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https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#1
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28812552/competition-along-trajectories-governs-adaptation-rates-towards-antimicrobial-resistance
#2
C Brandon Ogbunugafor, Margaret J Eppstein
The increasing availability of genotype-phenotype maps for different combinations of mutations has empowered evolutionary biologists with the tools to interrogate the predictability of adaptive evolution, especially in the context of the evolution of antimicrobial resistance. Large microbial populations are known to generate competing beneficial mutations, but determining how these mutations contribute to the adaptive trajectories that are most likely to be followed remains a challenge. Despite a recognition that there may also be competition between successive alleles on the same trajectory, prior studies have not fully considered how this impacts adaptation rates along, or likelihood of following, individual trajectories...
November 21, 2016: Nature ecology & evolution
https://www.readbyqxmd.com/read/28810125/cheminformatic-analysis-of-anti-malarial-chemical-space-illuminates-therapeutic-mechanisms-and-offers-strategies-for-therapy-development
#3
Julia Nogueira Varela, María Fernanda Fernanda Lammoglia Cobo, Sandip V Pawar, Vikramaditya G Yadav
The clear and present danger of malaria, which has been amplified in recent years by climate change, and the progressive thinning of our drug arsenal over the past two decades raise uncomfortable questions about the current state and future of anti-malarial drug development. Besides suffering from many of the same technical challenges that affect drug development in other disease areas, the quest for new anti-malarial therapies is also hindered by the complex, dynamic life cycle of the malaria parasite, P. falciparum, in its mosquito and human hosts, and its role thereof in the elicitation of drug resistance...
August 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28808396/catechin-isolated-from-garcinia-celebica-leaves-inhibit-plasmodium-falciparum-growth-through-the-induction-of-oxidative-stress
#4
Rizky Abdulah, Eka W Suradji, Anas Subarnas, Unang Supratman, Milyadi Sugijanto, Ajeng Diantini, Keri Lestari, Melisa I Barliana, Shinichiro Kawazu, Hiroshi Koyama
BACKGROUND: Resistance of antimalarial drugs to Plasmodium falciparum has become a major concern in malaria eradication. Although it is also affected by several socioeconomic factors, a new antiplasmodial agent is needed for a global malaria control program. OBJECTIVE: In this study, we attempted to uncover the antiplasmodial properties of Garcinia celebica, an Indonesian medicinal plant, along with the responsible compound and its possible mechanism. MATERIALS AND METHODS: The G...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808258/hexahydroquinolines-are-antimalarial-candidates-with-potent-blood-stage-and-transmission-blocking-activity
#5
Manu Vanaerschot, Leonardo Lucantoni, Tao Li, Jill M Combrinck, Andrea Ruecker, T R Santha Kumar, Kelly Rubiano, Pedro E Ferreira, Giulia Siciliano, Sonia Gulati, Philipp P Henrich, Caroline L Ng, James M Murithi, Victoria C Corey, Sandra Duffy, Ori J Lieberman, M Isabel Veiga, Robert E Sinden, Pietro Alano, Michael J Delves, Kim Lee Sim, Elizabeth A Winzeler, Timothy J Egan, Stephen L Hoffman, Vicky M Avery, David A Fidock
Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes...
August 14, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28806957/clinical-and-molecular-surveillance-of-artemisinin-resistant-falciparum-malaria-in-myanmar-2009-2013
#6
Myat Htut Nyunt, Myat Thu Soe, Hla Win Myint, Htet Wai Oo, Moe Moe Aye, Soe Soe Han, Ni Ni Zaw, Cho Cho, Phyo Zaw Aung, Khin Thiri Kyaw, Thin Thin Aye, Naychi Aung San, Leonard Ortega, Krongthong Thimasarn, Maria Dorina G Bustos, Sherwin Galit, Mohammad Rafiul Hoque, Pascal Ringwald, Eun-Taek Han, Myat Phone Kyaw
BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013...
August 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28804611/antimalarial-evaluation-of-selected-medicinal-plant-extracts-used-in-iranian-traditional-medicine
#7
Mohammad Hossein Feiz Haddad, Hamidreza Mahbodfar, Zahra Zamani, Ali Ramazani
OBJECTIVES: In an attempt to discover new natural active extracts against malaria parasites, the present study evaluated the antiplasmodial properties of selected plants based on Iranian traditional medicine. MATERIALS AND METHODS: Ten plant species found in Iran were selected and collected based on the available literature about the Iranian traditional medicine. The methanolic extracts of these plants were investigated for in vitro antimalarial properties against chloroquine-sensitive (3D7) and multi-drug resistant (K1) strains of Plasmodium falciparum...
April 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28800458/quinoline-hybrids-and-their-antiplasmodial-and-antimalarial-activities
#8
REVIEW
Yuan-Qiang Hu, Chuan Gao, Shu Zhang, Lei Xu, Zhi Xu, Lian-Shun Feng, Xiang Wu, Feng Zhao
Malaria, in particular infection with P. falciparum (the most lethal of the human malaria parasite species, responsible for nearly one million deaths every year), is one of the most devastating and common infectious disease throughout the world. Beginning with quinine, quinoline containing compounds have long been used in clinical treatment of malaria and remained the mainstays of chemotherapy against malaria. The emergence of P. falciparum strains resistant to almost all antimalarials prompted medicinal chemists and biologists to study their effective replacement with an alternative mechanism of action and new molecules...
