E. coli - available
Control ToolsDiagnostics availabilityMany kits are available for detection and identification of VTEC. Some are specific for human infections, other are specifically developed for food analyses. 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. 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. 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. GAP: If attenuated vaccines are developed, the vaccine strains must be discriminated from the field strains. Easy and rapid tests targeting the main non-O157 pathogenic serogroups are urgently required. GAP: This represents a critical gap - Array platforms, new media through testing isolates in phenotypic assays such as Biolog? - Development of standard methods for non-O157 in foods Vaccines availabilityA 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. 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 needed. We don’t know enough about colonization and mucocal 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. 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). Pharmaceutical availabilityIn 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. New developments for diagnostic testsRapid 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:
When the principles are defined, the development of tests is generally faster and less expensive than that of vaccines. 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 kits and a need for tests, then this almost automatically drive companies to market new methods. The validation of alternative tests is therefore “on the company”.
1. Increase knowledge on pathogenesis and involved virulence factors 2. Increased knowledge on immune response GAPS:
Not applicable. New developments for vaccinesSerotype independent (targeted against bacterial factors common to the main pathogenic VTEC serogroups). 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 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 pathotypoes and evolutionary pressures. New developments for pharmaceuticalsProbiotics 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, 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, vaccines and topicals. Disease detailsDescription and characteristics.Escherichia coli is a Gram negative bacterial species which is normally present in the gastrointestinal tract of humans and animals. Most E. coli are harmless commensals, however certain strains produce potent toxins and are known as verocytotoxin (Shiga toxin)-producing E. coli (VTEC/STEC). VTEC are zoonotic pathogens, which cause severe human illnesses and have ruminants, particularly cattle, as their natural reservoir. Strains of E. coli are classified into serotypes based on the somatic “O” and flagella “H” antigens. More than 100 different serotypes have been identified as VTEC, with O157:H7 as the serotype most commonly associated with severe human disease. GAPS:
VTEC can cause a wide spectrum of disease in humans, ranging from mild uncomplicated diarrhoea to severe bloody diarrhoea and the haemolytic uremic syndrome (HUS), a potentially life threatening condition which is mainly observed in children. The strains that are most frequently associated with HUS usually posses the intimin-coding eae gene, 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. VTEC are not important warmblood animal pathogens: some strains can cause colibacillosis in young calves and strains producing a porcine variant of VT cause the oedema disease in pigs. 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. Long-term (months to years) survival is reported in manure. The organism also survives in many food products, including highly acidic foods. GAP: more information needed on survival in soil and farm environments. Species involvedRuminants, particularly cattle, are the principal reservoir. 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. In particular, ruminants are healthy carriers of VTEC O157 and show no evidence of disease. Microscopic changes (attaching and effacing lesions) at the recto-anal junction are observed in colonized cattle. 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, the HUS (haemolytic uremic syndrome). 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. GAP: What about soil dwelling organisms? Earthworms etc. Ruminants, particularly cattle, are the main reservoir, particularly for VTEC O157. The organism survives well in the environment. GAPS:
Description of infection & disease in natural hostsIn ruminants, VTEC has a very low infectious dose and it is transmitted via the fecal-oral route. It can spread within the farm by direct contact, contamination of water, feed, environment, and by other animals like flies and birds. Contamination of feed troughs 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 (eg 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 subjects can excrete large numbers of organisms in their faeces. Other VTEC serotypes may cause disease with clinical signs in animals (see "Animal infected/carrier/disease") including dogs. Between 1 and 7 days (typically 2-3) in humans. Not known in animals. GAP: What about non-O157 VTEC? 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 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:
Zoonotic potentialSurveillance 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:
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:
Food at risk includes undercooked ground beef, unpasteurised milk and dairy products made of minimally heat treated milk,, fresh produce, 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 (kindergarden 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:
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:
Impact on animal welfare and biodiversityNone. 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 will be confirmed and if reliable and feasible methods for the identification of such animals become available. However, this option is object of debate, since the multiple hosts and the environmental persistence of the organisms could make the “eradication” policy ineffective. It would still be a massive step forward in the control of VTEC if super shedders could be identified. This would open for new control options: special logistics for the slaughter of these animals, the animals could be collected on special farms, the animals could be vaccinated, and the breeding programmes could aim at eradicating super shedders etc. GAPS:
Geographical distribution and spreadWorldwide, 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. 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. 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. Route of TransmissionIn ruminants, VTEC has a very low infectious dose and it is transmitted via the fecal-oral route. It can spread within the farm by direct contact, contamination of water, feed, environment, and by other animals like flies and birds. 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 (eg handling ground beef in the kitchen). GAPS:
Contamination of feed troughs 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). In humans, contacts with a contaminated environment (soil, swimming in lakes or pools) also represent a risk. 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:
Detection and Immune response to infectionThe 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.
Main means of prevention, detection and controlAlthough 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: method should aim at identifying any VTEC in persons with disease, to know if changes in the serotypes causing disease occur by time. Good tools are available:
Food and animal faeces: VTEC that are presumably poorly virulent to humans are abundant, so the methods should be targeted to the serogroups most associated with human disease. Good tools (cultural, molecular, immuno-detection) are available for the detection/isolation of VTEC O157. Efforts are presently made for developing PCR-based methods to detect the other pathogenic serogroups (O26, O103, O111, O145). 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. Adminstration 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:
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. Disease information from the OIENo. No No http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.09.11_VERO_E_COLI.pdf Socio-economic impactMost 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 treatments 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 control or own check. 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. Trade implicationsNo 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. Main perceived obstacles for effective prevention and controlMany 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:
Main perceived facilitators for effective prevention and controlBetter knowledge of the mechanisms of the pathogenesis of infection in humans and of colonization in livestock. GAPS:
RiskRisks 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.
Main critical gapsHuman infections
Animal infections
Food control
ConclusionSurveillance 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 needed for to identify the most suitable targets for diagnostics and vaccines. GAPS:
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