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
Reads0
Chats0
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
More filters
Journal ArticleDOI
Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children.
Patrick K Tumwebaze,Melissa D. Conrad,Andrew Walakira,Norbert P. LeClair,Oswald Byaruhanga,Christine Nakazibwe,Benjamin Kozak,Jessica Bloome,Jaffer Okiring,Abel Kakuru,Victor Bigira,James Kapisi,Jennifer Legac,Jiri Gut,Roland A. Cooper,Moses R. Kamya,Diane V. Havlir,Grant Dorsey,Bryan Greenhouse,Samuel L. Nsobya,Philip J. Rosenthal +20 more
TL;DR: Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda and may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.
Journal ArticleDOI
Target Validation and Identification of Novel Boronate Inhibitors of the Plasmodium falciparum Proteasome
Stanley C. Xie,David L. Gillett,Natalie J. Spillman,Christopher Tsu,Madeline R. Luth,Sabine Ottilie,Sandra Duffy,Alexandra E. Gould,Paul Hales,Benjamin A Seager,Carlie L. Charron,Frank Bruzzese,Xiaofeng Yang,Xiansi Zhao,Shih-Chung Huang,Craig A. Hutton,Jeremy N. Burrows,Elizabeth A. Winzeler,Vicky M. Avery,Lawrence R. Dick,Leann Tilley +20 more
TL;DR: This work provides a starting point for the identification of antimalarial drug leads that selectively target the P. falciparum 20S proteasome and reveals inhibitor features that enable retention of potent activity against the bortezomib-resistant line.
Journal ArticleDOI
Changing Antimalarial Drug Sensitivities in Uganda.
Stephanie A Rasmussen,Frida G. Ceja,Melissa D. Conrad,Patrick K Tumwebaze,Oswald Byaruhanga,Thomas Katairo,Samuel L. Nsobya,Philip J. Rosenthal,Roland A. Cooper +8 more
TL;DR: The sensitivities of 2016 community isolates to chloroquine, amodiaquine, and piperaquine improved, and changes were accompanied by decreased prevalence of transporter mutations associated with aminoquinoline resistance and low prevalence of polymorphisms recently associated with resistance to artemisinins or p Piperaquine.
Journal ArticleDOI
Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum
Talita Perez Cantuaria Chierrito,Anna Caroline Campos Aguiar,Anna Caroline Campos Aguiar,Isabel M de Andrade,Isabela P. Ceravolo,Regina Aparecida Correia Gonçalves,Arildo José Braz de Oliveira,Antoniana U. Krettli,Antoniana U. Krettli +8 more
TL;DR: Using a bio-monitoring approach, it was possible to attribute the anti-P.
Book ChapterDOI
Natural Products as Pharmaceuticals and Sources for Lead Structures
TL;DR: This chapter reviews the continuing value of natural products as sources of potential chemotherapeutic agents and describes methods of chemical syntheses that have the potential to produce base “natural product” molecules that can be optimized for specific medicinal chemistry purposes.
References
More filters
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.
Related Papers (5)
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Frédéric Ariey,Benoit Witkowski,Chanaki Amaratunga,Johann Beghain,Anne-Claire Langlois,Nimol Khim,Saorin Kim,Valentine Duru,Christiane Bouchier,Laurence Ma,Pharath Lim,Rithea Leang,Socheat Duong,Sokunthea Sreng,Seila Suon,Char Meng Chuor,Denis Mey Bout,Sandie Menard,William O. Rogers,Blaise Genton,Thierry Fandeur,Olivo Miotto,Pascal Ringwald,Jacques Le Bras,Antoine Berry,Jean Christophe Barale,Rick M. Fairhurst,Françoise Benoit-Vical,Odile Mercereau-Puijalon,Didier Menard +29 more
Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
Elizabeth A. Ashley,Mehul Dhorda,Rick M. Fairhurst,Chanaki Amaratunga,Pharath Lim,Seila Suon,Sokunthea Sreng,Jennifer M. Anderson,Mao S,Sam B,Chantha Sopha,Char Meng Chuor,Chea Nguon,Siv Sovannaroth,Sasithon Pukrittayakamee,Podjanee Jittamala,Kesinee Chotivanich,K Chutasmit,C Suchatsoonthorn,R Runcharoen,Tran Tinh Hien,Nguyen Thuy-Nhien,Thanh Nv,Nguyen Hoan Phu,Ye Htut,Han Kt,Kyin Hla Aye,Olugbenga A. Mokuolu,Rasaq Olaosebikan,Olaleke Oluwasegun Folaranmi,Mayfong Mayxay,Maniphone Khanthavong,Bouasy Hongvanthong,Paul N. Newton,M A Onyamboko,Caterina I. Fanello,Antoinette Tshefu,Neelima Mishra,Neena Valecha,Aung Pyae Phyo,François Nosten,Yi P,Rupam Tripura,Steffen Borrmann,Mahfudh Bashraheil,Judy Peshu,M A Faiz,Aniruddha Ghose,M A Hossain,Rasheda Samad,M. R. Rahman,Manal Hasan,Ashraful Islam,Olivo Miotto,Roberto Amato,Bronwyn MacInnis,Jim Stalker,Dominic P. Kwiatkowski,Zbynek Bozdech,Atthanee Jeeyapant,Phaik Yeong Cheah,Tharisara Sakulthaew,Jeremy Chalk,Benjamas Intharabut,Kamolrat Silamut,Lee Sj,Benchawan Vihokhern,Chanon Kunasol,Mallika Imwong,Joel Tarning,Taylor Wj,Shunmay Yeung,Charles J. Woodrow,Jennifer A. Flegg,Debashish Das,Jennifer L. Smith,Meera Venkatesan,Christopher V. Plowe,Kasia Stepniewska,Philippe J Guerin,Arjen M. Dondorp,Nicholas P. J. Day,Nicholas J. White +82 more
Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study
Aung Pyae Phyo,Standwell Nkhoma,Kasia Stepniewska,Kasia Stepniewska,Elizabeth A. Ashley,Elizabeth A. Ashley,Shalini Nair,Rose McGready,Rose McGready,Carit Ler Moo,Salma Al-Saai,Arjen M. Dondorp,Arjen M. Dondorp,Khin Maung Lwin,Pratap Singhasivanon,Nicholas P. J. Day,Nicholas P. J. Day,Nicholas J. White,Nicholas J. White,Tim J. Anderson,François Nosten,François Nosten +21 more