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Artemisinin resistance

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https://www.readbyqxmd.com/read/28212641/local-constraints-to-access-appropriate-malaria-treatment-in-the-context-of-parasite-resistance-in-cambodia-a-qualitative-study
#1
Jesse Verschuere, Tom Decroo, Dara Lim, Jean-Marie Kindermans, Chea Nguon, Rekol Huy, Yasmine Alkourdi, Koen Peeters Grietens, Charlotte Gryseels
BACKGROUND: Despite emerging drug resistance in Cambodia, artemisinin-based combination therapy (ACT) is still the most efficacious therapy. ACT is available free of charge in the Cambodian public sector and at a subsidized rate in the private sector. However, un- and mistreated cases in combination with population movements may lead to the further spread of resistant parasites, stressing the importance of understanding how the perceived aetiology of malaria and associated health-seeking behaviour may delay access to appropriate treatment...
February 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28196536/community-engagement-and-the-social-context-of-targeted-malaria-treatment-a-qualitative-study-in-kayin-karen-state-myanmar
#2
Kate Sahan, Christopher Pell, Frank Smithuis, Aung Kyaw Phyo, Sai Maung Maung, Chanida Indrasuta, Arjen M Dondorp, Nicholas J White, Nicholas P J Day, Lorenz von Seidlein, Phaik Yeong Cheah
BACKGROUND: The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context...
February 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28187990/how-to-contain-artemisinin-and-multidrug-resistant-falciparum-malaria
#3
REVIEW
Arjen M Dondorp, Frank M Smithuis, Charley Woodrow, Lorenz von Seidlein
In the Greater Mekong subregion (GMS), artemisinin resistance is increasingly compounded by partner drug resistance, causing high failure rates of artemisinin combination therapies in some areas. For its containment, an accelerated elimination strategy will be needed. This includes high-quality implementation of conventional malaria control measures: early case management with quality artemisinin combination therapies (avoiding artesunate monotherapies) and single gametocytocidal low dose of primaquine, vector control and surveillance...
February 7, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28179098/genome-wide-association-studies-of-drug-resistance-determinants
#4
REVIEW
Sarah K Volkman, Jonathan Herman, Amanda K Lukens, Daniel L Hartl
Population genetic strategies that leverage association, selection, and linkage have identified drug-resistant loci. However, challenges and limitations persist in identifying drug-resistance loci in malaria. In this review we discuss the genetic basis of drug resistance and the use of genome-wide association studies, complemented by selection and linkage studies, to identify and understand mechanisms of drug resistance and response. We also discuss the implications of nongenetic mechanisms of drug resistance recently reported in the literature, and present models of the interplay between nongenetic and genetic processes that contribute to the emergence of drug resistance...
October 27, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/28166813/hidden-reservoir-of-resistant-parasites-the-missing-link-in-the-elimination-of-falciparum-malaria
#5
Rashad Abdul-Ghani, Mohammed A K Mahdy, John C Beier, Leonardo K Basco
BACKGROUND: To successfully eliminate malaria, an integrated system that includes a number of approaches and interventions-aimed at overcoming the threat of antimalarial drug resistance-is required. Significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. To consolidate these gains, attention should be paid to the missing links in the elimination of malaria. One of these gaps is the residual reservoir of submicroscopic resistant parasites, which remains after case management or other control measures have been carried out...
February 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28161569/the-spread-of-artemisinin-resistant-plasmodium-falciparum-in-the-greater-mekong-subregion-a-molecular-epidemiology-observational-study
#6
Mallika Imwong, Kanokon Suwannasin, Chanon Kunasol, Kreepol Sutawong, Mayfong Mayxay, Huy Rekol, Frank M Smithuis, Tin Maung Hlaing, Kyaw M Tun, Rob W van der Pluijm, Rupam Tripura, Olivo Miotto, Didier Menard, Mehul Dhorda, Nicholas P J Day, Nicholas J White, Arjen M Dondorp
BACKGROUND: Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. METHODS: In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance)...
February 1, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28161568/evidence-of-a-hard-selective-sweep-for-artemisinin-resistant-plasmodium-falciparum
#7
Elizabeth Hemming-Schroeder, Eugenia Lo
No abstract text is available yet for this article.
