Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next?

Chemotherapy remains the only practicable tool to control falciparum malari a in sub-Saharan Africa, where > 90% of the world's burden of malaria morta lity and morbidity occurs. Resistance is rapidly eroding the efficacy of ch loroquine, and the combination pyrimethamine-sulfadoxine is the most common ly chosen alternative. Resistant populations of Plasmodium falciparum were selected extremely rapidly in Southeast Asia and South America. If this hap pens in sub-Saharan Africa, it will be a public health disaster because no inexpensive alternative is currently available. This article reviews the mo lecular mechanisms of this resistance and discusses how to extend the thera peutic life of antifolate drugs.