Performing Department
Veterinary Population Medicine
Non Technical Summary
The goal of this mastitis control project is todevelop, validate and then disseminate effective selective dry cow therapy (SDCT) program strategies to reduce antibiotic use at dry off while maintainingudder health, cow health and performance, and economic sustainability of U.S. dairy farms.Mastitis remains the most costly infectious disease affecting dairy herds, costing an estimated $140 to $300 per cow per year. In addition to the direct costs associated with treating clinical mastitis, mastitis is also an important animal welfare issue, being the second most common reported reason for culling cows, and the second most common cause of death in cattle. Finally, milk processors also incur losses, in that high SCC milk results in reduced cheese yields and shorter shelf life of dairy products, as well as restricted access of U.S. dairy products to some global markets. Antibiotics (Ab) have been an important tool on dairy farms, significantly improving the health, wellbeing and productivity of animals. However, public health concerns continue to mount regarding the potential for Ab use in food animals to promote antimicrobial resistance (AMR) in pathogens of importance to human health. Because the majority of Ab used on dairy farms is for the treatment or prevention of mastitis, we must adopt mastitis control practices that use Ab in the most judicious manner possible, while still maintaining or improving udder health, productivity and animal wellbeing.Given steady improvements in udder health, blanket dry cow therapy (BDCT), the practice of infusing long acting Ab into all quarters at dry off, may no longer be necessary on many U.S. dairy farms. Selective DCT (SDCT) is an approach whereby only cows or quarters likely to have intramammary infection would receive Ab treatment at dry off. The long-term goal of this project is validate and then disseminate logistically feasible and biologically effective SDCT program strategies to reduce Ab use at dry off while maintainingudder health, cow wellbeing and performance, and economic sustainability of the farm.The specific objectives of this project will be to:Objective 1. Complete a multi-location noninferiority randomized clinical trial to evaluate the effect of applying 2 different SDCT programs (vs BDCT) on measures of quarter health, cow health and performance, antibiotic use and economics: i) Culture-guided SDCT program targeting quarter level treatment decisions (C-SDCT) ii) Algorithm-guided SDCT program targeting cow level treatment decisions (A-SDCT)Objective 2. Describe the test characteristics of 3 newer rapid diagnostic tests for identifying quarters with intramammary infection at dry off. i) PortaSCC™ SCC test, ii) UdderCheck™ LDH test; and iii) Quick Mastitis Test (QMT™) milk lactate test (PortaScience, Portland,ME).Objective 3. Stochastic modeling to evaluate various means of employing SDCT versus BDCT and their impacts on cow health and performance, antibiotic use and economics.Objective 4. Describe the effect of antibiotic treatment of uninfected cows at dry off on the milk microbiome shortly after calving, and on udder health and cow performance in early lactation.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
The goal of this mastitis control project is todevelop, validate and then disseminate effective selective dry cow therapy (SDCT) program strategies to reduce antibiotic use at dry off while maintainingudder health, cow health and performance, and economic sustainability of U.S. dairy farms.Mastitis remains the most costly infectious disease affecting dairy herds, costing an estimated $140 to $300 per cow per year. In addition to the direct costs associated with treating clinical mastitis, mastitis is also an important animal welfare issue, being the second most common reported reason for culling cows, and the second most common cause of death in cattle. Finally, milk processors also incur losses, in that high SCC milk results in reduced cheese yields and shorter shelf life of dairy products, as well as restricted access of U.S. dairy products to some global markets. Antibiotics (Ab) have been an important tool on dairy farms, significantly improving the health, wellbeing and productivity of animals. However, public health concerns continue to mount regarding the potential for Ab use in food animals to promote antimicrobial resistance (AMR) in pathogens of importance to human health. Because the majority of Ab used on dairy farms is for the treatment or prevention of mastitis, we must adopt mastitis control practices that use Ab in the most judicious manner possible, while still maintaining or improving