Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes

Abstract

Mice infected with Trypanosoma brucei can be easily cured using the available trypanocidal drugs, provided treatment is given soon after the infection; however, if infection is allowed to continue for some time then it is extremely difficult to obtain a permanent cure, and after an aparasitaemic period the infection eventually relapses. It has been shown that a relatively small number of infective trypanosomes in the brain have escaped the action of the drug and these are able to replicate and eventually they re-establish a circulating parasitaemia. The number of infective trypanosomes remaining after chemotherapy varied according to the stabilate of T. brucei, but using the stabilate T. brucei GVR 35 there were up to, 5,000 infective trypanosomes 2 days after treatment, and this rapidly increased up to 50,000 trypanosomes at 7 days. Infected mice on histological examination exhibited a mild meningitis and this was exacerbated by Berenil therapy and 7 days posttreatment the mice had an acute meningoencephalitis. It would appear that if the infective trypanosomes are completely eliminated from the brain this exacerbated reaction does not occur. It has been found that combined treatment of chronic T. brucei infections with either diminazene aceturate or suramin followed by 5-substituted nitroimidazoles at appropriate dose levels will completely eliminate the infective trypanosomes from the brain and the mice are permanently cured.