Screening compounds for sleeping sickness therapy without relapse.
The finding of an intracellular stage of Trypanosoma brucei in ependymal cells of the choroid plexus (Abolarin et al., 1986) and of the lining of the ventricles (Ormerod and Hussein, 1986) has suggested a new technique for screening trypanocidal compounds against the failure of drugs to eliminate "occult" stages of the infection (Raseroka and Ormerod, 1986). A (donor) mouse, infected for 28 days, is dosed with a drug, or combination of drugs, and samples of blood, cerebral cortex, choroid plexus and lining of ventricle are injected into clean (recipient) mice. The response of recipient mice shows whether the part, under examination, of the donor mouse has been cleared of trypanosomes. Suramin clears the blood and cerebral cortex but not sites containing ependymal cells (i. e. choroid plexus and lining of ventricle). Melarsoprol is active in all sites but is not always effective. DFMO clears the ependymal cells but its action elsewhere is difficult to evaluate. Metronidazole (inactive on its own), when given with suramin is active at all sites. Bleomycin was the most effective single compound. Bleomycin, an anti-cancer agent registered for use in man, should receive clinical evaluation for sleeping sickness: there is evidence, however, of incompatibility with DFMO.
Ormerod
W E
WE
London School of Hygiene and Tropical Medicine.
Raseroka
B H
BH
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000518:Eflornithine / Q000494:pharmacology; D008549:Melarsoprol / Q000494:pharmacology; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D013498:Suramin / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D014344:Trypanocidal Agents; D001761:Bleomycin; D008795:Metronidazole; D013498:Suramin; D008549:Melarsoprol; D000518:Eflornithine