Hepatitis, Viral, Type A

Description

Hepatitis A is a viral infection of the liver caused by hepatitis A virus (HAV). HAV infection may be asymptomatic or its clinical manifestations may range in severity from a mild illness lasting 1-2 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.

Occurrence

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. Map 4-4 indicates the seroprevalence of antibody to HAV (total anti-HAV) as measured in selected cross-sectional studies among each country's residents.

Risk for Travelers

Hepatitis A is the most common vaccine-preventable infection acquired during travel. The risk for 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 other 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.

Clinical Presentation

The incubation period for hepatitis A averages 28 days (range 15-50 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 its duration is usually <2 months. No chronic or long-term infection is 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.

Prevention

Note: Updated childhood and adolescent immunization schedule (January 12, 2006)

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 vaccination for persons traveling for any purpose, frequency or duration to countries that have high or intermediate endemicity of HAV infection. In addition, health-care providers should be 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 1 year of age or older (Updated April 24, 2006): HAVRIX, manufactured by GlaxoSmithKline (Table 4-4), and VAQTA (manufactured by Merck & Co., Inc.) (Table 4-5). 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.

Table 4-4. Licensed schedule for HAVRIX¹

¹Hepatitis A vaccine, inactivated, GlaxoSmithKline
²EL.U. = enzyme-linked immunosorbent assay (ELISA) units

Table 4-5. Licensed schedule for VAQTA¹

¹Hepatitis A vaccine, inactivated, Merck & Co., Inc.

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 µg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose) (Table 4-6). 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.

Table 4-6. Licensed schedule for TWINRIX¹

¹Combined hepatitis A and hepatitis B vaccine, GlaxoSmithKline
²EL.U. = enzyme-linked immunosorbent assay (ELISA) units

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 smaller vaccine dosages are used, such as with the use of TWINRIX. Travelers who receive 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 likely will be at lower risk of infection than those who do not receive hepatitis A vaccine or IG. In the case of travel within 4 weeks of vaccine administration, a dose of immune globulin (0.02 mL/kg) may be given alone or in addition to hepatitis A vaccine, at a different site, for optimal protection. In the case of unavailability or refusal of immune globulin, administration of hepatitis A vaccine alone for this group is recommended, but they should be informed that they are not optimally protected from acquiring hepatitis A in the immediate future (i.e., the subsequent 2-4 weeks).

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 >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 IG or other commonly used vaccines for travelers, at different injection sites.

In adults and children who have completed the vaccine series, anti-HAV has been shown to persist for at least 5-10 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, 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 4-7). Those who do not receive vaccination and plan to travel 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.

Table 4-7. Immune globulin for protection against viral Hepatitis A

¹For intramuscular injection

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.

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. 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 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, Risks from Food and Drink.)

Treatment

No specific treatment is available for persons with hepatitis A. Treatment is supportive.

Bibliography

• Bell BP, Feinstone SM. Hepatitis A vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th edition. Philadelphia: W.B. Saunders, 2004.
• CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbid Mortal Wkly Rep MMWR. 1999; RR 48:1-37.
• Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis. 2004;38:705-15.
• Steffen R, Kane M, Shapiro C, et al. Epidemiology and prevention of hepatitis A in travelers. JAMA. 1994;272:885-9.
• Van Damme P, Banatvala J, Fay O, et al. Hepatits A booster vaccination: is there a need? Lancet. 2003;362:1065-71.
• Weinberg M, Hopkins J, Farrington L, et al. Hepatitis A in Hispanic children who live along the United States-Mexico border: the role of international travel and foodborne exposures. Pediatrics. 2004;114:e68-73.
• Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin Infect Dis. 1992;14:580-6.

- Anthony Fiore and Beth Bell