Total Protein and White Cell Changes in the Cerebrospinal Fluid of Vervet Monkeys Infected with Trypanosoma rhodesiense and the Post-treatment Reaction

Abstract

In an attempt to elucidate the events leading to the development of post-treatment reactive encephalopathy in human African trypanosomiasis (HAT), a group of vervet monkeys (Cercopithecus aethiops) were experimentally infected with Trypanosoma rhodesiense. When terminally sick on day 42, they were treated with either diminazene aceturate (Berenil®), suramin or melarsoprol. Trypanosomes appeared in the cerebrospinal fluid (CSF) by day 14 of infection and increased in numbers with progress of the disease. However, only marginal increases in CSF total proteins and white cells occurred during the same period. Treatment with Berenil resulted in persistence and increase in numbers of CSF trypanosomes, a dramatic increase in proteins and white cells, culminating in clinical encephalitis. Suramin cleared CSF trypanosomes within 4 weeks, with marginal increase in proteins and white cells up to 8 weeks after treatment, followed thereafter by a gradual and prolonged fall to pre-infection levels. Melarsoprol eliminated trypanosomes from the CSF in less than a week but the white cell and protein levels increased for another 4 weeks before finally falling. The post-treatment increase in white cell numbers and total proteins was therefore dependent on the trypanocidal drug, and was highest and most prolonged when Berenil was used and lowest with suramin. The present studies demonstrate that trypanocidal treatment of infected animals is followed by a post-treatment reaction in the central nervous system, the severity of which is related to the drug used and the presence of trypanosomes in the CSF. The vervet monkey therefore appears to be a good model for studying the reaction in HAT.