HEPATITIS E VIRUS (HEV) - SWINE STRAINS

LEVELS: Likely to occur: Effective control measures not fully understood; Occupational exposure risk: Non-foodborne transmission pathway(s) that are strongly associated with occupational exposure and can lead to human infection; Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission; Moderate: Clinical signs not unique but existing tests available at local/regional laboratory(s); Negligible: No measurable losses; Temporary disruption: Measureable negative effect on demand for less than a month when disease occurs on one or more farms; Minimal risk: Agent inherently unlikely to develop clinically important resistance to antibacterial or antiviral treatments; Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy; No availability: Effective treatments not currently available in the US (or have not been developed); No availability: Effective vaccines not currently available in the US (or have not been developed); Not feasible: Eradication extremely unlikely


OVERVIEW

Hepatitis E virus (HEV) is a significant zoonotic pathogen, with swine serving as a major reservoir for human infections in industrialized countries. HEV is a non-enveloped, positive-sense, single-stranded RNA virus in the family Hepeviridae. Within the species Paslahepevirus balayani, eight genotypes exist: HEV-1 and HEV-2 are restricted to humans; HEV-3 and HEV-4 infect humans, pigs, and other species and are zoonotic; HEV-5 and HEV-6 infect wild boars; and HEV-7 and HEV-8 infect camels. The first animal strain of HEV was isolated from pigs in the United States in 1997. HEV infection is ubiquitous in pigs worldwide, regardless of whether HEV is endemic in the local human population. Swine HEV infection is age-dependent: most pigs become infected at 2-3 months of age after maternal antibodies wane, with transient viremia lasting 1-2 weeks and fecal shedding for 3-7 weeks. Importantly, pigs remain clinically normal despite infection—HEV causes subclinical hepatitis in swine with no apparent clinical signs. The primary concern for swine HEV is its zoonotic risk and implications for pork safety. Humans can acquire infection through occupational exposure to pigs, consumption of undercooked pork liver or pork products, and environmental contamination. Swine veterinarians and pig workers have significantly higher HEV seroprevalence than the general population. HEV was recently ranked among the top three foodborne viral pathogens globally by FAO/WHO.


FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL

Level: Likely to occur: Effective control measures not fully understood

Swine HEV poses well-documented foodborne zoonotic risk. The chapter states: "Sporadic cases of acute hepatitis E have been linked to the consumption of contaminated raw and undercooked pig liver." Key evidence includes: (1) Contaminated retail products: "Approximately 2% of the pig liver sold in grocery stores in Japan and 11% in the United States tested positive for swine HEV RNA, and positive pig liver from the grocery stores in the United States was infectious"; (2) Pork products: "HEV RNA was also detected from pork products (e.g. sausage and chitterlings)"; (3) Slaughter-age pigs: "HEV RNA was detected in 6.3% of serum samples from market-weight pigs at 25 slaughterhouses in 10 US states"; (4) Thermal stability: "The infectivity of swine HEV present in commercial pig livers is inactivated by adequate cooking (e.g. frying or boiling for 5 minutes); however, incubation of the contaminated pig liver homogenates at 56°C for 1 hour did not abolish virus infectivity." HEV was ranked by FAO/WHO "in the top three foodborne viral pathogen along with norovirus and hepatitis A virus, and pork was identified as an important virus-commodity pair of global public health burden."


NON-FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL

Level: Occupational exposure risk: Non-foodborne transmission pathway(s) that are strongly associated with occupational exposure and can lead to human infection

Occupational exposure to pigs significantly increases HEV infection risk: (1) Swine veterinarians: "were 1.51 times more likely to be positive for anti-HEV antibodies than other blood donors"; (2) Pig workers: "swine workers in North Carolina, United States had a 4.5-fold higher HEV antibody prevalence rate (10.9%) than control subjects (2.4%)"; (3) Global pattern: "Pig caretakers and swine veterinarians in both developing and industrialized countries are at an increased risk of HEV infection." Additionally, environmental contamination poses indirect transmission risk: "HEV-infected pigs excrete HEV in feces, thus posing the potential for contamination of irrigation or coastal water and the subsequent contamination of produce or shellfish." HEV strains from swine have been detected in slaughterhouse sewage.


EFFECTIVENESS OF ON-FARM BIOSECURITY IN PREVENTING FARM-TO-FARM TRANSMISSION

Level: Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission

Swine HEV transmission occurs primarily through fecal-oral route and can be controlled through standard biosecurity: (1) Transmission route: "Swine HEV transmission among pigs is presumably fecal–oral, with feces from infected pigs serving as the primary source of the virus"; (2) Contact transmission: "naive pigs acquire infection through direct contact with infected pigs or through ingestion of feces-contaminated feed or water"; (3) Difficult oral infection: "experimental infection of pigs with swine HEV via the oral route of inoculation proved to be difficult. Therefore, other routes of transmission cannot be ruled out"; (4) No vectors or aerosol: No insect vectors are involved, and long-distance aerosol transmission is not documented. Standard biosecurity focusing on sanitation, preventing fecal contamination, and controlling pig movements can limit HEV transmission within and between herds.


