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
Citations
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Molecular surveillance of Pfcrt and k13 propeller polymorphisms of imported Plasmodium falciparum cases to Zhejiang Province, China between 2016 and 2018
TL;DR: The frequency and spatial distributions of Pfcrt and k13 mutations associated with drug resistance were determined and the genetic diversity of k13 was low in most regions of Africa and purifying selection was suggested by Tajima’s D test.
Journal ArticleDOI
K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients.
Carole Else Eboumbou Moukoko,Fang Huang,Sandrine E. Nsango,Loic Pradel Kojom Foko,Serge Bruno Ebong,Patricia Epee Eboumbou,He Yan,Livia Sitchueng,Bouba Garke,Lawrence Ayong +9 more
TL;DR: The data suggested the circulation of the non-synonymous K13 mutations in Cameroon, and there is need for continuous surveillance for earlier detection of resistance as long as ACTs are used and scaled up in the community.
Journal ArticleDOI
Surveillance of Genetic Variations Associated with Antimalarial Resistance of Plasmodium falciparum Isolates from Returned Migrant Workers in Wuhan, Central China.
Yi Yao,Kai Wu,Mingxing Xu,Yan Yang,Yijing Zhang,Wenjing Yang,Ronghua Shang,Weixing Du,Huabing Tan,Jiang-Tao Chen,Min Lin,Jian Li +11 more
TL;DR: Blood samples from returned Chinese migrant workers used to identify drug resistance-associated molecular markers suggested that Pfcrt, Pfmdr1, and K13-propeller polymorphisms are potential markers to assess drug resistance of P. falciparum in China, Africa, and SEA.
Journal ArticleDOI
No polymorphisms in K13-propeller gene associated with artemisinin resistance in Plasmodium falciparum isolated from Brazzaville, Republic of Congo
Pembe Issamou Mayengue,Roch Fabien Niama,Dezi Kouhounina Batsimba,Alida Malonga-Massanga,Igor Louzolo,Nadia Claricelle Loukabou Bongolo,Lucette Macosso,Reyna Ibara Ottia,Ghyslain Kimbassa Ngoma,Louis Regis Dossou-Yovo,Brice Pembet Singana,Gabriel Ahombo,Géril Sekangue Obili,Simon Charles Kobawila,Henri Joseph Parra +14 more
TL;DR: The current study shows a very limited polymorphism in the K13-propeller gene in isolates from the Republic of Congo and K13 polymorphisms associate with ACT resistance are not present in this country.
Journal ArticleDOI
Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal.
Amy Gaye,Mouhamad Sy,Tolla Ndiaye,Katherine J. Siddle,Daniel J. Park,Awa B. Deme,Aminata Mbaye,Baba Dieye,Yaye Die Ndiaye,Daniel E. Neafsey,Daniel E. Neafsey,Angela M. Early,Timothy Farrell,Mamadou S. Yade,Mamadou Alpha Diallo,Khadim Diongue,Amy K. Bei,Amy K. Bei,Ibrahima Ndiaye,Sarah K. Volkman,Sarah K. Volkman,Aida Sadikh Badiane,Daouda Ndiaye +22 more
TL;DR: An amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal, and the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia.
References
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