Therapeutic action of MK-436 (2,5-nitroimidazole) on Trypanosoma cruzi infections in mice: a parasitological, serological, histopathological, and ultrastructural study

Abstract

The anti-protozoal drug MK-436 (3-(1-methyl-5-nitroimidazol-2-yl)-3a,4,5,6,7,7a-hexahydro-1,2-benzisoxazole) was found to be effective against Trypanosoma cruzi infections in mice (2 daily doses of 250 mg per kg body weight). Parasitaemia disappeared within 24 hours of treatment which was commenced during the early or late stages of acute infection. Intracellular T. cruzi parasites were also affected by the drug, ultrastructural findings showing severe cytoplasmic vacuolization and membrane alterations. Positive serological responses persisted in the majority of treated and parasitologically cured mice in the study. Cure rates varied from 72% to 100% and were similar regardless of the T. cruzi strain used (Y strain, type I; 12 SF strain, type II; or Colombian strain, type III). However, the proportion of positive serological tests and the frequency of inflammatory lesions were greatest for mice that were infected with the Colombian strain of the parasite.