Potential Impact of Food Safety Vaccines on Health Care Costs

Abstract

Foodborne pathogens continue to cause several outbreaks every year in many parts of the world. Among the bacterial pathogens involved, Shiga toxin–producing Escherichia coli, Campylobacter jejuni, and nontyphoidal Salmonella species cause a significant number of human infections worldwide, resulting in a huge annual economic burden that amounts to millions of dollars in health care costs. Human infections are primarily caused by the consumption of contaminated food. Vaccination of food-producing animals is an attractive, cost-effective strategy to lower the levels of these pathogens that will ultimately result in a safer food supply and fewer human infections. However, producers are often reluctant to routinely vaccinate animals against these pathogens since they do not cause any detectable clinical symptoms. This review highlights recent approaches used to develop effective food safety vaccines and the potential impact these vaccines might have on health care costs.

Introduction

Foodborne illness causes several deadly outbreaks every year. It is estimated that the average Escherichia coli O157:H7 outbreak, for example, causes hemolytic uremic syndrome (HUS) complications in 7–10% of the affected cases, which are typically young children, and that can lead to a 0.5% overall death rate. As a result, health care services may be overwhelmed due to a spike in the number of patients affected with E. coli O157 (Frank et al., 2011). Campylobacter species are another leading foodborne bacterial pathogen that is estimated to cause 400 million human cases of gastroenteritis per year worldwide (Senok and Botta, 2009; Kirkpatrick and Tribble, 2011; Silva et al., 2011). However, although most of the cases are individual infections rather than outbreaks, Campylobacter species remain a significant economic burden on health care systems. Nontyphoidal Salmonella species cause an estimated 93.8 million cases of gastroenteritis annually, of which approximately 80.3 million cases are foodborne. In the United States, approximately 1 million incidents of human salmonellosis are estimated to occur each year, resulting in 19,336 hospitalizations, 17,000 quality-adjusted life years lost, and USD $3.3 billion in total medical expenditures and lost productivity annually (Cummings, 2012). Among the nontyphoidal Salmonella species, Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) and Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) are frequently associated with human infections, although other serovars have also been reported (Cummings, 2012).

Vaccination is one of the most effective strategies in preventing disease. Most of the available vaccines, however, target only the affected species rather than protecting humans indirectly by immunizing the animal source. Several important human diseases are foodborne in which the causative organism typically colonizes the animal host asymptomatically while causing clinical symptoms in humans (O'Brien, 2012). Vaccination of these animals has the potential to prevent or lower the incidence of human disease. Furthermore, developing a vaccine that targets domestic animals is cheaper, faster, and has fewer regulatory hurdles than developing a human vaccine counterpart (Kochhar et al., 2013). Therefore, intervention strategies at the farm level targeting human health would have a faster impact and would be more cost effective. Since foodborne illness is caused by a variety of viruses, bacteria, and parasites, this review will only focus on three of the major bacterial pathogens: Shiga toxin–producing E. coli, nontyphoidal Salmonella species, and Campylobacter jejuni.

Shiga Toxin–Producing E. coli (STEC)

The consumption of contaminated beef products is a major source of STEC infections and hence the term “hamburger disease.” Many recent outbreaks, however, demonstrated that salad leaves (Marder et al., 2014), cantaloupes (Bowen et al., 2006), cookie dough (Neil et al., 2012), and peanut butter (He et al., 2011) are also potential sources for human E. coli infections. The technological advances in investigative epidemiology, such as whole genome sequencing, have allowed for faster determination of outbreak sources, as well as rapid detection and control. However, these techniques are still used mainly in research laboratories and not used routinely by public health authorities.