July 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28798222/an-integrated-approach-to-explore-composition-and-dynamics-of-cholesterol-rich-membrane-microdomains-in-sexual-stages-of-malaria-parasite
#9
Federica Fratini, Carla Raggi, Gabriella Sferra, Cecilia Birago, Anna Sansone, Felicia Grasso, Chiara Curr Agrave, Anna Olivieri, Tomasino Pace, Stefania Mochi, Leonardo Picci, Carla Ferreri, Antonella Di Biase, Elisabetta Pizzi, Marta Ponzi
Membrane microdomains that include lipid rafts, are involved in key physiological and pathological processes and participate in the entry of endocellular pathogens. These assemblies, enriched in cholesterol and sphingolipids, form highly dynamic, liquid-ordered phases that can be separated from the bulk membranes thanks to their resistance to solubilization by non-ionic detergents. To characterize complexity and dynamics of detergent-resistant membranes of sexual stages of the rodent malaria parasite Plasmodium berghei, here we propose an integrated study of raft components based on proteomics, lipid analysis and bioinformatics...
August 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28797263/measuring-the-impact-of-seasonal-malaria-chemoprevention-as-part-of-routine-malaria-control-in-kita-mali
#10
Fatou Diawara, Laura C Steinhardt, Almahamoudou Mahamar, Tiangoua Traore, Daouda T Kone, Halimatou Diawara, Beh Kamate, Diakalia Kone, Mouctar Diallo, Aboubacar Sadou, Jules Mihigo, Issaka Sagara, Abdoulaye A Djimde, Erin Eckert, Alassane Dicko
BACKGROUND: Seasonal malaria chemoprevention (SMC) is a new strategy recommended by WHO in areas of highly seasonal transmission in March 2012. Although randomized controlled trials (RCTs) have shown SMC to be highly effective, evidence and experience from routine implementation of SMC are limited. METHODS: A non-randomized pragmatic trial with pre-post design was used, with one intervention district (Kita), where four rounds of SMC with sulfadoxine + amodiaquine (SP + AQ) took place in August-November 2014, and one comparison district (Bafoulabe)...
August 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28797235/polymorphisms-of-plasmodium-falciparum-k13-propeller-gene-among-migrant-workers-returning-to-henan-province-china-from-africa
#11
Chengyun Yang, Hongwei Zhang, Ruimin Zhou, Dan Qian, Ying Liu, Yuling Zhao, Suhua Li, Bianli Xu
BACKGROUND: Henan Province has been in the malaria elimination stage, with all reports of the disease being imported since 2012 and over 90% coming from Africa. Surveillance and population studies are essential for the early detection and subsequent prevention of the spread of drug resistance. The K13-propeller gene was recently identified as a proposed molecular marker of artemisinin (ART) resistance. In this study, we detected mutations of the K13-propeller gene in samples taken from imported malaria cases in Henan Province from 2012 to 2015...
August 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28793859/investigating-knockdown-resistance-kdr-mechanism-against-pyrethroids-ddt-in-the-malaria-vector-anopheles-funestus-across-africa
#12
Helen Irving, Charles S Wondji
BACKGROUND: Understanding the molecular basis of insecticide resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the knockdown resistance (kdr) mechanism. Here, we investigated the presence and contribution of knockdown resistance (kdr) to pyrethroids/DDT resistance observed in Anopheles funestus across Africa. RESULTS: Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An...
August 9, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28790788/artemisinin-naphthoquine-combination-a-directly-observed-treatment-option-in-malaria
#13
M S Mustafa, V Rastogi
Resistance to standard antimalarials has led to the need for newer options. Artemisinin-based combination therapies (ACTs), which require a tedious three-day treatment schedule, have been introduced for the treatment of drug-resistant malaria. Of late, the new generation artemisinin-naphthoquine (ANQ) combination has been developed, which requires a single dose treatment. Artemisinin initiates the action through the cleavage of the endoperoxide bridge while naphtoquine maintains the process by getting concentrated in the digestive vacuole of the parasite...
July 2017: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28777791/antimalarial-drug-resistance-linking-plasmodium-falciparum-parasite-biology-to-the-clinic
#14
REVIEW
Benjamin Blasco, Didier Leroy, David A Fidock
The global adoption of artemisinin-based combination therapies (ACTs) in the early 2000s heralded a new era in effectively treating drug-resistant Plasmodium falciparum malaria. However, several Southeast Asian countries have now reported the emergence of parasites that have decreased susceptibility to artemisinin (ART) derivatives and ACT partner drugs, resulting in increasing rates of treatment failures. Here we review recent advances in understanding how antimalarials act and how resistance develops, and discuss new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria...
