Island-wide diversity in single nucleotide polymorphisms of the <it>Plasmodium vivax </it>dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) in the <it>Plasmodium vivax </it>dihydrofolate reductase (<it>Pfdhfr</it>) and dihydropteroate synthetase (<it>Pvdhps</it>) genes cause parasite resistance to...

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Main Authors: Konradsen Flemming, Amerasinghe Priyanie H, Bygbjerg Ib C, Galappaththy Gawrie NL, Hapuarachchi Hapuarachchige C, Salanti Ali, Rajakaruna Rupika S, Schousboe Mette L, Alifrangis Michael
Format: Article
Language:English
Published: BMC 2007-03-01
Series:Malaria Journal
Online Access:http://www.malariajournal.com/content/6/1/28
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Summary:<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) in the <it>Plasmodium vivax </it>dihydrofolate reductase (<it>Pfdhfr</it>) and dihydropteroate synthetase (<it>Pvdhps</it>) 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 <it>Plasmodium falciparum </it>and/or <it>P. vivax </it>infections. CQ/PQ is still efficacious against <it>P. vivax </it>infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to <it>P. vivax </it>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 <it>P. vivax </it>SP resistance across Sri Lanka.</p> <p>Subjects and methods</p> <p><it>P. vivax-</it>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 <it>Pvdhfr </it>gene and 383, 553 and 585 of the <it>Pvdhps </it>gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format.</p> <p>Results</p> <p>In the study period, the government of Sri Lanka recorded 2,149 <it>P. vivax </it>cases from the nine districts out of which, 454 (21.1%) blood samples were obtained. <it>Pvdhfr </it>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 <it>Pvdhps </it>GAV haplotype, the remaining samples were wildtype. Geographical differences were apparent, notably a significantly higher frequency of mutant <it>Pvdhfr </it>haplotypes was observed in the Northern districts.</p> <p>Conclusion</p> <p>Since SP is rarely used in Sri Lanka, the high frequency and diversity of <it>Pvdhfr </it>mutations was unexpected indicating the emergence of drug resistant parasites despite a low level of SP drug pressure.</p>
ISSN:1475-2875