Am Fam Physician. 2006;73(12):2233-2242
See related article on page 2162.
Since the hepatitis A vaccine was licensed in 1996, disease rates have declined to the lowest level ever recorded. The Centers for Disease Control and Prevention has implemented its hepatitis A childhood immunization strategy incrementally, starting with the recommendation of the Advisory Committee on Immunization Practices (ACIP) in 1996 to vaccinate children living in communities with the highest disease rates and continuing in 1999 with ACIP’s recommendation for vaccination of children living in states, counties, and communities with consistently elevated rates of hepatitis A. ACIP now has released updated recommendations on the prevention of hepatitis A virus (HAV) infection through immunization; the report also includes new epidemiologic data and results of economic analyses of nationwide routine vaccination of children. The full report was published in the May 19, 2006, issue of Morbidity and Mortality Weekly Report and is available online athttp://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm.
Because most children have asymptomatic or unrecognized infections, they play a key role in HAV transmission and serve as a source of infection for others. Outbreaks and sporadic cases also can occur from exposure to fecally contaminated food or water, and uncooked foods have been recognized as a source of outbreaks. Cooked foods also can transmit HAV if cooking is inadequate to kill the virus or if food is contaminated after cooking. Waterborne outbreaks of hepatitis A are uncommon in developed countries with well-maintained sanitation and water supplies; most water-borne outbreaks are associated with sewage-contaminated or inadequately treated water. Outbreaks in the context of floods or other natural disasters (e.g., hurricanes) have not been reported in the United States.
Immune globulin (IG) provides protection against hepatitis A through passive transfer of antibody. When administered for preexposure prophylaxis, one dose of 0.02 mL per kg given intramuscularly confers protection for less than three months, and one dose of 0.06 mL per kg given intramuscularly confers protection for three to five months (Table 1). When administered within two weeks after an exposure to HAV, IG is 80 to 90 percent effective in preventing hepatitis A. Effectiveness is greatest when IG is administered early in the incubation period; when it is administered later, IG might only attenuate the clinical expression of HAV infection.
|Setting||Duration of coverage||Dose (mL per kg)|
|Preexposure prophylaxis||Short term (i.e., less than three months)||0.02|
|Long term (i.e., three to five months)*||0.06|
Serious adverse events from IG are rare. Anaphylaxis has been reported after repeated administration to persons with known immunoglobulin A (IgA) deficiency; thus, IG should not be administered to these persons. Pregnancy or lactation is not a contraindication to IG administration.
IG does not interfere with the immune response to oral poliovirus vaccine or yellow fever vaccine or, in general, to inactivated vaccines. However, IG can interfere with the response to other live, attenuated vaccines (e.g., measles, mumps, and rubella [MMR] vaccine, varicella vaccine) when administered as individual or combination vaccines. Administration of MMR should be delayed for at least three months and varicella vaccine for at least five months after administration of IG for hepatitis A prophylaxis. IG should not be administered less than two weeks after MMR or less than three weeks after varicella vaccine unless the benefits exceed the benefits of MMR and varicella vaccination. If IG is administered less than two weeks after MMR or less than three weeks after varicella vaccine, the patient should be revaccinated, but not sooner than three months after IG administration for MMR or five months for varicella vaccine.
HEPATITIS A VACCINE
Inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials. The vaccines containing HAV antigen that are currently licensed in the United States include the single-antigen vaccines Havrix and Vaqta, and the combination vaccine Twinrix, which contains HAV and hepatitis B virus (HBV) antigens (Table 2). All are inactivated vaccines.
|Vaccine||Patient’s age||Dose||Volume (mL)||Number of doses||Schedule (months)*|
|Hepatitis A vaccine, inactivated (Havrix)||12 months to 18 years||720 EL.U.||0.5||2||0, 6 to 12|
|19 years or older||1,440 EL.U.||1.0||2||0, 6 to 12|
|Hepatitis A vaccine, inactivated (Vaqta)||12 months to 18 years||25 U||0.5||2||0, 6 to 18|
|19 years or older||50 U||1.0||2||0, 6 to 18|
|Combined hepatitis A and hepatitis B vaccine (Twinrix)||18 years or older||720 EL.U. of hepatitis A antigen and 20 mcg of hepatitis B surface antigen protein||1.0||3||0, 1, and 6|
Vaqta is licensed in two formulations, which differ according to the patient’s age. Persons 12 months to 18 years of age should receive 25 U per dose in a two-dose schedule; persons older than 18 years should receive 50 U per dose in a two-dose schedule.
