Managing Salmonella Risk. Carl Heeder, DVM

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1 Managing Salmonella Risk Carl Heeder, DVM 1

2 Overview Levels of Disease Risk Management Disease Risk Equation Flock Immunity Exposure Risk Salmonella Challenge Data Salmonella enteriditis Salmonella heidelberg Key Points to Implement 2

3 Levels of Disease Risk Management Manage vs. Eradicate Disease Risk Manage IBV NDV LT IBD Marek LPAI Salmonella Control Principles Vaccination Limit Exposure Eradication HPAI END Control Principles Test Depopulate Extreme C&D 3

4 Disease Risk Balance Immunity High Risk Disease Risk Low Risk 1. Load 2. Virulence 4

5 Disease Risk Balance : Low Risk Immunity High Risk Disease Risk Low Risk 1. Load 2. Virulence 5

6 Disease Risk Balance: High Risk Immunity High Risk Disease Risk Low Risk 1. Load 2. Virulence Control what you can control: 1. Immunity 2. Load 6

7 Control the Load aka exposure to pathogens Cleaning and Disinfection Biosecurity Manage what comes onto your farm People Wild Birds Vectors Rodents Insects 7

8 Control Vectors Specifically for Salmonella control Rodents Flies Darkling Beetles 8

Rodents Rodent Droppings have been shown to have 10 4 10 6 salmonella per dropping.

9 Rodents Rodent Droppings have been shown to have salmonella per dropping.* Salmonella Challenge trial Typical Challenge trials use between salmonella * Davies RH and Wray C, Observations on disinfection regimens used on Salmonella enteritidis infected poultry units. Poultry Sci 74: (1995). 9

. Results 50 % of the flies became positive within 48 hours 30% of the flies were positive 15

10 Flies Peter Holt and Richard Gast USDA ARS Research Placed flies into a room with experimentally infect, SE, layer hens Monitored what happened to the flies.. Results 50 % of the flies became positive within 48 hours 30% of the flies were positive 15 days after introduction Flies can carry up to 10 4 Salmonella When 5 infected flies were fed to naïve hens 30% of the hens became positive 10

11 Darkling Beetles Darkling Beetles can be an issue on floor reared birds Much like flies these pests have been identified as vectors for a number of pathogens including Salmonella. 11

12 Control Your Flock s Immune Status Good Vaccination Technique Live Vaccines Keep vaccines alive Get the correct dose into each bird Get the vaccine into the correct part of the bird Killed Vaccines Proper Dose Correct injection technique Minimize Bird s Stress FLAW Feed Lighting Air Water 12

13 Vaccine Selection Live Vaccines Try to find one that is close to the wild type as possible. Apply Early Apply Often Killed Vaccines Specific Immunity Phage Type 13

14 Salmonella Vaccines Modified Live Vaccines Priming the System Stimulate GALT (Gut Associated Lymphoid Tissue) Cellular Immunity Inactivated Build Specific Immunity All commercial vaccines are currently labeled for 2 applications Who does 2 Killed Shots? 14

15 Field SE Challenge Trial Most of the US Layer industry uses only one dose of inactivated SE vaccine. While Poulvac SENDIB is labeled for two doses,we know most customers only use one dose. We designed a trial to investigate what type of protection would be seen when applied at the common practice of only one dose.. We also wanted to know what the result of a partial dose would be. This was meant to simulate a poorly administered dose. 15

16 Product Label Information Poulvac ST This vaccine is recommended for mass administration by spray to healthy chickens of 1 day of age, as an aid in the reduction of Salmonella enteritidis, Salmonella heidelberg or Salmonella typhimurium colonization of the internal organs, including the intestines and ceca. A second dose should be given at 2 weeks of age in the drinking water. Poulvac SENDIB An inactivated vaccine containing Salmonella enteritidis, phage types 4, 8 & 13a, infectious bronchitis virus and Newcastle disease virus. It is recommended for subcutaneous administration to healthy 12 week-old chickens as an aid in the reduction of Salmonella enteritidis colonization of the internal organs, including the reproductive tract and intestines, and as an aid in the prevention of the signs and lesions associated with Newcastle disease and infectious bronchitis. DOSE: Inject 0.3 ml (0.3 cc) subcutaneously using aseptic technique. Vaccinate only healthy birds. Administer two separate doses 3 to 4 weeks apart. 16

