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.Key Words: Meningococcal disease, Neisseria meningitidis, SerogroupsInvasive meningococcal disease (IMD) is a notifiable communicable disease that is monitored by a national surveillance program coordinated by the Division of Disease Surveillance and the Division of Respiratory Diseases, Centre for Infectious Disease Prevention and Control, Health Canada. Starting in 1971 and with the help of provincial public health officials, Health Canada began to collect data on the serogroup information on IMD cases. Also, isolates of meningococci collected from patients are routinely sent to Health Canada''s National Microbiology Laboratory (NML) in Winnipeg for further antigenic and genetic analyses.IMD is a serious disease globally but the serogroups of meningococci causing diseases in various countries may vary in frequency. For example, serogroup A is a major cause of disease in Africa and China (1), while serogroups B and C meningococci are the most frequent cause of IMD in Western countries (2). In Canada, most IMD cases are caused by meningococci belonging to serogroups B, C, Y and W135. Serogroups B and C account for over 75% of the isolates collected from patients (3).In the past decade, Neisseria meningitidis serogroup Y has emerged as a frequent cause of IMD in the United States (4,5). In view of these findings, it is important to monitor the incidence of serogroup Y disease. This report presents the frequency of isolation of serogroups of meningococci in normally sterile clinical specimens collected from patients (likely to be presented as IMD) in various parts of Canada and describes the distribution of serotypes and serosubtypes found among the serogroup Y isolates.     

The changing epidemiology of meningococcal disease in the United States, 1992-1996

New meningococcal vaccines are undergoing clinical trials, and changes in the epidemiologic features of meningococcal disease will affect their use. Active laboratory-based, population-based US surveillance for meningococcal disease during 1992-1996 was used to project that 2400 cases of meningococcal disease occurred annually. Incidence was highest in infants; however, 32% of cases occurred in persons >/=30 years of age. Serogroup C caused 35% of cases; serogroup B, 32%; and serogroup Y, 26%. Increasing age (relative risk [RR], 1.01 per year), having an isolate obtained from blood (RR, 4.5), and serogroup C (RR, 1.6) were associated with increased case fatality. Among serogroup B isolates, the most commonly expressed serosubtype was P1.15; 68% of isolates expressed 1 of the 6 most common serosubtypes. Compared with cases occurring in previous years, recent cases are more likely to be caused by serogroup Y and to occur among older age groups. Ongoing surveillance is necessary to determine the stability of serogroup and serosubtype distribution.     

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.     

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.     

Meningococcal disease: risk for international travellers and vaccine strategies

International travel and migration facilitate the rapid intercontinental spread of meningococcal disease. Serogroup A and, less so serogroup C, have been responsible for epidemics in the past (mainly in Africa). In recent years, W135 has emerged (first in Saudi Arabia, then in West Africa) as a serogroup that requires attention. Serogroups X and Y are infrequent, but associated with slowly rising trends. There are significant variations in the incidence of meningococcal disease and the distribution of serogroups responsible for meningococcal disease, both geographically and with time. Vaccine strategies need to address this variation, and broad coverage against all serogroups for which vaccines are currently available should be offered to travellers. Tetravalent polysaccharide meningococcal vaccines are limited by their poor immunogenicity in small infants and by the lack of long-term protection. In contrast, the novel tetravalent conjugate vaccine that is currently only available in North America is immunogenic in young infants, induces long-term protection and reduces nasopharyngeal carriage. The tetravalent conjugate meningococcal vaccine will be a leap forward in the control of meningococcal epidemics in affected countries. It will also boost the uptake of meningococcal vaccines in travellers because the duration of protection is longer and it eliminates the problem of immune hyporesponsiveness of serogroup C with repeated dosing. Current vaccine recommendations are to vaccinate all Hajj pilgrims, all travellers to areas with current outbreaks, travellers to the SubSaharan meningitis belt, and individuals with certain medical conditions.     

