BACKGROUND: Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of
livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually
useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have
found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide
isometamidium chloride (ISM) with two affordable veterinary antibiotics.
METHODOLOGY/PRINCIPAL FINDINGS: In a first experiment, groups of mice were inoculated with Trypanosoma congolense
strains resistant to ISM and either left untreated or treated with (i) tetracycline, (ii) ISM or (iii) the combination of the
antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to
treatment on the survival time. The groups treated with ISM (with or without antibiotic) survived significantly longer than
the groups that were not treated with ISM (P,0.01). The group treated with the combination trypanocide/antibiotic
survived significantly longer than the group treated with ISM (P,0.01). In a second experiment, groups of cattle were
inoculated with the same resistant trypanosome strain and treated with (i) ISM, (ii) ISM associated with oxytetracycline or (iii)
ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISMoxytetracycline
and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination
trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p,0.001). The
impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the
combination trypanocide/antibiotic (p,0.01).
CONCLUSIONS/SIGNIFICANCE: After optimization of the administration protocol, this new therapeutic combination could
constitute a promising treatment for livestock infected with drug resistant T. congolense.