Emerging Swine Zoonoses

Abstract

The majority of emerging infectious diseases are zoonotic in origin. Swine represent a potential reservoir for many novel pathogens and may transmit these to humans via direct contact with live animals (such as swine farmers and large animal veterinarians), or to the general human population via contaminated meat. We review recent emerging microbes associated with swine and discuss public health implications.

Introduction

T he majority of emerging diseases are zoonotic—transmitted between animal species (Woolhouse and Gowtage-Sequeria 2005, Jones et al. 2008). An emerging microbe may be described to be emerging if it is “newly recognized or newly evolved, or that has occurred previously but shows an increase in incidence or expansion in geographical, host or vector range” according to a report from the World Organization for Animal Health, the World Health Organization (WHO), and the Food and Agriculture Organization of the United Nations (http://whqlibdoc.who.int/hq/2004/who_cds_cpe_zfk_2004.9.pdf). Swine have been involved in the transmission of several novel infectious agents to humans, acting as either a primary or intermediary reservoir of infection. In addition to the potential to spread swine-associated infections from pigs to farmers and other individuals working in contact with live swine, pork is a central source of protein in diets worldwide. It is estimated that ∼99 million metric tons of pork was consumed worldwide in 2006 (USDA 2006). Therefore, swine and swine products have the potential to transmit infectious agents to human caretakers via direct contact on farms; to butchers and meat packers via contact with carcasses, and to the general community via contaminated food. Classic food-borne pathogens have included Trichinella and Salmonella species, but new pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile have had swine and/or pork products implicated as a potential vehicle of transmission, whereas novel swine-associated influenzas have emerged in the previous several years. Here we examine emerging zoonotic infections associated with live swine or swine products, focusing on viral and bacterial zoonoses that have been prominent in the past 5 years.

Methicillin-Resistant Staphylococcus aureus

MRSA has been an important nosocomial pathogen for the past 50 years. In the 1990s, this organism was unexpectedly found to be the cause of serious infections in individuals with no known risk factors for infection (CDC 1999a, Groom et al. 2001, Naimi et al. 2001). These types of MRSA have been referred to as hospital-associated MRSA and community-associated MRSA, respectively. In 2005, a novel type of MRSA was identified in swine farmers in the Netherlands, which has come to be characterized as livestock-associated MRSA (LA-MRSA) (Wulf and Voss 2008). Dutch studies found that swine farmers were colonized with MRSA at a rate of 760 times higher than that of the general population (Voss et al. 2005). Since then, LA-MRSA has been found in a number of countries, including Germany (Schwarz et al. 2008, Cuny et al. 2009), Denmark (Guardabassi et al. 2007, Lewis et al. 2008), Belgium (Denis et al. 2009, Van Hoecke et al. 2009), Italy (Battisti et al. 2009, Pan et al. 2009), Portugal (Pomba et al. 2009), Canada (Khanna et al. 2008), and the United States (Smith et al. 2009b). The majority of LA-MRSA identified to date has been a single type: multilocus sequence type ST398, or “nontypeable” MRSA (Bens et al. 2006).

While the majority of individuals colonized or infected with LA-MRSA have been swine workers, contact with cattle has also been identified as a risk factor (Wulf et al. 2006, Moodley et al. 2008). Additionally, colonization with ST398 has occurred in individuals lacking any identified contact with a livestock reservoir (Aires-de-Sousa et al. 2006, Bhat et al. 2009). It has been suggested that one mode of transmission into the community is via contaminated food; however, reports have varied widely as to the level of contamination on meat products. A study in the United States found MRSA in 5% of 120 meat samples (Pu et al. 2009), whereas two studies in the Netherlands found rates of 2.5% (van Loo et al. 2007) and 11.9% (de Boer et al. 2009). No cases of ST398 colonization or infection as a result of contact with contaminated meat products have been confirmed to date. While colonization with MRSA is not necessarily a health risk, it is a risk factor for the subsequent development of MRSA infections (Wertheim et al. 2005); as such, spread of MRSA via live animals or their meat products has been investigated as a public health risk

The study of LA-MRSA is still in its infancy. To date, most epidemiological research has focused on prevalence studies, which have often been carried out on farms. It is not currently known whether MRSA ST398 is a novel strain, or simply one that has been previously overlooked on livestock farms. Research is ongoing to investigate spread into the general population, the spectrum and incidence of infection with this type of MRSA, and to identify other strains of potentially zoonotic MRSA.

