Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
0Activity
0 of .
Results for:
No results containing your search query
P. 1
EHEC

EHEC

Ratings: (0)|Views: 1 |Likes:
Published by boboyoyot
Enterohaemorrhagic E. coli (EHEC) is a bacterium that can cause severe foodborne disease
Enterohaemorrhagic E. coli (EHEC) is a bacterium that can cause severe foodborne disease

More info:

Published by: boboyoyot on Mar 05, 2013
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

03/05/2013

pdf

text

original

 
National Reference Laboratory for Escherichia coli, Federal Institute for Risk Assessment, Berlin, Germany
Emerging Enterohaemorrhagic
Escherichia coli 
, Causes and Effects of the Rise of aHuman Pathogen
L. Beutin
Address of author: National Reference Laboratory for Escherichia coli (NRL-E.coli), Federal Institute for Risk Assessment(BfR), Diedersdorfer Weg 1, D-12277 Berlin, Germany; Tel.: +49 30 8412 2259; fax: +49 30 8412 2983;E-mail: l.beutin@bfr.bund.deReceived for publication November 10, 2004
Summary
Shiga toxin (Stx) [Verotoxin (VT)]-producing
Escherichia coli 
(STEC), also called enterohaemorrhagic
E. coli 
or VTEC areemergingzoonoticagentsandbecamemostimportantashumanpathogens, particularly in the industrialized countries. Produc-tion of cytotoxins, also called Stx or VT, is the major patho-genicity determinant of STEC, which can cause life-threateninghaemorrhagic diseases in humans. The spectrum of STECphenotypes is diverse and domestic and wildlife animals con-stitute important reservoirs for these bacteria. STECare spreadfrom animal faeces to the environment, water and food. Inges-tionofcontaminatedfoodstuandwater,aswellascontactwiththe environment, STEC-excreting animals or humans are themajor sources of human infection. Economical changes in ani-malandfoodproduction,alterationofconsumerhabitsandlackof specific immune response, particularly in urbanized popula-tions, have contributed to the recent spread of STEC as a zoo-notic agent. Supranational surveillance networks as well asnational reference laboratories as sentinels play an importantroleinthepreventionandcontrolofSTECinfectionsinhumans.Developmentofnewvaccinesandprobioticsmayserveasfuturetools to control the spread of STEC in animals and humans.
Introduction
Among the pathogenic
Escherichia col
types, enter-ohaemorrhagic
E. col
(EHEC) became most important ashuman pathogens, particularly in the industrialized countrieswith moderate climate. The rapid increase of human EHECinfections reported in the last decades has alarmed publichealth authorities and has raised a debate on the microbiolo-gical safety of food of animal origin, which is often incrim-inated as source of EHEC transmission to humans. Thereasons for the recent emergence and rapid spread of EHECinfections in different parts of the world were investigated fordifferent aspects and are far from being fully recognized.Current data indicate that manifold factors contribute to thechange in emergence of these bacterial pathogens and the aimof this review is to present some of the most important criteriawhich could have contributed to the spread of these pathogens.
Nomenclature
Enterohaemorrhagic
E. col
were defined as a subgroup of Shiga toxin (Stx)-producing
E. coli 
(STEC) which wereknown to cause haemorrhagic colitis (HC) and haemolyticuraemic syndrome (HUS) in humans (Levine, 1987). TheEHEC prototype strain,
E. coli 
O157:H7, became firstknown as a human pathogen in 1982 as causative agent infoodborne-outbreaks associated with consumption of undercooked beef (Riley et al., 1983). EHEC were definedas STEC showing similar clinical, epidemiological andpathogenic features as the EHEC prototype strain,
E. col
O157:H7 (Levine, 1987). Later, the term EHEC was used forthose STEC which have been demonstrated to causediarrhoea in humans (Anonymous, 1997) and it wasproposed to divide EHEC into
Ô
typical
Õ
and
Ô
atypical
Õ
according to the presence of other virulence attributes suchas the
eae
gene for bacterial intimate adherence and theplasmid located E-
hlyA
gene encoding production of enterohaemolysin (Nataro and Kaper, 1998). The divisionof Stx-producing strains into STEC and EHEC is notvery clear-cut, because it is not proved if any of thenaturally occurring STEC strains are apathogenic forhumans. To avoid confusion in nomenclature, the termSTEC will be used for all types of Stx-producing
E. coli 
inthis review.On the other hand, it is certain that STEC strains showconsiderable differences regarding their virulence and patho-genicity. The absence of virulence markers such as the
eae
-gene does not necessarily indicate that these strains possess alower virulence for humans (Paton et al., 1999). Apart fromSTEC O157:H7, certain other STEC types which representclonal groups, such as motile and non-motile strains of O26:[H11], O103:H2, O111:[H8] and O145:[H28] were associ-ated with increased virulence for humans and were morefrequently associated with HC and HUS than other STECtypes. Besides this well known
Ô
gang of five
Õ
, other emerginghighly virulent STEC types such as O118:[H16] andO121:[H19] were identified more recently (Maidhof et al.,2002; Tarr et al., 2002). The continuous evolution of thesepathogens is triggered by selective pressure from the hostimmune system and from the environment. It was demonstra-ted that STEC undergo frequent genetic rearrangements intheir chromosome, their virulence plasmids,
stx
-phages and inthe LEE pathogenicity islands coding for the attaching andeffacing (A/E) phenotype (Brunder et al., 1999; Beutin et al.,2005; Garrido et al., 2006). The future emergence of newgenetic variants of highly virulent STEC clones is thereforevery likely.
U. S. Copyright Clearance Center Code Statement:
09311793/2006/53070299$15.00/0 www.blackwell-synergy.com
J. Vet. Med. B
53,
299–305 (2006)
Ó
2006 The AuthorJournal compilation
Ó
2006 Blackwell Verlag, BerlinISSN 0931–1793
 
