Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy.
North-east India, being a corridor to South-east Asia, is believed to play an important role in transmitting drug resistant Plasmodium falciparum malaria to India and South Asia. North-east India was the first place in India to record the emergence of drug resistance to chloroquine as well as sulpha...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4153584?pdf=render |
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| author | Pradyumna Kishore Mohapatra Devojit Kumar Sarma Anil Prakash Khukumoni Bora Md Atique Ahmed Bibhas Sarma Basanta Kumar Goswami Dibya Ranjan Bhattacharyya Jagadish Mahanta |
| author_facet | Pradyumna Kishore Mohapatra Devojit Kumar Sarma Anil Prakash Khukumoni Bora Md Atique Ahmed Bibhas Sarma Basanta Kumar Goswami Dibya Ranjan Bhattacharyya Jagadish Mahanta |
| author_sort | Pradyumna Kishore Mohapatra |
| collection | DOAJ |
| description | North-east India, being a corridor to South-east Asia, is believed to play an important role in transmitting drug resistant Plasmodium falciparum malaria to India and South Asia. North-east India was the first place in India to record the emergence of drug resistance to chloroquine as well as sulphadoxine/pyrimethamine. Presently chloroquine resistance is widespread all over the North-east India and resistance to other anti-malarials is increasing. In this study both in vivo therapeutic efficacy and molecular assays were used to screen the spectrum of drug resistance to chloroquine and sulphadoxine/pyrimethamine in the circulating P. falciparum strains. A total of 220 P. falciparum positives subjects were enrolled in the study for therapeutic assessment of chloroquine and sulphadoxine/pyrimethamine and assessment of point mutations conferring resistances to these drugs were carried out by genotyping the isolates following standard methods. Overall clinical failures in sulphadoxine/pyrimethamine and chloroquine were found 12.6 and 69.5% respectively, while overall treatment failures recorded were 13.7 and 81.5% in the two arms. Nearly all (99.0%) the isolates had mutant pfcrt genotype (76 T), while 68% had mutant pfmdr-1 genotype (86 Y). Mutation in dhps 437 codon was the most prevalent one while dhfr codon 108 showed 100% mutation. A total of 23 unique haplotypes at the dhps locus and 7 at dhfr locus were found while dhps-dhfr combined loci revealed 49 unique haplotypes. Prevalence of double, triple and quadruple mutations were common while 1 haplotype was found with all five mutated codons (F/AGEGS/T) at dhps locus. Detection of quadruple mutants (51 I/59 R/108 N/164 L) in the present study, earlier recorded from Car Nicobar Island, India only, indicates the presence of high levels of resistance to sulphadoxine/pyrimethamine in north-east India. Associations between resistant haplotypes and the clinical outcomes and emerging resistance in sulphadoxine/pyrimethamine in relation to the efficacy of the currently used artemisinin combination therapy are discussed. |
| first_indexed | 2024-12-13T05:12:58Z |
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| institution | Directory Open Access Journal |
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| spelling | doaj.art-5d886543ff3c4dcbba181e2a504810252022-12-21T23:58:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10556210.1371/journal.pone.0105562Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy.Pradyumna Kishore MohapatraDevojit Kumar SarmaAnil PrakashKhukumoni BoraMd Atique AhmedBibhas SarmaBasanta Kumar GoswamiDibya Ranjan BhattacharyyaJagadish MahantaNorth-east India, being a corridor to South-east Asia, is believed to play an important role in transmitting drug resistant Plasmodium falciparum malaria to India and South Asia. North-east India was the first place in India to record the emergence of drug resistance to chloroquine as well as sulphadoxine/pyrimethamine. Presently chloroquine resistance is widespread all over the North-east India and resistance to other anti-malarials is increasing. In this study both in vivo therapeutic efficacy and molecular assays were used to screen the spectrum of drug resistance to chloroquine and sulphadoxine/pyrimethamine in the circulating P. falciparum strains. A total of 220 P. falciparum positives subjects were enrolled in the study for therapeutic assessment of chloroquine and sulphadoxine/pyrimethamine and assessment of point mutations conferring resistances to these drugs were carried out by genotyping the isolates following standard methods. Overall clinical failures in sulphadoxine/pyrimethamine and chloroquine were found 12.6 and 69.5% respectively, while overall treatment failures recorded were 13.7 and 81.5% in the two arms. Nearly all (99.0%) the isolates had mutant pfcrt genotype (76 T), while 68% had mutant pfmdr-1 genotype (86 Y). Mutation in dhps 437 codon was the most prevalent one while dhfr codon 108 showed 100% mutation. A total of 23 unique haplotypes at the dhps locus and 7 at dhfr locus were found while dhps-dhfr combined loci revealed 49 unique haplotypes. Prevalence of double, triple and quadruple mutations were common while 1 haplotype was found with all five mutated codons (F/AGEGS/T) at dhps locus. Detection of quadruple mutants (51 I/59 R/108 N/164 L) in the present study, earlier recorded from Car Nicobar Island, India only, indicates the presence of high levels of resistance to sulphadoxine/pyrimethamine in north-east India. Associations between resistant haplotypes and the clinical outcomes and emerging resistance in sulphadoxine/pyrimethamine in relation to the efficacy of the currently used artemisinin combination therapy are discussed.http://europepmc.org/articles/PMC4153584?pdf=render |
| spellingShingle | Pradyumna Kishore Mohapatra Devojit Kumar Sarma Anil Prakash Khukumoni Bora Md Atique Ahmed Bibhas Sarma Basanta Kumar Goswami Dibya Ranjan Bhattacharyya Jagadish Mahanta Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. PLoS ONE |
| title | Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. |
| title_full | Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. |
| title_fullStr | Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. |
| title_full_unstemmed | Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. |
| title_short | Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. |
| title_sort | molecular evidence of increased resistance to anti folate drugs in plasmodium falciparum in north east india a signal for potential failure of artemisinin plus sulphadoxine pyrimethamine combination therapy |
| url | http://europepmc.org/articles/PMC4153584?pdf=render |
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