Published online January 3, 2008
PEDIATRICS Vol. 121 Supplement January 2008, pp. S5-S14 (doi:10.1542/10.1542/peds.2007-1115B)
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SUPPLEMENT ARTICLE


New, and Some Not-so-New, Vaccines for Adolescents and Diseases They Prevent

Daniel B. Fishbein, MDa, Karen R. Broder, MD, FAAPa, Lauri Markowitz, MDb and Nancy Messonnier, MDa

a National Center for Immunization and Respiratory Diseases
b National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia


   ABSTRACT
TOP
 ABSTRACT
THE DISEASES AND THE...
 CONCLUSIONS
 REFERENCES
 
Adolescents in the United States now have the opportunity to receive new vaccines that prevent invasive meningococcal infections, pertussis (whooping cough), and cervical cancer. Except for their potential to cause serious illness, these infections could not be more different. Their incidence ranges from extremely low to quite high. Early clinical manifestations of infection range from none to life-threatening illness. Two of the vaccines are similar to those already in use, whereas 1 is completely new. In conjunction with the 4 vaccines previously recommended for adolescents (the tetanus and diphtheria booster, hepatitis B, measles-mumps-rubella, and varicella), the 3 new vaccines (meningococcal, human papillomavirus, and the tetanus-diphtheria-pertussis booster [which replaced the tetanus-diphtheria booster]) bring the number recommended for adolescents to 6. In this article, we describe key characteristics of the 3 new vaccines and infections they were designed to prevent. We also briefly discuss other vaccines recommended for all adolescents who have not already received them and new vaccines that are still under development.

Key Words: adolescent vaccination • new vaccines

Abbreviations: Td—tetanus and diphtheria toxoids • MMR—measles-mumps-rubella • AAP—American Academy of Pediatrics • ACIP—Advisory Committee on Immunization Practices • HPV—human papillomavirus • MPSV4—meningococcal polysaccharide vaccine • MCV4—meningococcal polysaccharide-protein conjugate vaccine • GBS—Guillain-Barré syndrome • TdaP—tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine • HbsAG—hepatitis B surface antigen

Before 2005, the only vaccine routinely recommended for healthy adolescents who had received all recommended childhood vaccinations was the tetanus and diphtheria toxoids (Td) booster.1 Three other vaccines (measles-mumps-rubella [MMR], hepatitis B, and varicella) were used as "catch-up vaccinations" for adolescents who did not receive these vaccines as children (and, in the case of varicella, had not had chickenpox). The second dose of MMR vaccine was first recommended for adolescents by the American Academy of Pediatrics (AAP) in 1989,2 whereas hepatitis B and varicella vaccines were first recommended for this age group in 1995 and 1996, respectively.3,4 These recommendations were consolidated in 1996, when the Advisory Committee on Immunization Practices (ACIP), AAP, American Academy of Family Physicians, and American Medical Association harmonized their recommendations. These organizations suggested that the recommended immunizations and other preventive services be delivered at a routine preventive visit at 11 to 12 years of age.1

Three new vaccines intended primarily for adolescents are now available. The first of these, a new vaccine effective for the prevention of disease caused by Neisseria meningitidis, was licensed in the United States in 2005 and officially recommended for use when the ACIP recommendations were published in May of that year.5,6 Two vaccines for adolescents, both of which prevent infections with Bordetella pertussis, tetanus, and diphtheria, were licensed in May and June of 2005, respectively, and recommendations were published in early 2006.7 A vaccine that prevents human papillomavirus (HPV), the cause of cervical cancer, was licensed in May 2006, and recommendations for its use were published in March 2007.8

All the diseases against which these new vaccines offer protection are potentially serious, but the clinical course for each could hardly be more different. A fulminant life-threatening course is common with disease caused by N meningitidis but extremely rare among adolescents and adults infected with B pertussis and does not occur with HPV infection. Pertussis rarely causes serious complications in adolescents but does cause substantial morbidity. Moreover, adolescents may transmit pertussis to infants who are at risk for death if they develop pertussis. HPV infections can cause genital warts and abnormal Papanicolaou test results in adolescents and adults, and persistent HPV infection can result in cervical cancer, usually many years after the initial infection. Similarly distinct is the past and present incidence of the diseases that are prevented by these vaccines (Table 1).


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  		TABLE 1 Annual Reported Cases of Disease Occurrences in the United States in the 20th and 21st Centuries

 
In this article, we focus primarily on these new vaccines and discuss the diseases the vaccines prevent and the similarities and differences among the vaccines themselves. We also briefly discuss and compare these vaccines with the 3 other vaccines (MMR, hepatitis B, and varicella) recommended for adolescents who have not previously received them and future vaccines that are still under development. A summary of vaccines in later stages of development as well as those recently licensed in the United States can be found at http://aapredbook.aappublications.org/news/vaccstatus.shtml.


   THE DISEASES AND THE VACCINES THAT PREVENT THEM
TOP
 ABSTRACT
 THE DISEASES AND THE...
CONCLUSIONS
 REFERENCES
 
Invasive Meningococcal Infections
Etiology, Pathogenesis, and Clinical Manifestations
N meningitidis is a Gram-negative diplococci that is classified antigenically into 13 distinct serogroups on the basis of their capsular polysaccharides. Worldwide, serogroups A, B, C, Y, and W-135 account for the majority of cases, although serogroup A disease is rare in the United States.9 Risk factors for infection include household exposure, crowding, concurrent upper respiratory tract infections, and active and passive smoking. N meningitidis colonizes the nasopharynx in 5% to 10% of the population, but only a minority of strains are pathogenic, and fewer than 1% of carriers develop disease. Transmission occurs when close, mouth-to-mouth contact permits the exchange of salivary secretions. Although close contacts of people who are ill with meningococcal disease are at much higher risk, most people contract the bacteria from asymptomatic carriers. When N meningitidis invades the bloodstream, it can cause a serious, rapidly progressing, and sometimes fatal disease. N meningitidis can be isolated from the bloodstream in up to three fourths of patients, but meningococcal sepsis, which is also called meningococcemia, occurs in only 5% to 20% of patients. Meningeal infection results from hematogenous spread and occurs in approximately one half of patients. Pneumonia is the third most common presentation, occurring in 5% to 15% of patients.10 The onset of disease is often abrupt, and its course is rapid. The death rate is 10% to 14%, and an additional 11% to 19% of survivors suffer serious sequelae, including deafness, neurologic deficit, or limb loss.5

