Meningococcal Disease In Canada Research Articles

Epidemiology of invasive meningococcal disease in Canada, 2012–2019

Epidemiology of invasive meningococcal disease in Canada, 2012–2019

Epidemiology of invasive meningococcal disease in Canada, 2012-2019.

A variety of routine childhood and adolescent meningococcal vaccination programs using monovalent (serogroup C) and quadrivalent (A, C, Y, W) conjugate vaccines have been implemented in Canada since 2002, resulting in a decrease in invasive meningococcal disease (IMD) incidence, particularly in serogroup C. Meningococcal vaccines have also been used for outbreak response, including the multicomponent vaccine serogroup B vaccine. This report describes the epidemiology of IMD in Canada from 2012 to 2019. Case data were obtained from the National Enhanced IMD Surveillance System between January 1, 2012 and December 31, 2019. Isolates were sent to the National Microbiology Laboratory for confirmation of serogroup and further studies including phenotype and clonal complex identification. A total of 983 cases of IMD were reported between 2012 and 2019. Overall, the age-adjusted incidence of IMD from 2012 to 2019 was 0.34 cases per 100,000 population per year when standardized to the Canadian 2011 population age distribution (95% CI: 0.32-0.36). Infants younger than one year of age had the highest average age-specific incidence rate (3.6 cases per 100,000 population per year, 95% CI: 2.8-4.3). The highest age-adjusted incidence rate was associated with serogroup B (0.17 cases per 100, 000 population per year, 95% CI: 0.16-0.19). Prior to 2015, most invasive serogroup W isolates were identified as clonal complex 22 (ST-22 CC) and the increase in serogroup W in Canada in recent years has been associated with the replacement of the endemic ST-22 CC with the hyper-virulent ST-11 CC. Invasive meningococcal disease is a rare but severe infection in Canada that mostly affects the very young. Serogroup B continues to account for the greatest proportion of disease. Serogroup W associated with ST-11 CC is becoming a growing contributor of disease in all age groups not protected by serogroup W-containing vaccines.

Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Neisseria meningitidis Strains and Their Predicted Coverage by the 4CMenB Vaccine.

The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%).IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.

Estimated susceptibility of Canadian meningococcal B isolates to a meningococcal serogroup B vaccine (MenB-FHbp)

BackgroundInvasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) remains a health risk in Canada and globally. Two MenB vaccines are now approved for use. An understanding of the genotype of Canadian strains and the potential strain coverage conferred by the MenB-FHbp vaccine is needed to inform immunization policies. MethodsSerogroup B Neisseria meningitidis strains responsible for meningococcal disease in Canada from 2006 to 2012 were collected as part of the Canadian Immunization Monitoring Program Active surveillance network. Genotypic analysis was done on MenB isolates from 2006 to 2012 with determination of fHbp surface expression for a subset of isolates: those occurring from 2010 to 2012. ResultsTwo clonal complexes (cc269 and cc41/44) were observed in 68.8% of the 276 isolates. A total of 50 different fHbp peptides were identified among isolates from 2006 to 2012. Surface expression of fHbp was detected on 95% of MenB isolates from 2010 to 2012 and 91% of isolates expressed fHbp at levels that are predicted to be susceptible to the bactericidal immune response elicited by the MenB-FHbp vaccine. Some regional differences were observed, particularly in isolates from British Columbia and Quebec. ConclusionThe majority of MenB isolates responsible for meningococcal disease in Canada expressed fHbp at levels predicted to be sufficient for complement mediated bactericidal activity in the presence of MenB-FHbp induced serum antibodies.

Epidemiology and Control of Meningococcal Disease in Canada: A Long, Complex, and Unfinished Story.

The epidemiology of meningococcal disease in Canada has been punctuated by outbreaks caused by serogroup A strains in the 1940s, virulent serogroup C clones from 1985 to 2001, a serogroup B clone in Quebec from 2003 to 2014, and more recently a W clone in British Columbia. Region- and province-wide immunization campaigns have been implemented to control these outbreaks using meningococcal C polysaccharide and conjugate vaccines, a quadrivalent ACWY conjugate vaccine, and a serogroup B protein-based vaccine. Meningococcal C conjugate vaccines have been included in routine immunization programs for children, and ACWY conjugate vaccines have been included in school-based programs for adolescents in most jurisdictions. In contrast, serogroup B protein-based vaccines were only recommended and used for high-risk individuals and to control outbreaks. Currently, the immunization schedules adopted in provinces and territories are not uniform. This is not explained by notable epidemiologic differences. Publicly funded immunization programs are the result of a complex decision-making process. Political factors including public opinion, media attention, interest groups' advocacy campaigns, decision-makers' priorities and budgetary constraints have played important roles in shaping meningococcal programs in Canada, and this should be recognized. As the recent occurrence of outbreaks caused by virulent W clones shows, continued investments in epidemiological surveillance at both the provincial and national levels are necessary, so there can be early warning and informed decisions can be made.

