Pediatric Annals

PEDIATRIC IMMUNIZATION UPDATE 

Meningococcal Disease and Vaccines

Peter Dull, MD; Nancy Rosenstein, MD

Abstract

EPIDEMIOLOGY

Neisseria meningitidis causes an estimated 120,000 cases of bacterial meningitis and sepsis worldwide each year, including 2,400 to 3,000 cases in the United States.1,2 Since 1960, rates in the United States have remained relatively stable at approximately 0.9 to 1.5 per ???,???.2 Rates are highest among infants younger than 1 year, decrease in children, and increase in adolescents and young adults. The overall case-fatality ratio is 9% to 12% and can be as high as 40% for patients with meningococcemia; among survivors, an additional 11% to 19% have significant sequelae, including neurologic disability, loss of a limb, or loss of hearing.3-4

Meningococci are classified into one of 13 serogroups based on the antigenic properties of their capsular polysaccharide. Serogroups A, B, and C account for more than 90% of disease worldwide, but most industrialized countries are affected predominantly by serogroups B and C.2,4 Recently, serogroup Y has emerged as a more important cause of disease in the United States. From 1996 to 1999, one-third of disease was caused by this serogroup (Figure).2,5,6

In the United States, the current frequency of localized outbreaks of meningococcal disease is increased compared with that of previous decades. Most have been due to serogroup C. However, in the past 3 years, outbreaks due to serogroup Y have also been reported.7 Outbreaks cause tremendous public concern and prompt considerable media attention, but only 2% to 3% of disease in the United States occurs in this category.8 Therefore, to achieve control of meningococcal disease, efforts focused primarily on outbreaks are not sufficient.

ANTIMICROBIAL CHEMOPROPHYLAXIS

Close contacts of patients with meningococcal disease are at elevated risk of disease. One study estimated the attack rate in this population to be 4 cases per 1,000 persons exposed, a rate 400 to 600 times that of the general population.9 Chemoprophylaxis of close contacts is effective in prevention of disease and should be administered expeditiously to household members, day care center contacts, and anyone directly exposed to the patient's oral secretions.10 If given more than 14 days after the onset of disease in the primary patient, chemoprophylaxis is probably of limited or no benefit. The use of rifampin, ciprofloxacin, or ceftriaxone will reduce pharyngeal carriage in close contacts by 90% to 95%.1112 Nasopharyngeal cultures are not helpful in determining the need for prophylaxis and may unnecessarily delay the institution of antibiotics. Because chemoprophylaxis is practiced so effectively in the United States, cases of disease among close contacts of patients are rare.

MENINGOCOCCAL VACCINE

Safety and Efficacy

Improved control and prevention of meningococcal disease will require more effective vaccines. The only meningococcal vaccine currently available in the United States is a quadrivalent vaccine that contains polysaccharides from serogroups A, C, Y, and W-135.13-14 Extensive experience with the vaccine has demonstrated it to be safe, with mild adverse reactions consisting principally of pain and redness at the injection site.10

The efficacy of serogroups A and C polysaccharide vaccines has been estimated at approximately 85% among older children and adults.1516 Among children younger than 24 months, serogroup C polysaccharide vaccine is poorly immunogenic and clinical efficacy is poor.17 In addition, antibody levels and clinical efficacies of serogroups A and C polysaccharide vaccines decline markedly during the first 3 years of life among infants and young children.18 Antibody levels also decrease in adults, although antibodies were detected 10 years after immunization in a study of U.S. military recruits.19 Serogroups Y and W-135 polysaccharide vaccines are safe and immunogenic in older children, although there are no data on efficacy and duration of protection. Based on immunogenicity study data, concern has been raised about the potential risk…

