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Open Access 01-12-2011 | Research

Molecular epidemiology of Plasmodium vivax anti-folate resistance in India

Authors: Surendra K Prajapati, Hema Joshi, Vas Dev, Virendra K Dua

Published in: Malaria Journal | Issue 1/2011

Abstract

Background

Sulphadoxine and pyrimethamine are anti-folate drugs that show synergistic anti-malarial effect. Point mutations in dihydrofolate reductase (dhfr) and dihydropteorate synthatase (dhps) cause anti-folate drug resistance phenotype in human malaria parasites. This study presents pattern of point mutations in dhfr/dhps genes among Indian sub-continent.

Methods

Microscopically diagnosed one hundred Plasmodium vivax field isolates were collected from five widely separated geographical regions of India. Dhfr and dhps genes were PCR amplified and sequenced. Previously published mutations data were collected and analyzed using Chi square test to identify geographical cluster of mutant/wild type genotypes.

Results

Sequence analysis revealed single (S58R), double (S58R/S117N) and quadruple (F57L/S58R/T61M/S117T/) point mutations at dhfr and single (A383G) to double (A383G/A553G) mutations at dhps in P. vivax field isolates. In addition, three new mutations were also observed at dhfr. Both, dhfr and dhps genes revealed tandem repeat variations in field isolates. Dhps revealed very low mutation frequency (14.0%) compared to dhfr (50.70%). Comparative analysis revealed a progressive increase in frequency of quadruple mutant dhfr genotype (p < 0.001) within five years in north-eastern state (Kamrup, Assam). Frequency of dhfr genotypes revealed three distinct geographical clusters of wild (northern India), double mutant (southern India), and quadruple mutant (north-eastern and island regions of India) on the Indian sub-continent.

Conclusion

Study suggests that SP may be susceptible to P. vivax in India, except Andaman and north-eastern state. The distinction of geographical regions with sensitive and resistant parasite phenotypes would be highly useful for designing and administering national anti-malarial drug policy.

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Title: Molecular epidemiology of Plasmodium vivax anti-folate resistance in India
Authors: Surendra K Prajapati
Hema Joshi
Vas Dev
Virendra K Dua
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI: https://doi.org/10.1186/1475-2875-10-102

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Conclusion

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