Epidemiology
Annually, 1400 to 2800 cases of invasive meningococcal disease occur in the United States. In the past 5 years, serogroups B, C, and Y each caused approximately one third of disease cases.9 Disease is seasonal, with cases peaking in December and January. Most cases (97%) are sporadic; only a minority (3%) are associated with outbreaks.11 In 1990–2002, the incidence of invasive meningococcal disease in the United States ranged from 0.5 to 1.1 cases per 100000 population.5,9 During these years, rates of meningococcal disease were highest among infants <1 year old (9.2 per 100000); the rate for youth 11 to 19 years old (1.2 per 100000) was also higher than that for the general population (Fig 1). 1 College freshmen living in dormitories are at a higher risk than college students in general. Although the disease is quite rare, every case triggers a costly public heath response.9


Figure 1
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  		FIGURE 1 Rates of meningococcal disease: United States, 1991–2002. a Per 100000 population. Source: Active Bacterial Core surveillance data (adapted from Bilukha OO, Rosenstein N; National Center for Infectious Diseases, Centers for Disease Control and Prevention. MMWR Recomm Rep. 2005;54[RR-7]:1–21).

 
Vaccines
The 2 vaccines available in the United States are derived from and protect against serogroups A, C, Y, and W-135 but not serogroup B, for which there is no licensed vaccine. Table 2 highlights the difference between these 2 vaccines. The older vaccine is a meningococcal polysaccharide vaccine (MPSV4), known by its trade name Menomune (sanofi pasteur: Swiftwater, PA). The newer vaccine, a meningococcal polysaccharide-protein conjugate vaccine (MCV4; trade-named Menactra [sanofi pasteur: Swiftwater, PA]), is similar to Haemophilus influenzae type b conjugate vaccine, pneumococcal conjugate vaccine, and the serogroup C meningococcal conjugate vaccines, which have been used routinely in the United Kingdom since 2001.5 Menactra was created by bonding the polysaccharide, which normally induces a weak antibody response, to diphtheria protein, which is a more potent source of antigen stimulation. Improved immunologic priming and antibody persistence are important aspects of long-term protection induced by conjugate vaccines, as is their ability to prevent nasal carriage.12 On the basis of evaluation of other conjugate vaccines, we hope that MCV4 will have a longer duration of protection than that of MPSV4.13 In times of MCV4 shortages, MPSV4 can be substituted for the vaccination of persons who have brief elevations in their risk for meningococcal disease (eg, travelers to areas in which meningococcal disease is hyperendemic or epidemic).14


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  		TABLE 2 Comparison of Menomune and Menactra Licensed for Use in Adolescents in the United States

 
In January 2005, the ACIP recommended routine vaccination with MCV4 for children who were 11 to 12 years old and catch-up vaccination of adolescents who have not already been vaccinated when they enter high school (ie, at ~15 years old) or as college freshmen (if they live in dormitories).5 Vaccination was also recommended for other persons at increased risk for meningococcal disease (ie, military recruits, travelers to areas in which meningococcal disease is hyperendemic or epidemic, microbiologists who are routinely exposed to isolates of N meningitidis, persons with anatomic or functional asplenia, and persons with terminal complement component deficiencies). ACIP recommendations and similar ones by the AAP and American Academy of Family Physicians have been published.5,6,15 These recommendations have now been expanded to include previously unvaccinated children who are 11 to 18 years old.16

The public health community faced a number of challenges in the first 18 months after ACIP recommendations were published. Shortly after the recommendations were published, demand outpaced supply and led to temporary shortages of the vaccine.14 The demand seems to have been caused by vaccination of adolescents of all ages during to the seasonal increase of visits to heath care providers that occurs each summer.17 During the summer of 2005 and again in 2006, the CDC recommended that providers defer vaccination of 11- to 12-year-olds but continue to vaccinate adolescents at high school entry who had not previously received MCV4 and college freshmen living in dormitories.14 Routine recommendations for adolescent vaccination with meningococcal conjugate vaccine were reinstated in November 2006 when supply improved. In October 2005, reports that indicated a possible association between receipt of MCV4 and Guillain-Barré syndrome (GBS) were made to the Vaccine Adverse Event Reporting System.18 Available data suggest a small increased risk for GBS after vaccination, but the inherent limitations of the passive reporting system and the uncertainty regarding background incidence rates for GBS require that these findings be viewed with caution. Because of the ongoing risk for meningococcal disease and limitations of the risk data, the CDC continues to recommend routine vaccination with meningococcal conjugate vaccine for persons in target groups described by the ACIP, but persons with a history of GBS should not receive meningococcal conjugate vaccine unless they are at a substantially elevated risk for meningococcal disease.19

