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1.
Hum Vaccin Immunother ; 20(1): 2378537, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39037011

ABSTRACT

Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.


The most common clinical manifestations of invasive meningococcal disease include meningitis and septicemia, which can be deadly, and many survivors suffer long-term serious after-effects. Most cases of invasive meningococcal disease are caused by six meningococcal serogroups (types), including serogroup B. Although vaccines are available against meningococcal serogroup B infection, these vaccines target antigens that are highly diverse. Consequently, the effectiveness of vaccination may vary from country to country because the meningococcal serogroup B strains circulating in particular regions carry different forms of the target vaccine antigens. This means it is important to test serogroup B strains isolated from specific populations to estimate the percentage of strains that a vaccine is likely to be effective against (known as 'vaccine strain coverage'). The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict strain coverage by the four-component meningococcal serogroup B vaccine, 4CMenB, against large numbers of serogroup B strains. In this study, we analyzed 284 invasive meningococcal serogroup B isolates collected between 2010 and 2014 in Argentina. Genetic analyses showed that the vaccine antigens of the isolates were diverse and some genetic characteristics had not been found in isolates from other countries. However, vaccine strain coverage estimated by gMATS was consistent with that reported in other parts of the world and with strain coverage results obtained for a subset via another method, the human serum bactericidal antibody (hSBA) assay. These results highlight the need for continued monitoring of circulating bacterial strains to assess the estimated strain coverage of meningococcal serogroup B vaccines.


Subject(s)
Antigens, Bacterial , Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup B , Humans , Argentina/epidemiology , Meningococcal Vaccines/immunology , Meningococcal Vaccines/administration & dosage , Meningococcal Infections/microbiology , Meningococcal Infections/prevention & control , Meningococcal Infections/epidemiology , Infant , Adolescent , Child , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Child, Preschool , Young Adult , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Neisseria meningitidis, Serogroup B/immunology , Adult , Female , Male , Whole Genome Sequencing , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Genotype , Adhesins, Bacterial/genetics , Adhesins, Bacterial/immunology , Middle Aged , Porins/genetics , Porins/immunology , Serum Bactericidal Antibody Assay , Aged , Neisseria meningitidis/genetics , Neisseria meningitidis/immunology , Neisseria meningitidis/isolation & purification , Neisseria meningitidis/classification
2.
Am J Case Rep ; 25: e943973, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011557

ABSTRACT

BACKGROUND Meningococcal meningitis is rare in Japan; however, when outbreaks do occur, they predominantly involve domestically infected cases rather than those contracted overseas. CASE REPORT A Japanese man with diabetes in his 50s experienced fever and loss of consciousness, with no history of international travel. In our hospital, gram-negative diplococci were detected in the cerebrospinal fluid (CSF) of the patient by Gram staining, although the rapid agglutination test and cultures of blood and CSF were negative. Multiplex polymerase-chain reaction (PCR) testing returned positive results for meningococcus and parechovirus. Brain MRI revealed a finding of meningitis, but there were no indications of encephalitis. To determine the serotype and genotype, we sent the sample to the National Institute of Infectious Diseases, which identified the serogroup and sequence type (ST) as type B and 2057, respectively. Despite the unknown antimicrobial susceptibility, the patient responded well to empirical treatment with ceftriaxone at 2 g every 12 h, and was discharged with remaining symptoms of dizziness, headache, difficulty hearing in the left ear, and tinnitus in the left ear. CONCLUSIONS In Japan, vaccines covering serogroups A, C, and W/Y are available but not routinely administered. According to epidemiological surveillance reports, serogroup B is the second most common cause of meningococcal meningitis in Japan, yet there is no corresponding vaccine available in the country. This case has prompted a review of the epidemiology of meningococcus in Japan, encompassing strategies for vaccination and hospital infection control to prevent droplet transmission, which includes post-exposure prophylaxis when no prior measures have been implemented.


Subject(s)
Meningitis, Meningococcal , Humans , Male , Middle Aged , Meningitis, Meningococcal/diagnosis , Japan , Neisseria meningitidis, Serogroup B/isolation & purification , Anti-Bacterial Agents/therapeutic use , East Asian People
3.
mSphere ; 9(6): e0022024, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38752729

ABSTRACT

Neisseria meningitidis serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium Neisseria meningitidis (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup B , Whole Genome Sequencing , Humans , Taiwan/epidemiology , Meningococcal Vaccines/immunology , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/classification , Neisseria meningitidis, Serogroup B/isolation & purification , Neisseria meningitidis, Serogroup B/immunology , Infant , Child, Preschool , Child , Adult , Adolescent , Young Adult , Meningococcal Infections/microbiology , Meningococcal Infections/prevention & control , Meningococcal Infections/epidemiology , Phylogeny , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Male , Female , Genotype , Vaccination Coverage/statistics & numerical data
4.
Emerg Infect Dis ; 30(5): 1009-1012, 2024 May.
Article in English | MEDLINE | ID: mdl-38666632

ABSTRACT

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.


