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Published online August 1, 2005
PEDIATRICS
Vol. 116 No. 2 August 2005, pp.
496-505
(doi:10.1542/peds.2005-1314)
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POLICY STATEMENT |
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ABSTRACT |
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20%). Epidemiologic studies also have demonstrated increased risk of IMD among college freshman living in dormitories compared with other college students and similarly aged persons in the general population. At least 75% of cases of IMD in 11- to 18-year-olds are caused by serogroups A, C, Y, and W-135; thus, IMD potentially is preventable by immunization with quadrivalent meningococcal vaccines. Meningococcal A, C, Y, W-135 conjugate vaccine (MCV4) was licensed in 2005 for use in people 11 to 55 years of age. On the basis of data indicating increased risk of meningococcal disease and fatality among certain adolescents and college students, the American Academy of Pediatrics recommends administration of MCV4 to young adolescents (at the 11- to 12-year visit), students entering high school or 15-year-olds, and college freshmen who will be living in dormitories. For pediatric patients 11 years and older who are at increased risk of meningococcal disease, MCV4 also is recommended. The purposes of this statement are to provide the rationale for routine use of MCV4 in adolescents and to update recommendations for use of the meningococcal polysaccharide vaccine in pediatric patients.
Key Words: meningococcal disease
Abbreviations: IMD, invasive meningococcal disease • CDC, Centers for Disease Control and Prevention • AAP, American Academy of Pediatrics • MPSV4, tetravalent meningococcal (A, C, Y, W-135) polysaccharide vaccine • FDA, Food and Drug Administration • MCV4, tetravalent meningococcal (A, C, Y, W-135) conjugate vaccine • SBA, serum bactericidal activity • rSBA, serum bactericidal assay using baby rabbit serum • GMT, geometric mean titer • Td, adult-type diphtheria and tetanus toxoids • OMP, outer membrane protein
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BACKGROUND INFORMATION |
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10% to 14% of cases, and significant sequelae including limb or digit amputation, skin scarring, neurologic disabilities, and hearing loss occur in 11% to 19% of cases.2 Although only a portion of these cases present clinically as meningitis, Neisseria meningitidis has become the leading cause of bacterial meningitis in children after the dramatic reductions in the incidence of Streptococcus pneumoniae and Haemophilus influenzae type b infections achieved after introduction of conjugate vaccines for these pathogens.
The incidence of IMD in pediatric patients has 2 peaks. The highest incidence of meningococcal disease is in infants younger than 12 months, but a second, lower peak occurs during adolescence.2 Adolescents 15 years or older are more likely than infants and children to have meningococcemia without meningitis (40% vs 20%, respectively), shock at presentation (69% vs 27%, respectively), and a fatal outcome (22.5% vs 4.6%, respectively).3 Not surprisingly then, adolescents have the highest case-fatality rate (estimated at 20%) of any age group. Survivors at any age are at risk of permanent sequelae.
The American Academy of Pediatrics (AAP) previously recommended tetravalent meningococcal (A, C, Y, W-135) polysaccharide vaccine (MSPV4 [Menomune-A/C/Y/W-135; Sanofi Pasteur, Swiftwater, PA]) for use in certain high-risk children and adolescents, including travelers to countries with epidemic or hyperendemic meningococcal disease, for people who have certain medical conditions (terminal complement component deficiencies and anatomic or functional asplenia), and for control of meningococcal disease outbreaks attributable to strains in the vaccine.4 Previous AAP guidelines for college freshmen have emphasized education about meningococcal disease and the availability of a meningococcal vaccine without recommending routine use of meningococcal polysaccharide vaccine.5
The new tetravalent meningococcal (A, C, Y, W-135) conjugate vaccine (MCV4 [Menactra; Sanofi Pasteur]), licensed by the Food and Drug Administration (FDA) on January 14, 2005, for use in people 11 to 55 years of age, should become an important addition to existing meningococcal disease–preventive measures. This statement provides the recommendations of the AAP for prevention and control of meningococcal disease in pediatric patients through immunization with MPSV4 as well as the new MCV4. More detailed information regarding contemporary epidemiology of IMD, evaluation and management of suspected outbreaks of IMD, cost-effectiveness analyses for meningococcal vaccines, and recommendations for use of meningococcal vaccines and chemoprophylaxis in adults can be found in the statement of the Advisory Committee on Immunization Practices of the CDC.2
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EPIDEMIOLOGY OF IMD |
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20%).
