Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study
Steve M. Taylor,Steve M. Taylor,Christian M. Parobek,Derrick K. DeConti,Kassoum Kayentao,Sheick Oumar Coulibaly,Brian Greenwood,Harry Tagbor,John V. Williams,Kalifa Bojang,Fanta Njie,Meghna Desai,Simon Kariuki,Julie Gutman,Don P. Mathanga,Andreas Mårtensson,Billy Ngasala,Melissa D. Conrad,Philip J. Rosenthal,Antoinette Tshefu,Ann M. Moormann,John M. Vulule,Ogobara K. Doumbo,Feiko O. ter Kuile,Feiko O. ter Kuile,Steven R. Meshnick,Jeffrey A. Bailey,Jonathan J. Juliano +27 more
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TLDR
An assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies is developed and validated by evaluating mixtures of laboratory parasite strains, and used to screen P. falciparum parasites from >1100 African infections collected since 2002.Abstract:
Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.read more
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Dissertation
Plasmodium falciparum et résistance aux antipaludiques : aperçu et conséquences des facteurs impliqués dans la sélection et la diffusion des parasites résistants
TL;DR: Une deuxieme partie explore, in vitro, the possibles consequences d'une utilisation prolongee des derives d'artemisinine sur le phenotype de P. falciparum, alors que la resistance a cette molecule est deja installee.
Journal ArticleDOI
Therapeutic efficacy of artemether–lumefantrine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016
Youssouf Diarra,Oumar Koné,Lansana Sangaré,Lassina Doumbia,Dade Bouye Ben Haidara,Mouctar Diallo,Ababacar Maïga,Hammadoun Aly Sango,Halidou Sidibé,Jules Mihigo,Douglas Nace,Dragan Ljolje,Eldin Talundzic,Venkatachalam Udhayakumar,Erin Eckert,Celia Jane Woodfill,Leah F. Moriarty,Pharath Lim,Donald J. Krogstad,Eric S. Halsey,Naomi W. Lucchi,O. Koita +21 more
TL;DR: Both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali, and no mutations associated with artemisinin resistance were identified in the Pfk13 gene.
DissertationDOI
Exploring the contributionof new genetic markers of drugresistance in human malaria parasites
TL;DR: The molecular work carried out here demonstrates that a Ser160Asn/Thr mutation in the pfap2-mu gene and an E1528D mutation inThe pfubp-1 gene might be associated with in vivo responses to artemisinin derivatives, which are implicated in ART resistance in P. falciparum.
Journal ArticleDOI
Multiple Phenotypic and Genotypic Artemisinin Sensitivity Evaluation of Malian Plasmodium falciparum Isolates.
Karamoko Niaré,Lucie Paloque,Sandie Menard,Pety Tor,Arba Pramundita Ramadani,Jean-Michel Augereau,Antoine Dara,Antoine Dara,Antoine Berry,Françoise Benoit-Vical,Ogobara K. Doumbo +10 more
TL;DR: The assays presented here appear as valuable tools for the monitoring of artemisinin sensitivity in the field and thus could help to evaluate the risk of emergence of art Artemisinin resistance in Africa.
Dissertation
Molecular methods in malaria control in the era of pre-elimination
TL;DR: The study revealed important characteristics of the remaining parasite populations, including intriguing trends in SNPs associated with antimalarial drug resistance that require further investigation in order to be fully understood.
References
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