Streptococcus suis

Streptococcus suis is a cause of serious infection in pigs, causing substantial economic losses to the pork industry (Gottschalk et al. 2007). The organism was first identified in swine in 1954 (Field et al. 1954) and affects mainly young pigs. Disease presentation in piglets includes sepsis, meningitis, and pneumonia. The first recorded case of human infection with S. suis occurred in Denmark in 1968 (Perch et al. 1968); since then, confirmed infections have been documented in Thailand (Fongcom et al. 2009), Vietnam (Wertheim et al. 2009), the Netherlands (van de Beek et al. 2008), Greece (Mazokopakis et al. 2005), Germany (Rosenkranz et al. 2003), Croatia (Kopic et al. 2002), New Zealand (Dickie et al. 1987), Canada (Haleis et al. 2009), and the United States (Willenburg et al. 2006, Lee et al. 2008), among other countries. Meningitis is the most common human presentation and deafness is a common sequela. Human fatality rate varies and is dependent on clinical manifestation, ranging from 2.6% in Vietnamese meningitis cases (Mai et al. 2008) up to 63% in China among patients with septic shock (Tang et al. 2006). Serological studies have suggested that infection with this organism is common in swine-exposed individuals (Robertson and Blackmore 1989, Smith et al. 2008), and it has been suggested that this organism may be underdiagnosed in human populations (Gottschalk 2004).

Although S. suis is present in swine worldwide, the vast majority of human disease has been reported in Asia, especially Thailand, China, and Hong Kong. In Hong Kong, S. suis is the third most common cause of bacterial meningitis (Hui et al. 2005). Although most cases have occurred in people in close contact with swine, including farmers, butchers, and veterinarians, a recent study has shown that a significant number of meningitis cases caused by S. suis have no known occupational exposure to live swine (Ma et al. 2008). In 2005 in China, the largest outbreak of S. suis ever recorded took place, sickening at least 204 and killing 38 (a 19% mortality rate) (Tang et al. 2006, Yu et al. 2006). This outbreak was due to a serotype 2 S. suis isolate (Tang et al. 2006, Ye et al. 2006). Of the 35 known serotypes of the bacterium, serotype 2 is the most common worldwide and by far the most common one to cause disease in humans (Lun et al. 2007). During the 2005 human outbreak, there was a concurrent epidemic in pigs and all of the human cases were reported to have contact with infected pigs before developing symptoms. Of the fatal cases, all but one developed streptococcal toxic shock-like syndrome; the other fatal case died of meningitis (Tang et al. 2006, Yu et al. 2006). Thus, it appears that a unique, highly virulent lineage of S. suis may be endemic in this region of China.

In contrast, human S. suis infections appear to be quite rare in North America. The first confirmed infection in the United States was reported in 2005 (Willenburg et al. 2006) and only a handful of additional infections reported (Lee et al. 2008, Fittipaldi et al. 2009). This may be due to underdiagnosis of the infection in the United States, the presence of less virulent strains in the swine population, or a combination of the two. Cultural differences in swine consumption and swine husbandry practices may also play a role. The most critical factors in these outbreaks remain to be determined.

Clostridium difficile

Like MRSA, the epidemiology of C. difficile has dramatically changed in the past decade. C. difficile has emerged as a prominent factor causing diarrhea in neonatal swine and hospital-acquired pseudomembranous colitis in humans (Indra et al. 2009). Diagnosed cases in both pigs and humans are increasing in many Midwestern states and Canadian provinces (Neutkens 2001, Yaeger et al. 2002, CDC 2005, Songer and Anderson 2006, Wilcox et al. 2008). Of particular concern is the emergence of serious C. difficile infections in individuals lacking healthcare exposure or prior antibiotic use (Freeman et al. 2010).

