The purpose of this retrospective cohort study was to evaluate the effects of the timing of hyperketonemia (HYK) diagnosis during early lactation on milk yield and composition, reproductive performance, and herd removal. Plasma β-hydroxybutyrate (BHB) was measured twice a week during the first 2 wk of lactation in 362 multiparous Holstein cows for the diagnosis of HYK. In each week, cows were diagnosed as HYK positive (HYK+) if the plasma BHB concentrations were ≥1.2 mmol/L in at least one of the tests for the week evaluated. Milk-related outcomes (first 10 monthly milk tests) included milk yield, milk fat and protein content, milk urea nitrogen (MUN), and linear score of somatic cell count. Other performance outcomes of interest included risk of pregnancy within 150 d in milk (DIM) and herd removal (i.e., culling or death) within 300 DIM. Statistical models were built separately for cows diagnosed with HYK during the first week of lactation (wk1) and for cows diagnosed during the second week of lactation (wk2). All models for wk2 were adjusted by HYK diagnosed in wk1, along with other potential confounder variables. The association between HYK in each week and milk-related outcomes was assessed using generalized estimated equation models that accounted for repeated measures. Time to pregnancy and time to herd removal were analyzed using Cox's proportional hazard regression models. Seventy-eight cows (21.5%) tested positive for HYK during wk1, 60 cows (16.6%) in wk2, and 29 cows (8.0%) in both weeks. Hyperketonemia during wk1 was associated with a milk yield reduction of 3.7 kg [95% confidence interval (CI): -6.67 to -0.76] per cow per day throughout the lactation. Meanwhile, we did not observe evidence of an association between HYK diagnosed during wk2 and milk yield. During the first 2 monthly milk tests, cows diagnosed as HYK+ in wk1 had greater fat (0.42%; 95% CI: 0.16 to 0.67) and MUN (0.75 mg/dL; 95% CI: 0.26 to 1.24) content in milk than HYK-negative (HYK-) cows. We did not detect any evidence of an association between HYK diagnosed in wk2 and these outcomes. The HYK+ cows in wk1 had a 30% [hazard ratio (HR) = 0.70; 95% CI: 0.48 to 1.01] lower risk of pregnancy within 150 DIM and 2.48 times (95% CI: 1.63 to 2.89) higher risk of herd removal within 300 DIM than HYK- cows. Conversely, no evidence of association was observed between HYK+ cows in wk2 and risk of pregnancy by 150 DIM (HR = 0.98; 95% CI: 0.64 to 1.51) or removal from the herd within 300 DIM (HR = 0.91; 95% CI: 0.52 to 1.60). Our findings indicate that HYK diagnosed during wk1 of lactation is associated with negative performance in terms of milk yield, reproduction, and herd removal. No evidence of association was found for the same outcomes when HYK was diagnosed in wk2. Our results suggest the need to consider the timing when HYK is diagnosed when investigating its association with performance outcomes.

Summary: On March 24, 2024, the US Department of Agriculture confirmed the first case of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in dairy cattle. Following this initial detection, the virus was found to have spread to other species, including humans. Since then, at least 192 dairy herds across 13 states have tested positive for the virus. Through this work, we discuss the epidemiological and clinical aspects of HPAI H5N1 in cattle by reviewing the spatiotemporal situation of the disease across the United States, the clinical signs and testing leading to a confirmed case, and the surveillance and control measures implemented at the national and state levels. Further, considering pathogenesis and risk factors, we discuss surveillance and control measures to implement within herds. We also note areas where research is needed to understand how to control this emerging disease. Graphical abstract created with BioRender.com.

Treatment of subclinical mastitis (SCM) during lactation is rarely recommended due to concerns related to both antimicrobial usage and the costs associated with milk discard. Nisin is a naturally produced antimicrobial peptide with a gram-positive spectrum that, when given to dairy cows, does not require milk discard. We evaluated the economic impact of the treatment of SCM during early lactation using a nisin-based intramammary treatment under different scenarios that included various treatment costs, milk prices, and cure rates. We stochastically simulated the dynamics of SCM detected during the first week of lactation. The net economic impact was expressed in US dollars per case. The probabilities of an event and their related costs were estimated using a model that was based on pathogen-specific assumptions selected from peer-reviewed articles. Nisin cure rates were based on results of pivotal studies included in the US Food and Drug Administration (FDA) approval submission. Based on our model, the average cost of a case of intramammary infection (i.e., only true-positive cases) in early lactation was $170 (90% = $148-$187), whereas the cost of a clinical mastitis case was $521 (90% range = $435-$581). Both estimates varied with etiology, parity, and stage of lactation. When comparing the net cost of SCM cases (i.e., CMT-positive tests) detected during the first week of lactation, nisin treatment generated an average positive economic impact of $19 per CMT-positive case. The use of nisin to treat SCM was beneficial 93% of the time. Based on the sensitivity analysis, treatment would result in an economically beneficial outcome for 95% and 73% of multiparous and primiparous cows, respectively. At the herd level, use of intramammary nisin to treat SCM in cows in early lactation was economically beneficial in most tested scenarios. However, the economic impact was highly influenced by factors such as rate of bacteriological cure, cost of treatment, and parity of the affected animal. These factors should be considered when deciding to use nisin as a treatment for SCM.

