Antifolate drug resistance: Novel mutations and haplotype distribution in dhps and dhfr from Northeast India
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Malaria is a major public health concern in Northeast India with a preponderance of drug-resistant strains. Until recently the partner drug for artemisinin combination therapy (ACT) was sulphadoxine pyrimethamine (SP). Antifolate drug resistance has been associated with the mutations at dihydropteroate synthase (dhps) and dihydrofolatereductase (dhfr) genes. This study investigated antifolate drug resistance at the molecular level. A total of 249 fever cases from Arunachal Pradesh, NE India, were screened for malaria, and of these, 75 were found to be positive for Plasmodium falciparum. Samples were sequenced and analysed with the help of BioEdit and ClustalW. Three novel point mutations were found in the dhps gene with 10 haplotypes along with the already reported mutations. A single haplotype having quadruple mutation was found in the dhfr gene. The study reports higher degree of antifolate drug resistance as evidenced by the presence of multiple point mutations in dhps and dhfr genes. The findings of this study strongly discourage the use SP as a partner drug in ACT.
Keywordsdhfr dhps Northeast India Plasmodium falciparum
We are grateful to Dr S Bhattcharjee, MO, Miao CHC, Arunachal Pradesh, for his support in collection of the samples. Technical assistance provided by Mr BK Goswami, Polash Borgohain, Manoj Dutta and Partho Protim Borah is highly acknowledged. This work was supported by a grant from the Qatar National Research Fund (NPRP- 5-098-3-021). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Qatar National Research Fund.
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