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In the United States, more than 98% of cases of IMD in children and adults are sporadic, but since 1991, the frequency of localized outbreaks has increased, especially in schools.6 The proportion of meningococcal disease caused by serogroup Y has increased from 2% in 1989–19917 to 37% in 1997–2002.2 Currently, serogroups B, C, and Y are the major causes of IMD in the United States, each being responsible for approximately one third of all cases. The proportion of cases caused by each serogroup varies by age group; more than half of cases among infants younger than 1 year are caused by serogroup B, for which no vaccine is licensed or available in the United States.8 Seventy-five percent of all cases of meningococcal disease in people 11 to 18 years of age are caused by serogroups (A, C, Y, or W-135) included in currently available vaccines.2 The incidence of IMD caused by these vaccine-preventable serotypes peaks in people 18 years of age (1.8 per 100000), is beginning to increase substantially at 15 years of age, and decreases by 19 years of age (Fig 2).
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600000 freshmen who lived in dormitories during this period, the rate (5.1 per 100000) was higher than any age group in the population other than children younger than 2 years but lower than the threshold of 10 per 100000 recommended for initiating meningococcal immunization campaigns.9
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In 2000, the Advisory Committee on Immunization Practices and AAP Committee on Infectious Diseases1,5 concluded that college students who live in dormitories are at increased risk of meningococcal disease relative to other people their age. They recommended that college students and their parents be informed by health care professionals of the risks of meningococcal disease and potential benefits of immunization with MPSV4, that college and university health services facilitate implementation of educational programs concerning meningococcal disease and availability of immunization services, and that the vaccine be made available to those requesting immunization. As of August 2004, 31 states have adopted legislation requiring colleges to provide information on risks of meningococcal disease to matriculating students and students residing on campus. Eleven of those states mandate immunization of students living on campus unless an immunization waiver is provided.
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MENINGOCOCCAL VACCINES |
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Meningococcal Polysaccharide Vaccine
Vaccine Composition and Administration
Each dose of MPSV4 consists of 50 µg each of the 4 (A, C, Y, and W-135) purified meningococcal capsular polysaccharides. MPSV4 (Menomune-A/C/Y/W-135) is available in single-dose (0.5-mL) and multiple-dose (5-mL) vials. MPSV4 is administered subcutaneously as a single 0.5-mL dose. MPSV4 can be administered concomitantly with other vaccines at different anatomic sites.12,13 Protective concentrations of antibodies usually are achieved within 7 to 10 days of immunization.14
Immunogenicity and Efficacy
MPSV4 (Menomune-A/C/Y/W-135) was licensed in the United States in 1981 on the basis of safety and immunogenicity data. Immunogenicity of this vaccine was compared with immunogenicity of an existing bivalent A and C meningococcal polysaccharide vaccine, which had demonstrated 97% efficacy against serogroup A and 90% efficacy against serogroup C meningococcal disease in military recruits.15 The immunologic criterion used for licensing was an increase in serum bactericidal activity (SBA) of fourfold or greater in 90% of adults 3 to 4 weeks after immunization.
