Trypanosoma brucei brucei: the response to Melarsoprol in mice with cerebral trypanosomiasis. An immunopathological study.

A murine model for cerebral trypanosomiasis was adapted to study the efficacy of Melarsoprol which was apparently curative in high intravenous doses (10 mg/kg, 3 x 10 mg/kg, 20 mg/kg) in advanced infection (6th week); only one relapse occurred, but observation time was limited. Deposits of Ig and C3 in the choroid plexuses tended to disappear after successful treatment. Circulating immune complexes increased in the 1st week after therapy and returned to normal values in the 2nd week. Such an increase could temporarily be prevented by chloroquine, which may explain the reported reduction of side-effects from Melarsoprol in man after use of chloroquine in sleeping sickness. Melarsoprol (3 x 3.6 mg/kg) given intraperitoneally showed apparent cures but also relapses. Melarsoprol in high intraperitoneal doses (3 x 10 mg/kg) showed an increasing number of relapses if related to the duration of infection. Morphologically, a diffuse interstitial distribution of the parasites appeared in the CNS after relapse had occurred (shift), contrasting with the preferential localization of the parasites in the choroid plexuses of untreated mice. Such a shift was best visualized by immunofluorescence using specific antitrypanosomal antibodies. Relapse-mice invariably showed increased levels of circulating immune complexes suggesting this serological test for early detection of relapses. Tissue parasites appeared to be a likely cause of relapses, irrespective of the duration of infection. A short observation time with no circulating blood parasites is no guarantee of cure. Benznidazole (3 x 1 g/kg) was ineffective in advanced infection.