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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Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015–2017
Maazza Hussien,Maazza Hussien,Muzamil Mahdi Abdel Hamid,Elamin Abdelkarim Elamin,Abdalla O. Hassan,Arwa Elaagip,Abusofyan Hamattallah A. Salama,Mohammed H. Abdelraheem,Mohammed H. Abdelraheem,Abdelrahim Osman Mohamed +9 more
TL;DR: There was high frequency of mutations in Pfcrt, PFDhfr and Pfdhps in this study, associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance.
Journal ArticleDOI
Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China
TL;DR: Based on the molecular epidemiological investigation on k13 mutations of Plasmodium isolates in Yunnan Province and the determination of the artemisinin resistance on falciparum malaria cases in Myanmar, the positively genetic correlated was found between the k13 locus mutations with artemis inin resistance phenotype.
Journal ArticleDOI
Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro.
TL;DR: The impact of short pulses of low temperature on ring-stage susceptibility of Plasmodium falciparum to artemisinin in vitro was examined and the possible activation of parasite stress responses, including the unfolded protein response, by hypo- or hyper-thermic conditions was discussed.
Journal ArticleDOI
Longitudinal Pooled Deep Sequencing of the Plasmodium vivax K12 Kelch Gene in Cambodia Reveals a Lack of Selection by Artemisinin
Nicholas F Brazeau,Nicholas J. Hathaway,Christian M. Parobek,Jessica T. Lin,Jeffrey A. Bailey,Chanthap Lon,David L. Saunders,Jonathan J. Juliano,Jonathan J. Juliano +8 more
TL;DR: Results suggest a lack of selection in the P. vivax population in Cambodia due to artemisinin drug pressure, and none of the SNPs were orthologous to art Artemisinin resistance-conferring mutations in PF3D7_1343700, and nonsynonymous changes did not persist through time within populations.
Journal ArticleDOI
Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi.
Steve M. Taylor,Steve M. Taylor,Steve M. Taylor,Brandt Levitt,Betsy Freedman,Mwayiwawo Madanitsa,Kyaw-Lay Thwai,Linda Kalilani-Phiri,Carole Khairallah,Victor Mwapasa,Feiko O. ter Kuile,Steven R Meshnick +11 more
TL;DR: The effectiveness on birthweight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP.
References
More filters
Journal ArticleDOI
The Sequence Alignment/Map format and SAMtools
Heng Li,Bob Handsaker,Alec Wysoker,T. J. Fennell,Jue Ruan,Nils Homer,Gabor T. Marth,Gonçalo R. Abecasis,Richard Durbin +8 more
TL;DR: SAMtools as discussed by the authors implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments.
Journal ArticleDOI
MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0
TL;DR: An advanced version of the Molecular Evolutionary Genetics Analysis software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis, is released, which enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny.
Journal ArticleDOI
Fast gapped-read alignment with Bowtie 2
TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Brief Communication MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0
TL;DR: The Molecular Evolutionary Genetics Analysis (MEGA) software as discussed by the authors provides facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis, including the inference of timetrees.
Journal ArticleDOI
APE: Analyses of Phylogenetics and Evolution in R language
TL;DR: UNLABELLED Analysis of Phylogenetics and Evolution (APE) is a package written in the R language for use in molecular evolution and phylogenetics that provides both utility functions for reading and writing data and manipulating phylogenetic trees.
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