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Bacterial nonhydrolyzing UDP-N-acetylglucosamine 2-epimerases catalyze the reversible interconversion of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmannosamine (UDP-ManNAc). UDP-ManNAc is an important intermediate in the biosynthesis of certain cell-surface polysaccharides, including those in some pathogenic bacteria, such as Neisseria meningitidis and Streptococcus pneumoniae. Many of these epimerases are allosterically regulated by UDP-GlcNAc, which binds adjacent to the active site and is required to initiate UDP-ManNAc epimerization. Here, two crystal structures of UDP-N-acetylglucosamine 2-epimerase from Neisseria meningitidis serogroup A (NmSacA) are presented. One crystal structure is of the substrate-free enzyme, while the other structure contains UDP-GlcNAc substrate bound to the active site. Both structures form dimers as seen in similar epimerases, and substrate binding to the active site induces a large conformational change in which two Rossmann-like domains clamp down on the substrate. Unlike other epimerases, NmSacA does not require UDP-GlcNAc to instigate the epimerization of UDP-ManNAc, although UDP-GlcNAc was found to enhance the rate of epimerization. In spite of the conservation of residues involved in binding the allosteric UDP-GlcNAc observed in similar UDP-GlcNAc 2-epimerases, the structures presented here do not contain UDP-GlcNAc bound in the allosteric site. These structural results provide additional insight into the mechanism and regulation of this critical enzyme and improve the structural understanding of the ability of NmSacA to epimerize modified substrates.

The aim of the present study was to evaluate the prevalence of serogroup A of Pasteurella multocida in Syrian Awassi sheep. Of 1630 samples collected from nasal swabs of healthy and pneumonic sheep (125 herds) and pneumonic sheep lungs, a total of 228 (13.9%) strains were isolated and identified as P. multocida subsp. multocida by phenotypic and biochemical characterisation. However, of them only 117 (51.3%) were identified as serogroup A of P. multocida when PCR assay with specific primers for serogroup A strains was applied. The highest rate of serogroup A isolation was from ap-parently healthy sheep (49.6%) with consideration that all lung isolates (23 isolates) belonged to se-rogroup A. Geographical and seasonal distribution showed that about 60% of positively isolated bac-teria originated from Syrian desert (29 isolates) and central parts of semi-arid step zone (41 isolates). A significant increase (P≤0.05) in the rate of positive isolates was observed in winter as compared to spring. Pathogenicity tests of 10 isolates with 50 or 10 LD50 values showed that 5 isolates were able to induce symptoms of fowl cholera in challenge-exposed chickens indicating that migratory Awassi sheep might serve as a carrier for serogroup A of P. multocida and that ovine isolates may be virulent for local breed of chickens.

Introduction: Neisseria meningitides is the leading cause of meningitis in the African Meningitis Belt. The objective of this study was to conduct a trend analysis of the burden of meningococcal meningitis in the African Meningitis Belt countries from 2009 to 2014. Methods: secondary data on incidence and death cases were collected from the World Health Organization (WHO) and analyzed to determine the trends of meningitis in the African Meningitis Belt countries using Microsoft excel and Stata 14. Results: these data show unstable meningococcal meningitis outbreaks in the Meningitis Belt before and after the introduction of meningococcal A vaccine (MenAfriVac). The vaccine was introduced at different times in the different countries. E.g. it was introduced in 2010 across Burkina Faso, Mali and Niger while it was introduced from 2011 to 2016 in other countries through mass campaigns. Ever since the vaccine was introduced, there has been a decrease in the number of cases in the countries hence a reduction in the burden of the disease. Conclusion: after the introduction of the MenAfriVac, there has been a decline in the meningitis cases in Benin, Burkina Faso, Chad, Ghana, Niger and Nigeria while Sudan shows a decrease only in 2014. [ABSTRACT FROM AUTHOR]

