COMBINATION CHEMOTHERAPY OF DRUG-RESISTANT TRYPANOSOMA-BRUCEI-RHODESIENSE INFECTIONS IN MICE USING DL-ALPHA-DIFLUOROMETHYLORNITHINE AND STANDARD TRYPANOCIDES

Combinations of DL-alpha-difluoromethylornithine (DFMO; eflornithine; Ornidyl) with either suramin or melarsen oxide were found to be effect ive against acute laboratory model infections,vith Trypanosoma brucei rhodesiense. We used clinical isolates known to be resistant to these drugs when used singly. An infection with a melarsen oxide-refractory isolate was cured by a combination of low-dose DFMO (0.5% in the drink ing water) plus low-dose suramin (1 mg/kg of body weight given intrape ritoneally). Another strain, moderately resistant to arsenical drugs, was cured with combinations of 4% DFMO with 5 mg of melarsen oxide per kg. Furthermore, a combination of DFMO (2% in the drinking water) and suramin (20 mg/kg) provided a 100% cure rate in a central nervous sys tem model, although the same doses of these drugs used singly were com pletely ineffective. The synergism of DEMO and suramin against an acut e infection was improved when suramin was given at the end of the DFMO administration. No adverse interactions were observed when high doses of DFMO combined with high doses of suramin were administered to unin fected mice. These results suggest that combinations of DEMO and suram in should be examined clinically for activity in arsenical-drug-refrac tory cases of East African sleeping sickness.