Although more than 100 serotypes of E. coli produce Shiga toxin, only a limited number of serotypes are actually pathogenic. STEC serotype O157:H7 is responsible for the majority of foodborne cases followed by STEC serotype O26 (Kaper and O'Brien, 2014). Another important serotype is O104:H4, which was responsible for a milestone outbreak in Germany in 2011 that caused the death of 56 people (Frank et al., 2011). STEC causes a variety of clinical signs in humans that include hemorrhagic colitis and HUS, the leading cause of chronic renal failure in children in several countries (Pennington, 2010). The main virulence factors responsible for these clinical outcomes are Shiga toxin types 1 and 2, which have the potential for causing lethal vascular and neurological effects (Trachtman et al., 2012). The main reservoir for STEC is cattle, which harbors this organism in the intestinal tract (Arthur et al., 2002; Hussein, 2007) at the rectum, a section of the intestine that is densely populated with lymphoid follicles (Naylor et al., 2003). Cattle do not show any clinical symptoms regardless of the bacterial load (Naylor et al., 2003). STEC gains entry into the human food chain from cattle through either fecal contamination of meat during slaughter, the use of feces as an organic fertilizer, or drinking water contamination (Arthur et al., 2002; Marder et al., 2014).

In addition to Shiga toxins, E. coli O157:H7 possess several virulence factors that facilitate the colonization of its host. Attaching and effacing (A/E) is a term used to describe a histopathological lesion (Pennington, 2010) that occurs as the result of bacteria manipulating host cellular structure through a chromosomally encoded pathogenicity island called the locus of enterocyte effacement (LEE) (Kenny et al., 1997). Specifically, LEE encodes a filamentous structure known as the type III secretion system (T3SS), which translocates effector proteins responsible for the A/E lesion into the host cell (Kenny et al., 1997). The translocated proteins contain Tir, a bacterial receptor that will embed itself in the host cell membrane and bind to the bacterial outer membrane protein intimin (Ide et al., 2001). In turn, this binding leads to the formation of the A/E lesion. Other STEC serotypes, including the reclassified O104:H4, use a biofilm-like aggregation mechanism to attach tightly to the intestinal wall and cause disease (Navarro-Garcia, 2014).

Some STEC virulence factors, such as intimin and EspB, induce an immune response during infection in cattle (Bretschneider et al., 2007) and patients with HUS (Li et al., 2000). Since these virulence factors have proven to be immunogenic, vaccination has emerged as an effective strategy to prevent E. coli O157:H7 infection. Various vaccine formulations have been tested with variable results in cattle (Potter et al., 2004; Dziva et al., 2007; Smith et al., 2009; McNeilly et al., 2010; Vilte et al., 2011) and in other animal models (Agin et al., 2005; Babiuk et al., 2008).

Two commercial vaccines that reduce the prevalence and duration of shedding of E. coli O157 have been approved by regulatory authorities. Econiche^™, which is produced by Bioniche Life Sciences (Belleville, ON), is composed of an extract of T3SS secreted proteins (Potter et al., 2004). It has been fully approved by the Canadian, Australian, and United Kingdom authorities in addition to conditional licensing in the United States. The recommended 3-dose vaccination regimen of feedlot cattle 3–4 weeks apart resulted in a 59–98% reduction in fecal shedding and a significant reduction in the duration of shedding (Potter et al., 2004). The other available vaccine is produced by Epitopix (Willmar, MN) and is only conditionally licensed in the United States and therefore is only available through veterinarians. The vaccine contains siderophore outer membrane receptor proteins and has demonstrated reductions of up to 85% in E. coli O157 shedding when given using the recommended 2-dose approach (Fox et al., 2009; Thomson et al., 2009). The siderophore receptor protein (SRP) vaccine, however, did not affect bacterial shedding of STEC serotype O26 when tested in cattle, limiting its efficacy to STEC serotype O157 (Paddock et al., 2014).

