A New Approach to Safer Food: Vaccinating Against Escherichia coli O157:H7 at the Source

Since September, it has been difficult to ignore what the media has been calling the largest recall of beef in Canadian history, originating from Escherichia coli O157:H7 contamination concerns at a large meat processing plant in Alberta. The Canadian Food Inspection Agency(CFIA) reported that it was a combination of a number of deficiencies that led to the mass recall, including E. coli O157:H7 control measures and sampling and testing procedures1.It is times like these that we are reminded that food safety control measures are not perfect, and we begin to ask what else can be done to ensure food safety. Large recalls like this are bound to get plenty of media attention, and may result in consumers having a negative image of the beef industry.

E. coli is a type of bacteria that is found in the digestive systems of not only cattle, but the majority of animals, including people. The majority of the strains of E. coli bacteria are harmless, and in fact play an important part in the digestion process. However, there are certain types of E. coli, including E. coli O157:H7, that can cause serious disease in people without causing disease in cattle. Infection in humans can occur upon consumption of contaminated food or water, or via direct contact with cattle and manure which often harbour E.coli. This also poses an occupational risk for individuals working with cattle, or even in animal exhibit settings, such as fairs and petting zoos. Infection with E. coli O157:H7 may lead to severe stomach cramps, bloody diarrhea, vomiting, and nausea2. Occasionally a serious condition called hemolytic uremic syndrome (HUS)can develop, which may result in kidney failure and possibly death, particularly in children and seniors.

Few farm level E. coli control strategies currently exist; therefore food safety is protected with a combination of post-harvest monitoring, contamination prevention, and food preparation techniques. Unfortunately, these strategies are not always 100 per cent effective, nor do they prevent E. coli O157:H7 from being spread into the environment prior to harvest, also known as environmental shedding. Environmental shedding may result in the contamination of drinking and recreational water, contamination of fruits and vegetables coming in contact with manure, infection via direct contact with cattle and manure, and further spread of the bacteria to other animals. In addition to this, studies have found that "super-shedders", cattle who shed high concentrations of E. coli O157:H7 in their feces, make up less than 10 per cent of cattle going to slaughter, but maybe responsible for over 96 per cent of the total E. coli O157 bacteria being shed3,4,5.

Currently, there is no human vaccine available for E. coli O157:H7. However, two commercial vaccines exist for use in cattle: a type III secreted proteins vaccine (Bioniche® Life Sciences Inc., Belleville, Ontario, Canada) and a siderophore receptor and porin protein (SRP) vaccine (Epitopix®, LLC, Wilmar, MN, USA). These vaccines work by reducing E. coli O157:H7's ability to grow in the cattle's digestive tract, which can therefore reduce the likelihood of the bacteria contaminating food and water and infecting humans (Figure 1). One of these vaccines, EconicheTM (Bioniche® Life Sciences Inc.) is currently licensed for use in Canada.

Photo of a dose of E. coli vaccine being administered to a cow
Figure 1. A dose of E. coli vaccine being administered to a cow in Canada (Photo credit: J. Shea).

Recently, a group of researchers in Guelph, Ontario, conducted an evaluation of the existing studies that examined how well these vaccines work on cattle as an intervention strategy before slaughter (i.e. pre-harvest)6. In total, 18 published studies met the three major criteria required to be included in this review. These criteria include: (1) weaned cattle in beef feedlot finishing systems under commercial conditions, (2) studies which examined the effect of a commercial vaccine on the presence or level of E. coli O157:H7 in cattle, (3) and randomized controlled trials. To evaluate these studies, analyses were conducted on pre-harvest outcomes, at-harvest outcomes and both pre-harvest and at-harvest outcomes combined. For study details see Supplementary section at the end of the article.

Results from the evaluation found that E. coli O157:H7 vaccination in cattle was consistently seen to be an effective control intervention (Table 1). For example, in studies examining pre-harvest E. coli shedding after two doses the vaccines, there was a significant reduction in E. coli O157:H7 with an estimated vaccine efficacy of 47 per cent (Figure 2). This means that under these conditions, cattle that received two doses of either vaccine had a 47 per cent reduction in E. coli O157:H7 shedding as compared to cattle who did not receive the vaccine.

Explanation of Figure 2
  • This is a forest plot of the effect of the two-dose regimen for the two commercial vaccines combined in reducing E. coli O157:H7 in pre-harvest samples.
  • The solid vertical line represents an effect size (ES) of one, corresponding to no treatment effect.
  • Point estimates to the left of the solid line denote a decrease in the prevalence of E. coli O157:H7 in each study. The farther the point estimates are to the left, the greater the reduction in E. coli O157:H7.
  • The grey boxes around the point estimates denote the weight given to the study in calculating the pooled effect size; a study with a greater weight contains greater information (e.g. had a larger sample size of cattle).
  • The solid horizontal lines represent the 95 per cent confidence intervals (CI), which gives us a measure of the precision around the point estimates.
  • The pooled effect size for all the studies combined is represented by the diamond at the bottom of the graph at 0.53, which equates to a 47 per cent vaccine efficacy under these conditions.

