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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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80017-6 |
| _version_ | 1819200235658805248 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T03:29:01Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T03:29:01Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-7ecd3ef5a9d34f1f890f91a36e6c1caa2022-12-21T18:01:46ZengNature PortfolioScientific Reports2045-23222021-01-011111810.1038/s41598-020-80017-6Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting techniqueAdeyemi T. Kayode0Fehintola V. Ajogbasile1Kazeem Akano2Jessica N. Uwanibe3Paul E. Oluniyi4Philomena J. Eromon5Onikepe A. Folarin6Akintunde Sowunmi7Dyann F. Wirth8Christian T. Happi9African Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityInstitute of Advanced Medical Research and Training, College of Medicine, University of IbadanDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthAfrican Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s UniversityAbstract 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.https://doi.org/10.1038/s41598-020-80017-6 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-80017-6 |
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