Many studies have suggested that exposure to antibiotics is a risk factor for the development of disease caused by C. difficile in both humans and swine (Neutkens 2001, Songer et al. 2001, Yaeger et al. 2002). It is hypothesized that exposure to antimicrobials disrupts normal flora of the host, allowing the Clostridium spores to germinate. Further, it has been suggested that more virulent strains of C. difficile may be emerging as a result of selective pressures for antibiotic resistance (Indra et al. 2009). The spores produced by C. difficile are also very resistant to disinfectants (Neutkens 2001), thus making eradication in the affected environment difficult.

More virulent isolates of C. difficile have been linked to hospital outbreaks in North America and Europe (Norman et al. 2009). The second most common strain causing human infection is also commonly found in swine (Goorhuis et al. 2008, Rupnik et al. 2008). One hypothesis indicates the increase and severity of C. difficile infections in humans could be caused by increased animal reservoir infections (Indra et al. 2009) and food-borne transmission (Songer et al. 2009, Weese 2010). While animal- or food-borne acquisition of C. difficile has not been conclusively demonstrated, studies investigating similarities of isolates between swine on 7 Dutch farms and human clinical isolates in the Netherlands have suggested interspecies transmission (Debast et al. 2009), further complicating efforts to reduce transmission.

Influenza Virus

Swine influenza was first recognized during the pandemic of 1918–1919. Epidemiologists and historians have noted, anecdotally, the concurrent outbreaks of influenza in swine and humans during this pandemic (Stuart-Harris et al. 1985), suggesting that these were caused by a single infectious agent. The first influenza virus from swine was isolated in 1930 (Shope and Lewis 1931). Although other serotypes of swine are currently more common than H1N1, this classic swine serotype of influenza, H1N1, has been maintained in the swine population until present day.

Human cases of swine influenza have been reported sporadically. The most well-known outbreak before 2009 occurred in 1976 at Fort Dix, NJ, where 1 person died and 12 others were sickened by an H1N1 swine flu virus (Gaydos et al. 1977b). Mild or subclinical cases were common: seroepidemiologic studies indicated that up to 230 individuals showed antibody response to the virus (Gaydos et al. 1977a). No evidence of contact with live swine was found in this outbreak.

A 2007 review identified 50 cases of zoonotic swine influenza infection reported in the literature between 1958 and 2005 (Myers et al. 2007), the majority of which were in individuals who had direct contact with swine. An additional outbreak was documented in fairgoers and pigs at an agricultural fair in Ohio in 2007 (Vincent et al. 2009). Although documented symptomatic infections with influenza viruses of swine origin were fairly uncommon before 2009, several research studies have demonstrated that individuals with occupational contact with swine (including swine farmers, swine veterinarians, and meat packers) demonstrate serological evidence of prior swine influenza infections (Myers et al. 2006, Ramirez et al. 2006, Gray et al. 2007). This suggests frequent cross-species transmission and subclinical or unrecognized infection. This is a cause for concern because swine have long been thought to act as mixing vessels for the generation of novel influenza viruses (Ma et al. 2009a).

In April 2009, the novel swine-origin H1N1 virus (Garten et al. 2009, Smith et al. 2009) was recognized in humans (Dawood et al. 2009, Neumann et al. 2009). Epidemiological data indicate that an outbreak of respiratory illness began in February 2009 in Veracruz, Mexico. Mexican public health authorities were alerted in early April and specimens were sent to Canada for analysis. Separately, specimens collected from children in California identified a unique swine-origin H1N1 virus (Neumann et al. 2009). This prompted a pandemic alert by the WHO, beginning at Phase 3 (sporadic cases or small clusters of a novel virus) and quickly increasing to Phase 4 and then Phase 5 (sustained human-to-human spread in at least two countries) on April 29, 2009. Phase 6—the highest phase marking sustained human-to-human transmission in multiple regions—was reached on June 11, 2009 (Chan 2009). The virus has since spread to over 200 countries (WHO 2009a). The Centers for Disease Control and Prevention (CDC) estimated that between 43 and 89 million individuals were infected in the United States between April 2009 and April 2010, resulting in 195,000–403,000 hospitalizations and 8870–18,300 deaths (CDC 2010a).

