Conference Agenda
Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).
|
Daily Overview |
| Session | |
|
CP15.1: Drugs & Drug Resistance 2 - 5 min talks sponsored by Institute for Biomedicine and Glycomics, Griffith University Location: Lecture Theatre 1 Session Chair: Jacinta Macdonald, Griffith University Session Chair: Rohith Kutty, Griffith University | |
    | |
The malaria drug proguanil demonstrates slow action in vitro activity against P. falciparum field isolates from Uganda. 1: Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, Australia; 2: Department of Medicine at the University of California, San Francisco (UCSF), USA Proguanil is a used in combination with atovaquone to prevent and treat malaria. Activity of proguanil is thought to be due to its ability to potentiate atovaquone activity and the potent antiplasmodial activity of its in vivo metabolite, cycloguanil. Plasmodium falciparum resistance to cycloguanil is known to be due to mutations in the dihydrofolate reductase, but studies on proguanil resistance are lacking given it was essentially considered a prodrug. We overturned this dogma showing that proguanil has slow action activity against P. falciparum laboratory lines in vitro (Pf3D7 IC50 110 nM)1. Here, we investigated thirteen culture-adapted P. falciparum isolates collected in eastern Uganda with low ex vivo sensitivity to proguanil2. The in vitro sensitivity of the culture-adapted isolates to proguanil was assessed using 48 h, 72 h and 96 h growth-inhibition assays. While proguanil resistance was not confirmed in these studies, proguanil demonstrated slow-action activity against field isolates with 96 h IC50 values of approximately 80-430 nM. These data extend our understanding of proguanil action to more clinically relevant field isolates, adding to findings that indicate that the antiplasmodial activity of the proguanil-atovaquone combination may be more complicated than previously thought. | |