C. jejuni

Campylobacter species are one of the leading causes of bacterial foodborne illness (Senok and Botta, 2009; Kirkpatrick and Tribble, 2011; Silva et al., 2011). The bacterium also causes a variety of sequelae in a limited number of cases that include reactive arthritis and the life-threatening neuropathy Guillain-Barré syndrome (Kirkpatrick and Tribble 2011; Silva et al., 2011). The number of human campylobacteriosis cases in developed countries is variable, but a minimum of 21.9 cases for every 100,000 people has been recorded in the United States (Samuel et al., 2004). The situation is more serious in developing countries, with reports of high annual infection rates that reach up to 60% in children under 5 years old, with many of those infected being asymptomatic but shedding the bacteria (Coker et al., 2002; Samuel et al., 2004). Therefore, Campylobacter species, which affect the health of millions of people worldwide, has a staggering estimated annual economic burden of up to US$ 1.7 billion in the United States alone (Hoffmann et al., 2012). The two main species that are responsible for the majority of the cases in the developing countries are C. jejuni and C. coli, with C. jejuni accounting for a higher percentage of infections consistently (Hoffmann et al., 2012).

Campylobacter infection in humans requires a small dose of ≈500 bacteria that preferably colonizes the distal ileum and colon (Kirkpatrick and Tribble, 2011; Silva et al., 2011). It is generally accepted that the bacteria preferentially resides in the mucosal layer until it disrupts the epithelial barrier, which will result in an inflammatory response. Consequently, a range of clinical symptoms develop that includes watery to voluminous and bloody diarrhea accompanied by abdominal pain, fever, and occasional vomiting (Kirkpatrick and Tribble, 2011). During its course of infection, C. jejuni uses a variety of virulence factors that include adhesions and outer membrane proteins that aid in bacterial adhesion or invasion in vitro (Guerry, 2007). Campylobacter also uses a variety of toxins that lead to epithelial cell death and therefore contributes to the disruption of the mucosa.

The main source of C. jejuni infection in humans is the consumption of fresh poultry products (Kirkpatrick and Tribble, 2011). Chickens get heavily colonized (up to 10⁹ per gram of intestinal content) early in their life and the bacteria have a predilection to the ceca part of the large intestine without any apparent signs of pathology (Beery et al., 1988). As broiler chicken barns are densely populated, C. jejuni spreads quickly throughout the entire flock, reaching up to 90% (Achen et al., 1998).

Developing a vaccine against a pathogen such as C. jejuni in poultry can be challenging for several reasons. In addition to safety and efficacy, a protective immune response must be mounted quickly and with a minimum number of vaccine doses due to the short lifespan of a broiler chicken. The ideal vaccine should also protect against several subtypes, as poultry flocks are usually colonized by more than one subtype (Kramer et al., 2000). Epidemiological modeling predicts that a reduction by 3 logs in the level of C. jejuni shedding by broilers would significantly reduce human infections (de Zoete et al., 2007; Singer et al., 2007).

Maternal antibodies might have a role in protecting broiler chicks for the first few days of their life. This is supported by evidence from a study where chicks hatching from a breeder that was colonized by C. jejuni had delayed shedding of up to 4 days compared to chicks from noninfected breeders (Sahin et al., 2003). The infective dose of chicks with no circulating maternal antibodies is 50% less than that of chicks with antibodies, confirming that an adaptive immune response induced by a vaccine might be protective (Sahin et al., 2003).

To date, there is no licensed vaccine against C. jejuni in broiler chickens. The vaccines that have been studied or are being developed are whole-cell killed or live attenuated vaccines, flagella-based vaccines, and subunit vaccines. Historically, whole-cell vaccines are used as a starting point for many vaccines. Despite the good results obtained by such vaccines with several bacterial pathogens, the success in preventing C. jejuni colonization of broiler chickens was limited at best (Rollwagen et al., 1993). When day-old broiler chickens were given 1×10⁹ colony-forming units (CFU) of a formalin-inactivated C. jejuni whole-cell vaccine multiple times and challenged using a seeder model (a small group of infected chickens housed with noninfected ones), the maximum reduction in colonization in the vaccinated group compared to the nonvaccinated group was 1.5 logs (Rice et al., 1997). The addition of E. coli heat-labile toxin, which acts as a mucosal adjuvant, did not enhance immunoglobulin A (IgA) levels or protection (Rice et al., 1997).

