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Environmental Assessment for Licensing Escherichia coli Vaccine, Live Culture in Canada

For Public Release

September 12, 2008

The information in this environmental assessment was current at the time of its preparation. It is possible that the situation may have changed since that time. If you have any questions, please contact the Veterinary Biologics Section.


Table of Contents

  • Summary
  • 1. Introduction
    • 1.1 Proposed Action
    • 1.2 Background
  • 2. Purpose and Need for Proposed Action
    • 2.1 Significance
    • 2.2 Rationale
  • 3. Alternatives
  • 4. Molecular and Biological Characteristics of Parental and Recombinant Organisms
    • 4.1 Identification, Sources, and Strains of Parental Organisms
    • 4.2 Source, Description and Function of Foreign Genetic Material
    • 4.3 Method of Accomplishing Genetic Modification
    • 4.4 Genetic and Phenotypic Stability of the Vaccine Organism
    • 4.5 Horizontal Gene Transfer and Potential for Recombination
    • 4.6 Host Range/Specificity, Tissue Tropism and Shed/Spread Capabilities
    • 4.7 Comparison of the Modified Organisms to Parental Properties
    • 4.8 Route of Administration/Transmission
  • 5. Human Safety
    • 5.1 Previous Safe Use
    • 5.2 Probability of Human Exposure
    • 5.3 Possible Outcomes of Human Exposure
    • 5.4 Pathogenicity of Parent Microorganisms in Humans
    • 5.5 Effect of Gene Manipulation on Pathogenicity in Humans
    • 5.6 Risk Associated with Widespread Use of the Vaccine
  • 6. Animal Safety
    • 6.1 Previous Safe Use
    • 6.2 Fate of the Vaccine in Target and Non-Target Species
    • 6.3 Potential of Shed and/or Spread from Vaccinate to Contact Target and Non-Target Animals
    • 6.4 Reversion to Virulence Resulting from Back Passage in Animals
    • 6.5 Effect of Overdose in Target and Potential Non-Target Species
    • 6.6 The Extent of the Host Range and the Degree of Mobility of the Vector
  • 7. Affected Environment
    • 7.1 Extent of Release into the Environment
    • 7.2 Persistence of the Vector in the Environment / Cumulative Impacts
    • 7.3 Extent of Exposure to Non-Target Species
    • 7.4 Behaviour of Parent Microorganisms and Vector in Non-Target Species
  • 8. Environmental Consequences
    • 8.1 Risks and Benefits
    • 8.2 Relative Safety Compared to Other Vaccines
  • 9. Mitigative Measures
    • 9.1 Worker Safety
    • 9.2 Handling Vaccinated or Exposed Animals
  • 10. Monitoring
    • 10.1 General
    • 10.2 Human
    • 10.3 Animal
  • 11. Consultations and Contacts
  • 12. Conclusions and Actions
  • 13. References

Summary

Escherichia coli Vaccine, Live Culture (Poulvac E. coli) consists of a live culture of an E. coli bacterial strain, which has been attenuated by the partial deletion of its aroA gene required for the biosynthesis of aromatic amino acids. This vaccine is administered to healthy chicks one day of age or older as an aid in the prevention of disease caused by avian pathogenic E. coli. A second vaccination is recommended for long-lived birds at 12-14 weeks of age. The vaccine was evaluated by the Veterinary Biologics Section of the Canadian Food Inspection Agency for licensing in Canada. As part of the requirements for licensing this product in Canada, an ‘Environmental Assessment,' was conducted and a public document containing information on the molecular and biological characteristics of the live genetically modified organism, target animal and non-target animal safety, human safety, environmental considerations and risk mitigating measures was prepared.

