Many kits are available for detection and identification of VTEC. Some are specific for human infections, other are specifically developed for food analyses. See also section [Main means for prevention, detection and control].
GAP:
Generally, need for better detection assays for non-O157.
Kits are available in Europe.
Several kits for the detection of E, coli O157 in food have been validated against accepted reference culture methods, i.e. the ISO 16654 method in EU. A PCR-based technical specification for the detection of the main non-O157 serogroups in food is in the process to be approved by ISO. These methods can be adapted for the analysis of animal faeces. LAMP assays are now available for E. coli.
GAPS
The immuno-magnetic concentration-based method ISO16654 for E. coli O157 in food. Commercial kits validated against this method. For the detection of the main non-O157 serogroups in food, a PCR-based technical specification is in the process to be approved by ISO. The OIE Terrestrial Animal Health Code and an EFSA guideline for monitoring of VTEC in animals published in 2009 describe how to adapt these methods to animal faeces. See also section [Main means for prevention, detection and control] and [Diagnostic kits validated by National or Internation Standards]. LAMP assays are now available for VTEC – Detection in 15 minutes.
Many diagnostic kits already available for the detection of VTEC O157, VT production and vtx genes. Tests targeting the main non-O157 pathogenic serogroups are urgently required. ELISA based tests are less sensitive than culture/PCR but faster.
GAPS:
Not applicable presently, although a vaccine is available now.
GAP:
If attenuated vaccines are developed, the vaccine strains must be discriminated from the field strains.
Only commercial vaccines are based on secreted proteins.
Easy and rapid tests targeting the main non-O157 pathogenic serogroups are urgently required.
GAP:
This represents a critical gap.
A vaccine directed against type III secreted proteins has obtained licensing approval from the Canadian Food Inspection Agency. Another product which targets bacterial surface proteins and protein receptors involved in iron uptake has recently obtained a conditional approval by the U.S. Department of Agriculture.
GAPS:
None for VTEC. Available for colibacillosis. Bioniche vaccine available for O157?
None.
None.
The efficacy of the available vaccines against VTEC O157 has still to be fully evaluated. The efficacy against other VTEC serotypes is unknown.
GAPS:
In general, more research is required. We don’t know enough about colonization and mucosal immunity to an otherwise commensal organism to understand which aspects of colonization would be best targeted.
Since cattle are asymptomatic there is little demand from farmers. Vaccination of feedlot calves could be required by companies purchasing the meat. In Member States where selling raw milk is allowed, the involved dairy farms would have a strong interest in vaccination.
GAPS:
Use of genetically modified vaccines might be problematic in some countries. The field trials may need specific regulation regarding the release of GMOs into the environment.
GMO E. coli vaccine for poultry recently launched by ZOETIS?
GAPS:
Feasible to produce but depends on demand.
Herd vaccination would be practical in an attempt to reduce infection in cattle.
Vaccination certification (rather than extensive testing for faecal excretion of O157 and negative certification of animals, which controversial) could be used to protect against (trade?) barriers.GAP:
Investigate whether vaccination of cattle prior to slaughter is a way to reduce the influx of VTEC into the abattoir.
The development of vaccines against non-O157 or the evaluation of the efficacy of the existing O157 vaccines against the main non-O157 pathogenic serogroups (some of the components can be in common with other serogroups).
In humans, antibiotic therapy is not recommended. Only supportive therapies.
No therapy for animals.
For reducing colonization and carriage in animals:
GAPS:
Limited potential, and dependant on policies in relation to VTEC infection in humans and the need to reduce infection in cattle.
None.
None.
Development of probiotics for preventing or reducing animal colonization.
Rapid tests to identify cattle infected with pathogenic VTEC.
Tests for the detection of the main non-O157 serogroups pathogenic to humans in food and animals.
Time and costs should be contained.GAPS:
Depending on when a new candidate vaccine could be identified the timescale could be 5-10 years. This will involve development of clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials. The time to commercial availability will depend on the outcome of these trials.
American data on O157 vaccination in feed lot cattle: there is a prompt immunological reaction, and a decrease in the shedding is also observed. The effects of the vaccines ceases after 2-3 months.The development and validation of new tests is resource demanding (time consuming and labour intensive). The costs cannot be specified as they will depend on the nature of the test, the cost of reagents and of reading or processing machines, if needed. Once validated, a commercial company willing to market the test will be needed.
GAP:
If there is a framework for the development of diagnostic kits and a need for tests, then this almost automatically drive companies to market new methods. The validation of alternative tests is then the responsibility of the respective company.
