Subcurative chemotherapy and fatal post-treatment reactive encephalopathies in African trypanosomiasis.
The treatment of late-stage African sleeping sickness in man is often complicated by a post-treatment reactive encephalopathy. The bases of this pathological reaction was investigated in a mouse model of African trypanosomiasis. Subcurative treatment with diminazene aceturate, which did not clear parasites from the central nervous system, resulted in a post-treatment meningoencephalitis similar to that seen in man. By contrast, a curative regimen of melaminylthioarsenite and 5-nitroimidazole, which cleared parasites from the central nervous system, did not cause any pathological reaction in the mice. This result indicates that subcurative treatment leads to the development of the post-treatment encephalopathy. Evidence that this may also be the case in man was provided by the detection of trypanosome DNA with the polymerase chain reaction in the brains of 9 patients who had died as the result of a post-treatment reaction. Our findings suggest that more aggressive treatment regimens, which ensure the elimination of trypanosomes from the central nervous system, may prevent post-treatment reactions in patients.
Department of Veterinary Medicine, University of Glasgow, UK.
C A
CA
Hunter
F W
FW
Jennings
J H
JH
Adams
M
M
Murray
P G
PG
Kennedy
D000293:Adolescent; D000328:Adult; D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage; D001921:Brain / Q000469:parasitology / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology / Q000469:parasitology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004133:Diminazene / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009593:Nitroimidazoles / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014346:Trypanosoma brucei brucei / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology
D001152:Arsenicals; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C062789:melaminylthioarsenate; C003915:diminazene aceturate; D004133:Diminazene; C052587:4-nitroimidazole