ENHANCED SENSITIVITY OF P FALCIPARUM TO SULPHALENE AS A CONSEQUENCE OF RESISTANCE TO PYRIMETHAMINE

Experiments were conducted with P. falciparum in volunteers concerning the increased sensitivity of the malaria to a sulphonamide (sulphalene) induced by the parasite's resistance to pyrimethamine (a dihydrofolate inductase inhibitor). The “normal” P. falciparum strain was relatively resistant to treatment with sulphalene; only 5 of 11 patients were cured by 2·5 grammes. After resistance to pyrimethamine was induced, the strain was much more sensitive to sulphalene: 9 of 11 patients were cured by 1 gramme. Evidence is presented for the postulate that the sulphonamide sensitivity of a strain depends on whether it does or does not synthesize its own folic acid. It is further postulated that P. falciparum is capable of either using exogenous folic acid or of synthesizing it. The parasites probably do not do both at the same time. © 1969 Royal Society of Tropical Medicine and Hygiene.