Anopheles darlingi are competent vectors for Plasmodium vivax, and they have been responsible for various malaria outbreaks in the coast of Brazil and the Amazon Region of South America...
February 14, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29439965/a-next-generation-sequencing-and-bioinformatics-protocol-for-malaria-drug-resistance-marker-surveillance-mars
#5
Eldin Talundzic, Shashidhar Ravishankar, Julia Kelly, Dhruviben Patel, Mateusz Plucinski, Sarah Schmedes, Dragan Ljolje, Brooke Clemons, Susan Madison-Antenucci, Paul M Arguin, Naomi Lucchi, Fredrik Vannberg, Venkatachalam Udhayakumar
The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug resistant parasites. To take advantage of this technology an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance in P. falciparum, called<u>Ma</u>laria<u>R</u>esistance<u>S</u>urveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing...
February 12, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29436997/pyrazole-schiff-base-hybrid-as-an-anti-malarial-agent-synthesis-in-vitro-screening-and-molecular-docking-study
#6
Shilpy Aggarwal, Deepika Paliwal, Dhirender Kaushik, Girish Kumar Gupta, Ajay Kumar
BACKGROUND: Malaria, one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need of identify new targets for chemotherapy Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P...
February 12, 2018: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29422423/use-of-artesunate-in-non-malarial-indications
#7
REVIEW
A Raffetin, F Bruneel, C Roussel, M Thellier, P Buffet, E Caumes, S Jauréguiberry
INTRODUCTION: Artesunate and other artemisinin derivatives are used in various infectious and non-infectious diseases. We aimed to analyze available data on artesunate and artemisinin derivatives activity in humans and their potential clinical benefits in non-malarial indications. MATERIAL AND METHODS: Literature review performed on PubMed and the Cochrane Library databases using the PRISMA method. We analyzed studies published in English from January 2008 to August 2017 using the same indicators of drug efficacy...
February 5, 2018: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/29422048/tools-for-surveillance-of-anti-malarial-drug-resistance-an-assessment-of-the-current-landscape
#8
REVIEW
Christian Nsanzabana, Djibrine Djalle, Philippe J Guérin, Didier Ménard, Iveth J González
To limit the spread and impact of anti-malarial drug resistance and react accordingly, surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established. Currently, surveillance of anti-malarial drug resistance is done by any of three approaches: (1) in vivo studies to assess the efficacy of drugs in patients; (2) in vitro/ex vivo studies to evaluate parasite susceptibility to the drugs; and/or (3) molecular assays to detect validated gene mutations and/or gene copy number changes that are associated with drug resistance...
February 8, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29410428/heterologous-expression-of-a-novel-drug-transporter-from-the-malaria-parasite-alters-resistance-to-quinoline-antimalarials
#9
Sarah M Tindall, Cindy Vallières, Dev H Lakhani, Farida Islahudin, Kang-Nee Ting, Simon V Avery
Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29408369/drug-targeting-of-one-or-more-aminoacyl-trna-synthetase-in-the-malarial-parasite-plasmodium-falciparum
#10
REVIEW
Manickam Yogavel, Rini Chaturvedi, Palak Babbar, Nipun Malhotra, Vitul Jain, Amit Sharma
Malaria remains a major infectious disease and, despite incidence reduction, it threatens resurgence in drug-resistant forms. Antimalarial drugs remain the mainstay of therapeutic options and hence there is a constant need to identify and validate new druggable targets. Plasmodium falciparum aminoacyl-tRNA synthetases (Pf-aaRSs) drive protein translation and are potent targets for development of next-generation antimalarials. Here, we detail advances made in structural-biology-based investigations in Pf-aaRSs and discuss their distribution of druggable pockets...
February 2, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29406996/the-role-of-antimalarial-quality-in-the-emergence-and-transmission-of-resistance
#11
Aleisha R Brock, Joshua V Ross, Sunil Parikh, Adrian Esterman
The emergence and transmission of antimalarial resistance is hampering malaria eradication efforts and is shortening the useful therapeutic life of currently available antimalarials. Drug selection pressure has been identified as a contributing factor to the emergence and transmission of resistance, especially population treatment coverage and sub-therapeutic concentrations of active pharmaceutical ingredient (API) in the bloodstream. Medicine quality can be defined as good quality or poor quality. Poor quality antimalarials can be falsified, substandard or degraded and are estimated to make up between 10 and 50% of the antimalarial market in developing countries, and can be a source of sub-therapeutic doses of antimalarial API(s)...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29405138/correlation-of-in-vitro-sensitivity-of-chloroquine-and-other-antimalarials-with-the-partner-drug-resistance-to-plasmodium-falciparum-malaria-in-selected-sites-of-india
#12
Supriya Sharma, Ram Suresh Bharti, Nitin Bhardwaj, Anupkumar R Anvikar, Neena Valecha, Neelima Mishra
BACKGROUND: Antimalarial drug resistance is a potential threat for control and elimination of malaria. To ascertain the status of antimalarial drug resistance at the study sites, correlation between in vitro drug sensitivity pattern and drug resistance molecular markers in Plasmodium falciparum malaria was undertaken. MATERIALS AND METHODS: Polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt) K76T and pfmdr1 N86Y were studied in relation to the in vitro susceptibility of P...
