Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
LG ANML CLIN SCI
Non Technical Summary
The prevalence of antimicrobial-resistant Salmonella Dublin (S. Dublin) infections in dairy cattle increased in the US and is perceived as a major health challenge in both the dairy and beef industries. Currently, no effective drug is allowed for treating this infection. Moreover, S. Dublin can cause fatal infections in humans. Thus, S. Dublin is also a public health concern due to the potential transmission of multi-resistant bacteria to humans. Therefore, reliable control strategies for S. Dublin are urgently needed in dairy farms. Vaccination of cows and calves could contribute to preventing and controlling S. Dublin in dairy herds. However, the only commercially available S. Dublin vaccine is licensed only for calves older than 2 weeks of age, but calves get infected before that time. Evidence regarding extra-label S. Dublin vaccination of younger calves or adult cows is scarce. Autologous vaccines could also be developed, but there is no evidence of their efficacy. Thus, we propose to (1) evaluate the effectiveness of potential extra-label usages of commercial and autologous vaccines to prevent and control S. Dublin infections in dairy farms, and (2) provide U.S. dairy stakeholders with the knowledge and tools needed to effectively control S. Dublin through evidence-based vaccination programs. Our project will fill the evidence and training gap to give dairy producers and veterinarians the tools needed to control this devastating infectious disease. Ultimately, this will result in lower antimicrobial usage and resistance, helping to ensure the long-term sustainability of US dairy production.
Animal Health Component
100%
Research Effort Categories
Basic
0%
Applied
100%
Developmental
0%
Goals / Objectives
The overall objective of this proposal is to reduce the devastating effects of S.Dublin infections on dairy production via optimization of vaccination protocols and training of relevant stakeholder groups. The prevalence of antimicrobial-resistant S.Dublin infections in dairy cattle increased in the US and is perceived as a major health challenge in both the dairy and beef industries. Vaccination of cows and calves could contribute to preventing and controlling S.Dublin in dairy herds. However, the efficacy of these approaches remains unexplored, leaving veterinarians and producers without tools to control and prevent S.Dublin successfully. Our research and extension group at Michigan State University actively supports sustainable food animal production through field-based projects that address veterinary and producer stakeholders' needs. This proposal is innovative because it will investigate extra-label usages of currently available vaccines and develop training materials that can be utilized immediately on dairy farms to limit the spread of S.Dublin. Thus, the proposed research addresses the "Crosscutting" AFRI Foundational Program Area and within the program area priority of "Critical Agricultural Research and Extension (A1701)" by producing results that lead to the establishment of evidence-based vaccination protocols that end-users can rapidly adopt to minimize the impact of S.Dublin to support efficient and safe dairy production. Furthermore, this will also contribute to reductions in therapeutical antimicrobial usage on dairy farms and the development of antimicrobial-resistant bacteria. We propose a combination of applied research, extension, and educational activities that will advance our understanding of the potential of vaccines to improve dairy cattle health. This will enhance cattle health and reduce economic losses and, therefore, increase the production efficiency and sustainability of the dairy industry.
Project Methods
We propose 3 aims to accomplish our objectives. Aim 1 will determine the extent to which vaccinating dry cows with an S.Dublin vaccine decreases in utero transmission and bacterial shedding at calving. For this, we will screen a total of 800 cows from 4 MI dairy farms with a history of S.Dublin in the previous 12 months for latent carrier status.At dry-off, latent carriers will be randomly allocated to receive either the commercial vaccine, the autologous vaccine, or placebo (0.9% NaCl). A booster of the vaccines will be administered 2 weeks after the initial dose. Cows in the placebo group will also receive another 2mL saline injection. At calving, samples of colostrum and feces will be collected from the dams by trained farm personnel and immediately kept frozen for subsequent microbiological analysis. Feces and colostrum samples will be analyzed for isolation, typification, and quantification of S. Dublin organisms following standardized protocols. To assess in utero transmission, a blood sample will be collected from all calves born to study cows before colostrum ingestion for quantification of antibodies against S.Dublin; and 9 bull calves born to latent carrier cows in each farm will be euthanized immediately at birth, kept frozen, and submitted to post-mortem examination. Samples from internal organs (liver, spleen, kidneys, and lymph nodes) will be harvested and subjected to microbiological analysis for isolation of S. Dublin. The results will be analyzed statistically via logistic regression to compare the likelihood of vertical transmission of S. Dublin and shedding of S. Dublin at calving among latent carriers that received the commercial vaccine, the autologous vaccine, and those that did not receive any vaccine. Furthermore, we will also compare the number of bacteria excreted in feces and colostrum among treatment groups cows via linear