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HEPATITIS A VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Hepatitis A virus (HAV).

SYNONYM OR CROSS REFERENCE: HAV, type A hepatitis, infectious hepatitis, epidemic hepatitis, epidemic jaundice, and catarrhal jaundice⁽¹^,²^,³^,⁴^,⁵^,⁶^,⁷^,⁸^,⁹^,¹⁰^,¹¹⁾.

CHARACTERISTICS: HAV is a member of the Picornaviridae family and Hepatovirus genus⁽¹^,²^,³^,¹¹⁾. It is an icosahedral, non-enveloped, positive-sense RNA virus and is 27 to 32 nm in diameter⁽²^,³^,⁴^,¹¹⁾. Seven HAV genotypes have been identified (I-VII), 4 of which are of human origin (I, II, III, and VII)⁽³⁾.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: HAV only causes acute hepatitis and is not associated with chronic liver disease⁽¹^,³⁾. Most individuals infected with HAV develop non-specific constitutional signs and symptoms followed by gastrointestinal symptoms. Symptoms include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice⁽²^,³^,⁴^,¹¹⁾. The disease course typically lasts less than 2 months⁽³⁾. In rare cases, HAV can cause severe cases of fulminant hepatitis with fatal outcomes in otherwise healthy adults⁽²^,³⁾.

EPIDEMIOLOGY: The World Health Organization estimates an annual total of 1.5 million case of hepatitis A worldwide, but seroprevalence data suggest that tens of millions of HAV infections occur each year⁽⁴⁾. Central and South America, Africa, India, the Middle East, and Asia have the highest seroprevalence rates, whereas North America, Japan, and Western Europe have among the lowest⁽²^,⁴⁾. The incidence level is highly related to the prevailing level of hygiene and sanitation, with the disease being most prevalent in less developed parts of the world⁽⁴⁾.

HOST RANGE: Humans⁽¹^,²^,³^,⁴^,⁷^,⁸^,¹⁰^,¹¹^,¹²⁾. Chimpanzees and other non-human primates such as marmosets, tamarins, owl monkeys, and Saimiri monkeys are also susceptible to HAV⁽¹^,³^,⁹^,¹¹^,¹²⁾.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: HAV transmission usually occurs via the faecal-oral route⁽¹^,²^,⁴⁾. The most common reported source of HAV infection is household or other close contact with an infected person. Other potential sources of infection include men having sex with men, travel to countries where HAV is endemic, and from contaminated drugs and needles following illicit drug use⁽³⁾. Consumption of contaminated food and water are infrequent modes of transmission, and transmission by transfusion of blood or blood products is even rarer⁽³⁾.

INCUBATION PERIOD: Average of 28 to 30 days (range of 15 to 50 days)⁽²^,³^,¹¹⁾.

COMMUNICABILITY: Maximum infectivity occurs in the latter half of incubation and continues a few days after the onset of jaundice⁽¹^,⁴^,¹¹⁾. Chronic shedding of HAV in faeces does not occur⁽¹¹⁾.

SECTION III - DISSEMINATION

RESERVOIR: Humans⁽¹^,²^,³^,¹¹⁾.

ZOONOSIS: None.

VECTORS: None.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Triazolo[4,3-b]pyridazine derivatives show antiviral activity against HAV⁽⁵⁾ but are not yet used clinically.

SUSCEPTIBILITY TO DISINFECTANTS: HAV is inactivated by 1 % sodium hypochlorite, formulations of quaternary ammonium compounds and HCl⁽⁷⁾, and 2 % glutaraldehyde⁽³^,⁴^,⁶⁾.

PHYSICAL INACTIVATION: Inactivation of HAV can be achieved by heating to greater than 85°C for 1 minute⁽³^,⁴⁾.

SURVIVAL OUTSIDE HOST: HAV is exceptionally stable at ambient temperature and at low pH, thus allowing it to survive in the environment and to be transmitted via contaminated foods and drinking water⁽¹^,⁹⁾.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: A number of techniques have been employed to detect HAV, including RT- PCR, radioimmunoassay, ELISA, immunoblotting, and dot-blot gold filtration⁽¹^,²^,⁷^,⁸^,¹⁰^,¹²⁾.

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

FIRST AID/TREATMENT: No specific treatment for HAV infection has been shown to be effective⁽²^,⁴⁾. Bed rest and balanced nutrition are recommended, as is the avoidance of alcohol or other hepatotoxins⁽²⁾.

