1. What we know (and don’t know) about pneumonia in beef calves prior to weaning David R. Smith, DVM, PhD Mississippi State University College of Veterinary Medicine

2. Is pneumonia an emerging disease of pre-weaned beef calves? Where do emerging diseases come from? System Dynamics Emergence of a novel agent Acquire new virulence factors Introduction into a new geo-political region Emergence of a known, previously controlled, agent Emergence of a susceptible host (genetic, nutritional …) Emergence of a production system that favors a particular pathogen Increased Awareness Mitigation of a disease of greater impact Social interest –everyone’s suddenly talking about it…

3. Pre-Weaning Pneumonia in Beef Calves

4. Host-pathogen interactions Population dynamics

5. Bovine Respiratory Disease Recent NAHMS surveys confirm that BRD is the leading cause of mortality in U.S. feedlot cattle, weaned dairy heifers, and nursing beef calves 3 weeks of age or older –all classes of cattle BRD deaths alone cost producers over $643 million annually (2010 estimate, USDA NASS) Thus BRD has a significant impact on the profitability of cattle operations and on the health and welfare of cattle

6. Cost of pre-weaning pneumonia

7. JAVMA, Vol 243, No. 4, August 15, 2013 538-547 Objective—To identify herd-level risk factors for bovine respiratory disease (BRD) in nursing beef calves. Design—Population-based cross-sectional survey. Sample—2,600 US cow-calf producers in 3 Eastern and 3 Plains states. Results –Bovine respiratory disease had been detected in at least 1 calf in 21% of operations

8. JAVMA, Vol 243, No. 4, August 15, 2013 538-547 “Detection of BRD in calves was significantly associated with large herd size, detection of BRD in cows, and diarrhea in calves. Calving season length was associated with BRD in calves in Plains states but not Eastern states. Cumulative incidence of BRD treatment was negatively associated with large herd size and examination of cows to detect pregnancy and positively associated with calving during the winter, introduction of calves from an outside source, offering supplemental feed to calves, and use of an estrous cycle synchronization program for cows.”

9. AABP Research Summaries, Milwaukee, WI. Sept 19, 2013 A survey of veterinarians in 6 U.S. states regarding their experience with nursing beef calf respiratory disease Amelia R. Woolums, Roy D. Berghaus, David R. Smith, Brad J. White, Terry J. Engelken, Max B. Irsik, Darin K. Matlik, A. Lee Jones, Isaiah J. Smith Results Respondents reported that 18% of their cow-calf clients had nursing calf BRD in the previous year, with 5% of their cow-calf clients having 5% or greater incidence, and 14% of their clients having at least one calf die of BRD.

10. AABP Research Summaries, Milwaukee, WI. Sept 19, 2013 A survey of veterinarians in 6 U.S. states regarding their experience with nursing beef calf respiratory disease Amelia R. Woolums, Roy D. Berghaus, David R. Smith, Brad J. White, Terry J. Engelken, Max B. Irsik, Darin K. Matlik, A. Lee Jones, Isaiah J. Smith Results From a list of possible risk factors for nursing calf BRD, at least 50% of respondents selected “weather”, “inadequate colostrum consumption”, “introducing new cattle”, “failure to give nursing calves BRD vaccines”, “failure to give cows BRD vaccines”, “calf diarrhea in the herd”, “vitamin/mineral deficiency for cows/calves”, “protein/energy deficiency for cows/calves”, “BVDV PI cattle in the herd”, and “calving cows and/or heifers in confinement” as contributing to nursing calf BRD. Component causes!

11. Component causes Disease is not observed until the sum of component causes complete a sufficient cause The agent may be necessary for disease The agent alone may not be sufficient to cause disease Sufficient cause 1Sufficient cause 2Sufficient cause 3…

12. Infection is common but disease is rare Until something makes the system “unstable” –then an apparent disease outbreak Complete a sufficient cause Introduce a new risk factor e.g. Bovine respiratory disease complex e.g. Salmonella Loss of herd immunity Age (e.g. neonatal calf diarrhea) Immunosuppression Remove antigenic challenge (e.g. stop vaccinating)  Disease control programs may create naïve subpopulations – susceptible to outbreaks! eg. BVDV Component Causes Explain Endemic Stability

13. Time dependent factors of the production system affect pathogen exposure and the immune response Passive immunity Age Pathogen survival Pathogen exposure Stressors Nutrition Parasitism Pregnancy Weaning Surgery Mud Heat Cold Nutrition, Genetics… Commingling

14. Immunity Exposure Time Exposure and immunity as a function of time BRD in Pre-weaned Calves: When and Why?

15. Agents

16. Immunity Active immune response PassiveAcquired Antibodies from colostrum Age

17. ImmunityPassive Age T 1/2 of antibodies from colostrum is 16 days Roth. 2009. Current Vet Therapy Food Anim Pract

18. Immunity Antibodies from colostrum Age T 1/2 of antibodies from colostrum is 16 days Roth. 2009. Current Vet Therapy Food Anim Pract 2048 512 128 Initial antibody titer

19. Immunity Active immune response Age The immune system is functional, but unprimed, at birth Prior to 5-8 months of age the immune response is weaker, slower, and easier to overcome. Cortese. 2009. Vet Clin NA, 25(1)221-227

20. Kirkpatrick JAVMA, Vol 233, No. 1, July 1, 2008

21. Kirkpatrick et al. JAVMA, Vol 233, No. 1, July 1, 2008 Early: 67d, 190d Late: 167d, 190d

22. Kirkpatrick et al. JAVMA, Vol 233, No. 1, July 1, 2008 Early: 67d, 190d Late: 167d, 190d

23. Age and immunity to BRD Incidence of BRD by age 14 years Pre-weaning data 14,792 steer calves Surviving to feedlot finish Smith DR. 2013. Unpublished

