Hepatitis B, a vaccine-preventable disease, continues to adversely affect adolescents and young adults in the United States. In 1996, more than 1900 acute hepatitis B cases were reported among adolescents and adults 15 to 24 years of age compared with only 279 cases reported for children 14 years of age and younger.1 Universal infant hepatitis B immunization, a current common practice, was not recommended before 1991.2 Hence, the vulnerability of today's generation of adolescents is mainly the result of a lack of systematic strategies and programs designed to ensure delivery of effective vaccines to this age cohort.
Support for universal adolescent vaccination is increasing with more than 40 national organizations endorsing the recently published adolescent immunization recommendations developed by the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics, the American Academy of Family Physicians and the American Medical Association.3 Specific recommendations include a routine health care visit for adolescents 11 to 12 years of age to (1) administer any needed hepatitis B, varicella virus or the second dose of measles, mumps and rubella vaccines; (2) administer tetanus and diphtheria toxoid booster vaccine; (3) administer other vaccines, such as hepatitis A, to appropriate adolescents; and (4) provide other preventative health care services.3
ADOLESCENT UNIVERSAL IMMUNIZATION IMPLEMENTATION ISSUES
In the United States, vaccination programs are implemented on a state-by-state basis. Lacking cost-effective infrastructures, most states have been reluctant to require hepatitis B vaccination for middle school entry, a strategy successfully used to increase vaccination coverage among children entering preschool and kindergarten. Additionally, the amount of federal and state dollars available and the eligibility criteria for subsidies have varied from year to year. For initial programs, certain age cohorts were not eligible for hepatitis B vaccine supplied through the federal Vaccines for Children (VFC) program. However, effective March 1, 1998, the ACIP expanded VFC eligibility for hepatitis B vaccination to include all children and adolescents ages 0 to 18 years (Table 1).4
Without financial support, individual out-of-pocket and societal costs for hepatitis B immunization after infancy are estimated to be greater than $200 for all three doses5 and $107 per dose, respectively (R Deuson, Ph.D., unpublished data). Societal costs include parents' missed wages and transportation costs associated with compliance with vaccination visits. Complex funding issues are compounded by minimal access to adolescents. Unlike infants, fewer adolescents are routinely scheduled for preventative or medical health care. Consequently, adolescents visit their health care providers, on average, less than once per year.6
The addition of adolescents to a predominantly infant universal vaccination schedule requires changing traditional perceptions and practices of health care providers, parents and adolescents. The key initiator for perception and practice change is the physician. Unfortunately, earlier studies showed minimal changes in physician practices after publication of the ACIP universal infant hepatitis B immunization recommendation.7 Surveys showed that even though 82% of pediatricians and 48% of family practitioners were aware of the recommendations, less than 38% of both groups agreed that all infants in their practice should be immunized for hepatitis B.7 Most likely, similar reluctance to routinely immunize all adolescent patients will continue following the ACIP universal adolescent hepatitis B recommendation. Moreover, in studies where physicians were able to initiate the hepatitis B series in adolescents and adults, completion of three doses ranged from 29% in a clinic for treatment of sexually transmitted diseases to 88% in a clinic for adolescents.8, 9 The latter clinic used a very aggressive, time-intensive tracking system for follow-up visits and contacted any individuals who missed scheduled visits.9 However, this report did not specify what percentage of the clinic's patient base elected to be vaccinated.
RESOLVING IMPLEMENTATION BARRIERS WITH SCHOOL-BASED VACCINATION PROGRAMS
Recognizing that new vaccine delivery models were needed to reach adolescents, the Louisiana State University Medical Center initiated school-based hepatitis B vaccination programs in 1992.10 School-based programs were pursued because they allowed easy access to adolescents without parent-assisted health care visits, and youths could be vaccinated before the age at which they were likely to engage in high risk behaviors.10 To aid with implementation and program costs, cooperation with the private sector was established. The initial program targeted one middle school in Baton Rouge with an existing school-based clinic and an enrollment of 654 students. Implementation required minimal support, and 76% of the students received two doses of hepatitis B vaccine and 65% completed the series.10
Based on ease of implementation and the success of the initial program, additional schools with school-based clinics were targeted for hepatitis B vaccination programs. During the 1995 to 1996 school year, three middle schools and one high school were selected to receive hepatitis B vaccine delivery. Among a total of 2750 enrolled students, 1258 received 1 dose and 1014 students received 2 to 3 doses of hepatitis B vaccine.11 A higher percentage of middle school students received 2 to 3 doses of hepatitis B compared with the high school students. This prompted further hepatitis B vaccination efforts to focus on younger (Grade 5) students. In addition, to reach adolescents who attended schools without school-based clinics, temporary vaccine clinics were established.
For the 1996 to 1997 school year, approximately 5000 fifth grade students were targeted for hepatitis B vaccination. Some of the schools had established school-based clinics, and at others, temporary vaccine clinics were set up in any available open space, such as gymnasiums and hallways. This multifaceted program administered 3 doses of hepatitis B vaccine to 3232 students and 2 doses to 171 students distributed among 68 schools (Table 2). Of the 4874 students enrolled, 563 students refused vaccination. Refusals were categorized as previously vaccinated (176 students), plans to be vaccinated by personal doctor or clinic (257 students), various other reasons (63 students) or no reason listed on signed refusal form (67 students). A total of 79% (3404 of 4311) of students who did not refuse vaccination took one dose and 75% (3232 of 4311) took 3 doses. Review of data by race showed that a greater proportion of white students (82%) completed a 2- to 3-dose regimen than did black students (68%). The cost to administer the program was approximately $40 per child given 3 doses.
