The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention has developed recommendations for the prevention of hepatitis A infection through active or passive immunization. The report appears in the October 1, 1999 issue of the recommendations and reports series (vol. 48; no. RR-12) of Morbidity and Mortality Weekly Report.
The ACIP recommendations were developed in response to the continuing high rates of hepatitis A in the United States and the frequency of community-wide outbreaks. The recommendations are an updated version of the 1996 ACIP report on the prevention of hepatitis A through immunization. The new report includes new data on the epidemiology of hepatitis A; recent findings about the effectiveness of community-based hepatitis A vaccination programs; and recommendations for the routine vaccination of children living in areas with rates of hepatitis that are at least twice the national average from 1987 through 1997 (see the accompanying table). The following information has been extracted from the report:
|State||Rate (per 100,000)||Cumulative average number of cases per year†||Cumulative percentage of cases||Cumulative percentage of U.S. population§|
Rationale for Prevention of Hepatitis A Through Routine Active Immunization
The incidence of hepatitis A has declined in the United States in the past several decades because of improved hygienic and sanitary conditions. However, the virus is still one of the most frequently reported diseases preventable by vaccination. The ongoing occurrence of communitywide outbreaks is evidence that hepatitis A continues to be a major public health problem.
The availability of hepatitis A vaccine provides an opportunity to lower the incidence of disease and has the potential to eventually eliminate infection. Immunization of persons in age groups with the highest rates of hepatitis A virus infection and who serve as a reservoir of infection is important for reducing the incidence.
The goals of hepatitis A immunization are to protect persons from infection, reduce the incidence of disease by preventing transmission and ultimately eliminate transmission. Children should be the main focus of immunization strategies because of their high incidence of disease and critical role in disease transmission. Routine vaccination of children would result in the following: prevention of infection in age groups that account for at least one third of hepatitis A virus infections; elimination of a main source of infection for other children and some adults; and eventual prevention of infection in all older persons as children who have been vaccinated become adults, because immunity seems to be long-lasting.
To achieve the goals of hepatitis A immunization, strategies have been developed and implemented based on the characteristics of hepatitis A epidemiology and the feasibility and effectiveness of vaccination. Vaccination of persons in groups that are at highest risk for infection will provide personal protection but will have little effect on national disease rates, because most cases do not occur among persons in these groups. Limiting vaccination to children who live in communities with high rates of hepatitis A might affect overall disease incidence, but only a small proportion of nationally reported hepatitis A cases occur in such communities.
More widespread routine vaccination of children is needed to achieve a sustained reduction in national incidence of hepatitis A. Using surveillance data to identify areas with consistently elevated rates of infection that contribute the majority of cases to the current national disease rate may help to focus routine vaccination strategies and substantially reduce national disease incidence.
Hepatitis A Vaccine
Two hepatitis A vaccines have been approved for use in the United States: Havrix and Vaqta. These vaccines are inactivated and should be administered intramuscularly into the deltoid muscle. A needle length appropriate for the person's age and size should be used. Havrix is available in two formulations. The formulation differs according to the person's age: persons two to 18 years of age should receive 720 ELISA units per dose in a two-dose schedule, and persons more than 18 years of age should receive 1,440 ELISA units per dose in a two-dose schedule. A pediatric formulation of 360 ELISA units per dose administered in a three-dose schedule is no longer available.
Vaqta is licensed in two formulations. The formulation differs according to the person's age: persons two to 17 years of age should receive 25 units per dose in a two-dose schedule, and persons more than 17 years of age should receive 50 units per dose in a two-dose schedule.
No serious adverse events were attributed definitively to the hepatitis A vaccine. Approximately 50,000 persons have received Havrix in clinical studies. Among adult study participants, the most frequently reported side effects that occurred within three days after the dose of 1,440 ELISA units were soreness at the injection site, headache and malaise. In children, the most frequently reported side effects included soreness at the injection site, feeding problems, headache and injection-site induration. Of the 9,200 persons who received Vaqta in clinical studies, no serious adverse events were reported. Among adult study participants, the most frequent side effects that occurred within five days after vaccination included tenderness, pain, warmth at the injection site and headache. Among children, the most common side effects were pain, tenderness and warmth at the injection site.