1. Introduction

1.1 Proposed Action

The Veterinary Biologics Section (VBS), Terrestrial Animal Health Division, Canadian Food Inspection Agency (CFIA) is responsible for licensing veterinary biologics for use in Canada. The legal authority for the regulation of veterinary biologics in Canada is provided under the Health of Animals Act and Regulations. Any veterinary biologic manufactured, sold, or represented for use in Canada must comply with the requirements specified by the CFIA regarding the safety, purity, potency, and efficacy of the product. Fort Dodge Animal Health (Fort Dodge, Iowa, USA) through Wyeth Animal Health (Canada) has submitted the following vaccine for licensing in Canada:

  • Escherichia coli Vaccine, Live Culture (Trade Name: Poulvac E. coli), USDA Product Code 1551.R0, VBS File Number 800VB/E2.0/F3.2.

This Environmental Assessment was prepared by VBS as part of the overall assessment for licensing the above vaccine in Canada.

1.2 Background

Escherichia coli Vaccine, Live Culture is manufactured by Fort Dodge Animal Health (US Veterinary Biologics Establishment License No. 112) and is currently licensed for sale in the U.S. This avian vaccine consists of a live culture of an E. coli bacterial strain that has been attenuated by deletion of part of its aroA gene required for aromatic amino acid biosynthesis. The vaccine is intended for administration to healthy chicks at one day of age or older as an aid in the prevention of disease caused by avian pathogenic E. coli.

Although non-pathogenic E. coli are normally found in the intestines of poultry, certain strains of E. coli will generate extra-intestinal infections, or colibacillosis, in chickens. Colibacillosis is frequently associated with poor animal husbandry, and is a common secondary infection following bacterial or viral infection. In severe cases, these pathogenic strains can invade and colonize internal organs, producing septicemia characterized by airsacculitis, perihepatitis, and/or pericarditis, which can be fatal. Colibacillosis is also a frequent cause of carcass condemnation at slaughter. Extra-intestinal pathogenic E. coli thus represents a significant animal health concern and an economic burden to poultry producers world-wide. In Canada, cellulitis, another lesion typical of colibacillosis, has been noted as a common reason for carcass condemnation of Canadian broiler chickens (Kumor et al., 1998).

The prophylactic administration of antibiotics is the primary treatment course for colibacillosis; however, many pathogenic E. coli strains have developed resistance to multiple antibiotics (Vandemaele et al., 2002; Gomis et al., 2001; Merck Veterinary Manual). Currently, there are no other live vaccines designed to combat colibacillosis-causing E. coli licensed for use in Canadian poultry flocks.

2. Purpose and Need for Proposed Action

2.1 Significance

The label indication for Escherichia coli Vaccine, Live Culture is for mass administration to healthy chickens one day of age or older by spray as an aid in the prevention of disease caused by Escherichia coli. A second vaccination is recommended for long-lived birds at 12–14 weeks of age.

2.2 Rationale

VBS evaluates veterinary biologic product submissions for licensure under the Health of Animals Act and Regulations. The general criteria for licensing are: a) the product must be pure, potent, safe and efficacious; b) the product must be licensed in the country of origin; c) vaccine components must be relevant to Canadian disease conditions; and d) the product must be produced and tested in accordance with generally accepted “good manufacturing practices.” This U.S.-origin vaccine meets these general criteria and presented no unacceptable importation risk, and therefore was evaluated for licensing by VBS.

3. Alternatives

The two alternative options being considered are: a) to issue a Permit to Import Veterinary Biologics to Wyeth Animal Health Canada for the importation of Escherichia coli Vaccine, Live Culture if all licensing requirements are satisfactory, or b) not to issue a Permit to Import Veterinary Biologics if licensing requirements are not met.

