African trypanosomiasis and drug-induced encephalopathy: risk factors and pathogenesis.
Data on 598 patients with Trypanosoma brucei gambiense sleeping sickness, with abnormal cerebrospinal fluid (CSF) and treated with melarsoprol, were reviewed to determine risk factors for drug-induced encephalopathy. The incidence of melarsoprol-induced encephalopathy was increased in patients with trypanosomes present in the CSF, in patients with a high CSF lymphocyte count, and among patients in whom no trypanosomes were found in either the blood or the lymph node aspirate. Among patients with trypanosomes in the CSF, the risk of encephalopathy was similar whether or not they also had trypanosomes seen in the haemolymphatic system. Dimercaprol, a heavy metal chelator, did not reduce the case-fatality rate of patients with encephalopathy. These observations and others are compatible with the hypothesis that an immune phenomenon is involved in the pathogenesis of melarsoprol-induced encephalopathy. Whether the basic mechanism relates to deposits of immune complexes in the central nervous system or to the release of trypanosomal antigens which subsequently bind to brain cells and attract antibodies or T lymphocytes, the rapidity with which trypanosomal antigens are released may be critical, and very aggressive therapeutic schemes may result in higher toxicity, especially in patients with an impaired blood-brain barrier.
Pepin
J
J
Medical Research Council Laboratories, Fajara, The Gambia.
Milord
F
F
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced*; D004112:Dimercaprol / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008549:Melarsoprol / Q000009:adverse effects*; D012307:Risk Factors; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000134:cerebrospinal fluid / Q000188:drug therapy*
D004112:Dimercaprol; D008549:Melarsoprol