1294_VTEC discontools

8/11/2019 1294_VTEC discontools

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Jeppe Boel

Division of Microbiology and Risk AssesmentNational Food InstituteTechnical Universitiy of Denmark

Verotoxin producing E s c h e r i c h i a c o l i (VTEC)Discontools:

Joint Meeting of Working Package 2 and 3 Prioritisation & Gap Analysis, Monday, 10th May 2010


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2 DTU Food, Technical University of Denmark

Verocytotoxin/Shiga toxin-producing Escherichia

coli (VTEC/STEC) Expert Group

Coordinator: Alfredo Caprioli, Istituto Superiore di Sanit,Community Reference Laboratory for E. coli, Rome, Italy

Gaia Scavia, Dept. Veterinary Public Health, Istituto

Superiore di Sanit, Rome, ItalyEpidemiology, burden of human

disease (HUS) estimation, risk

factors

6

Jeppe Boel, National Food Institute , Technical University ofDenmark, Copenhagen, Denmark

Food Microbiology5

Jeffrey T. LeJeune, Ohio Agricultural Research and

Development Center, US

Laboratory, animal colonization,

farm ecology

4

Lothar H. Wieler, Veterinary Faculty, Freie University

Berlin, Germany

Laboratory, pathogenesis, animal

colonization

3

Roberto M. La Ragione, Veterinary Laboratories Agency(Weybridge), UK, Med-Vet-Net Deputy Coordinator

Laboratory, pathogenesis, animalcolonization

2

John M. Fairbrother, OIE Reference Laboratory for

Escherichia coli, Facult de mdecine vtrinaire,Universit de Montral, Saint-Hyacinthe, Canada

Laboratory diagnostics, animals1

ExpertField


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Escherichia coli

Normal bacteria in warm-blooded animals and humans

Normal bacteria in many types of raw food

Human diarrhoeageic E. co l i

Non-zoonotic

EnteroPatogenic E. co l i (EPEC)

EnteroToxin producing E. co l i (ETEC)

EnteroInvasive E. co l i (EIEC)

En t e r o A g g r e g a t i v e E. c o l i (EAggEC)

D i f f u se ly A d h e r e n t E. c o l i (DAEC)

"Zoonotic Verocytotoxin producing E. co l i (VTEC)

Shiga toxin producing E. co l i (STEC)

(Enterohamorrhagic E. co l i (EHEC))


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Re p o r t e d n o t i f i c a t i o n z o o n o s e s r a t e s i n

co n f i r m e d h u m a n c a se s i n t h e EU , 2 0 0 8 ,

EFSA zo o n o s i s r e p o r t


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Healty Verocells: with Verotoxin

VCA positiv

1977: Konowalchuk et al. discoveres a cytotoxin that kills

Verocells, a kidney cell line from the Green African Veromonkey


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VTEC

> 100 different O:H serotypes identified as VTEC> 100 different O:H serotypes identified as VTEC

Varies in human pathogenic potential: harmlessVaries in human pathogenic potential: harmless fatalfatal

O157 (O157:H7/O157:HO157 (O157:H7/O157:H--) most important serogroup) most important serogroup

Other important serogroups: O26, O91, O103, O111, O145Other important serogroups: O26, O91, O103, O111, O145

Virulence factors:Virulence factors:

VT production (VT1 and/or VT2)VT production (VT1 and/or VT2)

Locus ofLocus of EnterocyteEnterocyte Effacement (LEE): Type 3 secretionEffacement (LEE): Type 3 secretionsystem,system, IntiminIntimin ((e a ee a e),), TirTir,, EspsEsps etc.etc.

Virulence plasmidVirulence plasmid EnterohaemolysinEnterohaemolysin ((e h xe h xAA,, ToxBToxB etc)etc)

TCCP/TCCP/espJespJ (non(non--LEE encoded type IIILEE encoded type III effectoreffector protein)protein) Others EAST1 (toxin),Others EAST1 (toxin), EfaEfa, SAA (adhesion factor), SAA (adhesion factor)


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VTEC clinical picture in humansOnset of diarrhoea: Typically 2-4 days post ingestion

Watery diarrhoea 1-2 daysAbdominal cramps/light fever Recovery

Bloody diarrhoa 4-10 daysSevere abdominal cramps/no fever

Haemolytic uremic Syndrome (HUS):Characterized by acute renal failure, haemolytic anaemiaHUS develops in up to 10% of VTEC O157 patients

Fatality rates ranging from 1 to 5%

infectious dose of VTEC (O157; O111, O26) low, probably less than 100


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VTEC serogroups in patients in

Europe, 2008 (ECDC)


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Haemolytic Uremic Syndrome (HUS) by ageand serogroup in EU, 2008 (EFSA data)


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Main gaps human infections

I d e n t i f ic a t i o n o f t h e m i n im a l s e t o f v i r u l e n ce g e n e s/ f a c t o r s( v i r u l o m e ) r e q u i r e d f o r c au s i n g s ev e r e d i se a se in h u m a n s .

B e t t e r d i a g n o s t i c m e t h o d s f o r t h e i d en t i f ic a t i o n o f h um a n V TECi n f e c t i o n s .

B e t t e r s u r v e i l la n c e sy s t e m s , w i t h i n c l u s io n o f V TEC n o n - O 1 5 7 a n dd e f i n i t i o n o f t h e s e r o t y p e s / c lo n e s as so c ia t e d w i t h s ev e r e

d i se a se s ( H U S a n d b l o o d y d i a r r h e a ) .

Es t i m a t i o n o f t h e b u r d e n o f V T EC i n f e c t i o n s , i n c l u d i n g c o s t s , in t h e p o p u l a t i o n ; a t p r e s en t , i t i s a v a i la b l e o n l y f o r a f e w c o u n t r i e s .