4. Molecular and Biological Characteristics of Parental and Recombinant Organisms

4.1 Identification, Sources, and Strains of Parental Organisms

The parental E. coli strain was isolated from a clinical case of avian colibacillosis. This strain is pathogenic to chickens, as it was shown to be invasive and capable of persisting for at least five weeks in specific pathogen-free (SPF) chicks. The parent E. coli is of serotype O78, which is a predominant serotype implicated in avian colibacillosis world-wide (Rodriguez-Siek et al., 2005). In Canada, the prevalence of this serotype is not fully known. One study examining 44 E. coli isolates associated with colibacillosis in western Canadian chickens and turkey, revealed that O78 was the most common serotype that could be identified, although this amounted to only 5 of the isolates (Allan et al., 1993). Similarly, 15 out of the 141 serotyped E. coli isolates from cellulitis and other colibacillosis lesions found in Saskatchewan broiler chickens were determined to be of the O78 serotype, again the most predominant serotype identified (Gomis et al., 2001).

It has been proposed that vaccine protection against avian pathogenic E. coli infection is significantly less efficient for heterologous strains than homologous strains (Kariyawasam et al., 2004; Dho-Moulin 1999; Merck Veterinary Manual). Since the vaccination-challenge studies conducted by the manufacturer utilized pathogenic O78 E. coli, it is unclear to what extent this vaccine will protect against E. coli of different serotypes. Post-licensure studies investigating the cross-protection of vaccinated birds against strains of E. coli other than O78 are being performed in the U.S.

4.2 Source, Description and Function of Foreign Genetic Material

The vaccine organism has not been modified by the addition of foreign genes. Rather, the endogenous aroA gene from the parental E. coli strain has been inactivated by allelic exchange with a mutant version. The aroA gene encodes 5-enolpyruvyl shikimate-3-phosphate synthase, which is required for the synthesis of aromatic metabolites, including tyrosine, phenylalanine, tryptophan, p-aminobenzoate (PABA), and 2,3-dihydroxybenzoate.

4.3 Method of Accomplishing Genetic Modification

The mutant aroA gene was created by separately polymerase chain reaction (PCR) amplifying the 5' and 3' portions of the wild type gene (omitting a 100 base pair (bp) region in the centre of the gene) and ligating these two PCR products together into a shuttle plasmid. The resultant aroA gene was thereby inactivated by the deletion of the internal 100bp region, and also by the incorporation of two stop codons via the internal PCR primers. The mutant aroA gene was subsequently sub-cloned into a mobilized suicide vector, which was transferred to the parental pathogenic E. coli strain via conjugation. The vaccine strain was isolated following a series of selection steps designed to identify double recombinants that had replaced the chromosomal aroA gene with the mutant allele, but did not retain the plasmid backbone. Details of the methods used to accomplish the genetic modification of the vaccine organism are on file with VBS.

4.4 Genetic and Phenotypic Stability of the Vaccine Organism

The manufacturer estimates that the reversion rate of the vaccine strain back to the parental strain is less than 10-11 for the aroA mutation. Indeed, deletion of a large part of a gene provides confidence that random spontaneous mutations will be unable to repair the loss of function, especially compared to a system of inactivation dependent on the modification of only a few nucleotides. The genetic stability of the master seed under normal culture conditions has been demonstrated up to n+5 passages, which is the upper limit of fermentation specified for the production of the vaccine.

As a consequence of the aroA gene mutation, the vaccine E. coli strain is auxotrophic for aromatic metabolites, including tyrosine, phenylalanine, tryptophan, and PABA. The requirement for PABA, a metabolite of limited availability in vertebrate tissues, is indicated as being primarily responsible for the attenuation of in vivo growth. It was not addressed to what extent a diet rich in PABA and other aromatic amino acids could influence the persistence of the vaccine strain in a vaccinated animal, particularly in the gastrointestinal tract. Sandhu and colleagues (1976) reported that mice with a high oral intake of PABA could restore the virulence of an otherwise nonpathogenic PABA-auxotrophic fungus.

4.5 Horizontal Gene Transfer and Potential for Recombination

The potential for genetic recombination occurring between the vaccine E. coli strain and the genome of the vaccinated animal should be less than that of the parental pathogenic E. coli, due to the vaccine strain's limited ability to survive and persist in the target animal (i.e. reduced exposure).

