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1.
Emerg Infect Dis ; 16(3): 465-72, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20202422

ABSTRACT

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.


Subject(s)
Disease Outbreaks/prevention & control , Meningococcal Infections/prevention & control , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/classification , Child , Child, Preschool , Germany/epidemiology , Humans , Incidence , Infant , Meningococcal Infections/microbiology , Neisseria meningitidis/classification , Neisseria meningitidis/genetics , Neisseria meningitidis, Serogroup B/genetics , Netherlands/epidemiology , Serum Bactericidal Test
2.
Infect Immun ; 77(7): 2989-94, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19451248

ABSTRACT

Changing antigenic structure such as with capsule polysaccharide is a common strategy for bacterial pathogens to evade a host immune system. The recent emergence of an invasive W:2a:P1.7-2,4 sequence type 11 (ST-11) strain of Neisseria meningitidis in New Zealand, an uncommon serogroup/serotype in New Zealand disease cases, was investigated for its genetic origins. Molecular typing of 107 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relationships. Results indicated that the W:2a:P1.7-2,4 strain had emerged via capsule switching from a group C strain (C:2a:P1.7-2,4). Neither the upstream nor downstream sites of recombination could be elucidated, but sequence analysis demonstrated that at least 45 kb of DNA was involved in the recombination, including the entire capsule gene cluster. The oatWY gene carried by the W:2a:P1.7-2,4 strain contained the insertion sequence element IS1301, one of five variants of oatWY found in group W135 strains belonging to the carriage-associated ST-22 clonal complex. This suggested that the origin of the capsule genes carried by the invasive W:2a:P1.7-2,4 strain is carriage associated. These results provide novel evidence for the long-standing dogma that disease-associated strains acquire antigenic structure from carriage-associated strains. Moreover, the capsule switch described here has arisen from the exchange of the entire capsule locus.


Subject(s)
Bacterial Capsules/genetics , Bacterial Capsules/immunology , Carrier State/microbiology , Meningococcal Infections/microbiology , Neisseria meningitidis/immunology , Neisseria meningitidis/pathogenicity , Bacterial Typing Techniques , Carrier State/immunology , Cluster Analysis , DNA Fingerprinting , DNA Transposable Elements , DNA, Bacterial/genetics , Genes, Bacterial , Humans , Meningococcal Infections/immunology , Molecular Sequence Data , Multigene Family , Neisseria meningitidis/classification , Neisseria meningitidis/genetics , New Zealand , Polymorphism, Restriction Fragment Length , Recombination, Genetic , Sequence Analysis, DNA , Virulence
3.
Pediatr Infect Dis J ; 28(5): 385-90, 2009 May.
Article in English | MEDLINE | ID: mdl-19384263

ABSTRACT

BACKGROUND: An outer membrane vesicle meningococcal vaccine (MeNZB), was developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7-2,4. METHODS: A phase II, randomized, observer blind, controlled study evaluating the safety, reactogenicity, and immunogenicity of MeNZB administered with routine New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375). Group 1 (n = 250) received 25 mug MeNZB and routine immunizations with a fourth MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine immunizations only. Sero-response was a > or =4-fold rise in vaccine strain serum bactericidal antibody titer compared with baseline or a titer of at least 1:8 for baselines <1:4. Reactogenicity was monitored for 7 days after vaccination. RESULTS: Sero-response in Group 1 was achieved in 53% (95% Confidence interval [CI]: 46-59, n = 239) and 69% (95% CI: 54-80, n = 45) with geometric mean antibody titers of 9 (95% CI: 7-10) and 22 (95% CI: 12-39) after the third and fourth doses, respectively. No negative interference by MeNZB on routine immunizations was detected. There were no serious adverse events judged to be vaccine related. CONCLUSIONS: In this group of New Zealand infants, 4 MeNZB doses were required to demonstrate titers comparable with those achieved after 3 doses in older children. MeNZB was safe when used concomitantly with routine New Zealand immunizations to 5 months of age.


