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Antimicrobial Agents and Chemotherapy, November 2004, p. 4097-4102, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4097-4102.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Modified Fixed-Ratio Isobologram Method for Studying In Vitro Interactions between Atovaquone and Proguanil or Dihydroartemisinin against Drug-Resistant Strains of Plasmodium falciparum

Quinton L. Fivelman,* Ipemida S. Adagu, and David C. Warhurst

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

Received 13 April 2004/ Returned for modification 21 May 2004/ Accepted 5 July 2004

A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure. While the interaction between atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the interaction displayed indifference tending toward antagonism against the atovaquone-sensitive strains tested. The relevance of in vitro interactions to in vivo treatment is discussed.

* Corresponding author. Mailing address: ITD, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 020 7927 2416. Fax: 020 7636 8739. E-mail: quinton.fivelman{at}lshtm.ac.uk.

Antimicrobial Agents and Chemotherapy, November 2004, p. 4097-4102, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4097-4102.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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