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Serogroups and strains differ by location, although hypervirulent strains were identified throughout the country.

We describe the epidemiology of invasive meningococcal disease in South Africa from August 1999 through July 2002, as reported to a laboratory-based surveillance system. Neisseria meningitidis isolates were further characterized. In total, 854 cases of laboratory-confirmed disease were reported, with an annual incidence rate of 0.64/100,000 population. Incidence was highest in infants <1 year of age. Serogroup B caused 41% of cases; serogroup A, 23%; serogroup Y, 21%; serogroup C, 8%; and serogroup W135, 5%. Serogroup B was the predominant serogroup in Western Cape Province, and disease rates remained stable. Serogroup A was most prevalent in Gauteng Province and increased over the 3 years. On pulsed-field gel electrophoresis analysis, serogroup A strains showed clonality, and serogroup B demonstrated considerable diversity. Selected isolates of serogroup A belonged to sequence type (ST)-1 (subgroup I/II) complex, serogroup B to ST-32/electrophoretic type (ET)-5 complex, and serogroup W135 to ST-11/ET-37 complex.

This study was performed to determine the incidence and serogroups of meningococcal disease in the Korean Army. From August 2000 to July 2001, we identified prospective cases in the Korean Army. Meningococcal disease was confirmed by isolation of Neisseria meningitidis or detection of its antigen by latex agglutination from cerebrospinal fluid (CSF) or blood. Polymerase chain reactions (PCRs) were performed in the crgA gene to identify N. meningitidis regardless of its serogroup, and then in orf-2 (serogroup A) and siaD (serogroups B, C, Y, and W135) respectively for serogroup prediction. During the study period, twelve patients (four meningitis and eight septicaemia) were identified. The annual incidence was 2.2 per 100,000 (95% confidence interval, 1.3-3.8) among 550,000 private soldiers. Latex agglutinations were positive to A/C/Y/W135 polyvalent latex, but not to B latex in all patients. PCRs of crgA gene were positive in ten patients, whose samples (2 isolates from CSF, 2 CSFs, and 6 sera) were stored. In PCRs for serogroup prediction, one isolate was serogroup A, and one isolate and two sera were serogroup C. The need for meningococcal vaccination would be considered in the Korean Army through the cost-benefit analysis based on the result of this study.

An outbreak of serogroup W-135 meningococcal disease occurred during the 2000 Hajj in Saudi Arabia. Disease was reported worldwide in Hajj pilgrims and their close contacts; however, most cases were identified in Saudi Arabia. Trends in Saudi meningococcal disease were evaluated and the epidemiology of Saudi cases from this outbreak described. Saudi national meningococcal disease incidence data for 1990 to 2000 were reviewed; cases from January 24 to June 5, 2000 were retrospectively reviewed. The 2000 Hajj outbreak consisted of distinct serogroup A and serogroup W-135 outbreaks. Of 253 identified cases in Saudi Arabia, 161 (64%) had serogroup identification; serogroups W-135 and A caused 93 (37%) and 60 (24%) cases with attack rates of 9 and 6 cases per 100,000 population, respectively. The 2000 Hajj outbreak was the first large serogroup W-135 meningococcal disease outbreak identified worldwide. Enhanced surveillance for serogroup W-135, especially in Africa, is essential to control this emerging epidemic disease.

Background

In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD) in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination.

Methodology

IMD cases reported to the provincial notifiable disease registry in 1991–2011 and isolates submitted for laboratory surveillance in 1997–2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST) by using multilocus sequence typing (MLST) were performed.

Results

Yearly overall IMD incidence rates ranged from 2.2–2.3/100,000 in 1991–1992 to 0.49/100,000 in 1999–2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997–2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups.

Conclusion

Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in guiding public policy decisions.

Background

The epidemiology of meningococcal disease in Mozambique and other African countries located outside the “meningitis belt” remains widely unknown. With the event of upcoming vaccines microbiological and epidemiological information is urgently needed.

Methods

Prospective surveillance for invasive bacterial infections was conducted at the Manhiça District hospital (rural Mozambique) among hospitalized children below 15 years of age. Available Neisseria meningitidis isolates were serogrouped and characterized by Multilocus Sequence Typing (MLST). Antibiotic resistance was also determined.

