The Adolescent Immunization Conundrum: Options for Breaking Through Barriers -- Part 3

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	Introduction Kenneth A. Alexander, MD, PhD Course Chair Chief, Section of Pediatric Infectious Diseases University of Chicago Chicago, Illinois
	Adolescent Immunization: What Is Recommended? How Do We Increase Rates? Amy B. Middleman, MD, MPH, MSEd Associate Professor of Pediatrics Director, Adolescent & Young Adult Immunization Baylor College of Medicine Houston, Texas
	Monitoring Vaccine Safety 9 Kenneth A. Alexander, MD, PhD Course Chair Chief, Section of Pediatric Infectious Diseases University of Chicago Chicago, Illinois
	Barriers to Adolescent Immunization 12 Amanda Frisch Dempsey, MD, PhD, MPH Assistant Professor Department of Pediatrics and Communicable Diseases University of Michigan Ann Arbor, Michigan

Introduction

As medical practitioners and as parents, we understand the value of infant immunization. Although the importance of vaccination for adolescents and young adults has been accepted by the infectious disease community and to a lesser extent by the larger medical community, many parents do not yet understand the importance of adolescent immunization. As a consequence, adolescent immunization is not yet an expectation.

Furthermore, as we look to the future of immunization, it appears that many of the vaccines under development will be directed toward teenagers. Thus, the number of vaccines that will be given to adolescents, and the ramifications of adolescent immunization for adult health, will continue to increase. Therefore, to promote adolescent health, and to increase the health of adults, it is imperative that parents come to expect adolescent immunization, and that the medical community meet these expectations.

To review adolescent immunization, and to examine means for increasing the use of recommended vaccines, Vindico Medical Education organized a panel of experts in the field of adolescent immunization. In this monograph, we review the latest ACIP recommendations, discuss vaccine safety concerns, and describe the barriers and approaches to adolescent immunization. I thank the participants for sharing their expertise and experience, and for contributing to the preparation of this monograph.

Kenneth A. Alexander, MD, PhD

Course Chair

 

Adolescent Immunization:
What Is Recommended?
How Do We Increase Rates?

Amy B. Middleman, MD, MPH, MSEd

Immunization is important for people of all ages, and developing methods to improve vaccine coverage in adolescents can serve as a model to increase immunization delivery to other age groups as well. Therefore, current immunization recommendations for adolescents and their rationale and expectations must be understood and clinicians must be aware of catch-up strategies and effective policies that can increase immunization rates. The latest recommendations from the Advisory Committee on Immunization Practices (ACIP) that relate to adolescents, published in Morbidity and Mortality Weekly Report and on the Centers for Disease Control and Prevention (CDC) Web site, are reviewed here.¹

Ten vaccines protecting against 14 diseases are recommended for adolescents and young adults aged 10 to 25 years (Figure 1). The meningococcal, human papillomavirus (HPV), influenza, and combined tetanus, diphtheria, and acellular pertussus (Tdap) vaccines are recommended for all adolescents in specific age groups. The hepatitis B, inactivated poliovirus, varicella, and the combined measles, mumps, rubella vaccines are recommended as catch up vaccines when previous immunization was not provided. Catch up schedules are also provided for older adolescents who have not received the HPV or Tdap vaccines. Other vaccines, such as the pneumococcal vaccine, are recommended for youth, adolescents, and adults with special risk factors for disease.² Vaccine recommendations are constantly evolving, as illustrated in the examples below.

Tdap: Tetanus, Diphtheria, Pertussis

In 2005, the Food and Drug Administration approved 2 combined tetanus, diphtheria, and acellular pertussis (Tdap) vaccines licensed as single-dose booster immunizations.³ In 2006, the ACIP recommended that the Tdap vaccine replace the diphtheria toxoid (Td) booster for adolescents aged 11 to 12 years, with a catch-up vaccination occurring for those aged 13 to 18 years.^4,5 A 5-year interval between Td and Tdap is encouraged, despite data showing that 2 years is an adequate interval between the 2 vaccines containing tetanus and diphtheria. This recommendation was based on uncertainty about the role of the diphtheria conjugate in the meningococcal vaccine (MCV4), which has diphtheria toxoid levels 4- to 6-fold higher than those in the diphtheria vaccines. If the risk of disease is high or if disease is endemic in the area, the benefit of immunizing outweighs the risk of local reaction and intervals of less than 2 or 5 years may be used. To avoid potential local injection site reactions, the MCV4 vaccine should ideally be given at the same time as the Tdap vaccine.

Between the ages of 10 to 18 years, Tdap can be given as 1 of 3 catch-up inoculations for those who are vaccine-naïve or have no documentation of their childhood DTaP series. Tdap is FDA-approved for 1-time use only; accordingly, catch-up vaccinations should include 1 Tdap and 2 Td vaccinations.

For those aged 19 to 64 years, a 2-year interval between Td and Tdap is acceptable. A provider should, however, consider the risk:benefit ratio of vaccine intervals; for example, if pertussis is epidemic in a community, then a shorter interval should be considered when the risk of getting the disease is higher than the potential risk of a comparatively minor injection site reaction.