The potential for horizontal gene transfer has not been investigated by the manufacturer and cannot be eliminated. E. coli are known to acquire foreign DNA through horizontal gene transfer, via conjugation (typically only plasmid DNA transferred), by transduction (involving bacteriophage), or by free DNA uptake (transformation). Moreover, it has been hypothesized that many genetic elements in septicemic E. coli might have originated from horizontal gene transfer events (Ron, 2006; Mokady et al., 2005). As the aroA mutation is the sole mechanism preventing the continued survival of the vaccine E. coli strain, restoration of this function through the incorporation of new genetic material would be of obvious benefit. The aroA gene is conserved in many species of bacteria and even has orthologs in some plants (Richards et al., 2006). Consequently, the nonpathogenic E. coli and other bacteria present in the gut of chickens and in the poultry barn environment could all serve as a potential source of genetic material capable of complementing the aroA vaccine mutation. In addition, because the aroA mutation is not a dominant negative, expression from a functional aroA gene, either incorporated elsewhere in the bacterial genome or in a plasmid, would be sufficient to restore the wild type phenotype (i.e. homologous recombination would not be required to remove the mutant allele). It is important to note, however, that such a horizontal gene transfer event would not increase the bacteria's pathogenicity beyond that of the wild type parental E. coli, which may already be present at the farm, or not unlike other pathogenic E. coli in the poultry flock being vaccinated. Further, the chances of horizontal gene transfer taking place after vaccination is significantly restricted, due to the inability of the vaccine organism to persist in an environment devoid of its requisite aromatic nutrients. Therefore, although in theory horizontal gene transfer could restore pathogenicity to a few aroA deleted E. coli from the vaccine, this threat does not warrant the restricted use of this veterinary biologic in Canada, because the resulting bacteria would not be unlike the strains of wild type pathogenic E. coli already present in Canada.

As a source of DNA, the vaccine strain poses no increased hazard compared to the parental E. coli strain. The system employed to construct the vaccine organism ensured the elimination of the antibiotic resistance markers present on the plasmid backbone. Consequently, the genetically modified organism in the vaccine cannot serve as a source of genetic material contributing to antibiotic resistance.

4.6 Host Range/Specificity, Tissue Tropism and Shed/Spread Capabilities

The wild type parental E. coli strain was reported to colonize the liver, spleen, heart, air sac, and caeca of SPF chicks. Studies conducted by the manufacturer suggest that the vaccine E. coli strain retains this tissue tropism, albeit with a reduced ability to colonize and persist in the internal organs, owing to its requirement for supplemental aromatic metabolites.

In a shed/spread study conducted by the manufacturer, swabs were taken from the feed bins, water bowls, floor, and top-front part of the cages following the vaccination of fifty chicks by coarse spray to monitor environment contamination by the vaccine organism.The vaccine organism was recovered from the environment at 3 and 7 days post-vaccination, but not after 10, 14, or 24 days, confirming the limited persistence of the aroA mutant E. coli. The manufacturer did not submit data on the rate of vaccine bacterial shedding in the faeces from vaccinated birds. The vaccine strain was not recovered from liver, heart, or air sac swabs that were taken from non-vaccinated contact birds necropsied at any of these same timepoints post-vaccination

4.7 Comparison of the Modified Organisms to Parental Properties

Due to the mutation of the aroA gene, the modified E. coli in the vaccine shows an impaired ability to persist in chickens and is consequently non-pathogenic. The aroA-mutant vaccine strain retains the expression of the surface appendages that have been shown to be important in the pathogenesis of avian colibacillosis, such as type 1 fimbriae and flagellae, which might aid in the generation of a robust and specific immune response.

4.8 Route of Administration/Transmission

Escherichia coli Vaccine, Live Culture is recommended to be administered to healthy chicks at one day of age or older by coarse spray. A second vaccination is recommended for long-lived birds at 12-14 weeks of age.