The use of flagellin and outer membrane proteins as vaccine candidates against C. jejuni infection was adopted as a strategy by several researchers based on their dominant immunogenicity (Khoury and Meinersmann, 1995; Widders et al., 1998; Wyszynska et al., 2004). Similarly, vaccination with an attenuated Salmonella Typhimurium strain expressing the CjaA protein was able to reduce C. jejuni colonization of chickens by approximately 6 logs compared to the control (Wyszynska et al., 2004). Likewise, a vaccine using a Salmonella strain expressing CjaD was able to lower C. jejuni shedding to <1×10³ CFU/g in broiler chickens immunized at the day of hatch and challenged 20 days later (Layton et al., 2011). The high levels of secretory IgA (sIgA) and circulating IgY associated with reduced shedding in the aforementioned studies suggests that the protection is a result of an adaptive immune response and therefore a vaccine is a promising approach to protect against C. jejuni colonization in broiler chickens.

Nontyphoidal Salmonella Species

Nontyphoidal Salmonella species are major foodborne pathogens in the United Kingdom, Europe, and North America. According to a recent study, 11% of retail poultry products tested in Washington State were positive for Salmonella species (Mazengia et al., 2014), while a similar study conducted in 38 cities in the United States demonstrated that <1% of retail raw ground beef and close to 1% of whole muscle beef was positive for Salmonella species (Vipham et al., 2012). Salmonella Enteritidis and Salmonella Typhimurium are frequently associated with poultry flocks, although Salmonella Heidelberg and Salmonella Kentucky are examples of other serovars that are commonly isolated as well (Foley et al., 2011; Wales and Davies, 2011). Salmonella Enteritidis and Salmonella Typhimurium infections in chickens rarely cause disease symptoms. The birds continue to shed the pathogens for extended periods, resulting in contamination of eggs and the surrounding environment, which ultimately poses a risk to human health (Van Immerseel et al., 2005). Human infections are typically characterized by a gastrointestinal disease that is cleared within a few days, although severe cases can require antibiotic treatment or even hospitalization (Feasey et al., 2012). Hence, this translates into a significant economic impact on both the health care system and the poultry industry.

Many preharvest strategies have been implemented across the world to control the levels of Salmonella Enteritidis and Salmonella Typhimurium, which have been met with considerable success. Examples of such intervention programs include the National Poultry Improvement Plan, regulation (EC) No 2160/2003 of the European Parliament, and the British Egg Industry Council “Lion code of practice” (Cogan and Humphrey, 2003; Foley et al., 2011). Vaccination of chickens forms an important component of these programs since reduced levels of Salmonella species will lower the risk of contaminating the food supply, resulting in fewer human infections (Beal and Smith, 2007; Gast, 2007; Jones et al., 2007; Collard et al., 2008).

Over the years, many Salmonella vaccines have been developed that are either live-attenuated, killed, or recombinant protein vaccines (Van Immerseel et al., 2005; Jones et al., 2007). Live-attenuated vaccines can be easily delivered to chickens of various ages and induce a rapid humoral and cellular immune response. On the other hand, such vaccines involve the introduction of a live virulent strain in the environment, which may persist for extended periods and may revert to the wild-type strain. In addition, live vaccine strains may produce false positives during routine Salmonella screening procedures in poultry flocks (Gast, 2007; Jones et al., 2007). Among the commercially available live attenuated Salmonella vaccines, Nobilis^® SG 9R (MSD Animal Health, Summit, NJ), TAD Salmonella vac^® E/T (Lohmann Animal Health, Cuxhaven, Germany), and Megan^® Vac 1 (Lohmann Animal Health) are well known. The Salmonella enterica serovar Gallinarum 9R vaccine strain (Nobilis^® SG 9R) contains a mutation in the lipopolysaccharide and has proven to be effective under field conditions where 2.5% of the immunized flocks were positive for Salmonella Enteritidis compared to 11.5% in the nonvaccinated group (Feberwee et al., 2001). Similarly, TAD Salmonella vac^® E/T is a live vaccine strain that has mutations in essential metabolic enzyme genes. Vaccination with the aforementioned strain led to a reduction in the number of Salmonella Enteritidis–positive internal organs and eggs, suggesting that this vaccine is effective (Gantois et al., 2006). However, the chickens were challenged intravenously, making it difficult to assess the impact of this vaccine under field conditions. Likewise, Megan^® Vac 1 is an adenylate cyclase and cyclic adenosine monophosphate receptor protein mutant live vaccine strain that was capable of lowering the presence of Salmonella Enteritidis in breeder flock hens and their progeny under field conditions to 38% and 14% in the ceca and reproductive tract, respectively, compared to the control group (64% in the ceca and 52% in the reproductive tract) (Dorea et al., 2010).

