Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014-2016.
Mie Ikeda,Megumi Kaneko,Shin-Ichiro Tachibana,Betty Balikagala,Miki Sakurai-Yatsushiro,Shouki Yatsushiro,Nobuyuki Takahashi,Masato Yamauchi,Makoto Sekihara,Muneaki Hashimoto,Osbert T. Katuro,Alex Olia,Paul S. Obwoya,Mary A. Auma,Denis A Anywar,Emmanuel I. Odongo-Aginya,Joseph Okello-Onen,Makoto Hirai,Jun Ohashi,Nirianne Marie Q. Palacpac,Masatoshi Kataoka,Takafumi Tsuboi,Eisaku Kimura,Toshihiro Horii,Toshihiro Mita +24 more
TLDR
Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.Abstract:
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.read more
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The Organization of Will
TL;DR: The process by which a group will is arrived at may be termed the organization of will as mentioned in this paper, and combining of the efforts of a number of persons for the accomplishment of a particular purpose results in the 'organization of effort'.
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Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments : a WWARN individual patient data meta-analysis
Chanaki Amaratunga,Voahangy Andrianaranjaka,Elizabeth A. Ashley,Delia Bethell,Anders Björkman,Craig A. Bonnington,Roland A. Cooper,Mehul Dhorda,Arjen M. Dondorp,Annette Erhart,Rick M. Fairhurst,Abul Faiz,Caterina I. Fanello,Mark M. Fukuda,Philippe J Guerin,Rob Hooft van Huijsduijnen,Tran Tinh Hien,N. V. Hong,Ye Htut,Fang Huang,Georgina S Humphreys,Mallika Imwong,Kalynn Kennon,Pharath Lim,Khin Lin,Chanthap Lon,Andreas Mårtensson,Mayfong Mayxay,Olugbenga A. Mokuolu,Ulrika Morris,Billy Ngasala,Alfred Amambua-Ngwa,Harald Noedl,François Nosten,Marie A. Onyamboko,Aung Pyae Phyo,Christopher V. Plowe,Sasithon Pukrittayakamee,Milijaona Randrianarivelojosia,Philip J. Rosenthal,David L. Saunders,Carol Hopkins Sibley,Frank Smithuis,Michele D. Spring,Paul Sondo,Sokunthea Sreng,Peter Starzengruber,Kasia Stepniewska,Seila Suon,Shannon Takala-Harrison,Kamala Thriemer,Nguyen Thuy-Nhien,Kyaw Myo Tun,Nicholas J. White,Charles J. Woodrow +54 more
TL;DR: An individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa demonstrates that 15 additional pfK13 alleles are associated strongly with the slow-clearing phenotype in Southeast Asia.
Journal ArticleDOI
Antimalarial drug resistance in Africa: the calm before the storm?
TL;DR: This Review summarises evolving patterns of antimalarial drug resistance in Africa and indicates that resistance to artemisinins or key partner drugs included in combination therapies does not appear to be a substantial problem in Africa.
Journal ArticleDOI
Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.
Olivo Miotto,Makoto Sekihara,Shin-Ichiro Tachibana,Masato Yamauchi,Richard D. Pearson,Richard D. Pearson,Roberto Amato,Sónia Gonçalves,Somya Mehra,Rintis Noviyanti,Jutta Marfurt,Sarah Auburn,Sarah Auburn,Sarah Auburn,Ric N. Price,Ric N. Price,Ric N. Price,Ivo Mueller,Mie Ikeda,Toshiyuki Mori,Makoto Hirai,Livingstone Tavul,Manuel W Hetzel,Manuel W Hetzel,Moses Laman,Alyssa E. Barry,Pascal Ringwald,Jun Ohashi,Francis Hombhanje,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Toshihiro Mita +31 more
TL;DR: It is suggested that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity.
Journal ArticleDOI
Changing Prevalence of Potential Mediators of Aminoquinoline, Antifolate, and Artemisinin Resistance Across Uganda.
Victor Asua,Melissa D. Conrad,Ozkan Aydemir,Marvin Duvalsaint,Jennifer Legac,Elias Duarte,Patrick K Tumwebaze,Deborah M Chin,Roland A. Cooper,Adoke Yeka,Moses R. Kamya,Grant Dorsey,Sam L. Nsobya,Jeffrey A. Bailey,Philip J. Rosenthal +14 more
TL;DR: Concerns are demonstrated concerning spread of mutations that may limit efficacies of key antimalarial drugs.
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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
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.
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