Arsenic and old taxa: subspeciation and drug sensitivity in Trypanosoma brucei

Resistance to the trypanocidal drugs atoxyl and tryparsamide was traditionally considered to be a diagnostic feature of rhodesian sleeping sickness and, consequently, of Trypanosoma rhodesiense. In examining the tryparsamide sensitivity of 13 isoenzymically defined stocks of the subgenus Trypanozoon, typical West African stocks showed no greater drug sensitivity than did those of East and Central Africa. The greatest resistance to tryparsamide was shown by two stocks isolated in the Ivory Coast. There was no evidence of strain differences in drug sensitivity to melarsoprol (Mel B) among 26 tested populations; none the less, differential melarsoprol sensitivity was evident in clones from a single mixed population. By contrast, isoenzymically defined West African stocks appeared to be less sensitive to pentamidine and diminazene aceturate (Berenil) than were typical East African stocks. Drug sensitivity was measured in a novel in vivo test designed to minimize the influence of host-parasite interactions, in particular trypanosome penetration of drug-inaccessible sites and host-antibody induced remission of parasitaemia. Drug effect was expressed as the DS0.1, the dose required to suppress parasitaemia to 0.1% of that in untreated control mice.