The immunogenicity and efficacy of serogroup A and C meningococcal polysaccharide vaccines are established. Serogroup A polysaccharide vaccine induces antibodies in some children as young as 3 months of age, although an immune response comparable to that in adults is not achieved until 4 to 5 years of age; serogroup C polysaccharide vaccine is poorly immunogenic in children younger than 24 months. Serogroup A and C polysaccharide vaccines have demonstrated estimated clinical efficacies of more than 85% in school-aged children and adults and are useful in controlling outbreaks.16,17 Serogroup Y and W-135 polysaccharide vaccines are safe and immunogenic in children older than 2 years and adults, and although clinical efficacy has not been documented, immunization with these polysaccharide vaccines induces high titers of serum bactericidal antibodies, a correlate of protection. The antibody responses to each of the 4 polysaccharides in the tetravalent polysaccharide vaccine are serogroup-specific and independent. Serogroup C polysaccharide vaccine can cause immunologic hyporesponsiveness (reduced antibody response after reimmunization with the same polysaccharide antigen), but the biological significance of this observation is unclear.18
Duration of Protection
In children 2 to 5 years of age, measurable concentrations of antibodies against group A and C polysaccharides decrease substantially during the first 3 years after a single dose of vaccine.19 Although vaccine-induced protection likely persists in school-aged children and adults for at least 3 years, the efficacy of the group A vaccine administered to children younger than 5 years may decrease markedly within this period of time. In one study, group A vaccine efficacy in children immunized at younger than 4 years decreased from more than 90% to less than 10%; in children given vaccine at older than 4 years of age, vaccine efficacy was 67% 3 years later.20
Precautions and Contraindications
MPSV4 has been used extensively in mass-immunization programs as well as in the military and among international travelers. Adverse reactions to MPSV4 generally are mild; the most frequent reaction is pain and redness at the injection site lasting for 1 or 2 days. Estimates of the incidence of such local reactions have varied, ranging from 4% to 56%. Transient fever occurs in up to 5% of vaccine recipients in some studies but is less common in older children and adults. Most studies report the rate of systemic allergic reactions (eg, urticaria, wheezing, and rash) as 0.0 to 0.1 per 100000 vaccine doses.21 Anaphylaxis has been documented in less than 0.1 per 100000 vaccine doses.22
Meningococcal Conjugate Vaccines
Theoretic Advantage of MCV4
Bacterial polysaccharides, including those comprising the capsule of N meningitidis, are T-cell–independent antigens. T-cell–independent antigens do not elicit a memory response. They stimulate mature B lymphocytes but not T lymphocytes, thus inducing a response that is neither long lasting nor characterized by anamnestic response after subsequent challenge with the same polysaccharide antigen.23 Meningococcal polysaccharide vaccines, therefore, have several inherent limitations. Meningococcal polysaccharide vaccines do not confer long-lasting immunity and do not elicit a sustainable reduction of nasopharyngeal carriage of N meningitidis to result in herd immunity.24
Conjugation (covalent coupling) of polysaccharide to a protein carrier that contains T-cell epitopes changes the expression of the immune response to the polysaccharide from T-cell independent to T-cell dependent, resulting in an improved primary response to the polysaccharide and a strong anamnestic response at reexposure.25 Both conjugate H influenzae type b and conjugate S pneumoniae vaccines introduced for mass infant immunization in the United States in 1990 and 2000, respectively, have been successful in reducing the incidence of disease caused by serotypes contained in the vaccines.1 In addition, both vaccines decrease asymptomatic carriage of the respective bacteria, thus protecting unimmunized individuals through a herd-immunity effect.1
Meningococcal Serogroup C Conjugate Vaccine in the United Kingdom
In November 1999, 3 monovalent serogroup C conjugate vaccines were introduced in the United Kingdom during a national immunization campaign. A routine 3-dose infant immunization series began at the same time as a mass catch-up campaign targeting all children between 12 months and 17 years of age.26 By 2001–2002, vaccine coverage in the United Kingdom was estimated at 80% in infants, 84% in toddlers, 76% in preschoolers, and 87% in school-aged children.27 Effectiveness of the meningococcal group C conjugate vaccines within the first year of immunization ranged from 88% to 98% in different age groups.28 Because the vaccine campaign was initiated in 1999, duration of protection data are not yet available. However, effectiveness among infants who received 3 doses of vaccine at 2, 3, and 4 months of age decreased by 81% after only 1 year.28 Although the number of cases remains low, likely in part because of vaccine-induced herd immunity, this study raises important questions about the meningococcal vaccine schedule and the need for a booster dose in infants. Carriage rates of group C meningococci in the United Kingdom decreased by 66% during the campaign; incidence of IMD decreased by 67% in unimmunized children 1 to 17 years of age, demonstrating the ability of the conjugate vaccine to elicit herd immunity.27
Vaccine Composition and Administration
MCV4 is a tetravalent meningococcal conjugate vaccine (Menactra) that contains capsular polysaccharides from serogroups A, C, Y, and W-135 (4 µg each) conjugated to 48 µg of diphtheria toxoid. MCV4 is available only in single-dose (0.5-mL) vials; vaccine is administered as a single 0.5-mL dose. Protective concentrations of antibodies are achieved within 8 days of immunization.
