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2.
Front Cell Infect Microbiol ; 14: 1407863, 2024.
Article in English | MEDLINE | ID: mdl-38808060

ABSTRACT

The genus Neisseria, which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic Neisseria species are closely related but cause quite different diseases, meningococcal sepsis and meningitis (Neisseria meningitidis) and sexually transmitted gonorrhea (Neisseria gonorrhoeae). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic Neisseria have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of Neisseria express broad-spectrum O-linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation (pgl) genes and polymorphic pgl gene content. The exact roles of glycosylation in Neisseria remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal Neisseria appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic Neisseria are summarized and discussed.


Subject(s)
Neisseria meningitidis , Glycosylation , Humans , Neisseria meningitidis/genetics , Neisseria meningitidis/metabolism , Glycoproteins/metabolism , Glycoproteins/genetics , Neisseria/genetics , Neisseria/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/metabolism , Neisseria gonorrhoeae/pathogenicity , Neisseria gonorrhoeae/immunology , Polysaccharides/metabolism
3.
Front Cell Infect Microbiol ; 14: 1389527, 2024.
Article in English | MEDLINE | ID: mdl-38756230

ABSTRACT

Neisseria meningitidis (Nm, the meningococcus) is considered an asymptomatic colonizer of the upper respiratory tract and a transient member of its microbiome. It is assumed that the spread of N. meningitidis into the bloodstream occurs via transcytosis of the nasopharyngeal epithelial barrier without destroying the barrier layer. Here, we used Calu-3 respiratory epithelial cells that were grown under air-liquid-interface conditions to induce formation of pseudostratified layers and mucus production. The number of bacterial localizations in the outer mucus, as well as cellular adhesion, invasion and transmigration of different carrier and disease N. meningitidis isolates belonging to MenB:cc32 and MenW:cc22 lineages was assessed. In addition, the effect on barrier integrity and cytokine release was determined. Our findings showed that all strains tested resided primarily in the outer mucus layer after 24 h of infection (>80%). Nonetheless, both MenB:cc32 and MenW:cc22 carrier and disease isolates reached the surface of the epithelial cells and overcame the barrier. Interestingly, we observed a significant difference in the number of bacteria transmigrating the epithelial cell barrier, with the representative disease isolates being more efficient to transmigrate compared to carrier isolates. This could be attributed to the capacity of the disease isolates to invade, however could not be assigned to expression of the outer membrane protein Opc. Moreover, we found that the representative meningococcal isolates tested in this study did not damage the epithelial barrier, as shown by TEER measurement, FITC-dextran permeability assays, and expression of cell-junction components.


Subject(s)
Bacterial Adhesion , Carrier State , Epithelial Cells , Meningococcal Infections , Nasopharynx , Neisseria meningitidis , Epithelial Cells/microbiology , Humans , Nasopharynx/microbiology , Neisseria meningitidis/metabolism , Meningococcal Infections/microbiology , Carrier State/microbiology , Cell Line , Cytokines/metabolism
4.
Int J Biol Macromol ; 269(Pt 1): 132081, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705330

ABSTRACT

3'-Sialyllactose (3'-SL), one of the abundant and important sialylated human milk oligosaccharides, is an emerging food ingredient used in infant formula milk. We previously developed an efficient route for 3'-SL biosynthesis in metabolically engineered Escherichia coli BL21(DE3). Here, several promising α2,3-sialyltransferases were re-evaluated from the byproduct synthesis perspective. The α2,3-sialyltransferase from Neisseria meningitidis MC58 (NST) with great potential and the least byproducts was selected for subsequent molecular modification. Computer-assisted mutation sites combined with a semi-rational modification were designed and performed. A combination of two mutation sites (P120H/N113D) of NST was finally confirmed as the best one, which significantly improved 3'-SL biosynthesis, with extracellular titers of 24.5 g/L at 5-L fed-batch cultivations. When NST-P120H/N113D was additionally integrated into the genome of host EZAK (E. coli BL21(DE3)ΔlacZΔnanAΔnanT), the final strain generated 32.1 g/L of extracellular 3'-SL in a 5-L fed-batch fermentation. Overall, we underscored the existence of by-products and improved 3'-SL production by engineering N. meningitidis α2,3-sialyltransferase.