Before the current pandemic, swine influenza had taken a backseat to increased research and surveillance investigating avian influenza, particularly H5N1 (Gambotto et al. 2008). However, the rapid emergence and spread of swine-origin H1N1 in the human population has documented the importance of maintaining surveillance programs for all types of potential emerging influenza viruses.

Nipah Virus

Nipah virus, a negative-strand RNA virus, was first isolated in Malaysia in 1999 during a simultaneous outbreak in humans and pigs (CDC 1999b, Weingartl et al. 2005). It was shown to have close phylogenetic and antigenic relationships with Hendra virus, a horse zoonosis first seen in Australia (Chua et al. 2000, AbuBakar et al. 2004). Due to the similarities between Nipah and Hendra viruses, they were classified into a new genus Henipavirus within the Paramyxoviridae family (Harcourt et al. 2000, 2001). Nipah illness in humans typically presents with fever and headache, and can lead to a deadly encephalitis in humans.

It has been postulated that flying foxes, fruit bats from the genus Pteropus, act as the natural reservoir of Nipah virus (Chua et al. 2002). While flying foxes can become infected with Nipah virus and will subsequently seroconvert, they display no signs of disease manifestation during this process (Weingartl et al. 2009). Nipah virus has been isolated from urine and partially eaten fruit of the flying fox, leading to the hypothesis that pigs contracted Nipah virus from these sources and subsequently passed the virus on to the humans handling them (Chua et al. 2002). Pigs have been identified as the amplifying host for human infections, with between 5% and 86% of reported human cases linked to porcine cases (CDC 1999c, Imada et al. 2004). Human-to-human transmission has also been suggested in outbreaks in Bangladesh in both 2004 (Gurley et al. 2007) and 2007 (Homaira et al. 2010).

The only major outbreak of Nipah virus occurred in Malaysia between 1998 and 1999, with 257 human cases reported (CDC 1999b). It is estimated that 85% of infected humans were symptomatic and that mortality of clinically diagnosed cases was around 40% (CDC 1999b, Weingartl et al. 2005). This high mortality rate has been attributed to the manifestation of acute encephalitic syndrome and has been suggested that both the brain stem and upper cervical cord are also affected (Weingartl et al. 2005). This outbreak was also devastating economically as over 800,000 pigs were culled during efforts to stop the spread of disease (CDC 1999c). The disease manifests in pigs as a febrile respiratory illness presenting with epistaxis, coughing, and dyspnea; some pigs continue to show neurological signs even after the virus has been cleared (Middleton et al. 2002). Mortality rates in pigs have been estimated between 1% and 5% (Weingartl et al. 2009).

Ebola Reston Virus

Reston ebolavirus (REBOV) is a member of the Filoviridae family, along with Marburgvirus and the other Ebolaviruses: Ebola Sudan, Ebola Zaire, Ebola Cote d'Ivoire, and Ebola Bundibugyo (Groseth et al. 2007, Towner et al. 2008). This virus family is associated with acute, fatal hemorrhagic diseases of humans and nonhuman primates.

Ebola Reston was discovered in 1989 as the cause of serious illness and death of nonhuman primates at a quarantine facility in Reston, VA (Jahrling et al. 1990). REBOV was found again in 1990 in the United States, in 1992 in Italy (CDC 1992), and in 1996 in the United States and the Philippines (CDC 1996, Miranda et al. 1999, Rollin et al. 1999). All cases were associated with primates exported from a single facility in the Philippines. While infection with the virus can be fatal in nonhuman primates, it does not result in clinically apparent infection in humans. This suggests that the virus is less pathogenic than the other viruses in the Filovirus family (Morikawa et al. 2007). It is still considered a high-hazard pathogen for humans, due to the potential for serious disease in humans and possible human-to-human transmission (www.cdc.gov/ncidod/dvrd/spb/outbreaks/qaEbolaRestonPhilippines.htm).

