Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal.
Amplicon deep sequencing
Artemisinin resistance
PfK13-propeller
Senegal
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
30 Mar 2020
30 Mar 2020
Historique:
received:
20
08
2019
accepted:
20
03
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
21
10
2020
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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.
RESULTS
RESULTS
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.
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 32228566
doi: 10.1186/s12936-020-03193-w
pii: 10.1186/s12936-020-03193-w
pmc: PMC7106636
doi:
Substances chimiques
Antimalarials
0
Artemisinins
0
Protozoan Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
134Subventions
Organisme : NIAID NIH HHS
ID : U19 AI089696
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Références
Genome Res. 2016 Sep;26(9):1288-99
pubmed: 27531718
Nucleic Acids Res. 2012 Jan;40(1):e2
pubmed: 22013163
Genome Biol. 2014;15(11):519
pubmed: 25403361
J Infect Dis. 2015 Apr 15;211(8):1352-5
pubmed: 25367300
Microbiol Spectr. 2016 Jun;4(3):
pubmed: 27337450
J Infect Dis. 2013 Dec 15;208(12):1998-2006
pubmed: 23908494
Biomed Res Int. 2018 Oct 3;2018:2305062
pubmed: 30402465
Malar J. 2017 May 12;16(1):195
pubmed: 28494763
Antimicrob Agents Chemother. 2015 Oct 26;60(1):624-7
pubmed: 26503652
BMC Med. 2019 Jan 17;17(1):1
pubmed: 30651111
Malar J. 2014 Dec 04;13:472
pubmed: 25471113
Genes (Basel). 2018 May 22;9(5):
pubmed: 29789467
Infect Drug Resist. 2018 Aug 28;11:1329-1338
pubmed: 30214253
Malar J. 2014 Nov 18;13:431
pubmed: 25404021
N Engl J Med. 2017 Mar 9;376(10):991-3
pubmed: 28225668
PLoS One. 2015 Aug 20;10(8):e0136099
pubmed: 26292024
Malar J. 2016 Dec 3;15(1):583
pubmed: 27912758
Nature. 2014 Jan 2;505(7481):50-5
pubmed: 24352242
J Infect Dis. 2016 Jan 1;213(1):165-6
pubmed: 26268852
Emerg Infect Dis. 2015 Jul;21(7):1237-9
pubmed: 26079933
BMC Infect Dis. 2018 Oct 29;18(1):538
pubmed: 30373565
Emerg Infect Dis. 2015 Mar;21(3):490-2
pubmed: 25695257
Antimicrob Agents Chemother. 2016 May 23;60(6):3821-3
pubmed: 27001821
Elife. 2016 Mar 04;5:
pubmed: 26943619
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Antimicrob Agents Chemother. 2017 Feb 23;61(3):
pubmed: 28069653
Antimicrob Agents Chemother. 2019 Sep 23;63(10):
pubmed: 31332065
J Infect Dis. 2015 Mar 1;211(5):680-8
pubmed: 25180240
Am J Trop Med Hyg. 2018 Dec;99(6):1357-1359
pubmed: 30426924
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427