Population genetics and molecular epidemiology of Neisseria meningitidis
WHO Collaborating Centre for Reference and Research on Meningococci, Department of Bacteriology, National Institute of Public Health, Oslo, Norway. Apmis
(Impact Factor: 2.04).
06/1998; 106(5):505-25. DOI: 10.1111/j.1699-0463.1998.tb01379.x
Under non-epidemic conditions, Neisseria meningitidis causes disease primarily in children under the age of 5 and the cases are sporadic without any evident relationship between them. Occasionally, localized outbreaks of meningococcal disease occur, and sometimes epidemic waves of disease may spread to several countries or even continents and constitute a pandemic. In the past 10 years or so, population genetic analyses have provided insights into the biology of the bacterium and the epidemiology of meningococcal disease, improving our understanding of the cause of epidemics. Through the application of molecular methods, and especially multilocus enzyme electrophoresis, to N. meningitidis strains of worldwide origin, it has been possible to identify virulent clones and provide a surveillance system to warn of meningococcal epidemics. The characteristics of the predominant clones which are nowadays causing meningococcal disease in the world are summarized here and the importance of population genetics in interpreting the epidemiological data is illustrated.
Available from: Alejandro Martin
- "The use of molecular typing methods has revolutionized the epidemiological study of N. meningitidis. Approaches such as multilocus enzyme electrophoresis, now replaced by multilocus sequence typing (MLST) (Maiden et al., 1998), have been used to monitor the global distribution and evolution of meningococcal strains (Caugant, 1998; Girard et al., 2006; Caugant, 2008). The discriminatory power of MLST has been enhanced with the inclusion of additional information about the variable regions of PorA, PorB and FetA (Jolley et al., 2007; Urwin et al., 2004), together with pulsed-field gel electrophoresis patterns (Chiou et al., 2006). "
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ABSTRACT: We investigated the population genetics in collections of meningococci sampled in Cuba during the period 1983-2005, thereby covering a period before and after the introduction of an antimeningococcal B-C vaccine. A total of 163 case isolates and 210 isolates from healthy carriers were characterized by multilocus sequence typing (MLST) and sequence determination of porA, porB and fetA genes. A total of 56 sequence types (STs) including 28 new STs were identified among these isolates. The analysis of surface antigens revealed variants 3-1 and 3-8 to be prevalent for porB; variant F5-1 was the most common FetA epitope, and variants 19 and 15 corresponded to the prevalent variable regions 1 (VR1) and VR2 PorA epitopes, respectively. The strongest associations between specific surface protein variants and clonal complexes were detected in lineages ST-32 and ST-53. All ST-32 complex isolates possessed porB3 alleles, and the most frequent antigen combination among ST-32 complex isolates was P1.19,15;F5-1. Variants PorB3-64 at PorB and P1.30 at PorA VR2, in combination with the PorA VR1 variants P1.12-1, P1.7 and P1.7-2 as well as the FetA variants F1-2 and F1-7, dominated the ST-53 complex organisms. Furthermore, we observed a statistically significant association between the most frequent porA, porB and fetA alleles and strain invasiveness. Finally, this study showed that the application of VA-MENGOC-BC((R)), the Cuban antimeningococcal vaccine, reduced the number and frequency of the hypervirulent Clonal Complexes ST-32 and ST-41/44, and also impacted on other lineages. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.
Available from: Paola Stefanelli
- "Despite low carriage rates, ST-11 meningococci continue to be associated with sporadic outbreaks worldwide . These hyper-invasive strains require massive public health investigations and interventions due to the high mortality among cases [19-21]. "
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ABSTRACT: To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005-2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies.
IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), porA VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures.
In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome.
Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005-2007 National Vaccine Plan.
Available from: Martin C J Maiden
- "Despite their high diversity, meningococcal populations are structured into lineages that are identified as clonal complexes (cc) by multilocus sequence typing (MLST) (Maiden et al., 1998). Only a minority of these, the socalled hyperinvasive lineages, are regularly associated with human disease (Caugant, 2001; Maiden et al., 1998; Yazdankhah et al., 2004). The prevalence of these lineages varies geographically and temporally but each complex tends to be associated with a particular repertoire of surface antigens (Urwin et al., 2004). "
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ABSTRACT: A comprehensive meningococcal vaccine is yet to be developed. In the absence of a vaccine that immunizes against the serogroup B capsular polysaccharide, this can only be achieved by targeting subcapsular antigens, and a number of outer-membrane proteins (OMPs) are under consideration as candidates. A major obstacle to the development of such a vaccine is the antigenic diversity of these OMPs, and obtaining population data that accurately identify and catalogue these variants is an important component of vaccine design. The recently proposed meningococcal molecular strain-typing scheme indexes the diversity of two OMPs, PorA and FetA, that are vaccine candidates, as well as the capsule and multilocus sequence type. This scheme was employed to survey 323 meningococci isolated from invasive disease in England and Wales from 1975 to 1995, before the introduction of meningococcal conjugated serogroup C polysaccharide vaccines in 1999. The eight-locus typing scheme provided high typeability (99.4 %) and discrimination (Simpson's diversity index 0.94-0.99). The data showed cycling of meningococcal genotypes and antigenic types in the absence of planned interventions. Notwithstanding high genetic and antigenic diversity, most of the isolates belonged to one of seven clonal complexes, with 11 predominant strain types. Combinations of PorA and FetA, chosen on the basis of their prevalence over time, generated vaccine recipes that included protein variants found in 80 % or more of the disease isolates for this time period. If adequate immune responses can be generated, these results suggest that control of meningococcal disease with relatively simple protein component vaccines may be possible.
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