Seroprevalence and immunological characterization of Trypanosoma evansi infection in livestock of four agro-climatic zones of Himachal Pradesh, India

Sharma, Diksha; Gupta, S. C.; Sethi, Khushboo; Kumar, Sanjay; Kumar, Rajender

doi:10.1007/s11250-022-03069-y

Cited by 3 publications

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“…The extracellular hemoflagellate, Trypanosoma evansi , has a wide spectrum of hosts and is responsible for surra in animals (Desquesnes et al 2013 ). Surra is a debilitating and economically significant illness of equines, bovines, and camelids, which is extensively dispersed in parts of Africa, Asia, and South America (Radwanska et al 2018 ; Aregawi et al 2019 ; Yadav et al 2019 ; Sharma et al 2022 ). Chemotherapy forms the mainstay for treatment and control of surra in animals (Giordani et al 2016 ).…”

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confidence: 99%

In vitro anti-trypanosomal effect of ivermectin on Trypanosoma evansi by targeting multiple metabolic pathways

Gupta

Vohra

Sethi

et al. 2022

Trop Anim Health Prod

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High cytotoxicity and increasing resistance reports of existing chemotherapeutic agents against T. evansi have raised the demand for novel, potent, and high therapeutic index molecules for the treatment of surra in animals. In this regard, repurposing approach of drug discovery has provided an opportunity to explore the therapeutic potential of existing drugs against new organism. With this objective, the macrocyclic lactone representative, ivermectin, has been investigated for the efficacy against T. evansi in the axenic culture medium. To elucidate the potential target of ivermectin in T. evansi , mRNA expression profile of 13 important drug target genes has been studied at 12, 24, and 48 h interval. In the in vitro growth inhibition assay, ivermectin inhibited T. evansi growth and multiplication significantly ( p < 0.001) with IC 50 values of 13.82 μM, indicating potent trypanocidal activity. Cytotoxicity assays on equine peripheral blood mononuclear cells (PBMCs) and Vero cell line showed that ivermectin affected the viability of cells with a half-maximal cytotoxic concentration (CC 50 ) at 17.48 and 22.05 μM, respectively. Data generated showed there was significant down-regulation of hexokinase ( p < 0.001), ESAG8 ( p < 0.001), aurora kinase ( p < 0.001), casein kinase 1 ( p < 0.001), topoisomerase II ( p < 0.001), calcium ATPase 1 ( p < 0.001), ribonucleotide reductase I ( p < 0.05), and ornithine decarboxylase ( p < 0.01). The mRNA expression of oligopeptidase B remains refractory to the exposure of the ivermectin. The arginine kinase 1 and ribonucleotide reductase II showed up-regulation on treatment with ivermectin. The ivermectin was found to affect glycolytic pathways, ATP-dependent calcium ATPase, cellular kinases, and other pathway involved in proliferation and maintenance of internal homeostasis of T. evansi. These data imply that intervention with alternate strategies like nano-formulation, nano-carriers, and nano-delivery or identification of ivermectin homologs with low cytotoxicity and high bioavailability can be explored in the future as an alternate treatment for surra in animals. Graphical abstract

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