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.Key Words: Capsule switching, Neisseria meningitidis, Serogroup YNeisseria meningitidis is a significant pathogen that causes invasive meningococcal disease (IMD). The average case fatality rate of 9% to 12% remains high despite the availability of effective antibiotics and vaccines (1). Laboratory study and surveillance of N meningitidis involves the characterization of a number of surface markers of the bacterium, including its capsule and outer membrane proteins (OMPs). Most epidemiological studies of meningococcal disease rely on differentiating meningococcal isolates based on their serogroup, serotype and serosubtype. Serogrouping is determined by the demonstration of serologically distinct epitopes present on chemically and structurally different capsules. Serotyping and serosubtyping rely on the detection of distinct epitopes present on three of five different classes of OMPs of N meningitidis. Serotyping epitopes are found on the class 2 or class 3 OMP (also called PorB) of N meningitidis; these OMPs are expressed in a mutually exclusively manner (ie, a strain will only express either a class 2 or class 3 OMP but not both). Serosubtyping epitopes are present on the class 1 OMP (also called PorA). Based on this nomenclature scheme, a strain can therefore be characterized by its antigenic formula; for example, B:15:P1.7,16 refers to serogroup B, serotype 15 and serosubtype P1.7,16.One of the most important virulence factors of meningococci is the capsular polysaccharide antigen, which is also the basis for serogrouping and is the target antigen for the currently licensed vaccines against A, C, Y and W135 organisms. Of the 13 known serogroups, five (serogroups A, B, C, Y and W135) are responsible for most of the meningococcal disease worldwide (2). In North America, most endemic and epidemic strains belong to serogroups B, C, Y and W135 (3,4). Capsules of serogroups B, C, Y and W135 meningococci contain sialic acid, either as a homopolymer of sialic acids assembled by alpha-2,8 linkages (serogroup B) or alpha-2,9 linkages (serogroup C), or as a heteropolymer of sialic acids with glucose (serogroup Y) or galactose (serogroup W135). Besides demonstrating structural similarities, these four serogroups of meningococci also have very similar capsule polysaccharide synthesis (cps) gene loci (5). Because of this similarity, capsule switching has been demonstrated in vivo and in vitro by specific gene replacement within the cps loci between different serogroups. To date, a number of IMD cases have been described in the literature to be caused by organisms in which capsule switching between serogroup B and C meningococci occurred (6-8).In the present paper, the authors describe three unusual serogroup B meningococci isolated from separate IMD cases in Nanaimo, British Columbia, that presented with the OMP antigens 2c:P1.5, characteristic of serogroup Y strains found in Canada (4). This antigenic profile prompted the authors to examine the relationship of these three serogroup B strains with antigenically similar serogroup Y organisms isolated in Canada. The authors describe the characterization of these antigenically similar isolates and postulate that the B:2c:P1.5 isolates arose by capsule switching from serogroup Y organisms.     

Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Emergence of endemic serogroup W135 meningococcal disease associated with a high mortality rate in South Africa.

BACKGROUND: In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (P<.001). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex. CONCLUSIONS: Serogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain.     

Meningococcal disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI)

The Global Meningococcal Initiative (GMI) is a global expert group, including scientists, clinicians and public health officials from a wide range of specialities. The goal of the GMI is to prevent meningococcal disease worldwide through education, research, and co-operation. The Chinese GMI roundtable meeting was held in June 2017. The GMI met with local experts to gain insight into the meningococcal disease burden in China and current prevention and vaccination strategies in place. China experienced five epidemics of serogroup A meningococcal disease (MenA) between 1938 and 1977, with peak incidence of 403/100,000 recorded in 1967. MenA incidence rates have significantly declined following the universal introduction of the MenA polysaccharide vaccine in China in the 1980s. Further, surveillance data indicates changing meningococcal epidemiology in China with the emergence of new clones of serogroup B from serogroup C clonal complex (cc) 4821 due to capsular switching, and the international spread of serogroup W cc11. The importance of carriage and herd protection for controlling meningococcal disease was highlighted with the view to introduce conjugate vaccines and serogroup B vaccines into the national immunization schedule. Improved disease surveillance and standardized laboratory techniques across and within provinces will ensure optimal epidemiological monitoring.     

Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine

The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.     

Trajectory of serogroups causing Invasive Meningococcal Disease in Santa Catarina state,Brazil (2007–2019)

The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.     