Virulence Factors
Shigatoxin-producing
E. coli 
and EHEC are characterized byproduction of Stx also called Verotoxins (VT). STEC (VT-producing
E. coli 
) strains can produce one or more differenttypes of Stx. Stx are
-glycosidases, enzymes which inhibitprotein synthesis in eucaryotic cells leading to cell death, tissuedamage and organ failure (Paton and Paton, 1998). The genesfor production of major Stx-types, called Stx1 (VT1) and Stx2(VT2), are located on the genome of temperate lambdoidbacteriophages, which are integrated in the chromosome of thebacteria.
Stx
phages can be induced to the lytic cycle and freephages can infect other bacteria resulting in horizontal genetransfer of 
stx
genes to
E. coli 
and other Enterobacteriaceae asshown by
in vivo
and
in vitro
experiments (Herold et al., 2004).As a consequence, the diversity of 
E. coli 
strains which areassociated with production of Stx is high and new STEC typesare still detected. Today, more than 200
E. col
serotypesrepresenting numerous STEC-clones are described (http://www.microbionet.com.au/vtectable.htm).Since the first description of Stx, a growing number of genetic variants of the prototype toxins Stx1 and Stx2 havebeen described (Scheutz et al., 2001). Human diseases causedby STEC show a broad spectrum, ranging from mild diarrhoeato HC and HUS. Primarily the production of Stx2 as well asthe presence of the
eae
gene encoding intimate adherence of thebacteria to the intestinal mucosa were associated withincreased virulence of STEC producing strains and with severeclinical manifestation (Boerlin et al., 1999; Friedrich et al.,2002, 2003; Beutin et al., 2004; Ethelberg et al., 2004). Othertoxin variants, such as Stx1c, Stx2-O118 and Stx2e wereassociated with more uncomplicated cases of diarrhoea(Friedrich et al., 2002, 2003) and newly described toxin typessuch as Stx1d, Stx2g and Stx2-NV206 have not yet beenexplored for their role in human pathogenicity (Bertin et al.,2001; Burk et al., 2003; Leung et al., 2003).
Disease Spectrum
The magnitude and the severity of STEC infections in humansand the impact of these pathogens on public health was thesubject of four international WHO consultations on foodborneand zoonotic aspects and on prevention and control between1994 and 1998 (Anonymous, 1995, 1996, 1997, 1998). Thespectrum of disease caused by different STEC is varying andhuman asymptomatic carriers as well as long-term excretorsare not infrequent in adults who were in contact with STEC-infected patients. Children and the elderly were identified asmajor risk groups for developing severe disease such as HUSand thrombotic thrombocytopenic purpura as sequelae fromSTEC infections (Taylor and Monnens, 1998). In consequence,surveillance of enteric HUS was established in many countriessince it was shown to be a reliable indicator for STECinfections in the human population. HUS is the major cause of acute renal failure in children and >90% of HUS cases arecaused by infections with STEC (Mahon et al., 1997).Although enteric infections with STEC are today notifiablein many countries their surveillance is still limited due tosuboptimal detection systems and in consequence to underre-porting. Epidemiological studies from different countries haveshown that diverse types of STEC may infect and cause illnessin humans and detection of 
