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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