GAPS:
Not applicable.
Serotype independent (targeted against bacterial factors common to the main pathogenic VTEC serogroups).
GAPS:
See section [Requirements for diagnostic development].
Depending on when a new candidate vaccine could be identified the timescale could be 5-10 years. This will involve development of clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials. The time to commercial availability will depend on the outcome of these trials.
American data on O157 vaccinaiton in feed loot cattle: there is a prompt immunological reaction, and a decrese in the shedding is also observed. The effects of the vaccines ceases after 2-3 months.
GAPS:
Expensive, with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trials will be difficult, as wells as the evaluation of the results. Since there is no disease, these will be expressed by measuring the VTEC shedding.
Increased knowledge on the colonization of cattle gut by VTEC.
GAPS: Increased knowledge on genotype and phenotype, emergence of new pathotypes and evolutionary pressures.
Probiotics effective against VTEC colonization.
Development of bacteriophages which have a wide spectrum of specificity for pathogenic VTEC serotypes, and which are active in vivo in the gut.GAPS:
Prebiotics, probiotics, synbiotics, phytochemicals topicals, vaccines? Bedding treatments etc.
Time to develop would depend on the product and the trials necessary to validate the efficacy and safety. Commercial production would then take further time. Five to 10 years seems a realistic timeframe.
Difficult to assess as it will depend on the product and the trials necessary to validate and license.
Increase research on the effects of probiotics against VTEC colonization.
GAPS:
Prebiotics, probiotics, synbiotics, phytochemicals, vaccines and topicals.
Escherichia coli is a Gram negative bacterium which is normally inhabitant of the gastrointestinal tract of humans and animals. Most E. coli strains are harmless commensals, however certain strains produce potent toxins and are known as verocytotoxin (Shiga toxin)-producing E. coli (VTEC/STEC/EHEC). VTEC are zoonotic pathogens, which cause severe clinical disease in humans. Ruminants are considered the primary reservoir for VTEC, with cattle playing the largest role.
Strains of E. coli are classified into serotypes based on their somatic “O” and flagella “H” antigens. More than 100 different serotypes of E. coli have been identified as VTEC, with O157:H7 as the serotype most commonly associated from severe human disease. Importantly, non-zoonotic VTEC have been identified as diseases causing organisms in pigs and chickens.GAPS:
VTEC can cause a wide spectrum of disease in humans, ranging from mild uncomplicated diarrhoea to severe bloody diarrhoea and haemolytic uraemic syndrome (HUS), a potentially life threatening condition which is mainly observed in children. The strains that are most frequently associated with HUS usually harbour the intimin gene (eae), associated with the attaching/effacing mechanism of intestinal adhesion, and belong to a restricted number of serogroups: O157, O26, O101, O111, O145, O121. In addition, eae-negative O91 strains are frequent in Europe, even if they have been less frequently associated with HUS. In 2011 a non-LEE positive E. coli O104 was associated with one of the largest outbreaks of human VTEC infection.
VTEC are not important animal pathogens: However, some strains can cause colibacillosis in young calves and strains producing a porcine variant of the VT cause the oedema disease in pigs. Furthermore some strains are associated with swollen head syndrome in poultry.
In the case of VTEC O157, infected cattle show no clinical signs. Cattle are the main reservoir, but VTEC are common in other ruminants sheep, goats, water buffalo and wild ruminants) and have also been isolated from other species, including pigs, horses, dogs, chicken, pigeon and wild birds.GAPS:
VTEC can survive in the environment for extended periods of time. Reports suggest that the organism can survive for more than 90 days in soil. In water the rate survival is inversely proportional to the temperature and general environmental conditions. Long-term (months to years) survival is reported in manure. The organism also survives in many food products, including highly acidic foods.
GAP:
Ruminants, particularly cattle, are the principal reservoir although many other species can be colonised with VTEC, including wild-life. VTEC are not important animal pathogens: some strains can cause colibacillosis in young calves and strains producing a porcine variant of VT cause the oedema disease in pigs and some strains are associated with swollen head syndrome in poultry. Ruminants harbour VTEC O157 and other serotypes without displaying any evidence of disease. However, microscopic changes (attaching and effacing lesions) can be observed in the intestinal tract of many animal species. The recto-anal junction appears to be the main site of colonisation in cattle, but not other species.
GAPS:
VTEC can cause a wide spectrum of disease in humans, ranging from asymptomatic carriage to mild uncomplicated diarrhoea, severe bloody diarrhoea and, in children, HUS, HC and TCP.
