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Antimicrobial Agents and Chemotherapy, March 2004, p. 879-889, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.879-889.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum Isolates in India Exhibit a Progressive Increase in Mutations Associated with Sulfadoxine-Pyrimethamine Resistance

Anwar Ahmed,1 Deepak Bararia,1 Sumiti Vinayak,1 Mohammed Yameen,1 Sukla Biswas,2 Vas Dev,2 Ashwani Kumar,2 Musharraf A. Ansari,2 and Yagya D. Sharma1*

Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029,1 Malaria Research Centre, 22 Sham Nath Marg, New Delhi 110054, India2

Received 28 August 2003/ Returned for modification 30 October 2003/ Accepted 12 November 2003

The combination of sulfadoxine-pyrimethamine (SP) is used as a second line of therapy for the treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria. Resistance to SP arises due to certain point mutations in the genes for the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) enzymes of the parasite. We have analyzed these mutations in 312 field isolates of P. falciparum collected from different parts of India to assess the effects of drug pressure. The rate of mutation in the gene for DHFR was found to be higher than that in the gene for DHPS, although the latter had mutations in more alleles. There was a temporal rise in the number of isolates with double dhfr mutations and single dhps mutations, resulting in an increased total number of mutations in the loci for DHFR and DHPS combined over a 5-year period. During these 5 years, the number of isolates with drug-sensitive genotypes decreased and the number of isolates with drug-resistant genotypes (double DHFR mutations and a single DHPS mutation) increased significantly. The number of isolates with the triple mutations in each of the genes for the two enzymes (for a total of six mutations), however, remained very low, coinciding with the very low rate of SP treatment failure in the country. There was a regional bias in the mutation rate, as isolates from the northeastern region (the state of Assam) showed higher rates of mutation and more complex genotypes than isolates from the other regions. It was concluded that even though SP is prescribed as a second line of treatment in India, the mutations associated with SP resistance continue to be progressively increasing.

* Corresponding author. Mailing address: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India. Phone: 91-11-26588145. Fax: 91-11-26589286. E-mail: ydsharma{at}hotmail.com.

Antimicrobial Agents and Chemotherapy, March 2004, p. 879-889, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.879-889.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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