Increase in ST-11 serogroup W Neisseria meningitidis invasive meningococcal disease in Canada, 2016-2018.

Many countries have experienced increases in invasive meningococcal disease (IMD) due to a serogroup W Neisseria meningitidis (MenW) strain of the multilocus sequence type (ST)-11 clonal complex (CC). MenW ST-11 was first reported in Ontario, Canada, in 2014. By 2016, this strain caused IMD in five provinces and was responsible for 18.8% of the IMD cases in Canada. To provide an update on invasive MenW disease in Canada including the strain characteristics, specimen source of isolates, age, sex and geographic distribution of cases. N. meningitidis from culture-positive IMD cases are routinely submitted to the National Microbiology Laboratory (NML) for serogroup, serotype, serosubtype and sequence type analysis. The data from January 1, 2016 to December 31, 2018 were analyzed by calculating the proportion of IMD cases caused by MenW compared with other serogroups. In addition, trends based on age, sex and geographic distribution of cases and specimen source of isolates were analyzed based on information on specimen requisition forms. Over the 3-year period, 292 individual IMD case isolates were analyzed. The percentage of IMD case isolates typed as MenW more than doubled from 19% (n=15) to 44% (n=51) in 2018 when MenW became the most common serogroup, exceeded the number of MenB, MenC or MenY. In total, 93 MenW case isolates were identified, 91% (n=85) belonged to the ST-11 CC. The increase in MenW affected all age groups (but was most common in those older than 60) and both sexes, and occurred across the country but most prevalent in western Canada. The most common specimen source was blood. In 2018, MenW was the most common serogroup for isolates received by the NML from culture-positive IMD cases in Canada. Over 90% of the MenW serogroup isolates belonged to the ST-11 CC. The quadrivalent ACWY meningococcal conjugate vaccine protects against IMD caused by strains in the A, C, W or Y serogroups and therefore may protect against IMD caused by the new MenW ST-11 strain; however, more research is needed. The emergence of variant strains highlight the importance of strain characterization in IMD surveillance and research.

Increase in ST-11 serogroup W Neisseria meningitidis invasive meningococcal disease in Canada, 2016–2018

Increase in ST-11 serogroup W Neisseria meningitidis invasive meningococcal disease in Canada, 2016–2018

Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease

ObjectivesThis study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. MethodsWhole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. ResultsWhole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. ConclusionsThe current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada.

Enhanced surveillance of invasive meningococcal disease in Canada, 2006-2011.

The purpose of this report is to describe the epidemiology of invasive meningococcal disease (IMD) in Canada from 2006 to 2011. Data from the Enhanced Invasive Meningococcal Disease Surveillance System and national population estimates were selected for descriptive and inferential analyses. The geographic, demographic, seasonal and subtype distributions as well as clinical characteristics of the IMD cases were examined. Incidence and mortality rates were calculated per 100,000 population per year; 95% confidence intervals (CI) were calculated for rate comparison. The direct method was used for age standardization. Proportions were compared using the chi-squared test at a p<0.05 significance level. During the study period, the mean incidence rates of IMD were 0.58 (total), 0.33 (serogroup B), 0.07 (serogroup C), 0.03 (serogroup W-135) and 0.10 (serogroup Y). The median age for serogroups B, C, W-135 and Y was 16, 43, 38 and 47 years respectively. The mean age-specific incidence rates among infants under 1 year of age (7.35, CI: 5.38-9.32) and children from 1 to 4 years of age (1.89, CI: 1.54-2.24) were significantly higher than those in any other age group. The mean case fatality ratio was 8.1% (range 4.3%-14.3%). The average number of cases that occurred per month was significantly higher (p<0.0001) in winter (18 cases) than in summer (12 cases). IMD is still endemic in Canada. Although individuals at any age can be affected, infants under 1 year of age are at the greatest risk, followed by children aged 1-4 years and individuals aged 15-19 years. Following the implementation of routine childhood immunization programs with monovalent meningococcal C conjugate vaccines (MenC) in all provinces and territories (beginning in 2007), the incidence of serogroup C has decreased significantly over the study period and is now at an all-time low. Serogroup B is the leading cause of IMD, and diseases of serogroup W-135 and Y have stabilized at relatively lower incidence rates. With the addition of immunization programs using quadrivalent conjugate meningococcal vaccines (MCV4), we would expect further reductions in the incidence of meningococcal infection in Canada.