5. Human Safety

5.1 Previous Safe Use

The vaccine strain has not been administered to humans.

5.2 Probability of Human Exposure

Human exposure is likely to be limited to employees in the manufacturing facility, veterinarians, animal technicians, and poultry farm operators. A withdrawal period of 21 days is indicated for this product, helping to reduce the likelihood of humans being exposed to the vaccine organism through consuming meat from the vaccinated chicken.

5.3 Possible Outcomes of Human Exposure

Human exposure is not expected to be of significant health concern. The requirement of the vaccine organism for exogenous aromatic amino acids and PABA should restrict its ability to colonize and infect humans, similar to what it does with exposed chickens. In addition, the vaccine strain was shown to be safe in mice and pigs, suggesting a general safety in mammals, including humans.

5.4 Pathogenicity of Parent Microorganisms in Humans

The pathogenicity of the parental E. coli strain in humans is unknown; however, E. coli of the O78 serotype can be pathogenic to humans, contributing to newborn meningitis, enteritis, and septicaemia (Ron, 2006; Chérifi et al., 1994).

5.5 Effect of Gene Manipulation on Pathogenicity in Humans

Deletion of the aroA gene reduces the potential for pathogenicity in humans, again because of the requirement for aromatic metabolite supplementation.

5.6 Risk Associated with Widespread use of the Vaccine

No risks associated with the widespread use of the vaccine have been identified.

6. Animal Safety

6.1 Previous Safe Use

The manufacturer reported no adverse effects, as measured by mortality, following the vaccination of chicks with the E. coli vaccine in any of their efficacy, safety or field safety trials, which amounted to over 90,000 chickens. In addition, the manufacturer tested the experimental vaccine on a small group of piglets (orally) and mice (intra-cerebrally and intra-peritoneally) to support its non-target animal safety.

6.2 Fate of the Vaccine in Target and Non-Target Species

In a study conducted by the manufacturer, 50 chicks were vaccinated by coarse spray at one day of age. Birds were subsequently necropsied at 4, 8, 11, 15, or 25 days of age (10 at each timepoint), with swabs taken from the air sac, heart, and lung to detect the presence of the vaccine strain. The vaccine strain was recovered from 1 of the 10 birds sacrificed at 4 days of age (from a liver swab), but was not recovered from any of the birds necropsied at any of the longer timepoints, suggesting that the avirulent E. coli is rapidly cleared from the vaccinate. Consistent with this result, the vaccine bacteria were detected in the environment at three and seven days post-vaccination, but were not identified in the environmental swabs taken at any of the later timepoints. A full biodistribution study was not undertaken, nor was the rate of faecal shedding, a primary source of contaminating E. coli, investigated (Ardrey et al., 1968; Merck Veterinary Manual).

6.3 Potential of Shed and/or Spread from Vaccinate to Contact Target and Non-Target Animals

In the shed/spread study conducted by the manufacturer, the vaccine E. coli strain could not be recovered from swabs of the liver, heart, and air sacs of necropsied non-vaccinated birds housed in close proximity to vaccinated chicks. Spread of the wild type E. coli is believed to occur through inhalation of contaminated faeces. Therefore, even though some vaccine organism can initially be found in the environment, it must not be of sufficient quantity or capacity to colonize the internal organs of in-contact non-vaccinates. Normal husbandry practices would be to vaccinate the entire group of chicks together anyway, and vaccination inside a biosecure rearing facility would prevent spread to non-target animals or to the outside environment.