Subject(s)
Escherichia coli , Metabolic Engineering , Neisseria meningitidis , Sialyltransferases , Escherichia coli/genetics , Escherichia coli/metabolism , Sialyltransferases/genetics , Sialyltransferases/metabolism , Metabolic Engineering/methods , Neisseria meningitidis/genetics , Neisseria meningitidis/enzymology , Mutation , Oligosaccharides/biosynthesis , Fermentation
5.
Hum Vaccin Immunother ; 20(1): 2346963, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38745461

ABSTRACT

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.


Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin G , Neisseria meningitidis , SARS-CoV-2 , Animals , Mice , Immunoglobulin G/blood , Neisseria meningitidis/immunology , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/immunology , SARS-CoV-2/immunology , Adjuvants, Immunologic/administration & dosage , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunity, Cellular , Immunity, Humoral , Mice, Inbred BALB C , Meningococcal Infections/prevention & control , Meningococcal Infections/immunology , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Vaccine/administration & dosage , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/immunology , Immunization/methods , Antibody Affinity , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Meningococcal Vaccines/immunology , Meningococcal Vaccines/administration & dosage , Immunologic Memory , Th1 Cells/immunology
7.
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
8.
Article in English | MEDLINE | ID: mdl-38594793

ABSTRACT

Abstract: In 2023, an increased number of urogenital and anorectal infections with Neisseria meningitis serogroup Y (MenY) were reported in New South Wales (NSW). Whole genome sequencing (WGS) found a common sequence type (ST-1466), with limited sequence diversity. Confirmed outbreak cases were NSW residents with a N. meningitidis isolate matching the cluster sequence type; probable cases were NSW residents with MenY isolated from a urogenital or anorectal site from 1 July 2023 without WGS testing. Of the 41 cases, most were men (n = 27), of whom six reported recent contact with a female sex worker. Five cases were men who have sex with men and two were female sex workers. Laboratory alerts regarding the outbreak were sent to all Australian jurisdictions through the laboratories in the National Neisseria Network. Two additional states identified urogenital MenY ST-1466 infections detected in late 2023. Genomic analysis showed all MenY ST-1466 sequences were interspersed, suggestive of an Australia-wide outbreak. The incidence of these infections remains unknown, due to varied testing and reporting practices both within and across jurisdictions. Isolates causing invasive meningococcal disease (IMD) in Australia are typed, and there has been no MenY ST-1466 IMD recorded in Australia to end of March 2024. Concerns remain regarding the risk of IMD, given the similarity of these sequences with a MenY ST-1466 IMD strain causing a concurrent outbreak in the United States of America.


Subject(s)
Meningococcal Infections , Neisseria meningitidis , Sex Workers , Sexual and Gender Minorities , Male , Humans , Female , Serogroup , Homosexuality, Male , Australia/epidemiology , Meningococcal Infections/epidemiology , Disease Outbreaks
9.
MMWR Morb Mortal Wkly Rep ; 73(15): 345-350, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38635488

ABSTRACT

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup B , Neisseria meningitidis , Humans , United States/epidemiology , Advisory Committees , Vaccines, Combined , Immunization , Meningococcal Infections/prevention & control
10.
BMC Infect Dis ; 24(1): 286, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38443838

ABSTRACT

BACKGROUND: Invasive meningococcal disease (IMD), including sepsis and meningitis, can develop when Neisseria meningitidis bacteria breach the barrier and gain access to the circulation. While IMD is a rare outcome of bacterial exposure, colonization of the oropharynx is present in approximately 10% of the human population. This asymptomatic carriage can be long or short term, and it is unknown which determining factors regulate bacterial colonization. Despite descriptions of many bacterial virulence factors and recent advances in detailed genetic identification and characterization of bacteria, the factors mediating invasion and disease vs. asymptomatic carriage following bacterial colonization remain unknown. The pharyngeal epithelia play a role in the innate immune defense against pathogens, and the aim of this study was to investigate the proinflammatory response of pharyngeal epithelial cells following meningococcal exposure to describe the potential inflammatory mediation performed during the initial host‒pathogen interaction. Clinically relevant isolates of serogroups B, C, W and Y, derived from patients with meningococcal disease as well as asymptomatic carriers, were included in the study. RESULTS: The most potent cellular response with proinflammatory secretion of TNF, IL-6, CXCL8, CCL2, IL-1ß and IL-18 was found in response to invasive serogroup B isolates. This potent response pattern was also mirrored by increased bacterial adhesion to cells as well as induced cell death. It was, however, only with serogroup B isolates where the most potent cellular response was toward the IMD isolates. In contrast, the most potent cellular response using serogroup Y isolates was directed toward the carriage isolates rather than the IMD isolates. In addition, by comparing isolates from outbreaks in Sweden (epidemiologically linked and highly genetically similar), we found the most potent proinflammatory response in cells exposed to carriage isolates rather than the IMD isolates. CONCLUSION: Although certain expected correlations between host‒pathogen interactions and cellular proinflammatory responses were found using IMD serogroup B isolates, our data indicate that carriage isolates invoke stronger proinflammatory activation of the epithelial lining than IMD isolates.


