Toward Control of Meningococcal Disease: Title and subTitle BreakReducing Risk in College Students

Neisseria meningitidis can cause rapid onset of meningitis and sepsis, leading to death or permanent disability. Meningococcal disease occurs globally, and while the largest outbreaks and preponderance of mortality and morbidity occur in the developing world, the disease continues to strike the young in developed countries.

The N meningitidis organism is usually classified in terms of serogroup, referring to the antigenic properties of the capsular polysaccharide. Most disease in the developed world is caused by organisms of serogroups B, C, Y, and W135 while serogroup A organisms cause the bulk of disease in the developing world.¹ Vaccines prepared with polysaccharides from A, C, Y, and W135 organisms are safe, immunogenic, and have been shown to be effective, particularly in providing short-term and medium-term protection against outbreaks caused by serogroups A and C organisms.² Serogroup B polysaccharide is not immunogenic. Preparation of vaccines from serogroup B proteins has been problematic, and efficacy of these products in young children, those at highest risk of disease, is disputed.² Thus, prevention of meningococcal disease through vaccination has relied on the use of the polysaccharide vaccines that are available for some but not all strains.

Polysaccharide vaccines are imperfect prevention tools. In general, the polysaccharide vaccines are less immunogenic in infants than in adults.² Furthermore, administration of vaccines with serogroup C antigen to young infants may hinder subsequent ability to generate antibody in response to later exposure to the antigen, a form of immunologic tolerance. Thus, vaccines containing serogroup C polysaccharide have not been adopted into routine infant immunization programs. The duration of protection provided by any of the polysaccharide antigens is unclear. In adults, antibody levels decline slowly to near baseline over a period of 5 to 10 years.³ Serogroup C polysaccharide vaccines are not effective in children younger than 2 years, and the efficacy of serogroup A polysaccharide vaccines given to children between the ages of 1 and 4 years disappears over a period of 3 years.⁴ Given these limitations, the polysaccharide vaccines have been recommended in the United States primarily for short-term to medium-term protection for (1) those traveling to countries with outbreaks of meningococcal disease; (2) high-risk groups, most prominently, military recruits, persons with specific immunodeficiencies, and laboratory workers directly handling the bacteria; and (3) emergency mass immunization of populations experiencing an outbreak of vaccine-preventable disease.⁵

In the last 10 years, small outbreaks and increased rates of serogroup C meningococcal disease have occurred in a number of western European and North American countries.^{6 - 7} The severity of the disease generated enormous concern resulting in mass immunization of large communities. Some of the outbreaks occurred on university or college campuses, raising the concern of increased risk in college students.

Several studies have attempted to clarify the question of increased risk of meningococcal disease in the college population. A questionnaire survey of university health services suggested higher risk among students living in dormitories, but there was a low response rate to the survey and more specific identification of risk factors was not performed.⁸ A study of Maryland residents found the risk for college students was not higher than for nonstudents of the same age, but students living on campus had higher rates than students living off campus. The small numbers of cases and limited geographic scope of this study, however, made it difficult to generalize the findings to the rest of the country.⁹ A study from England, where the epidemiology of meningococcal disease differs somewhat from that in the United States (including a higher baseline rate of disease), found that university students had a higher rate of disease than nonstudents and that risk was highest among students at universities with a high proportion of dormitory residents.¹⁰ These studies raised the possibility of a group that could potentially be targeted for immunization, but additional data were needed before more specific recommendations could be made for US students.

Two studies in this issue of THE JOURNAL provide information that may prove important for developing a rational approach to this problem. In the first, Harrison et al¹¹ characterize the occurrence of meningococcal disease in those aged 15 through 24 years. During the 10-year study period, 24% of all 295 meningococcal disease cases in Maryland occurred in this age group, which also had the highest case fatality rate (23%). More than 80% of meningococcal disease in this age group was caused by serogroups represented in the currently available vaccine. Both the highest mortality rate and the highest proportion of all disease preventable with the current vaccine occurred in this age group, supporting the concept of a logical target group for a vaccination program. However, even though the 15 through 24-year-old group had a higher risk of disease and greater potential benefit from the vaccine than children younger than 15 years, questions of overall costs and benefits of vaccinating the entire cohort of those aged 15 through 24 years remain. Several evaluations have suggested that from a societal perspective, vaccination of either the entire cohort, or college students alone, would not be cost saving.⁵

In the second study, Bruce et al¹² attempt to quantify the magnitude and distribution of meningococcal disease in college students. This nationwide study found that although college students in general had a lower rate of severe meningococcal disease than the general population of 18 to 23 year olds, the rate among freshmen living in dormitories was more than 3 times that in the general population. Furthermore, of the 79 case-patients for whom information was available, 68% had illness due to meningococcal serogroups that should be preventable with the current vaccine. Because freshmen living in dormitories comprised 4% of the total college population but 31% of all disease in college students occurred in this group, a major impact on meningococcal disease in college students could be made through immunization of a fairly small population.

Taken together, these studies demonstrate that meningococcal disease in this age group is severe, and a targeted approach of immunizing college freshmen who live in dormitories may be the most efficient way to make an impact on meningococcal disease. One could argue that immunizing all college freshmen would have a larger impact, albeit a less efficient one. The Advisory Committee on Immunization Practices has recommended that college students be advised of the risks and benefits of immunization and that the students should decide at that point whether they should be immunized.⁵

The solution to the problem of meningococcal disease in adolescents and young adults may require more effective vaccines that have long-lasting immunity and that can be administered with other routine infant immunizations. The development of serogroup C meningococcal conjugate vaccines is the first step in this direction. These vaccines, recently introduced in the United Kingdom and several other European countries, can be given safely and effectively in routine infant immunization settings¹³ and may provide long-term protection, which hopefully can last through late adolescence and early adulthood. The United Kingdom has already initiated routine administration of a 3-dose primary series of this conjugate vaccine in infants and a single dose to all children through the age of college entrance.¹⁴ Early results of surveillance data suggest efficacy of greater than 90% in toddlers and teenagers who received a single dose of serogroup C conjugate vaccine.¹⁵ Follow-up data are needed to determine whether booster doses will be required in addition to routine infant administration of a primary series. Long-term data from the United Kingdom and other countries introducing the serogroup C conjugate vaccine should help provide further information for designing optimal routine programs for these vaccines.

The serogroup C conjugate vaccine should provide an answer to disease caused by 1 major meningococcal serogroup. However, further development of Y and W135 conjugates and an effective serogroup B vaccine will be necessary to provide broad protection in the developed world. In the developing world, serogroup A disease exceeds other meningococcal serogroups in terms of disease burden and causes massive epidemics most prominently in sub-Saharan Africa.¹⁶ Promising serogroup A conjugate vaccines are now in preparation. Control of meningococcal disease through immunization is possible, but reaching this goal will require a combination of further vaccine development and careful assessment of the epidemiologic setting in which these new tools must function.