Pathogen Safety Data Sheets: Infectious Substances – Hepatitis E virus



NAME: Hepatitis E virus

SYNONYM OR CROSS REFERENCE: HEV, enterically transmitted or enteric non-A non-B hepatitis (ENANB), epidemic non-A non-B hepatitisFootnote 1Footnote 2Footnote 3Footnote 4, faecal-oral non-A non-B hepatitis, and A-like non-A non-B hepatitis.

CHARACTERISTICS: Hepatitis E virus (HEV) is classified as the only member of the genus Hepevirus in the family Hepeviridae Footnote 2 Footnote 4. It is identified as a non-enveloped, icosahedral shaped sphere Footnote 3, approximately 27-34 nm in diameter, and consisting of a single-stranded, positive sense RNA molecule about 7.5 kilobases (kb) in lengthFootnote 1Footnote 2Footnote 4Footnote 5. The surface of the particle consists of indentations and spikes, resulting in an appearance similar to that of calciviruses and it is often found in faeces of infected individuals Footnote 3.


PATHOGENICITY/TOXICITY: The disease caused by HEV is generally self-limiting with symptoms typical of acute viral hepatitis including, jaundice, malaise, anorexia, abdominal pain, nausea, fever, diarrhea, discoloured stool and/or urine, and hepatomegalyFootnote 1Footnote 2Footnote 3Footnote 5. Anicteric hepatitis and cholestasis are also observed in some cases. Mortality rate due to infection by hepatitis E have been reported to be as high as 1 % Footnote 2; however, the mortality rate may reach up to 20 % in pregnant women with each passing trimester, making HEV infection the most severe hepatitis in pregnancy of all recognized hepatitis viruses. Analysis of serum specimens collected from volunteer blood donors shows that the prevalence of HEV varies from region-to-region but is higher in endemic countries/regions as compared to developed countries Footnote 5. Hepatitis caused by HEV is clinically indistinguishable from hepatitis A diseaseFootnote 6.

EPIDEMIOLOGY: Phylogenetic studies indicate at least four distinct genotypes of HEV (1 – 4) based on geographical origin Footnote 5 Footnote 7. Genotypes 1 and 2 are considered more pathogenic, restricted to humans, and are responsible for the large majority of cases and outbreaks in endemic regions. Genotypes 3 and 4 are somewhat less pathogenic, infect humans, pigs, and other animal species, and are generally responsible for sporadic HEV infection cases within endemic and non-endemic regions. Outbreaks and sporadic cases of HEV have occurred over a large geographic area, most notable in regions with poor sanitation. There have been some cases of food-borne HEV infections, but the majority of confirmed cases have been associated with the consumption of water contaminated with feces. The attack rate of HEV is highest in young adults between ages of 15-40. Males are more likely to develop clinical hepatitis when infected with HEV as compared to females. In developed countries, HEV infection is generally reported from people who travel to HEV endemic or epidemic areas; however, some cases of locally-acquired (autochthonous) HEV infection have been observed in non-endemic countries including USA, Australia, France, Greece, New Zealand, Italy, and UK. Documented epidemic outbreaks have occurred in Algeria, Ivory Coast, Ghana, Chad, Ethiopia, Somalia, Namibia, India, former Soviet Union, Nepal, Pakistan, Burma, Myanmar, China, Vietnam, Indonesia, and Mexico Footnote 8.

HOST RANGE: Humans and animals, including swine Footnote 1. Several animal species have been experimentally infected with strains of HEV, including nonhuman primates such as African green monkeys, chimpanzees, cynomolgus macaques, owl monkeys, rhesus monkeys, tamarins, noninbred white mice and Wistar rats.


MODE OF TRANSMISSION: Four modes of transmission of HEV infection have been reported: faecal-oral transmission, food-borne transmission, blood-borne transmission, and vertical transmission Footnote 5Footnote 7. The most common mode of transmission of HEV, also responsible for the majority of the HEV infection outbreaks, is through the faecal-oral route, usually by ingestion of contaminated water. Potential exists for food-borne transmission and some cases have been observed where consumption of raw or uncooked meat from wild boar and deer has led to HEV infection. Blood-borne transmission is rare but has been documented in some cases involving blood transfusions. Some cases of vertical (perinatal) transmission from mother-to- child have been documented, particularly in India, but this is considered to be of minor importance as a mode of transmission for HEV and more investigation is required. Person-to- person transmission and secondary household cases are uncommon, particularly in epidemic (poor hygienic) conditions. In non-endemic regions, where autochthonous cases have been observed, zoonotic transmission has been considered as the likely mode of transmission, but more investigation is required Footnote 7.