Subject(s)
Meningococcal Infections , Neisseria meningitidis , Humans , Epithelial Cells , Pharynx , Epithelium
11.
Microb Biotechnol ; 17(3): e14446, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38536702

ABSTRACT

Developing protein-based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti-bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high-throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, 'immune interface interference' (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H-binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein-based vaccines to prevent bacterial infections.


Subject(s)
Meningococcal Vaccines , Neisseria meningitidis , Animals , Humans , Bacterial Vaccines/genetics , Bacterial Proteins/genetics , Antigens, Bacterial/genetics , Antibodies, Bacterial , Neisseria meningitidis/genetics
12.
J Infect ; 88(5): 106145, 2024 May.
Article in English | MEDLINE | ID: mdl-38552719

ABSTRACT

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.


Subject(s)
Meningitis, Bacterial , Meningitis, Viral , Vaccines, Conjugate , Humans , Child , Infant , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/microbiology , Child, Preschool , Adolescent , Female , Male , Prospective Studies , Meningitis, Viral/diagnosis , Meningitis, Viral/cerebrospinal fluid , Clinical Decision Rules , United Kingdom/epidemiology , Neisseria meningitidis/isolation & purification , Streptococcus pneumoniae/isolation & purification , Decision Support Techniques
13.
J Adolesc Health ; 74(6): 1068-1077, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38430074

ABSTRACT

Invasive meningococcal disease (IMD) is a rare but serious illness, and adolescents and young adults in the United States are at increased risk. Here, we discuss US IMD history and how successful disease prevention through routine vaccination against the most common disease-causing serogroups (A, B, C, W, and Y) can inform future recommendations. Before the introduction of quadrivalent meningococcal conjugate (MenACWY) vaccines, most US cases of IMD were caused by serogroups B, C, and Y. After recommendation by the Advisory Committee on Immunization Practices for routine MenACWY vaccination of 11-12-year-olds in 2005, followed by a 2010 booster recommendation, MenCWY disease incidence declined dramatically, and vaccine coverage remains high. Two serogroup B (MenB) vaccines are licensed in the United States, but uptake is low compared with MenACWY vaccines, likely because Advisory Committee on Immunization Practices recommends MenB vaccination subject to shared clinical decision-making rather than routinely for all adolescents. The proportion of adolescent IMD caused by MenB has now increased. Pentavalent vaccines that protect against serogroups A, B, C, W, and Y may provide an optimal strategy for improving vaccination rates to ultimately reduce MenB incidence while maintaining the historically low rates of IMD caused by serogroups A, C, W, and Y.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Humans , Meningococcal Vaccines/administration & dosage , United States , Adolescent , Meningococcal Infections/prevention & control , Vaccines, Conjugate/administration & dosage , Vaccination/statistics & numerical data , Neisseria meningitidis/immunology , Child
14.
Med Sci Monit ; 30: e942904, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520034

