Hepatitis A is an enterically transmitted viral disease which is highly endemic throughout the developing world but of low endemicity in developed countries such as the United States. In developing countries, hepatitis A virus (HAV) is usually acquired during childhood, most frequently as an asymptomatic or mild infection. Transmission may occur by direct person-to-person contact; or from contaminated water, ice, or shellfish harvested from sewage-contaminated water; or from fruits, vegetables or other foods which are eaten uncooked, but which may become contaminated during handling. HAV is inactivated by boiling or cooking to 85°C (1 minute); cooked foods cannot serve as vehicles for disease unless contaminated after cooking. Adequate chlorination of water as recommended in the United States will inactivate HAV.

The risk of acquiring HAV infection for U.S. citizens traveling abroad varies with living conditions, length of stay, and incidence of hepatitis A in the area visited. Travelers to North America except Mexico and developed countries in Europe, Japan, Australia, and New Zealand are at no greater risk of infection than in the United States. For travelers to developing countries, risk of infection increases with duration of travel, and will be highest in 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.

In developing countries, travelers should minimize their risk of hepatitis A and other enteric diseases by avoiding potentially contaminated water or food. Drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruits or vegetables which are not peeled or prepared by the traveler should be avoided.

Hepatitis A vaccine or immune globulin(IG) is recommended for all susceptible persons traveling to or working in countries with intermediate or high endemicity of infection (see map).

Vaccination of children 2 years of age and older, adolescents and adults with the age-appropriate dose (Table 12a.Recommended doses of HAVRIX®, Table 12b. Recommended doses of VAQTA®) is preferred for persons who plan to travel repeatedly or reside for long periods in these high risk areas. IG is recommended for travelers less than 2 years of age and for persons of all ages desiring only short term protection.

Figure: Geographic Distribution of Hepatitis A Prevalence

There are two hepatitis A vaccines currently licensed in the United States: HAVRIX® (manufactured by SmithKline Beecham Pharmaceuticals) and VAQTA® (manufactured by Merck & Co., Inc.). Both are inactivated vaccines, adsorbed to aluminum hydroxide as an adjuvant and prepared with 2-phenoxyethanol as the preservative.

The vaccine should be administered by intramuscular injection in the deltoid muscle. A needle length appropriate for the persons’s age and size should be used.

HAVRIX® is currently licensed in three formulations, and the formulation and number of doses vary accoring to the person’s age: for children and adolescents 2-18 years of age, 360 EL.U. per dose in a three-dose schedule and 720 EL.U. per dose in a two-dose schedule; for adults >18 years of age, 1,440 EL.U. per dose in a two-dose schedule (Table 12a). VAQTA® is licensed in two formulations, and the formulation and number of doses vary according to the person’s age: for children and adolescents 2-17 years of age, 25 U in a two-dose schedule and for adults >17 years of age, 50 U per dose in a two-dose schedule (Table 12b).

Travelers who are 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 hepatitis A for up to 3 months. For travel longer than 3 months, an IG dose of 0.06 mL/kg should be given and must be repeated if travel is longer than 5 months. See Table 11 for approximate IG dosages.

For some travelers, screening for total antibodies to HAV (anti-HAV) before travel may be useful to determine susceptibility and eliminate unnecessary vaccination or IG prophylaxis of immune persons. Such serologic screening for susceptibility may 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 interfere with subsequent receipt of vaccine or IG. Such persons may include those older than 40 years of age and persons born in parts of the world with intermediate or high endemicity (see map). Postvaccination testing for serologic response is not indicated.

Data on long-term persistence of antibody after hepatitis A vaccination are limited because the currently available vaccines have been under evaluation for only 4-5 years. Estimates of antibody persistence derived from kinetic models of antibody decline suggest that protective levels of anti-HAV could persist for at least 20 years.

Persons can be assumed to be protected by 4 weeks after receiving the first vaccine dose, although a second dose 6 to 12 months later is necessary for long-term protection. Because protection may not be complete until 4 weeks after vaccine administration, persons traveling to high risk areas less than 4 weeks after the initial dose should also be given IG(0.02 mL/kg), but at a different injection site.

Safety

Experience to date indicates that hepatitis A vaccine has an excellent safety profile. Approximatelly 50,000 persons have received HAVRIX® in clinical studies. No serious adverse events have been attributed definitively to hepatitis A vaccine. In adults, the most frequent side effect observed within 3 days after the 1440 EL.U. dose was soreness at the injection site (56%), followed by headache (14%) and malaise (7%), the incidence of side effects generally has been similar to that of hepatitis B vaccine. In clinical studies among children, the most common side effect reported was soreness (15%), followed by feeding problems (8%), headache (4%) and injection site induration (4%). No serious adverse events have been observed among approximately 40,000 children who have received the 360 EL.U. dose of hepatitis A vaccine in the protective efficacy study.

Approximately 9,200 persons have received VAQTA® in clinical studies. No serious adverse events were observed among participants in the clinical studies. Among adults, the most frequent side effects observed within 5 days following vaccination include tenderness at the injection site (53%), pain (51%) and warmth (17.3%), and headache (16.1%). Among children, the most common side effects reported were pain at injection site (19%), tenderness at injection site (17%), and warmth (9%).

An estimated 1.3 million persons have been vaccinated with HAVRIX® since it was licensed in Europe and Asia. Postlicensure reports, without regard to causality, of serious adverse events received by the vaccine manufacturer have included anaphylaxis, Guil-lain- Barré syndrome, brachial plexus neuropathy, transverse myelitis, multiple sclerosis, encephalopathy, and erthema multiforme (SmithKline Beecham Biologicals, unpublished data). Most of these events have occurred among adults, and approximately one third have occurred among persons receiving other vaccines concurrently. For serious adverse events for which background incidence data are known (e.g., Guillain-Barré syndrome and brachial plexus neuropathy, the rates among vaccine recipients are not higher than would be expected among an unvaccinated population (CDC, unpublished data). In Europe, the ratio of reported adverse events to number of doses distributed is similar for the manufacturer’s hepatitis A and hepatitis B vaccines (SmithKline Beecham Biologicals, unpublished data).

Because VAQTA® was just recently licensed, postmarketing data are limited. An esti-mated 20,000 persons have been administered VAQTA® since it was licensed in the United States and Germany, and no serious adverse events have been reported (Merck & Company, Inc., unpublished data).

Any adverse event suspected to be associated with hepatitis A vaccination should be reported to the Vaccine Adverse Event Reporting System (VAERS), VAERS forms can be obtained by calling 1-800-822-7967.

Hepatitis A vaccine should not be administered to persons with a history of hypersen-sitivity reactions to alum or the preservative 2-phenoxyethanol. Vaccination of an immune person is not contraindicated and does not increase the risk of adverse effects. Because the vaccine is inactivated, no special precautions need to be taken in vaccination of immunocompromised persons. 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 [HBV], hepatitis C virus [HCV] or human immunodeficiency virus [HIV]). Specific laboratory studies have shown that immune globulins prepared by cold ethanol fractionation (the standard procedure used in U.S.-manufactured preparations) carry no risk of transmission of HIV. Pregnancy is not a contraindication to using immune globulin.

Pregnancy

The safety of hepatitis A vaccination during pregnancy has not been determined. However, because hepatitis A vaccine is produced from inactivated HAV, the theoretical risk to the developing fetus is expected to be low. The risk of vaccination should be weighted against the risk of hepatitis A in women who may be at high risk for exposure to HAV.