Recently, a handful of studies have focused on live attenuated strains that are defective in the Salmonella T3SS (Matulova et al., 2012a, 2012b; De Cort et al., 2013). Salmonella Pathogenicity Island 1 and 2 (SPI-1 and SPI-2) encode for two T3SS that are used to inject virulence factors into host cells (Galan and Collmer, 1999; Galan 2001; Hensel, 2000; Hensel and Kuhle, 2004) and play an important role in Salmonella pathogenesis (Desin et al., 2009; Wisner et al., 2010). Immunization of chickens with a SPI-1 lon mutant vaccine strain (Lon protease is a negative regulator of SPI-1) resulted in lower levels of Salmonella Enteritidis in the internal organs as well as the cecal contents (Matulova et al., 2013b). Likewise, a Salmonella Enteritidis ΔhilAΔssrAΔfliG triple mutant vaccine strain that contains deletions in the SPI-1, SPI-2, and flagellar genes was effective in reducing the number of chickens that were positive for Salmonella Enteritidis postvaccination (De Cort et al., 2013). Moreover, another group has demonstrated that ΔSPI-1 mutants (entire SPI-1 region deleted) induce cross-protective immunity in chickens (Matulova et al., 2013a). Taken together, there is no doubt that the live vaccine strains described above (commercial vaccines and laboratory strains) are promising tools for Salmonella intervention programs. However, many of these vaccine strains need to be evaluated under field conditions where the situation resembles the natural settings encountered by poultry flocks. In addition, the vaccines need to provide cross-protection in order to minimize costs and the need for administering multiple vaccines (Gast, 2007; Jones et al., 2007; Desin et al., 2013). It is also important to note that when chickens are vaccinated a day after hatch, as in the Salmonella Enteritidis ΔhilAΔssrAΔfliG vaccine strain trial, it is possible that the protection observed is due to a colonization-inhibition effect in the intestinal tract (Bohez et al., 2007; Methner et al., 2011).

Killed vaccines comprise whole bacteria that are typically inactivated by heat, acetone, or formalin. They are delivered via the intramuscular or subcutaneous route and require more than one immunization. This class of vaccines is considered to be relatively safer due to the absence of a live Salmonella strain. Killed vaccines are known for inducing strong humoral responses, though they often require adjuvants (Gast, 2007; Jones et al., 2007). Salenvac^® (Merck, Summit, NJ), Layermune SE^® (Ceva Biomune, Lenexa, KS) Poulvac SE^® (Pfizer Animal Health, Florham Park, NJ), and Corymune^® 4K (CECA Corp., Libourne, France) are some of the well-known commercially available Salmonella inactivated vaccines. Salenvac^® is a killed vaccine grown under iron-limiting conditions. This vaccine has been shown to be highly effective in a vaccine trial where significant reduction of Salmonella Enteritidis shedding was observed following an intravenous bacterial challenge (Woodward et al., 2002). Layermune SE^® is another inactivated vaccine that contains several strains of Salmonella Enteritidis. Vaccination of chickens lead to a 1–2 log reduction in the levels of the challenge strain in layers but not breeder boiler chickens (Penha Filho et al., 2009). Likewise, immunization with Poulvac SE^® (consists of three inactivated Salmonella Enteritidis phage types) conferred protection to Salmonella Enteritidis but the bacterial load in the internal organs as well as the cecal contents was unaffected (Inoue et al., 2008). Corymune^® 4K is a multivalent killed vaccine that contains three Avibacterium paragallinarum serotypes and a Salmonella enteritidis strain. Vaccination with this multivalent vaccine resulted in a mild reduction in the levels of Salmonella species in the internal organs and the intestinal tract relative to the control group (Penha Filho et al., 2009). The aforementioned vaccines do confer protection to Salmonella Enteritidis to varying degrees. However, inactivated vaccines are often cleared by the host immune system rapidly, provide limited antigen exposure, and require adjuvants (Van Immerseel et al., 2005; Jones et al., 2007).