Results

Between 1998 and 2008, sixty-three cases of confirmed meningococcal disease (36 meningitis, 26 sepsis and 1 conjunctivitis) were identified among hospitalized children. The average incidence rate of meningococcal disease was 11.6/100,000 (8/100,000 for meningitis and 3.7/100,000 for meningococcemia, respectively). There was a significant rise on the number of meningococcal disease cases in 2005–2006 that was sustained till the end of the surveillance period. Serogroup was determined for 43 of the 63 meningococcal disease cases: 38 serogroup W-135, 3 serogroup A and 2 serogroup Y. ST-11 was the most predominant sequence type and strongly associated with serogroup W-135. Two of the three serogroup A isolates were ST-1, and both serogroup Y isolates were ST-175. N. meningitidis remained highly susceptible to all antibiotics used for treatment in the country, although the presence of isolates presenting intermediate resistance to penicillin advocates for continued surveillance.

Conclusions

Our data show a high rate of meningococcal disease in Manhiça, Mozambique, mainly caused by serogroup W-135 ST-11 strains, and advocates for the implementation of a vaccination strategy covering serogroup W-135 meningococci in the country.

During periods of endemic meningococcal disease, serogroup B Neisseria meningitidis is responsible for a significant percentage of invasive diseases, and no particular clone or strain predominates (F. E. Ashton and D. A. Caugant, Can. J. Microbiol. 47: 293-289, 2001), However, in the winter of 2004 to 2005, a cluster of serogroup B meningococcal disease occurred in one region in the province of Québec, Canada. The N. meningitidis strain responsible for this cluster of cases was identified as sequence type ST-269 with the antigenic formula B:17:P1.19. Retrospective analysis of isolates from 2000 onwards showed that this clone first emerged in the province of Québec in 2003. The emergence of this clone of serogroup B meningococci occurred after a mass vaccination against serogroup C N. meningitidis, suggesting possible capsule replacement.

An emerging serogroup B clone can be prevented by vaccines.

Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.

Background

Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern.

Methods

Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs).

Results

Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones.

Conclusion

Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001–2002.

In the era after the introduction of the meningococcal serogroup C conjugate vaccine, from 1 January 2003 to 31 December 2010, serogroup B meningococci were the major cause of invasive meningococcal disease in the province of Québec, Canada, being responsible for 72% of all meningococcal disease cases. Of the 334 invasive serogroup B Neisseria meningitidis strains analyzed, 53.9% belonged to the ST-269 clonal complex (CC). Since it first emerged in 2003, the percentage of invasive serogroup B isolates that belonged to the ST-269 CC had increased from 35% in 2003 to 76% in 2010. Among the 180 meningococci in the ST-269 CC, 91.7% belonged to a single ST (ST-269). The most common PorA genotypes identified in the ST-269 CC were (i) VR1 19-1, VR2 15-11, VR3 36 (84%) and (ii) VR1 18-7, VR2 9, VR3 35-1 (9%). Cases of invasive disease due to the ST-269 CC were commonly found in those aged 11 to 19 years (30.5%) and 20 to 40 years (25.5%). Meningococci of the ST-269 CC were uncommon in other Canadian provinces. In contrast to the ST-269 CC, invasive serogroup B meningococci that belonged to the ST-41/44 CC were much more diverse genetically. However, one ST (ST-571), which is uncommon in the United States, accounted for 35% of all cases due to this CC. The current finding suggests that the ST-269 clone may indeed represent an emerging hypervirulent clone of meningococci.

Neisseria meningitidis is a leading cause of bacterial meningitis and other serious infections worldwide. The epidemiology of N. meningitidis is highly changeable, with major changes in disease incidence and serogroup distribution. Six serogroups are responsible for most meningococcal disease worldwide, namely serogroups, A, B, C, W-135, X, and Y; the epidemiology of disease caused by each serogroup is unique. No vaccine is available for endemic disease caused by serogroup B strains. Two tetravalent (A/C/Y/W-135) meningococcal vaccines are licensed in the United States, a purified polysaccharide product and a polysaccharide–protein conjugate vaccine. The conjugate vaccine is recommended for all adolescents, although vaccine coverage remains low, and other high risk groups. A comprehensive program to prevent invasive meningococcal disease in the US will require immunization of infants; several conjugate vaccines for infants may become available in the near future. Broadly protective vaccines for endemic serogroup B disease are also needed.

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 μg/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Peni). Peni meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Peni was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P = 0.02). Pulsed-field gel electrophoresis grouped 63/82 Peni isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Peni isolates was not different from that of penicillin-susceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Peni isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Peni meningococcal isolates from sub-Saharan Africa.