Immunologic Correlates of Protection
Studies in military recruits conducted in the United States in the 1960s demonstrated that naturally acquired bactericidal antibodies measured by SBA confer protection from IMD. SBA titers of 
1:4 using human serum as an exogenous complement source (hSBA) are considered to be the correlate of protection against serogroup C meningococcal disease.29 This correlate of protection was used in the recent licensure of monovalent serogroup C meningococcal conjugate vaccines in the United Kingdom without the requirement for clinical efficacy trials.30 However, immunogenicity data supporting the use of these conjugate vaccines were generated by a serum bactericidal assay using baby rabbit serum (rSBA), rather than human serum, as an exogenous complement source.
Additional evaluation of rSBA threshold values were performed by using vaccine efficacy estimates from postlicensure surveillance in the United Kingdom. Postlicensure surveillance data suggested that an rSBA 4 weeks after immunization of 1:8 was most consistent with the observed protective effect.31 On the basis of these efficacy estimates, rSBA titers of <1:8 were proposed to be predictive of susceptibility to IMD. The proportion of responders in various clinical trials of meningococcal C conjugate vaccines and on the group C seroprevalence study conducted before introduction of group C conjugate vaccines also provide evidence that rSBA titers of 1:8 correlate with short-term protection.32 There exist little or no similar data linking immune response to efficacy for serogroups A, Y, or W-135.
MCV4 was licensed on the basis of demonstrated noninferiority to MPSV4 for immunogenicity and safety. MPSV4 had been licensed on the basis of efficacy against serogroup A and C meningococcal disease in military recruits.33 The primary criterion in determining immunogenic noninferiority of MCV4 to MPSV4 was the percentage of adolescents and adults who had an increase in SBA of fourfold or greater after receiving MCV4 compared with the percentage of those after MPSV4 was used. However, for licensure of MCV4, an rSBA of 1:128 was considered as "protective," because it would not only predict short-term but also long-term clinical efficacy.
Immunogenicity
A randomized, controlled trial compared the immunogenicity of MCV4 and MPSV4 in adolescents 11 to 18 years of age 28 days after immunization. A similar percentage of subjects achieved at least a fourfold increase in rSBA titers in the MCV4 and MPSV groups (Table 2). The percentage of adolescents with at least a fourfold increase in rSBA was highest for serogroup W-135 (96.7% for MCV4; 95.3% for MPSV4) and lowest for serogroup Y (81.8% for MCV4; 80.1% for MPSV4). The percentage of subjects achieving an rSBA geometric mean titer (GMT) of 1:128 was higher than 98% for all meningococcal serogroups in both MCV4 and MPSV4 recipients.34
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To date, the only data concerning reimmunization with MCV4 come from a study in which 76 adolescents previously immunized with MCV4 and 77 adolescents previously immunized with MPSV4 were compared with 88 age-matched vaccine-naive adolescents.34 rSBA was measured in sera from these adolescents before (day 0) and 8 and 28 days after immunization with MCV4 (Table 3). Adolescents initially immunized with MCV4 had higher rSBA GMT before reimmunization than adolescents initially immunized with MPSV4; this difference reached statistical significance for serogroup A (P < .001) and W-135 (P < .001) but not for serogroups C and Y. In addition, a higher percentage of adolescents initially immunized with MCV4 had protective rSBA titers of 1:128 compared with adolescents initially immunized with MPSV4 (Table 3). Vaccine-naive adolescents had low rSBA before immunization compared with adolescents who had received MCV4 or MPSV4 previously.
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1:128 before (day 0) and 8 and 28 days after administration of MCV4 and with vaccine-naive controls. All adolescents in each of the 3 groups achieved rSBA titers of 1:128 28 days after MCV4 (Table 3). Subjects initially primed with MCV4 achieved higher rSBA GMTs compared with vaccine-naive controls for all serogroups except serogroup A.
Concomitant Administration of MCV4 and Other Vaccines
Among adolescents 11 to 18 years of age, a randomized, controlled trial evaluated the immunogenicity and safety of MCV4 administered concomitantly with tetanus and diphtheria toxoids absorbed for adult use (Td; Sanofi Pasteur) versus Td administered concomitantly with placebo and then MCV4 administered 28 days later. Concomitant administration of Td and MCV4 did not adversely affect immune response to antigens in either vaccine.34 When MCV4 and Td were administered concomitantly, antibody response to diphtheria antigen 28 days after immunization was greater (diphtheria GMT: 120.9 IU/mL) than when Td and MCV4 were administered sequentially 28 days apart (diphtheria GMT: 8.4 IU/mL 28 days after Td dose).