For people aged 19 to 64 years, Tdap also replaces the Td booster and can be used for wound management on a 1-time basis. In addition, anyone in contact with infants or who has clinical exposure to patients should get the Tdap vaccine. Pregnancy is not a contraindication; in fact, the transmission of passive immunity may benefit the infant and protect the mother, who is often the source of disease for the infant. There is a theoretical concern that passive immunity to pertussis and tetanus may interfere with the infant’s response to active immunization at 2, 4, and 6 months of age, which precluded a recommendation for Tdap vaccine during pregnancy.⁶ A trial evaluating the safety and immunogenicity of Tdap during pregnancy, including its effect on the infant’s response to routine DTaP vaccination, is ongoing.⁷

Human Papillomavirus

HPV vaccination recommendations released in 2007 provide for immunization of females aged 11 to 12 years. In addition, according to the FDA indication, girls as young as 9 years may receive the HPV vaccine.⁸ Immunization is recommended for all females aged 13 to 26 years who were not previously vaccinated, which is one of the broadest vaccination recommendations ACIP has developed. It is also important to immunize younger adolescents because the HPV vaccine prevents disease but cannot treat disease. It is best to immunize younger adolescents before exposure to HPV has occurred. Similar to the meningococcal vaccine, it is important to vaccinate regardless of HPV or Papanicolaou test history. The HPV vaccine protects against 4 HPV genotypes (types, 6, 11, 16, and 18); accordingly, if there is a history of disease, immunization can provide protection against genotypes in the vaccine that the patient has not yet encountered.

Recommended routine dosing intervals should be followed for series catch-up (i.e., the second and third doses should be administered 2 and 6 months after the first dose), with the second dose given no less than 4 weeks after the first. The third dose should be given at least 12 weeks after the second dose and at least 24 weeks after the first dose.⁹

Meningococcus

From 1978 to 2005, the available meningococcal vaccine was a quadrivalent polysaccharide vaccine (MPSV4); a quadrivalent conjugate vaccine (MCV4) was introduced in 2005. The benefits expected by conjugating the polysaccharides to diphtheria toxoid include more durable protection, reduced carrier-state of asymptomatic Neisseria meningitidis, and herd immunity similar to that provided by other conjugate vaccines such as Haemophilus influenzae type B conjugate vaccine.¹⁰

Epidemiological data indicate that, after an initial peak in infants younger than 1 year, a secondary incidence rate peak occurs in adolescents aged 15 through 20 years.¹¹ In 2005, the ACIP recommended the MCV4 vaccine for adolescents aged 11 to 12, unvaccinated youth aged 15 years, and college freshmen living in dormitories. As vaccine supply improved in 2007, the recommendations were revised to include immunization with the conjugate vaccine for all people aged 11 through 18 years, retaining the primary recommendation of vaccinating at age 11 or 12 years, with catch-up immunization at ages 13 to 18 years.¹² Later in 2007, the recommendations were further expanded to include children aged 2 to 10 years who were at risk for the disease.¹³ More recently, the ACIP has recommended a second dose of MCV4 3 or 5 years after the first dose, based on patient age at first dose, for children and adolescents considered to be at high risk (not including those going to live in dormitories). Because of the multivalent nature of the vaccines, immunization is also advised for children with a history of meningitis.

Pneumococcal Polysaccharide Vaccine

A recent update to the pneumococcal polysaccharide vaccine recommendations included asthma and smoking as risk factors that warrant this vaccine in people 19 years of age or older.

Influenza

Influenza vaccine recommendations have also changed recently. In 2002, the ACIP recommended annual vaccination of children aged 6 to 23 months. The recommended age was extended to 59 months in 2006. In 2008, consideration of current data prompted a recommendation for universal annual influenza vaccination for all children aged 6 months through 18 years.^14,15 Of course, all of those at high risk for complications from influenza continue to be subject to the recommendation for annual influenza vaccination. Further progress toward universal immunization for adults is expected. In addition, in the context of potential influenza pandemics, having less circulating flu by achieving high immunization rates theoretically decreases the risk of genetic recombinations that lead to new strains.

Hepatitis A

Hepatitis A vaccination is recommended routinely for children up to the age of 2 years. When current hepatitis A vaccine programs exist for older children, for example, in areas where the disease rate is above a certain threshold, catch-up vaccination continues to be encouraged for all unvaccinated youth. At present, immunization can be considered for unvaccinated children from ages 2 through 18 years in other areas.

Varicella

Based on initial licensure studies, 1 dose of varicella vaccine was recommended for those under 13 years of age. Postlicensure studies that compared 1- and 2-dose regimens showed that 2 doses had significantly higher efficacy (92.9%-95.7% vs. 97.3%-99%, respectively; P<.001). In addition, protection against severe disease was ≥95% following 1 dose and 100% following 2 doses given at least 3 months apart among younger children. Accordingly, updated ACIP vaccination recommendations from 2005 and 2006 now specify that 2 doses of varicella vaccine be given 3 months apart for children aged 12 months to 12 years, and 2 doses 4 to 8 weeks apart for people aged 13 years or older.¹⁶

Healthy People 2010 Immunization Goals

Healthy People 2010, the comprehensive United States Department of Health and Human Services health initiative, includes a goal to increase the proportion of young children and adolescents who received all vaccines that have been recommended for at least 5 years.¹⁷ Specific targets aim to increase coverage rates for children aged 13 to 15 years to at least 90% for ≥3 hepatitis B, ≥2 measles, mumps, rubella (MMR), ≥1 varicella, and ≥1 Td vaccinations. No specific goals were established for newly recommended vaccines.