IMMUNIZATION: Several inactivated HAV vaccines have been shown to be effective (highly immunogenic and safe)⁽²^,⁴⁾.

PROPHYLAXIS: Individuals who are known to have been exposed to HAV should be administered HAV immune globulin (0.02ml/kg body weight) within two weeks of the initial exposure⁽¹^,²^,⁴⁾. Inactivated HAV vaccines are highly effective in pre-exposure prophylaxis for laboratory workers and travellers to HAV endemic areas⁽¹⁾. There is also some evidence for effective post-exposure prophylaxis with HAV vaccine⁽⁴⁾.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Unknown.

SOURCES/SPECIMENS: Faeces of infected humans and non-human primates⁽¹^,²^,³^,⁴^,⁹^,¹¹⁾. Other sources/specimens include blood, liver tissue, and bile⁽¹^,⁷^,⁸⁾.

PRIMARY HAZARDS: Ingestion of biological samples (faeces, blood) infected with HAV, or indirectly from contact with contaminated environmental surfaces⁽²^,⁶⁾.

SPECIAL HAZARDS: None.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2⁽¹³⁾.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, 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⁽¹⁴⁾.

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 other sharp objects should be strictly limited⁽¹⁴⁾. Additional precautions should be considered with work involving animals or large scale activities⁽¹⁴⁾.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectants starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)⁽¹⁴⁾.

DISPOSAL: Decontaminate all materials for disposal by steam sterilization, chemical disinfection, and/or incineration⁽¹⁴⁾.

STORAGE: In sealed containers that are appropriately labelled⁽¹⁴⁾.

SECTION IX – REGULATORY AND OTHER INFORMATION

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: September 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.

REFERENCES:

Martin, A., & Lemon, S. M. (2006). Hepatitis A virus: From discovery to vaccines. Hepatology, 43 (2 SUPPL. 1), S164-S172.
Kemmer, N. M., & Miskovsky, E. P. (2000). Hepatitis A. Infectious Disease Clinics of North America, 14 (3), 605-615.
Nainan, O. V., Xia, G., Vaughan, G., & Margolis, H. S. (2006). Diagnosis of hepatitis A virus infection: A molecular approach. Clinical Microbiology Reviews, 19 (1), 63-79.
Wasley, A., Fiore, A., & Bell, B. P. (2006). Hepatitis A in the era of vaccination. Epidemiologic Reviews, 28 (1), 101-111.
Shamroukh, A. H., & Ali, M. A. (2008). Anti-HAV activity of some newly synthesised triazolo[4,3- b]pyridazines. Arch. Pharm. Chem. Life Sci. 341(4):223-230., 4 (223), 230.
Mbithi, J. N., Springthorpe, V. S., & Sattar, S. A. (1990). Chemical disinfection of hepatitis A virus on environmental surfaces. Applied and Environmental Microbiology, 56 (11), 3601- 3604.
Wang, C. -., Tschen, S. -., Heinricy, U., Weber, M., & Flehmig, B. (1996). Immune response to hepatitis A virus capsid proteins after infection. Journal of Clinical Microbiology, 34 (3), 707-713.
Shao, Z. -., Xu, D. -., Yan, Y. -., Li, J. -., Zhang, J. -., Zhang, Z. -., & Pan, B. -. (2003). Detection of anti-HAV antibody with dot immunogold filtration assay. World Journal of Gastroenterology, 9 (7), 1508-1511.
McCaustland, K. A., Bond, W. W., Bradley, D. W., Ebert, J. W., & Maynard, J. E. (1982). Survival of hepatitis A virus in feces after drying and storage for 1 month. . J. Clin. Microbiol., 16 (5), 957-958.
Delem, A. D. (1992). Comparison of modified HAVAB and ELISA for determination of vaccine-induced Anti-HAV response. Biologicals, 20 (4), 289-291.
Heymann, D. L. (2004). An Official Report of the American Public Health Association. In D. L. Heymann (Ed.), Control of Communicable Diseases Manual. (18th ed., pp. 35-37). Washington, D.C.: American Public Health Association.
Purcell, R. H., Wong, D. C., & Moritsugu, Y. (1976). A microtiter solid phase radioimmunoassay for hepatitis a antigen and antibody. Journal of Immunology, 116 (2), 349-356.
Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57- 58 Elizabeth II, 2009. (2009).
Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.