October 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29398391/origins-of-the-current-outbreak-of-multidrug-resistant-malaria-in-southeast-asia-a-retrospective-genetic-study
#13
Roberto Amato, Richard D Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick M Fairhurst, Dominic P Kwiatkowski
BACKGROUND: Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin-piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. METHODS: We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013...
February 1, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29396203/evolutionary-arms-race-antimalarial-resistance-molecular-surveillance
#14
REVIEW
Christiane Prosser, Wieland Meyer, John Ellis, Rogan Lee
Molecular surveillance of antimalarial drug resistance markers has become an important part of resistance detection and containment. In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a consensus to upscale molecular surveillance. The most salient limitation to current surveillance efforts is that skill and infrastructure requirements preclude many regions. This includes sub-Saharan Africa, where Plasmodium falciparum is responsible for most of the global malaria disease burden...
January 23, 2018: Trends in Parasitology
https://www.readbyqxmd.com/read/29395997/prevention-of-malaria-in-pregnancy
#15
REVIEW
Meghna Desai, Jenny Hill, Silke Fernandes, Patrick Walker, Christopher Pell, Julie Gutman, Kassoum Kayentao, Raquel Gonzalez, Jayne Webster, Brian Greenwood, Michel Cot, Feiko O Ter Kuile
Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012...
January 30, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29394891/a-set-of-microsatellite-markers-to-differentiate-plasmodium-falciparum-progeny-of-four-genetic-crosses
#16
Christine E Figan, Juliana M Sá, Jianbing Mu, Viviana A Melendez-Muniz, Chia Hao Liu, Thomas E Wellems
BACKGROUND: Four Plasmodium falciparum genetic crosses (HB3×3D7, HB3×Dd2, 7G8×GB4, and 803×GB4) have produced sets of recombinant progeny that are widely used for malaria research, including investigations of anti-malarial drug resistance. It is critical to maintain the progeny free from cross-contamination. Microsatellite polymorphisms can be used to validate parasite identity. RESULTS: A set of 12 markers was developed that differentiates the parents of the four P...
February 2, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29393511/primaquine-or-other-8-aminoquinolines-for-reducing-plasmodium-falciparum-transmission
#17
REVIEW
Patricia M Graves, Leslie Choi, Hellen Gelband, Paul Garner
BACKGROUND: The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas...
February 2, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29390014/impact-of-treatment-and-re-treatment-with-artemether-lumefantrine-and-artesunate-amodiaquine-on-selection-of-plasmodium-falciparum-multidrug-resistance-gene-1-polymorphisms-in-the-democratic-republic-of-congo-and-uganda
#18
Vito Baraka, Hypolite Muhindo Mavoko, Carolyn Nabasumba, Filbert Francis, Pascal Lutumba, Michael Alifrangis, Jean-Pierre Van Geertruyden
BACKGROUND: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings...
2018: PloS One
https://www.readbyqxmd.com/read/29378713/enhanced-ex-vivo-plasmodium-vivax-intraerythrocytic-enrichment-and-maturation-for-rapid-and-sensitive-parasite-growth-assays
#19
Gabriel W Rangel, Martha A Clark, Usheer Kanjee, Caeul Lim, Kathryn Shaw-Saliba, Maria José Menezes, Anjali Mascarenhas, Laura Chery, Edwin Gomes, Pradipsinh K Rathod, Marcelo U Ferreira, Manoj T Duraisingh
Plasmodium vivax chloroquine resistance has been documented in nearly every region endemic for this malaria-causing parasite. Unfortunately, P. vivax resistance surveillance and drug discovery is challenging due to low parasitemias of patient isolates, and poor parasite survival through ex vivo maturation, that reduce the sensitivity and scalability of current P. vivax antimalarial assays. Using cryopreserved patient isolates from Brazil and fresh patient isolates from India, we established a robust enrichment method for P...
January 29, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29377434/a-herbicide-structure-activity-analysis-of-the-antimalarial-lead-compound-mmv007978-against-arabidopsis-thaliana
#20
Maxime G Corral, Julie Leroux, Stefan Tresch, Trevor Newton, Keith A Stubbs, Joshua S Mylne
BACKGROUND: To fight herbicide-resistant weeds, new herbicides are needed and particularly ones with new modes of action. Building on the revelation that many antimalarial drugs are herbicidal, here we focus on the Medicines for Malaria Venture antimalarial lead compound MMV007978 that has herbicidal activity against the model plant Arabidopsis thaliana. RESULTS: Twenty-two variations at the lead compound thiophenyl motif revealed that change was tolerated provided ring size and charge were retained...
January 27, 2018: Pest Management Science
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