stx
genes or production of Stx isthe only way to identify all types of STEC in any kind of sample (Bettelheim and Beutin, 2003). However, not all of surveillance systems established worldwide are based ondetection of Stx or the underlying genes and some nationalsurveillance programmes are more restricted only to identifi-cation of STEC O157, which is carried out by screening forphenotypical traits such as serotype and absence of sorbitolfermentation.
Type Spectrum
Remarkable differences were observed in the type spectrum of STEC isolated from humans in different countries. Oneexplanation could be that the identification and isolationmethods used in diagnostic laboratories differ largely forsensitivity and specificity. Sporadic infections with non-O157STEC types are frequent in many countries but are often notdetected due to inadequate testing methods. As a consequencesurveillance of these pathogens is less developed than for STECO157 (Mead et al., 1999; Anonymous, 2006). Only a fewreference laboratories worldwide have established the method-ologies for complete serotyping of O and H antigens of 
E. coli 
and it can be assumed that only a minor fraction of STECisolates from routine diagnostic laboratories are investigatedfor their serotypes and their virulence attributes. This practicemay result in delayed or in lack of detection of new emerginghuman pathogenic STEC types with the consequence thatadequatepreventionmeasuresarenottakeninatimelyfashion.The role of 
E. coli 
reference laboratories has proved to becrucial in detection of human infections with sorbitol-non-fermenting STEC O157:H7 in the USA in 1982 and 10 yearslater in detection of sorbitol-fermenting STEC O157 inGermany (Riley et al., 1983; Gunzer et al., 1992). Despitethe bias resulting from the use of STEC detection methods,which are not well comparable for their specificity andsensitivity, there is a considerable difference between countriesfor the frequency of human cases infected with these agentsand for the predominant types of STEC in different geograph-ical regions. The investigation of the animal reservoir for thepresence and type spectrum of STEC is important to monitortrends of emergence of known and new types of STEC, whichcan cause infections in humans. As an example, STECO118:[H16] became first prevalent in healthy and diarrhoeiccattle in Germany in 1989 and have emerged as humanpathogens since 1996. Most of the human infections wereassociated with a rural environment and direct transmissionfrom animals to humans was demonstrated (Wieler et al.,1996; Beutin et al., 2000). STEC isolates from cattle andhumans were found to be genetically closely related belongingto a clonal type which is widespread in Europe and SouthAmerica (Maidhof et al., 2002; de Castro et al., 2003).
Animal and Environmental Reservoir
Epidemiological analysis of outbreaks with EHEC O157revealed cattle as a major animal reservoir for these pathogens(Karmali, 1989). Until today, an increasing number of domestic and wildlife animal species, in particular ruminants,have been identified as natural reservoirs and sources of STECinfections (Caprioli et al., 2005). Over the last two decades,STEC were identified in almost all geographical regions of the
300 L. Beutin
 