GAPS:
VTEC are not vector-borne pathogens. However, VTEC can be recovered from many different domestic and wild animal species (horses, dogs, flies, rodents), presumably a result of transient infection from ruminant or environmental sources. These animals may act as vehicles of infection to humans. VTEC may also be transferred from on species to another by flies.
GAP:
Ruminants and particularly cattle are the main reservoirs for VTEC. VTEC O157 and O26 are particularly associated with bovine reservoirs. The organism survives well in the environment.
GAPS:
In ruminants, VTEC has a very low infectious dose and it is transmitted via the faecal-oral route. It can spread within the farm by direct contact, contamination of water, feed, environment, and by other animals such as flies and birds. Contamination of feed troughs and ropes can also occur through the saliva. Inter-herd transmission may occur by animal movements, but also via other animals, such as birds and fomites (trucks, equipment).
The infection can be transmitted to humans with a low infectious dose, and person-to-person transmission does occur. Routes of transmission include ingestion of contaminated foods of animal origin, especially beef and dairy products, water and vegetables contaminated with farm slurry, direct contact with live animals or contaminated animal products (e.g. handling ground beef in the kitchen). Contacts with a contaminated environment (soil, swimming in lakes or pools) also represent a risk.GAPS:
Not applicable.
Most VTEC infections in animals are asymptomatic, but some animals can excrete large numbers of organisms in their faeces. Other VTEC serotypes may cause disease with clinical signs in animals (see point 2.1), including dogs. Some evidence to suggest HUS in dogs?
GAP:
More information regarding clinical signs in companion animals.
Between 1 and 7 days (typically 2-3) in humans. Not known in animals.
GAP:
No mortality reported in ruminants with VTEC O157
Data are available for VTEC O157 only, and mainly in cattle. The shedding pattern is usually intermittent, in general much more intense in the warm season. Most animals excrete 102-103 CFU/g of the faeces. However, a few animals, defined as “super shedders” can excrete 104-105 CFU/g of the faeces, and can remain colonized for longer periods. These “super shedders” might play a major role in maintaining and spreading the infection and could represent the main target of control plans.
GAPS:
VT/ST production is the main virulence factor. The strains that have been consistently associated with HUS usually produce the VT2 variant of the toxin and posses the intimin-coding eae gene, associated with the attaching/effacing (AE) mechanism of intestinal adhesion. AE lesions are also observed at recto-anal junction in cattle and could explain how some animals are colonized more intensely (super-shedders).
GAPS:
Surveillance systems are in place in industrialized areas such as Europe, North America, Japan, and Australia. Data are also available for South America, especially Argentina. In the US, the incidence is estimated to be around 100,000 cases per year. The epidemiology of VTEC infection is poorly known in developing countries. Large community outbreaks associated with ingestion of contaminated food or water are frequently reported. However, most cases are sporadic. Many affected people do not seek medical attention and faecal samples are rarely examined. In most clinical laboratories the methods used for detection are specifically targeted to VTEC O157. This means that the presence of the other serotypes often remains undiagnosed.
GAPS:
Food at risk includes undercooked ground beef, unpasteurised milk and dairy products made of minimally heat treated milk, fresh produce (vegetables), and potable water. Infection can be acquired by direct or indirect contact with animals especially cattle, or through contact with water or soil contaminated with ruminants’ faeces. Inter-human transmission frequently occurs (kindergarten outbreaks, etc.).
GAPS:
VTEC can cause a wide spectrum of disease in humans, ranging from mild uncomplicated diarrhoea to severe bloody diarrhoea and, in children, the haemolytic uremic syndrome (HUS). The disease affects all ages with the young and elderly more likely to develop severe illness.
GAPS:
In most countries, high level of underreporting, especially for the uncomplicated cases, since the patients do not seek medical attention. Many clinical laboratories do not look for VTEC. Other laboratories only use methods that are specific for O157 and are unable to identify the presence of other VTEC serotypes.
GAPS:
Humans can acquire the infection by different ways. Infection can also spread from person to person due to the low infectious dose, even in settings with acceptable levels of personal hygiene.
GAPS:
None.
GAP: VTEC could have an impact on biodiversity, as they may have selective advantage in ruminant host gut and thereby reduce Enterobacteriaceae diversity?
No.
GAP:
Have some zoo animals been affected?
Not at present.
