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Artemisinin resistance

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https://www.readbyqxmd.com/read/28807879/apigenin-induced-abcc1-mediated-efflux-of-glutathione-from-mature-erythrocytes-inhibits-the-proliferation-of-plasmodium-falciparum
#1
Ohud Fallatah, Elias Georges
Plasmodium falciparum infection of mature normal erythrocytes leads to heightened oxidative stress that is tolerated in normal but not in erythrocytes from sickle-cell, β-thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency hosts. In this report, it was of interest to perturb the redox homeostasis of normal erythrocytes through drug-induced active efflux of glutathione via erythrocyte ABCC1 (member of the C- subfamily of the human ATP-binding cassette (ABC) transporters). To achieve this objective, we made use of apigenin, shown previously to activate ABCC1 glutathione efflux in mature erythrocytes...
August 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28806961/molecular-analysis-demonstrates-high-prevalence-of-chloroquine-resistance-but-no-evidence-of-artemisinin-resistance-in-plasmodium-falciparum-in-the-chittagong-hill-tracts-of-bangladesh
#2
Mohammad Shafiul Alam, Benedikt Ley, Maisha Khair Nima, Fatema Tuj Johora, Mohammad Enayet Hossain, Kamala Thriemer, Sarah Auburn, Jutta Marfurt, Ric N Price, Wasif A Khan
BACKGROUND: Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. METHODS: Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28806957/clinical-and-molecular-surveillance-of-artemisinin-resistant-falciparum-malaria-in-myanmar-2009-2013
#3
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/28806082/the-discovery-of-novel-antimalarial-aminoxadiazoles-as-a-promising-nonendoperoxide-scaffold
#4
Elena Sandoval, María José Lafuente-Monasterio, María J Almela, Pablo Castañeda, María Belén Jiménez Díaz, María S Martínez-Martínez, Jaume Vidal, Íñigo Angulo-Barturen, Paul Bamborough, Jeremy Burrows, Nicholas Cammack, María J Chaparro, José M Coterón, Cristina de Cozar, Benigno Crespo, Beatriz Díaz, Gerard Drewes, Esther Fernández, Santiago Ferrer-Bazaga, María Teresa Fraile, Francisco J Gamo, Sonja Ghidelli-Disse, Rubén Gómez, John Haselden, Sophie Huss, María Luisa León, Jaime de Mercado, Simon J F Macdonald, José Ignacio Martín Hernando, Sara Prats, Margarita Puente, Anne Rodríguez, Juan C de la Rosa, Lourdes Rueda, Carolyn Selenski, Paul Willis, David M Wilson, Michael Witty, Félix Calderón
Since the appearance of resistance to the current front-line antimalarial treatments, ACTs (artemisinin combination therapies), the discovery of novel chemical entities to treat the disease is recognized as a major global health priority. From the GSK antimalarial set, we identified an aminoxadiazole with an antiparasitic profile comparable with artemisinin (1), with no cross-resistance in a resistant strains panel and a potential new mode of action. A medicinal chemistry program allowed delivery of compounds such as 19 with high solubility in aqueous media, an acceptable toxicological profile, and oral efficacy...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28797235/polymorphisms-of-plasmodium-falciparum-k13-propeller-gene-among-migrant-workers-returning-to-henan-province-china-from-africa
#5
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/28790788/artemisinin-naphthoquine-combination-a-directly-observed-treatment-option-in-malaria
#6
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
#7
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
#8
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
#9
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/28755265/an-in-silico-strategy-for-identification-of-novel-drug-targets-against-plasmodium-falciparum
#10
Subhashree Rout, Namrata Priyadarshini Patra, Rajani Kanta Mahapatra
The apicomplexan parasite Plasmodium falciparum is responsible for global malaria burden. With the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. In our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti-malarial drug targets from PlasmoDB database...
July 28, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28749761/molecular-characterization-of-a-cluster-of-imported-malaria-cases-in-puerto-rico
#11
Stella M Chenet, Luciana Silva-Flannery, Naomi W Lucchi, Ljolje Dragan, Emilio Dirlikov, Kimberly Mace, Brenda Rivera-García, Paul M Arguin, Venkatachalam Udhayakumar
The Caribbean island of Hispaniola is targeted for malaria elimination. Currently, this is the only island with ongoing transmission of malaria in the Caribbean. In 2015, six patients from Puerto Rico and one from Massachusetts, who traveled to Punta Cana, Dominican Republic, were confirmed to be infected with Plasmodium falciparum. Additional molecular analysis was performed at the Centers for Disease Control and Prevention to characterize the drug-resistant alleles and Plasmodium population genetic markers...
