Artemisinin Resistance in Plasmodium falciparum Malaria
Arjen M. Dondorp,François Nosten,Poravuth Yi,Debashish Das,Aung Phae Phyo,Joel Tarning,Khin Maung Lwin,Frédéric Ariey,Warunee Hanpithakpong,Sue J. Lee,Pascal Ringwald,Kamolrat Silamut,Mallika Imwong,Kesinee Chotivanich,Pharath Lim,Trent Herdman,Sen Sam An,Shunmay Yeung,Pratap Singhasivanon,Nicholas P. J. Day,Niklas Lindegardh,Duong Socheat,Nicholas J. White +22 more
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TLDR
The overall median clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours in Wang Pha (P<0.001) in each of the two locations as discussed by the authors.Abstract:
We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate–mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P = 0. 31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco–endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.)read more
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Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: Synthesis, characterization and in vitro antimalarial activity
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Lack of artemisinin resistance in Plasmodium falciparum in Uganda based on parasitological and molecular assays
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TL;DR: Three isolates of Plasmodium falciparum isolated in Kampala in 2014 had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia, and there was no evidence for artemisinin resistance in Uganda.
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Artemisinin Resistance–Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010–2015
Costanza Tacoli,Prabhanjan P. Gai,Claude Bayingana,Kevin C. Sifft,Dominik Geus,Jules Ndoli,Augustin Sendegeya,Jean Bosco Gahutu,Frank P. Mockenhaupt +8 more
TL;DR: Establishing correlations with local treatment response and in vitro resistance assays are needed in addition to further monitoring K13 polymorphisms in the study area, which are infrequent but include variants associated with artemisinin resistance.
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Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials
Stephan Duparc,Isabelle Borghini-Fuhrer,Carl J Craft,Sarah Arbe-Barnes,Robert M Miller,Chang-Sik Shin,Lawrence Fleckenstein +6 more
TL;DR: Pyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases and met the requirements for use as first-line therapy.
References
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Journal ArticleDOI
Evidence of Artemisinin-Resistant Malaria in Western Cambodia
TL;DR: Artemisinins are potent and rapidly acting antimalarial drugs, and their widespread use for treating patients with Plasmodium falciparum malaria raises the question of emerging drug resistance.
Journal ArticleDOI
Artemisinins target the SERCA of Plasmodium falciparum
Ursula Eckstein-Ludwig,Richard Webb,I. D. A. van Goethem,J M East,Anthony G. Lee,Masatsugu Kimura,Paul M. O'Neill,Patrick G. Bray,Stephen A. Ward,Sanjeev Krishna +9 more
TL;DR: It is shown that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor).
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TL;DR: Artesunate should become the treatment of choice for severe falciparum malaria in adults because it is more rapidly acting than intravenous quinine in terms of parasite clearance and is simpler to administer.
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Qinghaosu (artemisinin): the price of success.
TL;DR: Artemisinin combination treatments are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries and a global subsidy would make these drugs more affordable and available.
Journal ArticleDOI
Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.
Ric N. Price,Ric N. Price,Anne-Catrin Uhlemann,Alan Brockman,Rose McGready,Elizabeth A. Ashley,L Phaipun,Rina Patel,Ken Laing,Sornchai Looareesuwan,Nicholas J. White,Nicholas J. White,François Nosten,Sanjeev Krishna +13 more
TL;DR: It is shown that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with mefloquine.
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