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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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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Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria.
Papa Alioune Ndour,Tatiana M. Lopera-Mesa,Seidina A. S. Diakite,Serena Chiang,Oussama Mouri,Camille Roussel,Stéphane Jauréguiberry,Sylvestre Biligui,Eric Kendjo,Antoine Claessens,Liliane Ciceron,Dominique Mazier,Marc Thellier,Mahamadou Diakite,Rick M. Fairhurst,Pierre Buffet +15 more
TL;DR: Antimalarial immunity correlates with fast artemisinin-induced parasite clearance and low pitting rates, and this mechanism may mitigate the emergence of artemis inin-resistant P. falciparum in Africa.
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Toxicity of six plant extracts and two pyridone alkaloids from Ricinus communis against the malaria vector Anopheles gambiae
Sabina Wachira,Sabina Wachira,Sabar Omar,Julia Wanjiru Jacob,Martin Wahome,Hans T. Alborn,David R. Spring,Daniel K. Masiga,Baldwyn Torto +8 more
TL;DR: Overall, these findings demonstrate that extracts from the six plant species exhibit varying bioactivity against the larvae and adult females of An.
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Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity
Kesara Na-Bangchang,Phunuch Muhamad,Ronnatrai Ruaengweerayut,Wanna Chaijaroenkul,Juntra Karbwang +4 more
TL;DR: Artemisinin-based combination therapy (ACT) would be expected to remain the key anti-malarial drug for treatment of multidrug resistance P. falciparum, and Amplification of pfmdr1 is a related molecular marker of artesunate-mefloquine resistance and seems to be a suitable molecular marker to predict occurrence of recrudescence.
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Efficacy and Safety of Artemether-Lumefantrine in the Treatment of Acute, Uncomplicated Plasmodium falciparum Malaria: A Pooled Analysis
Michael Makanga,Quique Bassat,Catherine O. Falade,Zulfiqarali Premji,Srivicha Krudsood,Philip Hunt,Verena Walter,Hans-Peter Beck,Anne-Claire Marrast,Marc Cousin,Philip J. Rosenthal +10 more
TL;DR: Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.
Journal ArticleDOI
Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs.
Bécaye Fall,Silmane Diawara,Kowry Sow,Eric Baret,Bakary Diatta,Khadidiatou Ba Fall,P. S. Mbaye,F. Fall,Yaya Diémé,Christophe Rogier,Boubacar Wade,Raymond Bercion,Bruno Pradines +12 more
TL;DR: The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components, however, the prevalence of the in vitro resistant isolates with reduced susceptibility has increased for both MQ and DOX.
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).
Journal ArticleDOI
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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