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Artemisinin resistance

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https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#1
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
#2
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
#3
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
#4
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...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28069653/the-molecular-epidemiology-of-pf-k13-mutations-in-senegal-using-targeted-amplicon-deep-sequencing
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28056979/malaria-epidemiology-in-central-myanmar-identification-of-a-multi-species-asymptomatic-reservoir-of-infection
#8
Isaac Ghinai, Jackie Cook, Teddy Tun Win Hla, Hein Myat Thu Htet, Tom Hall, Inke Nd Lubis, Rosanna Ghinai, Therese Hesketh, Ye Naung, Mya Mya Lwin, Tint Swe Latt, David L Heymann, Colin J Sutherland, Chris Drakeley, Nigel Field
BACKGROUND: The spread of artemisinin-resistant Plasmodium falciparum is a global health concern. Myanmar stands at the frontier of artemisinin-resistant P. falciparum. Myanmar also has the highest reported malaria burden in Southeast Asia; it is integral in the World Health Organization's plan to eliminate malaria in Southeast Asia, yet few epidemiological data exist for the general population in Myanmar. METHODS: This cross-sectional, probability household survey was conducted in Phyu township, Bago Region (central Myanmar), during the wet season of 2013...
January 5, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28043395/artesunate-tafenoquine-combination-therapy-promotes-clearance-and-abrogates-transmission-of-the-avian-malaria-parasite-plasmodium-gallinaceum
#9
Suchada Tasai, Tawee Saiwichai, Morakot Kaewthamasorn, Sonthaya Tiawsirisup, Prayute Buddhirakkul, Sirintip Chaichalotornkul, Sittiporn Pattaradilokrat
Clinical manifestations of malaria infection in vertebrate hosts arise from the multiplication of the asexual stage parasites in the blood, while the gametocytes are responsible for the transmission of the disease. Antimalarial drugs that target the blood stage parasites and transmissible gametocytes are rare, but are essentially needed for the effective control of malaria and for limiting the spread of resistance. Artemisinin and its derivatives are the current first-line antimalarials that are effective against the blood stage parasites and gametocytes, but resistance to artemisinin has now emerged and spread in various malaria endemic areas...
January 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28039354/changing-antimalarial-drug-resistance-patterns-identified-by-surveillance-at-three-sites-in-uganda
#10
Patrick Tumwebaze, Stephen Tukwasibwe, Aimee Taylor, Melissa Conrad, Emmanuel Ruhamyankaka, Victor Asua, Andrew Walakira, Joaniter Nankabirwa, Adoke Yeka, Sarah G Staedke, Bryan Greenhouse, Samuel L Nsobya, Moses R Kamya, Grant Dorsey, Philip J Rosenthal
We assessed Plasmodium falciparum drug resistance markers in parasites collected in 2012, 2013, and 2015 at 3 sites in Uganda. The prevalence and frequency of parasites with mutations in putative transporters previously associated with resistance to aminoquinolines, but increased sensitivity to lumefantrine (pfcrt 76T; pfmdr1 86Y and 1246Y), decreased markedly at all sites. Antifolate resistance mutations were common, with apparent emergence of mutations (pfdhfr 164L; pfdhps 581G) associated with high level resistance...
December 29, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28035111/comparison-of-who-mark-iii-and-hrp-ii-elisa-for-in-vitro-sensitivity-of-plasmodium-falciparum
#11
Supriya Sharma, Neelima Mishra, Neena Valecha, Anupkumar R Anvikar
BACKGROUND & OBJECTIVES: Antimalarial drug resistance is a serious challenge to malaria control worldwide. In vitro sensitivity assays provide an early indication of emerging drug resistance. In vitro susceptibility of field and culture adapted Plasmodium falciparum isolates to different antimalarials was compared using two Methods: World Health Organization (WHO) micro-test (MARK III) and histidine rich protein II (HRP II) based enzyme- linked immunosorbent assay (ELISA). METHODS: In total, 50 P...
October 2016: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/28028628/risk-of-drug-resistance-in-plasmodium-falciparum-malaria-therapy-a-systematic-review-and-meta-analysis
#12
Li-Juan Zhou, Jing Xia, Hai-Xia Wei, Xiao-Jun Liu, Hong-Juan Peng
Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases...
December 27, 2016: Parasitology Research
https://www.readbyqxmd.com/read/28025270/population-parameters-underlying-an-ongoing-soft-sweep-in-southeast-asian-malaria-parasites
#13
Timothy J C Anderson, Shalini Nair, Marina McDew-White, Ian H Cheeseman, Standwell Nkhoma, Fatma Bilgic, Rose McGready, Elizabeth Ashley, Aung Pyae Phyo, Nicholas J White, François Nosten
Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001-2014)...