For well over 100 years, meningococcal disease due to serogroup A Neisseria meningitidis (MenA) has caused severe epidemics globally, especially in the meningitis belt of sub-Saharan Africa. The article reviews the background and identification of MenA, the global and molecular epidemiology of MenA, and the outbreaks of MenA in the African meningitis belt. The implementation (2010) of an equitable MenA polysaccharide-protein conjugate vaccine (PsA-TT, MenAfriVac) and the strategy to control MenA in sub-Saharan Africa is described. The development of a novel multi-serogroup meningococcal conjugate vaccine (NmCV-5) that includes serogroup A is highlighted. The PubMed database (1996–2019) was searched for studies relating to MenA outbreaks, vaccine, and immunization strategies; and the Neisseria PubMLST database of 1755 MenA isolates (1915–2019) was reviewed. Using strategies from the successful MenAfriVac campaign, expanded collaborative partnerships were built to develop a novel, low-cost multivalent component meningococcal vaccine that includes MenA. This vaccine promises greater sustainability and is directed toward global control of meningococcal disease in the African meningitidis belt and beyond. The new WHO global roadmap addresses the continuing problem of bacterial meningitis, including meningococcal vaccine prevention, and provides a framework for further reducing the devastation of MenA. [ABSTRACT FROM AUTHOR]

Background In Burkina Faso, serogroup A meningococcal (NmA) conjugate vaccine (PsA-TT, MenAfriVac) was introduced through a mass campaign in children and adults in December 2010. Similar to a serological survey in 2011, we followed population-level antibody persistence for 5 years after the campaign and estimated time of return to previously-published pre-vaccination levels. Methods We conducted 2 cross-sectional surveys in 2013 and early 2016, including representative samples (N = 600) of the general population of Bobo-Dioulasso, Burkina Faso. Serum bactericidal antibody titers (rabbit complement) were measured against NmA reference strain F8236 (SBA-ref), NmA strain 3125 (SBA-3125), and NmA–specific immunoglobulin G (IgG) concentrations. Results During the 2016 survey, in different age groups between 6 and 29 years, the relative changes in geometric means compared to 2011 values were greater among younger age groups. They were between -87% and -43% for SBA-ref; -99% and -78% for SBA-3125; and -89% and -63% for IgG. In linear extrapolation of age-specific geometric means from 2013 to 2016, among children aged 1 – 4 years at the time of the PsA-TT campaign, a return to pre-vaccination levels should be expected after 12, 8, and 6 years, respectively, according to SBA-ref, SBA-3125, and IgG. Among older individuals, complete return to baseline is expected at the earliest after 11 years (SBA-ref and SBA-3125) or 9 years (IgG). Conclusions Based on SBA-3125, a booster campaign after 8 years would be required to sustain direct immune protection for children aged 1–4 years during the PsA-TT campaign. Antibodies persisted longer in older age groups. [ABSTRACT FROM AUTHOR]

In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.

The introduction of a serogroup A meningococcal conjugate vaccine in the African meningitis belt has been a remarkable success. Meningitis due to the serogroup A meningococcus, previously responsible for most epidemics, has fallen by 99% in vaccinated countries. Success must, however, not distract from the continuing burden of meningitis in this region of Africa. The number of all meningitis epidemics at health district level has fallen by 60% following vaccination, but epidemics due to other meningococcal serogroups continue and may be increasing. The introduction of low cost multivalent conjugate vaccines must be given high public health priority.

Meningococcal disease is a major public health problem and immunization is considered the best strategy for prevention. The introduction of meningococcal C conjugate immunization schedules that targeted adolescents, with catch-up programs in several European countries, Australia and Canada proved to be highly effective, with dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals. Meningococcal quadrivalent (A, C, W, Y) conjugate vaccines are now licensed and are being used in adolescent programs in North America and to control serogroup W disease in South America. In the African meningitis belt, a mass immunization campaign against serogroup A disease using a meningococcal A conjugate vaccine is now controlling the devastating epidemics of meningococcal disease. After introducing new immunization programs, it is of importance to maintain enhanced surveillance for a better understanding of the changing nature of disease epidemiology. This information is crucial for identifying optimal immunization policies. [ABSTRACT FROM AUTHOR]

