Adult and Adolescent Immunizations: When to Recommend the New Vaccines

June 2, 2008

During the past few years, several vaccines have been added to the adult immunization schedule. The human papillomavirus (HPV) vaccine is recommended for girls and women aged 11 to 26 years (minimum age, 9 years) to prevent cervical cancer, precancerous or dysplastic lesions, and genital lesions caused by HPV types 6, 11, 16, and 18.

Vaccination rates in adults are lower than those in children, but the consequences of lack of immunization in adults are just as significant. Barriers to adult immunization include patients' lack of knowledge or misconceptions about vaccines and health care providers' failure to recommend vaccination.1

More efforts are needed to increase vaccination rates and to achieve the goals of Healthy People 2010, a statement of national objectives that targets the most significant preventable threats to health. The goals of Healthy People 2010 include the elimination of diphtheria, measles, mumps, rubella, and tetanus. They also include a 75% reduction in the number of cases of hepatitis A and B, and 90% compliance with the routine administration of pneumococcal and influenza vaccines.2

In this article, we review the schedule and recommendations for adult and adolescent immunizations. The focus here is on recently approved vaccines: human papillomavirus (HPV); meningococcal conjugate; tetanus, diphtheria, and acellular pertussis (Tdap); and herpes zoster.

HUMAN PAPILLOMAVIRUS VACCINEHPV infection. In the United States, 6.2 million persons are infected with genital HPV each year. It is the most common sexually transmitted infection.3 About 15% of persons aged 15 to 49 years are currently infected. More than 50% of sexually active men and women acquire genital HPV infection during their lifetime.4

Persistent HPV infection can cause cervical cancer in women and anogenital cancer and genital warts in both men and women. Forty HPV types infect the genital area in humans. Fifteen types are classified as high-risk, 3 are classified as probable high-risk, and 12 are classified as low-risk.5

High-risk HPV types are detected in 99.7% of cervical cancers worldwide.6 About 70% of cervical cancers worldwide are caused by types 16 and 18. Infections with low-risk types 6 and 11 produce benign or low-grade cervical cell changes. Serotypes 6 and 11 are responsible for 90% of cases of genital warts and recurrent respiratory papillomatosis.7

Recommendations for HPV vaccine. In 2006, the FDA released for marketing the first vaccine (Gardasil) to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18; it was approved for use in girls and women 9 to 26 years of age.8 This quadrivalent vaccine is developed from noninfectious HPV-like particles.3,9

HPV vaccine is administered intramuscularly in 3 separate 0.5-mL doses. The second dose should be administered 2 months after the first dose. The third dose is administered 6 months after the first dose. The vaccine is available as a sterile suspension for injection in a single-dose vial or a prefilled syringe.3Efficacy of HPV vaccine. The vaccine is highly immunogenic among women with vaccine-type-specific antibodies at baseline and in HPV-naive women. The anti-HPV responses remain stable for 3 years. More studies about the duration of immunity are ongoing.10

In ideal settings, the reduction of disease approaches 100% for both cervical intraepithelial neoplasia (CIN) and genital warts. The efficacy in the general population is much lower; it ranges from 39% for CIN 2/3 to 68.5% for genital warts (Table 1). These clinical trials involved women aged 16 to 26 years.

To study the effect of the HPV vaccine in younger females, anti-HPV antibody titers in girls aged 9 to 15 years were compared with those in women aged 16 to 26 years. Antibody titers were the same at 1 month after dose 3, but they were 2- to 3-fold higher at 18 months after dose 3 in the younger group. This underscores the importance of vaccination at an earlier age.11Safety of HPV vaccine. The most common adverse effects of the HPV vaccine are local pain, swelling, and erythema. The majority of these reactions are of mild to moderate severity.