Meningococcal disease in Italy

In 1985, nationwide surveillance of meningococcal disease aimed at establishing appropriate guidelines for prophylaxis started in Italy. The incidence of disease was 1.1/100,000 in 1985 and 0.6/100,000 in 1987. This decreasing trend was particularly evident among military recruits (from 17.3/100,000 in 1985 to 5/100,000 in 1987), reflecting the use of bivalent serogroup (A + C) meningococcal polysaccharide vaccine in all new recruits since January 1987. The age distribution of cases was statistically different from that observed during the 1970s (P less than 0.001), with a shift towards older age groups. Men have been in the majority (516 vs. 358, P less than 0.0000001). Group C has been the most common serogroup encountered (72.2%), while only 18% of the isolates belonged to serogroup B. Among military recruits, serogroup C accounted for 92% (81/88) of the cases. The proportion of strains resistant to sulphonamides was 67%, while only 3% strains were resistant to rifampicin and to minocycline. Reduced susceptibility to ampicillin and to penicillin was observed in 3 and 4% strains respectively. Nine secondary cases were all due to failure in the administration of chemoprophylaxis (sulphonamide given in seven cases, prophylaxis not attempted in two cases). Immunisation of all new military recruits and effective chemoprophylaxis of close contacts of cases are the major guidelines provided by the National Meningitis Surveillance Programme.     

Laboratory Biosafety: Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of the current landscape of invasive meningococcal disease in children

BackgroundImmunizations have led to a decrease in the incidence of invasive meningococcal disease (IMD) in Canada, but this infection still leads to significant morbidity and mortality.ObjectivesThe purpose of this study was to determine the burden of illness and management of IMD in paediatric hospitals.MethodsData were collected on all cases of IMD in eight paediatric hospitals from 2013 to 2017.ResultsThere were 17 cases of IMD. Three of eight hospitals had no cases. Just over half of the cases were serogroup B (n=9); a quarter (n=4) were serogroup W; less than a quarter (n=3) were serogroup Y; and one was unknown. Two infected children were not started on antibiotics until day one and day five after the initial blood culture was collected, but had uneventful recoveries. Six cases required admission to intensive care units; two died. Six cases had probable or proven meningitis. Thrombocytopenia was documented in seven cases. All cases had elevated C-reactive protein levels. Seven children received more than seven days of antibiotics; of these seven, only two had complications that justified prolonged therapy (subdural empyema and septic knee). Six cases had a central line placed.ConclusionIMD is now rare in Canadian children, but about one-third of the cases in our study required treatment in the intensive care unit and two died. Clinicians appear to not always be aware that a five to seven-day course is adequate for uncomplicated cases of bacteremia or meningitis.     

Impact of the meningococcal C conjugate vaccine in Spain: an epidemiological and microbiological decision

The new meningococcal C conjugate vaccine became available in Spain and was included in the infant vaccination schedule in 2000. A catch-up campaign was carried out in children under six years of age. As a consequence, the incidence of meningococcal disease caused by serogroup C has fallen sharply during the last three epidemiological years in Spain. The risk of contracting serogroup C disease in 2002/2003 fell by 58% when compared with the season before the conjugate vaccine was introduced. There was also an important decrease in mortality. Three deaths due to serogroup C occurred in the age groups targeted for vaccination in 2002/2003, compared with 30 deaths in the same age groups in the season before the launch of the vaccine campaign. In the catch-up campaign the vaccine coverage reached values above 92%. For the 2001, 2002 and 2003 routine childhood immunisation programme coverage values ranged from 90% to 95%. During the past three years a total of 111 cases of serogroup C disease have been reported in patients in the vaccine target group. Most of the vaccination failures occurred during the epidemiological year 2002/2003. Eight (53%) vaccine failures occurred in children who had been routinely immunised in infancy, and could be related to a lost of protection with time since vaccination. The isolation of several B:2a:P1.5 strains (ST-11 lineage) is noteworthy. These may have their origin in C:2a:P1.5 strains which, after undergoing genetic recombination at the capsular operon level, express serogroup B. These strains could have relevant epidemic potential.     

