Trypanocidal effect of diamidine 98/202 in experimental Trypanosoma rhodesiense infection of the stumptailed macaque (Macaca arctoides).
The trypanocidal effect of preparation 98/202, a 6-Amidino-2-(4'-amidinophenyl)-thionaphthene dilactate, was investigated in 4 stumptailed macaques (Macaca arctoides) infected with Trypanosoma rhodesiense (strain: Hamburg, 1962), of which 2 animals had been treated previously with diminazene and pentamidine, respectively. The curative treatment with preparation 98/202 was carried out in all cases in the late stage of infection; at the beginning of treatment 3 of the 4 animals had already shown malaise with distinct affection of the central nervous system. The individual dose was 5 mg/kg (base) and was given by deep intramuscular injection on 2, 3 or 4 consecutive days. During the trial period elimination of the parasites from the blood was observed in all monkeys, and in 3 out of 4 animals also in the liquor cerebrospinalis. In one animal a parasitological cure could be demonstrated. Two animals died as a result of the very advanced infection, one animal had to be killed prematurely because of numerous deep skin necroses without healing tendency. In 2 animals previously treated with diminazene and pentamidine, respectively, the T. rhodesiense strain developed a distinct resistance to pentamidine, diminazene and preparation 98/202. The resistance induced with pentamidine against diminazene and preparation 98/202, however, was only transitory and disappeared after withdrawal of the preparation. A brief description of the course of infection is given and possible sites of action of preparation 98/202 are discussed.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier; D002555:Cerebrospinal Fluid / Q000469:parasitology; D004133:Diminazene / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005260:Female; D000882:Haplorhini; D008251:Macaca; D008297:Male; D008826:Microbial Sensitivity Tests; D010419:Pentamidine / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000517:prevention & control
D000578:Amidines; D014344:Trypanocidal Agents; D010419:Pentamidine; D004133:Diminazene