Role of calcium in trypanocidal drug action

The synergistic effect of serum on the drug combination of salicylhydroxamic acid plus glycerol, which is active against Trypanosoma brucei, is due to diffusible calcium ions. The synergistic activity can be removed by dialysis of the serum or by addition of calcium chelating agents. A buffer containing calcium can mimic the synergistic activity of serum. This finding may have important implications in the clinical management of African trypanosomiasis in humans. Calcium also has a synergistic effect on melarsoprol, the only drug available for treating sleeping sickness patients with central nervous system involvement, and the concentration of calcium has been reported to be depressed inthe serum of experimentally infected animals.