Treatment of chronic experimental Trypanosoma cruzi infections in mice with MK-436, a 2-substituted 5-nitroimidazole

The antiprotozoal drug 3-(1-methyl-5-nitroimidazol-2-yl)-3a, 4,5,6,7,7a-hexahydro-1,2-benzisoxazole (MK-436) is highly efficacious for treating mice chronically infected with different strains of Trypanosoma cruzi. The compound was administered by gavage in two daily doses of 250 mg per kg body weight to 130 mice that had been infected for 90 to 400 days with either type II or III strains of T. cruzi. The following parasitological cure tests were carried out: xenodiagnosis, haemoculture, and inoculation of blood into newborn mice. Indirect immunofluorescence tests and histopathological studies were also performed. The results indicate that the drug is highly efficacious against chronic infection caused by both type II (cure rate, 90%) and type III strains (cure rate, 95.7%). Histopathological examinations showed complete clearance of the cardiac and muscular lesions in 36% of the mice infected with type II strains and a decrease in the intensity and extension of the lesions in mice infected with type III strains. Indirect immunofluorescence tests were persistently positive for all the mice 3-6 months after the treatment.