In addition to bats (Leroy et al. 2005, Pourrut et al. 2009) and primates, swine have recently been implicated as a host for REBOV. In 2008, U.S. officials were asked to help with the diagnostic investigation of outbreaks of a respiratory and abortion disease syndrome in swine in the Philippines (Editorial Team 2009, WHO 2009b). Investigators found that the swine were infected with porcine reproductive and respiratory syndrome virus. However, they also found evidence of another virus, REBOV (Barrette et al. 2009). Based on phylogenetic evidence, it is speculated that REBOV has been circulating in swine for as long as it has in nonhuman primates, adding swine to the list of potential filovirus reservoirs, in addition to the previously implicated bat species (Barrette et al. 2009, Leroy et al. 2009, Pourrut et al. 2009).

In the Philippines outbreak, 6 out of 141 swine workers (4.3%) tested had positive serum immunoglobulin G (IgG) titers to REBOV (Barrette et al. 2009). Like the previous Reston outbreaks, there was no evidence of clinical disease in humans (Barrette et al. 2009, WHO 2009b). The exact role that swine play in the transmission cycle of this virus, whether as an incidental host or an essential component, has yet to be determined (Barrette et al. 2009). However, a cycle similar to that seen with Nipah virus—swine in contact with bats or bat excrement, and subsequent transmission to human caretakers—is possible.

Hepatitis E Virus

Hepatitis E virus (HEV) is a single-stranded RNA virus of the family Hepeviridae. HEV is a zoonotic pathogen with a worldwide distribution, and a major cause of acute hepatitis infection in tropical and subtropical regions (Kuniholm and Nelson 2008). In humans, HEV causes an acute, self-limiting infection that varies from inapparent to fulminant, with a mortality rate of 1%–4% or up to 20% in pregnant women (Purcell and Emerson 2008). Transmitted primarily through the fecal–oral route, HEV is most frequently associated with large epidemics of water-borne hepatitis due to water contamination in developing countries (Purcell and Emerson 2008).

HEV was first isolated from domestic pigs in the Midwestern United States in 1997 (Meng et al. 1997). Since then, HEV has been reported in swine in nearly all parts of the world (Munne et al. 2006, Kim et al. 2008, Purcell and Emerson 2008, Zhao et al. 2009). Swine are a reservoir for HEV and colonization is thought to occur between 2 and 3 months of age with the majority of swine >3 months of age being seropositive. In 2006, Fernandez-Barredo et al. reported that throughout the stages of production, on average 23% of swine were excreting HEV RNA (Fernandez-Barredo et al. 2006). With a few exceptions, HEV does not appear to cause apparent disease in swine, although microscopic evidence of hepatitis has been seen in naturally infected swine (Meng et al. 1997, Martin et al. 2007, Purcell and Emerson 2008).

Five major genotypes of HEV have been reported, each with distinct host and geographic ranges. While some exclusively infect humans (genotypes 1 and 2), others (genotypes 3 and 4) are known to infect humans as well as other animals, including swine (Dalton et al. 2008, Meng 2010). Genotype 3 was first isolated from a human case of hepatitis in the United States and, since then, has been found in other industrialized countries, including the United Kingdom, France, Netherlands, Spain, Austria, Greece, Italy, Japan, Australia, and New Zealand (Garkavenko et al. 2001, Banks et al. 2004, Dalton et al. 2008, Rutjes et al. 2009). Genotype 4 is similarly found in industrialized countries such as China, Taiwan, Japan, and Vietnam (Wu et al. 2000, Wang et al. 2001, Koizumi et al. 2004). Genotypes 3 and 4 have been recovered from swine in these areas, as well as areas where genotypes 1 and 2 are endemic. It is thought that genotypes 3 and 4 do not commonly affect humans in areas where genotypes 1 and 2 are endemic despite their presence in swine herds because genotypes 1 and 2 are more virulent (Purcell and Emerson 2008).