EPIDEMIOLOGY

Neisseria meningitidis causes an estimated 120,000 cases of bacterial meningitis and sepsis worldwide each year, including 2,400 to 3,000 cases in the United States.1,2 Since 1960, rates in the United States have remained relatively stable at approximately 0.9 to 1.5 per ???,???.2 Rates are highest among infants younger than 1 year, decrease in children, and increase in adolescents and young adults. The overall case-fatality ratio is 9% to 12% and can be as high as 40% for patients with meningococcemia; among survivors, an additional 11% to 19% have significant sequelae, including neurologic disability, loss of a limb, or loss of hearing.3-4

Meningococci are classified into one of 13 serogroups based on the antigenic properties of their capsular polysaccharide. Serogroups A, B, and C account for more than 90% of disease worldwide, but most industrialized countries are affected predominantly by serogroups B and C.2,4 Recently, serogroup Y has emerged as a more important cause of disease in the United States. From 1996 to 1999, one-third of disease was caused by this serogroup (Figure).2,5,6

In the United States, the current frequency of localized outbreaks of meningococcal disease is increased compared with that of previous decades. Most have been due to serogroup C. However, in the past 3 years, outbreaks due to serogroup Y have also been reported.7 Outbreaks cause tremendous public concern and prompt considerable media attention, but only 2% to 3% of disease in the United States occurs in this category.8 Therefore, to achieve control of meningococcal disease, efforts focused primarily on outbreaks are not sufficient.

ANTIMICROBIAL CHEMOPROPHYLAXIS

Close contacts of patients with meningococcal disease are at elevated risk of disease. One study estimated the attack rate in this population to be 4 cases per 1,000 persons exposed, a rate 400 to 600 times that of the general population.9 Chemoprophylaxis of close contacts is effective in prevention of disease and should be administered expeditiously to household members, day care center contacts, and anyone directly exposed to the patient's oral secretions.10 If given more than 14 days after the onset of disease in the primary patient, chemoprophylaxis is probably of limited or no benefit. The use of rifampin, ciprofloxacin, or ceftriaxone will reduce pharyngeal carriage in close contacts by 90% to 95%.1112 Nasopharyngeal cultures are not helpful in determining the need for prophylaxis and may unnecessarily delay the institution of antibiotics. Because chemoprophylaxis is practiced so effectively in the United States, cases of disease among close contacts of patients are rare.

MENINGOCOCCAL VACCINE

Safety and Efficacy

Improved control and prevention of meningococcal disease will require more effective vaccines. The only meningococcal vaccine currently available in the United States is a quadrivalent vaccine that contains polysaccharides from serogroups A, C, Y, and W-135.13-14 Extensive experience with the vaccine has demonstrated it to be safe, with mild adverse reactions consisting principally of pain and redness at the injection site.10

The efficacy of serogroups A and C polysaccharide vaccines has been estimated at approximately 85% among older children and adults.1516 Among children younger than 24 months, serogroup C polysaccharide vaccine is poorly immunogenic and clinical efficacy is poor.17 In addition, antibody levels and clinical efficacies of serogroups A and C polysaccharide vaccines decline markedly during the first 3 years of life among infants and young children.18 Antibody levels also decrease in adults, although antibodies were detected 10 years after immunization in a study of U.S. military recruits.19 Serogroups Y and W-135 polysaccharide vaccines are safe and immunogenic in older children, although there are no data on efficacy and duration of protection. Based on immunogenicity study data, concern has been raised about the potential risk of immunosuppression associated with multiple doses of serogroup C (and, more recently, serogroup A) polysaccharide vaccine, although no clinical data exist.20,21

Recommendations

Because of the relative ineffectiveness of the vaccine in children younger than 2 years and the limited duration of protection, routine immunization of infants with meningococcal polysaccharide vaccine is not recommended.10-22 In the United States, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination for certain high-risk groups, including military recruits, individuals with terminal complement component deficiencies or anatomic or functional asplenia, and laboratory workers who are at high risk.10 Vaccination may benefit travelers to areas where meningococcal disease is epidemic or hyperendemic, such as sub-Saharan Africa.

Figure. Age-specific incidence of meningococcal disease by serogroup- United States, 1990-1998.

Figure. Age-specific incidence of meningococcal disease by serogroup- United States, 1990-1998.