Subject(s)
Meningococcal Infections , Neisseria meningitidis, Serogroup B , Humans , England/epidemiology , Aged , Meningococcal Infections/epidemiology , Meningococcal Infections/microbiology , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Male , Aged, 80 and over , Genomics/methods , Female , History, 21st Century , Genome, Bacterial , Middle Aged
5.
Pan Afr Med J ; 47: 56, 2024.
Article in English | MEDLINE | ID: mdl-38646132

ABSTRACT

Introduction: the laboratory diagnosis of meningococcal meningitis relies on conventional techniques. This study aims to evaluate the correlation between the reduced sensitivity to penicillin G of Neisseria meningitidis (N.m) strains and the expression of the altered PBP 2 gene. Methods: out of 190 strains of N.m isolated between 2010 and 2021 at the bacteriology laboratories of Ibn Rochd University Hospital Centre (IR-UHC) in Casablanca and the UHC Mohammed VI in Marrakech, 23 isolates were part of our study. We first determined their state of sensitivity to penicillin G by E-Test strips and searched for the expression of the penA gene by PCR followed by Sanger sequencing. Results: of all the confirmed cases of N.m, 93.15% (n=177) are of serogroup B, 75.2% (n = 143) are sensitive to penicillin G and 24.73% (n = 47) are of intermediate sensitivity. No resistance to penicillin G was observed. Reduced sensitivity to penicillin G in N.m is characterized by mutations namely F504 L, A510 V, I515 V, G541 N and I566 V located in the C-terminal region of the penA gene encoding the penicillin-binding protein 2 (PBP2) (mosaic gene). Conclusion: our study presents useful data for the phenotypic and genotypic monitoring of resistance to penicillin G in N.m and can contribute to the analysis of genetic exchanges between different Neisseria species.


Subject(s)
Anti-Bacterial Agents , Hospitals, University , Meningitis, Meningococcal , Microbial Sensitivity Tests , Neisseria meningitidis , Penicillin G , Morocco , Humans , Anti-Bacterial Agents/pharmacology , Neisseria meningitidis/genetics , Neisseria meningitidis/drug effects , Neisseria meningitidis/isolation & purification , Penicillin G/pharmacology , Meningitis, Meningococcal/microbiology , Meningitis, Meningococcal/drug therapy , Polymerase Chain Reaction , Mutation , Penicillin-Binding Proteins/genetics , Bacterial Proteins/genetics , Penicillin Resistance/genetics , Drug Resistance, Bacterial/genetics , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Neisseria meningitidis, Serogroup B/drug effects
6.
mBio ; 12(3)2021 05 18.
Article in English | MEDLINE | ID: mdl-34006659

ABSTRACT

Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.IMPORTANCE The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact fHbp genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Carrier State/microbiology , Genetic Variation , Meningococcal Infections/microbiology , Neisseria meningitidis, Serogroup B/genetics , Students/statistics & numerical data , Universities , Antigens, Bacterial/classification , Carrier State/epidemiology , Disease Outbreaks , Genotype , Humans , Meningococcal Infections/epidemiology , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/isolation & purification , Serogroup , United States/epidemiology
7.
BMC Infect Dis ; 21(1): 499, 2021 May 29.
Article in English | MEDLINE | ID: mdl-34051739

ABSTRACT

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is associated with various complications. PMA (primary meningococcal arthritis) is a rare meningococcus-associated disease causing arthritis of the knee usually, without any signs of invasive meningococcal disease. No case of PMA in a COVID-19 (coronavirus disease, 2019) patient has yet been described. PMA mainly strikes young adults. PMA is not associated with any immunocompromising condition. It has a better outcome than usual septic arthritis CASE PRESENTATION: Herein, we report an 18-year-old man diagnosed with COVID-19, later admitted with persistent fever, right knee arthralgia and maculopapular rash. Due to family history, psoriasis and Henoch-Schönlein purpura were hypothesized and ruled out. Finally, synovial fluid culture confirmed Neisseria meningitidis serogroup B arthritis without any other symptoms of invasive meningococcal disease. Healing was achieved quickly with surgery and antibiotics. We concluded in a PMA. CONCLUSION: We describe here the first primary meningococcal arthritis in a COVID-19 patient and we hope to shine a light on this rare but serious complication.


