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Antimicrobial Agents and Chemotherapy, March 2007, p. 857-863, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01200-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Similar Trends of Pyrimethamine Resistance-Associated Mutations in Plasmodium vivax and P. falciparum{triangledown}

Mohammad Tauqeer Alam,1 Hema Bora,1 Praveen K. Bharti,2 Muheet A. Saifi,3 Manoj K. Das,4 Vas Dev,5 Ashwani Kumar,6 Neeru Singh,2 Aditya P. Dash,7 Brahmananda Das,8 Wajihullah,3 and Yagya D. Sharma1*

Department of Biotechnology, All India Institute of Medical Sciences, New Delhi,1 National Institute of Malaria Research, Field Station Jabalpur, Madhya Pradesh,2 Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh,3 National Institute of Malaria Research, Field Station Car Nicobar, Andaman and Nicobar Islands,4 National Institute of Malaria Research, Field Station Sonapur, Assam,5 National Institute of Malaria Research, Field Station Goa,6 National Institute of Malaria Research, Delhi,7 Department of Medicine, S. C. B. Medical College, Cuttack, Orissa, India8

Received 25 September 2006/ Returned for modification 12 November 2006/ Accepted 11 December 2006

The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat Plasmodium falciparum malaria. However, they can also affect the Plasmodium vivax parasite if it coexists with P. falciparum, as both species have common drug targets. Resistance to the antifolate drugs arises due to point mutations in the target enzymes of the respective parasite. To assess the cross-species impact of antifolate drug treatment, we describe here the dihydrofolate reductase (DHFR) mutations among field isolates of P. vivax and P. falciparum. The overall DHFR mutation rate for P. vivax was lower than that for P. falciparum. However, both species of Plasmodium followed similar trends of DHFR mutations. Similar to P. falciparum, the DHFR mutation rate of P. vivax also varied from region to region. It was lower in P. vivax-dominant regions but higher in the P. falciparum-dominated areas and highest where antifolates are used as the first line of antimalarial treatment. In conclusion, the antifolate treatment of falciparum malaria is proportionately affecting the DHFR mutations of P. vivax, suggesting that the drug should be used with caution to minimize the development of cross-species resistance in the field.

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

{triangledown} Published ahead of print on 28 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 857-863, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01200-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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