THE EFFICACY OF ANTIFOLATE ANTIMALARIAL COMBINATIONS IN AFRICA - A PREDICTIVE MODEL-BASED ON PHARMACODYNAMIC AND PHARMACOKINETIC ANALYSES

At present, effective treatment for non-severe malaria is the most imp ortant malaria control strategy in Africa. Pyrimethamine-sulfadoxine ( PSD) is rapidly becoming the first-line treatment in areas of chloroqu ine resistance, although the parasite chemoresistance factors that dis pose towards clinical failure with PSD are still unclear!ear. Here, Bi ll Watkins and colleagues analyse the relationship between the pharmac okinetic properties of two treatment combinations (PSD and chlorprouan il-dapsone) in vivo and the respective in vitro isobolograms for paras ites with specific drug-resistance patterns. From this relationship, t hey develop a hypothesis that may explain clinical drug failure and di fferential efficacy between treatments. The deductions can be tested i n field studies to validate or refute the model.