Subject(s)
Arthritis, Infectious/diagnosis , COVID-19/complications , Meningococcal Infections/diagnosis , Adolescent , Anti-Bacterial Agents , Arthritis, Infectious/microbiology , Exanthema/microbiology , Humans , Knee Joint/microbiology , Male , Neisseria meningitidis, Serogroup B/isolation & purification , Synovial Fluid/microbiology
8.
Int J Infect Dis ; 104: 189-197, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33227521

ABSTRACT

OBJECTIVE: This narrative review considers the epidemiology of invasive meningococcal disease (IMD) in North Africa and the adequacy of current preventive measures to provide guidance for future vaccination strategies. METHODS: Literature searches were conducted using PubMed for articles published from 1998 onwards to identify publications on IMD in North Africa. Additional relevant articles not included within the search results and data sources were identified from the reference lists of identified publications, authors' personal files, and publicly available government or regional surveillance data. RESULTS: Although IMD is an endemic and notifiable disease in several North African countries, inadequacies exist regarding each country's surveillance, vaccination strategies, and disease understanding. Studies showed bacterial meningitis in North Africa caused by Neisseria meningitidis mostly affects young children (aged <5 years), with meningococcal serogroup B (MenB) being the most frequently identified serotype. Importantly, MenB isolates were genetically heterogeneous. Serogroup A incidence and meningococcal outbreaks decreased over time in Morocco and Egypt, possibly because of their nationwide or school-based vaccination programs. Within the region, meningococcal vaccines are only included in the national immunization program of Egypt. CONCLUSIONS: Improving IMD diagnosis and surveillance would provide a reliable estimate of IMD burden, leading to better vaccination strategies.


Subject(s)
Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Meningococcal Vaccines/therapeutic use , Vaccination/methods , Adolescent , Africa, Northern/epidemiology , Aged , Child , Child, Preschool , Disease Outbreaks , Egypt/epidemiology , Female , Humans , Immunization Programs/methods , Incidence , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/prevention & control , Morocco/epidemiology , Neisseria meningitidis/genetics , Neisseria meningitidis/isolation & purification , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Serogroup
9.
Infect Immun ; 88(12)2020 11 16.
Article in English | MEDLINE | ID: mdl-32958529

ABSTRACT

Factor H binding protein (FHbp) is an important Neisseria meningitidis virulence factor that binds a negative regulator of the alternative complement pathway, human factor H (FH). Binding of FH increases meningococcal resistance to complement-mediated killing. FHbp also is reported to prevent interaction of the antimicrobial peptide (AMP) LL-37 with the meningococcal surface and meningococcal killing. FHbp is a target of two licensed group B-directed meningococcal (MenB) vaccines. We found a new FHbp variant, peptide allele identification no. 896 (ID 896), was highly expressed by an emerging meningococcal pathotype, the nonencapsulated urethritis clade (US_NmUC). This clade has been responsible for outbreaks of urethritis in multiple U.S. cities since 2015, other mucosal infections, and cases of invasive meningococcal disease. FHbp ID 896 is a member of the variant group 1 (subfamily B), bound protective anti-FHbp monoclonal antibodies, bound high levels of human FH, and enhanced the resistance of the clade to complement-mediated killing in low levels of human complement likely present at human mucosal surfaces. Interestingly, expression of FHbp ID 896 resulted in augmented killing of the clade by LL-37. FHbp ID 896 of the clade was recognized by antibodies elicited by FHbp in MenB vaccines.


Subject(s)
Antigens, Bacterial/metabolism , Bacterial Proteins/metabolism , Meningitis, Meningococcal/immunology , Meningococcal Vaccines/immunology , Neisseria meningitidis/metabolism , Urethritis/immunology , Urethritis/microbiology , Amino Acid Sequence , Antigens, Bacterial/chemistry , Antigens, Bacterial/genetics , Antimicrobial Cationic Peptides/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Cell Survival/genetics , Complement Factor H/immunology , Databases, Genetic , Genomics , Humans , Meningococcal Infections , Neisseria meningitidis/genetics , Neisseria meningitidis/immunology , Neisseria meningitidis/pathogenicity , Neisseria meningitidis, Serogroup B/immunology , Neisseria meningitidis, Serogroup B/isolation & purification , Phylogeny , Protein Binding , Sequence Alignment , Cathelicidins
11.
mSphere ; 5(2)2020 03 04.
Article in English | MEDLINE | ID: mdl-32132156

ABSTRACT

The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%).IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.