This study aimed to characterize the highly pathogenic avian influenza (HPAI) hemagglutinin type 5 and neuraminidase type 1 (H5N1) clade 2.3.4.4b outbreak in dairy cattle and to estimate the effect of the outbreak on health, productivity, and economics at the herd and individual levels for 130 d from the outbreak. Herd records from a Michigan dairy farm, confirmed as affected based on PCR testing in milk, were used for this cohort study. Records included daily bulk tank information, herd management and feed intake data, and temperature alerts generated from cows' intraruminal automated sensor devices during the year of the outbreak and the previous year. Health indicators included fever (used to determine the cumulative incidence of HPAI H5N1-affected cows and outbreak length), culling, death, SCC, and DMI. Productivity was estimated based on milk yield and composition. The outbreak and postoutbreak periods were compared with the same periods of the previous year using joinpoint segmented regression analysis. Analyses included 486 daily bulk tank observations and 13,542 fever alerts from 437 Holstein dairy cows. Based on these outcomes, we estimated the economic effect of HPAI H5N1 at the herd and individual level using a stochastic simulation model. Cumulative incidence was 32% of the herd during the outbreak lasting 45 d. The outbreak led to an average milk yield reduction of 5.7%, with a peak in reduction of 22% lower than the preoutbreak average. The total milk drop was 324 kg of milk per cow in the herd, or 1,014 kg per affected cow. A lengthy recovery of milk yield began 19 d after the onset of the outbreak, reaching the previous year's yield 132 d (4.4 mo) later. The bulk tank SCC (BTSCC) peaked at 296,703 cells/mL, marking a 3-fold increase from preoutbreak levels. This tipping point occurred 22 d after the outbreak onset. The BTSCC gradually returned to preoutbreak levels 46 d after the outbreak began, coinciding with the outbreak's conclusion. During the outbreak, the average DMI consumed by lactating cows was reduced by 1.5 kg/d per cow (3.5%), whereas affected cows reduced DMI on average 4.7 kg/d over the outbreak. The cost of HPAI H5N1 for affected cows based on milk reduction, replacement, treatment costs, and reduced DMI was estimated at $504 (90% range = $422-$597). At the herd level, for a 500-cow herd, the economic effect was estimated at $79,145 (90% range = $56,726-$84,994). The economic effect of the outbreak per cow in the herd averaged $158 (90% range = $132-$184; i.e., averaged over the entire herd). Milk reduction represented 92.3% of the total economic losses, followed by death-related costs (4.7%), treatment and labor costs (1.6%), and culling costs (1.5%). Reduced DMI saved an estimated $11,705 in feed expenses for a 500-cow herd. The effect of HPAI H5N1 on health, productivity, and economics was both severe and immediate, challenging the economic sustainability of the dairy farms. These findings emphasize the urgent need for strong biosecurity measures to prevent and control such outbreaks effectively to limit the high burden estimated.

Monitoring the body condition score (BCS) of dairy cows is a management strategy that can assist dairy producers in decision-making. The BCS and its variations reflect the level of body fat reserves and fat mobilization throughout the different stages of lactation. Cows that mobilize excessive amounts of fat reserves in response to the increased energy requirements of the transition period are more likely to have higher beta-hydroxybutyrate (BHB) concentration in blood, leading to a higher incidence of hyperketonemia postpartum. In this study, our main objective was to evaluate how both BCS (at 21 d prior to the expected calving date, −21 BCS) and change in BCS during the late dry period (−21 d to calving, ∆BCS) are associated with temporal patterns of blood BHB concentrations during the first two weeks of lactation. Our secondary objective was to characterize the relationship between the change in BCS in the late dry period, and milk yield and milk composition in the first milk test postpartum. In this retrospective cohort study, we assessed BCS at 21 (±3) days before the expected calving date and within three days after calving. Blood BHB concentration was measured at days 3 (±1), 7 (±1), and 14 (±1) postpartum. Hyperketonemia (HYK) was defined as blood BHB ≥ 1.2 mmol/L. To evaluate how −21 BCS and ∆BCS during the late dry period were associated with BHB in early lactation, linear mixed-effects regression models with an unstructured covariate matrix were performed. The association between ∆BCS and incidence of postpartum HYK were determined using a multivariable log-binomial model. A linear regression model was used to evaluate the association between ∆BCS and milk yield and milk composition in the first monthly test-day. Covariates used for model adjustment include parity, season, and baseline BCS. We observed that cows with BCS ≥ 4.0 at 21 d before their expected calving date had the highest BHB concentration postpartum, but no evidence that BCS ≥ 4.0 at 21 d was associated with fluctuations of BHB over time. Cows that experienced a large BCS loss (larger than 0.5 units) during the late dry period had a 61% (95% CI: 1.04, 2.50) higher risk of developing HYK in early lactation and had higher BHB concentrations during early lactation compared with cows with no ∆BCS prepartum. These associations were observed independently of the BCS at −21 d prepartum (baseline). In addition, cows that lost more than 0.5 BCS unit in the late dry period produced 3.3 kg less milk (95% CI: −7.06, 0.45) at the first milk test compared to cows that had no ∆BCS during the late dry period. No evidence of an association between −21 BCS and ∆BCS in the late dry period and milk composition was observed in our study. These results suggest that dynamic measures of BCS during the late dry period, such as ∆BCS, are better at evaluating blood BHB patterns in early lactation than BCS measured at a single time point. Cows with larger BCS loss during the late dry period and with greater parity are more likely to have higher concentrations of blood BHB postpartum, with the highest concentrations reported at 7 d post-calving.