Subunit vaccines are a unique class of vaccines that comprise either a single or a group of well-defined antigens that confer protection against a particular pathogen. Such vaccines are relatively safe but generally require at least one booster immunization (Jones et al., 2007). To date, there are no commercially available subunit vaccines for nontyphoidal Salmonella species. In one study, the authors immunized chickens twice with Salmonella Enteritidis FliC (forms the flagellar filament) and observed a significant 2 log unit reduction in Salmonella Enteritidis levels in the cecal contents in the vaccinated group compared to the control (Toyota-Hanatani et al., 2009). Vaccination with type I fimbriae, on the other hand, resulted in lower levels of Salmonella Enteritidis in egg shells and the reproductive tract, but not in the cecal contents and internal organs (De Buck et al., 2005). However, in this vaccine trial, the authors administered the bacterial challenge via the intravenous route, making the comparison with other similar studies difficult. In a more recent study, immunization of chickens with SPI-1 and SPI-2 proteins demonstrated a mild reduction of the challenge strain in the internal organs while the cecal colonization was unaffected (Desin et al., 2011; Wisner et al., 2011). This suggests that a combination of Salmonella T3SS and flagellar proteins (and possibly other candidate proteins) may form a highly effective vaccine since live vaccine strains that contain deletions in T3SS genes as well as flagellar genes have shown to be promising.

The demand for vaccines that are safer, effective, and well defined for the poultry industry has caused animal health companies to shift their research toward alternative vaccine technologies. These include DNA vaccines, RNA vaccines, bacterial vectors (attenuated Salmonella strains used as platforms for delivery of antigens), or viral vectors (Ulmer et al., 2012; Desin et al., 2013). For protection against Salmonella species, it is highly likely that the next generation of vaccines will move toward viral vectors (Desin et al., 2013). These vectors confer several advantages including the following: ease of handling and manipulation; wide tissue tropism; inability to form a fully functional virus; induce long-lasting Th1, Th2, and mucosal immune responses; require a single immunization; can be easily stored; and can be delivered via needle-free systems (Ferreira et al., 2005). Recombinant adenovirus vectors are excellent candidates for expressing bacterial antigens because they have been extensively studied (Ferreira et al., 2005; Lasaro and Ertl, 2009), and two recent studies have shown great promise with the use of this technology (Worgall et al., 2007; Zhou et al., 2007). Hence, a viral vector expressing recombinant Salmonella antigens would be an ideal vaccine for the poultry industry, especially if it can protect against multiple pathogens, possibly as a multivalent vaccine. This technology can then be further enhanced by delivering it in ovo as this will allow for massive immunization of flocks and will significantly lower the administration costs, making the vaccine cheaper and more attractive to the poultry industry (Desin et al., 2013).