Subject(s)
Genetic Variation , Meningococcal Infections/epidemiology , Meningococcal Vaccines/analysis , Neisseria meningitidis, Serogroup B/genetics , Adolescent , Adult , Aged , Canada/epidemiology , Child , Child, Preschool , Colony Count, Microbial , DNA, Bacterial/genetics , Epidemiological Monitoring , Genotype , Humans , Infant , Middle Aged , Neisseria meningitidis, Serogroup B/isolation & purification , Serogroup , Young Adult
13.
N Engl J Med ; 382(4): 318-327, 2020 01 23.
Article in English | MEDLINE | ID: mdl-31971677

ABSTRACT

BACKGROUND: The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. METHODS: We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline. RESULTS: A total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P = 0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified. CONCLUSIONS: Among Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT03089086.).


Subject(s)
Carrier State/prevention & control , Meningococcal Infections/prevention & control , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/isolation & purification , Neisseria meningitidis/isolation & purification , Adolescent , Australia/epidemiology , Carrier State/epidemiology , Female , Humans , Male , Neisseria meningitidis/genetics , Odds Ratio , Prevalence , Risk Factors , Serogroup , Single-Blind Method
14.
J Pediatric Infect Dis Soc ; 9(4): 454-459, 2020 Sep 17.
Article in English | MEDLINE | ID: mdl-31634404

ABSTRACT

BACKGROUND: Neisseria meningitidis serogroup B (MenB) is the most frequent cause of invasive meningococcal disease (IMD) in Spain. The multicomponent vaccine against MenB (4CMenB) was approved in Spain in January 2014. METHODS: We present 4 cases of children who developed MenB-associated IMD despite previous vaccination with 4CMenB. Extensive immunologic diagnostic work-up was performed in order to rule out any immunodeficiency. Also, molecular characterization of the MenB strain was conducted to determine whether bacterial antigens matched vaccine antigens. RESULTS: Among the 4 patients (2 girls), 2 had previous risk factors for IMD (recurrent bacterial meningitis of unknown origin and treatment with eculizumab). All patients developed meningitis, but only 2 developed septic shock; they were all cured without sequelae. No other primary or secondary immunodeficiencies were detected. MenB sequence type 213 was identified in 3 cases. With the exception of neisserial heparin-binding antigen peptide 465 present in 1 isolate, the rest of the isolated strains harbored vaccine antigen variants that did not match antigen variants included in the vaccine. CONCLUSIONS: We present 4 children who developed MenB-associated IMD despite previous vaccination with 4CMenB. In 2 cases, the antibodies induced by 4CMenB likely were not effective against the isolated strains. A high level of suspicion for IMD seems advisable regardless of the patient's vaccination history.


Subject(s)
Meningococcal Infections/microbiology , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/isolation & purification , Child , Child, Preschool , Female , Humans , Infant , Male , Meningococcal Infections/immunology , Meningococcal Infections/prevention & control , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/immunology , Risk Factors , Spain
15.
J Infect ; 79(5): 426-434, 2019 11.
Article in English | MEDLINE | ID: mdl-31505201

ABSTRACT

OBJECTIVES: Two Neisseria meningitidis serogroup B (NmB) vaccines are licensed in the United States. To estimate their potential coverage, we examined the vaccine antigen diversity among meningococcal isolates prior to vaccine licensure. METHODS: NmB vaccine antigen genes of invasive isolates collected in the U.S. from 2009 to 2014 were characterized by Sanger or whole-genome sequencing. RESULTS: During 2009-2014, the predominant antigen types have remained similar to those reported in 2000-2008 for NmB and 2006-2008 for NmC, NmY, with the emergence of a few new types. FHbp of subfamily B or variant 1 (B/v1) remained prevalent among NmB whereas FHbp of subfamily A or variant 2 and 3 (A/v2-3) were more prevalent among non-NmB. FHbp peptide 1 (B24/1.1) remains the most prevalent type in NmB. Full-length NadA peptide was detected in 26% of isolates, primarily in NmB and NmW. The greatest diversity of NhbA peptides was detected among NmB, with p0005 as the most prevalent type. CONCLUSIONS: The prevalence and diversity of the NmB vaccine antigens have remained stable with common antigen types persisting over time. The data collected prior to NmB vaccine licensure provide the baseline to understand the potential impact of NmB vaccines on antigen diversity and strain coverage.


