Prevention
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. Health-care providers should administer hepatitis A vaccine, IG, or both (see below) for persons traveling for any purpose, frequency or duration to countries that have high or intermediate endemicity of HAV infection (1). In addition, health-care providers should be on the alert to opportunities to provide vaccination for all travelers whose plans might include travel at some time in the future to an area of high or intermediate endemicity, including those whose current medical evaluation is for travel to an area where hepatitis A vaccination is not currently recommended.
VACCINE AND IMMUNE GLOBULIN
Two monovalent hepatitis A vaccines are currently licensed in the United States for persons at least 12 months of age: HAVRIX, manufactured by GlaxoSmithKline (Table 4-3), and VAQTA (manufactured by Merck & Co., Inc.) (Table 4-4). 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 (1). The vaccine is administered as a 2 dose series with at least a 6 month interval between doses
TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons 18 years old or older, containing 720 EL.U. of hepatitis A antigen (50% of the HAVRIX adult dose) and 20 µg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose) (Table 4-5). 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 adjuvants and 2-phenoxyethanol as a preservative. An accelerated schedule of Twinrix (i.e., doses at days 0, 7, and 21) for travelers has been approved by the FDA. For this accelerated schedule, a booster dose should be given at 1 year.
The first dose of hepatitis A vaccine should be administered as soon as travel to countries with high or intermediate endemicity is considered. One dose of monovalent hepatitis A vaccine administered at any time before departure can provide adequate protection for most healthy persons aged <40 years (9). Completion of the vaccine series according to the licensed schedule is necessary for long-term protection. For optimal protection, older adults, immunocompromised persons, and persons with chronic liver disease or other chronic medical conditions planning to depart to an area in less than 2 weeks should receive the initial dose of vaccine along with IG (0.02 mL/kg) at a separate anatomic injection site. 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 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 smaller vaccine dosages are used, such as with the use of TWINRIX. Travelers who receive hepatitis A vaccine less than 2 weeks before traveling to an endemic area and who do not receive immune globulin (either by choice or because of lack of availability) will be at lower risk of infection than those who receive neither hepatitis A vaccine nor IG.
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 before travel. Such travelers may include those older than 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 (1).
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 IG or other commonly used vaccines for travelers, at different injection sites (1,2).
In adults and children who have completed the vaccine series, anti-HAV has been shown to persist for at least 5-12 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 (6). Serologic testing to assess antibody levels after vaccination is not indicated.
Travelers who are younger than 12 months of age, 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 HAV infection for up to 3 months (Table 4-6). Those who do not receive vaccination and plan to travel for longer than 3 months should receive an IG dose of 0.06 mL/kg, which must be repeated if the duration of travel is longer than 5 months (1,7).
(This section has been updated as of March 5, 2009.)
Adverse Reactions
Among adults, the most frequently reported side effects occurring 3-5 days after a vaccine dose are tenderness or pain at the injection site (53%-56%) or headache (14%-16%). Among children, the most common side effects reported are 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 (1).
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 (1).
Precautions and Contraindications
These vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component. 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 (1).
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 developing 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 (see Chapter 2) (8).