Es t i m a t i o n o f t h e p o s s i b l e r o l e o f h u m a n s a s a r e s e r v o i r f o rs o r b i t o l f e r m e n t i n g V TEC O 1 5 7 a n d s om e VTEC n o n - O 1 5 7 ( e g ,

O 2 6 V T2 + v e ) p a t h o g e n i c c l o n e s?

Re se a r ch o n V T g e n e t i c v a r i a t i o n a n d e x p r e ss io n a n d o n t h ed i se a se s p o t e n t i a l o f t h e d i f f e r e n t t o x i n v a r i a n t s ; m e ch a n i s m s o fV T b l o o d t r a n s p o r t a t i o n d u r i n g H U S.


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VTEC animal reservoirsRuminants (cattle, sheep, goat, deer)

VTEC does not affect animals (with a fewexceptions)

Pigs and poultry: Not significant reservoirs


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VTEC: human infection routes

Foods: Beef meat (minced)

unpasteurized milk and by-products

unpasteurized juice (cider)Fresh produce incl. sprouts

All faecally contaminated products

Person to person transmission

Direct animal contact

Drinking water

Bathing (sea, lakes, swimming and paddling pools)

Both sporadic cases and large epidemic outbreaksMost outbreaks caused by VTEC O157


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Classical food borne VTEC outbreaks

Butchers shop (catering - gravy)400/1796 Skotland

O157

Sausage made of sheep meat18 cases/1

10 HUS cases

06: Norway

O103:H25

Sprouts10.000/1196, Sakai, JapanO157

Jack in the Box Hamburger700/493 Washington,Idaho, California,

Nevada, USA

O157

Hamburgers26/082 Oregon, USA

O157

SourceCases/No. of deathsOutbreak


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Prevalence of VTEC in ruminants (cattle) andmeat hereof the rough picture

VTEC

Faeces: Up to 100%?Hides at slaughter: Up to 100%Fresh meat of bovine origin Up to 40%

VTEC O157

Faeces, typically 3-10% (variation 0-100%)Hides at slaughter >10%-100%Fresh meat of bovine origin 0-5%

Other important O-groups: (O26, O91, O111, O103, O145)

Sparse amount of data


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Cattle and VTEC (O157)

VTEC incl. O157 can be isolated from mostcattle herds

No specific management factors have beenidentified to control the problem at herdlevel

Shedding is intermittent

Super shedders exists (>10E5 CFU pergram faeces)


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Tools to identify super shedders

Vaccination

Probiotics Phage therapy

Antimicrobials

Some of these options could also be used on the abattoir

Animals: Control options?


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Main gaps Animal infections

I n g e n e r a l , t o e x t e n d t h e k n o w l ed g e g a i n e d o n V TEC O 1 5 7 t o t h em a in p a t h o g e n i c V TEC n o n - O 1 5 7 s e r o g r o u p s .

B e t t e r u n d e r s t a n d i n g o f c o l o n i z a t i o n a n d p e r s i s t e n c e o f V T ECO1 5 7 a n d n o n - O1 5 7 i n r u m i n a n t s .

B e t t e r u n d e r s t a n d i n g o f t h e b i o l o g y o f t h e su p e r s h e d d e r p h e n om e n o n a n d o f t h e r o l e o f t h e se su b j e c t s in t h e in f e c t i o nc y c l e s .

B e t t e r u n d e r s t a n d i n g o f t h e i m m u n e r e s p o n s e i n a n im a ls ,

p a r t i cu l a r l y t o b a c t e r i a l s t r u c t u r e s t h a t c o u l d r e p r e s en t v a c c i n ec o m p o n e n t s .

Re se ach o n i n t e r - a n d i n t r a - f a r m sp r e ad o f V TEC: h o w h eo r g a n ism i s sp r e ad b e t w e en o n e f a r m t o t h e o t h e r , a n d h o wa n im a l s a r e e x p o se d w i t h i n a s in g l e f a r m . Be t t e r u n d e r s t a n d i n go f t h e e n v i r o n m e n t a l su r v i v a l .

Re se a r c h o n t h e u se o f p r o b i o t i cs a n d p h a g e t h e r a p y t o p r e v e n tc o l o n i z a t i o n .

M o d e l l i n g t h e co s t / b e n e f i t o f co n t r o l m e asu r e s i n t e r m o fr e d u c t i o n o f t h e b u r d e n o f V T EC i n f e c t i o n s i n h u m a n s .


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Main gaps: Food control

Ea s y a n d r a p i d t e s t s t a r g e t i n g t h e m a in V T EC n o n - O 1 5 7p a t h o g e n i c se r o g r o u p s a r e r e q u i r e d . V TEC t h a t a r e p r e s u m a b l y

p o o r l y v i r u l e n t t o h u m a n s a r e a b u n d a n t i n a n im a l s an d f o o d , so t h e

m e t h o d s s h o u l d b e t a r g e t e d t o t h e s e r o g r o u p s / c lo n e s m o s t

a ss o c i a t e d w i t h h u m a n d i se a se .

Ro l e o f v e g e t a b l es : s t u d i e s o n t h e i n t e r a c t i o n b e t w e e n b a c t e r i aa n d p l a n t o r g a n i s m s an d m o d e ls f o r c r o p co n t a m i n a t i o n v i a m a n u r e

a n d / o r i r r i g a t i o n .


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VTECVTEC

HP-

VTEC

O1570103

026

0111 ..

VTEC and Human Pathogenic VTEC?

Many food and

animals

isolates

Limited range ofseropathotypes


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Ruminants(cattle)

Meat(minced) Other foods

Dairyproducts

(unpast)

Humans

Other animals

Recreational

water

Drinking

water

Transmission of VTEC between reservoirs

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1294_VTEC discontools