Location: Animal Disease Research Unit
Title: Enhanced anti-Babesia efficacy of buparvaquone and imidocarb when combined with ELQ-316 in vitro culture of Babesia bigeminaAuthor
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CARDILLO, NATALIA - Washington State University |
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VILLARINO, NICOLAS - Veterans Affairs Medical Center - Portland |
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Lacy, Paul |
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DOGGETT, JOSEPH - Oregon Health & Science University |
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RICOE, MICAEL - Oregon Health & Science University |
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SUAREZ, CARLOS - Retired ARS Employee |
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Ueti, Massaro |
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Chung, Chungwon |
Submitted to: Pharmaceuticals
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 2/5/2025 Publication Date: 2/6/2025 Citation: Cardillo, N.M., Villarino, N.F., Lacy, P.A., Doggett, J.S., Ricoe, M.K., Suarez, C.E., Ueti, M.W., Chung, C.J. 2025. Enhanced anti-Babesia efficacy of buparvaquone and imidocarb when combined with ELQ-316 in vitro culture of Babesia bigemina. Pharmaceuticals. 18(2):218. https://doi.org/10.3390/ph18020218. DOI: https://doi.org/10.3390/ph18020218 Interpretive Summary: B. bigemina causes a vector-borne cattle disease transmitted by ticks. The identification of effective and safe therapies is urgently needed for global disease control. In this study the anti-babesial effects of ELQ-316, BPQ, ID, and the combinations of ID + ELQ-316 and BPQ + ELQ-316, were evaluated based on in vitro B. bigemina survival test. All tested single and combination drugs significantly inhibited (p<0.05) the growth of B. bigemina at 2% parasitemia. Of all tested treatment groups, the combination of ID + ELQ-316 had lower IC50% (9.2) than others. The parasites were no longer viable after treatment with the BPQ + ELQ-316 combination, and BPQ alone at a concentration of 1200 nM. Therefore, ELQ-316 combination either with BPQ or ID could be a promising treatment option to control B. bigemina Technical Abstract: Background/Objectives: B. /Jigemina is a highly pathogenic and widely distributed vector-borne disease transmitted by ticks. The development of effective and safe therapies for global disease control is urgently needed. The aim of this study was to compare the effects of ELQ-316, BPQ, ID, and the combinations of ID+ ELQ-316 and BPQ + ELQ-316, on B. bigemina survival in vitro. Methods: Parasites at a starting parasitemia level of 2%, were incubated with the drugs and combination of drugs, ranging from 25 to 1200 nM over four consecutive days. The inhibitory concentration IC50% and TC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Kruskall-Wallis test. Results: All drugs tested significantly inhibited (p<0.05) the growth of B. bigemina at 2% parasitemia. The combination of ID+ ELQ- 316 exhibited a lower IC50%: 9.2; IC 95%: 8.7 - 9.9) compared to ID (1C50%: 61.5; IC 95%: 59.54 - 63.46), ELQ-316 (IC50%: 48.10; IC 95%: 42.76-58.83), BPQ (IC50%: 44.66; IC 95%: 43.56-45.81), and BPQ + ELQ-316 (IC50%: 27.59; IC 95%: N/A). The parasites were no longer viable in cultures treated with the BPQ + ELQ-316 combination, as well as with BPQ alone at a concentration of 1200 nM, on days 2 and 3 of treatment, respectively. Conclusions: ELQ-316 combination either with BPQ or ID highlights the potential additive or synergistic effects, which can lead in a promising and more safety option of the traditional ID treatment used against B. bigemina. |