Efficacy in US cattle of a novel fixed-dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against naturally acquired gastrointestinal nematode infections

Abstract

Reports of macrocyclic lactone (ML) loss of efficacy suggest ML resistance in gastrointestinal nematodes (GINs) is a growing problem in the US cattle industry. Empirical and modeling data support combining an ML and second anthelmintic from a different drug class to help ML resistance development while effectively treating existing resistant parasite populations. Here, we present a novel fixed-dose combination injectable (FDCI) solution for cattle that delivers 0.2 mg of doramectin and 6.0 mg of levamisole hydrochloride (HCl) per kg of body weight. Field studies were conducted at six sites across the Midwest United States to investigate the efficacy of a single administration of the FDCI in treating common cattle GINs. Cattle (n = 425) with GIN infections confirmed by fecal egg count (FEC) on Day −10( ± 2) were randomly allocated to the control (saline) or treatment (FDCI) group. On Day 0, pre-treatment fecal samples were collected, and cattle were administered a single subcutaneous injection of saline (n = 106) or FDCI (n = 319). Post-treatment fecal samples were collected on Day 14. Fecal egg count reduction tests (FECRTs) were conducted using Day 0 and Day 14 FECs. Efficacy was evaluated using Day 14 FECs (FDCI-treated versus saline-treated). Within treatment, samples collected on Days 0 and 14 with ≥ 20 eggs per gram (EPG) were cultured for nematode larvae recovery and identification. Day −10 FECs for enrolled animals were similar between treatment groups. Coprocultures from cattle with FEC ≥ 20 EPG (n = 68 saline; n = 211, FDCI) on Day 0 showed the presence of Cooperia punctata, Ostertagia spp., Haemonchus spp., C. oncophora, Oesophagostomum spp. and Trichostrongylus spp. Day 14 FECs for FDCI-treated cattle were significantly reduced (0–3 EPG) compared to saline-treated cattle (0–1252 EPG) (p ≤ 0.0042). At all study sites, the efficacy of the new FDCI was ≥ 99.4% and the FECR was 0.99 or 1.00. Day 14 coprocultures from control cattle showed infections of common GIN genera, confirming the efficacy of the FDCI against GINs in the field. A single administration of the doramectin + levamisole HCl combination injectable effectively treats common and economically important cattle GINs.