Enhanced surveillance of invasive meningococcal disease in Canada, 2006-2011

Enhanced surveillance of invasive meningococcal disease in Canada, 2006-2011

Immunization for meningococcal serogroup B: What does the practitioner need to know?

Most invasive meningococcal disease in Canada is now caused by serogroup B organisms. A vaccine directed against this serogroup (4CMenB) is newly licensed in Canada. A decision will need to be made by all provinces and territories regarding whether a routine infant immunization program is warranted. This decision will need to take into account factors such as uncertain estimates for the effectiveness of the vaccine, the high incidence of fever from the vaccine and the burden of introducing more injections into the current immunization schedule, and consider them against the potentially preventable mortality and morbidity that result from a rare but very serious disease.

The Disease Burden of Invasive Meningococcal Serogroup B Disease in Canada

Invasive meningococcal disease remains a rare but deadly infection in Canada. New serogroup B vaccines may offer the potential for prevention and control. This report examines the disease burden caused by serogroup B invasive meningococcal infections. From 2002 to 2011, active, population-based metropolitan area surveillance for adult and pediatric hospital admissions for adult and pediatric hospital admissions for laboratory-confirmed infection with Neisseria meningitidis, was conducted by the 12 centers of the Canadian Immunization Monitoring Program, Active. A total of 769 invasive meningococcal cases occurred from 2002 to 2011; 54% (n = 413) in children with a peak incidence of 6.16 (95% confidence interval: 3.18-10.76) per 100,000 in children aged <1 year in 2009. Serogroup B accounted for the largest proportion of cases and had the highest incidence of all serogroups across all ages, with a peak incidence of 0.31 (0.23-0.40) per 100,000 in 2007. Serogroup B case fatality rate was 4.3% in children, and 21% of pediatric survivors had sequelae. B:17:P1.19 ST-269 was the most frequently detected antigenic type. Serogroup B invasive meningococcal infections caused substantial morbidity and mortality and are the leading cause of invasive meningococcal disease in Canada. The proportion of cases potentially preventable with the new serogroup B vaccines should be evaluated to determine whether universal immunization programs are warranted.

From genes to vaccine: A breakthrough in the prevention of meningococcal group B disease

Although safe and effective vaccines exist for meningococcal serogroups A, C, W-135 and Y, no vaccine is available for routine use against disease caused by serogroup B (MenB). Consequently, MenB is now the most common cause of invasive meningococcal disease in Canada. MenB causes more than 80% of invasive meningococcal disease in infants and can occur at any age. The mortality and morbidity rates related to this disease are very high. Vaccine development against MenB has been hampered by the fact that MenB polysaccharide is not immunogenic in humans. Although vaccines derived from the outer membrane vesicle have been effective in controlling MenB outbreaks, such vaccines protect against the outbreak strain only. A new vaccine development strategy, reverse vaccinology, has led to the identification of genes coding for surface-exposed proteins, which are able to induce bactericidal antibodies against a broad range of MenB strains. A new vaccine containing a combination of these proteins has been tested in different age groups, in several clinical trials. The data available provide hope that control of MenB through routine vaccination will soon be possible.

Vaccinating adolescents against meningococcal disease in Canada: A cost-effectiveness analysis

One dose of serogroup C meningococcal conjugate vaccine (MCV-C) at 12 months of age is the most common immunization schedule in Canada, but immunity may wane over time. To assess the cost-effectiveness of a booster dose at 12 years of age with either MCV-C or a quadrivalent ACYW135 meningococcal conjugate vaccine (MCV-4). A simulation model for assessing both the direct and indirect effects of vaccination was developed. Age- and serogroup-specific incidence and fatality rates were derived from Canadian surveillance data. Vaccine efficacy was estimated from data from the U.K. and Spain, assuming an age-dependent decline of vaccine efficacy over time. Expected vaccine coverage rates were 90% at 12 months, and 70% at 12 years. Herd immunity was modeled using UK data. Vaccine purchase price per dose was $23 for MCV-C and $70 for MCV-4. Costs and health outcomes were discounted at 3% per year. Results, expressed in 2004 Canadian $ and from a societal perspective, were presented for a steady state situation and a population of 1 million. Under the "no vaccination" base scenario, 5.7 cases of vaccine-preventable meningococcal disease would occur each year. Vaccination at 12 months using MCV-C would reduce the burden of disease by 32%. Adding MCV-C at 12 years of age would reduce the number of cases by 55% at no marginal cost, while using MCV-4 would result in a disease reduction of 78% for a marginal cost of $31000 per QALY gained. Comparing MCV-4 with MCV-C as a booster dose, the incremental cost-effectiveness ratio would be $113000 per QALY. The efficacy of C-MCV vaccination at 12 months and the differential price between the two vaccines were the parameters having the strongest impact on the cost/QALY ratios. Any increase in the incidence of serogroup Y will improve the marginal cost-effectiveness ratio associated with MCV-4. Adolescent revaccination would be beneficial. Using C-MCV would be the most cost-effective option, while using MCV-4 would be more effective but would also require more investment.