Pertussis
Etiology, Pathogenesis, and Clinical Manifestations
B pertussis is a fastidious Gram-negative coccobacillus that has no known animal or environmental reservoir20 or clinically significant carrier state.21 However, B pertussis infections are highly communicable, especially during the catarrhal and early paroxysmal phases of illness, and attack rates can be as high as 80% to 90% among nonimmune household contacts. Young infants (<6 months old) have the highest incidence of pertussis and are the most likely age group to have hospitalizations, complications, or death related to the disease.22 In contrast, hospitalization and deaths related to pertussis are rarely reported for adolescents and adults.7

The clinical presentation of pertussis is influenced by a number of factors including age, level of immunity, and use of antimicrobial agents early in the course of the illness.23,24 After an incubation period of 7 to 10 days, the disease sometimes progresses through 3 classic phases: catarrhal, paroxysmal, and convalescent. Illness often begins with mild cold-like symptoms that include coryza and a mild cough.24 It may progress over a period of 1 to 2 weeks to classic paroxysmal spasms of coughing, posttussive vomiting, and whooping.20,24 Among adolescents reported to have pertussis, the most common serious manifestations include pneumonia (2%), rib fractures (1%), and loss of consciousness (1%). A prolonged cough is a common feature of pertussis in adolescents, whereas a classic whoop is much less common. In Massachusetts, 38% of adolescents with pertussis had been coughing for at least 1 month at the time of diagnosis.7 In a Canadian study, 47% of adolescents with pertussis reported a cough duration of >9 weeks.25 Adolescents with pertussis and the people who care for them frequently miss school or work; for instance, in a study performed in Massachusetts, 83% of adolescents missed a mean of 5.5 days of school, and 43% of their parents missed a mean of 2.4 days of work.26 Unfortunately, there are few distinguishing epidemiologic or clinical characteristics of pertussis in adolescents or adults except for prolonged illness with cough.24 Diagnosis, therefore, relies on culture and single serologic testing but limited availability and lack of sensitivity, specificity, or both. Recently, polymerase chain reaction, in combination with cultures (to determine antibiotic susceptibility), has proven to be useful for appropriate clinical management and public health response.27 The use of improved diagnostic tests, in conjunction with surveillance, antibiotic prophylaxis, isolation of infected cases, and enhanced communication and education, offers the prospect of better control of pertussis outbreaks.28

Epidemiology
Pertussis vaccines administered to infants and young children in the United States have been effective at reducing the incidence of childhood pertussis cases and deaths. After the introduction of routine childhood immunization against pertussis in the 1940s and 1950s, the number of reported cases fell to a nadir of 1010 (0.5 per 100000 population) in 1976 (Fig 2). 29,30 Since then, the number of reported cases has increased, reaching 8.9 per 100000 population in 2004 and 2005.31 Of the 25827 cases of pertussis reported in the United States in 2004, 8897 (34%) were in adolescents 11 to 18 years old.7


Figure 2
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  		FIGURE 2 Reported cases of pertussis: United States, 1922–2004. (Adapted from Broder KR, Cortese MM, Iskander JK, et al. MMWR Recomm Rep. 2006;55(RR-3):1–34.)

 
It is unclear as to what proportion of the increase is attributable to an actual increase in cases and how much is attributable to better recognition, wider availability of diagnostic tests, or a higher proportion being reported to public health authorities.32 At least part of the increase is attributable to waning immunity, which leads to increased susceptibility to pertussis ~5 to 10 years after completing childhood vaccination,33 and there is also little doubt that there are many more cases than reported. For example, a study with careful follow-up revealed the incidence of pertussis among persons who were ≥15 years old ranged from 370 to 450 cases per 100000 person-years.23 Data from Massachusetts are likely to provide a more accurate picture of the epidemiology of the disease, because the state has especially good pertussis surveillance and uses a validated serology test to confirm cases in adolescents and adults. In 2004, Massachusetts reported 10% of the total adolescent pertussis cases in the United States, although it accounted for only 2% of the adolescent population (CDC, unpublished data, 2006). During 1996–2004, the rate of pertussis among adolescents 11 to 18 years old in Massachusetts was 93 per 100000. By contrast, the incidence among adolescents in the rest of the United States (excluding Massachusetts) was 7.3 per 100000 population.7

Vaccines
During 2005, 2 tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (TdaP) products formulated for use in adolescents (and, for 1 product, use in adults) were licensed in the United States. Table 3 highlights the differences between these 2 vaccines. Boostrix (GlaxoSmithKline, Philadelphia, PA) was licensed on May 3, 2005, for use in children 10 to 18 years old, and Adacel (sanofi pasteur, Swiftwater, PA) was licensed on June 10, 2005, for use in children and adults from 11 to 64 years old. The 2 vaccines contain similar tetanus, diphtheria, and pertussis components to those included in the childhood diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP), although some antigens are present in reduced amounts. The tetanus and diphtheria toxoid composition of TdaP are both lower than that of childhood DTaP but similar to that of licensed adult formulations of Td. A single TdaP booster was recommended to replace the Td booster previously recommended for all adolescents.7,34 The preferred age for this booster is 11 to 12 years; however, all 11- to 18-year-old adolescents who have not received Td or TdaP should receive a single dose of TdaP. Among adolescents who already received Td, TdaP is encouraged 5 or more years after the Td dose to reduce the risk for local and systemic reactions after TdaP vaccination. However, vaccine providers can administer TdaP after Td at shorter intervals, particularly when the benefit of protecting against pertussis is likely to be increased (eg, during outbreaks or periods of increased pertussis activity in the community). The safety of an interval as short as ~2 years between Td and TdaP is supported by a Canadian study among children and adolescents.7,35 Providers should administer TdaP and MCV4 to 11- to 18-year-old adolescents during the same visit if both vaccines are indicated and available.7


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  		TABLE 3 Comparison of Boostrix and Adacel, Adsorbed Products Licensed in the United States

 
Infections Caused by HPV
Epidemiology
HPV is the most common sexually transmitted infection in the United States and around the world.36,37 HPV acquisition often occurs within the first few years after sexual debut. In 15- to 24-year-olds, the average annual incidence of HPV infection is ~12000 per 100000, with prevalence reaching ~25000 per 100000 for young adults in their early 20s.37 The total number of new infections in the United States among those who are 15 to 44 years old is estimated to be ~6.2 million, with 4.6 million of these (74%) occurring in those who are 15 to 24 years old. Modeling estimates suggest that up to 80% of women will acquire HPV infection by the age of 50.38 Increased risk of infection is associated with early initiation of sexual activity and multiple sex partners.