Subject(s)
Antigens, Viral/genetics , Genetic Variation , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/microbiology , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Viral/analysis , Child , Child, Preschool , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neisseria meningitidis, Serogroup B/classification , Prevalence , United States/epidemiology , Young Adult
16.
Sci Rep ; 9(1): 9990, 2019 07 10.
Article in English | MEDLINE | ID: mdl-31292501

ABSTRACT

Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaDB) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.


Subject(s)
Carrier State/epidemiology , Meningococcal Infections/epidemiology , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B/classification , Pharynx/microbiology , Adolescent , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Bacteriological Techniques , Disease Outbreaks , England , Humans , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification , Phylogeny , Porins/genetics , Whole Genome Sequencing/methods
17.
Pediatr Infect Dis J ; 38(4): 416-418, 2019 04.
Article in English | MEDLINE | ID: mdl-30882736

ABSTRACT

Although bacterial meningitis is a rare presentation of a congenital immunodeficiency, invasive meningococcal disease is classically associated with complement deficiencies. We report a patient from a consanguineous kindred presenting with an invasive meningococcal disease caused by serogroup B meningococcus that revealed an underlying C5 deficiency caused by a novel mutation in the C5 gene.


Subject(s)
Complement C5/deficiency , Family Health , Genetic Predisposition to Disease , Meningitis, Meningococcal/genetics , Meningitis, Meningococcal/pathology , Child , Complement C5/genetics , Female , Humans , Mutant Proteins/genetics , Mutant Proteins/metabolism , Neisseria meningitidis, Serogroup B/isolation & purification , Portugal
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(2): 153-158, 2019 Feb 06.
Article in Chinese | MEDLINE | ID: mdl-30744288

ABSTRACT

Objective: To investigate the molecular characteristics of serogroup B neisseria meningitidis in China. Methods: Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed. Results: The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types. Conclusion: CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.


Subject(s)
Neisseria meningitidis, Serogroup B/genetics , Antigens, Bacterial/genetics , China , Humans , Meningococcal Infections/microbiology , Meningococcal Vaccines , Multilocus Sequence Typing , Neisseria meningitidis, Serogroup B/isolation & purification
19.
Vaccine ; 37(7): 991-1000, 2019 02 08.
Article in English | MEDLINE | ID: mdl-30661831

ABSTRACT

BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.


Subject(s)
Antigens, Bacterial/genetics , Genotype , Genotyping Techniques/methods , Meningitis, Meningococcal/microbiology , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/classification , Global Health , Humans , Meningitis, Meningococcal/epidemiology , Molecular Epidemiology/methods , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification
20.
PLoS One ; 13(12): e0209919, 2018.
Article in English | MEDLINE | ID: mdl-30592763

ABSTRACT

Herd protection, resulting from the interruption of transmission and asymptomatic carriage, is an important element of the effectiveness of vaccines against the meningococcus. Whilst this has been well established for conjugate polysaccharide vaccines directed against the meningococcal capsule, two uncertainties surround the potential herd protection provided by the novel protein-based vaccines that are used in place of serogroup B (MenB) polysaccharide vaccines (i) the strain coverage of such vaccines against carried meningococci, which are highly diverse; and (ii) the generation of a protective immune response in the mucosa. These considerations are essential for realistic estimates of cost-effectiveness of new MenB vaccines. Here the first of these questions is addressed by the whole genome sequence (WGS) analysis of meningococci isolated from healthy military recruits and university students in Greece. The study included a total of 71 MenB isolates obtained from 1420 oropharyngeal single swab samples collected from military recruits and university students on voluntary basis, aged 18-26 years. In addition to WGS analysis to identify genetic lineage and vaccine antigen genes, including the Bexsero Antigen Sequence Type (BAST), the isolates were examined with the serological Meningococcal antigen Typing System (MATS) assay. Comparison of these data demonstrated that the carried meningococcal population was highly diverse with 38% of the carriage isolates showed expression of antigens matching those included in the 4CMenB vaccine. Our data may suggest a limited potential herd immunity to be expected and be driven by an impact on a subset of carriage isolates.


Subject(s)
Genetic Variation , Genome, Bacterial , Genome-Wide Association Study , High-Throughput Nucleotide Sequencing , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup B , Female , Greece , Humans , Male , Meningitis, Meningococcal/genetics , Meningitis, Meningococcal/microbiology , Meningitis, Meningococcal/prevention & control , Neisseria meningitidis, Serogroup B/genetics , Neisseria meningitidis, Serogroup B/isolation & purification
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