Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019).
Artemisinin combination therapy
Equatorial Guinea
Genes
Malaria
Resistance
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
14 Dec 2021
14 Dec 2021
Historique:
received:
28
09
2021
accepted:
01
12
2021
entrez:
15
12
2021
pubmed:
16
12
2021
medline:
1
1
2022
Statut:
epublish
Résumé
Malaria is one of the deadliest diseases in the world, particularly in Africa. As such, resistance to anti-malarial drugs is one of the most important problems in terms of global malaria control. This study assesses the evolution of the different resistance markers over time and the possible influence of interventions and treatment changes that have been made in Equatorial Guinea. A total of 1223 biological samples obtained in the period 1999 to 2019 were included in the study. Screening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes was carried out by nested PCR and restriction-fragment length polymorphisms (RFLPs), and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations. The partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time. Moreover, in 2019, the fully resistant haplotype was found to be increasing, although its super-resistant counterpart remains much less prevalent. A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT. In addition, the non-synonymous A578S mutation, which is the most frequent on the African continent, was detected in 2013, although not in the following years. Withdrawal of the use of chloroquine (CQ) as a treatment in Equatorial Guinea has been shown to be effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in sulfadoxine-pyrimethamine (SP) resistance markers suggest its misuse, either alone or in combination with artesunate (AS) or amodiaquine (AQ), in some areas of the country, as was found in a previous study conducted by this group, which allows selective pressure from SP to continue. Single nucleotide polymorphisms (SNPs) 540E and 581G do not exceed the limit of 50 and 10%, respectively, thus meaning that SP is still effective as an intermittent preventive treatment (IPT) in this country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACT. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria is one of the deadliest diseases in the world, particularly in Africa. As such, resistance to anti-malarial drugs is one of the most important problems in terms of global malaria control. This study assesses the evolution of the different resistance markers over time and the possible influence of interventions and treatment changes that have been made in Equatorial Guinea.
METHODS
METHODS
A total of 1223 biological samples obtained in the period 1999 to 2019 were included in the study. Screening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes was carried out by nested PCR and restriction-fragment length polymorphisms (RFLPs), and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations.
RESULTS
RESULTS
The partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time. Moreover, in 2019, the fully resistant haplotype was found to be increasing, although its super-resistant counterpart remains much less prevalent. A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT. In addition, the non-synonymous A578S mutation, which is the most frequent on the African continent, was detected in 2013, although not in the following years.
CONCLUSIONS
CONCLUSIONS
Withdrawal of the use of chloroquine (CQ) as a treatment in Equatorial Guinea has been shown to be effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in sulfadoxine-pyrimethamine (SP) resistance markers suggest its misuse, either alone or in combination with artesunate (AS) or amodiaquine (AQ), in some areas of the country, as was found in a previous study conducted by this group, which allows selective pressure from SP to continue. Single nucleotide polymorphisms (SNPs) 540E and 581G do not exceed the limit of 50 and 10%, respectively, thus meaning that SP is still effective as an intermittent preventive treatment (IPT) in this country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACT. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008.
Identifiants
pubmed: 34906159
doi: 10.1186/s12936-021-04000-w
pii: 10.1186/s12936-021-04000-w
pmc: PMC8670137
doi:
Substances chimiques
Antimalarials
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
463Subventions
Organisme : Instituto de Salud Carlos III
ID : TRPY111/2018 (PI17CIII/0016)
Informations de copyright
© 2021. The Author(s).