Study of the epidemiologic trends in meningococcal disease is important in understanding infection dynamics and developing timely and appropriate public health interventions. We studied surveillance data from the New York City Department of Health and Mental Hygiene, which showed that during 1989–2000 a decrease occurred in both the proportion of patients with serogroup B infection (from 28% to 13% of reported cases; p<0.01) and the rate of serogroup B infection (from 0.25/100,000 to 0.08/100,000; p<0.01). We also noted an increased proportion (from 3% to 39%; p<0.01) and rate of serogroup Y infection (from 0.02/100,000 to 0.23/100,000; p<0.01). Median patient age increased (from 15 to 30 years; p<0.01). The case-fatality rate for the period was 17%. As more effective meningococcal vaccines become available, recommendations for their use in nonepidemic settings should consider current epidemiologic trends, particularly changes in age and serogroup distribution of meningococcal infections.

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN  =  0.0033 and average πS  =  0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease.

Meningococcal disease is characterized by cyclic fluctuations in incidence, serogroup distribution, and antigenic profiles. In greater São Paulo, Brazil, there has been a constant increase in the incidence of serogroup C meningococcal disease since the late 1980s. To gain an understanding of changes in serogroup C meningococcal disease over three decades in greater São Paulo, Brazil, 1,059 invasive Neisseria meningitidis serogroup C isolates from 1976 and 2005 were analyzed. Three major clone complexes, sequence type (ST)-11, ST-8, and ST-103, were identified by multilocus sequence typing, and the isolates were characterized by serotyping and 16S rRNA typing. During the 30-year period, there were two major antigenic replacements: from 2a:P1.(5,2) to 2b:P1.3 and subsequently to 23:P1.14-6. All strains of clone ST-103 were characterized as serotype 23 and serosubtype P1.14-6. The origin of 23:P1.14-6 ST-103 complex strains is unknown, but efforts are needed to monitor its spread and define its virulence. The antigenic replacements we observed likely represent a mechanism to sustain meningococcal disease in the population as immunity to circulating strains accumulated.

Invasive meningococcal disease occurs worldwide causing an estimated 50,000–135,000 deaths each year in addition to significant sequelae. In developed countries the disease is usually sporadic but outbreaks and epidemics, usually due to serogroups B and C, have occurred. In the US, an increasing number of cases are due to serogroup Y. In developing nations, epidemics due to serogroups A and more recently W-135, are common. The tetravalent meningococcal conjugate vaccine to serogroups A, C, Y, and W-135 (MCV4) has been demonstrated to be highly immunogenic and promote immune memory. This article will describe the rationale for the vaccine and its potential role to significantly decrease mortality and morbidity of meningococcal disease in those areas and populations at greatest risk from these serogroups.

SUMMARY

Meningococcal disease is mostly endemic in Latin America, with periodic occurrences of outbreaks and epidemics over the last few decades. This literature review summarizes the available epidemiological data for this region between 1945 and 2010. Incidence rates and serogroup distribution differ from country to country and over time. Serogroups A, B, and C have all been major causes of meningococcal disease since the 1970s. In the last decade serogroups W135 and Y may now be emerging in certain countries, with serogroup A virtually disappearing. Although progress has been made in improving and coordinating the surveillance of invasive disease, the uniformity and quality of reported data reflect the fact that the current surveillance systems focus on passive rather than active reporting, hence the reliability of data may vary between countries. Consideration of vaccination policies to control meningococcal disease can only be made with a sufficient understanding of the changing epidemiology in the region.

A bivalent factor H binding protein (fHBP) vaccine for the prevention of disease caused by Neisseria meningitidis serogroup B is currently in clinical development. Since fHBP is also expressed by other meningococcal serogroups, antifHBP antibodies may have bactericidal activity against meningococci independent of serogroup. To begin examining the susceptibility of other meningococcal serogroups to anti-fHBP antibodies, meningococcal serogroup C invasive isolates (n = 116) were collected from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) sites during 2000–2001. These isolates were analyzed for the presence of the fhbp gene. All serogroup C isolates contained the gene, and sequence analysis grouped the proteins into two subfamilies, A and B. Flow cytometry analysis demonstrated that fHBP was expressed on the surface of ∼70% of isolates in vitro with varying levels of expression. fHBP was accessible to antibodies on the cell surface even in the presence of the polysaccharide capsule. Nine isolates from different geographic regions were identified which harboured an identical single nucleotide deletion that could result in a truncated subfamily B fHBP. Analysis by flow cytometry using a polyclonal fHBP antibody preparation revealed that a subpopulation of each of these isolates expressed fHBP. rabbit and non-human primate immune sera generated with bivalent fHBP vaccine were tested for bactericidal activity against a panel of diverse serogroup C clinical isolates using human complement. Sera from both species demonstrated serum bactericidal antibody activity against the serogroup C isolates tested. These promising findings suggest that a bivalent fHBP vaccine may be capable of providing protection against meningococcal disease caused by both serogroup C and B.