February 1, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28153004/efficacy-of-artemether-lumefantrine-artesunate-amodiaquine-and-dihydroartemisinin-piperaquine-for-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-angola-2015
#8
Mateusz M Plucinski, Pedro Rafael Dimbu, Aleixo Panzo Macaia, Carolina Miguel Ferreira, Claudete Samutondo, Joltim Quivinja, Marília Afonso, Richard Kiniffo, Eliane Mbounga, Julia S Kelley, Dhruviben S Patel, Yun He, Eldin Talundzic, Denise O Garrett, Eric S Halsey, Venkatachalam Udhayakumar, Pascal Ringwald, Filomeno Fortes
BACKGROUND: Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013. METHODS: During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP)...
February 2, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28148267/reduced-ex-vivo-susceptibility-of-plasmodium-falciparum-after-oral-artemether-lumefantrine-treatment-in-mali
#9
Souleymane Dama, Hamidou Niangaly, Amed Ouattara, Issaka Sagara, Sekou Sissoko, Oumar Bila Traore, Amadou Bamadio, Niawanlou Dara, Moussa Djimde, Mohamed Lamine Alhousseini, Siaka Goita, Hamma Maiga, Antoine Dara, Ogobara K Doumbo, Abdoulaye A Djimde
BACKGROUND: Artemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. However, recent studies conducted in Mali showed an increased frequency of recurrent parasitaemia following artemether-lumefantrine (AL) treatment. METHODS: Study samples were collected during a large WANECAM study. Ex-vivo Plasmodium falciparum sensitivity to artemether and lumefantrine was assessed using the tritiated hypoxanthine-based assay...
February 2, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28137815/k13-propeller-mutations-in-plasmodium-falciparum-populations-in-malaria-endemic-regions-of-vietnam-from-2009-to-2016
#10
Nguyen Thuy-Nhien, Nguyen Kim Tuyen, Nguyen Thanh Tong, Tuong Vy, Ngo Viet Thanh, Huynh Thuy Van, Pham Huong-Thu, Huynh Hong Quang, Maciej F Boni, Christiane Dolecek, Jeremy Farrar, Guy E Thwaites, Olivo Miotto, Nicholas J White, Tran Tinh Hien
The spread of artemisinin resistant P. falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACT) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant for Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum The propeller domain gene of K13, a molecular marker of artemisinin resistance, was sequenced successfully in 1060 P. falciparum isolates collected at 3 malaria hotspots in Vietnam between 2009 and 2016...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28137810/pfk13-independent-treatment-failure-in-four-imported-cases-of-plasmodium-falciparum-malaria-given-artemether-lumefantrine-in-the-uk
#11
Colin J Sutherland, Paul Lansdell, Mandy Sanders, Julian Muwanguzi, Donelly A van Schalkwyk, Harparkash Kaur, Debbie Nolder, Julie Tucker, Hayley M Bennett, Thomas D Otto, Matthew Berriman, Trupti A Patel, Roderick Lynn, Effrossyni Gkrania-Klotsas, Peter L Chiodini
We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015-16. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitaemia within 6 weeks of treatment with no intervening travel to malarious countries. Parasite isolates, all of African origin, harboured variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28128956/accepting-the-invitation-to-open-innovation-in-malaria-drug-discovery-synthesis-biological-evaluation-and-investigation-on-the-structure%C3%A2-activity-relationships-of-benzo-b-thiophene-2-carboxamides-as-antimalarial-agents
#12
Marco Pieroni, Elisa Azzali, Nicoletta Basilico, Silvia Parapini, Michal Zolkiewski, Claudia Beato, Giannamaria Annunziato, Agostino Bruno, Federica Vacondio, Gabriele Costantino
Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the "Malaria Box"...
January 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28122617/in-vitro-activity-of-anti-malarial-ozonides-against-an-artemisinin-resistant-isolate
#13
Fabian Baumgärtner, Joëlle Jourdan, Christian Scheurer, Benjamin Blasco, Brice Campo, Pascal Mäser, Sergio Wittlin
BACKGROUND: Recently published data suggest that artemisinin derivatives and synthetic peroxides, such as the ozonides OZ277 and OZ439, have a similar mode of action. Here the cross-resistance of OZ277 and OZ439 and four additional next-generation ozonides was probed against the artemisinin-resistant clinical isolate Plasmodium falciparum Cam3.I, which carries the K13-propeller mutation R539T (Cam3.I(R539T)). METHODS: The previously described in vitro ring-stage survival assay (RSA0-3h) was employed and a simplified variation of the original protocol was developed...
