#Meningococcal #quinolone #resistance originated from several commensal #Neisseria species (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Meningococcal quinolone resistance originated from several commensal Neisseria species

Mingliang Chen, Chi Zhang, Xi Zhang, Min Chen

DOI: 10.1128/AAC.01494-19



Quinolone resistance is increasing in Neisseria meningitidis, with high prevalence in China (>70%), but its origin remains unknown. The aim of this study was to investigate donors of mutation-harboring gyrA alleles in N. meningitidis. A total of 198 N. meningitidis and 293 commensal Neisseria isolates were collected between 2005 and 2018 in Shanghai, China. Minimum inhibitory concentrations (MICs) of ciprofloxacin were determined using agar dilution method. Resistance-associated genes gyrA and parC were sequenced for all isolates, while a few isolates were performed Illumina sequencing. The prevalence of quinolone resistance in N. meningitidis and commensal Neisseria was 67.7% (134/198) and 99.3% (291/293), respectively. All 134 quinolone-resistant N. meningitidis isolates possessed mutations in T91 (n=123) and/or D95 (n=12) of GyrA, with 7 isolates also harboring ParC mutations and exhibiting higher MICs. Phylogenetic analysis of the gyrA sequence identified six clusters. Among the 71 mutation-harboring gyrA alleles represented by 221 N. meningitidis isolates and genomes (n=221), 12 alleles (n=103, 46.6%) were included in N. meningitidis cluster, while 20 alleles (n=56) in N. lactamica cluster, 27 alleles (n=49) in N. cinerea cluster, and 9 alleles (n=10) in N. subflava cluster. Genomic analyses identified the exact N. lactimica donors of seven mutation-harboring gyrA alleles (gyrA92, gyrA97, gyrA98, gyrA114, gyrA116, gyrA151, and gyrA230) and the N. subflava donor isolate of gyrA171, with recombinant fragment ranging from 634 to 7499 bp. Transformation of gyrA fragments from these donor strains into a meningococcal isolate increased its ciprofloxacin MIC from 0.004 μg/ml to 0.125 or 0.19 μg/ml, and to 0.5 μg/ml with further transformation of an additional ParC mutation. Over half of quinolone-resistant N. meningitidis isolates acquired resistance by horizontal gene transfer from three commensal Neisseria species. Quinolone resistance in N. meningitidis increases in a stepwise manner.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Neisseria meningitidis; Meningococcal meningitis; Quinolones.


#Genomic analysis of #Neisseria meningitidis carriage isolates during an #outbreak of serogroup C clonal complex 11, #Tuscany, #Italy (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]


Genomic analysis of Neisseria meningitidis carriage isolates during an outbreak of serogroup C clonal complex 11, Tuscany, Italy

Luigina Ambrosio, Arianna Neri , Cecilia Fazio , Gian Maria Rossolini, Paola Vacca, Eleonora Riccobono, Fabio Voller, Alessandro Miglietta, Paola Stefanelli

Published: May 28, 2019 / DOI: https://doi.org/10.1371/journal.pone.0217500




In 2015–2016, a cross-sectional carriage survey was performed in Tuscany Region, Italy, during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C clonal complex 11 (MenC:cc11). This study aims to evaluate the genomic profile of meningococcal carriage isolates collected during the survey.


Whole-genome sequencing (WGS) was performed using Illumina MiSeq on 85 cultivated meningococcal carriage isolates received at the Dept. of Infectious Disease, National Institute of Health (Istituto Superiore di Sanità, ISS), as National Reference Laboratory (NRL) for Invasive Meningococcal Disease (IMD). De novo assembled genomes were scanned by the BIGSdb platform to assign: the genotypic profiles, the cgMLST, the vaccine antigen variants and allele types of antimicrobial resistance associated genes, together with denitrification pathway loci.


Capsule null and non-groupable meningococci accounted for 52.9% and 10.6%, respectively. Among the remaining carriage isolates, serogroup B was the predominant (71.0%). Serogroup C meningococci were culture negative and unavailable for WGS. Overall, 64 genotypic profiles were identified and, based on cgMLST, isolates clustered according to clonal complexes. Eight isolates (9.4%) harbored at least one gene encoding a 4CMenB vaccine antigen. Mutated penAalleles were found in more than 82%. Finally, complete aniA and norB coding sequences were detected among 71.8% of carriage isolates.


Meningococcal carriage isolates collected during the MenC:cc11 outbreak were characterized by an extensive genetic diversity. The lack of outbreak-related isolates among carriage might be attributable to the high transmissibility with low duration of colonization of MenC:cc11 meningococci.


Citation: Ambrosio L, Neri A, Fazio C, Rossolini GM, Vacca P, Riccobono E, et al. (2019) Genomic analysis of Neisseria meningitidis carriage isolates during an outbreak of serogroup C clonal complex 11, Tuscany, Italy. PLoS ONE 14(5): e0217500. https://doi.org/10.1371/journal.pone.0217500

Editor: Daniela Flavia Hozbor, Universidad Nacional de la Plata, ARGENTINA

Received: January 25, 2019; Accepted: May 13, 2019; Published: May 28, 2019

Copyright: © 2019 Ambrosio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The genome sequences of the isolates have been deposited in the PubMLST Neisseria database (https://pubmlst.org/neisseria/) and all relevant data are within the paper.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Neisseria meningitidis sg C; Meningococcal meningitis; Italy.


Standing on the shoulders of giants: two #centuries of #struggle against #meningococcal disease (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Standing on the shoulders of giants: two centuries of struggle against meningococcal disease

Prof Pere Domingo, MD, Virginia Pomar, MD, Albert Mauri, MD, Nicolau Barquet, MD

Published: April 30, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30040-4



Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future.