Références
Int J Parasitol Drugs Drug Resist. 2015 Jun 29;5(3):92-9
pubmed: 26236581
Malar J. 2014 Jul 09;13:264
pubmed: 25007802
Am J Trop Med Hyg. 2017 Jul;97(1):222-224
pubmed: 28719312
Mol Cell. 2000 Oct;6(4):861-71
pubmed: 11090624
Malar J. 2017 Jan 13;16(1):28
pubmed: 28086777
Malar J. 2017 Jan 23;16(1):38
pubmed: 28114990
Int J Parasitol Drugs Drug Resist. 2020 Dec;14:208-217
pubmed: 33197753
Trends Parasitol. 2013 Oct;29(10):505-15
pubmed: 24028889
Am J Trop Med Hyg. 1995 Nov;53(5):526-31
pubmed: 7485712
Malar J. 2017 Mar 27;16(1):130
pubmed: 28347314
N Engl J Med. 2016 Jun 23;374(25):2453-64
pubmed: 27332904
J Trop Med. 2009;2009:781865
pubmed: 20339460
Infect Drug Resist. 2018 Aug 28;11:1329-1338
pubmed: 30214253
Science. 2012 Apr 6;336(6077):79-82
pubmed: 22491853
Infect Drug Resist. 2020 Apr 28;13:1203-1212
pubmed: 32431521
Malar J. 2019 Oct 7;18(1):343
pubmed: 31590670
J Infect Dis. 2015 Apr 15;211(8):1352-5
pubmed: 25367300
Trans R Soc Trop Med Hyg. 2002 Apr;96 Suppl 1:S199-204
pubmed: 12055839
PLoS One. 2009 Aug 26;4(8):e6762
pubmed: 19707564
Malar J. 2018 Mar 9;17(1):107
pubmed: 29523144
Am J Trop Med Hyg. 2006 Jul;75(1):155-61
pubmed: 16837724
PLoS One. 2014 Aug 21;9(8):e105690
pubmed: 25144768
Antimicrob Agents Chemother. 2015 Jan;59(1):734-7
pubmed: 25403659
PLoS One. 2019 Sep 3;14(9):e0221895
pubmed: 31479501
Int J Parasitol Drugs Drug Resist. 2016 Jan 12;6(1):54-59
pubmed: 27054064
Malar J. 2021 Mar 17;20(1):152
pubmed: 33731134
Malar J. 2018 Oct 16;17(1):364
pubmed: 30326904
FEBS J. 2017 Aug;284(16):2569-2578
pubmed: 28580606
Nature. 2014 Jan 2;505(7481):50-5
pubmed: 24352242
Infect Genet Evol. 2018 Dec;66:222-228
pubmed: 30316883
Malar J. 2019 Mar 12;18(1):76
pubmed: 30871535
J Infect Dis. 2003 Jun 15;187(12):1870-5
pubmed: 12792863
J Clin Invest. 2004 Apr;113(8):1084-92
pubmed: 15085184
Am J Trop Med Hyg. 2013 Jun;88(6):1087-1092
pubmed: 23530078
Am J Trop Med Hyg. 1995 Jun;52(6):565-8
pubmed: 7611566
Malar J. 2021 Jun 22;20(1):275
pubmed: 34158055
Lancet Infect Dis. 2003 Jun;3(6):349-58
pubmed: 12781507
Malar J. 2018 Jan 09;17(1):17
pubmed: 29316929
Malar Res Treat. 2018 May 2;2018:7071383
pubmed: 29854394
Malar J. 2018 Jun 4;17(1):222
pubmed: 29866192
Elife. 2016 Mar 04;5:
pubmed: 26943619
Malar J. 2014 Feb 24;13:68
pubmed: 24564912
Parasitol Res. 2018 Mar;117(3):801-807
pubmed: 29332155
N Engl J Med. 2006 Nov 9;355(19):1959-66
pubmed: 17093247
N Engl J Med. 2014 Jul 31;371(5):411-23
pubmed: 25075834
Malar J. 2019 Mar 7;18(1):60
pubmed: 30846002
Am J Trop Med Hyg. 2014 Oct;91(4):833-843
pubmed: 25048375
J Infect Dis. 2005 Mar 15;191(6):1014-7
pubmed: 15717281
Malar J. 2014 Dec 04;13:472
pubmed: 25471113
J Antimicrob Chemother. 2018 Oct 1;73(10):2704-2715
pubmed: 30053021
Malar J. 2019 Mar 21;18(1):88
pubmed: 30898164
Jpn J Infect Dis. 2012;65(6):465-75
pubmed: 23183197
Am J Trop Med Hyg. 2018 May;98(5):1360-1366
pubmed: 29582728
PLoS One. 2013 May 13;8(5):e64299
pubmed: 23675533
J Mol Biol. 1990 Oct 5;215(3):403-10
pubmed: 2231712
Am J Trop Med Hyg. 2003 May;68(5):598-601
pubmed: 12812353
J Antimicrob Chemother. 2015 Sep;70(9):2566-71
pubmed: 26080363
J Infect Dis. 2014 Aug 1;210(3):344-53
pubmed: 24610872