Vaccine data for teenage patients have been available from the National Immunization Survey (NIS) since 2007. Available data indicate that coverage levels are considerably lower than those projected in the Healthy People 2010 document. For several vaccines, however, there are some encouraging data. Although still at only 32.4%, MCV4 coverage increased almost 3-fold from 2006 to 2007, and HPV coverage (having received at least 1 dose) of 25.1% was achieved in the first year of licensure. In addition, hepatitis B vaccination rates are approaching the Healthy People 2010 goal of 90% of patients having 3 or more doses, after a 1997 baseline of 48%.¹⁸

Policies That Can Increase Adolescent Immunization Rates

Current vaccine recommendations are directed to youth aged 11 and 12 years because younger adolescents often access preventive healthcare more frequently than older adolescents.¹⁹ The CDC and ACIP acknowledge, however, that a standard immunization platform for adolescents is needed, which would put the focus on disease prevention across ages 11 through 18 years and beyond, and would present opportunities for improved comprehensive care (Figure 2). Ongoing CDC projects are investigating whether children who go to clinics for immunizations have more opportunities to receive full comprehensive care, including screening and prevention of risk behaviors. However, providers may not have the expertise and comfort level to provide these services, even when adolescents are present. Therefore, it is important to devise a mechanism to ensure immunizations are effectively delivered to adolescents and that other primary care screening processes follow. This may prove more successful than attempting to add immunizations to a system that is currently not accessing adolescents for comprehensive care.

A platform structure with established adolescent immunization visits would create both parental and provider expectations, similar to the 2-, 4-, and 6-month vaccination schedule for infants. A physician primarily sees an infant aged 4 months for immunizations and adds anticipatory guidance. This would be ideal for adolescents as well, and a 3-visit platform during adolescence is endorsed by both the Society for Adolescent Medicine and the Infectious Disease Society of America (IDSA).^20,21 This structure would allow for a primary immunization visit at ages 11 to 12 years, followed by a visit at ages 14 to 15 years to catch up on any missed vaccines or complete multidose regimens, with a final visit at age 17 to 18 years to update vaccinations that were missed or that are newly recommended while teens still have insurance coverage or qualify for entitlement programs for vaccines.

State mandates that require vaccination for school entry can improve adolescent vaccination coverage, and communities with policies that allow easily obtained opt-out for immunizations are more vulnerable to disease. Adolescents are more likely to complete the hepatitis B vaccine series in states with mandates (75%) than without (39%, P <.001).²² In Florida, a 380% increase in vaccines administered to children aged 10 to 14 years was reported 1 year after the mandate compared with the percentage of vaccinations during a similar period prior to the mandate.²³ In California, vaccine coverage of 7th graders who were subject to a mandate (60%) was significantly higher than that of 5th and 6th graders 1 year before the requirement (13%) and 8th through 12th graders for whom vaccination was not mandated (27%; P<.001).²⁴ Additionally, if adequately funded, appropriately vetted among school entities, and accepted by the parents and adolescents in the community, school mandates can help eliminate preventive care disparities among population groups.

Other policy actions to be considered include national and state provision of resources for immunization information systems and promotion of their use. Incorporating different sites of care, including schools, can be facilitated by changing consent laws similar to the federal statutes that do not require a signature for matters of public health; the use of alternative sites, most notably schools, for adolescent vaccination will likely be required to increase coverage rates among this very busy population. Strengthening reimbursement and supporting insurance reform are other key policy issues that must be addressed to maximize adolescent immunization coverage.

Policy change is required to help achieve recommended adolescent vaccination goals. Delaying action may further constrain immunization coverage as additional vaccines targeting adolescents are introduced.