August 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28774303/comparison-of-anti-malarial-drugs-efficacy-in-the-treatment-of-uncomplicated-malaria-in-african-children-and-adults-using-network-meta-analysis
#15
Solange Whegang Youdom, Rachida Tahar, Leonardo K Basco
BACKGROUND: Artemisinin-based combination therapy (ACT) and novel drug combinations are available and used in African countries to treat uncomplicated malaria. Network meta-analysis methods are rarely and poorly applied for the comparison of their efficacies. This method was applied on a set of randomized controlled trials to illustrate its usefulness. METHODS: A literature review available in Pubmed was conducted in July 2016. Eligible studies, conducted in sub-Saharan Africa, published between 2002 and 2016, focused on randomized controlled trials of at least two artemisinin-based combinations to treat uncomplicated malaria in children and adults...
August 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28770814/malaria
#16
REVIEW
Margaret A Phillips, Jeremy N Burrows, Christine Manyando, Rob Hooft van Huijsduijnen, Wesley C Van Voorhis, Timothy N C Wells
Malaria is caused in humans by five species of single-celled eukaryotic Plasmodium parasites (mainly Plasmodium falciparum and Plasmodium vivax) that are transmitted by the bite of Anopheles spp. mosquitoes. Malaria remains one of the most serious infectious diseases; it threatens nearly half of the world's population and led to hundreds of thousands of deaths in 2015, predominantly among children in Africa. Malaria is managed through a combination of vector control approaches (such as insecticide spraying and the use of insecticide-treated bed nets) and drugs for both treatment and prevention...
August 3, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28768767/iron-is-a-substrate-of-the-plasmodium-falciparum-chloroquine-resistance-transporter-pfcrt-in-xenopus-oocytes
#17
Naziha Bakouh, Sebastiano Bellanca, Britta Nyboer, Sonia Moliner Cubel, Zoubida Karim, Cecilia P Sanchez, Wilfred D Stein, Gabrielle Planelles, Michael Lanzer
The chloroquine resistance transporter of the human malaria parasite Plasmodium falciparum, PfCRT, is an important determinant of resistance to several quinoline and quinoline-like antimalarial drugs. PfCRT also plays an essential role in the physiology of the parasite during development inside erythrocytes. However, the function of this transporter besides its role in drug resistance is still unclear. Using electrophysiological and flux experiments conducted on PfCRTexpressing Xenopus laevis oocytes, we show here that both wild type PfCRT and a PfCRT variant associated with chloroquine resistance transport both ferrous and ferric iron, albeit with different kinetics...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28764792/deployment-and-use-of-mobile-phone-technology-for-real-time-reporting-of-fever-cases-and-malaria-treatment-failure-in-areas-of-declining-malaria-transmission-in-muheza-district-north-eastern-tanzania
#18
Filbert Francis, Deus S Ishengoma, Bruno P Mmbando, Acleus S M Rutta, Mwelecele N Malecela, Benjamin Mayala, Martha M Lemnge, Edwin Michael
BACKGROUND: Early detection of febrile illnesses at community level is essential for improved malaria case management and control. Currently, mobile phone-based technology has been commonly used to collect and transfer health information and services in different settings. This study assessed the applicability of mobile phone-based technology in real-time reporting of fever cases and management of malaria by village health workers (VHWs) in north-eastern Tanzania. METHODS: The community mobile phone-based disease surveillance and treatment for malaria (ComDSTM) platform, combined with mobile phones and web applications, was developed and implemented in three villages and one dispensary in Muheza district from November 2013 to October 2014...
August 1, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28762197/sequence-structural-analysis-and-metrics-to-define-the-unique-dynamic-features-of-the-flap-regions-among-aspartic-proteases
#19
REVIEW
Lara McGillewie, Muthusamy Ramesh, Mahmoud E Soliman
Aspartic proteases are a class of hydrolytic enzymes that have been implicated in a number of diseases such as HIV, malaria, cancer and Alzheimer's. The flap region of aspartic proteases is a characteristic unique structural feature of these enzymes; and found to have a profound impact on protein overall structure, function and dynamics. Flap dynamics also plays a crucial role in drug binding and drug resistance. Therefore, understanding the structure and dynamic behavior of this flap regions is crucial in the design of potent and selective inhibitors against aspartic proteases...
July 31, 2017: Protein Journal
https://www.readbyqxmd.com/read/28759591/genome-wide-diversity-and-differentiation-in-new-world-populations-of-the-human-malaria-parasite-plasmodium-vivax
#20
Thais C de Oliveira, Priscila T Rodrigues, Maria José Menezes, Raquel M Gonçalves-Lopes, Melissa S Bastos, Nathália F Lima, Susana Barbosa, Alexandra L Gerber, Guilherme Loss de Morais, Luisa Berná, Jody Phelan, Carlos Robello, Ana Tereza R de Vasconcelos, João Marcelo P Alves, Marcelo U Ferreira
BACKGROUND: The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax. METHODS: We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P...
July 2017: PLoS Neglected Tropical Diseases
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