Effectiveness of the Two-Dose Treatment for Two Commercial E. coli O157:H7
Figure 2. Effectiveness of the Two-Dose Treatment for Two Commercial E. coli O157:H7

Text Equivalent of Diagram

These study findings demonstrate the possibility of an effective multi-pronged approach to controlling the spread of E. coli O157:H7 to humans by targeting the disease at the source. This intervention may help reduce not only the amount of E. coli O157:H7 being shed into the environment, but may also reduce the risk and burden of the bacteria entering slaughter houses, possibly by "super-shedders". However, it should be noted that because the vaccines are not 100 per cent effective, and we must not dismiss the importance of ongoing food safety measures along the entire farm-to-fork continuum. Nevertheless, E. coli O157:H7 vaccination at the farm level appears to be an effective proactive strategy that can improve the safety of our food, protect the public's health, and reassure consumers that Canadian beef is a premium and safe product.

For more information about the Guelph study, or the studies that were evaluated, please see the full article (Varela, Dick, and Wilson, 2012) in Zoonoses and Public Health6. For more information about the E. coli O157:H7 vaccines, please consult your veterinarian.

References:

1 Canadian Food Inspection Agency (CFIA). (2012). Questions and Answers: Recall of Specific Products from XL Foods Inc. - Establishment 28, Brooks, Alberta. Accessed online October 3, 2012, from http://www.inspection.gc.ca/food/consumer-centre/food-safety-investigations/xl-foods/questions-and-answers/eng/1348090287501/1348090501848.

2CFIA. (2012). Food poisoning: E. coli O157:H7 - bacteria. Accessed online October 3, 2012, from http://www.inspection.gc.ca/food/consumer-centre/food-safety-tips/food-poisoning/e-coli/eng/1332539377584/1332539833416

3Chase-Topping, M.E., et al. (2007).Risk factors for the presence of high-level shedders of Escherichia coli O157 on Scottish farms.J. Clin. Microbiol. 45:1594-1603.

4Omisakin, F., MacRae, M., Ogeden, I.D., and Strachan, N.J.C. (2003).Concentration and prevalence of Escherichia coli O157 in cattle faeces at slaughter.Appl. Environ. Microbiol. 69:2444-2447.

5Chase-Topping, M., Gally, D., Low, C., Matthews, L., and Woolhouse, M. (2008).Super-shedding and the link between human infection and livestock carriage of Escherichia coli O157.Nature Reviews Microbiology. 6:904-912.

6Varela, N. P., Dick, P. and Wilson, J. (2012), Assessing the Existing Information on the Efficacy of Bovine Vaccination against Escherichia coli O157:H7 - A Systematic Review and Meta-analysis.Zoonoses and Public Health.doi: 10.1111/j.1863-2378.2012.01523.x

Supplementary Information

Explanation of Supplementary Table 1.
  • This table shows the effect size and vaccine efficacy estimates derived from meta-analyses of clinical trials examining the efficacy of the two E. coli O157 vaccines in reducing the prevalence of E. coli O157:H7 in weaned cattle in beef feedlot finishing systems.
  • The Table is adapted from Table 5 in the original Varela, Dick, and Wilson (2012) study.
  • Vaccine efficacy is examined under different study outcomes (pre-harvest only, at-harvest only, and pre-harvest and at-harvest combined), the two different vaccines (EconicheTM only, Epitopix SRP® only, and EconicheTM and Epitopix SRP® combined), and different dosing regimens.
  • Where homogeneity was demonstrated, the studies being compared were very similar; where heterogeneity was demonstrated, there were differences detected in how these studies were conducted.
     
  • Table 1. Effect Size and Vaccine Efficacy Estimates

    Outcome Vaccine Doses # of studies # of comparisons Effect size Estimated vaccine efficacy (%) Conclusion regarding heterogeneity
    Pre-harvest (faecal, environmental, hides, recto-anal mucosal swab) EconicheTM or Epitopix SRP® All 8 19 0.46 54 Heterogeneity across studies
    Two-dose 5 12 0.53 47 Homogeneity
    Epitopix SRP® only All 1 5 0.59 41 Not assessed (one study only)
    EconicheTM only All 7 14 0.42 58 Heterogeneity
    Two-dose 3 4 0.49 51 Homogeneity
    Two-dose (faecal) 3 4 41 59 Homogeneity
    Two-dose (hides) 1 2 0.52 48 Not assessed (one study only)
    Three-dose 5 5 0.41 59 Heterogeneity
    At-harvest (terminal rectal mucosa) EconicheTM only All 3 3 0.09 91 High heterogeneity
    Pre- and at-harvest combined (faecal, environmental, hides, recto-anal mucosal swab, terminal rectal mucosa) EconicheTM or Epitopix SRP® All 9 22 0.43 57 Heterogeneity
    EconicheTM or Epitopix SRP® Two-dose 6 14 0.52 48 Homogeneity
    EconicheTM only All 8 17 0.38 62 Heterogeneity
    Two-dose 5 9 0.45 55 Heterogeneity
    Three-dose 5 6 0.32 68 High heterogeneity

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