July 24, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28746333/transmission-dynamics-of-co-endemic-plasmodium-vivax-and-p-falciparum-in-ethiopia-and-prevalence-of-antimalarial-resistant-genotypes
#12
Eugenia Lo, Elizabeth Hemming-Schroeder, Delenasaw Yewhalaw, Jennifer Nguyen, Estifanos Kebede, Endalew Zemene, Sisay Getachew, Kora Tushune, Daibin Zhong, Guofa Zhou, Beyene Petros, Guiyun Yan
Ethiopia is one of the few African countries where Plasmodium vivax is co-endemic with P. falciparum. Malaria transmission is seasonal and transmission intensity varies mainly by landscape and climate. Although the recent emergence of drug resistant parasites presents a major issue to malaria control in Ethiopia, little is known about the transmission pathways of parasite species and prevalence of resistant markers. This study used microsatellites to determine population diversity and gene flow patterns of P...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28738892/challenges-to-replace-act-as-first-line-drug
#13
Aung Pyae Phyo, Lorenz von Seidlein
The spread of artemisinin and partner drug resistance through Asia requires changes in first-line therapy. The traditional modus has been the replacement of one first-line anti-malarial regimen with another. The number of anti-malarial drug candidates currently in development may have given false confidence in the expectation that resistance to artemisinin-based combination therapy (ACT) can be solved with a switch to the next anti-malarial drug regimen. A number of promising anti-malarial drug regimens did not succeed in becoming first-line drugs due to safety concerns or rapid development of resistance...
July 24, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28738840/progress-towards-malaria-elimination-in-zimbabwe-with-special-reference-to-the-period-2003-2015
#14
Shadreck Sande, Moses Zimba, Joseph Mberikunashe, Andrew Tangwena, Anderson Chimusoro
BACKGROUND: An intensive effort to control malaria in Zimbabwe has produced dramatic reductions in the burden of the disease over the past 13 years. The successes have prompted the Zimbabwe's National Malaria Control Programme to commit to elimination of malaria. It is critical to analyse the changes in the morbidity trends based on surveillance data, and scrutinize reorientation to strategies for elimination. METHODS: This is a retrospective study of available Ministry of Health surveillance data and programme reports, mostly from 2003 to 2015...
July 24, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28732806/artemisia-annua-dried-leaf-tablets-treated-malaria-resistant-to-act-and-i-v-artesunate-case-reports
#15
Nsengiyumva Bati Daddy, Luc Malemo Kalisya, Pascal Gisenya Bagire, Robert L Watt, Melissa J Towler, Pamela J Weathers
BACKGROUND: Dried leaf Artemisia annua (DLA) has shown efficacy against Plasmodium sp. in rodent studies and in small clinical trials. Rodent malaria also showed resiliency against the evolution of artemisinin drug resistance. PURPOSE: This is a case report of a last resort treatment of patients with severe malaria who were responding neither to artemisinin combination therapy (ACT) nor i.v. artesunate. STUDY DESIGN: Of many patients treated with ACTs and i...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28726171/qsar-modeling-docking-and-admet-studies-for-exploration-of-potential-anti-malarial-compounds-against-plasmodium-falciparum
#16
Tabish Qidwai
Development of resistance in the Plasmodium falciparum to Artemisinin, the most effective anti-malarial compound, threatens malaria elimination tactics. To gain more efficacious Artemisinin derivatives, QSAR modeling and docking was performed. In the present study, 2D-QSAR model and molecular docking were used to evaluate the Artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity. Moreover, ADMET-related descriptors have been calculated to predict the pharmacokinetic properties of the effective compounds...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#17
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#18
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28723328/artemisinin-resistant-plasmodium-falciparum-in-africa
#19
LETTER
Feng Lu, Richard Culleton, Jun Cao
No abstract text is available yet for this article.
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28723327/artemisinin-resistant-plasmodium-falciparum-in-africa
#20
LETTER
Charlotte Rasmussen, Myaing M Nyunt, Pascal Ringwald
New England Journal of Medicine, Volume 377, Issue 3, Page 305-306, July 2017.
July 20, 2017: New England Journal of Medicine
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