In vitro and in vivo efficacy of diamidines against Trypanosoma equiperdum strains

Abstract

AbstractTrypanosoma equiperdum is a protozoan parasite responsible for causing Dourine, a debilitating neglected veterinary disease, found worldwide affecting equids. It is the only pathogenic trypanosome species that does not require an invertebrate vector for transmission, thus being passed from animal to animal via coitus. At present, there is no officially recognized form of chemotherapeutic treatment and therefore all confirmed (or suspected) cases of infected animals must be slaughtered immediately. For many global communities and farming populations, which rely heavily on their animals for their livelihood, such stringent regulations can seriously enhance the socio-economic problems attributing to poverty. Two reference drugs, together with 37 novel diamidine compounds were tested in vitro using a 72 h drug sensitivity assay to determine their efficacy against two axenically adapted T. equiperdum strains. Further in vivo investigations in mouse models of infection against 4 ‘true’ T. equiperdum strains were performed using the 17 most active diamidines. Single bolus doses of 10 mg kg−1, given i.p. were administered to NMRI mice infected with one of the 4 T. equiperdum strains. The results obtained from this study show that experimentally T. equiperdum can indeed be effectively treated with chemotherapy using in vivo mouse models of infection.