ABSTRACT

BACKGROUND Bacterial meningitis is a serious and life-threatening condition that requires prompt diagnosis and treatment. This retrospective study aimed to identify causes, presentation, and predictive factors for outcomes of community-acquired bacterial meningitis in 86 adults in Vilnius, Lithuania between 2018 and 2021. MATERIAL AND METHODS We performed a retrospective study of demographic, clinical, and laboratory records of 86 adult patients admitted to Vilnius University Hospital Santaros Clinics with a diagnosis of acute bacterial meningitis during the period of 2018-2021. RESULTS Of 86 patients, 54 (62.79%) were men. The median (Md) age of patients was 58 (range, 18-83) years and the median duration of hospitalization was 20 (range, 3-92) days. Patients were first hospitalized in the Intensive Care Unit (ICU) in 59.3% of cases. The most prevalent concerns were headache (66.28%), febrile temperature (56.98%), general fatigue (53.49%), and confusion/sleepiness (52.33%). Of 57 (66.28%) etiologically confirmed cases, the most prevalent agent was Listeria monocytogenes (29.82%), followed by Streptococcus pneumoniae (28.07%) and Neisseria meningitidis (28.07%). Patients with meningitis caused by L. monocytogenes were the oldest (P=0.003) and had the longest hospitalization (P<0.001). Fatigue was the prominent symptom in patients with meningococcal meningitis (81.2%, P=0.010). Twelve patients (13.95%) have died. Advanced age and low (<100 cells per µL) white blood cell (WBC) count in cerebrospinal fluid (CSF) were associated with lethal outcome, whereas headache was associated with favorable outcome. CONCLUSIONS Clinical characteristics of community-acquired acute bacterial meningitis differ based on etiological factors. Patient age, CSF WBC count, and headache may be significant predictive factors for outcomes of bacterial meningitis.


Subject(s)
Meningitis, Bacterial , Neisseria meningitidis , Male , Adult , Humans , Infant, Newborn , Infant , Female , Retrospective Studies , Lithuania/epidemiology , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Headache/etiology
15.
Public Health ; 230: 163-171, 2024 May.
Article in English | MEDLINE | ID: mdl-38555685

ABSTRACT

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.


Subject(s)
Meningococcal Vaccines , Neisseria meningitidis , Nurses , Humans , Spain , Vaccines, Conjugate , Choice Behavior , Pharmaceutical Preparations
16.
Ann Clin Microbiol Antimicrob ; 23(1): 28, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38555443

ABSTRACT

BACKGROUND: Neisseria meningitidis can cause life-threatening meningococcal meningitis and meningococcemia. Old standard microbiological results from CSF/blood cultures are time consuming. This study aimed to combine the sensitivity of loop-mediated isothermal nucleic acid amplification (LAMP) with the specificity of CRISPR/Cas12a cleavage to demonstrate a reliable diagnostic assay for rapid detection of N. meningitidis. METHODS: A total of n = 139 samples were collected from patients with suspected meningococcal disease and were used for evaluation. The extracted DNA was subjected to qualitative real-time PCR, targeting capsular transporter gene (ctrA) of N. meningitidis. LAMP-specific primer pairs, also targeting the ctrA, were designed and the LAMP products were subjected to CRISPR/Cas12 cleavage reaction. the readout was on a lateral flow strip. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LAMP-CRISPR/Cas was compared with real-time PCR assays. The limit of detection (LOD) was established with serial dilutions of the target N. meningitidis DNA and calculated by Probit regression analysis. RESULTS: Six LAMP assay-specific primers were developed targeting the ctrA gene of N. meningitidis, which is conserved in all meningococcal serogroups. The LAMP primers did not amplify DNA from other bacterial DNA tested, showing 100% specificity. The use of 0.4 M betaine increased the sensitivity and stability of the reaction. LAMP-CRISPR/Cas detected meningococcal serogroups (B, C, W). The assay showed no cross-reactivity and was specific for N. meningitidis. The LOD was 74 (95% CI: 47-311) N. meningitidis copies. The LAMP-CRISPR/Cas performed well compared to the gold standard. In the 139 samples from suspected patients, the sensitivity and specificity of the test were 91% and 99% respectively. CONCLUSION: This developed and optimized method can complement for the available gold standard for the timely diagnosis of meningococcal meningitis and meningococcemia.