24. Pre-weaning BRD Herd 1 Age distribution of 87 pneumonia cases from among 296 pre-weaned calves from a Nebraska ranch 29% cumulative incidence

25. Pre-weaning BRD Herd 2 Age distribution of 49 pneumonia cases from among 255 pre-weaned calves from a Nebraska ranch 19% cumulative incidence

26. Pre-weaning BRD Herd 3 Age distribution of 96 summer pneumonia cases from 2,065 calves born over a 4 year period. 5% cumulative incidence

27. Pre-weaning BRD Herd 4 Age distribution of 138 summer pneumonia cases from 630 calves born in 2012 22% cumulative incidence

28. 110,412 calves 20 years

29. “…there seem to be two periods of increasing BRD transmission rate (0 to 20, and 70 to 100 d of age)…. Epidemiological studies of these phases may lead to management alternatives to decrease BRD incidence.” Snowder et al. 2005. J Anim Sci 110,412 calves 20 years

30. “The greater incidence between 75 and 170 d of age may be partially attributed to increased commingling of animals during the breeding season when cows were frequently gathered for AI.” Snowder et al. 2005. J Anim Sci 110,412 calves 20 years

31. Herd immunity Transmission is hindered because a majority of animals are immune –inefficient transmission means the pathogen may “die out” (R 0 <1) before everyone is exposed Results in protection of susceptible animals within the group Better to be the susceptible calf within a pen of well-immunized cattle, than the only one vaccinated For this reason successful vaccine programs are “group-based”

32. BRSV SN titers 179 calves serially sampled As calves in the population age the distribution of titers shifts to the left Leaving a smaller proportion of calves protected and a larger proportion of calves susceptible Data provide by A Woolums

33. BRSV SN titers 179 calves serially sampled As calves in the population age the distribution of titers shifts to the left Leaving a smaller proportion of calves protected and a larger proportion of calves susceptible Data provide by A Woolums

34. BRSV SN titers 179 calves serially sampled As calves in the population age the distribution of titers shifts to the left Leaving a smaller proportion of calves protected and a larger proportion of calves susceptible Data provide by A Woolums

35. Epidemic Curve Herd 1 Epidemic curve of BRD in Herd 1. Lines represent the proportion of calves at least 100 or 120 days of age each week.

36. Epidemic Curve Herd 2 Epidemic curve of BRD in Herd 2. Lines represent the proportion of calves at least 100 or 120 days of age each week.

37. Epidemic Curve Herd 4 Epidemic curve of BRD in Herd 4. Lines represent the proportion of calves at least 100 or 120 days of age each week.

38. Age and immunity to BRD Incidence of BRD by age 14 years Pre-weaning data 14,792 steer calves Surviving to feedlot finish Smith DR. 2013. Unpublished

39. Age and BRD by year Mean days of age at BRD treatment = 89.4 Median = 91.4 14 years Pre-weaning data 14,792 steer calves Surviving to feedlot finish Error bars = 1 stdev Smith DR. 2013. Unpublished

40. BRD by year 14 years Pre-weaning data 14,792 steer calves Surviving to feedlot finish Significant differences by year in BRD cumulative incidence Smith DR. 2013. Unpublished

42. Ranch vs Feedlot BRD Incidence of BRD on the ranch appeared unrelated to incidence of feedlot BRD Smith DR. 2013. Unpublished Line of equivalence Ranch incidence greater Feedlot incidence greater

43. Ranch vs Feedlot BRD Some years calves with BRD on the ranch were at greater risk for BRD in the feedlot, some years it was the opposite. Smith DR. 2013. Unpublished

44. Calf gender is associated with BRD risk 5,078 calf records from 4 ranches and 20 management groups. Adjusting for age of the dam, heifer calves were less likely (OR = 0.83) and bull calves more likely (OR = 1.46) than steers to develop BRD prior to weaning (p=0.01)

45. Age of the dam is associated with BRD risk 5,078 calf records from 4 ranches and 20 management groups. Adjusting for gender, compared to calves born to cows 4 years or older, calves with two year old dams and 3 year old dams had 1.67 and 1.11 times greater odds for BRD (p=0.0004)

46. Conclusions from ranch BRD outbreak investigations Calf level characteristics: Age of the dam affects BRD risk Gender of the calf may affect BRD risk Herd level characteristics: Two patterns of occurrence of pneumonia sporadically in young calves large sudden outbreaks in older calves

47. Conclusions from ranch BRD outbreak investigations The explanation of these two patterns may be: failure of passive transfer resulting in more sporadic cases in very young calves Loss of herd immunity resulting in outbreaks of pneumonia in older calves.

48. Conclusions from ranch BRD outbreak investigations Herd immunity (or lack of it) may play an important role in the occurrence of pneumonia in ranch calves. Increased incidence of BRD in calves ~90-150 days of age Sudden outbreaks of BRD when a large portion of the herd is in this age range Lose endemic stability Susceptible = potentially infective resulting in overwhelming exposure Other time related environmental/management factors may affect pathogen exposure and host susceptibility

49. Acknowledgements Amelia Woolums, UGA Dale Grotelueschen, UNL GPVEC Suzanne Genova, MSU Russ Daly, SDSU Gerald Stokka, NDSU Al Doster, Dustin Loy, Bruce Brodersen UNL VDC Many ranchers and veterinarians throughout the US A contribution of the Beef Cattle Population Health Program at Mississippi State University. Supported by the Mikell and Mary Cheek Hall Davis Endowment for Beef Cattle Health and Reproduction. Supported in part by a grant from Zoetis