COMBINATION CHEMOTHERAPY OF CNS TRYPANOSOMIASIS

The progress which has been -ade in the treatment of experimental CNS trypanosomiasis with combination chemotherapy is reviewed. The most significant has been the use of four specific 5-nitroimidazoles in combination with either suramin or the arsenicals. The latter combination of MK 436 and Mel Cy, producing a rapid cure of CNS trypanosomiasis with only a two dose regimen and thus, would make an ideal universal treatment for both early- and late-stage trypanosomiasis. However, the 5-nitroimidazoles, because they are Ames' positive, are unlikely to be developed for use in humans. The combination chemotherapeutic regimen of eflornithine and arsenicals would allow the use of reduced quantities of melarsoprol to be used with similar or increased efficacy. As these drugs are already approved for use in humans, they could be applied immediately to the human disease; however, the quantities of eflornithine required for cures and the basic cost of this compound may limit its use in human medicine. Investigations of the post-treatment reactive encephalopathies (PTRE) which occur after non-curative treatment of trypanosome infections have shown that they are essentially caused by the presence of a residual focus of living trypanosomes in the CNS. If all trypanosomes are eliminated from the CNS (curative treatment) then there are no PTRE and when non-curative treatment is used the reaction can be reduced or ameliorated by supportive treatment with anti-inflammatory drugs such as prednisolone, dexamethasone or azathioprine.