Hepatitis A virus (HAV) particles are environmentally hardy organisms that can be transmitted by contaminated food, water, environmental surfaces (e.g., contaminated table tops, cooking utensils) and through direct or indirect person-to-person contact. Although HAV cannot grow in the environment, they are considered to be extremely stable under a wide range of environmental conditions, including freezing, heat, chemicals, and desiccation. Concentrations of disinfectants commonly used against pathogenic bacteria are not considered effective against these viruses.
There are six HAV genotypes (I-VI), as determined by RNA sequence analysis at the VP1-2A junction of the virus genome. Genotypes I, II, and III contain strains associated with human infections, with the majority of human strains grouped within genotypes I and III. Genotypes I-III have been further divided into sub-genotypes A and B for each genotype. Most non-human primate strains are grouped within genotypes IV, V, and VI. Despite the identification of multiple genotypes/strains, this is the only known serotype for HAV. Humans and several species of non-human primates are the only known natural hosts for HAV.
HAV is classified with the enterovirus group of the Picornaviridae family, genus Hepatovirus, and is comprised of single positive-stranded RNA genome of approximately 7.5 kilobases. This RNA molecule is protected from the environment by a protein capsid (“shell”) comprised of multiple copies of three or four proteins. HAV is a non-enveloped (i.e., no lipid-containing envelope), hydrophobic virus 22 to 30 nm in size, with icosahedral symmetry with 20 sides.
• Mortality: The overall death rate among people with hepatitis A (that is, liver involvement; the term “hepatitis A” is used to refer to the disease, not to the virus) is approximately 2.4%. Increased age (over 50 years old) slightly increases the death rate. Overall, hepatitis A accounts for < 0.001% of all foodborne-associated deaths. Although fulminant (severe, rapidly progressing) disease is rare, the mortality rate is much higher, at 70% to 80%, as noted in the Illness / complications section, below.
• Infective Dose: The infective dose of HAV is presumed to be low (10 to 100 viral particles), although the exact dose is unknown. The viral particles are excreted in the feces of ill people (symptomatic and asymptomatic) at high densities (106 to 108/gm) and have been demonstrated to be excreted at these levels for up to 36 days post-infection.
• Onset: In symptomatic patients, mean incubation phase is 30 days (range 15 to 50 days).
• Illness / complications: HAV infections can be asymptomatic or symptomatic. Infections usually are asymptomatic in children younger than age 6 and symptomatic in older children and adults. When disease does occur, it is usually mild and recovery is complete within 1 to 2 weeks, although it may last up to several months, in which case it is also generally self-limiting. HAV infection is not considered to be chronic; however, a prolonged or relapsing disease lasting up to 6 months in 10-15% of patients has been reported. Patients feel chronically tired during convalescence, and their inability to work can cause financial loss. An atypical, and rare, clinical outcome of acute HAV infection is fulminant hepatitis or fulminant hepatic disease, which occurs in less than 1% to 1.5% of cases. This more severe outcome of acute HAV infection and illness involves massive hepatic necrosis, with acute liver failure, and has a high case-fatality rate (70% to 80%). The reasons for progression to acute, severe, or fulminant hepatitis remain unclear; however, it is known that patients with an underlying chronic liver disease are at particularly high risk for fulminant disease or liver failure. Factors that may play a role in severe hepatic disease progression include the nature of the host response (e.g., genetic, immunologic, or physiologic), the viral pathogen (e.g., strain virulence), and/or viral dosage (e.g., viral inoculums, patient viral load, or levels of viral replication). A hepatitis A vaccine is available.
• Symptoms: Symptoms associated with HAV infection include fever, anorexia, nausea, vomiting, diarrhea, myalgia, hepatitis, and, often, jaundice. Jaundice generally occurs 5 to 7 days after onset of gastrointestinal symptoms; however, in 15% of reported jaundice cases, the jaundice was not preceded by gastrointestinal symptoms.
• Duration: Typically 1 to 2 weeks, although prolonged or relapsing cases may continue for up to 6 months in a minority of patients.
• Route of entry: HAV may cause infection through various routes. The route of entry for the foodborne infection is oral.
• Pathway: The exact mechanism of HAV pathogenesis is not fully understood. The route of entry for foodborne HAV typically is the gastrointestinal tract. From the intestinal tract, the virus is transported to the liver via the blood, where hepatocytes generally are thought to be the site of viral replication. The virus is thought to be excreted by the hepatocytes and transported to the intestinal tract via bile. However, some studies suggest that initial replication may occur in crypt cells of the small intestine.
An estimated 1,566 cases of hepatitis A from consumption of contaminated food occur annually in the United States. This constitutes a small portion (1% to 1.5%) of the total number of patients infected with HAV. Overall, hepatitis A accounts for < 0.001% of all foodborne-associated hospitalizations in the U.S. Hepatitis A from any cause (i.e., not just the foodborne illness) has a worldwide distribution occurring in both epidemic and sporadic fashion. In the U.S., from 1980 through 2001, an average of 25,000 cases of hepatitis A was reported to the Centers for Disease Control and Prevention (CDC) annually. However, correcting for under-reporting and asymptomatic infections, CDC estimates that an average of 263,000 HAV infections, from all causes, occurred annually in the U.S. during this period.
Until 1995, the overall incidence of HAV infection in the U.S. was cyclic, with nationwide increases occurring every 10 to 15 years (Figure 1). Since 1995, the estimated overall number of reported HAV infections in the U.S. has been declining. This significant decrease (with the most significant decrease occurring in children) appears to coincide with the vaccination program, for children and adolescents 2 to 12 years old that began in the U.S. in 1996.