References

1. Center of Disease Control and Prevention. ACIP recommendations. Vaccines and Immunizations. Available at: http://www.cdc.gov/vaccines/pubs/ACIP-list.htm.
2. Recommended immunization schedule for adolescents ages 10-25 years. Available at: www.adolescenthealth.org/200803_Recommended_Immunization_Schedule_for_Adolescents.pdf.
3. Committee on Infectious Disease Policy Statement. Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Pediatrics. 2006 Mar; 117(3): 965-978.
4. Center of Disease Control and Prevention. Preventing tetanus, diphtheria, and pertussis among adolescents: Use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines. Morbidity and Mortality Weekly Report: Recommendations and Reports. 2006 Feb; 55(Early Release): 1-34.
5. Center of Disease Control and Prevention. Preventing tetanus, diphtheria, and pertussis among adults: Use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. Morbidity and Mortality Weekly Report: Recommendations and Reports. 2006 Dec; 55(RR 17): 1-44.
6. Center of Disease Control and Prevention. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports. 2008 May; 57(RR-4): 1-56.
7. National Institute of Allergy and Infectious Diseases. Pertussis vaccine in healthy pregnant women. Available at: http://clinicaltrials.gov./ct2/show/NCT00707148?term=Pertussis+ Vaccine+in+Healthy +Pregnant+Women&rank=1.
8. Center of Disease Control and Prevention. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports. 2007 Mar; 56(RR-2): 1-32.
9. Center of Disease Control and Prevention. Recommended immunization schedules for persons aged 0 Through 18 years --- United States, 2009. Morbidity and Mortality Weekly Report: Recommendations and Reports. 2009 Jan; 57(51&52): Q1-Q4.
10. Center of Disease Control and Prevention. Epidemiology and Prevention of Vaccine Preventable Diseases. 11th ed. 2009. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/pink chapters.htm.
11. Center of Disease Control and Prevention. Prevention and control of meningococcal disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports. 2005 May; 54(RR-7): 1-21.
12. Center of Disease Control and Prevention. Notice to readers: Revised recommendations of the Advisory Committee on Immunization Practices to vaccinate all persons aged 11--18 years with meningococcal conjugate vaccine. Morbidity and Mortality Weekly Report. 2007 Aug; 56(31): 794-795.
13. Center of Disease Control and Prevention. Notice to readers: recommendation from the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent Meningococcal Conjugate Vaccine (MCV4) in children aged 2--10 years at increased risk for invasive meningococcal disease. Morbidity and Mortality Weekly Report. 2007 Dec; 56(48): 1265-1266.
14. Center of Disease Control and Prevention. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports. 2006 Jul; 55(RR-10): 1-42.
15. Advisory Committee on Immunization Practices meeting notes, February 27, 2008. Center of Disease Control and Prevention. Atlanta, GA.
16. Center of Disease Control and Prevention. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports. 2007 Jun; 56(RR-4): 1-40.
17. United States Department of Health and Human Services. Healthy people 2010. Available at: http://www.healthypeople.gov/document/html/objectives/14-27.htm.
18. Center of Disease Control and Prevention. Vaccination coverage among adolescents aged 13 17 years --- United States, 2007. Morbidity and Mortality Weekly Report. 2008 Oct; 57(40): 1100-1103.
19. Rand CM, Auinger P, Klein JD, Weitzman M. Preventive counseling at adolescent ambulatory visits. The Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine. 2005 Aug; 37(2): 87-93.
20. Middleman AB, Rosenthal SL, Rickert VI, Neinstein L, Fishbein DB, D'Angelo L. Adolescent immunizations: A position paper of the Society for Adolescent Medicine. The Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine. 2006 Mar; 38(3): 321-327.
21. Infectious Diseases Society of America. Actions to strengthen adult and adolescent immunization coverage in the United States: Policy principles of the Infectious Diseases Society of America. Clinical Infectious Diseases. 2007 Jun; 44(12): e104-108.
22. Jacobs RJ, Meyerhoff AS. Effect of middle school entry requirements on hepatitis B vaccination coverage. The Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine. 2004 May; 34(5): 420-423.
23. Center of Disease Control and Prevention. Effectiveness of a seventh grade school entry vaccination requirement -- Statewide and Orange County, Florida, 1997-1998. Morbidity and Mortality Weekly Report. 1998 Sep; 47(34): 711-715.
24. Averhoff F, Linton L, Peddecord KM, Edwards C, Wang W, Fishbein D. A middle school immunization law rapidly and substantially increases immunization coverage among adolescents. American Journal of Public Health. 2004 Jun; 94(6): 978-984.

Monitoring Vaccine Safety

Kenneth A. Alexander, MD, PhD

A few minutes spent reading the newspaper, listening to talk radio, or watching television show that vaccine safety is a significant public concern. Although concerns about autism have not been raised with adolescent vaccines, other issues related to vaccine safety have received significant public attention. In the following discussion of vaccine safety, the human papillomavirus (HPV) vaccine will be examined as a case study for how safety concerns with adolescent vaccines have emerged, and how these concerns can be addressed.

The original studies of the quadrivalent HPV vaccine showed efficacy approaching 100% for prevention of genital warts, cervical intraepithelial neoplasia (CIN) grade 1, and CIN 2/3 caused by vaccine serotypes. A vaccine with efficacy close to 100% is unusual; accordingly, this vaccine has been one of the more impressive vaccines to be released in recent years. Based on efficacy and safety data, the quadrivalent HPV vaccine was licensed in the United States in June 2006. The vaccine is indicated for females aged 9 to 26 years, with dosing at 0, 2, and 6 months. Following vaccine licensure by the Food and Drug Administration (FDA), the Advisory Committee on Immunization Practices (ACIP) recommended that HPV immunization efforts be targeted to girls aged 11 to 12 years. Reasons behind the ACIP’s recommendations for targeting 11 to 12 year-old females include coordination with recommended adolescent healthcare visits, and the intent to promote administration of the vaccine when it would be most efficacious: prior to acquisition of HPV infection.

Safety data from prelicensure, randomized, controlled trial data were obtained from more than 20,000 subjects in phase 2 and 3 studies. Safety data are now available for more than 25,000 subjects. Throughout these studies, the only adverse events caused by administration of quadrivalent HPV vaccine were injection site-related; primarily arm pain, not dissimilar to that experienced with other vaccines. Clinical trial data showed that pain, swelling, erythema, pruritus, and bruising occurred at rates higher than those experienced by subjects given saline placebo.¹

Following FDA approval of the vaccine, fainting was observed among girls being vaccinated. This was, to some degree, unexpected, because fainting was not seen in the prelicensure trials. This could be due to the fact that, in the clinical trials, subjects were kept under observation for 20 minutes after the vaccination, during which time they remained seated. This observation time is not expended in a clinical office; therefore, the young women were receiving their vaccine and then fainting in the waiting room or on the way out of the clinic. The FDA concluded that the fainting was due to the vaccination process, and not due to the HPV vaccine per se, because young women fainted following administrations of other adolescent-recommended vaccines as well. Practitioners should take precautions to avoid adolescent girls fainting, which can include giving the vaccine to girls who are sitting or supine. Immunizers should also ensure the patient is seated under observation in the waiting room for several minutes after receiving the vaccine.

Despite the impressive safety profile of the quadrivalent HPV vaccine, fainting has not been the only adverse event reportedly associated with the HPV vaccine. Unfortunately, following vaccine licensure, both the media and anti-immunization advocacy groups presented stories of healthy young women who received the vaccine and subsequently experienced seizures, paralysis, and sudden death—all billed as consequences of HPV immunization.

