Dr. Fabio Vannucci - Diagnostic Considerations in a Growth-Promoter Free Industry - Back to the...

Back to the future – Diagnostic considerations in a

growth promoters-free industry

Fabio Vannucci

Outline

• History

• EU experiences

o Disease incidence

• USA scenario

o Diagnostics

• USA and EU: compare/contrast

• Considerations for future scenarios

Overview

• 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

• 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

• 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

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



Denmark

- Production data: mortality, ADG, Feed conversion



- Overall trends on antimicrobial consumption (therapeutic use)

Sweden Norway



- Overall trends on antimicrobial consumption (therapeutic use)

Denmark Netherlands



- Age groupsSweden (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



- Antimicrobial classes (Denmark)



- Antimicrobial classes (Netherlands)

Switzerland



- Clinical signs, age group, # days and animals treated

• 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

OverviewAutolysis Non-autolysis

USA Scenario: Diagnostics

• 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)


• Enterotoxigenic Escherichia coli (ETEC)

OverviewUSA Scenario: Diagnostics

UMN-VDL: Enterotoxigenic E. coli 2010-2016 (n=2206)

Overview

F18F4

Neg

Others (F41, F5, F6)

F18.LT

F18.STb

F18.STX2eF4.LT

F4.STaF4.STb

F4. STa.STb

F4.LT.STa.STb

Weber et al (2016), 24th IPVS


UMN-VDL: Antimicrobial susceptibility (2006-2016)

Overviewβ-

hem

olyt

ic E

. col

i

Ampicillin

Enrofloxacin

Trimethoprim/SulphaGentamicinNeomycinFlorfenicol

Sulpha

Oxytetracycline

TiamulinChlortetracycline


• Brachyspiral colitis

Overview

“B. suanatina” Swine Swine dysentery-like“B. hampsonii” Swine Swine dysentery-like

Strongly

β-hemolytic

Weakly

β-hemolytic


UMN-VDL: B. pilosicoli isolation (2011-2016)

Overview

0

1

2

3

4

5

6

7

8

9

Num

ber o

f B. p

ilosi

coli


UMN-VDL: Antimicrobial susceptibility (2009-2013)


Sweden: Antimicrobial susceptibility (AGP free scenario)


• 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 22weeks

0

10

20

30

40

50

60

70

5 7 10 13 16 19 22weeks

Feca

l PC

RSe

rolo

gy

o Clinical presentation (Acute/Chronic/Subclinical)


• 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

Log 10

Law

soni

a in

trac

ellu

laris

bac

teria

/g fe

ces

Ct value

UMN-VDL

- One Log10 increase in LI load increases OR for a pig to have a low growth rate by 2 times


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

Ct v

alue

25%

34%

41%


Overview

UMN-VDL: Antimicrobial susceptibility


• 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

Overview

Europe United StatesWeaning age 28-30 days 21 daysPRRS status Neg (some countries) PosPig/farm density Low/variable HighLawsonia vaccine usage Low Widely usedCarbadox 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

• 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)

Outline

• Talking about additional regulation…

Considerations on future scenarios

©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 [email protected]

Date post:	12-Jan-2017
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Dr. Fabio Vannucci - Diagnostic Considerations in a Growth-Promoter Free Industry - Back to the...

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