6.4 Reversion to Virulence Resulting from Back Passage in Animals

Two reversion-to-virulence studies were undertaken by the manufacturer. In the first study, swabs were taken from the air sac, heart, and liver of necropsied chicks seven days post-vaccination to create a pooled suspension combining the swabs from all 10 birds. A portion of this pooled suspension (7.64x104 cfu/dose) was given intratracheally to a second group of chicks. Seven days post-exposure, the vaccine E. coli strain was recovered from 1 of the 10 birds in this second group; however, when the samples from all birds in the second group were pooled together, the titre of bacteria was too low to quantify. No vaccine strain or wild type E. coli was isolated from chicks that were administered this second pooled suspension. In a second reversion-to-virulence study, 3 groups of birds (10 chicks each) were administered the master seed, and were subsequently necropsied at either 4 days, 8 days, or 21 days post-vaccination. No vaccine or wild type E. coli was recovered from swabs taken from the heart, air sac, and lungs at any of these timepoints. In addition, no lesions characteristic of colibacillosis, were observed in any of the vaccine-exposed birds. Taken together, these data suggest that the vaccine organism does not revert to virulence when passaged through a host animal.

6.5 Effect of Overdose in Target and Potential Non-Target Species

The manufacturer reported that no death or adverse events attributable to the vaccine were observed following vaccination of day-old chicks with approximately 250x the minimum vaccine dose required at serial release, indicating a comfortable margin of safety.

6.6 The Extent of the Host Range and the Degree of Mobility of the Vector

The full host range of the vaccine is unknown.

7. Affected Environment

7.1 Extent of Release into the Environment

The manufacturer presented data indicating that the vaccine strain of bacteria could be detected in the environment at 3 and 7 days post-vaccination, but not after 10, 14, or 21 days post vaccination. The sensitivity of the assay (no enrichment culture) used by the manufacturer to detect E. coli was not provided. The potential for environmental contamination by the vaccine is increased by the route of administration (coarse spray). It is unclear at what rate the vaccine is shed by vaccinated animals, which may be important if chicks are vaccinated in the hatchery and then moved to a broiler house shortly after vaccination. It has been estimated that the related aroA mutant Salmonella typhimurium vaccine in chickens can be shed for up to 26 days post vaccination (Tan et al., 1997).

7.2 Persistence of the Vector in the Environment / Cumulative Impacts

According to the environmental monitoring done by the manufacturer, the vaccine organism does not appear to persist in the environment. The aroA defect means that the vaccine E. coli strain cannot survive without supplemental aromatic amino acids or PABA, which are not readily available in the environment.

7.3 Extent of Exposure to Non-Target Species

The extent of exposure to non-target species is expected to be low, because vaccine administration predominantly occurs in housed domestic poultry. In addition, even though chicken litter is often spread on neighbouring fields, the limited environmental persistence of the aroA-mutant E. coli should prevent non-target animal exposure by this route.

7.4 Behaviour of Parent Microorganisms and Vector in Non-Target Species

The behaviour of the parental E. coli strain in non-target species is unknown. However, E. coli of serotype O78 can be pathogenic to humans, as well as bovine, ovine, and porcine animals (Ewers et al., 2004; Wray et al., 1993; Dassouli-Mrani-Belkebir et al., 1988). In addition, based on clonal relationships, it has been suggested that the pathogenic E. coli O78 strains infecting humans and animals might be related (Chérifi et al., 1994).

8. Environmental Consequences

8.1 Risks and Benefits

For any vaccine, risks of vaccination can be attributed to potential adverse reactions. In numerous laboratory and field studies, the vaccine strain indicated no apparent risk, and demonstrated its safety in chickens. The benefit of the vaccine is its ability to protect chickens against pathogenic serotype O78 E. coli challenge, as shown in the efficacy studies performed by the manufacturer.

8.2 Relative Safety Compared to other Vaccines

This live E. coli vaccine does not contain any selectable antibiotic resistance markers. Other live vaccines intended for use against avian pathogenic E. coli have yet to be submitted for licensure in Canada.

