Chemosensitization of Trypanosoma congolense Strains Resistant to Isometamidium Chloride by Tetracyclines and Enrofloxacin

Abstract

BackgroundBecause 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 FindingsIn 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 ISM-oxytetracycline 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/SignificanceAfter optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense.

Evaluation of The In Vitro And In Vivo Inhibitory Effects of Enrofloxacin On the Growth of Babesia Species and Theileria Equi

“…orally for 30 days treated dogs inoculated by L. infantum without toxic side effects [14]. Combined treatment of enrofloxacin at 5 mg/kg with diminazene aceturate at 12.5 efficiently inhibited the progression of B. microti and this in accord with results of previous studies that used a mixture of enrofloxacin with other drugs such as doxycycline, metronidazole, and isometamidium chloride to control several protozoan infections [13,14,16,37]. Therefore, combination therapy of enrofloxacin might be used for babesiosis.…”

“…Enrofloxacin showed good in vitro inhibitory effects on T. equi and three Babesia species and in vivo inhibitory effects on Leishmania infantum and Trypanosoma conglense; thus, we evaluated the in vivo repressive activity of enrofloxacin on B. microti in mice. Enrofloxacin inhibited the growth of B. microti [14,16]. Treatment with 10 mg/kg B.W.…”

“…Enrofloxacin inhibits DNA gyrase, a prokaryotic type II topoisomerase, therefore, blocks prokaryotic DNA replication by hindering the untangling DNA during replication, and results in the linearization of the circular DNA, thus causing the death of prokaryotic organisms without affecting the mammalian topoisomerase [9][10][11]. DNA gyrase is made of two subunits, namely, DNA gyrase subunit A and DNA gyrase subunit B. Enrofloxacin has antibacterial, anti-anaplasma, antileishmanial, antitrypanosomal, anti-neospora, and anti-toxoplasma activities [12][13][14][15][16][17][18]. It is used clinically for treating bacterial infections in farm animals; therefore, it will be of economic value for treating piroplasmosis caused by Babesia and Theileria species by clinically available medicine.…”

PCR and microsatellite analysis of diminazene aceturate resistance of bovine trypanosomes correlated to knowledge, attitude and practice of livestock keepers in South-Western Ethiopia

“…Even if DA resistance is present, the effect of treatment on the PCV is still observable. This phenomenon was previously observed in cattle and goats inoculated with drug resistant trypanosomes and treated with trypanocidal drugs (Delespaux et al, 2010;Vitouley et al, 2012).…”

Field detection of resistance to isometamidium chloride and diminazene aceturate in Trypanosoma vivax from the region of the Boucle du Mouhoun in Burkina Faso

“…The impact of the infection on the PCV was not very pronounced with an average PCV reduction 8 to 14 weeks after treatment of only 5.9% (95% CI: 4.5-7.3) (Delespaux et al, 2010).…”