Safety
Among adolescents 11 to 18 years of age, safety of administering MCV4 and MPSV4 was assessed in 2 randomized, controlled trials.34 The percentage of subjects reporting systemic adverse events was similar in both groups (Table 4). Approximately half of the adolescents experienced at least 1 systemic adverse reaction, but less than 5% experienced at least 1 severe systemic reaction. Fever was reported by 3.4% to 5.1% of adolescents who received MCV4 and by 2.5% to 3.0% of adolescents who received MPSV4, a difference that was not significant.
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Cost of Meningococcal Vaccines
Whether universal immunization of adolescents with tetravalent A, C, Y, W-135 meningococcal vaccine would result in a net cost or a net savings to society depends on IMD incidence, which varies by year, the rates of death or permanent sequelae, and the cost of immunization. A recent study from the CDC suggests that universal immunization of adolescents would be cost-effective.35 However, variations in the epidemiology of and outcomes from IMD by region make it impossible to generate a precise estimate of the cost benefit. If, as expected, universal adolescent immunization with MCV4 becomes a reality in the next few years, more precise estimates should become available.
The total cost of immunizing a single adolescent with MCV4 includes direct and indirect costs. The direct costs include supplies (eg, vaccine [MCV4 = $82.00 and MPSV4 = $86.10 per dose], syringe with needle), personnel, and administrative expenses. Public and private insurers should be responsible for payment of costs for MCV4. MCV4 is included in the Vaccines for Children program. For private insurers, avoiding financial responsibility by transferring this to intermediate risk-bearing entities (eg, independent practice associations or other physician groups), individual physicians, or college health services will result in adolescents not being immunized in a timely fashion. Physicians incur significant administrative expenses when ensuring that adolescents are immunized with recommended vaccines in a timely fashion, including explaining risk and benefits of immunization to adolescents and parents; ordering, purchasing, storing, and administering the vaccine; recording immunizations in records; and other activities. Physicians should receive reimbursement for expenses associated with each vaccine administration.
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FUTURE NEEDS |
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MCV4 and other meningococcal conjugate vaccines may be licensed in the United States in the near future for use in other age groups, including children 2 to 10 years of age and infants. Such vaccines are undergoing clinical trials and are likely to be more immunogenic in infants and young children compared with MPSV4, which currently is the only meningococcal vaccine licensed in the United States for use in young children.
Because meningococcal serogroup B capsular polysaccharide is poorly immunogenic in humans, vaccine development has focused on common surface proteins, including the outer membrane proteins (OMPs) of specific epidemic strains.36 OMP vaccines have shown good efficacy in older children and adults, but efficacy in infants and young children, in whom rates of disease are highest, has not been demonstrated. In addition, the variability in OMP strains causing endemic disease likely will limit their usefulness in the United States.37
Because of the potential limitations of these vaccines, other new approaches to meningococcal serogroup B vaccines are being pursued. With the recent sequencing of the serogroup B meningococcal genome, several new genes encoding putative membrane proteins have been identified, suggesting potential new targets for serogroup B vaccines. The availability of new meningococcal conjugate vaccines as well as the pursuit of new vaccine strategies should lead to substantial improvements in control and prevention of meningococcal disease in the United States and globally.
Although the signs and symptoms of IMD frequently are nonspecific, increasing awareness of meningococcal disease can result in people seeking medical care earlier and improved clinical outcome. In addition, educating adolescents and their parents about the benefits of receiving MCV4 is critical to prevention of a substantial number of cases of IMD. However, parents and adolescents must understand that MCV4 will not prevent all meningococcal disease, and at least 25% of cases in adolescents are caused by serogroup B.1 Educating the general public about the benefits of being immunized with MCV4 may foster increased immunization coverage rates for adolescents and substantially decrease the burden of meningococcal disease in the United States.