9. Mitigative Measures

9.1 Worker Safety

The vaccine will be manufactured at Fort Dodge Animal Health (Iowa, USA), a veterinary biologics establishment licensed by the US Department of Agriculture. Individuals working with the vaccine, such as employees in the production facility, veterinarians, animal technicians, or poultry operators, can be exposed to the live genetically modified organism. Since the vaccine E. coli strain is attenuated by the genetic manipulation, it is not anticipated to cause human pathogenicity.

9.2 Handling Vaccinated or Exposed Animals

Exposure through handling vaccinated chicks is not expected to be significant, since chicks reared in a biosecure facility are not typically handled directly by humans without taking precautionary biosafety measures.

10. Monitoring

10.1 General

The vaccine licensing regulations in Canada require manufacturers to report all suspected significant adverse reactions to the CFIA within 15 days of receiving notice from an owner or a veterinarian. Veterinarians may also report suspected adverse reactions directly to the CFIA. If an adverse reaction complaint is received by VBS, the manufacturer is asked to investigate and prepare a report for the owner's veterinarian and the CFIA. If the problem is resolved to the satisfaction of the veterinarian/client, no further action is usually requested by VBS. However, if the investigation is unsatisfactory, VBS may initiate regulatory action depending on the case, which may include further safety testing, temporarily stopping sales of the product, or product withdrawal from the market.

10.2 Human

No special monitoring of the human safety of the product will be carried out.

10.3 Animal

Veterinarians, vaccinators, and producers should report any suspected adverse reactions to VBS as indicated above. For reporting purposes, adverse reactions are divided into Type 1, 2, and 3 reactions. Type 1 reactions are defined as any systemic adverse reaction, anaphylactic or hypersensitivity, requiring veterinary treatment including: persistent fever, recumbency, persistent lethargy, decrease in activity, muscle tremors, shivering, hypersalivation, dyspnea and other respiratory problems, cyanosis, diarrhea, vomiting, colic and other gastrointestinal problems, eye problems, abortions and other reproductive problems, and neurological signs. Type 2 reactions are defined as death or an increase in mortality rate following vaccination. Type 3 reactions are defined as local persistent reactions, such as edema, abscess, granuloma, fibrosis, alopecia, hyperpigmentation, and excessive pain at the injection site. Suspected adverse reactions should be reported using the form Notification of Adverse Reactions to Veterinary Biologics (CFIA/ACIA 2205).

11. Consultations and Contacts

Manufacturer

Fort Dodge Animal Health
800 5th Street North West
Fort Dodge, Iowa, USA 50501

Canadian Distributer

Wyeth Animal Health
A Division of Wyeth Canada
400 Michener Road
Guelph, Ontario, Canada N1K 1E4

12. Conclusions and Actions

Based on our assessment of the available information, VBS has concluded that the importation and use of Escherichia coli Vaccine, Live Culture (Trade Name: Poulvac EC) in Canada would not be expected to have any significant adverse effect on the environment, when manufactured and tested as described in the approved Outline of Production, and used according to label directions.

Following this assessment and the completion of the Canadian veterinary biologics licensing process, the Permit to Import Veterinary Biologics of Wyeth Animal Health (Canada) may be amended to allow the importation and distribution of the following product in Canada:

  • Escherichia coli Vaccine, Live Culture (Trade Name: Poulvac E. coli), USDA Product Code 1551.R0, VBS File Number 800VB/E2.0

All serials of this product must be released by the USDA prior to importation into Canada. All conditions described in the Permit to Import Veterinary Biologics must be followed with respect to the importation and sale of this product.

13. References

Allan B.J., van den Hurk J.V., & Potter A.A. (1993) Characterization of Escherichia coli isolated from cases of avian colibacillosis. Canadian Journal of Veterinary Research 57(3):146-51.

Ardrey, W.B., Peterson, C.F., & Haggart, M. (1968) Experimental colibacillosis and the development of carriers in laying hens. Avian Disease 12(3): 505-11.