Subject(s)
Meningitis, Meningococcal , Meningococcal Infections , Neisseria meningitidis , Sepsis , Humans , Neisseria meningitidis/genetics , Meningitis, Meningococcal/diagnosis , Meningitis, Meningococcal/microbiology , Meningococcal Infections/diagnosis , Meningococcal Infections/microbiology , Sensitivity and Specificity , DNA, Bacterial/genetics
17.
Expert Rev Vaccines ; 23(1): 445-462, 2024.
Article in English | MEDLINE | ID: mdl-38517733

ABSTRACT

INTRODUCTION: The epidemiology of invasive meningococcal disease (IMD), a rare but potentially fatal illness, is typically described as unpredictable and subject to sporadic outbreaks. AREAS COVERED: Meningococcal epidemiology and vaccine use during the last ~ 200 years are examined within the context of meningococcal characterization and classification to guide future IMD prevention efforts. EXPERT OPINION: Historical and contemporary data highlight the dynamic nature of meningococcal epidemiology, with continued emergence of hyperinvasive clones and affected regions. Recent shifts include global increases in serogroup W disease, meningococcal antimicrobial resistance (AMR), and meningococcal urethritis; additionally, unvaccinated populations have experienced disease resurgences following lifting of COVID-19 restrictions. Despite these changes, a close analysis of meningococcal epidemiology indicates consistent dominance of serogroups A, B, C, W, and Y and elevated IMD rates among infants and young children, adolescents/young adults, and older adults. Demonstrably effective vaccines against all 5 major disease-causing serogroups are available, and their prophylactic use represents a powerful weapon against IMD, including AMR. The World Health Organization's goal of defeating meningitis by the year 2030 demands broad protection against IMD, which in turn indicates an urgent need to expand meningococcal vaccination programs across major disease-causing serogroups and age-related risk groups.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis , Child , Infant , Adolescent , Young Adult , Humans , Child, Preschool , Aged , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Disease Outbreaks , Serogroup , Vaccines, Combined
18.
Pan Afr Med J ; 47: 11, 2024.
Article in English | MEDLINE | ID: mdl-38524112

ABSTRACT

On 6 March 2023, Neisseria meningitidis serogroup C was isolated from a cerebral spinal fluid sample from Obongi District, Uganda. This sample was one of many from patients who were presenting with fever, convulsions, and altered consciousness. We investigated to determine the scope of the meningitis cluster, identify risk factors of contracting meningitis, and inform control measures. We reviewed medical records, conducted active community case finding, and conducted key informant interviews in the affected communities to identify cases and factors associated with contracting meningitis. We analysed case data by person, place, and time. Between 22 December 2022 and 1 May 2023, 25 cases with 2 deaths of bacterial meningitis occurred in Palorinya Refugee Settlement, Obongi District. Of these, 4 were laboratory-confirmed with Neisseria meningitidis serogroup C, 6 were probable cases, and 15 were suspected cases. Most (76%) of case-patients were <18 years old with a median age of 12 years (range 1-66 years). None of the case-patients was vaccinated against Neisseria meningitidis serogroup C. Each case-patient was from a different household and there was no epidemiological link between any of the cases. This meningococcal meningitis cluster caused by Neisseria meningitidis serogroup C occurred among non-vaccinated persons mostly aged <18 years in Palorinya Refugee Settlement. We recommended vaccination of at-risk persons.


Subject(s)
Meningitis, Meningococcal , Neisseria meningitidis, Serogroup C , Neisseria meningitidis , Refugees , Humans , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Uganda/epidemiology , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/prevention & control , Vaccination
19.
Emerg Infect Dis ; 30(3): 460-468, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38407254

ABSTRACT

During January 28-May 5, 2019, a meningitis outbreak caused by Neisseria meningitidis serogroup C (NmC) occurred in Burkina Faso. Demographic and laboratory data for meningitis cases were collected through national case-based surveillance. Cerebrospinal fluid was collected and tested by culture and real-time PCR. Among 301 suspected cases reported in 6 districts, N. meningitidis was the primary pathogen detected; 103 cases were serogroup C and 13 were serogroup X. Whole-genome sequencing revealed that 18 cerebrospinal fluid specimens tested positive for NmC sequence type (ST) 10217 within clonal complex 10217, an ST responsible for large epidemics in Niger and Nigeria. Expansion of NmC ST10217 into Burkina Faso, continued NmC outbreaks in the meningitis belt of Africa since 2019, and ongoing circulation of N. meningitidis serogroup X in the region underscore the urgent need to use multivalent conjugate vaccines in regional mass vaccination campaigns to reduce further spread of those serogroups.


Subject(s)
Meningitis , Neisseria meningitidis, Serogroup C , Neisseria meningitidis , Humans , Burkina Faso/epidemiology , Serogroup , Neisseria meningitidis, Serogroup C/genetics , Disease Outbreaks , Neisseria meningitidis/genetics
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