world. Direct and indirect animal contact was identified asimportant transmission route for STEC in the environmentfollowed by person to person spread of STEC as second mostimportant way of transmission (Anonymous, 1997; Meadet al., 1999). As a consequence of faecal shedding of STEC byanimals, the degree of environmental contamination with thesebacteria is important. Studies have shown that EHEC O157may persist as viable bacteria in animal faeces over more than20 months and contamination of soil with effluents fromagriculture, abattoirs and sewage water is important partic-ularly in areas with high density of cattle and other domesticanimals (Maule, 2000). Contamination of farmland soilassociated with contamination of surface and drinking waterresulted in human infections from environmental sources asdemonstrated in numerous cases (Williams et al., 2005).Water-borne outbreaks have gained importance and countfor 9% of 350 outbreaks in the USA, which were notifiedwithin a 20-years time period (Rangel et al., 2005). Extremeweather conditions such as heavy rainfall and elevated airtemperatures were related to increased water-borne outbreakswith STEC O157 and other bacteria (Thomas et al., 2006) andSTEC infections were generally found to increase in the warmseason (Barkocy-Gallagher et al., 2003; Anonymous, 2004).Environmental contamination of farmland and irrigationwater with STEC explains their finding in vegetables, andconsumption of STEC O157 contaminated radish sproutsaccounted for the world’s largest outbreak in Sakai City,Japan in 1996, with more than 6000 cases of illness (Michinoet al., 1999). The dimension of environmental contaminationwith STEC becomes apparent by the presence of these agentsin shellfish collected in coastal areas polluted with effluentsfrom farmland (Gourmelon et al., 2006). Studies on dissem-ination of STEC on farms demonstrated the presence of theagent at multiple sites in the farm environment (Schoutenet al., 2005). Farm and wildlife animals such as insects, rodentsand wild birds may serve as possible vectors of transmission(Ejidokun et al., 2006).
Epidemiology
Epidemiological studies have shown that STEC are present innumerous serotypes in cattle and other domestic animalsworldwide, independent of geographical regions, animal race,husbandry and climate. The close association of cattle andother ruminants with STEC points to an ecological role of STEC in domestic and wildlife ruminants which may beexplained more by symbiosis than by simple parasitism.Elucidation of the ecological role of STEC in ruminantswould contribute to understand the nature of the animalreservoir and help to develop future prevention strategies.Differences between countries, regions, farms and animalherds were found in regard to prevalence and shedding of highly virulent STEC types such as O157:H7, O26:[H11] andothers. For O157, so-called super-shedding animals werefound in studies on cattle herds in Scotland and it wascalculated that 80% of transmission arises from 20% of mostinfective individual animals (Matthews et al., 2006a). Only 2%of Scottish farms showed high incidence of O157 sheddinganimals compared to 78% of Scottish cattle farms that werenegative for O157 (Matthews et al., 2006b). Early detection of super-shedding animals and a better understanding of themechanisms which convert individual animals to this state willcertainly be very useful for prevention of STEC entry in thefood chain. Shedding of STEC from animals was found to beinfluenced by many factors such as animal age, diet, stress,housing conditions and season. Longitudinal studies on STECexcretion by animals have shown that resident types of STECstrains such as O116:H21 in cattle can be excreted over monthsby the same animal and are widespread within animal herdsprobably due to transmission from animal to animal (Beutinet al., 1997). Typical resident STEC strains from cattle orsheep appear to be quite specific for their animal host and arerarely isolated from other animals or human patients, incontrast to human pathogenic STEC types which show abroad host range and are therefore found in different animalspecies including man (Trevena et al., 1996; Leomil et al.,2005). Typical human pathogenic STEC do not normallyrepresent the major STEC flora of animals but can exception-ally become the prominent type in herds and individualanimals as
Ô
super-shedders
Õ
. The reasons for these findings arenot well known, but future strategies should investigate thepossibility of using animal host-specific STEC strains asprobiotics in animals for possible prevention of colonizationwith human virulent STEC types such as O157:H7.
Prevalence in Humans
Prevalence rates and types of STEC found in human patientsvary also between different regions in the same country, asreported from the UK (Anonymous, 2004) Canada and theUSA. In the USA, incidence rates for O157 are higher in thenorthern than in the southern states which could be explainedwith large rural populations in the northern States andincreased contact to farm animals (Fey et al., 2000). Highcattle density and application of manure to the surface of farmland was related to high incidence of STEC infections inhumans (Valcour et al., 2002). On the other hand, theelevated exposure of the rural population to STEC comparedwith urban residents has resulted in an elevated seroresponseto Stx1 and Stx2 in the rural population and the presence of anti-shigatoxin antibodies was suggested to play a role inprotective immunity (Karmali et al., 2003). Acquired immu-nity might therefore play an important role for prevention of STEC infections in early childhood. As a result from aCanadian study, many dairy farm residents experiencesubclinical immunizing STEC infections at a young age,which frequently involve non-O157 STEC found in cattle(Wilson et al., 1996).Besides Stx, intimin (
eae
) plays a major role in the virulenceof human pathogenic STEC and also in Stx-negative entero-pathogenic
E. coli 
(EPEC), and
eae
-positive STEC areassociated with high pathogenicity for humans (Boerlin et al.,1999). In patients, a strong relationship was found betweeninfections with intimin-positive STEC, young age, and severeclinical picture. In contrast, adult patients were more fre-quently infected with
eae
-negative STEC with a milder clinicaloutcome (Beutin et al., 2004). Modified intimin was thereforeproposed as a candidate for vaccination of humans againstvirulent STEC types as it worked in an experimental animalmodel (Agin et al., 2005). In regions where EPEC expressingintimin and LPS similar to those of STEC are endemic, anti-intimin and anti-LPS antibodies are found in the humanpopulation indicating cross-reactive immunity to EPEC andSTEC (Ghaem-Maghami et al., 2001; Palmeira et al., 2005).Emerging and Rapid Spread of EHEC Infections 301

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->