As of June 30, 2007, there were 13 reports of Guillain-Barr syndrome (GBS) that occurred after administration of the HPV vaccine. Only 2 met the case definition of GBS and occurred within 6 weeks after vaccination in patients who had received the HPV vaccine alone. This number is still within the expected number of natural occurrences of GBS (1 to 2 per 100,000 person-years) in persons who have not been vaccinated.12MENINGOCOCCAL VACCINEMeningococcal infection. This infection manifests itself as meningitis (49%), meningococcemia (33%), or pneumonia (9%).13 Five serogroups (A, B, C, Y, and W-135) cause the majority of cases worldwide. However, only B, C, and Y serogroups are found in the United States. Serogroup B is responsible for more than 50% of cases among infants; serogroups C, Y, and W-135 cause 75% of cases among persons 11 years and older.14

The causative agents for bacterial meningitis have changed over time. Haemophilus influenzae was formerly the most common (45% of cases), followed by Streptococcus pneumoniae (18%) and Neisseria meningitidis (14%). The number of H influenzae type b meningitis cases has dropped by 94% after the H influenzae type b conjugate vaccine was introduced 18 years ago.15 The incidence of invasive pneumococcal disease also declined after the introduction of the pneumococcal conjugate vaccine in 2000.16 N meningitidis is now the leading cause of bacterial meningitis in the United States.14Efficacy of meningococcal conjugate vaccine. Conjugation is defined as the covalent coupling of a polysaccharide to a protein carrier that contains T-cell epitopes. It changes the nature of the immune response to the polysaccharide from T-cell-independent to T-cell-dependent. This leads to a long-lasting, amnestic response. Both conjugate H influenzae and S pneumoniae vaccines reduced the incidence of disease and the asymptomatic carriage of vaccine-preventable serotypes.14

Immunogenicity achieved by the conjugate meningococcal vaccine is similar to that of the polysaccharide vaccine. However, the antibody titers produced by the conjugate vaccine are higher 3 years after administration. The conjugate vaccine provides more durable protection and reduces nasopharyngeal carriage.17 In the United Kingdom, serogroup C meningococcal disease was eliminated in persons who received serogroup C conjugate vaccine (96% reduction in incidence)18; the vaccine also reduced asymptomatic carriage by 66%19 and reduced the incidence of the disease among unvaccinated persons by 35%.18 In 2005, the FDA approved the tetravalent meningococcal conjugate vaccine (Menactra) for use in persons 11 to 55 years of age.

Safety of meningococcal conjugate vaccine. Cases of GBS that occurred within 6 weeks of administration of the meningococcal vaccine have been reported. Whether the vaccine increases the risk of GBS is unknown. The CDC recommends that persons with a history of GBS who are not at high risk for invasive meningococcal disease should not receive the tetravalent meningococcal conjugate vaccine. The recommendations for vaccinations with the meningococcal vaccine did not change, and the CDC continues to monitor any occurrences.20TETANUS, DIPHTHERIA, AND REDUCED ACELLULAR PERTUSSIS VACCINEThe burden of pertussis. Immunity against pertussis that results from childhood vaccination or natural illness wanes over time, leaving adolescents and adults susceptible to the disease. Since the 1980s, the number of cases has increased among adolescents and adults in contrast to a decline in cases among children.21 Studies have shown that older children and parents infect other household members, including young children and newborns. A more severe illness develops in unvaccinated or partially vaccinated infants and children.22Efficacy of Tdap vaccine. The efficacy of the Tdap vaccine was evaluated among 2781 healthy participants between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial. The vaccine offered 92% protection, based on confirmed pertussis cases.23

In 2005, 2 Tdap products (Boostrix and Adacel) were licensed for use in single doses in the United States. Boostrix is licensed only for adolescents aged 10 to 18 years, and Adacel is licensed for adolescents and adults aged 11 to 64 years.21

The availability of the Tdap vaccine for adults affords an opportunity to reduce the burden of pertussis in the United States. The objective of adolescent and adult Tdap vaccination is to protect adults against pertussis. This will reduce the reservoir of pertussis in the population at large and thus decrease transmission to high-risk persons, such as unvaccinated or partially vaccinated infants.21ZOSTER VACCINEVaricella and herpes zoster. Varicella-zoster virus causes 2 distinct diseases. The primary infection, varicella (chickenpox), occurs in epidemics among susceptible children. Herpes zoster (shingles), caused by the reactivation of the dormant virus in the dorsal ganglia, results in a localized cutaneous eruption. Declining cell-mediated immunity caused by aging and immunosuppressive illnesses increases the risk of zoster.24