January 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28018925/parasite-clearance-and-artemether-pharmacokinetics-parameters-over-the-course-of-artemether-lumefantrine-treatment-for-malaria-in-human-immunodeficiency-virus-hiv-infected-and-hiv-uninfected-ugandan-children
#14
Richard Kajubi, Liusheng Huang, Moses Were, Sylvia Kiconco, Fangyong Li, Florence Marzan, David Gingrich, Myaing M Nyunt, Joshua Ssebuliba, Norah Mwebaza, Francesca T Aweeka, Sunil Parikh
BACKGROUND: Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized. METHODS: Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL)...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28004634/polymorphisms-in-k13-pfcrt-pfmdr1-pfdhfr-and-pfdhps-in-parasites-isolated-from-symptomatic-malaria-patients-in-burkina-faso
#15
Anyirékun Fabrice Somé, Hermann Sorgho, Issaka Zongo, Thomas Bazié, Frédéric Nikiéma, Amadé Sawadogo, Moussa Zongo, Yves-Daniel Compaoré, Jean-Bosco Ouédraogo
BACKGROUND: The emergence of resistance to artemisinin derivatives in western Cambodia is threatening to revert the recent advances made toward global malaria control and elimination. Known resistance-mediating polymorphisms in the K13, pfcrt, pfmdr1, pfdhfr, and pfdhps genes are of greatest importance for monitoring the spread of antimalarial drug resistance. METHODS: Samples for the present study were collected from 244 patients with uncomplicated malaria in health centers of Bobo-Dioulasso, Burkina Faso...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27997206/nanomolar-antimalarial-agents-against-chloroquine-resistant-plasmodium-falciparum-from-medicinal-plants-and-their-structure-activity-relationships
#16
Bin Zhou, Yan Wu, Seema Dalal, Emilio F Merino, Qun-Fang Liu, Cheng-Hui Xu, Tao Yuan, Jian Ding, David G I Kingston, Maria B Cassera, Jian-Min Yue
Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chloranthus genus, many species of which are named "Sikuaiwa" in TCM and have long been used to treat malaria. The compounds consisted of 41 sesquiterpenoid dimers and three monomers, including the 12 new dimers 1-12 isolated from Chloranthus fortunei...
December 20, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27994102/intermittent-preventive-treatment-with-sulfadoxine-pyrimethamine-more-than-just-an-antimalarial
#17
EDITORIAL
Julie Gutman, Laurence Slutsker
Malaria in pregnancy is associated with increased risk for both maternal and neonatal adverse outcomes, notably low birthweight and neonatal mortality.(1) Since 2004, following studies that showed that intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) reduced the risk of these adverse events,(2) the World Health Organization (WHO) recommended IPTp-SP for all areas in Africa with moderate-to-high malaria transmission.(3) IPTp-SP is associated with significant reductions in low birthweight, with a protective efficacy of approximately 26% in an analysis of national survey data from 32 countries...
December 19, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27988484/fixed-dose-artesunate-amodiaquine-combination-vs-chloroquine-for-treatment-of-uncomplicated-blood-stage-p-vivax-infection-in-the-brazilian-amazon-an-open-label-randomized-controlled-trial
#18
Andre M Siqueira, Aline C Alencar, Gisely C Melo, Belisa L Magalhaes, Kim Machado, Aristóteles C Alencar Filho, Andrea Kuehn, Marly M Marques, Monica Costa Manso, Ingrid Felger, José L F Vieira, Valerie Lameyre, Claudio T Daniel-Ribeiro, Marcus V G Lacerda
BACKGROUND: Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. METHODS: This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop(®) (ASAQ) versus CQ for treatment of uncomplicated P...
January 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27986683/high-rate-of-treatment-failures-in-nonimmune-travelers-treated-with-artemether-lumefantrine-for-uncomplicated-plasmodium-falciparum-malaria-in-sweden-retrospective-comparative-analysis-of-effectiveness-and-case-series
#19
Klara Sondén, Katja Wyss, Irina Jovel, Antero Vieira da Silva, Anton Pohanka, Muhammad Asghar, Manijeh Vafa Homann, Lars L Gustafsson, Urban Hellgren, Anna Färnert
BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults. METHODS: A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures...
October 24, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27978709/a-malaria-transmission-blocking-usnic-acid-derivative-prevents-plasmodium-zygote-to-ookinete-maturation-in-the-mosquito-midgut
#20
Rebecca Pastrana-Mena, Derrick K Mathias, Michael Delves, Krithika Rajaram, Jonas G King, Rebecca Yee, Beatrice Trucchi, Luisella Verotta, Rhoel R Dinglasan
The evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. Recent emergence of artemisinin resistance in Southeast Asia underscores the need to develop novel antimalarials and identify new targetable pathways in Plasmodium parasites. Transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with antimalarials that target erythrocytic stages will not only cure malaria but will also prevent subsequent transmission...
December 16, 2016: ACS Chemical Biology
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