Screening compounds for sleeping sickness therapy without relapse
Ormerod, W.E.; Raseroka, B.H.
Bulletin de la Societe de Pathologie Exotique et de Ses Filiales 81(3 Pt 2): 543-547
1988
ISSN/ISBN: 0037-9085 PMID: 2461813 Document Number: 322796
The finding of an intracellular stage of Trypanosoma brucei in the ependymal cells of the choroid plexus and of the lining of the ventricles suggested a new technique for screening trypanocides against the failure of drugs to eliminate "occult" stages of the infection. Donor mice infected for 28 days were dosed with various drugs and recipient mice were inoculated with samples of blood, cerebral cortex, choroid plexus and lining of ventricles; the response of the recipient showed whether trypanosomes had been cleared from the tissue under consideration. Suramin cleared the blood and cerebral cortex only. SHAM plus glycerol cleared the blood only. Melarsoprol showed some activity within the ependymal cells but had only very limited activity in the brain. Pentamidine and diminazine were unable to penetrate the blood-brain barrier, and consequently all recipients inoculated with brain tissues became infected. Isometamidium had some activity in the choroid plexus but little activity in the brain itself. Ethidium and nifurtimox showed little direct action on blood forms. Fexinidazole showed some activity on all tissues. Difluoromethylornithine (DFMO) cleared the ependymal cells but the results were difficult to evaluate. Bleomycin was the single most effective drug, clearing parasites from all tissues and sinefungin was also very active. Pairs of drugs were more effective than single drugs: suramin plus nifurtimox, metronidazole (ineffective on its own), sinefungin or DFMO, melarsoprol and nifurtimox, sinefungin and nifurtimox or metronidazole gave complete cures.