Increase in Serogroup C Meningococcal Disease in Canada Is Associated with Antigenic Changes in the Protein Antigens of the ET‐15 Clone ofNeisseria meningitidis

Increase in Serogroup C Meningococcal Disease in Canada Is Associated with Antigenic Changes in the Protein Antigens of the ET‐15 Clone of<i>Neisseria meningitidis</i>

Potential Capsule Switching from Serogroup Y to B: The Characterization of Three such Neisseria meningitidis Isolates Causing Invasive Meningococcal Disease in Canada

Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST) 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

Should university students be vaccinated against meningococcal disease in Canada?

To evaluate the benefit and costs of vaccination of university students against invasive meningococcal disease (IMD) in Canada. Published studies were reviewed and a simulation model was used. IMD risk seems to be of low magnitude, but consequences can be dramatic. Over a 10-year period, IMD risk reduction would be slightly greater using a monovalent C conjugate vaccine than a quadrivalent polysaccharide vaccine. From a societal perspective, costs per quality-adjusted life-years gained would be between $135,000 and $698,000, according to epidemiological scenarios and with vaccine purchase prices between $35 and $50 per dose. Economic indices exceed proposed criteria for cost effective public health programs, but from the perspective of students and parents, the cost of vaccination might be worth the benefit.

Characterization of Neisseria meningitidis strains isolated from invasive meningococcal disease cases in Canada in 2001.

With the recent introduction of polysaccharide-protein conjugated vaccines for the control of serogroup C meningococcal disease and the emergence of different variants of serogroup C meningococci, it is likely the epidemiology of meningococcal disease in many countries may be affected. We have therefore analysed and reported the characteristics of Neisseria meningitidis strains collected in 2001 from the Canadian surveillance program on invasive meningococcal disease. Only strains collected from normally sterile clinical sites of patients were studied. Of the 289 isolates obtained from individual patients, 173 (59.9%) were serogroup C, 76 (26.3%) were serogroup B, 30 (10.4%) were serogroup Y, and 10 (3.5%) were serogroup W135. Ninety-six percent of the serogroup C isolates belonged to the ET-15 clone, with an additional 2.3% belonging to other electrophoretic types within the ET-37 clonal complex. Different antigenic variants of the endemic serogroup C ET-15 clone were responsible for localized outbreaks in different parts of the country. One novel variant with the antigenic composition of C:2a:P1.1,7 was reported in two provinces, Quebec and Ontario. Eighteen percent of the meningococci isolated from patients in Ontario belonged to serogroup Y, compared with only 8% in the rest of Canada. The current data highlight the importance of strain characterization by serogroup, serotype, and serosubtype antigens in providing useful information for the surveillance of meningococcal disease in Canada.

Distribution of serogroups of Neisseria meningitidis and antigenic characterization of serogroup Y meningococci in Canada, January 1, 1999 to June 30, 2001.

The relative frequency of serogroups of Neisseria meningitidis associated with meningococcal disease in Canada during the period January 1, 1999 to June 30, 2001 was examined. Of the 552 strains of N meningitidis collected from clinical specimens of normally sterile sites, 191 (34.6%), 276 (50.0%), 61 (11.1%) and 23 (4.2%) were identified by serological and molecular methods as serogroups B, C, Y and W135, respectively. About half (50.8%) of the serogroup Y isolates were isolated in the province of Ontario. The two most common serotypes found were 2c and 14. Most of the serogroup Y strains isolated from patients in Ontario were serotype 2c, while serotype 14 was the most common serotype associated with disease in the province of Quebec. The two most common serosubtypes found among the serogroup Y meningococci were P1.5 and P1.2,5. Laboratory findings, based on antigenic analysis, did not suggest that these serogroup Y strains arise by capsule switching from serogroups B and C strains. This study documented a higher incidence of finding serogroup Y meningococci in clinical specimens from patients in Ontario compared to the rest of Canada, and parallels the increase in serogroup Y meningococcal disease reported in some parts of the United States.

The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis

The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis