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
Citations
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Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response to Plasmodium falciparum.
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Ozonide Antimalarial Activity in the Context of Artemisinin-Resistant Malaria.
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Optimization of a Ligase Detection Reaction-Fluorescent Microsphere Assay for Characterization of Resistance-Mediating Polymorphisms in African Samples of Plasmodium falciparum
Norbert P. LeClair,Melissa D. Conrad,Frederick N. Baliraine,Christian Nsanzabana,Samuel L. Nsobya,Philip J. Rosenthal +5 more
TL;DR: The results suggest that the LDR-FM system offers an accurate high-throughput means of classifying genetic polymorphisms in field samples of P. falciparum and estimates that it offers much higher throughput and lower cost than RFLP.
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Absence of association between polymorphisms in the K13 gene and the presence of Plasmodium falciparum parasites at day 3 after treatment with artemisinin derivatives in Senegal
Marylin Madamet,Mame Bou Kounta,Khalifa Ababacar Wade,Gora Lo,Silman Diawara,Mansour Fall,Raymond Bercion,Aminata Nakoulima,Khadidiatou Ba Fall,Nicolas Benoit,Mamadou Wague Gueye,Bécaye Fall,Bakary Diatta,Bruno Pradines +13 more
TL;DR: The results suggest that K13 is not the best predictive marker for artemisinin resistance in Africa, and more isolates from clinical failure cases or patients with delayed parasite clearance after treatment with art Artemisinin derivatives are necessary to identify new molecular markers.
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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