mixed models, ensuring homoscedasticity. Alpha will be 5%, and "farm" will be included as a random effect in all statistical models.Aim 2 will investigate the effectiveness of different vaccination strategies to improve newborn calf immunity against S.Dublin. Our hypothesis is that extra-label vaccination of pregnant cows and newborn calves will reduce disease severity and incidence. To test this hypothesis, we will conduct two trials: (1) a challenge study to determine the effect of the vaccination strategies on S. Dublin disease progression, and (2) a clinical efficacy trial in 5 commercial dairy herds to assess the effect of the vaccination strategies on calf health. For the challenge study, forty-two (42) newborn bull calves will be purchased from a commercial farm with no history of S. Dublin and housed in the MSU Beef Research Center for this challenge study. Colostrum will be sourced from cows in the farm of origin. Calves will be randomly allocated at birth to one of the following treatment groups (6 calves/treatment):Control: 4 L of quality-tested (Brix>22%) colostrum from non-vaccinated cows.Colostrum-LiveVaccine: 4 L of Brix>22% colostrum from cows vaccinated during the dry period with a commercial live vaccine as per Aim 1.LiveVaccine: 4 L of Brix>22% colostrum from non-vaccinated cows + S. Dublin intranasal live vaccine given at birth.Colostrum-LiveVaccine + LiveVaccine: 4 L of Brix>22% colostrum from cows vaccinated during the dry period with a commercial live vaccine + S. Dublin intranasal live vaccine given at birth.Colostrum-AutologousVaccine: 4 L of Brix>22% colostrum from cows vaccinated during the dry period with an autologous vaccine against the S. Dublin isolate used in the challenge.AutologousVaccine: 4 L of Brix>22% colostrum from non-vaccinated cows + S. Dublin intranasal autologous vaccine given at birth.Colostrum-AutologusVaccine + AutologousVaccine: 4 L of Brix>22% colostrum from cows vaccinated during the dry period with an autologous vaccine + S.Dublin intranasal autologous vaccine given at birth.At 10 days of age, all calves will be challenged orally with 1010 CFU of a field S. Dublin strain. Calves will then be subjected to health scoring twice daily to monitor disease progression (e.g., rectal temperature, respiratory distress, diarrhea, etc.). Ten days after the challenge, all calves will be euthanized and necropsied. A standardized scale, will be used to evaluate lesion severity. Also, the bacterial load among the different treatments will be compared using microbiological cultures. The results will be compared statistically among groups using linear mixed models, ensuring homoscedasticity. A repeated measures statement will be included when appropriate for outcomes variables measured repeatedly in the same animals. Tukey's honestly significant difference test will be used for pairwise post-hoc comparisons. Statistical significance will be declared at P < 0.05. For the clinical efficacy study, we will recruit 5 commercial Michigan dairy herds with confirmed S.Dublin infections in the last 12 months that do not currently vaccinate for S. Dublin. In each farm, 147 heifer calves will be randomly allocated at birth to one of the treatments outlined for the challenge study (21 heifers/treatment/farm). Farm staff will be blinded to treatment allocation. Heifers from all groups will be managed together following the established protocols in their herds and subjected to weekly health scoring from birth to weaning by the research team. Diagnosis and treatment of sick heifers will be completed following a standardized protocol. Morbidity and mortality data until 10 months of age will be collected from farm records.Morbidity and mortality risks among groups will be compared using cox proportional hazard models or a suitable survival analysis alternative if the proportional hazard assumption of the models is not met. Survival models will include "farm" as a factor to account for farm-to-farm variation. Weekly health scores will be compared using a linear mixed model with repeated measures using "calf" and "farm" as random effects. Homoscedasticity will be assessed and ensured through data transformation if required. Alpha will be 5% in all analyses.Aim 3 will concentrate our extension efforts by training the relevant stakeholders (veterinarians and dairy farm staff) in evidence-based control and prevention strategies. Collectively, these aims will provide the scientific evidence and the training needed for effectively reducing and controlling S.Dublin infections in dairy herds. For this, we will develop a multi-pronged extension program addressing S.Dublin management, including prevention and control via vaccination. This program will be composed of both online and in-person activities. Throughout this 3-year proposal, we will develop 2 different online training courses, one targeting veterinary professionals and another targeting dairy farm employees. Given that an important portion of the US dairy industry workforce is of Hispanic origin, the course targeting farm staff will be offered in English and Spanish. To increase our reach to dairy producers and veterinarians, we will organize in-person training workshops throughout the State of Michigan. These sessions will be used to engage dairy producers and veterinarians that prefer in-person demonstrations over online learning. These workshops will leverage the location and offices of the county-based MSU Extension Dairy Educators, which are already strategically assigned to the main dairying areas of Michigan. Veterinarians will receive continuing education credit for their participation in these activities.