Potential Impact of Food Safety Vaccines on Health Care Costs

The rise of noncommunicable diseases, such as cardiovascular conditions and diabetes, in modern societies has resulted in policymakers overlooking the importance of foodborne diseases despite their economic impact. It is estimated that foodborne diseases cost the United Kingdom £1.5 billion every year, while in the United States and New Zealand the estimated annual cost is USD$ 150 billion and NZ$ 260 million, respectively (O'Brien, 2012). The estimated costs vary from country to country, depending on the type of health care system, access to hospitals, and surveillance programs (Akhtar et al., 2014).

In order to determine whether vaccinating particular species of animals against a specific pathogen to prevent disease in humans is cost effective, it is imperative to calculate the annual health care costs associated with the disease. For example, it is estimated that infection with E. coli O157:H7 costs the Canadian health care system CAD$ 403.9 million annually using cost-of-illness approach and based on conservative estimates (Thomas et al., 2008). Using a cost estimate of $3 per head, the annual cost of a national vaccination program in feedlot cattle would be CAD $55.3 million, which equals about 20% reduction in human cases. Based on the available information from the field trials cited by the companies selling E. coli O157 vaccines, a 100% adoption rate will lead to a 60% reduction in human infections, which exceeds the break-even point immensely (Thomas et al., 2008). This conclusion, however, is based on a linear prediction model (Vogstad et al., 2013) that might not necessarily fit the distribution of STEC O157 and assumes that the mere presence of the pathogen in an animal is a good predictor for illness in humans. Although simplistic in approach, such estimation can lead to the conclusion that high adoption rates are required. In the case of STEC O157 vaccines, the ability of the available vaccines to reduce shedding by 50% might be sufficient to stop the bacteria from spreading to humans, since human infections are directly related to the bacterial load in the intestines of cattle. As long as the levels of STEC O157 are maintained below the critical threshold of 1300 CFU/g of intestinal content in cattle, as a result of vaccination, human disease will be reduced by an estimated 83% (Matthews et al., 2013).

Similarly, according to a recent report, a basic cost of illness model predicts the cost associated with human Salmonella foodborne infections to be USD $4.4 billion per year in the United States, while an enhanced cost of illness model predicts a value of USD $11.3 billion per year (Scharff, 2012). Although vaccination of chickens is not mandatory in the United States, unlike the United Kingdom, implementation of the “new egg rule” in the United States has been estimated to cost $24,100 per farm site, which translates into about $0.30 cents per laying hen. Consequently, this should decrease Salmonella in plants by 60%, save at least 30 lives per year, and reduce the total number of salmonellosis cases by 79,000 in the United States (Cummings, 2012). Vaccination of chickens is more cost effective relative to the aforementioned egg rule; hence, this should be attractive to the poultry industry since there has been a drastic reduction in human Salmonella cases in the United Kingdom and Europe after the widespread use of Salmonella vaccines (Cogan and Humphrey, 2003; Collard et al., 2008; Newell et al., 2010).

Conclusions

Despite the overwhelming evidence for the potential impact vaccines against foodborne pathogens might have on curbing the rate of human infections and consequently reducing the cost of health care, the rate of adoption of available commercial vaccines is low. One of the most critical questions for an intervention program is who will bear the cost of vaccination. The targeted pathogens discussed here cause no clinical symptoms and have no detectable effect on growth or product quality and therefore producers do not have the incentive to immunize. The meat and poultry industry are still required by law to thoroughly test their products or send samples for testing and therefore will not have an advantage in paying for the immunization unless there are legal consequences for selling nonvaccinated products. Subsidization by health care regulatory agencies could also be an alternative but it faces several hurdles, especially in the case of enterohemorrhagic E. coli as other serotypes such as O103 and O104 also cause the disease, while the current vaccine confers protection from only one serotype. Taken together, governments and regulatory agencies should provide incentives for vaccination of food-producing animals in order to provide consumers with a safe food supply and to lower the associated economic burden on the health care system. The adoption of complex simulation models that clearly demonstrate the cost-benefit of vaccinating animals could be a key factor in swaying public health agencies to invest in vaccination against foodborne illness as an integral part of health care.

Footnotes

Disclosure Statement

No competing financial interests exist.

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