The most aggressive hepatitis B vaccination program for adolescents in the Greater Baton Rouge area is ongoing. To reach 10 000 fifth grade students in an area that includes 10 parishes (counties) during the 1997 to 1998 school year, hepatitis B vaccination is being facilitated by school-based clinics, temporary vaccination clinics and mobile public health units. The mobile public health units are able to reach rural parishes that surround Baton Rouge.
The different facets of the school-based adolescent vaccination programs implemented in the Greater Baton Rouge area during the past 6 years have required similar activities. In addition to students and parents, individuals and groups, such as principals, school boards and school nurses, had to be persuaded to "buy in" to the benefits of adolescent hepatitis B vaccination. Various on-site educational efforts facilitated program acceptance. Collection of consent forms was required, and for the last 2 years, collection was facilitated with use of teacher incentives for high return rates. Students' insurance status had to be identified and tracked per requirements of the VFC program. All programs required some form of database management. As the program expanded, it was necessary to hire a program coordinator and a part-time database manager.
SCHOOL-BASED HEPATITIS B VACCINATION PROGRAMS AND THE THREE-DOSE REGIMEN
The traditionally followed schedule for infant and childhood hepatitis B immunization is vaccination at 0, 1 and 6 months of age. Within a 9-month school calendar, it is difficult to maintain a 1-month interval after the first dose and a 5-month interval after the second dose. Many hepatitis B school-based programs, including the programs in the Greater Baton Rouge area, vaccinate at 2-month intervals (dose at 0, 2 and 4 months).12, 13 This schedule meets the ACIP adolescent recommendation of "the second dose [of hepatitis B vaccine] should be administered at least 1 month after the first dose and the third dose should be administered at least 4 months after the first dose and at least 2 months after the second dose."3
Based on the production of greater than or equal to 10 mIU/ml of antibody to hepatitis B surface antigen, the accelerated 0-, 2-, 4-month regimen has been shown to be effective. Studies with the hepatitis B vaccine (recombinant), 5 μg/0.5 ml, showed that both the standard regimen at 0, 1 and 6 months and the regimen at 0, 2 and 4 months provided more than 95% seroprotection in healthy adolescents.14 Furthermore, more than 95% and more than 40% of adolescents were seroprotected after a two-dose 0- and 6-month regimen and a one-dose regimen, respectively.14 Different dosing regimens did produce varied geometric mean titers of antibody to hepatitis B surface antigen, with response after the traditional dose regimen at 0, 1 and 6 months being greater than the 0-, 2- and 4-month regimen.14
The United States initially instituted universal infant hepatitis B immunization recommendations partly because it was perceived that adolescents would be a difficult cohort to reach. Schools, however, enroll 99.7% of all children ages 7 to 13 years,15 offering an established setting to access adolescents. In addition, there are approximately 900 school-based clinics distributed throughout the United States.16 As shown by the initial Baton Rouge program, school-based clinics can vaccinate numerous susceptible adolescents with minimal increase in financial and personnel resources. Other vaccine delivery models are essential to reach adolescents in settings ranging from rural to urban. The use of temporary clinics in schools in Baton Rouge and surrounding parishes provides access to an adolescent population approximately 9 times as large as the population of students attending schools with school-based clinics. Similarly, adding mobile health units is expected to increase by one-third the number of students vaccinated compared with the previous year's program. The targeted adolescent population in the Greater Baton Rouge area for hepatitis B vaccination has grown from 654 students in 1992 to 1993 to approximately 10 000 students in 1997 to 1998.
The continued success of hepatitis B vaccination of adolescents in Baton Rouge has evolved through use of a multifaceted program. In addition to numerous vaccination delivery models, the three-dose regimen of 0, 2 and 4 months facilitated scheduling of multiple school visits. Data show that using this accelerated regimen does not compromise seroprotection rates.14 In support of accelerated regimens, studies among adults in France showed a seroprotection rate of 70% 1 month after completion of a 3-week (0-, 10- and 21-day) regimen.17 This extremely accelerated regimen is intended for possible use among travelers and military personnel and is to be followed by a booster dose at Day 365.17 Additionally, seroprotection data show that even if one or two doses of hepatitis B vaccine are received, some level of protection is acquired, thus mitigating the barrier that noncompliance with the entire three-dose regimen renders.14
As demonstrated by the faculty at the Louisiana State University Medical Center in cooperation with the private sector, barriers to vaccination of adolescents can be eliminated. School-based vaccination programs, with or without the use of a school-based clinic, can easily access adolescents. The successful hepatitis B vaccination of approximately 5000 adolescents, coupled with ongoing efforts, will provide Louisiana with a large, protected cohort of young adults in the near future.
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Proceedings of the Satellite Symposium held at the 37th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); Toronto, Ontario, Canada; September, 1997