A quadrivalent meningococcal serogroup A, C, W and Y conjugate vaccine (ACWY), utilising tetanus toxoid (TT) as its carrier protein (ACWY-TT; Nimenrix™, GlaxoSmithKline Vaccines, Rixensart, Belgium) has been demonstrated to be safe and immunogenic when administered to young children from 12 months of age, older children, adolescents, and adults. Administration of a single dose of ACWY-TT induces protective serum bactericidal antibodies against all four serogroups as well as good antibody persistence. Coadministration studies have demonstrated that ACWY-TT can be administered with diphtheria, tetanus, three-component acellular pertussis, hepatitis B, inactivated polio virus and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-HBV/Hib, Infanrix™ hexa; GlaxoSmithKline Vaccines, Rixensart, Belgium); measles, mumps, rubella, varicella vaccine (Priorix-Tetra™; GlaxoSmithKline Vaccines, Rixensart, Belgium); 10-valent pneumococcal conjugate vaccine (Synflorix; GlaxoSmithKline Vaccines, Rixensart, Belgium); hepatitis A and B vaccine (Twinrix; GlaxoSmithKline Vaccines, Rixensart, Belgium); and seasonal influenza vaccine (Fluarix™; GlaxoSmithKline Vaccines, Rixensart, Belgium). Studies in young infants from 2 months of age have now commenced but immunisation with a single dose of ACWY-TT from 12 months of age is a safe and immunogenic option in the prevention of meningococcal disease. [ABSTRACT FROM AUTHOR]

The epidemiology of bacterial meningitis will change with introduction of meningococcal and pneumococcal conjugate vaccines in the African meningitis belt. The principal objectives of surveillance are to evaluate the impact of vaccination, to detect and investigate epidemics and provide material for research. The capacity of existing surveillance activities in the meningitis belt to meet these objectives varies due to infrastructural and financial constraints. Impact assessment of conjugate vaccine against meningococcal serogroup A will be limited to comparing incidence trends from a few surveillance sites with data obtained before vaccine introduction and to comparing trends in the incidence of suspected cases or localised epidemics in most other settings. The timeliness of detection of epidemics and identification of epidemic meningococcal serogroups could be improved in most countries by analysing suspected case data in health centre level resolution and by investigating outbreaks with mobile teams. For research and impact assessment of pneumococcal conjugate vaccines, several surveillance sites covering at least 0.5 million inhabitants should be maintained which undertake exhaustive case finding and systematic laboratory confirmation of meningitis and pneumonia. Molecular diagnostics will facilitate surveillance in remote areas, but the available techniques should be evaluated for diagnostic performance in the field and long-term sustainability. [ABSTRACT FROM AUTHOR]

Abstract: This study compares the immunogenicity and safety of a single dose of a new meningococcal A conjugate vaccine (PsA-TT, MenAfriVac™, Serum Institute of India Ltd., Pune) against the meningococcal group A component of a licensed quadrivalent meningococcal polysaccharide vaccine (PsACWY, Mencevax ACWY ®, GSK, Belgium) 28 days after vaccination in Indian children. This double-blind, randomized, controlled study included 340 Indian children aged 2–10 years enrolled from August to October 2007; 169 children received a dose of PsA-TT while 171 children received a dose of PsACWY. Intention-to-treat analysis showed that 95.2% of children in PsA-TT group had a ≥4-fold response in serum bactericidal titers (rSBA) 28 days post vaccination as compared to 78.2% in the PsACWY group. A significantly higher rSBA GMT (11,209, 95%CI 9708–12,942) was noted in the PsA-TT group when compared to PsACWY group (2838, 95%CI 2368–3401). Almost all children in both vaccine groups had a ≥4-fold response in group A-specific IgG concentration but the IgG GMC was significantly greater in the PsA-TT group (89.1μg/ml, 95%CI 75.5–105.0) when compared to the PsACWY group (15.3μg/ml, 95%CI 12.3–19.2). Local and systemic reactions during the 4 days after immunization were similar for both vaccine groups except for tenderness (30.2% in PsA-TT group vs 12.3% in PsACWY group). None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children. [Copyright &y& Elsevier]