The incidence of zoster among persons older than 75 years exceeds 10 cases per 1000 person-years; this is almost 5 times the incidence in the general population. More than half of all persons in whom herpes zoster develops are older than 60 years. Complications occur in almost 50% of older persons with zoster.24,25Efficacy of zoster vaccine. The zoster vaccine is a live, attenuated, lyophilized intramuscular vaccine that is indicated for patients 60 years and older. Immunization reduced the incidence of herpes zoster and postherpetic neuralgia by an average of 51% (P < .001). The greatest reduction was in persons 60 to 69 years of age.25 The lowest reduction (only 18%) was among persons older than 80 years.26 In 2006, the FDA licensed the zoster vaccine (Zostavax) for use in adults 60 years and older. A single dose of zoster vaccine is indicated regardless of whether the patient previously had herpes zoster. The benefit of vaccination may be limited soon after a prior episode; however, no data specify a time frame for effectiveness.27Safety of zoster vaccine. The most common adverse effects of the herpes zoster vaccine are local pain, swelling, pruritus, erythema, and a varicella-like rash at the injection site. Compared with placebo, there was no difference in the occurrence of adverse systemic events.25PNEUMOCOCCAL AND INFLUENZA VACCINESPneumococcal pneumonia and influenza. Each year 50,000 to 70,000 previously healthy adults die of pneumococcal infection and influenza. Both infections are preventable by vaccination.28 Rates of pneumococcal vaccination have increased from 15% to 64%, and rates of annual influenza vaccination have risen from 33% to 70%. As a result, mortality associated with both illnesses has declined.29 Although pneumonia and influenza together constituted the eighth leading cause of death in the United States in 2004, the number of deaths had fallen 7.3% from 2003.30Influenza vaccine. A goal for Healthy People 2010 is to increase the influenza immunization rate to 90% for non-institutionalized adults 65 years and older; the rate was 60% in 2005. Immunization rates were much lower among African Americans and Hispanics: 40% and 43%, respectively, in 2005.31

The inactivated influenza vaccine is administered intramuscularly, and the live, attenuated vaccine is given intranasally. The live, attenuated influenza vaccine, which is indicated for use in healthy persons aged 5 to 49 years, has broadened the options for vaccinating healthy adults.32

Jefferson and colleagues33 reviewed the effects of vaccinating persons 65 years and older with inactivated vaccine in nursing homes and in the community. In nursing homes, immunization reduced the incidence of influenza-like illness by 23% and of pneumonia by 46%, hospital admissions by 45%, deaths from influenza or pneumonia by 42%, and all-cause mortality by 60%, but it did not reduce influenza occurrence (relative risk [RR], 1.04; 95% confidence interval [CI], 0.43-2.51). Among elderly persons living in the community, vaccines were not significantly effective against influenza (RR, 0.19; 95% CI, 0.02-2.01), influenza-like illness (RR, 1.05; 95% CI, 0.58-1.89), or pneumonia (RR, 0.88; 95% CI, 0.64-1.20). However, they decreased hospital admissions for influenza and pneumonia by 26% and all-cause mortality by 47%.33 Pneumococcal vaccine. One of the objectives of Healthy People 2010 is to achieve a pneumococcal immunization rate of 90%. The rate was 56% in 2005. However, the rates were much lower among African Americans and Hispanics: 40% and 29%, respectively, in 2005.31CONTRAINDICATIONS AND ADVERSE-EVENT REPORTING
The CDC has developed an online guide to contraindications to vaccines.35 The live-virus MMR and varicella vaccines should not be given to pregnant women, and the varicella vaccine should not be given to persons with HIV infection.36 All adverse events should be reported to the United States Department of Health and Human Services using the Vaccine Adverse Events Reporting System ( or 800-822-7967).

During 2005 to 2007, 463 episodes of post-vaccination syncope were reported; 33 (7%) were serious. Most of the serious episodes occurred in girls and women aged 11 to 18 years, and they usually happened within 15 minutes of vaccination. The CDC recommends observing patients for 15 minutes after vaccination.37STRATEGIES TO INCREASE VACCINATION RATES
Immunizations play a crucial role in protecting patients' health throughout their lifetime. More efforts are needed to increase vaccination rates and achieve the Healthy People 2010 goals. Among the office-based strategies that can be used are the following:

• Reminder systems for patients and providers.
• Standing orders for nurses to give vaccines.
• Careful attention to pretravel evaluation and education of high-risk groups, which can help reduce the likelihood of illness during travel.

In addition, health fairs and other approaches to promote awareness of immunizations, particularly in communities where there is a high prevalence of risk factors, can improve vaccination rates.





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