The time between initial HPV infection and cervical cancer can be several decades. Cervical cancer was once one of the most common causes of cancer death for American women, and it remains the second most common cancer in women in less-developed countries, where cervical cancer screening and treatment are not widely available. Worldwide, there are an estimated 274000 deaths per year.39 In the United States, primarily because of the screening that detects precancerous lesions and allows for treatment before they can progress to cancer, deaths decreased from 10 to 3 per 100000 during the last half of the 20th century.40 In 2002, the age-standardized cervical cancer incidence in the United States was 8.7 per 100000.41 In part, however, because of differences in cervical cancer screening, there are substantial racial and ethnic differences in the incidence of cervical cancer in the United States.42

Vaccines
A quadrivalent vaccine has been licensed for use in the United States,8 and a bivalent vaccine is in the final stages of clinical development (Table 4) . Both the licensed and candidate vaccines are made from noninfectious HPV-like particles composed of the L1 major capsid protein. The quadrivalent vaccine is directed against HPV types 16 and 18, which are responsible for ~70% of cervical cancers, and HPV types 6 and 11, which cause ~90% of genital warts; the bivalent vaccine contains types 16 and 18 only. In clinical trials among adolescent girls and young women without evidence of the relevant HPV infection at enrollment, these vaccines have demonstrated 100% efficacy in preventing vaccine-type HPV-related cervical, vaginal, and vulvar cancer precursors.43–46 In addition to preventing cervical cancer, HPV vaccines will reduce the risk of, and procedures needed to treat, patients with abnormal Papanicolaou test results.43 The quadrivalent vaccine has also been shown to have high efficacy in preventing genital warts caused by HPV types 6 and 11.8 Neither vaccine is effective in modifying disease or potential complications attributable to vaccine serotypes in women who were infected before vaccination.47,48


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  		TABLE 4 Comparison of Gardasil and Cervarix (HPV Vaccines)

 
Hepatitis B
Etiology, Pathogenesis, Clinical Manifestations, and Epidemiology
The hepatitis B virus is a member of the Hepadnavirus family of double-stranded DNA viruses. Although acute infection in adolescents can be temporarily incapacitating, chronically infected people remain responsible for a majority of the morbidity and mortality and, therefore, the economic burden of disease. Chronically infected persons are also the source of most transmissions. Cirrhosis and hepatocellular carcinoma are responsible for an estimated 5000 deaths per year among persons with chronic hepatitis B infection.49 Before childhood hepatitis B vaccination programs became routine in the United States, an estimated 30% to 40% of chronic infections resulted from perinatal or early childhood transmission. As of 2004, among US children aged 19 to 35 months, >92% had been fully vaccinated with 3 doses of hepatitis B vaccine.50 Vaccination coverage among adolescents has also increased substantially. Preliminary data demonstrate that 50% to 60% of adolescents aged 13 to 15 years have records indicating that they have completed hepatitis B vaccination. The effectiveness of these childhood and adolescent vaccination efforts seem primarily responsible for a 75% decrease in the incidence of acute hepatitis B in the United States during 1990–2004 and the low number of cases of hepatitis B among adolescents (Table 1).51 The greatest decline in cases has occurred among children and adolescents, coincident with an increase in hepatitis B vaccine coverage.52,53 Nonetheless, coverage among adolescents who were born in the 1990s varies considerably depending primarily on the state of implementation of childhood vaccination programs, the presence and enforcement of primary and middle school–entry laws,54–56 and the presence of Health Plan Employer Data and Information Set requirements.57

Vaccine
A serum-based vaccine was licensed in 1981 and became available in 1982. The current recombinant hepatitis B vaccine is safe and confers a protective immune response in >95% of infants, children, and adolescents. Vaccination provides long-term protection, with breakthrough infections being extremely rare and usually transient and asymptomatic. Vaccination was first recommended by the ACIP in 1982 for adults who had a high risk of infection (eg, health care workers, men who have sex with men, injecting drug users).58 Routine maternal screening for hepatitis B surface antigen (HBsAg) and immunization of infants born to HBsAg-positive mothers was recommended in 1988.59 Difficulties in implementing targeted recommendations for adults and recognition of the substantial burden of hepatitis B–related disease resulting from infections during childhood led to the development of a new strategy. In 1991, a comprehensive strategy to eliminate hepatitis B transmission was implemented with a recommendation to vaccinate all infants.60 A primary focus of this strategy, which was updated in 2005, is the universal vaccination of infants, beginning at birth, to prevent early childhood hepatitis B infection and to eventually protect adolescents and adults from infection.61 Other components include routine screening of all pregnant women for HBsAg and postexposure immunoprophylaxis of infants born to HBsAg-positive women, vaccination of children and adolescents who were not previously vaccinated, and vaccination of unvaccinated adults who are at increased risk for infection. This strategy led to a recommendation for vaccination of adolescents 11 to 12 years old in 199562 and all adolescents in 1999.63 Despite these recommendations, the success of catch-up vaccination efforts during childhood and middle school has been inconsistent, particularly among children and teens not covered by the recommendation for universal infant immunization against hepatitis B. Most of the success has been the result of primary and middle school vaccination requirements.64

Varicella
Etiology, Pathogenesis, and Clinical Manifestations
Like other members of the herpesvirus group, varicella zoster virus manifests first as a primary infection (chickenpox) and has the capacity to persist in the body (latent infection) and recur (shingles).3 It is transmitted through respiratory contact and the conjunctiva, replicating at the site of entry and the lymph nodes. A primary viremia follows, but it is not until a secondary viremia that skin infection manifests. Although considered by many to be a benign disease, varicella can result in serious complications, sequelae, and death.