A “stamping out” approach could be considered if the role of super shedder animals was confirmed and reliable and feasible methods for the identification of such animals becomes available. However, this option is object of debate, since the multiple hosts and the environmental persistence of the organisms could make the “eradication” policy un-effective.GAPS:
Worldwide, but there is some evidence that there is variability in the geographic distribution of serotypes involved in human infections.
GAPS:
Is the variability in the distribution of VTEC serotypes among countries due to a true difference in the epidemiology or is it due to different sensitivities of the surveillance systems in place?
In animals, endemic. Not Epizootic as animals are carriers. In humans, endemic (most cases are sporadic) with frequent outbreaks.
GAPS:
Knowledge of the geographic distribution of the different VTEC sero-pathotypes
There is a seasonal trend for colonisation of cattle in the summer and this is reflected in the peak incidence of disease in the human population which also occurs in the summer months. However, cattle may become colonized at any time of the year or under diverse environmental conditions.
There may be seasonal outbreaks when pastured cattle die during drought and subsequent heavy rains result in contamination of surface waters, as occurred in southern Africa.GAPS:
In humans, outbreaks can be associated with foods that are widely distributed to many persons and spread over very large geographical areas.
GAPS:
Speed of spread? How fast?
Spread via animals, movement of animals and export of contaminated foods, e.g. frozen beef, fruits, vegetables.
GAP:
Refine trade, try to develop production system that reduce animal transport.
GAPS:
The presence of VTEC O157 in a farm may not depend on poor) hygiene and management, which conversely have an important role in the following steps of the food chain for transmission to humans.
GAPS:
The immune response varies. In humans, VTEC infection results in the production of antibodies against the toxin, intimin and other factors involved in adhesion, and the O serogroup-specific LPS antigen. The immune response in animals has been less investigated: cattle develop anti-O157 antibodies, but rarely anti-VT antibodies.
GAPS:
LPS-antibodies detection is used for diagnosis of human infections. Serology is not used for diagnosis in animals.
GAP:
Other specific / protective surface antigens should be identified and could used in diagnostics.
Although many sanitary interventions have been proposed, none have proven to significantly impact O157 carriage among cattle. High cattle density on farms is associated with increased O157 prevalence.
GAPS:
To control the spread within the farm:
GAPS:
In general, the laboratory tools for VTEC O157 detection are adequate, while those for VTEC Non-O157 detection are poor.
Human infections: methods should aim at identifying any VTEC in peoples with disease, to know if changes in the serotypes causing disease occur over time. Good tools are available:
GAPS:
Experimental vaccines to contrast the colonization of cattle with VTEC O157 have been developed but their efficacy is still controversial.
A vaccine directed against type III secreted proteins has obtained licensing approval from the Canadian Food Inspection Agency. Another product which targets bacterial surface proteins and protein receptors involved in iron uptake. has recently obtained a conditional approval by the U.S. Department of Agriculture.In cattle, neomycin administration is effective at eliminating most O157 in cattle but its use is complicated by the possibility of promoting antibiotic resistant organisms. Use of antimicrobial growth promoters is not effective and may increase VTEC O157 excretion (these are now banned in the EU).
Administration of sodium chlorate immediately pre-harvest is effective at reducing many Gram-negative facultative anaerobes (including E. coli O157) from the gastrointestinal tract of ruminants. Currently under regulatory approval process in the US.
In humans, antimicrobial therapy is controversial and may be contraindicated due to a possible increase in the release of VT in the gut.GAPS:
The low infective dose for humans requires care in handling animals. Good food hygiene is essential to prevent zoonotic transmission. Also, care is required in handling cultures and samples in the laboratory and during transport between laboratories and countries.
GAPS:
None in place for animals, as carrier animals may be intermittent excretors of VTEC.
Movement of VTEC strains, cultures and positive samples across borders is very restricted for some countries. Movement of cultures by air transport is restricted, as VTEC are considered Category A by IATA. Movement of foods such as meat may require negative testing for entry into some countries.Hygiene and good practice at:
GAPS:
Passive surveillance in animals, through examination of faecal samples collected on farm or during surveys at the abattoir.
Surveillance of human infections to promptly detect outbreaks and to follow the trend of serotypes. Some regions have active surveillance programs.
GAPS:
Prevention of infection in livestock is difficult. Irradiation of foods is the only assured way to remove/eliminate the pathogen from products, but may present social acceptance challenges. Probiotics are used widely in the US. Livestock vaccination attempts and phage therapy are still in the experimental stages. Most efforts have been made on ensuring that food and water are not contaminated with VTEC from cattle faeces.