Vaccine Surveillance

At present, roughly 30 million doses of the HPV vaccine have been distributed, indicating that approximately 10 million women have received 1, 2, or 3 doses of HPV vaccine. Because of the ongoing systems for postlicensure vaccine adverse effect monitoring, we now have a substantial body of data that can be used to assess the safety of HPV vaccines. The most well-known vaccine safety surveillance program is the Vaccine Adverse Event Reporting System (VAERS), created in 1990 as part of the United States National Childhood Vaccine Injury Compensation Act.² VAERS is a passive monitoring system. As such, it depends upon (in fact, it obliges) immunizers to report vaccine adverse events and accepts reports from anyone. VAERS receives approximately 30,000 vaccine adverse event reports annually, of which about 10% to 15% are classified as “serious” by the Centers for Disease Control and Prevention (CDC). Because VAERS is a passive reporting system, accurate incidence rates cannot be obtained. Furthermore, VAERS data are unfiltered; all reports to VAERS are posted. In addition, VAERS data lack a denominator. Accordingly, VAERS data can be used to generate a hypothesis but cannot be used to test a hypothesis. Restated, VAERS can detect a potential problem with a vaccine, but cannot be used as proof that a problem really exists. A well-known example is the VAERS data that suggested an association between the original rotavirus vaccine and intussusception. Subsequent investigations, prompted by VAERS data, led to the vaccine’s withdrawal from the market. With respect to the quadrivalent HPV vaccine, VAERS reports of sudden cardiac death, with a subsequent diagnosis of pulmonary embolism, were reported. Reviews of these cases found that vaccinees were taking oral contraceptives, a known risk factor for pulmonary embolism in young women. A review of clinical trial data revealed similar pulmonary embolism incidences in the placebo (0.02%) and vaccine (0.02%) groups.¹

Almost three-fourths of VAERS reports are received from vaccine manufacturers (42%) and healthcare providers (30%), with the remaining from state immunization programs (12%), vaccine recipients or their parent/guardians (7%), and other sources (9%).³ Accepting reports from anyone presents the proverbial double-edge sword. Accepting adverse events reports from all sources makes VAERS exquisitely sensitive for the detection of vaccine-related adverse events; however, like all very sensitive detection methods, VAERS suffers from a lack of specificity. Fortunately, subsequent CDC investigations often resolve discrepancies and inaccuracies. For example, while following up a hearsay report of vaccine-induced paralysis, CDC investigators found that the subject fainted following the injection, sustained a laceration on her head that required sutures, and returned to school the next day. Thus, the posting of a potential adverse effect on the VAERS Web site can lead the misguided to conclude that the vaccine is indeed causing the putative adverse outcome. It must be understood that such an erroneous interpretation of VAERS data can lead to incorrect cause-and-effect conclusions, linking coincidental or even spurious events with vaccines. Of even more concern, the VAERS reporting system can also be abused, as shown in a recent report that described plaintiffs’ attorneys in vaccine injury cases filing fictitious VAERS reports in an attempt to lend credibility to their cases.³

In the United States, active surveillance for vaccine-related adverse events is accomplished through the Vaccine Safety Datalink (VSD)⁴

network and through manufacturers’ postmarketing data collection. VSD is a collaborative project between the CDC’s Vaccine Safety Program and 8 large managed care organizations. Prespecified protocols are followed, and a denominator—the 8.8 million people covered by the plans—is available. Accordingly, the VSD cohort provides efficient access to information, including health records, on approximately 3% of the United States population. The VSD “rapid cycle analysis” process allows the VSD program to monitor new vaccines for adverse events. Adverse event rates are sampled weekly using a series of prespecified queries and comparisons using a control population that did not receive the vaccine. Rapid cycle analysis is currently being used to evaluate conjugated meningococcal vaccine, rotavirus vaccine, measles, mumps, and rubella (MMR) vaccine, tetanus, diphtheria, and pertussis (Tdap) vaccine, HPV vaccine, and seasonal influenza vaccine. In addition, several other priority projects are underway studying potential relationships between specific adverse events and individual vaccines.⁴

Manufacturers’ postmarketing surveillance studies provide additional active monitoring of vaccine safety. Postmarketing studies are often part of the company’s risk management plan and can be part of a regulatory commitment made upon receiving the vaccine license. Predesigned studies are used to investigate specific adverse events. Furthermore, studies can be designed to identify adverse event safety signals related to the vaccine use. Reports of a potential adverse event received by manufacturers are generally transferred to VAERS.

The Clinical Immunization Safety Assessment (CISA) Network is another means for studying vaccine-associated adverse effects. The CISA, also under the CDC umbrella, is an academic collaborative network between the Immunization Safety Office, 6 medical research centers, and insurance companies.⁵ Its mission is to:

• Conduct clinical trials on immunization-associated health risks
• Provide clinicians with evidence-based advice
• Empower individuals to make informed immunization decisions
• Assist domestic and global vaccine safety policy makers in the recommendation of exclusion criteria for at-risk individuals
• Enhance public confidence in sustaining immunization benefits for all populations

In summary, immunizations are not taking place in a vacuum. Surveillance programs with documented competencies identifying true issues with vaccine safety are in place and are proven effective for detection of vaccine-associated adverse events. These programs address both scientific and public concerns, ensuring that potential vaccine-associated risks are evaluated scientifically. The HPV vaccine is a case study of how the extensive surveillance for a single vaccine can be used to rapidly assess vaccine safety. Regarding the HPV vaccine, injection site reactions are the only adverse events attributable to the quadrivalent HPV vaccine. Other potential vaccine-associated events have not been substantiated statistically.

