Hepatitis, Viral, Type A
Hepatitis A is a viral infection of the liver caused by hepatitis A virus (HAV). The clinical manifestations of HAV infection range in clinical severity from no symptoms to a mild illness lasting 12 weeks to a severely disabling disease lasting several months. Clinical manifestations of hepatitis A often include fever, malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice.
HAV is shed in the feces of persons with HAV infection. Transmission can occur through direct person-to-person contact; through exposure to contaminated water, ice, or shellfish harvested from sewage-contaminated water; or from fruits, vegetables, or other foods that are eaten uncooked and that were contaminated during harvesting or subsequent handling.
HAV infection is common (high or intermediate endemicity) throughout the developing world, where infections most frequently are acquired during early childhood and usually are asymptomatic or mild. In developed countries, HAV infection is less common (low endemicity), but communitywide outbreaks still occur in some areas of the United States.
Risk for Travelers
The risk of acquiring HAV infection for U.S. residents traveling abroad varies with living conditions, length of stay, and the incidence of HAV infection in the area visited. Travelers to North America (except Mexico), Japan, Australia, New Zealand, and developed countries in Europe are at no greater risk for infection than in the United States. For travelers to low-income countries, risk for infection increases with duration of travel and is highest for those who live in or visit rural areas, trek in back country areas, or frequently eat or drink in settings of poor sanitation. Nevertheless, many cases of travel-related hepatitis A occur in travelers to developing countries with standard tourist itineraries, accommodations, and food consumption behaviors.
The incubation period for hepatitis A averages 28 days (range 1550 days). Hepatitis A typically has an abrupt onset of symptoms that can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The likelihood of having symptoms with HAV infection is related to the infected person's age. In children <6 years old, most (70%) infections are asymptomatic; if illness does occur it is not usually last <2 months. There is no chronic or long-term infection associated with hepatitis A, but 10% of infected persons will have prolonged or relapsing symptoms over a 6- to 9-month period. The overall case-fatality rate among cases reported to CDC is 0.3%; however, the rate is 1.8% among adults >50 years of age.
Hepatitis A is one of the most common vaccine-preventable diseases in travelers. Hepatitis A vaccine, immune globulin (IG), or both, are recommended for all susceptible persons traveling to or working in countries with an intermediate or high endemicity of HAV infection.
Vaccine and Immune Globulin
Two monovalent hepatitis A vaccines are currently licensed in the United States for persons >2 years of age: HAVRIX, manufactured by GlaxoSmithKline (Table 34), and VAQTA (manufactured by Merck & Co., Inc.) (Table 35). Both vaccines are made of inactivated hepatitis A virus adsorbed to aluminum hydroxide as an adjuvant. HAVRIX is prepared with 2-phenoxyethanol as a preservative, while VAQTA is formulated without a preservative. All hepatitis A vaccines should be administered intramuscularly in the deltoid muscle
TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons >18 years of age, containing 720 EL.U. of hepatitis A antigen (50% of the HAVRIX adult dose) and 20 ΅g of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose) (Table 36). Primary immunization consists of three doses, given on a 0-, 1-, and 6-month schedule, the same schedule as that commonly used for monovalent hepatitis B vaccine. TWINRIX contains aluminum phosphate and aluminum hydroxide as adjuvant and 2-phenoxyethanol as a preservative.
The first dose of hepatitis A vaccine should be administered as soon as travel to countries with high or intermediate endemicity is considered. One month after receiving the first dose of monovalent hepatitis A vaccine, 94%100% of adults and children will have protective concentrations of antibody. The final dose in the hepatitis A vaccine series is necessary to promote long-term protection. The immunogenicity of TWINRIX is equivalent to that of the monovalent hepatitis vaccines when tested after completion of the licensed schedule.
Many persons will have a detectable antibody to hepatitis A virus (anti-HAV) response to the monovalent vaccine by 2 weeks after the first vaccine dose. The proportion of persons who develop a detectable antibody response at 2 weeks may be lower when lower vaccine dosages are used. Travelers who need optimal protection earlier than 4 weeks after the first dose of vaccine should also receive immune globulin with the first vaccine dose (0.02 mL/kg), at a different injection site. Travelers who receive their hepatitis A vaccine <2 weeks before traveling to an endemic area and who do not receive immune globulin either by choice or because of lack of availability need to realize that they are still at risk of infection with Hepatitis A.
