Surveillance for invasive infection due to N. meningitides
» Background
Meningococcal infections rank second in Canada among bacteria
causing life-threatening infection in children and adolescents
with a recent overall incidence of 0.8 per 100,000. The peak incidence
is in children under 1 year of age (at 10-15 per 100,000 per year)
but a secondary peak is also apparent in the adolescent age group.
Bloodstream invasive infections can progress very rapidly, causing
shock and microvascular damage, with high mortality. Overall mortality
averaged 6.5% in recent Canadian data. Permanent sequelae including
deafness, amputations and neurological deficits occur in about
15% of cases, with highest rates following group C disease. In
a earlier Canadian report of pediatric meningococcal cases in
1991-3, 83 cases were identified and half needed initial intensive
care. Mean length of stay in hospital was 12.6 days. A fatal outcome
occurred in 7.3%.
Prevention of meningococcal infections using vaccines is complicated
by the existence of multiple serogroups, which are immunologically
unrelated. Antibodies directed against the capsular polysaccharide
afford protection against the particular serogroup but do not
cross-react with other serogroups. Purified polysaccharides are
the basis of first generation vaccines, which typically contain
antigens of serogroups A, C, Y and W-135. The capsule of group
B strains is not immunogenic so no licensed vaccine is available.
This is an unfortunate gap because group B strains cause a substantial
portion of infections in young children. The polysaccharide-based
meningococcal vaccines are poorly immunogenic in young children
and protect for only a few years. Thus their use has been limited
to control of outbreaks and protection of individuals at increased
risk.
Recently a second generation of meningococcal vaccines was established
in which capsular polysaccharide is chemically linked to a carrier
protein. These “conjugate” vaccines are able to elicit
protective responses from 2 months of age and establish immunologic
memory, which is expected to result in long-lasting immunity.
To date, only group C meningococcal conjugate vaccines have been
licensed in Canada. Their safety and effectiveness were demonstrated
in a nationwide program in the United Kingdom. Group C conjugate
vaccines are recommended for routine administration to infants
and children but only a few provinces (AB, BC, QUE, PEI) have
implemented programs as yet.
Conjugate vaccines against all four of the preventable meningococcal
serogroups would be desirable, and are under development. They
include serogroups A, C, Y and W-135. Group Y meningococci have
increased in importance during the past decade in Canada and the
USA and now account for one-third of cases in the USA and about
12% in Canada. Highest rates occur in adolescents and young adults.
More information is needed about the strains involved in this
upsurge and about the epidemiology of cases. Meningococci of group
W-135 typically cause sporadic cases but have the potential to
cause outbreaks. Serogroup A strains have not been endemic in
Canada for several decades but cause epidemic disease in other
parts of the world (e.g. sub-Saharan Africa). Protection is desirable
for travelers to endemic areas and residents therein. Population
immunity may help to prevent re-introduction of group A strains
to Canada. Finally, potential shifts in serogroup predominance
due to programs aimed at preventing group C disease should be
considered.
It is particularly timely to undertake enhanced surveillance
of meningococcal infections in children and adults. Robust surveillance
systems are necessary in order to determine the impact of new
vaccination strategies for targeted or universal vaccination strategies.
Just as the use of conjugated pneumococcal vaccine in infants
has caused a decrease in the incidence of invasive disease in
adults, the implications of such programs for meningococcal disease
in the entire populations are critical. Data from 2002-2003 will
provide baseline information for most provinces, against which
the benefits of new immunization programs using group C conjugate
vaccine, can be measured. The relative importance of other serotypes
will be of interest, particularly any shifts upward in incidence
rates as group C disease is curbed. When multi-valent conjugate
vaccines are licensed decisions about their routine use will require
detailed information about group-specific risks of disease, complications
and deaths. This study will be a principal source of such information.
» Methods
The Toronto public health laboratory, and each microbiology laboratory
within Toronto, Peel, Durham, York, Simcoe, Halton and Hamilton
will review their records to identify all patients with a positive
sterile site culture for N. meningitides from January 1, 2002
until June 1, 2004 whose postal code of resident lies within the
study area. Cases confirmed by PCR testing (where available) will
also be reported. After June 1, 2004, cases will be identified
as usual for active surveillance and laboratories will call the
study office whenever an isolate is identified from a sterile
site by culture or PCR. Data will be collected by chart review,
using the previously approved data collection form. The family
physician or health department may be contacted to obtain pertinent
immunization information only. As with other TIBDN surveillance
requiring chart review only, the name of patient will remain on
a yellow “sticky” on the tracking record until the
data collection is complete, and will then be discarded.
Coded data forms (coded, with date of birth and first three digits
of postal code as most specific identifiers) will be shipped to
the IMPACT central office in British Columbia. Isolate studies
will be performed by Health Canada at the National Microbiology
Laboratory. Only the patient code will link isolate and case report
forms.
» Analysis
All data forms with only study code number will be submitted
to IMPACT for inclusion in aggregated analysis of data from across
Canada.
