Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal
Open Access
- 30 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Malaria Journal
- Vol. 19 (1), 1-8
- https://doi.org/10.1186/s12936-020-03193-w
Abstract
In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether–lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. Here, 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. In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.Keywords
Funding Information
- Université Cheikh Anta Diop de Dakar
This publication has 31 references indexed in Scilit:
- Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013Malaria Journal, 2014
- Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samplesGenome Biology, 2014
- Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009–2013)Malaria Journal, 2014
- K13-Propeller Polymorphisms in Plasmodium falciparum Parasites From Sub-Saharan AfricaThe Journal of Infectious Diseases, 2014
- Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic StudyThe Journal of Infectious Diseases, 2014
- A molecular marker of artemisinin-resistant Plasmodium falciparum malariaNature, 2013
- Pooled Deep Sequencing of Plasmodium falciparum Isolates: An Efficient and Scalable Tool to Quantify Prevailing Malaria Drug-Resistance GenotypesThe Journal of Infectious Diseases, 2013
- Integrative Genomics Viewer (IGV): high-performance genomics data visualization and explorationBriefings in Bioinformatics, 2012
- A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEffFly, 2012
- Ultrasensitive detection of rare mutations using next-generation targeted resequencingNucleic Acids Research, 2011