Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator
TLDR
The parasite clearance estimator provides a consistent, reliable and accurate method to estimate the lag phase and malaria parasite clearance rate and could be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds which affect ring-stage clearance.Abstract:
Background
A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT), signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in Plasmodium falciparum. The slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-malarial effect. However, an initial lag phase of numerical instability often precedes a steady exponential decline in the parasite count after the start of anti-malarial treatment. This lag complicates the clearance estimation, introduces observer subjectivity, and may influence the accuracy and consistency of reported results.read more
Citations
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Journal ArticleDOI
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
TL;DR: Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing, and the incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission.
Journal ArticleDOI
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
TL;DR: Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance.
Journal ArticleDOI
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
TL;DR: Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially, with experts predicting resistance will reach rates reported in western Cambodia in 2–6 years.
Journal ArticleDOI
Genetic architecture of artemisinin-resistant Plasmodium falciparum.
Olivo Miotto,Roberto Amato,Elizabeth A. Ashley,Bronwyn MacInnis,Jacob Almagro-Garcia,Chanaki Amaratunga,Pharath Lim,Daniel Mead,Samuel O. Oyola,Mehul Dhorda,Mallika Imwong,Charles J. Woodrow,Magnus Manske,Jim Stalker,Eleanor Drury,Susana Campino,Lucas Amenga-Etego,Thanh T-Nn.,Hien Tinh Tran,Pascal Ringwald,Delia Bethell,François Nosten,Aung Pyae Phyo,S Pukrittayakamee,Kesinee Chotivanich,Char Meng Chuor,Chea Nguon,Seila Suon,Sokunthea Sreng,Paul N. Newton,Mayfong Mayxay,Maniphone Khanthavong,Bouasy Hongvanthong,Ye Htut,K T Han,Myat Phone Kyaw,MA Faiz,Caterina I. Fanello,M A Onyamboko,Olugbenga A. Mokuolu,Christopher G Jacob,Shannon Takala-Harrison,Christopher V. Plowe,Nicholas P. J. Day,Arjen M. Dondorp,Spencer Cca.,Gil McVean,Rick M. Fairhurst,Nicholas J. White,Dominic P. Kwiatkowski +49 more
TL;DR: Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance.
Journal ArticleDOI
Novel phenotypic assays for the detection of artemisinin- resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies
Benoit Witkowski,Chanaki Amaratunga,Nimol Khim,Sokunthea Sreng,Pheaktra Chim,Saorin Kim,Pharath Lim,Pharath Lim,Sivanna Mao,Chantha Sopha,Baramey Sam,Jennifer M. Anderson,Socheat Duong,Char Meng Chuor,Walter R. J. Taylor,Seila Suon,Odile Mercereau-Puijalon,Rick M. Fairhurst,Didier Menard +18 more
TL;DR: The in-vitro RSA of 0-3 h ring-stage parasites provides a platform for the molecular characterisation of artemisinin resistance and the ex-vivo RSA can be easily implemented where surveillance for artemis inin resistance is needed.
References
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Artemisinin Resistance in Plasmodium falciparum Malaria
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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.
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