CME Author: Zeena Nackerdien
Study Authors: Sarah A. Mbaeyi, Sandeep J. Joseph, et al.
Target Audience and Goal Statement:
Pediatricians, infectious disease specialists, and primary care physicians
The goal is to learn more about the incidence and characteristics of meningococcal disease in college-age young adults in the U.S.
The authors addressed the following questions:
- What was the epidemiology of meningococcal disease in college students?
- What was the relative risk (RR) of meningococcal disease in college students versus non-college students among individuals, ages 18 to 24 years?
- Would it be possible to characterize the disease-causing strains?
Synopsis and Perspective:
Neisseria meningitides is a human pathogen that is commonly responsible for bacterial meningitis in children and adults. If left untreated, consequences could be severe and include death. This is due to the endotoxin-induced vascular collapse frequently induced by the organism.
Worldwide, it has been estimated that 1.2 million cases of invasive meningococcal infections occur, resulting in 135,000 deaths. While the disease has declined in the U.S. since the 1990s, college freshmen living in residence halls had previously been identified as being at an increased risk for meningococcal disease versus non-college students of the same age.
It is worth noting the historical context of prior evaluations, when disease rates were higher among college students and serogroup C was the predominant cause of disease. The vaccines for meningococcal serogroups A, C, W-135, and Y (MenACWY) and serogroup B (MenB) disease had not yet become available, and the ability to characterize the molecular features of N. meningitides strains in this population had not yet been developed. Therefore, there remained an unmet need to gain a comprehensive understanding of the current epidemiology and risks of meningococcal disease among college students, according to Sarah A. Mbaeyi, MD, MPH, of the CDC in Atlanta, and colleagues.
Effective polysaccharide and polysaccharide-protein conjugate vaccines are currently available for the prevention of MenACWY, and two MenB vaccines have also now been approved by the FDA.
Using 2014-2016 data from the National Notifiable Disease Surveillance System and enhanced meningococcal disease surveillance from 45 states (representing 98% of the population), the researchers compared the incidence and RR of meningococcal disease among college and non-college students (ages 18-24 years).
A total of 166 cases of meningococcal disease occurred among individuals, ages 18-24 years, including 83 who were college students, corresponding to an average annual incidence of 0.17 cases per 100,000 population versus an incidence of 0.05 cases per 100,000 population for persons of the same age who were not attending college. In the entire 18-24 cohort, 58.3% of cases were serogroup B. Among college students, 76.9% of cases were serogroup B versus 38.4% of cases in non-college students. About 13% of cases were serogroup C and 10% serogroup Y.
Compared with non-college students, college students with meningococcal disease were more likely to be younger (ages 18-20), and to have received ≥1 dose of the MenACWY vaccine. According to the American Academy of Pediatrics (AAP), “students entering college and planning to live in dorms have also historically been at a higher risk than other people of the same age for meningococcal serogroup C and Y infections and are routinely recommended to receive the quadrivalent meningococcal conjugate (MenACWY) vaccine.”
On the other hand, “the MenB vaccine series may be administered to individuals ages 16 to 23 years, with the preferred age of 16 to 18 years, on the basis of clinical decision-making,” Mbaeyi and colleagues noted.
Estimated coverage of at least one dose of MenB vaccine among those ages 16-18 years was <10% by the end of 2017. The authors identified six serogroup B outbreaks on college campuses, accounting for 31.7% of serogroup B cases in college students during the study period. Mbaeyi and colleagues found that the RR for the development of serogroup B cases on college campuses was much higher than the RR for serogroups C, W, and Y combined cases (3.54, 95% CI 2.21-5.41 vs 0.56, 95% CI 0.27-1.14).
The elevated risk (2.76, 95% CI 1.73-4.4) for MenB infection remained, even when only sporadic cases, and the first case associated with outbreaks, were included in the analysis. The most common serogroup B clonal complexes identified were CC32/ET-5 and CC41/44 lineage 3.
A study limitation was that the authors were unable to assess the expected strain coverage of MenB vaccines in this population “because we did not evaluate levels of gene expression and isolate susceptibility to antibodies induced by vaccine antigens.” But 47% of serogroup B isolates in college students and 67% in non-college students possessed ≥1 MenB vaccine sub-variants included in MenB-4C or MenB-FHbp vaccines, raising the possibility that they might still be covered through cross-reactivity.
Source Reference: Pediatrics, January 2019; DOI:10.1542/ peds. 2018- 2130
Study Highlights: Explanation of Findings
Although college students, ages 18-24 years, experienced a low incidence of meningococcal disease, they were at increased risk for sporadic and outbreak-associated MenB disease compared with students who did not attend college. This group also had a low incidence of serogroups C, W, and Y.
In an accompanying editorial, Lucila Marquez, MD, MPH and Sheldon L. Kaplan, MD, both of Baylor College of Medicine in Houston, wrote that when the Advisory Committee on Immunization Practices (ACIP) of the CDC deliberated MenB vaccines in June 2015, “college attendance was not identified as a risk factor for MenB infections.”
ACIP considered this point and other factors in their decision to make MenB adolescent vaccination a category B (formerly known as “permissive”) rather than a category A (formerly known as “universal”) recommendation. This meant that the determination regarding the appropriateness of a vaccine was made in the context of interactions between patients and physicians, rather than issuing a blanket recommendation to apply to all persons in an age- or risk-based group, they noted.
In February 2015, the ACIP recommended use of MenB vaccines among certain groups, ages ≥10 years, who are at increased risk for serogroup B meningococcal disease. Given current results showing an increased risk for MenB disease, the question raised by the current study was if a change was needed in the MenB vaccine recommendations, Marquez and Kaplan stated.
However, they said it was difficult to recommend MenB shots for adolescents and young adults based on disease burden alone. For instance, there were only 130 cases in MenB disease in the U.S. in 2016. A total of 41 cases occurred in those ages 16-23 years. Yet meningococcal disease remains life-threatening, and evidence from other countries proved compelling in determining the effectiveness of MenB shots. In England there was a 50% incidence rate ratio reduction in MenB cases after implementation of a two-dose infant schedule, but questions remained regarding duration of protection, effect on carriage, and strain coverage.
The AAP commented that, with respect to a MenB vaccine, “overall coverage rates from a herd immunity standpoint are low thus far, with only 2% of colleges requiring the vaccine and less than 10% of 16-18-year olds having received this newer vaccine.” This may partly be due to the fact that less than half of the parents of those ages 16-19 said they were aware of MenB availability, and only 70% of pediatricians and 21% of family practitioners reported being “very aware” of MenB vaccines, according to separate studies.
Marquez and Kaplan stated that “pediatricians should educate students and families regarding the increased risk of MenB infections in college students in the U.S. and inform them that 2 vaccines are available that can potentially protect college students from this infection.” They also noted that side effects due to MenB vaccinations were “relatively minimal.”
Original story for MedPage Today by Molly Walker
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco