Hepatitis A

Hepatitis A is a viral infection of the liver found throughout the world, though the incidence is relatively low in the United States and other developed countries. After travelers' diarrhea, hepatitis A is the most common travel-related infection. The disease may be acquired by direct contact with infected persons; from contaminated water or ice, including shellfish harvested from sewage-contaminated water; or from foods contaminated by infected food handlers. Symptoms may include fever, malaise, jaundice, nausea, vomiting, and abdominal pain. Most cases resolve without complications, though hepatitis A occasionally causes severe liver damage. The disease is diagnosed by the presence of hepatitis A IgM antibodies in the blood. There is no treatment.

Hepatitis A vaccine is recommended for all travelers to developing countries. Two vaccines are currently available in the United States: VAQTA (Merck and Co., Inc.) (PDF) and Havrix (GlaxoSmithKline) (PDF). Both are well-tolerated. Side-effects are generally mild and may include soreness at the injection site, headaches, and malaise. More serious events, including severe allergic reactions, Guillain-Barre syndrome, brachial plexus neuropathy, transverse myelitis, encephalopathy, and erythema multiforme, have been reported after hepatitis A vaccine, generally in adults also receiving other vaccines. The relationship between hepatitis A and these occurrences remains unclear. No serious adverse events have ever been definitively attributed to hepatitis A vaccine. Hepatitis A vaccine should not be given to anyone with a history of hypersensitivity to alum, which is a component of both vaccines. Also, those allergic to 2-phenoxyethanol should not be given HAVRIX. The safety of hepatitis A vaccine in pregnancy has not been determined. However, since the vaccine is made from inactivated virus, the risk is thought to be very low.

For both vaccines, the recommended adult dosage is 1.0 ml by intramuscular injection into the deltoid muscle. The dosage should be reduced to 0.5 ml for those between 2 and 18 years of age. The vaccine should be given at least two weeks prior to departure in order for antibody titers to rise to sufficient levels to confer immunity. A booster dose should be given 6-12 months later to provide long-term immunity. Two doses of hepatitis A vaccine appear to confer protection for at least ten years. Recent evidence indicates that the duration of protection after two doses is probably 20 years or greater.  VAQTA is approved for those greater than 12 months of age. Havrix is approved for children greater than 2 years of age.

Older adults, immunocompromised persons, and those with chronic liver disease or other chronic medical conditions who have less than two weeks before departure should receive a single intramuscular dose of immune globulin (0.02 mL/kg) at a separate anatomic injection site in addition to the initial dose of vaccine. Travelers who are less than one year of age or allergic to a vaccine component should receive a single intramuscular dose of immune globulin (0.02 mL/kg), which provides effective protection for up to three months, in the place of vaccine. If the travel period is expected to be greater than two months, the dosage of immune globulin should be 0.06 mL/kg; administration must be repeated if the travel period is greater than five months. Measles, mumps, rubella, and varicella vaccines should not be given for 3-11 months after immune globulin, depending on the quantity administered (see Spacing of Immunobiologics on the CDC website).

A combined hepatitis A and hepatitis B vaccine (Twinrix; GlaxoSmithKline) (PDF) is now available. A full series consists of three intramuscular doses given at times 0, 1, and 6 months, as for hepatitis B vaccine. An accelerated dosing schedule of 0, 7, 21-30 days and a month 12 booster dose was recently approved by the FDA. Adverse reactions appear comparable to those reported for previously licensed hepatitis A and B vaccines. In the United States, the vaccine is approved for those 18 years or older. In other parts of the world, including Canada and Europe, a pediatric formulation (Twinrix Junior) is available. For travelers who require immunization against both types of hepatitis, Twinrix will reduce the number of total injections from five to three, though it will not change the minimum time necessary for immunization. The amount of hepatitis A antigen in Twinrix is half that in single antigen hepatitis A vaccine (Havrix). Hepatitis A antibody levels are high after Twinrix, but it is unknown whether or not the lower dose will affect the duration of immunity.

On December 10, 2001, the U.S. Food and Drug Administration recalled certain lots of VAQTA, listed on its website, because some prefilled syringes were found not to contain enough antigen. Those who received the adult formulation after May 29, 2001, or the pediatric formulation after August 9, 1999, may be affected. See the Centers for Disease Control for details. In Europe, all stocks of VAQTA have been withdrawn from the market pending further inquiry.  Those who received vaccine which has been recalled may not be adequately protected against hepatitis A and should either be revaccinated or tested for immunity before departure.

In Canada, two additonal hepatitis A vaccines have been licensed. See Health Canada for further information.

From the World Health Organization

Hepatitis A (brief introduction)

Hepatitis A vaccine

Safety of hepatitis A vaccine

Global distribution of hepatitis A, B and C, 2001. Weekly Epidemiological Record, 8 February 2002 (PDF)

From the Centers for Disease Control (CDC)

Hepatitis, Viral, Type A

Viral Hepatitis A Fact Sheet

Viral Hepatitis A Frequently Asked Questions

Twinrix: Combined Hepatitis A and Hepatitis B Vaccine

FDA Approval for a Combined Hepatitis A and B Vaccine

Chiefly for physicians:

Update: Prevention of Hepatitis A After Exposure to Hepatitis A Virus and in International Travelers. Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP)

Licensure of Inactivated Hepatitis A Vaccine and Recommendations for Use Among International Travelers (PDF) (MMWR)

Prevention of Hepatitis A Through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices (PDF) (latest recommendations for hepatitis A vaccine, not specifically for travelers) (MMWR)

Sources of Immune Globulin for Intramuscular Administration (IMIG)

From Health Canada

Statement on Hepatitis A Vaccines for Travellers

Supplementary Statement on Hepatitis A Vaccine

Statement on Combination Vaccines against Hepatitis A and Hepatitis B

From the National Travel Health Network and Centre (U.K.)

Hepatitis A

From the U.K. Health Protection Agency

Guidelines for the control of hepatitis A infection