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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Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon
Sylvatrie Danne Dinzouna-Boutamba,Berthe A. Iroungou,Falone Larissa Akombi,Lauriane Yacka-Mouele,Zin Moon,Ja Moon Aung,Sanghyun Lee,Dong-Il Chung,Yeonchul Hong,Youn-Kyoung Goo +9 more
TL;DR: In this paper , the authors evaluated the frequency of the polymorphisms and genetic diversity associated with this phenomenon among the parasites isolates in Gabon and found that the patterns of multiple polymorphisms were consistent with selection owing to drug pressure.
Journal ArticleDOI
Gene mutations in parasitic diseases Part II: Parasite gene mutations
TL;DR: In this article, the authors present mechanisms of drug resistance due to parasite gene mutations, with special emphasis on anti-malarial drugs, albendazole, metronidazole and other drugs used in treatment of African trypanosomiasis and toxoplasmosis.
Journal ArticleDOI
Screening for antifolate and artemisinin resistance in Plasmodium falciparum clinical isolates from three hospitals of Eritrea
TL;DR: These findings highlight first reports in Eritrea, which verify the underlying genetic mechanism of antifolate resistance, and are reliable markers for the sulfadoxine-pyrimethamine quintuple mutant haplotype combination.
Journal ArticleDOI
Adherence to Dihydroartemisinin + Piperaquine Treatment Regimen in Low and High Endemic Areas in Indonesia
TL;DR: It is suggested that the adherence to ACT medication among population in the study setting is considered to be less than 80%, which needs to be elevated to avoid the growing trend of treatment failure as seen globally.
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