Havrix is available in two formulations, which differ according to the patient’s age; persons 12 months to 18 years of age should receive 720 EL.U. per dose in a two-dose schedule; and persons older than 18 years should receive 1,440 EL.U. per dose in a two-dose schedule. A children’s formulation of 360 EL.U. per dose administered in a three-dose schedule is no longer available.
Twinrix is licensed for use in persons 18 years and older. It is a combined hepatitis A and hepatitis B vaccine containing 720 EL.U. of hepatitis A antigen and 20 mcg of recombinant hepatitis B surface antigen protein. Primary immunization consists of three doses, administered on a zero-, one-, and six-month schedule, the same schedule as that commonly used for single-antigen hepatitis B vaccine. After three doses of Twinrix, antibody responses to both antigens are equivalent to responses noted after the single-antigen vaccines are administered separately on standard schedules.
Prevaccination Serologic Testing for Susceptibility
Vaccination of a person who is immune because of previous infection does not increase the risk of adverse events. However, in populations with expected high rates of previous HAV infection, prevaccination testing may be considered to reduce costs. Testing of children is not indicated because of their expected low prevalence of infection. For adults, the decision to test should be based on the expected prevalence of immunity, the cost of vaccination compared with the cost of serologic testing (including the cost of an additional visit), and the likelihood that testing will not interfere with initiation of vaccination. For example, if the cost of screening (including laboratory and office visits) is one third the cost of the vaccine series, screening potential recipients in populations for which the prevalence of infection is likely to be more than 33 percent should be cost-effective.
Persons in whom prevaccination testing likely will be most cost-effective include adults who were born in or lived for extensive periods in geographic areas that have a high or intermediate endemicity of hepatitis A; older adolescents and adults in certain population groups (i.e., American Indians, Alaska Natives, and Hispanics); and adults in certain groups that have a high prevalence of infection (e.g., injection-drug users). In addition, prevalence might be high enough among all older adults to warrant prevaccination testing. Overall anti-HAV prevalence among persons older than 40 years is more than 33 percent. Therefore, if the cost of screening is one third the cost of the vaccine series, prevaccination testing of any person older than 40 years likely would be cost-effective. Commercially available tests for total anti-HAV should be used for prevaccination testing.
Postvaccination Testing for Serologic Response
Postvaccination testing is not indicated because of the high rate of vaccine response among adults and children. In addition, not all testing methods approved for routine diagnostic use in the United States have the sensitivity to detect low anti-HAV concentrations after vaccination.
All children should receive hepatitis A vaccine at one year of age (i.e., 12 to 23 months). Vaccination should be completed according to the licensed schedules and integrated into the routine childhood vaccination schedule. Children who are not vaccinated by two years of age can be vaccinated at subsequent visits.
States, counties, and communities with existing hepatitis A vaccination programs for children two to 18 years of age are encouraged to maintain these programs. In these areas, new efforts focused on routine vaccination of children at one year of age should enhance, not replace, ongoing programs directed at a broader population of children. In areas without existing hepatitis A vaccination programs, catch-up vaccination of unvaccinated children two to 18 years of age may be considered. Such programs might especially be warranted in the context of increasing incidence or ongoing outbreaks among children or adolescents.
OTHER PERSONS AT INCREASED RISK OF INFECTION WHO SHOULD BE VACCINATED
Persons Traveling to Countries That Have High or Intermediate Endemicity of Infection
All susceptible persons traveling to countries that have high or intermediate hepatitis A endemicity should be vaccinated or receive IG before departure. Hepatitis A vaccination at the age-appropriate dose is preferred. Prevaccination testing should be considered for older travelers or for younger persons in certain population groups.