Safety Resources to Share with Parents

Several publically available resources provide reliable vaccine safety information (Table). Web sites should be shared proactively with parents to promote the use of factual information that can defuse the spurious claims proliferated by a plethora of scientifically inaccurate sources.

References

1. Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2008.
2. Center of Disease Control and Prevention. Vaccine Adverse Event Reporting System (VAERS). Available at: http://www.cdc.gov/vaccinesafety/vaers.
3. Goodman MJ, Nordin J. Vaccine adverse event reporting system reporting source: A possible source of bias in longitudinal studies. Pediatrics. 2006 Feb; 117(2): 387-390.
4. Center of Disease Control and Prevention. Vaccine Safety Datalink (VSD) project. Available at: http://www.cdc.gov/vaccinesafety/vsd.
5. Center of Disease Control and Prevention. Clinical Immunization Safety Assessment (CISA) network. Available at: http://cdc.gov/vaccinesafety/cisa.

Barriers to Adolescent Immunization

Amanda Frisch Dempsey, MD, PhD, MPH

Significant barriers to effectively delivering vaccines to adolescents exist. The National Immunization Survey Teen Study data from 2007 revealed mixed utilization of adolescent-targeted vaccines. For example, measles, mumps, rubella (MMR), varicella, and hepatitis B vaccines had reasonable coverage (70% to 87%) of adolescents 13 to 17 years of age, while coverage for the newer adolescent-specific vaccines such as tetanus, diphtheria, pertussis (Tdap) (11%), and human papillomavirus (HPV) (25% for first dose, 6% for completion of the series) was very low. Coverage for all vaccines is below the Healthy People 2010 goal of 90%.¹

Situation Analysis: Ways to Assess Vaccine Coverage at the Practice Level

Multiple strategies can be used by providers to determine immunization rates and vaccination goal achievement in their practices. Here we present 3 strategies for providers to consider. First and simplest, a review of 100 adolescent patient charts can determine the proportion of patients who are current on their vaccines. In addition to providing a rough estimate of overall vaccine status in the practice, it can identify problematic vaccines. A random sample of 100 adolescents should require no more than a few hours to review.

Second, a more comprehensive means of assessing individual practice immunization rates is through immunization assessment programs run by local or state health departments, most of which have staff designated to provide assistance to providers on all aspects of immunization delivery. Some health departments provide services on-site. State and national level data can be provided so that a direct comparison to a physician’s practice data can be made.

Third, and considered the gold standard for comprehensive data acquisition, is the 4-phase AFIX program, an acronym for assessment, feedback, incentives, and exchange.² AFIX was shown in several trials to be an effective assessment tool as well as a catalyst to improve immunization rates. Information from immunization information systems or registries can be managed with the Comprehensive Clinic Assessment Software Application (CoCASA), which is available as a free download from the Centers for Disease Control and Prevention (CDC) Web site.³ Several state health departments will perform AFIX as a public service, with or without CoCASA, and some states have immunization information systems that can generate utilization reports.

The AFIX Web site provides instructions for its implementation in individual practices. In the first AFIX segment, assessment, coverage data for a specific population such as adolescent vaccines are acquired. Feedback consists of a status report for the individual provider or practice and identifies areas for improvement that may be vaccine- or population-specific. CoCASA has many built-in tools to assist with the assessment and feedback functions. The incentives phase follows a second assessment, allowing providers or practices with improved performance to be recognized and rewarded. Incentives can be sponsored by local businesses, coalitions, professional organizations, managed care or HMOs, and vaccine manufacturers. The fourth component, exchange, spans the entire AFIX procedure, comprising the exchange of healthcare information and resources that can facilitate improvement in vaccine immunization rates.

Barriers to Adolescent Immunization

Barriers to immunization comprise 2 major categories: Attitudes/knowledge and infrastructure (Figure). Attitudes and knowledge about vaccines can vary among parents, adolescent patients, and medical providers. Infrastructural or practice-level barriers can be amenable to resolution at the practice level, or they may be imposed on practices by outside policies.

Attitudes and knowledge

Most parents support getting their children vaccinated. However, most parents are not aware that specific immunizations are recommended for the adolescent age group. Accordingly, the need to be vaccinated may not motivate parents to bring adolescents to the medical clinic as it does when children are younger.

Although most studies show that adolescents look to their parents for cues on health behaviors, including immunization, adolescents are generally healthy and visit the doctor for preventive services less frequently than younger children. In addition, most vaccine-preventable diseases are, in general, rare; accordingly, both parents and adolescents might not recognize the need for and benefits of vaccination.

Parental attitudes are important; however, adolescents have their own attitudes, which can produce separate barriers. An adolescent is going to have an opinion about vaccination, and it is just as necessary to convince the youth and obtain his or her assent as it is to obtain parental consent. Thus, there needs to be an agreement regarding immunization between the parent and adolescent. This may be especially an issue with the HPV vaccine, which protects against a sexually transmitted disease. For example, parents might want to have their child vaccinated, but the teenager may be concerned that her peers will make assumptions about her sexual behavior if she gets the vaccine. Alternatively, an adolescent may want to get immunized but the parent disagrees.

Conflicting knowledge can be a barrier to receiving vaccines. Popular media figures may report shocking stories about health issues they claim are associated with vaccinations. Often, these anti-vaccine messages are more accessible and compelling than those offered by many members of the medical community, whose messages are typically drier and possibly confusing. This dichotomy can lead to public distrust, which can propagate familiar fears such as vaccines causing autism, autoimmune problems, or other health issues. Accordingly, messages from the medical community about vaccines should be clear as well as compelling.