January 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#14
Peng Cao, Dongjin Leng, Ying Li, Ziwei Zhang, Lei Liu, Xiaoyan Li
Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe(3+) than normal cells, there are a large number of transferrin receptors on the tumor cell membrane...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28086777/profile-of-molecular-mutations-in-pfdhfr-pfdhps-pfmdr1-and-pfcrt-genes-of-plasmodium-falciparum-related-to-resistance-to-different-anti-malarial-drugs-in-the-bata-district-equatorial-guinea
#15
Pedro Berzosa, Andrés Esteban-Cantos, Luz García, Vicenta González, Marisa Navarro, Taiomara Fernández, María Romay-Barja, Zaida Herrador, José Miguel Rubio, Policarpo Ncogo, María Santana-Morales, Basilio Valladares, Matilde Riloha, Agustín Benito
BACKGROUND: The emergence of drug resistance in Plasmodium falciparum has been a major contributor to the global burden of malaria. Drug resistance complicates treatment, and it is one of the most important problems in malaria control. This study assessed the level of mutations in P. falciparum genes, pfdhfr, pfdhps, pfmdr1, and pfcrt, related to resistance to different anti-malarial drugs, in the Continental Region of Equatorial Guinea, after 8 years of implementing artesunate combination therapies as the first-line treatment...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28086775/rapid-decline-in-the-susceptibility-of-plasmodium-falciparum-to-dihydroartemisinin-piperaquine-in-the-south-of-vietnam
#16
Ngo Viet Thanh, Nguyen Thuy-Nhien, Nguyen Thi Kim Tuyen, Nguyen Thanh Tong, Nguyen Thuy Nha-Ca, Le Thanh Dong, Huynh Hong Quang, Jeremy Farrar, Guy Thwaites, Nicholas J White, Marcel Wolbers, Tran Tinh Hien
BACKGROUND: Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. METHODS: In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28072872/population-pharmacokinetic-properties-of-piperaquine-in-falciparum-malaria-an-individual-participant-data-meta-analysis
#17
Richard M Hoglund, Lesley Workman, Michael D Edstein, Nguyen Xuan Thanh, Nguyen Ngoc Quang, Issaka Zongo, Jean Bosco Ouedraogo, Steffen Borrmann, Leah Mwai, Christian Nsanzabana, Ric N Price, Prabin Dahal, Nancy C Sambol, Sunil Parikh, Francois Nosten, Elizabeth A Ashley, Aung Pyae Phyo, Khin Maung Lwin, Rose McGready, Nicholas P J Day, Philippe J Guerin, Nicholas J White, Karen I Barnes, Joel Tarning
BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine...
2017: PLoS Medicine
https://www.readbyqxmd.com/read/28069653/the-molecular-epidemiology-of-pf-k13-mutations-in-senegal-using-targeted-amplicon-deep-sequencing
#18
Eldin Talundzic, Yaye D Ndiaye, Awa B Deme, Christian Olsen, Dhruviben S Patel, Shweta Biliya, Rachel Daniels, Fredrik O Vannberg, Sarah K Volkman, Venkatachalam Udhayakumar, Daouda Ndiaye
The emergence of Plasmodium falciparum (Pf) resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the Pf kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28069075/domestic-trends-in-malaria-research-and-development-in-china-and-its-global-influence
#19
Yang-Mu Huang, Lu-Wen Shi, Rui She, Jing Bai, Shi-Yong Jiao, Yan Guo
BACKGROUND: Though many countries, including China, are moving towards malaria elimination, malaria remains a major global health threat. Due to the spread of antimalarial drug resistance and the need for innovative medical products during the elimination phase, further research and development (R&D) of innovative tools in both epidemic and elimination areas is needed. This study aims to identify the trends and gaps in malaria R&D in China, and aims to offer suggestions on how China can be more effectively involved in global malaria R&D...
January 10, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28068997/absence-of-in-vivo-selection-for-k13-mutations-after-artemether-lumefantrine-treatment-in-uganda
#20
Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H Ntege, Daisuke Ito, Eizo Takashima, Nirianne Marie Q Palacpac, Thomas G Egwang, Joseph Okello Onen, Masatoshi Kataoka, Eisaku Kimura, Toshihiro Horii, Takafumi Tsuboi
BACKGROUND: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein...
January 9, 2017: Malaria Journal
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