17 Study outline Treatment 3 Days 28 Days 11 Weeks 19 Weeks 20 Weeks No killed PV ST PV ST None Move Challenge 1/3 dose PV ST PV ST SE-ND-IB Move Challenge Full dose PV ST PV ST SE-ND-IB Move Challenge SPF controls None None None Ship Challenge Vaccinations all done by the one best crew member Leg band all birds in study Cages all on same row and alternating by treatment Serology taken at 11, 15, 20 weeks of age 17

18 18

Results 90% 80% 70% Internal Organ Pools : 10 6 Challenge Culture Positive b Unvaccinated b Percent Positive 60% 50% 40% 30% Industry Standard Program a* a 20% 10% 0%

19 Results 90% 80% 70% Internal Organ Pools : 10 6 Challenge Culture Positive b Unvaccinated b Percent Positive 60% 50% 40% 30% Industry Standard Program a* a 20% 10% 0% Full Dose Third Dose No Inactivated SPAFAS Treatment Group * Different letters denote statistical difference p< Data on file, Study Reports AQO Zoetis Inc.

20 Salmonella Grp D GMT by Treatment Group Grp D Titer Live Prime 4 Weeks post Injection 7 Weeks Post injection No Inactivated /3 dose Full Dose Full Doses

21 How good is good enough? logt LKS 1 0 GMT=250? GMT=1000? Higher ELISA titers were found to be significantly related to higher protection (p value<0.05) as indicated by liver/kidney/spleen, however the predictive value was low with an R 2 = Data on file, Study Reports AQO Zoetis Inc. 21

22 In-house direct comparison studies of all three ST vaccines Cookson, K.C. and H. Fan. A comparison of 3 live salmonella vaccines against group C and D salmonella challenge. 51st WPDC, pp.12-13,

23 Comparison study design ST Vaccines day one spray, d.14 drinking water Poulvac ST (Single Gene Deletion) Product DGD (Double Gene Deletion) Challenge isolates orally at day 42, re-isolation at 49 days S. kentucky S. enteritidis 23

24 Results- S. kentucky Challenge Product DGD 24

25 Results- SE Challenge Product DGD 25

26 Comparison studies Product DGD only gave internal organ protection, despite the same label recommendations as Poulvac ST -- all vaccines were potent based on titration Under identical conditions, Poulvac ST gave the best protection against both S. enteritidis and S. kentucky 26

27 Compatibility of Two Live ST Vaccines and SubQ Gentamicin as Measured by ST Challenge UC-Davis School of Veterinary Medicine Andres Montoya and Pat Wakenell,

28 Two Doses of Poulvac ST With SubQ Gentamicin Show Significantly Better Internal Organ Protection 100 A % Re-isolation C C C B 0 Poulvac ST DOA / 2 Wk Poulvac ST DOA+GM / 2 Wk Product DGD DOA / 2 Wk Product DGD DOA+GM / 2 Wk No Vaccine DOA Hatchery Spray; 2 Weeks - Water 28 Different subscripts indicate significant differences P<0.05

29 Two Doses of Poulvac ST With SubQ Gentamicin Show Significantly Better Intestinal Protection % Re-isolation C Poulvac ST DOA / 2 Wk BC Poulvac ST DOA+GM / 2 Wk B Product DGD DOA / 2 Wk A Product DGD DOA +GM / 2 Wk A No Vaccine DOA Hatchery Spray; 2 Weeks - Water 29 Different subscripts indicate significant differences P<0.05

