Diagnostic Considerations in a Growth-Promoter Free Industry - Back to the Future - Dr. Fabio Vannucci, College of Veterinary Medicine, University of Minnesota, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA. More presentations at http://www.swinecast.com/2016-leman-swine-conference-material

1. Back to the future – Diagnostic considerations in a
growth promoters-free industry
Fabio Vannucci

2. Outline
• History
• EU experiences
o Disease incidence
• USA scenario
o Diagnostics
• USA and EU: compare/contrast
• Considerations for future scenarios
Overview

3. • Use of antimicrobial growth promoter (AGP)
- Late 1940s: Chickens fed with fermentation waste
from tetracycline production as a source of vit B12
OverviewHistory
- Better growth performance due to residual tetracycline: “Animal protein factor”
- Early 1950 (Cunha et al, Luecke et al):
o The effect of vitamin B12, animal protein factor and streptomycin on the growth of young pigs

4. • Use of antimicrobial growth promoter and antimicrobial resistance
OverviewHistory
- Inaction (UK and other EU countries): tylosin, spiramycin, avoparcin…
- Action (Sweden): consumers → Federation of Swedish Farmers → ban in 1986
- Mid 1960 (UK): Multi-drug-resistant salmonella
- “Sufficient sound basis for action”
- Recommendations for using on animal feed:
o Little or none application for therapeutic purposes in human or animals
o Not impair the efficacy of a prescribed therapeutic drugs through development of resistance
o Tylosin should be available only for therapeutic purposes

5. • Use of antimicrobial growth promoter and antimicrobial resistance
OverviewHistory
- Vancomycin (glycopeptide antimicrobial): discovered early 1960s
o 1980s: widely used in humans for treatment of resistant Gram positive bacteria
o 1993: Vancomycin resistant enterococci isolated from humans and animals (Bates et al 1993)
Not been used in food animal
o Cross-resistance with Avoparcin: commonly used for growth promotion in food animal
EU banned in 1997
- AGP termination
Sweden: 1986 Norway: 1995 Switzerland: 1999 Finland: 1999
Denmark: 2000 EU: 2006

6. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Indirect method for occurrence of disease
o Antimicrobial usage ONLY for therapeutic or preventive purposes (assumption after AGP ban)
o Recording antimicrobial usage for a given clinical syndrome
- Production data: mortality, ADG, Feed conversion
- Diagnostic data (lab accessions)
o High specificity but questionable sensitivity
o Confounders - emerging disease, surveillance, detection vs disease

7. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
Denmark
- Production data: mortality, ADG, Feed conversion

8. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Overall trends on antimicrobial consumption (therapeutic use)
Sweden Norway

9. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Overall trends on antimicrobial consumption (therapeutic use)
Denmark
Netherlands

10. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Age groups
Sweden (1986) – first 4 years after
o Increase post-weaning diarrhea
(> 1.5% mortality)
o 5-6 more days to reach 25 kg
o ↓ 1.5% feed efficiency in finishers

11. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Antimicrobial classes (Denmark)

12. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Antimicrobial classes (Netherlands)
Switzerland

13. OverviewEuropean experiences: disease incidence
• How to measure disease incidence (before/after AGP ban)?
- Clinical signs, age group, # days and animals treated

14. • Enteric pathogens after AGP ban
o Significant increase in diarrhea (nursery)
- Post-weaning diarrhea: β-hemolytic E. coli
- Spirochetal colitis (Brachyspira pilosicoli)
- Clinical ileitis
• ↓50-120g ADG
• ~ 7 additional days from weaning to 30Kg
OverviewEuropean experience: disease incidence
Weber et al (2016), 24th IPVS
1 days 5 days 2 weeks 3 weeks 5 weeks 10 weeks 28 weeks Adult
Escherichia coli
Brachyspiral colitis
Lawsonia intracellularis
Neonatal Nursery Finishing

15. Overview
Autolysis Non-autolysis
USA Scenario: Diagnostics

16. • Enterotoxigenic Escherichia coli (ETEC)
o Post-weaning diarrhea: β-hemolytic E. coli
o High morbidity and variable mortality
Overview
o Virulence
- Fimbria (F18, F4) + Enterotoxins (LT, STa, STb, EAST1, Stx2e, AIDA)
- Stx2e: Sudden death (CNS signs may be present)
USA Scenario: Diagnostics