Epidemiology
In the prevaccine era, virtually all people in the United States acquired varicella by adulthood, with the highest age-specific incidence in children 1 to 4 years old.65 During 1990–1994, before implementation of the varicella vaccination program, an estimated 4 million cases, 11000 hospitalizations, and 100 deaths were attributed to varicella disease each year in the United States.66 After recommendation of the vaccine for children 12 to 18 months old in 1996, vaccine-coverage rates increased from 26% in 1997 to 87% in 2004.67 Although national surveillance for varicella cases remains incomplete, active surveillance in limited geographic areas and national mortality data revealed marked decreases in varicella incidence, varicella-related hospitalizations, and deaths in all age groups.64,68–70 Varicella cases decreased 71% to 84% and mortality decreased by 66%.70 Cases among vaccinated individuals are now increasing, which is believed to be happening because of waning immunity.58

Vaccine
A vaccine was first licensed in 1995 and recommended for children and all adolescents 11 and 12 years old in 1996.3 For adolescents, emphasis was placed on administering the vaccine at the age of 11 or 12 years.3 Vaccination of adolescents at >13 years old has focused only on groups at increased risk of transmission, and outbreaks in older adolescents have continued to occur. The ACIP has now recommended 2-dose vaccination of children and a second dose of vaccine for children, adolescents, and adults who previously received 1 dose of the vaccine.71

Measles-Mumps-Rubella
Elimination of measles has been a public health goal in the United States since the late 1970s.72 After steady progress in the 1980s, a major resurgence of measles began in 1989 in children and adolescents.73 With the recommendation for a second dose of measles vaccine in 19892 and passage and enforcement of school-entry requirements for second-dose vaccination,74 indigenous transmission has been eliminated.75 At the same time, rubella and congenital rubella syndrome were eliminated in this country.76 Nonetheless, adherence to the recommended 2-dose regimen is essential for avoiding transmission in the face of importations into the United States, which continue to occur occasionally.77 The importance of maintaining a high level of coverage with MMR is further underscored by recent outbreaks of mumps in the United States and other developed countries.78,79

Future Vaccines
Of the >80 known infectious agents that are pathogenic to humans, there are now >30 vaccines against 26, mainly viral and bacterial infections.80,81 Many important vaccines that would likely be recommended for administration during adolescence remain elusive, in part because these vaccines need to stimulate both cell-mediated and humoral immune responses. Such vaccines include ones against herpes simplex, cytomegalovirus, chlamydia, group B streptococcus, tuberculosis, and HIV.

Herpes simplex virus type 2 may cause lifelong infection and significant medical and psychosocial morbidity. Vaccines that prevent herpes simplex virus infection may not only decrease acquisition but also disease severity, neonatal herpes, and the transmission of HIV.82,83 Cytomegalovirus has also been the target of vaccine-development efforts. Cytomegalovirus is the most common intrauterine infection in the United States. A vaccine targeting it would decrease both morbidity and mortality, primarily by preventing congenital infection.84,85 By 2015, it is possible that vaccines against HIV and tuberculosis will be introduced; at least some of these will be intended primarily for adolescents. Although most of these vaccines are the subject of active research, it is likely that the majority may not be clinically available until the middle of the next decade.


   CONCLUSIONS
TOP
 ABSTRACT
 THE DISEASES AND THE...
 CONCLUSIONS
REFERENCES
 
Vaccines and vaccination programs are among the greatest public health accomplishments of the 20th century.86 Decades of efforts have been needed to realize these achievements. With the development of new vaccines, new diseases in adolescents have become vaccine preventable, and the burden of these vaccine-preventable diseases is substantial.

A number of factors will make delivery of these vaccines a challenge. The high cost of the vaccines and the difficulty in reaching adolescents for vaccination and other health care issues (see Szilagyi et al,87 Broder et al,88 and Sneller et al89) have suggested that a new paradigm may be necessary. We must be able to explain to adolescents, their parents, and public health decision-makers the special place that vaccines hold among clinical preventive services (see Broder et al88). Unlike many other clinical preventive services that are recommended for adolescents, their effectiveness is not in doubt.90 However, immunization advocates need to concede that numerous other clinical90 and community preventive services are of tremendous value in reducing the burden of disease and injury among adolescents.89 Furthermore, the challenge of implementing even the most strongly recommended preventive services cannot be underestimated.90,91 Analyses of the cost-effectiveness of mature vaccination programs and comparisons between vaccines and other preventive services continue to be conducted and are essential to guiding public policy.92–94


   ACKNOWLEDGMENTS
 
We thank Mary McCauley, Susan Wang, Eric Mast, Gary Freed, Charles Irwin, Jeanne Santoli, Megan Lindley, Amanda Cohn, and Kristin Brown for their scientific and editorial suggestions.


   FOOTNOTES
 
Accepted Aug 22, 2007.

Address correspondence to Daniel B. Fishbein, MD, National Center for Preparedness, Detection, and Control of Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mail Stop E-03, Atlanta, GA 30333. E-mail: dfishbein{at}cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.


