Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense.
DL-alpha-Difluoromethylornithine is an enzyme-activated inhibitor of ornithine decarboxylase and an antagonist of polyamine metabolism that has been successful in clinical trials against West African sleeping sickness caused by Trypanosoma brucei gambiense. Its potential for use against the more virulent East African form of the disease, caused by T. brucei rhodesiense, is not certain. We examined 14 East African clinical isolates from the Kenya Trypanosomiasis Research Institute strain bank plus 2 established isolates for susceptibility to DL-alpha-difluoromethylornithine and to standard trypanocides. Seven of 16 strains were partially or totally refractory to DL-alpha-difluoromethylornithine in our test system. Four strains were also refractory to arsenical drugs, and five were refractory to diamidines. The results indicate that other novel agents or combinations of established agents may be needed for chemotherapy of East African disease.
Bacchi
C J
CJ
Haskins Laboratories, Pace University, New York, New York 10038.
Nathan
H C
HC
Livingston
T
T
Valladares
G
G
Saric
M
M
Sayer
P D
PD
Njogu
A R
AR
Clarkson
A B
AB
D000818:Animals; D004351:Drug Resistance; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D051379:Mice; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development
D014344:Trypanocidal Agents; D000518:Eflornithine