Meningococcal disease and vaccination in North America

Abstract

In North America, meningococcal disease occurs at a rate of I case per 100000 population per year, producing 2725 cases notified in the US in 1998 and 155 laboratory confirmed cases in Canada in the same year. A majority of these cases occur in the winter season and in early childhood, with a case fatality rate of approximately 10%. There has been an increase in the proportion of cases due to serogroup Y meningococci over the past decade: in 1995-98 in the US, 33% of cases were due to serogroup B, 28% were due to serogroup C and 34% were due to serogroup Y; in Canada in 1995-96, 47% of cases were due to serogroup B, 40% were due to serogroup C and 10% were due to serogroup Y. Outbreaks due to serogroup C were more common in the 1990s in the US and a number of outbreaks have occurred in Canada due to organisms from the hypervirulent ET-37 complex. College freshmen in the US in dormitories were found to be at an increased risk of disease. In addition, over the past 10 years, an outbreak of serogroup B disease occurred in the Pacific North-west of the US, with a fourfold increased rate of disease in that region. The explanations for these changes in epidemiology are unknown, but probably reflect the appearance of hypervirulent clones of meningococci and/or changing levels of population immunity. Meningococcal serogroup C polysaccharide-protein conjugate vaccines have been introduced recently in the UK, seem efficacious and offer the potential to reduce the burden of disease in the US and Canada too. Because serogroups other than serogroup C are prevalent in North America, a combination polysaccharide-protein vaccine, including C, Y and possibly W135 serogroups, would be attractive for this population. Although not currently an issue in industrialized nations, inclusion of serogroup A conjugates in any future vaccine policy would be an important decision in driving global prevention of meningococcal disease. A meningococcal conjugate vaccine against serogroup C was licensed in Canada in April 2001.

Biochemical and Biophysical Characterization of the Sialyl-/Hexosyltransferase Synthesizing the Meningococcal Serogroup W135 Heteropolysaccharide Capsule

“…Common to members of this group is the EX 7 E motif, a part of the so called nucleotide recognition domain 1␣ (16,34). Mutation of the first conserved glutamic acid residue in the EX 7 E motif has been demonstrated to inactivate retaining GTs (35)(36)(37)(38). In line with these earlier data we show here that the position (Glu-307) is essential also in SiaD W-135.…”

“…Serogroup W-135 meningococci caused an outbreak of disease among pilgrims in 2000 (4) and an epidemic in Burkina Faso in 2002 with over 13,000 cases and more than 1,400 fatalities (5,6). Furthermore, an increase in serogroup Y disease was observed in the 1990s in North America (7).…”

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents

“…While serogroup C disease remains of particular epidemiologic concern globally, in several countries including the United States, serogroup Y has emerged as a significant contributor to invasive disease incidence. 13 One limitation of this study is that the population represented only a subset of the full cohort of subjects vaccinated in the initial study. 6 Nevertheless, the consistency of results among the cohorts included in the persistence study and those in the primary study indicate that the immune responses of the subset the target enrollment goal was 200 MenACWY-CRM and 200 MCV4 subjects from the parent study, and 100 naïve subjects at each time point.…”

Interactions between Neisseria meningitidis and the complement system

“…Most disease in wealthy countries is caused by serogroup B and C strains. Large-scale outbreaks of serogroup W135 N. meningitidis have occurred most notably in West Africa following spread from the Hajj pilgrimage [42,43], while cases of serogroup Y infection have been increasing in North America [44]. Interestingly, all these capsules are composed principally of sialic acid, so bacteria are effectively using one of the mechanisms employed by host cells (that are also decorated with this molecule) to prevent complement-mediated lysis [45].…”