Abstract: Prior to the introduction of the MenAfriVac™ serogroup A glycoconjugate vaccine in September 2010, serogroup A was the major epidemic disease-causing meningococcal serogroup in the African meningitis belt. However, recently serogroup X meningococcal (MenX) disease has received increased attention because of outbreaks recorded in this region, with increased endemic levels of MenX disease over the past 2 years. Whereas polysaccharide–protein conjugate vaccines against meningococcal serogroups A, C, W and Y (MenA, MenC, MenW, MenY) are on the market, a vaccine able to protect against MenX has never been achieved. The structure of serogroup A, C, W and Y meningococcal polysaccharides has been already fully elucidated by NMR. MenX capsular polysaccharide (MenX CPS) structure is also documented but fewer characterization data have been published. We have applied here 1H NMR, 31P NMR and HPLC to evaluate the stability of MenX CPS in aqueous solution as compared to MenA capsular polysaccharide (MenA CPS). The stability study demonstrated that MenA CPS is more susceptible to hydrolytic degradation than MenX CPS. The different stereochemistry of the N-acetyl group at position C2 of mannosamine (MenA CPS) and glucosamine (MenX CPS) respectively might play a fundamental role in this susceptibility to polysaccharide chain degradation. The satisfactory stability of MenX CPS predicts the possibility that a stable fully-liquid MenX polysaccharide or glycoconjugate vaccine could be developed. [Copyright &y& Elsevier]

Neisseria meningitidis serogroup  A accounted for 95% of cases of meningococcal disease in China during the last century. To understand the circulation of these organisms in China over a 50-year period, 275 serogroup  A meningococcal isolates collected between 1956 and 2005 were characterised by multilocus sequence typing (MLST) and PorA typing. In total, 44 sequence types (STs), belonging to five hyperinvasive lineages, and ten singletons were identified in this collection. The ST-5 complex and the ST-1 complex represented 52.8% (86/163) and 44.2% (72/163), respectively, of isolates from cases of infection and, overall, 93.1% (256/275) of all isolates. Three prevalent clones (ST-5, P1.5-2,10; ST-3, P1.7-1,10; and ST-5, P1.20,9) were involved in four national epidemics in 1959, 1967, 1977 and 1984. ST-5 was replaced by ST-7 in the late 1980s, such that ST-7 isolates with P1.20,9 represented >86% of isolates from cases of infection after 2000. The data also revealed that the collection contained 19 PorA VR types, of which P1.7-1,10 and P1.20,9 were the predominant types in the ST-1 and ST-5 common lineages, respectively. Three other hyperinvasive lineages (ST-11 complex, ST-32 complex and ST-4821 complex) were isolated only from carriers. It was concluded that serogroup  A meningococci of the ST-5 complex and the ST-1 complex were responsible for most cases of meningococcal disease in China during the past 50 years. [ABSTRACT FROM AUTHOR]

Abstract: Neisseria meningitidis bacteria of serogroup A are causing recurring meningitis epidemics on the African continent. An outer membrane vesicle (OMV) vaccine against serogroup A meningococci made from a subgroup III serogroup A meningococcal strain was previously shown to induce antibodies with serum bactericidal activity (SBA) in mice. We have here further investigated the properties of OMV vaccines made from five different subgroup III serogroup A meningococcal strains grown in a synthetic medium with low iron content. In addition to the major outer membrane proteins (PorA, PorB, RmpM, Opa and OpcA), small amounts of the NadA, TdfH, Omp85, FetA, FbpA and NspA outer membrane proteins, as well as lipooligosaccharides, were detected in the vaccines. The OMV vaccines were used to immunise mice. Anti-meningococcal IgG antibodies in the mouse sera were analysed by immunoblotting and by enzyme-linked immunosorbent assay against OMVs, and against live meningococcal cells in SBA and a flow-cytometric assay. The vaccines induced antibodies with high SBA and opsonophagocytic activity. The strongest IgG responses were directed against PorA. Significant SBA responses were also observed against a subgroup III strain, which did not express PorA, whereas no SBA was observed against a clone IV-1 serogroup A strain. An OMV vaccine from serogroup A meningococci may be an alternative to polysaccharide and conjugate polysaccharide vaccines for Africa. [Copyright &y& Elsevier]

Serogroup A Neisseria meningitidis organisms of the subgroup III have caused epidemics of meningitis in sub-Saharan Africa since their introduction into the continent in 1987. The population structure of these bacteria is basically clonal, and these meningococci are strikingly similar in their major outer membrane antigens PorA and PorB. Protein-based vaccines might be an alternative to prevent epidemics caused by these meningococci; thus, we developed an outer membrane vesicle (OMV) vaccine from a serogroup A meningococcal strain of subgroup III. The serogroup A OMV vaccine was highly immunogenic in mice and elicited significant bactericidal activity towards several other serogroup A meningococci of subgroup III. The IgG antibodies generated were in immunoblot shown to be mainly directed towards the PorA outer membrane protein. The results presented demonstrate the potential of an OMV vaccine as an optional strategy to protect against meningococcal disease caused by serogroup A in Africa. [Copyright &y& Elsevier]

