Abstract
BackgroundTreatment is the principle way to control and eliminate piroplasmosis. The search for new chemotherapy against Babesia and Theileria has become increasingly urgent due to parasite resistance to current drugs. Ivermectin (IVM) was the world’s first endectocide, capable of killing a wide variety of parasites and vectors, both inside and outside the body. It is currently authorized to treat onchocerciasis, lymphatic filariasis, strongyloidiasis, and scabies. The current study documented the efficacy of IVM on the growth of Babesia and Theileria in vitro and in vivo.MethodsThe fluorescence-based assay was used for evaluating the inhibitory effect of IVM on four Babesia species, including B. bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi, the combination with diminazene aceturate (DA), clofazimine (CF), and atovaquone (AQ) on in vitro cultures, and on the multiplication of a B. microti-infected mouse model. The cytotoxicity of compounds was tested on Madin–Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3 T3), and human foreskin fibroblast (HFF) cell lines.ResultsThe half-maximal inhibitory concentration (IC50) values determined for IVM against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi were 53.3 ± 4.8, 98.6 ± 5.7, 30.1 ± 2.2, 43.7 ± 3.7, and 90.1 ± 8.1 μM, respectively. Toxicity assays on MDBK, NIH/3 T3, and HFF cell lines showed that IVM affected the viability of cells with a half-maximal effective concentration (EC50) of 138.9 ± 4.9, 283.8 ± 3.6, and 287.5 ± 7.6 μM, respectively. In the in vivo experiment, IVM, when administered intraperitoneally at 4 mg/kg, significantly (p < 0.05) inhibited the growth of B. microti in mice by 63%. Furthermore, combination therapies of IVM–DA, IVM–AQ, and IVM–CF at a half dose reduced the peak parasitemia of B. microti by 83.7%, 76.5%, and 74.4%, respectively. Moreover, this study confirmed the absence of B. microti DNA in groups treated with combination chemotherapy of IVM + DA and IVM + AQ 49 days after infection.ConclusionsThese findings suggest that IVM has the potential to be an alternative remedy for treating piroplasmosis.
Highlights
Treatment is the principle way to control and eliminate piroplasmosis
González et al showed the failure, ineffectiveness, adverse reaction, and relapsing babesiosis of clindamycin and quinine combination treatment in splenectomized patients infected by B. divergens or B. microti [7], while Hatcher et al showed that patients affected by severe babesiosis had adverse reactions to quinine treatment and persistently high parasitemia more than 10 days after treatment with a combination of AQ and azithromycin [8]
We evaluated the effects of IVM against the growth of B. bigemina, B. bovis, B. divergens, B. caballi, and T. equi in vitro as well as the chemotherapeutic potential of IVM on B. microti in vivo
Summary
The search for new chemotherapy against Babesia and Theileria has become increasingly urgent due to parasite resistance to current drugs. B. bigemina, and B. divergens infect cattle, causing bovine babesiosis. Treatment of babesiosis and theileriosis in animals depends on two common drugs, namely diminazene aceturate (DA) and imidocarb dipropionate, while human babesiosis has been managed with a combination of atovaquone (AQ) and azithromycin and a combination of clindamycin and quinine [6]. González et al showed the failure, ineffectiveness, adverse reaction, and relapsing babesiosis of clindamycin and quinine combination treatment in splenectomized patients infected by B. divergens or B. microti [7], while Hatcher et al showed that patients affected by severe babesiosis had adverse reactions to quinine treatment and persistently high parasitemia more than 10 days after treatment with a combination of AQ and azithromycin [8]. Research to find new drugs and drug targets is the fundamental approach for addressing current limitations
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