Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To...
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| Format: | Article |
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Elsevier
2016-12-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320716300197 |
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| author | Mary C. Oguike Catherine O. Falade Elvis Shu Izehiuwa G. Enato Ismaila Watila Ebenezer S. Baba Jane Bruce Jayne Webster Prudence Hamade Sylvia Meek Daniel Chandramohan Colin J. Sutherland David Warhurst Cally Roper |
| author_facet | Mary C. Oguike Catherine O. Falade Elvis Shu Izehiuwa G. Enato Ismaila Watila Ebenezer S. Baba Jane Bruce Jayne Webster Prudence Hamade Sylvia Meek Daniel Chandramohan Colin J. Sutherland David Warhurst Cally Roper |
| author_sort | Mary C. Oguike |
| collection | DOAJ |
| description | There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north.
Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing.
The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common.
All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015. |
| first_indexed | 2024-12-10T08:49:27Z |
| format | Article |
| id | doaj.art-7108561fc2b34820ae9f709ae9d0ccea |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-10T08:49:27Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-7108561fc2b34820ae9f709ae9d0ccea2022-12-22T01:55:38ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072016-12-016322022910.1016/j.ijpddr.2016.08.004Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431VMary C. Oguike0Catherine O. Falade1Elvis Shu2Izehiuwa G. Enato3Ismaila Watila4Ebenezer S. Baba5Jane Bruce6Jayne Webster7Prudence Hamade8Sylvia Meek9Daniel Chandramohan10Colin J. Sutherland11David Warhurst12Cally Roper13Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, NigeriaDepartment of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Enugu Campus, Enugu, NigeriaDepartment of Child Health, University of Benin Teaching Hospital, Benin City, NigeriaDepartment of Paediatrics, Specialist Hospital Maiduguri, Borno State, NigeriaMalaria Consortium, Regional Office for Africa, Kampala, UgandaDepartment of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomMalaria Consortium, London, United KingdomMalaria Consortium, London, United KingdomDepartment of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomThere are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.http://www.sciencedirect.com/science/article/pii/S2211320716300197Sulfadoxine-pyrimethaminedhpsdhfrmutationsNigeria |
| spellingShingle | Mary C. Oguike Catherine O. Falade Elvis Shu Izehiuwa G. Enato Ismaila Watila Ebenezer S. Baba Jane Bruce Jayne Webster Prudence Hamade Sylvia Meek Daniel Chandramohan Colin J. Sutherland David Warhurst Cally Roper Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V International Journal for Parasitology: Drugs and Drug Resistance Sulfadoxine-pyrimethamine dhps dhfr mutations Nigeria |
| title | Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V |
| title_full | Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V |
| title_fullStr | Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V |
| title_full_unstemmed | Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V |
| title_short | Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V |
| title_sort | molecular determinants of sulfadoxine pyrimethamine resistance in plasmodium falciparum in nigeria and the regional emergence of dhps 431v |
| topic | Sulfadoxine-pyrimethamine dhps dhfr mutations Nigeria |
| url | http://www.sciencedirect.com/science/article/pii/S2211320716300197 |
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