Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique

Abstract In 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of uncompli...

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Autores principales: Adeyemi T. Kayode, Fehintola V. Ajogbasile, Kazeem Akano, Jessica N. Uwanibe, Paul E. Oluniyi, Philomena J. Eromon, Onikepe A. Folarin, Akintunde Sowunmi, Dyann F. Wirth, Christian T. Happi
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:7ecd3ef5a9d34f1f890f91a36e6c1caa2021-12-02T15:23:02ZPolymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique10.1038/s41598-020-80017-62045-2322https://doaj.org/article/7ecd3ef5a9d34f1f890f91a36e6c1caa2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80017-6https://doaj.org/toc/2045-2322Abstract In 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of uncomplicated falciparum malaria. However, SP is used as an intermittent preventive treatment of malaria in pregnancy (IPTp) and seasonal malaria chemoprevention (SMC) in children aged 3–59 months. There have been increasing reports of SP resistance especially in the non-pregnant population in Nigeria, thus, the need to continually monitor the efficacy of SP as IPTp and SMC by estimating polymorphisms in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes associated with SP resistance. The high resolution-melting (HRM) assay was used to investigate polymorphisms in codons 51, 59, 108 and 164 of the dhfr gene and codons 437, 540, 581 and 613 of the dhps gene. DNA was extracted from 271 dried bloodspot filter paper samples obtained from children (< 5 years old) with uncomplicated malaria. The dhfr triple mutant I51R59N108, dhps double mutant G437G581 and quadruple dhfr I51R59N108 + dhps G437 mutant haplotypes were observed in 80.8%, 13.7% and 52.8% parasites, respectively. Although the quintuple dhfr I51R59N108 + dhps G437E540 and sextuple dhfr I51R59N108 + dhps G437E540G581 mutant haplotypes linked with in-vivo and in-vitro SP resistance were not detected, constant surveillance of these haplotypes should be done in the country to detect any change in prevalence.Adeyemi T. KayodeFehintola V. AjogbasileKazeem AkanoJessica N. UwanibePaul E. OluniyiPhilomena J. EromonOnikepe A. FolarinAkintunde SowunmiDyann F. WirthChristian T. HappiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adeyemi T. Kayode
Fehintola V. Ajogbasile
Kazeem Akano
Jessica N. Uwanibe
Paul E. Oluniyi
Philomena J. Eromon
Onikepe A. Folarin
Akintunde Sowunmi
Dyann F. Wirth
Christian T. Happi
Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
description Abstract In 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of uncomplicated falciparum malaria. However, SP is used as an intermittent preventive treatment of malaria in pregnancy (IPTp) and seasonal malaria chemoprevention (SMC) in children aged 3–59 months. There have been increasing reports of SP resistance especially in the non-pregnant population in Nigeria, thus, the need to continually monitor the efficacy of SP as IPTp and SMC by estimating polymorphisms in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes associated with SP resistance. The high resolution-melting (HRM) assay was used to investigate polymorphisms in codons 51, 59, 108 and 164 of the dhfr gene and codons 437, 540, 581 and 613 of the dhps gene. DNA was extracted from 271 dried bloodspot filter paper samples obtained from children (< 5 years old) with uncomplicated malaria. The dhfr triple mutant I51R59N108, dhps double mutant G437G581 and quadruple dhfr I51R59N108 + dhps G437 mutant haplotypes were observed in 80.8%, 13.7% and 52.8% parasites, respectively. Although the quintuple dhfr I51R59N108 + dhps G437E540 and sextuple dhfr I51R59N108 + dhps G437E540G581 mutant haplotypes linked with in-vivo and in-vitro SP resistance were not detected, constant surveillance of these haplotypes should be done in the country to detect any change in prevalence.
format article
author Adeyemi T. Kayode
Fehintola V. Ajogbasile
Kazeem Akano
Jessica N. Uwanibe
Paul E. Oluniyi
Philomena J. Eromon
Onikepe A. Folarin
Akintunde Sowunmi
Dyann F. Wirth
Christian T. Happi
author_facet Adeyemi T. Kayode
Fehintola V. Ajogbasile
Kazeem Akano
Jessica N. Uwanibe
Paul E. Oluniyi
Philomena J. Eromon
Onikepe A. Folarin
Akintunde Sowunmi
Dyann F. Wirth
Christian T. Happi
author_sort Adeyemi T. Kayode
title Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
title_short Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
title_full Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
title_fullStr Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
title_full_unstemmed Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique
title_sort polymorphisms in plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in nigerian children with uncomplicated malaria using high-resolution melting technique
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/7ecd3ef5a9d34f1f890f91a36e6c1caa
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