Trypanosoma evansi: in vivo and in vitro determination of trypanocide resistance profiles

We have determined the in vivo and in vitro sensitivities to six common trypanocides of two groups of trypanosomes, (1) two Trypanosoma equiperdum clones and three Trypanosoma evansi clones originating from Asia, Latin America, and Africa; and (2) six laboratory-derived drug-resistant subclones from two of the T. evansi and one of the T. equiperdum clones. We found that (1) we could induce trypanocide resistance by successive passage through mice treated with subtherapeutic doses of drugs; (2) clones selected for resistance to berenil and cymelarsan are not cross-resistant to suramin; (3) clones resistant to berenil, cymelarsan, and suramin are more sensitive to quinapyramine in vivo than the parental clones; (4) berenil resistance is stable; (5) some berenil-resistant clones acquire resistance to cymelarsan; (6) in vivo resistance to isometamidium is not detectable in vitro; and (7) the in vitro sensitivities to berenil and cymelarsan of parental clones and their laboratory-derived resistant subclones generally agreed with the in vivo results. We conclude that with further refinement the in vitro assay procedure may be useful for rapid determination of the sensitivity of trypanosome isolates to some current drugs and for screening new trypanocides. Our data also raise the possibility that conventional treatment regimens should be reevaluated and support the presence of at least two drug-resistance mechanisms in T. evansi and T. equiperdum, single drug resistance (berenil), and cross-resistance (berenil and cymelarsan).