Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka
Abstract Background Single nucleotide polymorphisms (SNPs) in the Plasmodium vivax dihydrofolate reductase ( Pfdhfr ) and dihydropteroate synthetase ( Pvdhps ) genes cause parasite resistance to the antifolate drug combination, sulphadoxine/pyrimethamine (SP). Monitoring these SNPs provide insights...
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ftdoajarticles:oai:doaj.org/article:4082b3672d404410980b77f2c8f88f87 2023-05-15T15:17:52+02:00 Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka Konradsen Flemming Amerasinghe Priyanie H Bygbjerg Ib C Galappaththy Gawrie NL Hapuarachchi Hapuarachchige C Salanti Ali Rajakaruna Rupika S Schousboe Mette L Alifrangis Michael 2007-03-01T00:00:00Z https://doi.org/10.1186/1475-2875-6-28 https://doaj.org/article/4082b3672d404410980b77f2c8f88f87 EN eng BMC http://www.malariajournal.com/content/6/1/28 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-6-28 1475-2875 https://doaj.org/article/4082b3672d404410980b77f2c8f88f87 Malaria Journal, Vol 6, Iss 1, p 28 (2007) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2007 ftdoajarticles https://doi.org/10.1186/1475-2875-6-28 2022-12-31T05:53:16Z Abstract Background Single nucleotide polymorphisms (SNPs) in the Plasmodium vivax dihydrofolate reductase ( Pfdhfr ) and dihydropteroate synthetase ( Pvdhps ) genes cause parasite resistance to the antifolate drug combination, sulphadoxine/pyrimethamine (SP). Monitoring these SNPs provide insights into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP resistance across Sri Lanka. Subjects and methods P. vivax- positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene and 383, 553 and 585 of the Pvdhps gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format. Results In the study period, the government of Sri Lanka recorded 2,149 P. vivax cases from the nine districts out of which, 454 (21.1%) blood samples were obtained. Pvdhfr haplotypes could be constructed for 373 of these. The FSTS wild-haplotype was represented in 257 samples (68.9%), the double mutant LRTS haplotype was the most frequently observed mutant (24.4%) while the triple mutation (LRTN) was only identified once. Except for two samples of the single mutated Pvdhps GAV haplotype, the remaining samples were wildtype. Geographical differences were apparent, notably a significantly higher frequency of mutant Pvdhfr haplotypes was observed in ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 6 1 28 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Konradsen Flemming Amerasinghe Priyanie H Bygbjerg Ib C Galappaththy Gawrie NL Hapuarachchi Hapuarachchige C Salanti Ali Rajakaruna Rupika S Schousboe Mette L Alifrangis Michael Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Single nucleotide polymorphisms (SNPs) in the Plasmodium vivax dihydrofolate reductase ( Pfdhfr ) and dihydropteroate synthetase ( Pvdhps ) genes cause parasite resistance to the antifolate drug combination, sulphadoxine/pyrimethamine (SP). Monitoring these SNPs provide insights into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP resistance across Sri Lanka. Subjects and methods P. vivax- positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene and 383, 553 and 585 of the Pvdhps gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format. Results In the study period, the government of Sri Lanka recorded 2,149 P. vivax cases from the nine districts out of which, 454 (21.1%) blood samples were obtained. Pvdhfr haplotypes could be constructed for 373 of these. The FSTS wild-haplotype was represented in 257 samples (68.9%), the double mutant LRTS haplotype was the most frequently observed mutant (24.4%) while the triple mutation (LRTN) was only identified once. Except for two samples of the single mutated Pvdhps GAV haplotype, the remaining samples were wildtype. Geographical differences were apparent, notably a significantly higher frequency of mutant Pvdhfr haplotypes was observed in ... |
format |
Article in Journal/Newspaper |
author |
Konradsen Flemming Amerasinghe Priyanie H Bygbjerg Ib C Galappaththy Gawrie NL Hapuarachchi Hapuarachchige C Salanti Ali Rajakaruna Rupika S Schousboe Mette L Alifrangis Michael |
author_facet |
Konradsen Flemming Amerasinghe Priyanie H Bygbjerg Ib C Galappaththy Gawrie NL Hapuarachchi Hapuarachchige C Salanti Ali Rajakaruna Rupika S Schousboe Mette L Alifrangis Michael |
author_sort |
Konradsen Flemming |
title |
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
title_short |
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
title_full |
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
title_fullStr |
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
title_full_unstemmed |
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka |
title_sort |
island-wide diversity in single nucleotide polymorphisms of the plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in sri lanka |
publisher |
BMC |
publishDate |
2007 |
url |
https://doi.org/10.1186/1475-2875-6-28 https://doaj.org/article/4082b3672d404410980b77f2c8f88f87 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 6, Iss 1, p 28 (2007) |
op_relation |
http://www.malariajournal.com/content/6/1/28 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-6-28 1475-2875 https://doaj.org/article/4082b3672d404410980b77f2c8f88f87 |
op_doi |
https://doi.org/10.1186/1475-2875-6-28 |
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Malaria Journal |
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6 |
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28 |
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