Meningococcal disease occurs worldwide with incidence rates varying from 1 to 1000 cases per 100,000. The causative organism, Neisseria meningitidis, is an obligate commensal of humans, which normally colonizes the mucosa of the upper respiratory tract without causing invasive disease, a phenomenon known as carriage. Studies using molecular methods have demonstrated the extensive genetic diversity of meningocococci isolated from carriers, in contrast to a limited number of genetic types, known as the hyperinvasive lineages, associated with invasive disease. Population and evolutionary models that invoke positive selection can be used to resolve the apparent paradox of virulent lineages persisting during the global spread of a non-clonal and normally commensal bacterium. The application of insights gained from studies of meningococcal population biology and evolution is important in understanding the spread of disease, as well as in vaccine development and implementation, especially with regard to the challenge of producing comprehensive vaccines based on sub-capsular antigens and measuring their effectiveness.

An analysis of 219 confirmed cases of bacterial meningitis among Navajo Indians during a 5-year period, July 1, 1968, through June 30, 1973, revealed that 56 percent were caused by Haemophilus influenzae, 26 percent by Neisseria meningitidis, 6 percent by Mycobacterium tuberculosis, and 6 percent by other organisms. The annual incidence of H. influenzae meningitis (17.7 per 100,000 persons) and that of pneumococcal meningitis (8.0 per 100,000) were much higher than the rates for these diseases reported from other population groups. The annual incidence of meningococcal meningitis (2.0 per 100,000) was similar to that found elsewhere. There was an ususual concentration of cases during the first year of life; 78 percent of H. influenzae, 64 percent of pneumococcal, and 50 percent of meningococcal meningitis occurred during this time. However, bacterial meningitis during the first month of life was not frequent (0.29 per 1,000 live births). Case fatality rates were similar to those reported for other population groups.

Complement deficiency has been associated with increased susceptibility to meningococcal disease. In order to determine whether special meningococcal strains caused disease in complement-deficient (CD) patients, 17 Neisseria meningitidis strains recovered from patients in the Western Cape Province, South Africa, known to be CD were compared with 124 routine isolates obtained from patients living in the same area. Serogrouping of the strains from the CD subjects revealed that the common serogroups, particularly serogroup B, predominated. However, the prevalence of rare serogroups among isolates from CD subjects was significantly higher than that found among isolates from the control group. Sero- and subtyping of the class 1 and class 2 or 3 outer membrane proteins showed no significant difference between isolates from CD subjects and the routine clinical isolates. Multilocus enzyme electrophoresis of the 141 isolates revealed six clusters of electrophoretic types (ETs) and two unrelated ETs. The same degree of genetic diversity existed in ETs of isolates from CD subjects and the control group. However, the ET-5 complex, which is known to be associated with epidemic disease, was found in 22 (18%) of the routine clinical isolates but in none of the isolates from the CD subjects. This difference was marginally significant. What was highly significant was the finding that 8 of the 17 isolates from CD subjects were in one ET cluster, cluster F, which comprised a total of 20 isolates. Thus, our results show a difference in the clonal compositions of the strains that infect CD subjects in comparison with the clonal compositions of those that cause clinical infections in the population at large.

Background

Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age.

Methods

We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.

Results

For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20%; (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation.

Conclusions

With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide.

