Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 9:6:28.
doi: 10.1186/1475-2875-6-28.

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

Mette L Schousboe  1 , Rupika S Rajakaruna, Ali Salanti, Hapuarachchige C Hapuarachchi, Gawrie N L Galappaththy, Ib C Bygbjerg, Priyanie H Amerasinghe, Flemming Konradsen, Michael Alifrangis
Affiliations

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

Mette L Schousboe et al. Malar J. .

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 the Northern districts.

Conclusion: Since SP is rarely used in Sri Lanka, the high frequency and diversity of Pvdhfr mutations was unexpected indicating the emergence of drug resistant parasites despite a low level of SP drug pressure.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The distribution of Plasmodium vivax dhfr haplotypes at c57 (F->L), 58 (S->R), 61 (T) and 117 (S->N) in samples collected from P. vivax positive patients in 9 districts of Sri Lanka. The number in brackets is the actual number of P. vivax positive cases reported by Anti Malaria Campaign of Sri Lanka in the study period September 2004–March 2006. In red: the wild type to mutant type change in amino acids
See this image and copyright information in PMC

References

    1. Mendis K, Sina BJ, Marchesini P, Carter R. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg. 2001;64:97–106. - PubMed
    1. Pukrittayakamee S, Imwong M, Looareesuwan S, White NJ. Therapeutic responses to antimalarial and antibacterial drugs in vivax malaria. Acta Trop. 2004;89:351–356. doi: 10.1016/j.actatropica.2003.10.012. - DOI - PubMed
    1. Eldin P, Basco LK, Tahar R, Ouatas T, Mazabraud A. Analysis of the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene sequence. Gene. 1998;211:177–185. doi: 10.1016/S0378-1119(98)00118-8. - DOI - PubMed
    1. Hastings MD, Porter KM, Maguire JD, Susanti I, Kania W, Bangs MJ, Hopkins SC, Baird JK. Dihydrofolate Reductase Mutations in Plasmodium vivax from Indonesia and Therapeutic Response to Sulfadoxine Plus Pyrimethamine. J Infect Dis. 2004;189:744–750. doi: 10.1086/381397. - DOI - PubMed
    1. Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis. 2002;185:380–388. doi: 10.1086/338566. - DOI - PubMed

MeSH terms

LinkOut - more resources