The in vitro and in vivo effects of metronidazole and chloroquine on Trypanosoma brucei brucei

Bloodstream forms of Trypanosoma brucei brucei were grown over baby hamster kidney cells in minimum essential medium with various concentrations of metronidazole (Flagyl) and chloroquine. Both drugs inhibited the multiplication of the parasite in vitro. The least effective concentrations for metronidazole and chloroquine were 0.003 mg/ml and 0.0024 mg/ml, respectively. Groups of 12-day-old female CDI mice were treated with 1 of the 2 drugs at 24, 48, and 72 hr after T. brucei infection. The drugs administered stat or daily reduced the number of parasites in the mice but did not effect a cure; they prolonged the survival period of the animals. However, metronidazole (0.1 mg/kg body weight) and chloroquine (0.08 mg/kg body weight) combined and given daily for 4 consecutive days cleared the infection. No trypanosomes were detected in the blood of these mice 3 mo after treatment. The dosages for both the in vitro (metronidazole 0.003 mg/ml; chloroquine 0.0024 mg/ml) and in vivo (metronidazole 0.1 mg/kg body weight; chloroquine 0.08 mg/kg body weight) were well below those prescribed for humans.