Travelers to Australia, Canada, western Europe, Japan, or New Zealand (i.e., countries in which endemicity is low) are at no greater risk of infection than persons in the United States. Data are not available regarding the risk of hepatitis A in persons traveling to certain areas of the Caribbean, although vaccine or IG should be considered if travel to areas that have questionable sanitation is anticipated.
The first dose of hepatitis A vaccine should be administered as soon as travel is considered. Travelers can be assumed to be protected within four weeks after receiving the first dose. Persons who receive single-antigen hepatitis A vaccine often will produce detectable anti-HAV levels two weeks after the first dose; the proportion of persons who will have detectable anti-HAV levels at two weeks might be lower when lower vaccine dosages are used; however, no data are available about the risk of hepatitis A among persons vaccinated two to four weeks before departure. Because protection might not be complete until four weeks after vaccination, persons traveling to a high-risk area less than four weeks after the initial dose also may receive IG (0.02 mL per kg) at a different injection site. Travelers departing in less than four weeks who do not or cannot receive IG should nonetheless receive hepatitis A vaccine and be informed that they may not be optimally protected from acquiring hepatitis A in the immediate future (i.e., two to four weeks). Completion of the vaccine series according to the licensed schedule is necessary for long-term protection.
Travelers who are allergic to a vaccine component or who choose not to be vaccinated should receive a single dose of IG (0.02 mL per kg), which provides effective protection against hepatitis A for up to three months. Persons whose travel period is greater than two months should be given IG at 0.06 mL per kg; administration must be repeated if the travel period is greater than five months.
Men Who Have Sex with Men
Adolescent males and adult men who have sex with men should be vaccinated. Prevaccination testing is not indicated for adolescents and young adults in this population but may be warranted for older adults. Studies have suggested that most men who have sex with men would accept hepatitis A vaccination if it was recommended by their physicians. Primary care physicians for men who have sex with men should offer hepatitis A vaccine to patients at risk. Implementation strategies to overcome barriers and increase coverage (e.g., use of standing orders) should be considered.
Users of Injection and Noninjection Drugs
Vaccination is recommended for users of injection and noninjection illicit drugs. Prevaccination testing is not indicated for adolescent users of illicit drugs but may be warranted for certain adults. The need might depend on the characteristics of the population, including the type and duration of drug use. Physicians should obtain a thorough history to identify patients who use or are at risk for using illicit drugs and who might benefit from hepatitis A vaccination. Implementation strategies to overcome barriers and increase coverage (e.g., use of standing orders) should be considered.
Persons Who Have Occupational Risk for Infection
Persons who work with HAV-infected primates or with HAV in a research laboratory setting should be vaccinated. Studies of U.S. workers exposed to raw sewage do not indicate increased risk of HAV infection. No other populations have been shown to be at increased risk for HAV infection because of occupational exposure.
Persons with Clotting Factor Disorders
Susceptible persons who receive clotting factor concentrates, especially solvent-detergent–treated preparations, should receive hepatitis A vaccine. Changes in clotting factor preparation practices and donor screening have greatly reduced the risk of hepatitis A for recipients of clotting factors.
Persons with Chronic Liver Disease
Susceptible persons with chronic liver disease should be vaccinated. Available data do not indicate a need for routine vaccination of persons with chronic HBV or hepatitis C virus infections without evidence of chronic liver disease. Susceptible persons who are awaiting or have received liver transplants should be vaccinated.
VACCINATION DURING OUTBREAKS
If community-wide outbreaks occur, accelerated vaccination may be considered as an additional control measure. Factors to consider in deciding whether to initiate an outbreak-control vaccination program include program cost and the feasibility of rapidly vaccinating the target population of children, adolescents, or young adults. Ongoing vaccination of children should be sustained to maintain high levels of immunity and prevent future epidemics.