   REFERENCES
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 ABSTRACT
 THE DISEASES AND THE...
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  1. American Academy of Pediatrics, Committee on Infectious Diseases. Immunization of adolescents: recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. Pediatrics. 1997;99 :479 –488[Abstract/Free Full Text]
  2. Centers for Disease Control and Prevention. Measles prevention. MMWR Morb Mortal Wkly Rep. 1989;38(suppl 9) :1 –18
  3. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1996;45 :1 –36[Medline]
  4. Centers for Disease Control and Prevention. Update: recommendations to prevent hepatitis B virus transmission—United States. MMWR Morb Mortal Wkly Rep. 1995;44 :574 –575[Medline]
  5. Bilukha OO, Rosenstein N; National Center for Infectious Diseases, Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005;54 (RR-7):1–21
  6. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients. Pediatrics. 2005;116 :496 –505[Abstract/Free Full Text]
  7. Broder KR, Cortese MM, Iskander JK, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55 (RR-3):1–34
  8. Markowitz L, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56 (RR-2):1–24
  9. Raghunathan PL, Bernhardt SA, Rosenstein NE. Opportunities for control of meningococcal disease in the United States. Annu Rev Med. 2004;55 :333 –353[CrossRef][Web of Science][Medline]
  10. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med. 2001;344 :1378 –1388[Free Full Text]
  11. Brooks R, Woods CW, Benjamin DK Jr, Rosenstein NE. Increased case-fatality rate associated with outbreaks of Neisseria meningitidis infection, compared with sporadic meningococcal disease, in the United States, 1994–2002. Clin Infect Dis. 2006;43 :49 –54[CrossRef][Web of Science][Medline]
  12. Kelly DF, Pollard AJ, Moxon ER. Immunological memory: the role of B cells in long-term protection against invasive bacterial pathogens. JAMA. 2005;294 :3019 –3023[Abstract/Free Full Text]
  13. Vu DM, Welsch JA, Zuno-Mitchell P, Dela Cruz JV, Granoff DM. Antibody persistence 3 years after immunization of adolescents with quadrivalent meningococcal conjugate vaccine. J Infect Dis. 2006;193 :821 –828[CrossRef][Web of Science][Medline]
  14. Centers for Disease Control and Prevention. Notice to readers: limited supply of meningococcal conjugate vaccine, recommendations to defer vaccination of persons age 11–12 years. MMWR Morb Mortal Wkly Rep. 2006;55 :567 –568
  15. Campos-Outcalt D. Meningococcal vaccine: new product, new recommendations. J Fam Pract. 2005;54 :324 –326[Web of Science][Medline]
  16. Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. Revised recommendations of the Advisory Committee on Immunization Practices to vaccinate all persons aged 11–18 years with meningococcal conjugate vaccine. MMWR Morb Mortal Wkly Rep. 2007;56 :794 –795[Medline]
  17. Lorick S, Fishbein DB, Wortley P, Weintraub E, Kong Y, Lee G. Menactra's uptake patterns among adolescents—United States, 2005. Presented at Prevention 2007, Annual Meeting of the American Academy of Preventive Medicine. Miami, FL: 2007
  18. Centers for Disease Control and Prevention. Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine: United States, June-July 2005. MMWR Morb Mortal Wkly Rep. 2005;54 :1023 –1025[Medline]
  19. Centers for Disease Control and Prevention. Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine: United States, October 2005-February 2006. MMWR Morb Mortal Wkly Rep. 2006;55 :364 –366[Medline]
  20. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18 :326 –382[Abstract/Free Full Text]
  21. Linnemann CC Jr, Bass JW, Smith MH. The carrier state in pertussis. Am J Epidemiol. 1968;88 :422 –427[Abstract/Free Full Text]
  22. Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy TV. Trends in pertussis among infants in the United States, 1980–1999. JAMA. 2003;290 :2968 –2975[Abstract/Free Full Text]
  23. Ward JI, Cherry JD, Chang SJ, et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med. 2005;353 :1555 –1563[Abstract/Free Full Text]
  24. Hewlett EL, Edwards KM. Clinical practice: pertussis—not just for kids. N Engl J Med. 2005;352 :1215 –1222[Free Full Text]
  25. De Serres G, Shadmani R, Duval B, et al. Morbidity of pertussis in adolescents and adults. J Infect Dis. 2000;182 :174 –179[CrossRef][Web of Science][Medline]
  26. Lee GM, Lett S, Schauer S, et al. Societal costs and morbidity of pertussis in adolescents and adults. Clin Infect Dis. 2004;39 :1572 –1580[CrossRef][Web of Science][Medline]
  27. Sotir MJ, Cappozzo DL, Warshauer DM, et al. Evaluation of polymerase chain reaction and culture for diagnosis of pertussis in the control of a county-wide outbreak focused among adolescents and adults. Clin Infect Dis. 2007;44 :1216 –1219[CrossRef][Web of Science][Medline]
  28. Davis JP. Clinical and economic effects of pertussis outbreaks. Pediatr Infect Dis J. 2005;24 :S109 –S116[CrossRef][Web of Science][Medline]
  29. Bisgard KM, Pascual B, Tiwaria T, Murphy T. Pertussis. In: Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. 3rd ed. Atlanta, GA: US Department of Health and Human Services; 2002
  30. Centers for Disease Control and Prevention. Pertussis: United States, 1997–2000. MMWR Morb Mortal Wkly Rep. 2002;51 :73 –76[Medline]
  31. McNabb SJ, Jajosky RA, Hall-Baker PA, et al. Summary of notifiable diseases 2005. MMWR Recomm Rep. 2007;54 :1 –92
