TRYPANOSOMA-BRUCEI-RHODESIENSE - USE OF AN ANTIGEN-DETECTION ENZYME-IMMUNOASSAY FOR EVALUATION OF RESPONSE TO CHEMOTHERAPY IN INFECTED VERVET MONKEYS (CERCOPITHECUS-AETHIOPS)

Thirty eight Trypanosoma brucei rhodesiense-infected vervet monkeys (C ercopithecus aethiops) in the late (meningoencephalitic) stage of dise ase, treated with various trypanocidal drugs, were monitored for a per iod of more than 600 days to assess the rate of clearance of trypanoso me antigens from serum and cerebrospinal fluid (CSF). There was a comp lete but gradual reduction in antigen titres, as assessed by ELISA, in animals treated intravenously with melarsoprol, the standard drug for the late stage disease. In 8 of the 9 monkeys treated with melarsopro l, the antigen titres, as assessed by optical density values, dropped by 50% within 252 days (mean value 68 days for antigens in CSF and 116 for serum) following treatment. The remaining animal in this group, t hat displayed persistent antigenaemia, had been treated with a sub-cur ative drug dosage level. Thus, if time to 50% reduction in antigen lev els were to be taken as an index to predict cure, the follow-up period after melarsoprol treatment could have been reduced from 600 to 252 d ays for 8 of the 9 animals, leaving only one animal for further follow up. The animals treated with experimental drug combinations displayed a variable picture: Five monkeys showed a persistence of antigens in both serum and CSF throughout the observation period, suggesting failu re of the drugs to cure the infection. Parasitologically confirmed rel apse of the infection was indeed observed in all the five monkeys. In some monkeys, the parasite antigens eventually cleared from serum and CSF completely, but this took a longer time duration than in the melar soprol treated animals; others showed persistence of parasite antigens in serum, but the parasites were not detected in blood or CSF through out the entire follow-up period. These results suggest that the experi mental drug combinations used were not effective in clearing the paras ites from cryptic foci and hence the persistence of antigens in serum and/or CSF. Antigen ELISA would, thus, appear to be a useful tool for evaluation of response to chemotherapy.