Provider attitudes are an important factor affecting vaccination rates, especially related to the HPV vaccine. Numerous studies show that provider recommendation is one of the most influential factors that motivate parents to get their children vaccinated. It is important, therefore, for providers to recognize personal biases that can affect their practices. For example, prelicensure surveys of OB/GYNs, nurse practitioners, pediatricians, and family medicine providers showed these healthcare professionals were more willing to recommend HPV vaccination to older adolescents rather than to younger adolescents, despite understanding that 11-12 year olds were the preferred age for vaccination.^4-7 This demonstrates that knowledgeable providers may be reluctant to follow the recommended vaccination schedule. Recognizing this emotional influence may help practitioners empathize with reluctant parents and ensure that their staff is properly motivated to support the recommendations.

Inconvenience is also a barrier to immunization. Adolescents are busy people with many competing demands that may not be conducive to vaccination. As an example, adolescents may decline vaccination because they want to avoid having a sore arm during a sporting event scheduled for later that day. These time demands may also make it difficult for adolescents to make a timely return to the office for additional doses of vaccines, as is needed for HPV. Reassurance and education should lead to avoiding this possible missed opportunity.

Infrastructure barriers

For many providers, a primary infrastructural barrier is the lack of adolescent visits. Accordingly, practitioners often have less experience discussing the importance of vaccines for the adolescent age group. The infrequent visits can also lead to difficulties in tracking which patients need vaccines. Finally, providers who do not see many adolescents may not accept the financial burden of keeping adolescent-specific vaccines in stock.

Another concern is that insurance coverage for vaccines fluctuates more as adolescents age. As an example, for the HPV vaccine, some insurance providers cover the vaccine until age 16 years, whereas other providers might limit coverage to girls aged ≤14 years and others may extend coverage to age 18 years.

Strategies to Overcome Barriers to Adolescent Immunization

Changes can be made within individual practices to overcome the barriers to adolescent immunization. Six key strategies can be implemented at the practice level to improve adolescent vaccine coverage.

1. Start early to change the culture of adolescent immunization

Parent and patient immunization expectations should be established during childhood. Medical providers should work to foster parental acceptance that vaccination will be a routine part of adolescent healthcare, just as it was during early childhood. Emphasize the importance of immunization at visits for children aged 9 and 10 years, when parents can be given information sheets about the vaccines the child will be getting at age 11 or 12 years when he or she comes in for the next well-child examination.

Staff should also be counseled that vaccination is a priority area, and their input solicited. They may have ideas based on their familiarity with the patient population and their interactions with patients that are valuable and easily implemented. A teamwork approach will also help promote a sense of shared responsibility and reinforce that vaccination is an important focus of the medical practice itself, not just of the doctors.

In addition, the practice should determine whether community outreach opportunities are available to promote adolescent vaccination as a general health behavior. To evolve, a positive vaccination culture requires involvement of the practice, the patients, and the community.

2. Use outreach mechanisms to capture teenagers for immunization

Several effective outreach methods are available. In some instances, schools may provide a venue for delivering vaccines, and this strategy could become more important as additional vaccines are recommended for the adolescent age group. Some health departments have special programs that provide vaccines at no cost, eliminating the need for insurance billing, which can be a major barrier to delivering vaccines at school. The Rhode Island Department of Health launched a “Vaccinate Before You Graduate” program in 2001, which works to assure that “no child transitions to adulthood with any missing vaccinations.”⁸ Incentives encourage participation, including no cost vaccinations through age 18 years. The success of the program resulted in development and implementation of spinoff programs in several other states.

There are, however, constraints associated with in-school vaccination programs. In general, adolescents are not allowed to self-consent to vaccination so parental consent must be obtained. After-hours school-based immunization clinics where parents accompany the adolescent may facilitate parental consent, or consent forms can be sent home before the vaccination date.

Special walk-in adolescent vaccination clinics that are not associated with schools can be established within individual practices. Clinics during summer breaks and after-hours can be successful. Mailed reminders advertising the clinics may increase attendance.

Advanced technology including email, text messaging, and Web sites that promote adolescent vaccination can also potentially improve outreach ease and efficiency. Current research is exploring the use of text messaging to remind people to get influenza vaccines, and whether parents are amenable to using this method as a reminder for other adolescent vaccines.

3. Use automated procedures to promote vaccination

Effective procedures to promote vaccination can also be instituted in the clinic. Standing orders, which can be a simple order sheet with a checklist that a medical assistant or nurse can use to check needed vaccines, are one intervention that has been shown to be highly effective. The physician merely signs the standing order if vaccination is agreed upon. Another example is allowing “immunization-only” appointments where subsequent vaccine doses can be provided by a nurse and do not require physician interaction.

Reminders, sent before the immunization is due, and recall systems, sent when a person is overdue for immunization, can also increase compliance. Low technology tools such as post cards are not obsolete for this purpose. In addition, stickers on the front of patient charts can remind physicians to order vaccines. Immunization registries often have built-in reminder/recall systems that can facilitate the process; providers should know whether their states have registries and, if so, how to use them. There are also immunization information systems specific to individual practices, which may be able to self-generate reminder/recall systems.

Creativity is not required—many of these tools are freely downloadable from health department Web sites. For example, the Alliance in Immunization in Michigan (AIM) has an online toolkit (www.aimtoolkit.org) that has a wealth of resources for both reminder/recall systems and standing orders. Typically, other information is available for immunization providers, which may include sections dedicated to adolescents.