  32. Cherry JD, Grimprel E, Guiso N, Heininger U, Mertsola J. Defining pertussis epidemiology: clinical, microbiologic, and serologic perspectives. Pediatr Infect Dis J. 2005;24(suppl 5) :S25 –S34
  33. Forsyth KD, Campins-Marti M, Caro J, et al. New pertussis vaccination strategies beyond infancy: recommendations by the global pertussis initiative. Clin Infect Dis. 2004;39 :1802 –1809[CrossRef][Web of Science][Medline]
  34. American Academy of Pediatrics, Committee on Infectious Diseases. Policy statement: prevention of pertussis among adolescents—recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Available at: www.aap.org/advocacy/releases/Tdap121205.pdf. Accessed July 8, 2007
  35. Halperin SA, Sweet L, Baxendale D, et al. How soon after a prior tetanus-diphtheria vaccination can one give adult formulation tetanus-diphtheria-acellular pertussis vaccine? Pediatr Infect Dis J. 2006;25 :195 –200[CrossRef][Web of Science][Medline]
  36. Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006;24(suppl 1) :S1 –S15
  37. Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health. 2004;36 :6 –10[CrossRef][Web of Science][Medline]
  38. Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol. 2000;151 :1158 –1171[Abstract/Free Full Text]
  39. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancers statistics, 2002. CA Cancer J Clin. 2005;55 :74 –108[Abstract/Free Full Text]
  40. Goldie SJ, Grima D, Kohli M, Wright TC, Weinstein M, Franco E. A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine. Int J Cancer. 2003;106 :896 –904[CrossRef][Web of Science][Medline]
  41. US Cancer Statistics Working Group. United States Cancer Statistics: 2003—Incidence and Mortality. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, and the National Cancer Institute; 2006
  42. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005 [published correction appears in CA Cancer J Clin. 2005;55:259]. CA Cancer J Clin. 2005;55 :10 –30[Abstract/Free Full Text]
  43. Franco EL, Harper DM. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine. 2005;23 :2388 –2394[CrossRef][Web of Science][Medline]
  44. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002;347 :1645 –1651[Abstract/Free Full Text]
  45. Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005;6 :271 –278[CrossRef][Web of Science][Medline]
  46. Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367 :1247 –1255[CrossRef][Web of Science][Medline]
  47. Markowitz LE. HPV vaccines prophylactic, not therapeutic. JAMA. 2007;298 :805 –806[Free Full Text]
  48. Hildesheim A, Herrero R, Wacholder S, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA. 2007;298 :743 –753[Abstract/Free Full Text]
  49. Margolis HS, Coleman PJ, Brown RE, Mast EE, Sheingold SH, Arevalo JA. Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA. 1995;274 :1201 –1208[Abstract/Free Full Text]
  50. Centers for Disease Control and Prevention. National, state, and urban area vaccination coverage among children aged 19–35 months: United States, 2004. MMWR Morb Mortal Wkly Rep. 2005;54 :717 –721[Medline]
  51. Centers for Disease Control and Prevention. Acute hepatitis B among children and adolescents: United States, 1990–2002. MMWR Morb Mortal Wkly Rep. 2004;53 :1015 –1018[Medline]
  52. Goldstein ST, Alter MJ, Williams IT, et al. Incidence and risk factors for acute hepatitis B in the United States, 1982–1998: implications for vaccination programs. J Infect Dis. 2002;185 :713 –719[CrossRef][Web of Science][Medline]
  53. Perz JF, Elm JL Jr, Fiore AE, Huggler JI, Kuhnert WL, Effler PV. Near elimination of hepatitis B virus infections among Hawaii elementary school children after universal infant hepatitis B vaccination. Pediatrics. 2006;118 :1403 –1408[Abstract/Free Full Text]
  54. Wilson TR, Fishbein DB, Ellis PA, Edlavitch SA. The impact of a school entry law on adolescent immunization rates. J Adolesc Health. 2005;37 :511 –516[CrossRef][Web of Science][Medline]
  55. Fogarty KJ, Massoudi MS, Gallo W, Averhoff FM, Yusuf H, Fishbein D. Vaccine coverage levels after implementation of a middle school vaccination requirement, Florida, 1997–2000. Public Health Rep. 2004;119 :163 –169[Web of Science][Medline]
  56. 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. Am J Public Health. 2004;94 :978 –984[Abstract/Free Full Text]
  57. Rickert D, Deladisma A, Yusuf H, Averhoff F, Brink E, Shih S. Adolescent immunizations: are we ready for a new wave? Am J Prev Med. 2004;26 :22 –28[CrossRef][Web of Science][Medline]
  58. Centers for Disease Control and Prevention. Recommendation of the Immunization Practices Advisory Committee (ACIP): inactivated hepatitis B virus vaccine. MMWR Morb Mortal Wkly Rep. 1982;31 :317 –322, 327–328[Medline]
  59. Centers for Disease Control and Prevention. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR Morb Mortal Wkly Rep. 1988;10(37) :341 –346, 351
  60. Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. MMWR Recomm Rep. 1991;40 (RR-13):1–19
  61. Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1—immunization of infants, children, and adolescents [published correction appears in MMWR Morb Mortal Weekly Rep. 2006;55:158–159]. MMWR Recomm Rep. 2005;54(RR-16) :1 –31
  62. Centers for Disease Control and Prevention. Prevention and control of influenza recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1995;44 :1 –22[Medline]
  63. Centers for Disease Control and Prevention. Update: recommendations to prevent hepatitis B virus transmission—United States. MMWR Morb Mortal Wkly Rep. 1999;48 :33 –34[Medline]