Although vaccination of an immune traveler is not contraindicated and does not increase the risk of adverse effects, screening for total anti-HAV before travel can be useful in some circumstances to determine susceptibility and eliminate unnecessary vaccination or IG prophylaxis of immune travelers. Such serologic screening for susceptibility might be indicated for adult travelers who are likely to have had prior HAV infection if the cost of screening (laboratory and office visit) is less than the cost of vaccination or IG prophylaxis and if testing will not delay vaccination and interfere with timely receipt of vaccine or IG prior to travel. Such travelers may include those >40 years of age and those born in areas of the world with intermediate or high endemicity. Postvaccination testing for serologic response is not indicated.
Using the vaccines according to the licensed schedules is preferable. However, an interrupted series does not need to be restarted. Given their similar immunogenicity, a series that has been started with one brand of monovalent vaccine (i.e., HAVRIX or VAQTA) may be completed with the other brand. Hepatitis A vaccine may be administered at the same time as other commonly used vaccines for travelers or as IG, at different injection sites.
In adults and children who have completed the vaccine series, anti-HAV has been shown to persist for at least 58 years after vaccination. Results of mathematical models indicate that after completion of the vaccination series, anti-HAV will likely persist for 20 years or more. For children and adults who complete the primary series, booster doses of vaccine are not recommended. Serologic testing to assess antibody levels after vaccination is not indicated.
Travelers who are <2 years of age, allergic to a vaccine component, or otherwise elect not to receive vaccine should receive a single dose of IG (0.02 mL/kg), which provides effective protection against HAV infection for up to 3 months (Table 37). Anyone traveling for >3 months should receive an IG dose of 0.06 mL/kg, which must be repeated if the duration of travel is >5 months.
Among adults, the most frequently reported side effects occurring 35 days after a vaccine dose were tenderness or pain at the injection site (53%56%) or headache (14%16%). Among children, the most common side effects reported were pain or tenderness at the injection site (15%19%), feeding problems (8% in one study), or headache (4% in one study). No serious adverse events in children or adults that could be definitively attributed to the vaccine or increases in serious adverse events among vaccinated persons compared with baseline rates have been identified.
Immune globulin for intramuscular administration prepared in the United States has few side effects (primarily soreness at the injection site) and has never been shown to transmit infectious agents (hepatitis B virus, hepatitis C virus [HCV], or HIV). Since December 1994, all IG products commercially available in the United States have had to undergo a viral inactivation procedure or be negative for HCV RNA before release.
Precautions and Contraindications
These vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component including alum. HAVRIX or TWINRIX should not be administered to travelers with a history of hypersensitivity reactions to the preservative 2-phenoxyethanol. TWINRIX should not be administered to persons with a history of hypersensitivity to yeast. Because hepatitis A vaccine consists of inactivated virus and hepatitis B vaccine consists of a recombinant protein, no special precautions need to be taken for vaccination of immunocompromised travelers.
Pregnancy. The safety of hepatitis A vaccine for pregnant women has not been determined. However, because hepatitis A vaccine is produced from inactivated HAV, the theoretical risk to either the pregnant woman or the developing fetus is thought to be very low. The risk of vaccination should be weighed against the risk of hepatitis A in women travelers who might be at high risk for exposure to HAV. Pregnancy is not a contraindication to using IG.
Other Prevention Tips
Boiling or cooking food and beverage items for at least 1 minute to 185° F (85° C) inactivates HAV. Foods and beverages heated to this temperature and for this length of time cannot serve as vehicles for HAV infection unless they become contaminated after heating. Adequate chlorination of water as recommended in the United States will inactivate HAV. Travelers should be advised that, to minimize their risk of hepatitis A and other enteric diseases in resource-poor countries, they should avoid potentially contaminated water or food. Travelers should also be advised to avoid drinking beverages (with or without ice) of unknown purity, eating uncooked shellfish, and eating uncooked fruits or vegetables that are not peeled or prepared by the traveler personally.
No specific treatment is available for persons with hepatitis A. Treatment is supportive.
Miriam Alter, Beth Bell, Anthony Fiore, Eric Mast, Linda Moyer
This page last reviewed June 30, 2003