In areas where genotypes 3 or 4 are dominant, varying levels of anti-HEV antibodies have been observed in humans as well as animals, including swine, horses, rats, dogs, cats, cattle, sheep, and camels (Dalton et al. 2008, Rutjes et al. 2009). In these areas, prevalence of HEV IgG in healthy individuals may be as high as 21% in the United States or as low as 3% in Japan (Ding et al. 2003, Kuniholm et al. 2009). The disparity between the low frequency of hepatitis E infections and occasionally high seroprevalence in nonendemic areas is not well understood, but indicates that subclinical infection is common and zoonotic spread suggested to be at least partly responsible (Dalton et al. 2008, Rutjes et al. 2009). In the United States, a 21% anti-HEV-IgG reactivity rate (demonstrating exposure to any of the genotypes) was found among serum samples collected from the Third National Health Nutrition Examination Survey (NHANES). Risk factors associated with increased odds of seropositivity were the consumption of liver or organ meat more than once a month, contact with live swine by individuals such as farmers and veterinarians, or contact with swine products by slaughterhouse workers and butchers (Kuniholm et al. 2009).

The first example of hepatitis E infection attributed to zoonotic spread came from a case of autochthonous hepatitis E in the United States. This infection was caused by a genotype 3 strain with a high level of sequence similarity to an HEV genotype 3 strain isolated from a swine herd in the United States (Meng et al. 1997, Schlauder et al. 1998). Several other sources also suggest that HEV from swine may be transmitted to humans through consumption of contaminated meat (Mizuo et al. 2005, Wichmann et al. 2008, Colson et al. 2010, Teo 2010). As meat products with infectious HEV have been documented (Feagins et al. 2007), there is a need for continued surveillance for this virus in both animal populations and meat products to better understand zoonotic spread and its consequences.

Norovirus

Norovirus (NoV), belonging to the family Caliciviridiae, is one of the leading agents of nonbacterial acute gastroenteritis worldwide. The Norwalk virus, originally discovered in 1968 in an elementary school outbreak of acute gastroenteritis in Norwalk, OH, was considered the prototype strain of the NoV (Adler et al. 1969).

The main route of transmission is fecal–oral. NoVs can also be transmitted by aerosolization of infected vomitus, touching contaminated surfaces, and ingestion of contaminated food (Graham et al. 1994, Green et al. 2001, CDC 2010b). Factors contributing to spread of the virus include an infectious dose as low as 10 particles (CDC 2010b), resistance to disinfection, strain-specific and short-term immunity, and the potential for multiple routes of transmission (Ando et al. 2000).

NoVs have high genetic diversity and are divided into 29 genotypes within 5 genogroups. Of the five recognized NoV genogroups GI, GII, and GIV are commonly known to affect humans (CDC 2010b). NoVs have a broad host range and have been isolated from humans and animals, including swine, cattle, mink, dogs, cats, rabbits, sea lion, and mice. Molecular and phylogenetic analyses have demonstrated that porcine or swine NoVs are most closely related to human NoVs (van der Poel et al. 2000, Wang et al. 2005).

NoVs in animals were first isolated from stools of young calves (Woode and Bridger 1978) and pigs (Bridger 1980, Saif et al. 1980) with diarrhea. In 1997, a prototype strain of NoV, SW918, was detected in cecal contents of healthy adult pigs in Japan (Sugieda et al. 1998). It has been established that the SW918 and other swine strains are genetically and antigenically related to human NoVs, resulting in their classification into the human GII genogroup (Sugieda et al. 1998, 2002, Farkas et al. 2005, Wang et al. 2005).

Porcine and bovine strains have been isolated from farm animals in the Netherlands (van der Poel et al. 2000), the United States (Wang et al. 2005), Hungary (Reuter et al. 2007), Slovenia (Mijovski et al. 2010), Canada (Mattison et al. 2007, L'Homme et al. 2009), Belgium (Mauroy et al. 2008), New Zealand (Wolf et al. 2009), and most recently in Latin America (Cunha et al. 2010). Fecal samples for these studies were obtained from both young and adult farm animals, either asymptomatic or those which demonstrated clinical signs and symptoms of the disease. There has also been some success in isolating NoV strains from slaughterhouse (Wang et al. 2005), abbatoir (L'Homme et al. 2009), and necropsy (Mauroy et al. 2008) samples. One study conducted in Canada isolated NoV from one sample of raw pork out of 156 meat samples tested (Mattison et al. 2007). However, these studies did not directly investigate the possibility of transmission of NoV strains isolated from swine into the human population.

