Innate lack of susceptibility of Ugandan Trypanosoma brucei rhodesiense to DL-alpha-difluoromethylornithine (DFMO).
Trypanosoma brucei rhodesiense isolates from South East Uganda were characterized for susceptibility to the drugs suramin, nifurtimox, melarsoprol and DL-alpha-difluoromethylornithine (DFMO). Two different assays were used to determine the drug susceptibility of the field isolates: the [3H]hypoxanthine incorporation assay (24 hours) and the long term viability assay (10 days). All trypanosome stocks were susceptible to suramin and nifurtimox. Differences in the susceptibility to melarsoprol were observed in the [3H]hypoxanthine incorporation assay, but could not be confirmed in the long term viability assay. All T. b. rhodesiense stocks were found in vitro to have innate tolerance to DFMO, under conditions where T. b. gambiense stocks from West Africa were susceptible to the drug. Ugandan T. b. rhodesiense stocks did respond to 25-100 micrograms/ml after 10 days of drug exposure, but the DFMO level reached in cerebrospinal fluid during treatment is only 16.3 +/- 7.8 micrograms/ml. Therefore, DFMO is not an appropriate alternative or backup drug for treatment of Rhodesian sleeping sickness in Uganda.
Iten
M
M
Swiss Tropical Institute, Basel, Switzerland.
Matovu
E
E
Brun
R
R
Kaminsky
R
R
D000818:Animals; D004351:Drug Resistance; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D008549:Melarsoprol / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009547:Nifurtimox / Q000494:pharmacology; D013045:Species Specificity; D013498:Suramin / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000453:epidemiology / Q000469:parasitology*; D014454:Uganda / Q000453:epidemiology
D007042:Hypoxanthines; D014344:Trypanocidal Agents; D019271:Hypoxanthine; D013498:Suramin; D009547:Nifurtimox; D008549:Melarsoprol; D000518:Eflornithine