In response to an increase in the incidence in invasive meningococcal disease (IMD) due to Neisseria meningitidis, a system of hospital- and laboratory-based surveillance was used in a prospective epidemiological and clinical assessment of IMD in children 0–13 years of age hospitalized in the Athens area between 1 January 1999 and 31 December 2000. The annual incidence of laboratory-confirmed disease was 10.2/100 000. Serogroup B strains were predominant. There was a sharp decrease in serogroup C from 19% of cases in 1999 to 3% in 2000 (P=0.013). Of note was the emergence of serogroup A responsible for 7% of the cases. The overall case fatality rate was 4.5%, but 2.8% for microbiologically confirmed cases. A remarkable decrease in disease severity assessed by admissions to intensive care units was noted during the second study year. Polymerase chain reaction-based methods for detection of meningococcal DNA were the sole positive laboratory test in 45% of the cases and the only test on which serogroup determination was based in 52% of groupable cases. The epidemiological and clinical profile of meningococcal disease appears to be rapidly evolving and close monitoring is required particularly for input into decisions regarding use of meningococcal vaccines. [Copyright &y& Elsevier]

To describe Neisseria meningitidis strains in the African meningitis belt in 2003, we obtained 2,389 oropharyngeal swabs at 5 monthly visits in a representative population sample (age range 4–29 years) in Bobo-Dioulasso, Burkina Faso. A total of 152 carriage isolates were grouped, serotyped, and genotyped. Most isolates were NG:NT:NST sequence type (ST) 192 (63% of all N. meningitidis), followed by W135:2a:P1.5,2 of ST-11 (16%) and NG:15:P1.6 of ST-198 (12%). We also found ST-2881 (W135:NT:P1.5,2), ST-751 (X:NT:P1.5), and ST-4375 (Y:14:P1.5,2) but not serogroups A or C. Estimated average duration of carriage was 30 days (95% confidence interval 24–36 days). In the context of endemic group W135 and meningococcal A disease, we found substantial diversity in strains carried, including all strains currently involved in meningitis in this population, except for serogroup A. These findings show the need for large samples and a longitudinal design for N. meningitidis serogroup A carriage studies.

Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in Africa. The capsular polysaccharide is the main virulence factor and the target antigen for polysaccharide- and conjugate vaccines. Three tetravalent conjugate vaccines against serogroups A, C, Y and W have been licensed and the monovalent MenAfriVac® was introduced to address the high burden of serogroup A disease in the Meningitis Belt of sub-Saharan Africa. Three of these four vaccines are lyophilized due to the instability of the serogroup A antigen (MenA) in aqueous solution, resulting in a two vial presentation with concomitant additional costs for storage and distribution. Replacement of the saccharide ring oxygen with a methylene group is a promising approach to preparing a stable oligosaccharide MenA analogue (Carba-MenA) vaccine suitable for a liquid formulation. However, to be effective, Carba-MenA must elicit an immune response that is cross-reactive to the native MenA. Here we employ microsecond molecular dynamics simulations of ten repeats of MenA and Carba-MenA to establish that there are significant differences in the conformation and dynamics of these antigens in solution. Carba-MenA has a more random extended, conformation than MenA; MenA has a significant population of compact S-bend conformations that are absent in the analogue. We also find that the disaccharides are poor models of the conformational behaviour of longer chains. This information is relevant for the rational design of optimal analogues for conjugate vaccines. Image 1 • MenA and Carba-MenA molecular dynamics simulations show conformational differences. • Carba-MenA analogue has more random and extended conformations than MenA. • Compact S-bend conformations of MenA are absent in the analogue. • Disaccharides are poor models of the conformation of longer chains. • Modeling can provide information for the design of optimal vaccines. [ABSTRACT FROM AUTHOR]