4. Develop compelling ways to communicate the importance of vaccination

Many resources are available to assist with relaying the importance of immunization to parents and adolescent patients. To effectively communicate this information, it is helpful to be familiar with both reputable and anti-vaccine Web sites. Be cautious about misleading Web site names such as the National Vaccine Information Center that may suggest advocacy when, in fact, they are against vaccination. The CDC Web site has a wealth of information available and often has special ongoing initiatives, such as the Pre-Teen Vaccine Campaign, with posters and brochures that can be downloaded and printed. “Six Common Misconceptions about Vaccination and How to Respond to Them” from the CDC can provide guidance to practitioners for addressing general fears parents might have about vaccines.

“One size fits all” does not apply to vaccination counseling. Staff in practices that serve specific demographics should be familiar with cultural beliefs or practices that might influence the motivation for vaccination. In addition, individual cases may benefit more from emphasis on factual messages (for example, the likelihood of contracting a specific vaccine-preventable disease) compared with emotional messages (for example, “If it were my teenage daughter, yes, I would have her get the HPV vaccine”). Practitioners should endeavor to acquire intuitive discretion regarding the appropriate approach.

Real-world examples can be valuable, presented in a context parents can understand, emphasizing that much of the information they receive from the press about the supposed risks of vaccination is false. Comparative statistics can make a point, such as “The risk of contracting Guillain-Barré syndrome after MCV4 vaccination is 10 times less than the risk of getting in a car accident in the next year.” Furthermore, the lack of proven causality should also be emphasized.

Certain parental concerns come up more frequently than others. As such, practitioners should have preset answers ready to address these concerns. For example, some parents worry that providing the HPV vaccine will result in changes in their adolescent’s sexual behavior. The “seat belt” example can be useful here, where laws requiring seat belts in cars were not accompanied by an expectation that people would begin to drive recklessly because they had an extra level of protection. Likewise, if parents say “I don’t want my daughter vaccinated against HPV because she is not having sex yet,” the “fluoride treatment example” can be used, as everyone knows fluoride for dental health is used to prevent, not treat, cavities.

5. Try to make every visit an opportunity for vaccination

Making every visit an opportunity for vaccination can be difficult, and studies show many opportunities are missed. Standing orders and reminder/recall systems can be particularly helpful, as can other procedures that make remembering the vaccine an automated process regardless of the visit focus.

Practitioners must be educated about vaccine contraindications and should share them with parents. Most parents believe that fever and mild illness are contraindications for vaccination; however, in general this is not true.

6. Encourage multiple vaccines

When applicable, multiple vaccines at each immunization visit should be encouraged. There is no contraindication for simultaneous administration of any vaccines if administered at different injection sites. The HPV vaccination schedule spans 6 months; therefore, for most adolescents, at least 1 dose will be given during the expanded influenza vaccination season. Providers should consider mechanisms that systematically assess for influenza vaccination as part of HPV vaccine delivery. In general, providers should strive to implement the “adolescent platform” of vaccines where HPV, MCV4, Tdap, and, when applicable, influenza are given at the same visit.

Immunization Visits as an Opportunity for Adolescent Well Visits

With the new focus on adolescent vaccination, particularly the HPV vaccine, which requires multiple doses – there are opportunities to broaden adolescent preventive services. When parents make immunization-related appointments for the second or third doses of HPV vaccines, there may be opportunities for nurses or medical assistants to provide other screening or counseling. For example, at an HPV vaccination visit, a nurse could assess a patient’s body mass index, provide information on diet and nutrition, and schedule a follow-up appointment with the physician if the patient is found to be at an unhealthy weight.

In conclusion, addressing barriers to adolescent immunization is facilitated by understanding the individual practice’s status with regard to vaccine delivery. Although some barriers are outside the practice’s control, many effective strategies can be implemented to increase vaccine coverage among adolescents.

References

1. United States Department of Health and Human Services. Healthy people 2010. Available at: http://www.healthypeople.gov/document/html/objectives/14-27.htm.
2. Center of Disease Control and Prevention. AFIX Overview. Vaccines and Immunizations. Available at: http://www.cdc.gov/vaccines/programs/afix/overview.htm.
3. Center of Disease Control and Prevention. Comprehensive Clinical Assessment Software Application (CoCASA). Vaccines and Immunizations. Available at: http://www.cdc.gov/vaccines/ programs/ cocasa/default.htm.
4. Raley JC, Followwill KA, Zimet GD, Ault KA. Gynecologists' attitudes regarding human papilloma virus vaccination: A survey of Fellows of the American College of Obstetricians and Gynecologists. Infectious Diseases in Obstetrics and Gynecology. 2004 Sep-Dec; 12(3-4): 127 133.
5. Mays RM, Zimet GD. Recommending STI vaccination to parents of adolescents: The attitudes of nurse practitioners. Sexually Transmitted Diseases. 2004 Jul; 31(7): 428-432.
6. Kahn JA, Zimet GD, Bernstein DI, Riedesel JM, Lan D, Huang B, Rosenthal SL. Pediatricians' intention to administer human papillomavirus vaccine: The role of practice characteristics, knowledge, and attitudes. Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine. 2005 Dec; 37(6): 502-510.
7. Riedesel JM, Rosenthal SL, Zimet GD, Bernstein DI, Huang B, Lan D, Kahn JA. Attitudes about human papillomavirus vaccine among family physicians. Journal of Pediatric and Adolescent Gynecology. 2005 Dec; 18(6): 391-398.
8. Rhode Island Department of Health. Immunization Program. Available at: http://www.health.ri. gov/ immunization/ adolescent-vbyg.php.