DIFFICULTY OF DETECTING AND CONFIRMING INFECTION

Level: Moderate: Clinical signs not unique but existing tests available at local/regional laboratory(s)

Detection is complicated by the subclinical nature of infection but laboratory methods are available: (1) No clinical signs: Pigs are clinically normal during infection—there are no signs to trigger investigation in swine; (2) No efficient cell culture: "Swine HEV cannot be efficiently propagated in cell culture, and only a few strains of swine HEV can be grown in vitro"; (3) PCR-based detection: "the diagnosis of swine HEV infection is based on PCR"—methods are available and validated; (4) ELISA serology: Available using capsid antigen; "results of an ELISA based on swine HEV-3 capsid antigen correlated well with those obtained with a human HEV-1 capsid antigen." The challenge is recognizing when to test, since pigs show no clinical signs. Detection in the context of food safety surveillance or zoonotic investigations is straightforward with established molecular methods.


FINANCIAL IMPACT ON FARM'S COST OF PRODUCTION

Level: Negligible: No measurable losses

Swine HEV causes no production losses in pigs: (1) Subclinical infection: "Pigs experimentally infected with swine HEV remained clinically normal"; (2) No gross lesions: "mild-to-moderate enlargement of hepatic and mesenteric lymph nodes was observed" experimentally, but no production-affecting disease; (3) Microscopic changes only: "Microscopic lesions characterized by mild-to-moderate multifocal lymphoplasmacytic hepatitis and focal hepatocellular necrosis were commonly observed in infected pigs" but without clinical impact; (4) Normal reproduction: "Pregnant gilts infected with swine HEV had mild hepatitis... but HEV-associated lesions in the reproductive tract or fetuses were absent." The economic concern for HEV is entirely related to food safety and zoonotic implications rather than swine production losses.


EFFECT ON DOMESTIC OR EXPORT MARKETS

Level: Temporary disruption: Measureable negative effect on demand for less than a month when disease occurs on one or more farms

While HEV does not directly cause swine disease, its zoonotic significance has market implications: (1) Food safety concern: "The major concern for swine HEV is its zoonotic risk and pork safety"; (2) Top-ranked pathogen: "HEV was ranked #6 for risk of spillover and zoonotic infection" and among "top three foodborne viral pathogen" by FAO/WHO; (3) Retail contamination documented: Infectious virus detected in retail pork products creates potential for consumer concern and regulatory attention; (4) Export considerations: Countries with heightened food safety awareness may impose testing or certification requirements. While HEV does not currently trigger trade restrictions like WOAH-listed diseases, increased regulatory scrutiny of pork safety due to HEV's zoonotic significance represents a moderate market concern.


PATHOGEN'S ABILITY TO DEVELOP AND SPREAD RESISTANCE

Level: Minimal risk: Agent inherently unlikely to develop clinically important resistance to antibacterial or antiviral treatments

HEV is an RNA virus (family Hepeviridae) that does not carry, acquire, or transmit antimicrobial resistance genes. The virus poses no AMR concerns. Genetic diversity exists among genotypes, but this represents natural viral evolution rather than antimicrobial resistance.


AMR DEVELOPMENT DRIVEN BY DISEASE MANAGEMENT

Level: Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy

No antiviral treatments exist for swine HEV, and since pigs remain clinically healthy during infection, there is no indication for treatment. Antimicrobials are not used for HEV management in swine. No AMR pressure is generated by this disease.


AVAILABILITY OF EFFECTIVE TREATMENT OPTIONS

Level: No availability: Effective treatments not currently available in the US (or have not been developed)

No specific treatments exist for HEV infection in pigs. More importantly, treatment is not needed because "pigs experimentally infected with swine HEV remained clinically normal." Infected pigs clear the infection through their immune response. In humans, chronic HEV cases may be treated with ribavirin, but this is not applicable to swine production.


AVAILABILITY OF EFFECTIVE VACCINES OR BACTERINS

Level: No availability: Effective vaccines not currently available in the US (or have not been developed)

No HEV vaccine is licensed for use in swine. The chapter notes: "A commercial vaccine against HEV ('HEV 239') is currently licensed for human use in China." Regarding swine vaccination, the chapter states: "It may be advantageous to vaccinate pigs to decrease the potential for zoonotic transmission and eliminate pork safety concerns." Experimental data support vaccine potential—prior infection provides cross-protection against challenge with different genotypes, and maternal antibodies protect piglets. However, no commercial swine vaccine exists currently.


FEASIBILITY OF ERADICATING THE DISEASE FROM THE US

Level: Not feasible: Eradication extremely unlikely

HEV eradication from US swine is not feasible: (1) Ubiquitous infection: "HEV infection is ubiquitous in pigs worldwide, regardless of whether HEV is endemic in the respective human population"; (2) High seroprevalence: Most pigs older than 3 months are seropositive; infection occurs routinely at 2-3 months after maternal antibody wanes; (3) Subclinical nature: No clinical signs to identify infected animals for removal; (4) Environmental contamination: Fecal shedding for 3-7 weeks contaminates environment; virus detected in slaughterhouse sewage and can contaminate water; (5) Wild boar reservoir: HEV-5 and HEV-6 infect wild boars, providing wildlife reservoir; (6) Multi-host virus: HEV-3 and HEV-4 infect humans, pigs, and other species. Vaccination of pigs might reduce zoonotic risk but would not eliminate the virus from swine populations.