PHENOTYPIC AND GENOTYPIC VARIATION IN GIARDIA-LAMBLIA ISOLATES DURINGCHRONIC INFECTION

Two Giardia isolates were axenised in vitro after recovery by duodenal aspiration from a man with hypo-gamma globulinaemia and chronic giard iasis, before and after three unsuccessful courses of metronidazole. I n vitro drug sensitivity assays showed that the pretreatment isolate w as sensitive to metronidazole with minimum inhibitory concentration (M IC) and dose that inhibited growth by 50% (ED(50)) values of 0.1 and 0 .03 mu mol/l, respectively. The post-treatment isolate was 20-fold mor e resistant (MIC and ED(50) 4.3 and 0.58 mu mol/l, respectively). Diff erences between these isolates were also found in the surface protein profiles after radioiodination, metabolic labelling patterns with S-35 -methionine, malic enzyme isoenzyme patterns, and by DNA fingerprintin g with a M-13 bacteriophage probe. The phenotypic and genotypic differ ences between the pretreatment and posttreatment isolates suggest that we have isolated two different strains from the same patient and that treatment with metronidazole resulted in selection of the more resist ant strain.