GAPS:
Surveys are expensive, and testing cannot ensure food safety as re-infection occurs readily. An effective pre-harvest intervention could be cost-effective, even if cost-effectiveness is difficult to evaluate, as there is no disease in animals to measure. Contamination may be sporadically located on hides or carcasses, and prevention will be critical. It must be considered that any intervention will likely increase the cost of production to the farmer.
GAP:
Modelling the cost/benefit of control measures in term of reduction of the burden of VTEC infections in humans.
Reporting not required as there is no disease in animals. Human outbreaks and sporadic cases are reported through surveillance systems (e.g., CDC in the US and ECDC in the EU). Contaminated food and feed are reported in the RASFF managed by the EU Commission.
GAP:
Link of surveillance data from animals and humans at the same time and geographic area
No
No
http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.09.11_VERO_E_COLI.pdf
VTEC infections are probably a worldwide problem. However, systematic collection of information occurs only in industrialized areas (see section [Reported incidence in humans]).
Most affected people recover in 5 to 10 days. However, long term sequelae may occur in children with HUS, who may develop chronic renal failure.
GAPS:
Cases of severe disease are often hospitalized, especially children and elderly people. HUS is major public health concern in many countries. In the acute phase it often requires prolonged hospitalization and dialysis, and can result in acquired chronic renal failure. Consequently, the costs medical treatment are substantial. Estimated cost per illness in the US is $6,506 (2008) USD.
GAP:
Estimation of the burden of VTEC infections, including costs, in population is available only for a few countries.
None.
Surveys on farms and at abattoir are expensive, as well as the tests performed on food both as official controls or own checks.
The large outbreaks have had serious consequences on the agri-food industry. In the US, fast food operations had a crisis after the outbreaks occurring between the end of the 1980s and the 1990s. The more recent spinach outbreak has caused a crisis of the consumption of this produce.
Petting zoos and dairy or other farms receiving tourists are tested for O157 and may be shut down when it is detected, in certain countries.No specific international standards for control of VTEC. No mention in the OIE Terrestrial Animal Health Code.
As for other foodborne pathogens.
As for other foodborne pathogens.
Many reservoir hosts, many routes of transmission, the persistence of environmental contamination represent the primary obstacles for control. E. coli are dynamic organisms which are continuously evolving. Vaccination, if effective, is currently restricted to VTEC O157.
Socio-economic problems related with interventions:
GAPS:
Better knowledge of the mechanisms of the pathogenesis of infection in humans and of colonization in livestock.
GAPS:
As stated above, there is a summer peak in both the prevalence of cattle colonization and the incidence of human disease. However, animal and human infections can occur any time of the year. See above.
GAPS:
No.
Heavy rainfall may facilitate sewage systems overflow and the spread of ruminant manure in the environment and may also affect the efficiency of drinking water filtration systems. Some important waterborne outbreaks have occurred after heavy rainfalls. Muddy conditions in livestock pens may increase prevalence and subsequent increase in carcass contamination at harvest.
GAP:
Impact of global warming/more extreme weather (precipitation, temperature, flooding etc).
No.
Risks for animals are unlikely, but the appearance of new VTEC organisms which can cause disease in animals is possible. The emergence of new serotypes causing disease in humans must be verified through constant surveillance activities, until they become evident and or predominant.
GAP:
Possible emergence of multiple antibiotic resistance and its role in favouring the spread of clones in animal reservoirs
Human infections
Animal infections
Food control
Surveillance systems must provide updated information on the VTEC serogroups causing human infections. These will represent the targets for control activities in animals and food.
A better knowledge of the mechanisms of the pathogenesis of infection in humans and of colonization in livestock is required to identify the most suitable targets for diagnostics and vaccines.GAPS:
Expert group members are included where permission has been given
Roberto La Ragione - University of Surrey, UK - [Leader]
Gad Frankel - Imperial College, UK
Christian Menge - Friedrich Loeffler Institut, Germany
Project Management Board.
10th of March 2015
Accessed 24th February 2015
OIE
http://www.oie.int/eng/normes/MMANUAL/A_index.htm
http://www.oie.int/eng/maladies/en_alpha.htm?e1d7
http://www.oie.int/eng/normes/mcode/en_chapitre_1.8.4.htm#rubrique_echinococcose_hydatidose_commerce
WHO
http://www.who.int/zoonoses/neglected_zoonotic_diseases/en/index.html
CDC
http://www.cdc.gov/nczved/dfbmd/disease_listing/stec_gi.html
HPA
EFSA
http://www.efsa.europa.eu/en/efsajournal/scdoc/1366.htm