Meningococcal disease

Due to a high complication and case fatality rate, meningococcal diseases are important health problems both in tropical countries experiencing severe epidemics as well as in countries of moderate climate zones. Worldwide N. meningitidis of sero-groups A, B, and C are predominant and to a lesser extent serogroups W (135) and Y play a role, whereas in Europe more than 90 % of meningococcal diseases are caused by serogroups B and C of N. meningitidis. In Germany and other developed countries the majority of cases occur in very young children and adolescents. Since many years, meningococcal polysaccharide vaccines against diseases due to N.meningitidis serogroup A, C, Y and W (135) are commercially available. Unfortunately, a vaccine against diseases caused by N. meningitidis serogroup B is still under development. The recently developed and licensed conjugated meningococcal vaccines against N. meningitidis serogroup C are also protective against disease in very young children. Eight countries in Western Europe as well as Australia have already established country-wide immunization programs for children and adolescents. Within only 2 to 3 years, well managed programs have achieved far-reaching control of meningococcal C disease in UK and the Netherlands. In Germany, the Advisory Committee on Immunization (STIKO recommends immunization for selected risk groups. The current increase of the percentage of meningococcal C diseases to 28 - 30 % gives reason for further discussion regarding immunization strategies. How-ever, the STIKO expressively declares, that in addition to the recommendation for risk groups, the physician can use all vaccines licensed in Germany without any restriction. It is his/her responsibility to advice the patients regarding immunization possibilities against the life-threatening meningococcal disease, particularly if cases are occurring.     

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province,Italy, December 2019 to January 2020

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.     

Epidemiology of meningococcal disease in Denmark 1980-1988.

Based on epidemiological data of notified cases of meningococcal disease (MD) in Denmark during the period 1980-88 the recommendations for prophylaxis are evaluated. In 1986 the incidence of MD increased about 60% to 5.5 per 100,000 population. The clinical diagnosis of MD was verified by culture of Neisseria meningitidis in 79% of notified cases. About 40% of all patients were less than 4 years of age. The mortality in 1988 was found to be 10%. Serogroup B disease accounted for about 80% of the cases. Two co-primary and 28 secondary cases were registered. Two major outbreaks of serogroup C disease occurred in 1984 and 1986, respectively. In small clusters of 2-3 cases within socially well-defined groups the recommendations for prophylaxis are sufficient. But for the new pattern of clusters spread over months to years in certain geographical areas or open social groups, especially among teenagers, the existing recommendations are insufficient. The occurrence of localized clusters of serogroup B disease emphasises the need for a vaccine against serogroup B disease.     

Invasive haemophilus influenzae and meningococcal infections in Finland. A climatic, epidemiologic and clinical approach

A nationwide epidemiological survey on invasive (blood and/or CSF culture positive) Haemophilus influenzae (HI) and meningococcal infections was performed in Finland in 1976-1980. The mean annual incidence of HI infection was 3.4/100,000 inhabitants (813 cases) vs. 2.0/100,000 (469 cases) of meningococcal infection. HI infections showed no geographical predilection, but meningococcal disease, mainly of group B, was more common in northern than in southern Finland (p less than 0.005). Meningitis accounted for 61% of the HI and 91% of the meningococcal infections. The overall fatality rates were 3.1% and 7.9%, respectively. Children accounted for 94% of the HI and 59% of the meningococcal cases. The overall annual incidence of bacterial meningitis in children (less than 15 years) was 19/100,000; in children less than 5 years it was 52/100,000. HI was the most common (62%) causative agent, followed by meningococci (18%) and pneumococci (5%). The fatality rate was 4%. Major neurological sequelae were found in 5%, minor ones in 16%. It was calculated that 42% of the cases of meningitis could have been prevented by vaccines now available on the market. Vaccines now under field investigation may increase the preventability to about 65%.     

Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci

Objective To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. Methods Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. Results Twenty‐nine studies satisfied the inclusion criteria. Twenty‐five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer‐membrane vaccines on overall and/or serogroup‐specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup‐specific carriage; seven of these focussed on high‐risk groups and had a short follow‐up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer‐membrane protein vaccines showed no effect on carriage. Conclusions A few well‐designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa.