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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Transmission of artemisinin-resistant malaria parasites to mosquitoes under antimalarial drug pressure
Kathrin Witmer,Farah A. Dahalan,Michael J. Delves,Sabrina Yahiya,Oliver J Watson,Ursula Straschil,Darunee Chiwcharoen,Boodtee Sornboon,Sasithon Pukrittayakamee,Richard D. Pearson,Virginia M. Howick,Mara K. N. Lawniczak,Nicholas J. White,Nicholas J. White,Arjen M. Dondorp,Arjen M. Dondorp,Lucy C Okell,Kesinee Chotivanich,Andrea Ruecker,Andrea Ruecker,Jake Baum +20 more
TL;DR: Results indicate that, under artemisinin drug pressure, while sensitive parasites are blocked, resistant parasites continue transmission, which could have profound implications for the spread of multidrug-resistant malaria beyond Southeast Asia.
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Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya.
Zaydah R. de Laurent,Zaydah R. de Laurent,Lorna J. Chebon,Luicer A. Ingasia,Hoseah M. Akala,Ben Andagalu,Lynette Isabella Ochola-Oyier,Lynette Isabella Ochola-Oyier,Edwin Kamau,Edwin Kamau +9 more
TL;DR: The type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods were shown.
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Plasmodium falciparum endoplasmic reticulum-resident calcium binding protein is a possible target of synthetic antimalarial endoperoxides, N-89 and N-251.
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Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.
TL;DR: It is revealed that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations in circulation in these two regions.
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Ahead of the curve: next generation estimators of drug resistance in malaria infections
Nicole Mideo,David A. Kennedy,David A. Kennedy,Jane M. Carlton,Jeffrey A. Bailey,Jonathan J. Juliano,Andrew F. Read,Andrew F. Read +7 more
TL;DR: In this article, the authors proposed a selection differential approach to detect drug resistance in malaria parasites through a phenotypic signature: individual parasite variants clearing more slowly following drug treatment, which can be used to uncover the true scale of the drug resistance problem.
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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Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.
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.
Journal ArticleDOI
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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