Reports of serious adverse events, without regard to causality, following approval of Havrix in Europe and Asia included anaphylaxis, Guillain-Barré syndrome, brachial plexus neuropathy, transverse myelitis, multiple sclerosis, encephalopathy and erythema multiforme. Most of these events occurred in adults, and about one third occurred among persons receiving other vaccines concurrently. For serious adverse events for which background incidence data were known, the rates for vaccine recipients were not higher than would be expected in an unvaccinated population. No serious adverse events are thought to be associated with the use of Vaqta, although postmarketing data are limited.
Any adverse events that seem to be associated with hepatitis A vaccination should be reported to the national Vaccine Adverse Events Reporting System. Reporting forms can be obtained by calling 800-822-7967 and information on how to report adverse events is available on the Web at http://www.fda.gov/cber/vaers/vaers.htm.
Preexposure Protection Against Hepatitis A Virus Infection
Hepatitis A vaccination provides preexposure protection from hepatitis A virus infection in children and adults. The vaccination is recommended for persons who are at increased risk of infection and for persons who wish to obtain immunity. ACIP makes the following recommendations for preexposure protection for populations at increased risk for hepatitis A virus infection:
CHILDREN WHO SHOULD BE ROUTINELY VACCINATED OR CONSIDERED FOR VACCINATION
Children who live in areas in which the rates of hepatitis A virus infection are at least twice the national average should be routinely vaccinated. This includes children who live in states, counties or communities in which the average annual infection rate during 1987 through 1997 was at least 20 cases per 100,000 persons. For children who live in areas in which the rates of infection are between 10 and 19 cases per 100,000 persons, routine vaccination should be considered. For children who live in areas in which the rates of infection are lower than the national average, the decision of whether to adopt a local vaccination strategy should include considerations such as feasibility of implementation and whether the plan is likely to lower overall disease incidence in the state.
When determining the age groups that should be recommended for vaccination, community disease patterns should be considered. In communities with high rates of hepatitis A, such as American-Indian reservations and Alaskan-Native villages, routine vaccination of children starting at two years of age and catch-up vaccination of preschool-aged children should receive the highest priority. To more effectively prevent hepatitis A epidemics in these communities, vaccination of previously unvaccinated older children (e.g., 10 to 15 years of age) continues to be recommended. Prevaccination serologic testing is not indicated for vaccination of previously unvaccinated children in this setting.
Other strategies for routine childhood vaccination include vaccination of one or more single-age cohorts of children or adolescents, vaccination of children and adolescents in selected settings, such as day care facilities, and vaccination of children and adolescents over a wide range of ages in a variety of settings, such as when they seek health care for other reasons.
PERSONS WHO TRAVEL TO OR WORK IN COUNTRIES THAT HAVE HIGH OR INTERMEDIATE ENDEMICITY OF HEPATITIS A VIRUS INFECTION
Hepatitis A vaccination at the age-appropriate dose is recommended for children, adolescents and adults who plan frequent travel or who reside for long periods of time in high-risk areas. Immune globulin is recommended for travelers less than two years of age because the vaccine is currently not licensed for use in this age group. Prevaccination testing is encouraged for older travelers or for younger persons in certain population groups.
Travelers should receive the first dose of vaccine at least four weeks before travel. If the dose is administered less than four weeks before travel, the traveler should also receive immune globulin (0.02 mL per kg), but at a different anatomic injection site. A second dose of vaccine administered according to the recommended schedule is necessary for long-term protection.