udder health, productivity and animal wellbeing.Given steady improvements in udder health, blanket dry cow therapy (BDCT), the practice of infusing long acting Ab into all quarters at dry off, may no longer be necessary on many U.S. dairy farms. Selective DCT (SDCT) is an approach whereby only cows or quarters likely to have intramammary infection would receive Ab treatment at dry off. The long-term goal of this project is validate and then disseminate logistically feasible and biologically effective SDCT program strategies to reduce Ab use at dry off while maintainingudder health, cow wellbeing and performance, and economic sustainability of the farm.The specific objectives of this project will be to:Objective 1. Complete a multi-location noninferiority randomized clinical trial to evaluate the effect of applying 2 different SDCT programs (vs BDCT) on measures of quarter health, cow health and performance, antibiotic use and economics: i) Culture-guided SDCT program targeting quarter level treatment decisions (C-SDCT) ii) Algorithm-guided SDCT program targeting cow level treatment decisions (A-SDCT)Objective 2. Describe the test characteristics of 3 newer rapid diagnostic tests for identifying quarters with intramammary infection at dry off. i) PortaSCC™ SCC test, ii) UdderCheck™ LDH test; and iii) Quick Mastitis Test (QMT™) milk lactate test (PortaScience, Portland,ME).Objective 3. Stochastic modeling to evaluate various means of employing SDCT versus BDCT and their impacts on cow health and performance, antibiotic use and economics.Objective 4. Describe the effect of antibiotic treatment of uninfected cows at dry off on the milk microbiome shortly after calving, and on udder health and cow performance in early lactation.
Project Methods
Herd and Cow Selection. A total of at least seven large commercial herds (> 1,000 cows) will be enrolled from the Northeast (NY), Midwest (MN, IA) and Western (CA) dairy regions. Cows will be eligible for enrollment if they have 4 functioning quarters, have received no parenteral or IMM treatment with an Ab or anti-inflammatory medication during the 14 day period immediately before dry off, be clinically healthy, and show no signs of clinical mastitis when assessed at enrollment or on the day of dry off. Cows must have an anticipated dry period length of between 30 and 90 days.Cow Enrollment, Sampling and Randomization to Treatment (Day 0; Figure 1). Study personnel will visit the farm on a regularly scheduled weekly visit 2 days before the weekly dry off day. For cows due to dry off that week, current lactation records will be downloaded from on-farm record keeping software to be evaluated for recent treatments, DHIA test day SCC data, and previous clinical mastitis treatment events. Cows to be dried off two days later will enter the parlor for regular morning milking and be assessed for eligibility by visual inspection for clinical signs of illness that might require exclusion including a very low body condition score (< 1.75; scale of 1 to 5), moderate to severe lameness, fewer than 4 functional quarters, or signs of clinical mastitis (i.e. visibly abnormal milk ± swollen quarter). Treatment allocation will be assigned at the cow level. Eligible cows will be identified with a uniquely colored leg band and then randomly assigned to one of the 3 DCT programs (BDCT, C-SDCT, A-SDCT), with randomization blocked within farm on each day of enrollment. Premilking aseptic duplicate dry off (DO) quarter milk samples (Sample 1 and 2 = S1, S2) will be collected from all eligible cows using strict aseptic sampling techniques as described by the National Mastitis Council (NMC; 2017) (58). Milk samples will be placed on ice immediately after collection. After sampling, cows will undergo regular milking and then exit the parlor.Milk Sample Testing Using Rapid Test Methods (Figure 1). Immediately following D0 sampling, milk samples will be transported on ice to the regional lab (MN, IA, NY or CA). The first of each pair of duplicate quarter samples from all cows (S1; BDCT, C-SDCT, and A-SDCT groups) as well as the second of each pair of duplicate quarter samples (Sample 2) from the BDCT and A-SDCT groups will be immediately frozen at -20 °C. The second of each pair of duplicate quarter milk samples (S2) collected from the C-SDCT group will be plated onto an OFC system (MN Easy™ 4Cast™ plate). Briefly, a sterile single used disposable cotton swab will be dipped into each quarter sample and then used to apply approximately 0.1 mL of milk to the correct quadrant of the plate (1 quadrant for each quarter). The plate will be identified by cow and quarter ID and then incubated at 37 °C for the next 36 hrs. The same quarter