Polysaccharide vaccine is also recommended to help control vaccine-preventable meningococcal outbreaks. The ACIP recommends that mass vaccination of individuals 2 years and older be considered when two or more cases of vaccinepreventable meningococcal disease (ie, serogroups A, C, Y, or W-135) occur in a single community or organization (eg, school) within a period of 3 months or less, and the attack rate reaches 10 cases per 100,000 population.23

In the past 10 years, rates of meningococcal disease in the United States have increased among adolescents and young adults.24 Several recent studies have identified college freshmen who live in dormitories or residence halls to be at a modestly increased risk compared with other undergraduates or individuals of the same age who do not attend college.25"27 As a result of these findings, the ACIP and the American Academy of Pediatrics (AAP) have recently recommended that health care providers and colleges educate freshman (especially those who live in dormitories) and their parents about the increased risk of disease and the potential benefits of immunization. This will then allow informed decisions to be made regarding vaccination.22'28 The students and their parents should understand that use of the current vaccine will decrease but not eliminate the risk of disease. This is because it is not 100% efficacious against the serogroups it targets (ie, A, C, Y, and W-135) and it does not protect against serogroup B, a serogroup causing onethird of meningococcal disease.

FUTURE DEVELOPMENTS

The serogroup B capsule is poorly immunogenic in humans, probably because of its structural similarities to a glycoprotein found in human neural tissue.29 Therefore, immunization strategies have focused on noncapsular antigens. Outer membrane protein vaccines have been successful with strains of serogroup B meningococci that cause outbreaks.30-31 However, their efficacy has not been demonstrated in young children, and variability in the strains causing endemic disease may limit their future use.32 Researchers are pursuing other potential vaccines against serogroup B disease, including more simplified candidates that incorporate common antigens, which may be effective against all serogroups.14 Ultimately, such new approaches to develop a single vaccine to target all serogroups may be preferable.

In the next 5 years, meningococcal conjugate vaccines should become available and offer an opportunity to repeat the impressive success of Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccines: invasive Hib disease has decreased by more than 99% since their introduction from 1987 to 1990 .33 Meningococcal conjugate vaccines provoke a T-cell-dependent response, which elicits an improved immune response in infants and primes immunologic memory. This contrasts with the T-cell-independent response induced by the unconjugated polysaccharide antigens. Similar to Hib vaccines, meningococcal conjugate vaccines may also produce herd immunity by decreasing nasopharyngeal colonization, an attribute lacking with the current polysaccharide vaccine.

In the United Kingdom, where rates of serogroup C disease are higher than in the United States, a meningococcal serogroup C conjugate vaccine was introduced into the childhood vaccination schedule in late 1999. This was the first routine use of such a vaccine on a large scale and impressive reductions in disease have already been observed in targeted groups.34 Conjugate vaccine formulation for the United States is somewhat more complicated and would likely need to include serogroups C and Y.35 A broader vaccine, which also includes serogroups A and W-135, may be preferable to optimize flexibility. Further, this would address the clear need for a conjugate vaccine containing serogroup A, a strategy representing the best hope for prevention of epidemic meningococcal disease in sub-Saharan Africa.36

CONCLUSION

The near elimination of invasive Hib disease and the likely impact of the recent introduction of pneumococcal conjugate vaccines37 will further change the epidemiology of bacterial meningitis, increasing the prominence of meningococcal disease. Although a serogroup B vaccine awaits further technical advances, meningococcal conjugate vaccines should be available in the United States in the next 2 to 5 years and will be candidates for incorporation into the childhood vaccination schedule. Unresolved scientific issues concerning these new vaccines include duration of protection and herd immunity. Strategic issues such as target age groups, vaccine formulation, and combination with other vaccines to simplify crowded childhood vaccination schedules must also be addressed. However, these challenges are surmountable and, in the near future, meningococcal conjugate vaccines should provide a tremendous opportunity to reduce the burden of meningococcal disease in the United States and globally.

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10.3928/0090-4481-20010601-12

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