Limited outbreaks, especially those involving adults at increased risk (e.g., illicit drug users, men who have sex with men), are likely to continue until higher vaccine coverage is achieved in these populations. Vaccination programs to control these outbreaks have been difficult to implement. Programs to control hepatitis A outbreaks among users of illicit drugs focused on vaccination in county jails and similar venues (e.g., court-ordered diversion programs); these programs have had limited success, at least in terms of the provision of vaccine. In general, efforts to control and prevent hepatitis A outbreaks among adults in these populations should be focused primarily on initiating and sustaining routine vaccination of these persons.
The frequency of outbreaks in child care centers also has decreased in recent years and should continue to decrease with more widespread vaccination of young children. Limited data exist about the role of hepatitis A vaccine in controlling outbreaks in these settings. If outbreaks are recognized in child care centers, the use of IG is effective in limiting transmission to employees and families of attendees. Previously unvaccinated children receiving postexposure prophylaxis with IG also should receive hepatitis A vaccine.
Persons who work as food handlers can contract hepatitis A and can potentially transmit HAV to others. One national economic analysis concluded that routine vaccination of all food handlers would not be economical. Nonetheless, to decrease the frequency of evaluations of food handlers with hepatitis A and the need for postexposure prophylaxis of restaurant patrons, vaccination can be considered for employees who work in areas where state and local health authorities or private employers determine that vaccination is appropriate.
POSTEXPOSURE PROPHYLAXIS WITH IG
Persons who have been exposed recently to HAV and who have not received hepatitis A vaccine previously should be administered a single dose of IG (0.02 mL per kg) as soon as possible. The effectiveness of IG when administered more than two weeks after exposure has not been established. Persons who have received one dose of hepatitis A vaccine at least one month before exposure to HAV do not need IG.
Because hepatitis A cannot be diagnosed reliably by clinical presentation alone, serologic confirmation of HAV infection in index patients by IgM anti-HAV testing is recommended before postexposure treatment of contacts. Screening of contacts for immunity before administering IG is not recommended.
If hepatitis A vaccine is recommended for a person receiving IG (e.g., someone with a recent exposure but also an indication for vaccination), it may be administered simultaneously with IG at a separate injection site. Unlike IG, hepatitis A vaccine is not licensed for post-exposure prophylaxis.
IG should be administered to previously unvaccinated persons in the following situations:
Close personal contact. IG should be administered to all previously unvaccinated household and sexual contacts of persons with serologically confirmed hepatitis A. In addition, persons who have shared illicit drugs with a person who has serologically confirmed hepatitis A should receive IG and hepatitis A vaccine. Consideration also should be given to providing IG to persons with other types of ongoing, close personal contact with a person who has hepatitis A (e.g., regular babysitting).
Child care centers. IG should be administered to all previously unvaccinated staff and attendees of child care centers where one or more cases of hepatitis A are recognized in children or employees or where cases are recognized in two or more households of center attendees. In centers that do not provide care to children who wear diapers, IG should be administered only to classroom contacts of the index patient. When an outbreak occurs (i.e., cases in three or more families), IG also should be considered for members of households that have children (center attendees) in diapers. Hepatitis A vaccine may be administered at the same time as IG for children receiving postexposure prophylaxis in child care centers.
Common-source exposure. If a food handler is diagnosed with hepatitis A, IG should be administered to other food handlers at the same establishment. Because common-source transmission to patrons is unlikely, IG administration to patrons typically is not indicated, but it may be considered if the food handler directly handled uncooked foods or foods after cooking and had diarrhea or poor hygienic practices, and if patrons can be identified and treated within two weeks after the exposure. In settings in which repeated exposures to HAV might have occurred (e.g., institutional cafeterias), stronger consideration of IG use may be warranted. In the event of a common-source outbreak, IG should not be administered to exposed persons after cases have begun to occur because the two-week period during which IG is effective will have been exceeded.
Schools, hospitals, and work settings. IG is not routinely indicated when a single case occurs in an elementary or secondary school, an office, or other work settings and the source of infection is outside the school or work setting. Similarly, when a person who has hepatitis A is admitted to a hospital, staff should not routinely be administered IG; instead, careful hygienic practices should be emphasized. IG should be administered to persons who have close contact with index patients if an epidemiologic investigation indicates that HAV transmission has occurred among students in a school or patients or between patients and staff in a hospital.