Travelers who are allergic to one of the components of the vaccine or who elect not to receive the vaccine should receive a single dose of immune globulin (0.02 mL per kg). Travelers whose travel period exceeds two months should receive immune globulin at 0.06 mL per kg; administration of the vaccine must be repeated if the travel period exceeds five months.
MEN WHO HAVE SEX WITH MEN
Vaccination is recommended for sexually active men who have sex with men. This includes adolescents and adults. Prevaccination testing is not indicated for the vaccination of adolescents and young adults in this group, but might be warranted for older adults.
PERSONS WHO USE INJECTING OR NONINJECTING ILLEGAL DRUGS
Vaccination is recommended for users of injecting and noninjecting illegal drugs. Prevaccination testing is not indicated for the vaccination of adolescents who use illegal drugs but might be warranted for adults.
PERSONS WHO HAVE OCCUPATIONAL RISK FOR INFECTION WITH HEPATITIS A VIRUS
Vaccination is recommended for persons who work with primates that are infected with hepatitis A virus and for those who work with the virus in a research laboratory setting. No other groups seem to be at increased risk for hepatitis A virus infection because of occupational exposure.
PERSONS WHO HAVE CLOTTING-FACTOR DISORDERS
Vaccination is recommended for susceptible persons who receive clotting-factor concentrates, especially those who receive solvent-detergent-treated preparations.
PERSONS WHO HAVE CHRONIC LIVER DISEASE
Vaccination is recommended for susceptible persons who have chronic liver disease. Data do not indicate a need for routine vaccination of persons with chronic hepatitis B virus or hepatitis C virus infections without evidence of chronic liver disease. Susceptible persons who are awaiting or have received liver transplants should also be vaccinated.
Vaccination in Outbreak Settings
When deciding to vaccinate for outbreak control, the characteristics of hepatitis A epidemiology in the community and existing hepatitis A vaccination programs should be considered.
OUTBREAKS IN COMMUNITIES THAT HAVE HIGH RATES OF HEPATITIS A VIRUS INFECTION
For outbreaks in communities with high rates of hepatitis A virus infection, routine vaccination programs should achieve at least 70 percent vaccination coverage of preschool and school-age children. In communities with less than 70 percent coverage, intensified and accelerated vaccination efforts should be implemented. The upper age for vaccination of older, previously unvaccinated children should be determined using age-specific rates of hepatitis A or seroprevalence data, if available, but will usually be between 10 and 15 years of age. To prevent future outbreaks, ongoing vaccination of young children should be maintained as soon as the outbreak has subsided.
OUTBREAKS IN COMMUNITIES THAT HAVE INTERMEDIATE RATES OF HEPATITIS A VIRUS INFECTION
For outbreaks in communities with intermediate rates of hepatitis A virus infection, routine vaccination is recommended. Implementation of vaccination programs will eventually prevent outbreaks. If routine childhood vaccination has not been implemented, this should be initiated as recommended.
Accelerated vaccination may be considered as an additional measure to control outbreaks. Because these communities are often located in large cities or counties, widespread vaccination might not be feasible. Outbreaks in these communities often involve children and adults; local surveillance and epidemiologic data should be used to define populations or areas within the community that have the highest rates of disease.
When deciding whether to initiate an outbreak-control vaccination program, the following factors should be considered: the feasibility of rapidly vaccinating the target population of children, adolescents and adults, and the cost of such programs.
Because the results of vaccination programs to control hepatitis A outbreaks in communities that have intermediate rates of disease have been variable, evaluation of the effectiveness should be an essential element of programs in these settings. In all of these communities, ongoing vaccination of children should be sustained to maintain high levels of immunity and prevent future epidemics.