Subject(s)
Bacterial Outer Membrane Proteins/immunology , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/immunology , Antibodies, Bacterial/blood , Drug Administration Schedule , Female , Humans , Immunization Schedule , Infant , Male , Meningitis, Meningococcal/blood , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/immunology , Meningococcal Vaccines/adverse effects , Meningococcal Vaccines/immunology , New Zealand/epidemiology , Single-Blind Method
4.
J Clin Microbiol ; 43(2): 838-42, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15695689

ABSTRACT

Since mid-1991, New Zealand has experienced an epidemic of meningococcal disease. The epidemic has been caused by serogroup B meningococci expressing PorA type P1.7-2,4, belonging to the ST-41/ST-44 complex, lineage III. Most B:P1.7-2,4 meningococci express type 4 PorB (87.0%), although case isolates with porB other than type 4 have been identified throughout the duration of the epidemic. To assess the genetic relatedness of case isolates with an alternative porB gene, multilocus restriction typing validated against multilocus sequence typing was used. This determined that B:P1.7-2,4 meningococci with a porB gene that was other than type 4 had the same clonal origin. It was concluded that strains with alternative porB genes had diverged from the original type 4 porB. Variation in porB was also shown to be associated with the uptake of DNA encoding one or two of the PorB variable regions leading to mosaic porB. Point mutation rather than horizontal transfer and recombination was implicated as the mechanism of sequence variation in some strains. This work will serve as a reference point to determine if the administration of a strain-specific vaccine increases the level of porB divergence and variation already observed in New Zealand case isolates. It also complements the study undertaken of PorA stability which showed that variation in P1.7-2,4 PorA was almost exclusively due to deletions in the P1.4 epitope of the epidemic strain.


Subject(s)
Disease Outbreaks , Genetic Variation , Meningococcal Infections/epidemiology , Neisseria meningitidis, Serogroup B/genetics , Porins/chemistry , Amino Acid Sequence , Humans , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/microbiology , Meningitis, Meningococcal/prevention & control , Meningococcal Infections/microbiology , Meningococcal Infections/prevention & control , Meningococcal Vaccines/administration & dosage , Molecular Sequence Data , Neisseria meningitidis, Serogroup B/classification , Neisseria meningitidis, Serogroup B/immunology , New Zealand/epidemiology , Point Mutation , Polymerase Chain Reaction , Porins/genetics , Sequence Analysis, DNA
5.
J Clin Microbiol ; 42(4): 1731-3, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15071034

ABSTRACT

porB PCR-amplicon restriction endonuclease analysis is a rapid, simple method developed to assess porB variation in nonserotypeable meningococci isolated during New Zealand's epidemic of meningococcal disease. Most nonserotypeable meningococci isolated between 1990 and 1999 inclusively either were type 4 (40.5%) or contained the porB variable region 1 (VR1)-19, VR2-D, VR3-7, and VR4-14a sequences (45.1%).


Subject(s)
DNA Restriction Enzymes/metabolism , Genetic Variation , Neisseria meningitidis/classification , Polymerase Chain Reaction/methods , Porins/genetics , Amino Acid Sequence , Bacterial Typing Techniques , Disease Outbreaks , Humans , Meningococcal Infections/epidemiology , Meningococcal Infections/microbiology , Molecular Sequence Data , Neisseria meningitidis/genetics , New Zealand/epidemiology , Reproducibility of Results , Sequence Analysis, DNA , Serotyping
6.
J Clin Microbiol ; 42(4): 1742-5, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15071037

ABSTRACT

A multilocus restriction typing (MLRT) method was developed to reduce the number of sequencing reactions required to determine the clonal relationships among serogroup B meningococci causing an epidemic in New Zealand. MLRT was a rapid, simple, and inexpensive method, and the results had an excellent correlation with multilocus sequence typing results.