17. • Enterotoxigenic Escherichia coli (ETEC)
OverviewUSA Scenario: Diagnostics

18. UMN-VDL: Enterotoxigenic E. coli 2010-2016 (n=2206)
Overview
F18F4
Neg
Others
(F41, F5, F6)
F18.LT
F18.STb
F18.STX2e
F4.LT
F4.STaF4.STb
F4. STa.STb
F4.LT.STa.STb
Weber et al (2016), 24th IPVS
USA Scenario: Diagnostics

19. UMN-VDL: Antimicrobial susceptibility (2006-2016)
Overviewβ-hemolyticE.coli
Ampicillin
Enrofloxacin
Trimethoprim/Sulpha
Gentamicin
Neomycin
Florfenicol
Sulpha
Oxytetracycline
Tiamulin
Chlortetracycline
USA Scenario: Diagnostics

20. • Brachyspiral colitis
Overview
“B. suanatina” Swine Swine dysentery-like
“B. hampsonii” Swine Swine dysentery-like
Strongly
β-hemolytic
Weakly
β-hemolytic
USA Scenario: Diagnostics

21. UMN-VDL: B. pilosicoli isolation (2011-2016)
Overview
0
1
2
3
4
5
6
7
8
9
NumberofB.pilosicoli
USA Scenario: Diagnostics

22. UMN-VDL: Antimicrobial susceptibility (2009-2013)
OverviewUSA Scenario: Diagnostics

23. Sweden: Antimicrobial susceptibility (AGP free scenario)
OverviewUSA Scenario: Diagnostics

24. • Proliferative enteropathy (ileitis): Lawsonia intracellularis
Overview
o Endemically distributed worldwide
o Classically affected growing-finishing pigs
0
10
20
30
40
50
60
70
2 5 7 10 13 16 19 22
weeks
0
10
20
30
40
50
60
70
5 7 10 13 16 19 22
weeks
FecalPCRSerology
o Clinical presentation (Acute/Chronic/Subclinical)
USA Scenario: Diagnostics

25. • Proliferative enteropathy (ileitis): Lawsonia intracellularis
o Clinical/subclinical PCR threshold to justify the treatment (?)
Overview
1.00E+00
1.00E+01
1.00E+02
1.00E+03
1.00E+04
1.00E+05
1.00E+06
1.00E+07
1.00E+08
1.00E+09
1.00E+10
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Log10Lawsoniaintracellularisbacteria/gfeces
Ct value
UMN-VDL
- One Log10 increase in LI load increases OR for a pig to have a low growth rate by 2 times
USA Scenario: Diagnostics

26. Overview
UMN-VDL: Lawsonia intracellularis PCR detection - 2013-2016 (n=3577)
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
10/3/2013 4/21/2014 11/7/2014 5/26/2015 12/12/2015 6/29/2016
Ctvalue
25%
34%
41%
USA Scenario: Diagnostics

27. Overview
UMN-VDL: Antimicrobial susceptibility
USA Scenario: Diagnostics

28. • Increasing of enteric bacterial infection (not much respiratory)
OverviewUSA and EU: compare/contrast
o Porcine Respiratory Disease Complex (PRDC)
- Success controlling primary triggers – vaccination, elimination
o Porcine Enteric Disease Complex (PEDC) – What the heck?
- Enteric bacteria as primary cause
- Synergism: Rotavirus – Clostridium perfringens, E.coli (?)
o Microbiome complexity

29. Overview
Europe United States
Weaning age 28-30 days 21 days
PRRS status Neg (some countries) Pos
Pig/farm density Low/variable High
Lawsonia vaccine usage Low Widely used
Carbadox Banned Widely used*
Zinc oxide Partial restrictions Widely used
USA and EU: compare/contrast
• Management/alternative strategies
• Systematic approach to measure disease incidence
• Scale matters

30. • AGP ban (EU)
– Enteric bacterial pathogens (diarrhea): When to act (?)
• Lawsonia PCR positive: “how much” to justify treatment (?) and for how long (?)
• Beta-hemolytic E coli with virulence factor + diarrhea
OutlineConsiderations for future scenarios
– Followed by additional regulation → Long term benefits
• Denmark (Yellow card regulations)
• Germany (DART, German Antibiotic Resistance Strategy)
• Netherlands (Netherlands Veterinary Medicines Authority - SDa)

31. Outline
• Talking about additional regulation…
Considerations on future scenarios

32. ©2014 Regents of the University of Minnesota. All rights reserved.
The University of Minnesota is an equal opportunity educator and employer.
• Dr. Peter Davies
• Dr. Connie Gebhart
• Dr. Julio Alvarez
AknowledgementsAcknowledgements
Fabio Vannucci
vannu008@umn.edu