OUTBREAKS IN COMMUNITIES THAT HAVE LOW RATES OF HEPATITIS A VIRUS INFECTION
Communitywide outbreaks are uncommon in areas with low rates of hepatitis A virus infection. If outbreaks occur, the response should be based on an examination of the epidemiologic characteristics of the outbreak. Because vaccination programs to control outbreaks among adults in high-risk groups have been difficult to implement, efforts to control and prevent outbreaks should focus on initiating and sustaining routine vaccination. For outbreaks among children, implementing programs similar to those recommended for intermediate rate communities can be considered. If outbreaks among children occur, implementation of programs similar to those recommended for intermediate-rate communities can be considered, including ongoing routine vaccination of children.
OUTBREAKS IN OTHER SETTINGS
In settings such as day care centers, hospitals, institutions and schools, the frequency of hepatitis A outbreaks is not high enough to warrant routine vaccination of persons specifically because they are in these settings. When outbreaks occur in day care settings, aggressive use of immune globulin should limit transmission of the virus. When outbreaks occur in hospitals, institutions and schools, the use of immune globulin is recommended for persons in close contact with infected patients.
Persons who work as food handlers can contract and possibly transmit hepatitis A to others. Vaccination of employees who work in areas where state and local health authorities or private employers determine that vaccination is cost-effective should be considered.
Postexposure Prophylaxis with Immune Globulin
Persons who have been exposed recently to hepatitis A virus and who have not previously received hepatitis A vaccine should be given a single intramuscular dose of immune globulin (0.02 mL per kg) as soon as possible within two weeks after exposure. Persons who have received one dose of the vaccine at least one month before exposure to the virus do not need immune globulin. Serologic confirmation of hepatitis A virus infection of index patients is recommended before postexposure treatment of contacts.
If vaccination is recommended for a person being given immune globulin, they can be given simultaneously at separate anatomic injection sites. Use of the vaccine alone is not recommended for postexposure prophylaxis.
Immune globulin should be administered to previously unvaccinated persons in the following situations:
CLOSE PERSONAL CONTACT
All previously unvaccinated household and sexual contacts of persons with serologically confirmed hepatitis A should receive immune globulin. Persons who have shared illegal drugs with the confirmed carrier should receive immune globulin and vaccination. Providing immune globulin to persons with other types of ongoing, close personal contact, such as regular babysitters, should also be considered.
DAY CARE CENTERS
Immune globulin should be given to all previously unvaccinated employees and attendees of day care centers or homes if: (1) at least one case of hepatitis A is recognized in children or employees or (2) cases are recognized in two or more households of those who attend the center. In centers that do not provide care to children who wear diapers, immune globulin should only be given to classroom contacts of an index-case patient. If an outbreak occurs, administration of immune globulin should be considered for members of households that have children in diapers.
When a food handler is infected with hepatitis A virus, immune globulin should be given to other food handlers at the same establishment. Because common-source transmission to patrons is unlikely, administration of immune globulin to patrons is usually not recommended. Administration to patrons may be considered if (1) the food handler directly handled uncooked foods or foods after cooking and had diarrhea or poor hygienic practices; and (2) patrons can be identified and treated within two weeks after the exposure. Stronger consideration of immune globulin use might be warranted in settings where repeated exposure to hepatitis A might have occurred. In the event of common-source outbreak, immune globulin should not be given to exposed persons after cases have begun to occur because the two-week period during which immune globulin is effective will have been exceeded.
SCHOOLS, HOSPITALS AND WORK SETTINGS
If a single case of infection occurs in a school, hospital or work setting and the source of infection is outside of that setting, immune globulin is not routinely indicated. Instead, careful hygienic practices should be emphasized. Immune globulin should be given to persons who have close contact with index patients if an epidemiologic investigation indicates that transmission of the virus has occurred among students in a school, or among patients and staff in a hospital.
The ACIP report also includes information on the features of hepatitis A virus, epidemiology and prevention of hepatitis A virus, route of transmission, surveillance and seroprevalence data, sources of infection, and future considerations for the vaccine.
Copies of the complete ACIP statement are available at $5 each by writing Massachusetts Medical Society, C.S.P.O. Box 9120, Waltham, MA 02254-9120.