milk sample (S2) from only C-SDCT quarters will then be used to perform the following 3 rapid tests: i) PortaSCC™ SCC test, ii) UdderCheck™ LDH test, and iii) Quick Mastitis Test (QMT™) milk lactate test (PortaScience, Portland, ME).Cow and Quarter Classification for the SDCT Programs. Between D0 and day of dry off (2 days later), for cows assigned to the A-SDCT group a technician will compile the required lactation records and results of visual inspection of milk at the farm. Using the algorithm developed by Dr. Nydam, cows will then be classified as low (Neg) or high (Pos) risk, where low risk cows have a SCC < 200,000 cells/mL at last test, an average SCC < 200,000 on the last 3 tests, no signs of mastitis at the D0 herd visit, and no more than 1 clinical mastitis event in the current lactation. For cows assigned to the C-SDCT group, on the morning of dry off (after 36 hrs of incubation) the study technicians will interpret the results of the OFC plates, and record a result of bacterial growth (Pos; record number of colonies) or no growth (Neg) for each quarter. Cow and Quarter Treatment on Day of Dry Off (Figure 1). The technicians will then return to the dairy each week to help the producer administer the appropriate DC treatments. All enrolled cows will enter the parlor for the final milking, immediately after which they will be treated according to the treatment assigned by the study dry off protocol. For cows in the BDCT group, all four quarters will be infused with an Ab (Spectramast DC, Zoetis) followed by infusion with an ITS (OrbeSeal™, Zoetis). For cows in the C-SDCT group, quarters classified as Neg will be infused with the ITS only, while quarters classified as Pos will be infused with the Ab followed by ITS. For cows in the A-SDCT group, all 4 quarters of cows classified as Neg will be infused with the ITS only, while all 4 quarters of cows classified as Pos will be infused with the Ab followed by ITS. For all groups, intramammary infusion with Ab and/or ITS will follow strict aseptic techniques (58) according to the manufacturer's directions. Following treatment, all quarters of all cows will be dipped with a post-milking teat disinfectant and cows will exit the parlor.Postcalving Sampling and Follow-up (Figure 1). During the period between dry off and calving, cows will be managed as per each farm's usual routines. Following calving, study technicians will visit the herds once per week on a regularly scheduled day to collect post-calving (PC) aseptic duplicate quarter milk samples (S1, S2) once for each cow between 1 to 7 days in milk (DIM). Farm staff, who will be blinded to treatment, will record any clinical mastitis events (cow, quarter, date) for all cows experiencing a clinical mastitis event between enrollment and 120 DIM. After all post-calving samples are collected, a study technician will visit the herd on a bimonthly basis until all cows have completed the 120 DIM follow-up period. At each bimonthly visit they will downloaded from on-farm record keeping software, gathering lactation information for study cows such calving date, DHIA test-day measures (e.g. SCC, milk yield), and all health or removal events (e.g. clinical mastitis; death; culling). Laboratory Culture (Reference Test) of DO and PC Quarter Milk Samples. As previously mentioned, subsequent to collection, all DO and PC quarter milk samples will be frozen at -20 °C in the mastitis lab of the participating state. Laboratory culture will be conducted using the first of each duplicate pair of samples (S1) for each of the 2 sample types (DO, PC). Microbiologic procedures for isolation of bacteria from milk will be standardized across all labs and will be as defined by standard industry guidelines for mastitis diagnosis (NMC, 2017) (58). Following initial bacterial isolation, organism identification will be completed using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF Biotyper. Bruker Corp. Bremen, Germany). Results recorded for each sample will include farm, cow, quarter, sample type and date (DO, PC), date, bacterial growth (yes/no), colony count, and bacterial species identified.Data Analysis:Noninferiority analysis (67), mixed logistic regression, mixed linear regression, and/or Cox proportional hazards regression (survival analysis) will be conducted, as appropriate for the different outcome variables of interest, to describe the effect of treatment group (C-SDCT or A-SDCT versus BDCT) on quarter-level outcomes (e.g. cure rate, new IMI rate, risk for new IMI, prevalence of IMI after calving, clinical mastitis risk to 120 DIM), and on cow-level outcomes (e.g. DHIA test day SCC, milk yield, clinical mastitis risk, death or culling risk to 120 DIM).