30 Two Doses of Poulvac ST With SubQ Gentamicin Show Significantly Better Cecal Protection 100 A A BC B % Re-isolation C Poulvac ST DOA / 2 Wk Poulvac ST DOA+GM / 2 Wk Product DGD DOA / 2 Wk Product DGD DOA +GM / 2 Wk No Vaccine DOA Hatchery Spray; 2 Weeks - Water 30 Different subscripts indicate significant differences P<0.05

31 Summary of Gentamicin Compatibility Study Poulvac ST gives significantly better intestinal and cecal protection than Product DGD Comparison of groups not receiving gentamicin Poulvac ST immunized successfully even when gentamicin was given subq on the same day Highly significant resistance to DT-104 challenge (P<0.001) No compromise in internal organ protection Intestinal/cecal protection was not significantly compromised Product DGD plus same-day gentamicin resulted in no intestinal or cecal protection 31

32 Final Comments Poulvac ST in the hatchery is the best option when gentamicin is also being given subcutaneously Advantage of controlled day of age spray vs. 2-3 day field vaccination Advantage of earliest possible ST vaccination Aro-A deletion does not persist in the environment or the bird 32

33 Poulvac ST vaccination & challenge model In-house study methodology SPF leghorns raised in isolator units Poulvac ST vaccination Day of age coarse spray Drinking water at 2 weeks of age Salmonella virulent challenge Oral challenge at 6 weeks of age Re-isolation from organs 1 week later Compilation of several studies 33

34 Poulvac ST effect on Internal Organ colonization by serotypes B, C and D vaccinated controls 100 Percent Positive ST S. heidelberg SE S. hadar S. kentucky Data on file, Study Reports TIA#20061, TIA#22497, B Phase4A&B, Zoetis Inc. 34

35 Poulvac ST effect on Cecal Pouch colonization by serotypes B, C and D vaccinated controls 100 Percent Positive ST S. heidelberg SE S. hadar S. kentucky Data on file, Study Reports TIA#20061, TIA#22497, B Phase4A&B, Zoetis Inc. 35

36 SH Challenge Trial Design 29 Week Challenge Salmonella Heidelberg Birds vaccinate with 2 Poulvac ST, 3 and 28 days of age Poulvac SENDIB 11 weeks 11 and 15 weeks # Isolator Tx Material Dose Vol. 10 week injection 14 week injection Challenge Dose Birds per Isolator* Units* Total Birds T01 Commercial Full dose Poulvac SENDIB 0.30 ml 1 dose IM-L N/A 1x10 6 cfu/bird T02 Commercial Two doses Poulvac SENDIB 0.30 ml 1 dose IM-L 1 dose IM-R 1x10 6 cfu/bird T03 SPAFAS N/A N/A N/A Controls 1x10 6 cfu/bird Abbreviations: Tx = Treatment; IM-L/R = Intramuscular-left(right) breast. Data on file, Study Reports AQO Zoetis Inc

37 Trial Results For the cecum, both the single and double dose of Poulvac ST showed significantly lower positive for Salmonella than the SPAFAS non-vaccinated challenged controls. % Positive Ceca Culture 50.0% 45.0% 40.0% 35.0% 30.0% 25.0% 20.0% 15.0% 10.0% 5.0% 0.0% b a a* One Dose Two Doses SPAFAS Non vaccinated birds were 16 times more likely to be positive than single dose birds 37 * Different letters denote statistical difference p<.05 Data on file, Study Reports AQO Zoetis Inc.

38 Control the Controllable Manage Flock Immunity Minimize bird stress Ensure good vaccine procedures Inspect what you expect PVE & Crew Serology Manage Exposure Good Biosecurity Clean Control Vectors Mice Flies/Beetles 38

39 Key Take Home Message Any vaccine program can be overwhelmed Control the Controllable Exposure Immunity More than just antibody level Poulvac ST Cross Protection Poulvac SENDIB Protects against SE challenge Phage Type Specific Inspect what you expect 39

Salmonella Control Programs in the USA

Salmonella Control Programs in the USA Hector Cervantes, DVM, MSc, DACPV, Hon. MAM Senior Manager Poultry Veterinary Services Adjunct Prof. of Avian Medicine College of Veterinary Medicine University of