Intragenogroup recombinant strains have been identified in humans, swine, and cattle (Han et al. 2004, Wang et al. 2005, Phan et al. 2007). Human NoVs have been shown to be adept at replicating in gnotobiotic pigs under experimental conditions (Cheetham et al. 2006) and recombinant human NoV-like particles have been shown to bind to gut epithelium of pigs (Tian et al. 2007), suggesting that transmission of this pathogen can be bi-directional. Presence of porcine-human recombinant strains in swine in conjunction with the observation that infected pigs commonly remain asymptomatic (Scipioni et al. 2007) pose challenges in surveillance for zoonotic NoV infections in swine population.

Existing knowledge on zoonotic potential of NoV is mostly speculative. Animal NoVs have not been isolated from humans; nevertheless, there is some evidence for human infection with the bovine strain suggested by high levels of antibodies in veterinarians (Widdowson et al. 2005). As per an algorithm developed for risk assessment of emerging zoonotic potential of animal diseases, the porcine NoV or human-porcine NoV recombinants can be considered at “Level 1” of potential zoonosis, considering that we cannot exclude the possibility of human pathogenicity (Palmer et al. 2005). In contrast to the evidence of NoV infection in swine, circulation of porcine NoVs among individuals with occupational exposure or those in close contact with swine is lacking. Further research is warranted in identifying potential and biologically plausible transmission routes of NoV strains between humans and swine. It is crucial to monitor for emerging strains and increase public health surveillance in view of the possible emergence of NoV zoonoses between human and swine.

Discussion

Given the sheer number of swine present worldwide, and the large percentage of the population that consume pork, swine represent a significant reservoir of confirmed or potential zoonoses. A 2005 report noted that the typical U.S. consumer averages 51 pounds of pork eaten per year (www.ers.usda.gov/publications/LDP/may05/ldpm13001/ldpm13001.pdf), and that most of that is consumed at home, resulting in considerable exposure to pathogens associated with raw meat products. Further, individuals worldwide working as swine farmers, veterinarians, butchers, or food-processing workers may also be exposed to swine-associated pathogens.

Largely due to advances in farming and food-processing practices, classic swine-borne zoonoses, such as Trichinella, have all but disappeared in the United States: only 66 cases were submitted to the CDC between 2002 and 2007. Of those, five were confirmed to be related to commercial pork consumption in the United States (Kennedy et al. 2009). However, intensive farming practices may also lead to the emergence of novel zoonotic diseases (Silbergeld et al. 2010). While illness as a result of food-borne pathogens has leveled off in recent years in the United States (CDC 2010c), the zoonoses we review here demonstrate that the definition of food-borne infections may need to be broadened to include routes of transmission other than ingestion, and presentation of illness other than typical intestinal symptoms. Individuals with occupational contact with swine should also be monitored to uncover novel emerging infections, including new strains of known pathogens such as influenza and MRSA.

While we have sought to cover a diversity of emerging pathogens, our review is certainly incomplete. Additional pathogens, including porcine endogenous retroviruses (Boneva and Folks 2004) and Japanese encephalitis virus (Weaver and Reisen 2010), have also been implicated in zoonotic transfer between pigs and humans. Finally, transmission of pathogens is not always a one-way street. For example, though molecular analysis has shown that the novel H1N1 virus was a recombinant of swine viruses, it only came to the attention of public health professionals due to the recognition of symptomatic human infections. The virus was later transmitted to swine in North America and elsewhere (Howden et al. 2009), but molecular analyses suggest that it may have been circulating undetected for up to a decade (Garten et al. 2009, Smith et al. 2009a). Other organisms, including NoV and MRSA, may also show this bidirectional spread, moving back and forth between swine and humans. Much progress has been made in controlling swine-associated disease in humans, but as the emergence of novel swine pathogens demonstrates, we must remain vigilant to identify and control new organisms as they surface.

Footnotes

Disclosure Statement

No competing financial interests exist.

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