  64. Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med. 2005;352 :450 –458[Abstract/Free Full Text]
  65. Khoshnood B, Debruyne M, Lancon F, et al. Seroprevalence of varicella in the French population. Pediatr Infect Dis J. 2006;25 :41 –44[CrossRef][Web of Science][Medline]
  66. Galil K, Lee B, Strine T, et al. Outbreak of varicella at a day-care center despite vaccination. N Engl J Med. 2002;347 :1909 –1915[Abstract/Free Full Text]
  67. Luman ET, Ching PL, Jumaan AO, Seward JF. Uptake of varicella vaccination among young children in the United States: a success story in eliminating racial and ethnic disparities. Pediatrics. 2006;117 :999 –1008[Abstract/Free Full Text]
  68. Lopez AS, Lett SM, Yih WK, Northrup J, Jumaan AO, Seward JF. Increasing evidence of immunity to varicella among children in Massachusetts, 1999–2003. Am J Prev Med. 2006;30 :232 –236[CrossRef][Web of Science][Medline]
  69. Hall S, Maupin T, Seward J, et al. Second varicella infections: are they more common than previously thought? Pediatrics. 2002;109 :1068 –1073[Abstract/Free Full Text]
  70. Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States, 1995–2000. JAMA. 2002;287 :606 –611[Abstract/Free Full Text]
  71. American Academy of Pediatrics, Committee on Infectious Diseases. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007;120 :221 –231[Abstract/Free Full Text]
  72. Richmond JB. Measles elimination: why not now? JAMA. 1979;242 :1175 –1176[Abstract/Free Full Text]
  73. Atkinson WL, Orenstein WA, Krugman S. The resurgence of measles in the United States, 1989–1990. Annu Rev Med. 1992;43 :451 –463[CrossRef][Web of Science][Medline]
  74. Kolasa MS, Klemperer-Johnson S, Papania MJ. Progress toward implementation of a second-dose measles immunization requirement for all schoolchildren in the United States. J Infect Dis. 2004;189(suppl 1) :S98 –S103
  75. Gindler J, Tinker S, Markowitz L, Atkinson W, Dales L, Papania MJ. Acute measles mortality in the United States, 1987–2002. J Infect Dis. 2004;189 (suppl 1):S69 –S77[CrossRef][Web of Science][Medline]
  76. Centers for Disease Control and Prevention. Achievements in public health: elimination of rubella and congenital rubella syndrome—United States, 1969–2004. MMWR Morb Mortal Wkly Rep. 2005;54 :279 –282[Medline]
  77. Yeung LF, Lurie P, Dayan G, et al. A limited measles outbreak in a highly vaccinated US boarding school. Pediatrics. 2005;116 :1287 –1291[Abstract/Free Full Text]
  78. Centers for Disease Control and Prevention. Mumps epidemic: Iowa, 2006. MMWR Morb Mortal Wkly Rep. 2006;55 :366 –368[Medline]
  79. Gupta RK, Best J, MacMahon E. Mumps and the UK epidemic 2005. BMJ. 2005;330 :1132 –1135[Free Full Text]
  80. Ada G. Overview of vaccines and vaccination. Mol Biotechnol. 2005;29 :255 –272[CrossRef][Web of Science][Medline]
  81. Ada G. Vaccines and vaccination. N Engl J Med. 2001;345 :1042 –1053[Free Full Text]
  82. Aurelian L. Herpes simplex virus type 2 vaccines: new ground for optimism? Clin Diagn Lab Immunol. 2004;11 :437 –445[CrossRef][Medline]
  83. Jones CA, Knipe D. Herpes simplex virus vaccines. Pediatr Infect Dis J. 2003;22 :1003 –1005[CrossRef][Web of Science][Medline]
  84. Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R; National Vaccine Advisory Committee. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004;39 :233 –239[CrossRef][Web of Science][Medline]
  85. Schleiss M. Progress in cytomegalovirus vaccine development. Herpes. 2005;12 :66 –75[Medline]
  86. Centers for Disease Control and Prevention. Impact of vaccines universally recommended for children: United States, 1990–1998. MMWR Morb Mortal Wkly Rep. 1999;48 :243 –248[Medline]
  87. Szilagyi P, Rand CM, McLaurin J, et al. Delivering adolescent vaccinations in the medical home: a new era? Pediatrics. 2007;121 :S15–S24
  88. Broder KR, Cohn AC, Schwartz B, et al. Adolescent immunizations and other clinical preventive services: a needle and a hook? Pediatrics. 2007;121 :S25–S34
  89. Sneller V-P, Fishbein, DF, Weinbaum CM, et al. Vaccinating adolescents in high-risk settings: lessons learned from experiences with hepatitis B vaccine. Pediatrics. 2007;121 :S55 –S62
  90. Moyer VA, Butler M. Gaps in the evidence for well-child care: a challenge to our profession. Pediatrics. 2004;114 :1511 –1521[Abstract/Free Full Text]
  91. Task Force on Community Preventive Services, Zaza S, Briss PA. The Guide to Community Preventive Services: What Works to Promote Health? New York, NY: Oxford University Press; 2005
  92. Yarnall KS, McBride CM, Lyna P, et al. Factors associated with condom use among at-risk women students and nonstudents seen in managed care. Prev Med. 2003;37 :163 –170[CrossRef][Web of Science][Medline]
  93. Zwanziger J, Szilagyi PG, Kaul P. Evaluating the benefits of increasing measles immunization rates. Health Serv Res. 2001;36 :885 –909[Web of Science][Medline]
  94. Maciosek MV, Coffield AB, Edwards NM, Flottemesch TJ, Goodman MJ, Solberg LI. Priorities among effective clinical preventive services: results of a systematic review and analysis. Am J Prev Med. 2006;31 :52 –61[CrossRef][Web of Science][Medline]
  95. Coffield AB, Maciosek MV, McGinnis JM, et al. Priorities among recommended clinical preventive services. Am J Prev Med. 2001;21 :1 –9[Web of Science][Medline]
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