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RATIONALE FOR MENINGOCOCCAL VACCINE RECOMMENDATIONS |
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 TOPABSTRACTBACKGROUND INFORMATIONEPIDEMIOLOGY OF IMDMENINGOCOCCAL VACCINESFUTURE NEEDS RATIONALE FOR MENINGOCOCCAL... RECOMMENDATIONSCOMMITTEE ON INFECTIOUS...LIAISONSEX OFFICIOCONSULTANTSTAFFREFERENCES |
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Because the initial supply of MCV4 will be limited for the next 2 to 3 years, initially only 2 cohorts can be recommended to be immunized routinely. The first cohort, young adolescents at the 11- to 12-year visit, was selected because this is the age at which a booster dose of Td already is recommended and when well visits to the pediatrician are more likely to occur than in older adolescents.2 The AAP also emphasizes the importance of more pediatric patients of this age having well visits for preventive services other than immunization. A recommendation to immunize all 11- to 12-year-olds, therefore, not only is more likely to be feasible compared with older adolescents but also should be associated with enhancing the importance of the young adolescent visit. The second cohort, entering high school students or 15-year-olds, whichever comes first, was chosen on the basis of 2 factors: the peak IMD incidence and routine medical visits by adolescents 13 years and older. The peak incidence of disease occurs after 15 years of age, but less than 20% of adolescents 16 to 18 years of age have routine medical visits to pediatricians. Some states already have high school entry laws requiring certain vaccines. Once MCV4 supply is abundant, routine immunization of all adolescents likely will be recommended. Also, within 3 years, information on duration of immunity and need for reimmunization, if any, should become available. To date, the vaccine uptake by adolescents suggests that pediatricians should do everything possible to use other medical visits (eg, sports or camp preparticipation physical examinations or evaluations for minor illnesses such as upper respiratory tract infections) to ensure that recommended vaccines are administered.
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RECOMMENDATIONS |
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• adolescents who have a terminal complement deficiency or adolescents who have anatomic or functional asplenia (evidence grade II-3); or
• adolescents who travel to or reside in countries in which N meningitidis is hyperendemic or epidemic (CDC Travelers' Health Hotline 877-FYI-TRIP or online at www.cdc.gov/travel) (evidence grade II-3).
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COMMITTEE ON INFECTIOUS DISEASES, 2004–2005 |
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H. Cody Meissner, MD, Vice Chairperson
*Carol J Baker, MD
Robert S. Baltimore, MD
Joseph A. Bocchini, Jr, MD
John S. Bradley, MD
Penelope H. Dennehy, MD
Robert W. Frenck, Jr, MD
Caroline B. Hall, MD
Sarah S. Long, MD
Julia A. McMillan, MD
Keith R. Powell, MD
Lorry G. Rubin, MD
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LIAISONS |
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American Academy of Family Physicians
Steven Cochi, MD
Centers for Disease Control and Prevention
Joanne Embree, MD
Canadian Paediatric Society
Marc A. Fischer, MD
Centers for Disease Control and Prevention
Benjamin Schwartz, MD
National Vaccine Program Office
Mamodikoe Makhene, MD
National Institutes of Health
Douglas Pratt, MD
Food and Drug Administration
Jeffrey R. Starke, MD
American Thoracic Society
Jack Swanson, MD
Practice Action Group
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EX OFFICIO |
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Red Book Editor
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CONSULTANT |
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STAFF |
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FOOTNOTES |
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REFERENCES |
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The following policy statement has been revised:
This article has been cited by other articles:
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  D. B. Fishbein, K. R. Broder, L. Markowitz, and N. Messonnier New, and Some Not-so-New, Vaccines for Adolescents and Diseases They Prevent Pediatrics, January 1, 2008; 121(Supplement_1): S5 - S14. [Abstract] [Full Text] [PDF]
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 L. Rubin AAP, CDC issue meningococcal vaccine update AAP News, December 1, 2006; 27(12): 8 - 8. [Full Text]
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S. L. Kaplan, G. E. Schutze, J. A.D. Leake, W. J. Barson, N. B. Halasa, C. L. Byington, C. R. Woods, T. Q. Tan, J. A. Hoffman, E. R. Wald, et al. Multicenter Surveillance of Invasive Meningococcal Infections in Children Pediatrics, October 1, 2006; 118(4): e979 - e984. [Abstract] [Full Text] [PDF]
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Committee on Infectious Diseases Prevention of Pertussis Among Adolescents: Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine Pediatrics, March 1, 2006; 117(3): 965 - 978. [Abstract] [Full Text] [PDF]
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Committee on Infectious Diseases Recommended Childhood and Adolescent Immunization Schedule--United States, 2006 Pediatrics, January 1, 2006; 117(1): 239 - 240. [Full Text] [PDF]
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 Meningococcal Infections Red Book, January 1, 2006; 2006(1): 452 - 460. [Full Text]
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