The main approach to controlling epidemics of meningococcal meningitis in the African meningitis belt has been reactive vaccination campaigns with serogroup A polysaccharide vaccine once the outbreak reached an incidence threshold. Early reactive vaccination is effective in reducingmorbidity and mortality. A recent paper in International Health has shown that earlier reactive vaccination campaigns may be even more effective than increasing the coverage area of vaccination. Monovalent serogroup A conjugate vaccine programs have recently been launched to prevent transmission in endemic areas in the African meningitis belt. Conjugate vaccines can induce immunological memory and have impact on pharyngeal carriage. However, reactive vaccination still has a role to play taking into account the dynamic changes in the epidemiology of meningitis in this area. [ABSTRACT FROM AUTHOR]

Background Epidemics of meningococcal meningitis occur periodically in the African ‘meningitis belt’ and are mainly, but not only, due to serogroup A. Methods We tested a dipstick as a rapid detection test (RDT) to detect serogroup A using 401 cerebrospinal fluid (CSF) samples. Results The detection limits were 105 CFU/ml with sensitivity and specificity for detecting serogroup A in CSF samples of 88% and 99%, respectively. Conclusions The new RDT can be used in field surveillance of meningococcal meningitis to help characterize meningitis cases particularly after introduction of the conjugate vaccine against serogroup A. [ABSTRACT FROM PUBLISHER]

Objectives: The bacterial pathogen Neisseria meningitidis is able to escape the currently available capsule-based vaccines by undergoing capsule switching. In this study, we investigated whether capsule switching has occurred in a recently emerged sequence type (ST) 7 serogroup X isolate in China, for which currently no vaccine is available., Methods: To identify capsule switching breakpoints, the capsule locus and flanking regions of the ST-7 serogroup X isolate and three endemic ST-7 serogroup A isolates were sequenced and compared. To obtain further insight into capsule switching frequency and length of DNA fragments involved, capsule switching assays were performed using genomic DNA containing combinations of antibiotic selection markers at various locations in the capsule locus and flanking regions., Results: Sequence analyses showed that capsule switching has occurred and involved a 8450 bp serogroup X DNA fragment spanning the region from galE to ctrC. Capsule switching assays indicate that capsule switching occurs at a frequency of 6.3 × 10 -6 per bacterium per μg of DNA and predominantly involved DNA fragments of about 8.1-9.6 kb in length., Conclusions: Our results show that capsule switching in N. meningitidis occurs at high frequency and involves recombination in the flanking regions of the capsule biosynthesis genes., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Neisseria meningitidis causes meningococcal disease, often resulting in fulminant meningitis, sepsis, and death. Vaccination programs have been developed to prevent infection of this pathogen, but serogroup replacement is a problem. Capsular switching has been an important survival mechanism for N. meningitidis , allowing the organism to evolve in the present vaccine era. However, related mechanisms have not been completely elucidated. Genetic analysis of capsular switching between diverse serogroups would help further our understanding of this pathogen. In this study, we analyzed the genetic characteristics of the sequence type 7 (ST-7) serogroup X strain that was predicted to arise from ST-7 serogroup A at the genomic level. By comparing the genomic structures and sequences, ST-7 serogroup X was closest to ST-7 serogroup A, whereas eight probable recombination regions, including the capsular gene locus, were identified. This indicated that serogroup X originated from serogroup A by recombination leading to capsular switching. The recombination involved approximately 8,540 bp from the end of the ctrC gene to the middle of the galE gene. There were more recombination regions and strain-specific single-nucleotide polymorphisms in serogroup X than in serogroup A genomes. However, no specific gene was found for each serogroup except those in the capsule gene locus., (Copyright © 2017 American Society for Microbiology.)

Abstract: Analysis of meningococcal strains recovered from outbreaks and epidemics in the African meningitis belt, using molecular methods, has demonstrated for nearly 20 years the dominance among serogroup A organisms of a single clone complex, the sequence type 5 (ST-5) complex. However, a shift was observed since the mid-1990s when ST-5 gradually was replaced by ST-7 in all countries of the region. Since 2001, outbreaks caused by serogroup W135 strains belonging to the ST-11 complex became an additional problem. Monitoring of the clones responsible for meningococcal disease provides important insights on the biology and epidemiology of this most serious pathogen. [Copyright &y& Elsevier]

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.