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Artemisinin resistance

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https://www.readbyqxmd.com/read/27920563/assessing-parasite-clearance-during-uncomplicated-plasmodium-falciparum-infection-treated-with-artesunate-monotherapy-in-suriname
#1
Stephen Gs Vreden, Rakesh D Bansie, Jeetendra K Jitan, Malti R Adhin
BACKGROUND: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life...
2016: Infection and Drug Resistance
https://www.readbyqxmd.com/read/27919903/high-throughput-screening-and-prediction-models-building-for-novel-hemozoin-inhibitors-using-physicochemical-properties
#2
Nguyen Tien Huy, Pham Lan Chi, Jun Nagai, Tran Ngoc Dang, Evaristus Chibunna Mbanefo, Ali Mahmoud Ahmed, Nguyen Phuoc Long, Le Thi Bich Thoa, Le Phi Hung, Titouna Afaf, Kaeko Kamei, Hiroshi Ueda, Kenji Hirayama
It is essential to continue the search for novel antimalarial drugs due to current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. The in vitro colorimetric high throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9600 structurally diverse compounds. Physicochemical properties of positive hits and randomly selected compounds were extracted from ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27915001/the-threat-of-artemisinin-resistant-malaria-in-southeast-asia
#3
EDITORIAL
Borimas Hanboonkunupakarn, Nicholas J White
No abstract text is available yet for this article.
November 30, 2016: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#4
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#5
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27899115/characterizing-the-impact-of-sustained-sulfadoxine-pyrimethamine-use-upon-the-plasmodium-falciparum-population-in-malawi
#6
Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri, Anja Terlouw, Alister Craig, Susana Campino, Harold Ocholla, Taane G Clark
BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used...
November 29, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27895269/stability-of-dihydroartemisinin-piperaquine-tablet-halves-during-prolonged-storage-under-tropical-conditions
#7
Eva Maria Hodel, Harparkash Kaur, Dianne J Terlouw
Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#8
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27886547/comprehensive-review-on-various-strategies-for-antimalarial-drug-discovery
#9
Mitali Mishra, Vikash K Mishra, Varsha Kashaw, Arun K Iyer, Sushil Kumar Kashaw
The resistance of malaria parasites to existing drugs carries on growing and progressively limiting our ability to manage this severe disease and finally lead to a massive global health burden. Till now, malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. Very few new antimalarials were developed in the past 50 years. Among recent approaches, identification of novel chemotherapeutic targets, exploration of natural products with medicinal significance, covalent bitherapy having a dual mode of action into a single hybrid molecule and malaria vaccine development are explored heavily...
November 12, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27872816/evidence-of-triple-mutant-pfdhps-isgnga-haplotype-in-plasmodium-falciparum-isolates-from-north-east-india-an-analysis-of-sulfadoxine-resistant-haplotype-selection
#10
Manuj K Das, Sumi Chetry, Mohan C Kalita, Prafulla Dutta
BACKGROUND: North-east region of India has consistent role in the spread of multi drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After rapid clinical treatment failure of Artemisinin based combination therapy-Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine (ACT-AL) combination therapy was introduced in the year 2012 in this region for the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based polymorphism analysis, seven codons of P...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27856948/impact-of-introducing-subsidized-combination-treatment-with-artemether-lumefantrine-on-sales-of-anti-malarial-monotherapies-a-survey-of-private-sector-pharmacies-in-huambo-angola
#11
Cristina Lussiana, Marco Floridia, Joana Martinho do Rosário, Filomeno Fortes, Richard Allan
BACKGROUND: Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. METHODS: Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses...
November 17, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27853513/south-east-asian-strains-of-plasmodium-falciparum-display-higher%C3%A2-ratio-of-non-synonymous-to-synonymous-polymorphisms-compared-to-african-strains
#12
Gajinder Pal Singh, Amit Sharma
Resistance to frontline anti-malarial drugs, including artemisinin, has repeatedly arisen in South-East Asia, but the reasons for this are not understood. Here we test whether evolutionary constraints on Plasmodium falciparum strains from South-East Asia differ from African strains. We find a significantly higher ratio of non-synonymous to synonymous polymorphisms in P. falciparum from South-East Asia compared to Africa, suggesting differences in the selective constraints on P. falciparum genome in these geographical regions...
