Randomized, noninferiority trial evaluating the efficacy of a novel teat sealant in pasture grazed dairy cows

Abstract

The intramammary infusion at the end of lactation of a bismuth subnitrate internal teat sealant (ITS), with no antibiotic component has been shown to be an effective means of reducing new intramammary infections over the dry period. There has, however, been very few comparative studies between different brands of ITS under grazed pasture conditions. The objectives of this study were, therefore, to determine if a new bismuth subnitrate internal teal sealant (ShutOut, MSD Animal Health) was noninferior to Teatseal (Zoetis) regarding end-points such as (a) detection of the ITS product after calving, (b) clinical mastitis during the dry period and early lactation, and (c) subclinical mastitis at 30 to 60 d in milk. A total of 1,105 mixed-age cattle were enrolled across 2 farms comparing 2 ITS products for detection of the ITS at calving and prevention of clinical and subclinical mastitis. Both ITS contained 65% (2.6 g) bismuth salts emulsified in ≤ 1.4 g of mineral oil (ShutOut as investigational product, IVP; Teatseal as control product, CPT). At dry-off, treatment was allocated to every second cow. All cows met industry best practice criteria for using ITS treatment without antibiotics. Outcomes included detection of ITS at first stripping of the udder by the farmer, clinical mastitis (CM) from dry-off to 30 d following calving and subclinical mastitis at 30 to 60 d following calving. For ITS detection, a generalized mixed linear regression model was used to model the data, with clustering of quarters within cow accounted for by including cow as a random intercept. Clinical mastitis was analyzed at the cow-level using a Fisher's exact test, and SCC was modeled using a negative binomial distribution. The IVP was noninferior to the CPT for ITS detection following calving. There were 1344/1800 (71.5%) of quarters with ITS detection in the IVP in comparison to 1076/1604 (67.1%) of quarters in the CPT treated group. The quarter-level CM incidence risk was low (45 cases out 4,324 quarters; 1.04%). The overall cow-level CM risk was 4.1% (44/1081), with 20/540 (3.7%) cases in animals in the IVP group and 24/541 (4.4%) cases in animals in the CPT group. The IVP was noninferior to the CPT for cow-level mastitis incidence. The median SCC for all animals was 23,000 cells/mL, with a mean of 92,000 cells/mL. The back-transformed estimated marginal mean estimated SCC was 84,800 (95% CI 75,200-95,600) cells/mL for animals in the IVP group, and 98,800 (95% CI 87,600-111,300) cells/mL for animals in the CPT group. The IVP was, therefore, noninferior for all outcomes measured.