Chérifi, A., Contrepois, M., Picard, B., Goullet, P., Ørskov, I., & Ørskov, F. (1994) Clonal relationships among Escherichia coli serogroup O78 isolates from human and animal infections. Journal of Clinical Microbiology 32(5): 1197-1202.

Dassouli-Mrani-Belkebir, A., Contrepois, M., Girardeau, J.P., & der Vartanian, M. (1988) Characters of Escherichia coli O78 isolated from septicemic animals. Veterinary Microbiology 17(4): 345-56.

Dho-Moulin, M., Fairbrother, J.M. (1999) Avian pathogenic Escherichia coli (APEC). Veteterinary Research 30(2-3): 299-316.

Ewers, C., Schüffner, Claudia, Weiss, R., Baljer, G., & Wieler. L.H. (2004) Molecular characteristics of Escherichia coli serogroup O78 strains isolated from diarrheal cases in bovines urge further investigations on their zoonotic potential. Molecular Nutrition and Food Research 48(7): 504-14.

Gomis, S.M., Riddell, C., Potter, A.A., & Allan, B.J. (2001) Phenotypic and genotypic characterization of virulence factors of Escherichia coli isolated from broiler chickens with simultaneous occurrence of cellulitis and other colibacillosis lesions. Canadian Journal of Veterinary Research 65(1): 1-6.

Kariyawasam, S., Wilkie, B.N., & Gyles, C.L. (2004) Construction, characterization, and evaluation of the vaccine potential of three genetically defined mutants of avian pathogenic Escherichia coli. Avian Disease 48(2): 287-99.

Kumor, L.W., Olkowski, A.A., Gomis, S.M., & Allan, B.J. (1998) Cellutis in broiler chickens: epidemiological trends, meat hygiene, and possible human health implications. Avian Disease 42(2):285-91.

Merck Veterinary Manual 9th edition Whitehouse Station, NJ: Merck & Co., Inc. 2005.

Mokady, D., Gophna, I., & Ron, E.Z. (2005). Extensive gene diversity in septicemic Escherichia coli strains. Journal of Clinical Microbiology 43(1): 66-73.

Richards, T.A., Dacks, J.B., Campbell, S.A., Blanchard, J.L., Foster, P.G., McLeod, R.& Roberts, C.W. (2006) Evolutionary origins of the eukaryotic shikimate pathway: Gene fusions, horizontal gene transfer, and endosymbiotic replacements. Eukaryotic Cell 5(9): 1517-31.

Rodriguez-Siek, K.E., Giddings, C.W., Doetkott, C., Johnson, T.J., & Nolan, L.K. (2005) Characterizing the APEC pathotype. Veteterinary Research 36(2): 241-56.

Ron, E.Z. (2006) Host specificity of septicemic Escherichia coli: human and avian pathogens. Current Opinion in Microbiology 9(1): 28-32.

Sandhu, D.K., Sandhu, R.S., Khan, Z.U., & Damodaran, V.N. (1976) Conditional virulence of a p-aminobenzoic acid-requiring mutant of Aspergillus fumigatus. Infection and Immunity 13(2): 527-32.

Tan, S., Gyles, C.L., & Wilkie, B.N. (1997) Evaluation of an aroA mutant Salmonella typhimurium vaccine in chickens using modified semisolid Rappaport Vassiliadis medium to monitor faecal shedding. Veterinary Microbiology 56(1-2): 79-86.

Vandemaele, F. Vereecken, M., Derijcke, J., & Goddeeris, B.M. (2002) Incidence and antibiotic resistance of pathogenic Escherichia coli among poultry in Belgium. Veteterinary Records 151: 355-6.

Wray, C., McLaren, I.M., & Carroll, P.J. (1993) Escherichia coli isolated from farm animals in England and Wales between 1986 and 1991. Veteterinary Records 133(18): 439-42.


Prepared by:

Veterinary Biologics Section
Terrestrial Animal Health Division
Canadian Food Inspection Agency