Subject(s)
DNA Restriction Enzymes/metabolism , Disease Outbreaks , Meningococcal Infections/epidemiology , Neisseria meningitidis, Serogroup B/classification , Neisseria meningitidis, Serogroup B/genetics , Sequence Analysis, DNA , Alleles , Bacterial Typing Techniques , Humans , Meningococcal Infections/microbiology , New Zealand/epidemiology , Predictive Value of Tests
7.
Aust N Z J Obstet Gynaecol ; 42(2): 182-6, 2002 May.
Article in English | MEDLINE | ID: mdl-12069147

ABSTRACT

OBJECTIVES: To determine in New Zealand women the prevalence of group B Streptococcus (GBS) carriage late in pregnancy and to identify GBS colonisation risk factors, antibiotic susceptibility and serotype distribution. DESIGN: Prospective, observational study. SETTING: Community and hospital antenatal clinics in Wellington and Auckland during 1998-1999. SAMPLE: Convenience sample of 240 women between 35-37 weeks gestation. METHODS: Sociodemographic data, obstetric details and anogenital swabs were collected from each subject. Swabs were inoculated into selective media. GBS isolates underwent serotyping and antibiotic susceptibility testing. RESULTS: Two hundred and forty women (9% Maori, 11% Pacific) aged 15-41 years were recruited. Fifty-two (22%; 95% CI 17, 27) were colonised by GBS. Carriage was independently associated with younger age (59% < or = 30 years; adjusted OR 3.25; 95% CI 1.53, 6.95) and least social deprivation (57% NZ Dep 96 score +/- 3; adjusted OR 1.22; 95% CI 1.06,1.39). All GBS isolates were penicillin-susceptible, but resistance to clindamycin (15%) and erythromycin (7.5%) was detected and associated with serotype V strains. Predominant serotypes were: III (29%), Ia (21%), Ib (20%) and V (20%). CONCLUSIONS: Approximately 20% of New Zealand women carry GBS late in pregnancy, with young age a major risk factor. Increased risk in the socially advantaged, development of resistance to erythromycin and clindamycin, and emergence of new GBS serotypes are findings with important implications for prevention strategies requiring further confirmation.


Subject(s)
Carrier State/epidemiology , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/epidemiology , Streptococcal Infections/epidemiology , Streptococcus agalactiae/isolation & purification , Adolescent , Adult , Analysis of Variance , Anti-Bacterial Agents/pharmacology , Carrier State/diagnosis , Colony Count, Microbial , Confidence Intervals , Female , Humans , Microbial Sensitivity Tests , New Zealand/epidemiology , Odds Ratio , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Trimester, Third , Prenatal Care , Prevalence , Probability , Prospective Studies , Risk Factors , Sampling Studies , Streptococcal Infections/diagnosis , Streptococcal Infections/transmission , Streptococcus agalactiae/drug effects , Vaginal Smears
8.
Clin Infect Dis ; 34(1): 28-38, 2002 Jan 01.
Article in English | MEDLINE | ID: mdl-11731942

ABSTRACT

Classic M protein serotyping has been invaluable during the past 60 years for the determination of relationships between different group A streptococci (GAS) strains and the varied clinical manifestations inflicted by these organisms worldwide. Nonetheless, during the past 20 years, the difficulties of continued expansion of the serology-based Lancefield classification scheme for GAS have become increasingly apparent. By use of a less demanding sequence-based methodology that closely adheres to previously established strain criteria while being predictive of known M protein serotypes, we recently added types emm94-emm102 to the Lancefield scheme. Continued expansion by the addition of types emm103 to emm124 are now proposed. As with types emm94-emm102, each of these new emm types was represented by multiple independent isolates recovered from serious disease manifestations, each was M protein nontypeable with all typing sera stocks available to international GAS reference laboratories, and each demonstrated antiphagocytic properties in vitro by multiplying in normal human blood.


Subject(s)
Antigens, Bacterial , Bacterial Outer Membrane Proteins/genetics , Carrier Proteins/genetics , Streptococcus pyogenes/classification , DNA, Bacterial/analysis , Humans , Phylogeny , Serologic Tests , Serotyping , Streptococcus pyogenes/genetics , Streptococcus pyogenes/isolation & purification
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