In South Africa, serogroup B meningococcal disease is sporadic. The aim of this study was to characterize serogroup B strains causing invasive meningococcal disease (IMD) in South Africa from 2005 to 2008. Isolates, collected through a national, laboratory-based surveillance program for IMD, were characterized by multilocus sequence typing (MLST). Two thousand two hundred thirty-four cases were reported, of which 1,447 had viable isolates. Intermediate resistance to penicillin was observed in 2.8% (41/1,447) of all strains. Serogroup B was the second most common serogroup (17%, 251/1,447) and increased from 14% (58/414) in 2005 to 25% (72/290) in 2008 (P < 0.001); however, incidence remained stable during the study period (average incidence, 0.13/100,000 population) (P = 0.54). Serogroup B was predominantly characterized by three clonal complexes, namely, ST-41/44/lineage 3, ST-32/ET-5, and the new complex ST-4240/6688, which accounted for 27% (65/242), 23% (55/242), and 16% (38/242) of isolates, respectively. ST-4240/6688 was more prevalent among young children (<5 years) than other clonal complexes (27/37 [73%] versus 108/196 [55%]; P = 0.04). In the most densely populated province of South Africa, Gauteng, the prevalence of ST-32/ET-5 increased from 8% (2/24) in 2005 to 38% (9/24) in 2008 (P = 0.04). Capsular switching was observed in 8/242 (3%) strains. The newly assigned clonal complex ST-4240/6688 was more common in young children.

Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, −63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.

INTRODUCTION

Serogroup A Neisseria meningitidis has repeatedly caused epidemics of invasive meningococcal disease (IMD) in developing nations since the 1960s. The present study is the first detailed study of serogroup A bacteria isolated in Canada.

METHODS

Thirty-four serogroup A meningococcal isolates collected from individuals with IMD in Canada between 1979 and 2006 were characterized by serology and multilocus sequence typing of seven housekeeping enzyme genes and genes encoding three outer membrane protein antigens.

RESULTS

Isolates were assigned to either the sequence type (ST)-1 or the ST-5 clonal complex. Clones within the ST-1 complex were recovered between 1979 and 1992, while clones of the ST-5 complex were isolated between 1987 and 2006; respectively, they accounted for 70.6% and 29.4% of all isolates studied. Isolates of the ST-1 complex were characterized by serosubtype antigen P1.3 or P1.3,6 with PorB allele 60 (serotype 4) and FetA sequence F5-1, while isolates of the ST-5 complex were characterized by serosubtype antigen P1.9 with PorB allele 47 (also serotype 4) and FetA sequence F3-1.

CONCLUSIONS

The Canadian serogroup A IMD isolates likely originated in travellers returning from hyperendemic or epidemic areas of the globe where serogroup A bacteria circulate. Although the Canadian cases of serogroup A IMD were caused by clones known to have caused epidemics in developing countries, disease incidence remained low in Canada.

The human bacterial pathogen Neisseria meningitidis remains a serious worldwide health threat, but progress is being made toward the control of meningococcal infections. This review summarizes current knowledge of the global epidemiology and the pathophysiology of meningococcal disease, as well as recent advances in prevention by new vaccines. Meningococcal disease patterns and incidence can vary dramatically, both geographically and over time in populations, influenced by differences in invasive meningococcal capsular serogroups and specific genotypes designated as ST clonal complexes. Serogroup A (ST-5, ST-7), B (ST-41/44, ST-32, ST-18, ST-269, ST-8, ST-35), C (ST-11), Y (ST-23, ST-167), W-135 (ST-11) and X (ST-181) meningococci currently cause almost all invasive disease. Serogroups B, C, and Y are responsible for the majority of cases in Europe, the Americas, and Oceania; serogroup A has been associated with the highest incidence (up to 1000 per 100,000 cases) and large outbreaks of meningococcal disease in sub-Saharan Africa and previously Asia; and serogroups W-135 and X have emerged to cause major disease outbreaks in sub-Saharan Africa. Significant declines in meningococcal disease have occurred in the last decade in many developed countries. In part, the decline is related to the introduction of new meningococcal vaccines. Serogroup C polysaccharide-protein conjugate vaccines were introduced over a decade ago, first in the UK in a mass vaccination campaign, and are now widely used; multivalent meningococcal conjugate vaccines containing serogroups A, C, W-135, and/or Y were first used for adolescents in the US in 2005 and have now expanded indications for infants and young children, and a new serogroup A conjugate vaccine has recently been introduced in sub-Saharan Africa. The effectiveness of these conjugate vaccines has been enhanced by the prevention of person-to-person transmission and herd immunity. In addition, progress has been made in serogroup B-specific vaccines based on conserved proteins and outer membrane vesicles. However, continued global surveillance is essential in understanding and predicting the dynamic changes in the epidemiology and biological basis of meningococcal disease and to influence the recommendations for current and future vaccines or other prevention strategies.