Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice.
Chemotherapy for human African trypanosomiasis (HAT), or sleeping sickness, is unreliable because of resistance, refraction and toxic and adverse side-effects. Using a long-term experimental model of HAT with involvement of the central nervous system (CNS), we tested the ability of a megazol and suramin combination treatment to eliminate CNS trypanosomes. This consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.), followed 24 h later by 4 daily doses (80 mg/kg) of megazol given either i.p. or per os. One week post-treatment, neurological disorders had disappeared. One of 15 mice relapsed in each application group at 81 and 98 days after treatment, respectively. At six months, no signs of relapse were seen in remaining mice, indicating that this chemotherapy regimen was curative. Immunohistochemical (astrocytosis) and histological (inflammatory lesions) examinations of brain tissues showed that animals returned to normal from 2 months post-treatment. These results suggest that the megazol-suramin combination reversed the CNS pathology in this model.
Enanga
B
B
Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Limoges, France.
Keita
M
M
Chauvière
G
G
Dumas
M
M
Bouteille
B
B
D000818:Animals; D001835:Body Weight; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D012008:Recurrence; D013498:Suramin / Q000627:therapeutic use*; D013830:Thiadiazoles / Q000627:therapeutic use*; D013997:Time Factors; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000473:pathology
D013830:Thiadiazoles; D014344:Trypanocidal Agents; C013378:megazol; D013498:Suramin