2016: F1000Research
https://www.readbyqxmd.com/read/27843298/endoperoxide-antimalarials-development-structural-diversity-and-pharmacodynamic-aspects-with-reference-to-1-2-4-trioxane-based-structural-scaffold
#13
REVIEW
Mithun Rudrapal, Dipak Chetia
Malaria disease continues to be a major health problem worldwide due to the emergence of multidrug-resistant strains of Plasmodium falciparum. In recent days, artemisinin (ART)-based drugs and combination therapies remain the drugs of choice for resistant P. falciparum malaria. However, resistance to ART-based drugs has begun to appear in some parts of the world. Endoperoxide compounds (natural/semisynthetic/synthetic) representing a huge number of antimalarial agents possess a wide structural diversity with a desired antimalarial effectiveness against resistant P...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27825353/analysis-of-anti-malarial-resistance-markers-in-pfmdr1-and-pfcrt-across-southeast-asia-in-the-tracking-resistance-to-artemisinin-collaboration
#14
Krongkan Srimuang, Olivo Miotto, Pharath Lim, Rick M Fairhurst, Dominic P Kwiatkowski, Charles J Woodrow, Mallika Imwong
BACKGROUND: Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. METHODS: The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011-2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27821166/limited-genetic-diversity-in-the-pvk12-kelch-protein-in-plasmodium-vivax-isolates-from-southeast-asia
#15
Meilian Wang, Faiza Amber Siddiqui, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Mutations in the Kelch propeller domain of PfK13 are the only known molecular markers for artemisinin resistance in this parasite. Over 100 non-synonymous mutations have been identified in PfK13 from various malaria endemic regions. This study aimed to investigate the genetic diversity of PvK12, the Plasmodium vivax ortholog of PfK13, in parasite populations from Southeast Asia, where artemisinin resistance in P...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27821095/treatment-of-a-chemoresistant-neuroblastoma-cell-line-with-the-antimalarial-ozonide-oz513
#16
Don W Coulter, Timothy R McGuire, John G Sharp, Erin M McIntyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R Alexander, Nagendra K Chatuverdi, Shantaram S Joshi, Xiaoyu Chen, Jonathan L Vennerstrom
BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27818097/a-surrogate-marker-of-piperaquine-resistant-plasmodium-falciparum-malaria-a-phenotype-genotype-association-study
#17
Benoit Witkowski, Valentine Duru, Nimol Khim, Leila S Ross, Benjamin Saintpierre, Johann Beghain, Sophy Chy, Saorin Kim, Sopheakvatey Ke, Nimol Kloeung, Rotha Eam, Chanra Khean, Malen Ken, Kaknika Loch, Anthony Bouillon, Anais Domergue, Laurence Ma, Christiane Bouchier, Rithea Leang, Rekol Huy, Grégory Nuel, Jean-Christophe Barale, Eric Legrand, Pascal Ringwald, David A Fidock, Odile Mercereau-Puijalon, Frédéric Ariey, Didier Ménard
BACKGROUND: Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. Genetic tools to detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance. We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures...
November 3, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27818095/genetic-markers-associated-with-dihydroartemisinin-piperaquine-failure-in-plasmodium-falciparum-malaria-in-cambodia-a-genotype-phenotype-association-study
#18
Roberto Amato, Pharath Lim, Olivo Miotto, Chanaki Amaratunga, Dalin Dek, Richard D Pearson, Jacob Almagro-Garcia, Aaron T Neal, Sokunthea Sreng, Seila Suon, Eleanor Drury, Dushyanth Jyothi, Jim Stalker, Dominic P Kwiatkowski, Rick M Fairhurst
BACKGROUND: As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. METHODS: We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine...
November 3, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27809883/alternatives-to-currently-used-antimalarial-drugs-in-search-of-a-magic-bullet
#19
REVIEW
Akshaya Srikanth Bhagavathula, Asim Ahmed Elnour, Abdulla Shehab
Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners' collaboration...
November 4, 2016: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/27809844/failure-of-dihydroartemisinin-piperaquine-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-a-traveller-coming-from-ethiopia
#20
Federico Gobbi, Dora Buonfrate, Michela Menegon, Gianluigi Lunardi, Andrea Angheben, Carlo Severini, Stefania Gori, Zeno Bisoffi
BACKGROUND: Artemisinin combination therapy (ACT) is used worldwide as the first-line treatment against uncomplicated Plasmodium falciparum malaria. Despite the success of ACT in reducing the global burden of malaria, the emerging of resistance to artemisinin threatens its use. CASE REPORT: This report describes the first case of failure of dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of P. falciparum malaria diagnosed in Europe. It occurred in an Italian tourist returned from Ethiopia...
November 3, 2016: Malaria Journal
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