Incidence of Acute, Symptomatic Hepatitis A – United States, 1980-2008
Centers for Disease Control and Prevention. Accessed May 2011.
HAV is excreted in feces of infected people and can produce clinical disease when susceptible people consume contaminated water or foods. Cold cuts and sandwiches, fruits and fruit juices, milk and milk products, vegetables, salads, shellfish, and iced drinks are commonly implicated in outbreaks. Water, shellfish, and salads are the most frequent sources. Contamination of foods by infected workers in food-processing plants and restaurants also is common.
In the U.S., the estimated transmission rate of this virus by person-to person contact was 22%. Of that, 8% was associated with day-care settings, 5% with international travel, 5% with illegal injectable drug use, and 4% with consumption of common-source contaminated food or water. The transmission routes for 65% of cases are unknown. Low income, low education level, crowding, and lack of access to safe drinking water and sanitation facilities are associated with increased rates of HAV infection.
Clinical diagnosis of an HAV infection can be achieved by performing the appropriate analytical tests on serum or stool specimens. HAV diagnosis is generally performed by immunoglobulin (Ig) anti-hepatitis A antibody tests, IgM or IgG, in which an increase in virus-specific serum antibody titers is indicative of a recent HAV infection. One notable limitation for these antibody- based tests is that they cannot readily distinguish a recent HAV infection from increased antibody titer due to immunization, which can lead to elevated IgG and/or IgM being elicited against HAV. In addition to antibody testing, which also includes the use of immunoelectron microscopy, the use of molecular tests premised on reverse transcription polymerase chain reaction (RT-PCR) can also be utilized. Commercial kits are available to assist in HAV diagnosis.
6. Target Populations
All people are considered susceptible to HAV infection. Immunity can be developed by exposure and/or immunization that elicit an immune response that confers long-term immunity. In the U.S., the percentage of adults with immunity increases with age (10% for those 18 to 19 years of age to 65% for those over 50 years old). The increased number of susceptible people allows common-source epidemics to evolve rapidly.
7. Food Analysis
Methods have been developed to detect HAV in the food commodities most often implicated in HAV-associated illnesses; most notably, produce and shellfish. The manner in which the food is analyzed is dependent on the presumed location of contamination. For example, produce methods generally use a method to wash the viruses from the surface, whereas shellfish methods extract the virus from the digestive tract. Following extraction, the viruses are concentrated to suitable levels, so that detection via RT-PCR can be performed. These methods currently used by specialized regulatory laboratories to analyze suspected food for HAV are undergoing rigorous validation to verify that they are suitable for routine analysis.
8. Examples of Outbreaks
Hepatitis A is endemic throughout much of the world. Major national epidemics occurred in 1954, 1961, and 1971. Foods continue to be implicated in HAV outbreaks, which continue to occur in the U.S. following consumption of contaminated produce and shellfish. The most notable recent HAV outbreaks, in the U.S., that were associated with foods include:
• 1987 – Louisville, Kentucky- lettuce (imported)
• 1998 – Ohio- green onions (Mexico/California)
• 2000 – Kentucky and Florida- green onions (from Mexico) or tomatoes (California)
• 2003 – Tennessee, North Carolina, Georgia, Pennsylvania – green onions (Mexico)
• 2005 – Tennessee, Alabama – oysters (Louisiana) Case Example: In August 2005, at least 10 clusters of hepatitis A illness, totaling 39 people, occurred in four states among restaurant patrons who ate oysters. Epidemiologic data indicated that oysters were the source of the outbreak. Trace-back information showed that the implicated oysters were harvested from a specific Gulf Coast shellfish-growing area. A voluntary recall of oysters was initiated in September. HAV was detected in multiple 25-gm portions in one of two recalled samples, indicating that as many as 1 of every 15 oysters from this source was contaminated (Shieh, 2007). Other examples include:
- CDC Morbidity and Mortality Weekly Report: Hepatitis A Virus Provides a list of CDC Morbidity and Mortality Weekly Reports relating to this organism.
- NIH/PubMed: Hepatitis A Virus Provides a list of research abstracts contained in the National Library of Medicine’s MEDLINE database for this organism.
- Agricola: Hepatitis A Virus Provides a list of research abstracts contained in the National Agricultural Library database.
9. Other Resources
• Shieh YC, Khudyakov YE, Xia G, Ganova-Raeva LM, Khambaty FM, Wood JW, Veazey JE, Motes ML, Glatzer MB, Bialek SR, and Fiore AE. 2007. Molecular confirmation of oysters as the vector for hepatitis A in a 2005 multistate outbreak. J. Food Prot. 70:145-150.
• HAV Definition and MeSH headings from the National Library of Medicine
- Carl’s Jr. Hepatitis A Outbreak – Washington
- Chi-Chi’s Hepatitis A Outbreak – Pennsylvania
- Chipotle Grill Hepatitis A Outbreak – California
- D’Angelo’s Deli Hepatitis A Outbreak – Massachusetts
- Friendly’s Hepatitis A Exposure – Massachusetts
- Houlihan’s Hepatitis A Exposure – Illinois
- Maple Lawn Dairy Hepatitis A Outbreak – New York
- McDonald’s Hepatitis A Outbreak – Washington
- McDonald’s Hepatitis A Outbreak – Illinois
- Quizno’s Hepatitis A Exposure – Massachusetts
- Soleil Produce Hepatitis A Outbreak – California
- Subway Hepatitis A Outbreak – Washington
- Taco Bell Hepatitis A Outbreak – Florida