INCUBATION PERIOD: Incubation period for HEV infection in humans ranges from 15-60 days with a mean 40 days Footnote 1Footnote 8.

COMMUNICABILITY: Unknown. Person-to-person transmission has been documented but appears to be uncommon Footnote 5. HEV has been detected in the stools of infected patients after the onset of illness (jaundice) for up to 14 days Footnote 9. Maximal HEV shedding occurs during the incubation period and during early acute stage of the disease.


RESERVOIR: Humans and animals, including monkeys, swine, rats, boars, deer, cows, sheep, goats, camels, horses, dogs, cats, and mongoose(5,10). All have been shown to be susceptible to infection with HEV and may act as reservoirs for the infectious agent; however, the source(s) of HEV for some of these wild animals has yet to be determined.

ZOONOSIS: Hepatitis E is now considered a zoonotic disease where domestic pigs and wild boars are the main reservoirs Footnote 10. Zoonotic transmission from deer has also been documented. Transmission may also occur from other animals, including chickens, cats, and rats, but further investigation is yet required.




SUSCEPTIBILITY TO DISINFECTANTS: HEV is susceptible to iodinated disinfectants (0.075g/L or 1 % iodine)(10). It may also be sensitive to hypochlorites (1 % sodium hypochlorite), formaldehyde (18.5 g/L; 5 % formalin in water), and glutaraldehyde Footnote 11.

PHYSICAL INACTIVATION: HEV is more heat labile than Hepatitis A virus (HAV) and most strains can be inactivated at temperature ≥60 °C for 15 minutes or more Footnote 12. The heat sensitivity of HEV, however, depends on the heating conditions Footnote 13. Hepatitis E in PBS is inactivated quickly at 60 C, but in an albumin solution is inactivated more slowly. When HEV is added to freeze-dried fibrinogen containing stabilizers and subjected to dry heat, it is inactivated to below detection limit within 24 hours at 80 C, but is inactivated more slowly at 60 C. It is also susceptible to low storage temperatures (between -70 °C and +8 °C) Footnote 1.

SURVIVAL OUTSIDE HOST: Unknown. Since HEV survives the conditions within the intestinal tract, it is considered relatively stable in acidic and mild alkaline conditions Footnote 4. Since HEV mainly spreads through the faecal-oral route, it must be relatively stable under environmental conditions Footnote 1, possibly similar to HAV (i.e. in water and sewage for long periods).


SURVEILLANCE: Monitor for symptoms of disease. Confirm using serological or nucleic acid tests, and by exclusion of hepatitis A and B viruses Footnote 5. Serological tests involve enzyme-linked immunosorbent assays (i.e. ELISA) for the detection of antibodies to HEV (IgM, IgA, and IgG), and nucleic acid tests involve reverse transcription-polymerase chain reaction (RT-PCR) assays for the detection of HEV RNA in serum, bile, and/or faecal samples.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Rest. No specific treatment currently available Footnote 4.




LABORATORY-ACQUIRED INFECTIONS: No cases of laboratory-acquired have been reported to date.

SOURCES/SPECIMENS: The main sources are of HEV are feces and sera of infected human, nonhuman primates, pigs, and some other animals Footnote 1.

PRIMARY HAZARDS: Ingestion of feces or stool samples and other contaminated materials. Importance of aerosol exposure has not been demonstrated.



RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 14.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures.

PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes Footnote 15.

OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and sharp objects should be strictly limited Footnote 15. Additional precautions should be considered with work involving animals or large scale activities Footnote 15.


SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min) Footnote 15.

DISPOSAL: Decontaminate, either by steam sterilization, incineration, or chemical disinfection, before disposal Footnote 15.

STORAGE: The infectious agent should be stored frozen in sealed containers that are appropriately labelled, preferably at -70 °C or lower Footnote 15.


REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: August 2010

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2010 Canada

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