Keywords: Meningococcal disease; Antibiotics; Drugs Resistance; Serotherapy; History.


#Outbreak of #Neisseria meningitidis serogroup C outside the #meningitis belt—#Liberia, 2017: an epidemiological and laboratory #investigation (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt—Liberia, 2017: an epidemiological and laboratory investigation

Catherine H Bozio, PhD *, Jeni Vuong, MSc *, E Kainne Dokubo, MD *, Mosoka P Fallah, PhD *, Lucy A McNamara, PhD, Caelin C Potts, PhD, John Doedeh, MD, Miatta Gbanya, MPH, Adam C Retchless, PhD, Jaymin C Patel, PhD, Thomas A Clark, MD, Henry Kohar, MSc, Thomas Nagbe, MPH, Peter Clement, MD, Victoria Katawera, MSc, Nuha Mahmoud, MD, Harouna M Djingarey, MD, Anne Perrocheau, MD, Dhamari Naidoo, MSc, Mardia Stone, MD, Roseline N George, MPH, Desmond Williams, MD, Alex Gasasira, MD, Tolbert Nyenswah, MPH †, Xin Wang, PhD †, LeAnne M Fox, MD  † for theLiberian Meningococcal Disease Outbreak Response Team ‡

Published: October 15, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30476-6




On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain.


We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage.


28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217.


This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt.


US Global Health Security.

Keywords: N. meningitidis; Meningococcal Meningitis; Liberia.


Interconnected #clusters of invasive #meningococcal disease due to #Neisseria meningitidis serogroup C ST-11 (cc11), involving bi- & MSM, with discos and gay-venues #hotspots of #transmission, Tuscany, #Italy, 2015 to 2016 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Interconnected clusters of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11), involving bisexuals and men who have sex with men, with discos and gay-venues hotspots of transmission, Tuscany, Italy, 2015 to 2016

Alessandro Miglietta1,2,3, Cecilia Fazio2,4, Arianna Neri2,4, Patrizio Pezzotti2, Francesco Innocenti1, Chiara Azzari5, Gian Maria Rossolini6,Maria Moriondo5, Francesco Nieddu5, Stefania Iannazzo7, Fortunato D’Ancona2,7, Francesco Paolo Maraglino7, Raniero Guerra7,Giovanni Rezza2, Fabio Voller1, Paola Stefanelli2

Affiliations: 1 Regional Health Agency of Tuscany, Epidemiologic Observatory, Florence, Italy; 2 Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy; 3 Units of Epidemiology and Preventive Medicine, Central Tuscany Health Authority, Florence, Italy; 4 These authors contributed equally to this work; 5 Laboratory of Immunology and Infectious Diseases, Anna Meyer Children’s University Hospital, University of Florence, Florence, Italy. 6 Department of Experimental and Clinical Medicine, University of Florence, and Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; 7 Ministry of Health, Directorate-General of health prevention, Rome, Italy

Correspondence:  Paola Stefanelli

Citation style for this article: Miglietta Alessandro, Fazio Cecilia, Neri Arianna, Pezzotti Patrizio, Innocenti Francesco, Azzari Chiara, Rossolini Gian Maria, Moriondo Maria,Nieddu Francesco, Iannazzo Stefania, D’Ancona Fortunato, Maraglino Francesco Paolo, Guerra Raniero, Rezza Giovanni, Voller Fabio, Stefanelli Paola. Interconnected clusters of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11), involving bisexuals and men who have sex with men, with discos and gay-venues hotspots of transmission, Tuscany, Italy, 2015 to 2016. Euro Surveill. 2018;23(34):pii=1700636. https://doi.org/10.2807/1560-7917.ES.2018.23.34.1700636

Received: 14 Sep 2017;   Accepted: 22 Mar 2018



In 2015 an increased incidence of invasive meningococcal disease due to serogroup-C (MenC) occurred in Tuscany, Italy. This led the Regional Health Authority of Tuscany to implement a reactive immunisation campaign and to launch an epidemiological field investigation aiming to address targeted immunisation interventions. In 2011–14, 10 MenC cases had been reported compared with 62 cases in 2015–16. The case fatality rate was 21% (n = 13) and 51 cases (82.3%) were confirmed as C:P1.5–1,10–8:F3–6:ST-11(cc11). Overall, 17 clusters were recognised. Six discos and four gay-venues were found to have a role as transmission-hotspots, having been attended by 20 and 14 cases in the 10 days before symptoms onset. Ten and three cases occurred, respectively, among men who have sex with men (MSM) and bisexual individuals, who were involved in 11 clusters. In addition, heterosexual cases (n = 5) attending gay-venues were also found. Secondary cases were not identified. Molecular typing indicated close relationship with MenC clusters recently described among gay, bisexual and other MSM in Europe and the United States, suggesting a possible international spread of the serogroup-C-variant P1.5–1,10–8:F3–6:ST-11(cc11) in this population-group; however, epidemiological links were not identified. In December 2016, a targeted vaccination campaign involving discos and lesbian, gay, bisexual, and transgender (LGBT) associations was implemented. During 2017, 10 cases of MenC occurred, compared with 32 and 30 cases reported in 2015 and 2016 respectively, suggesting the effectiveness of the reactive and targeted immunisation programmes.

©   This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Meningococcal disease; Neisseria meningitidis; Italy.


Mass #chemoprophylaxis for #control of #outbreaks of #meningococcal disease (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Mass chemoprophylaxis for control of outbreaks of meningococcal disease

Lucy A McNamara, PhD, Jessica R MacNeil, MPH, Amanda C Cohn, MD, Prof David S Stephens, MD

Published: 29 May 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30124-5

© 2018 Elsevier Ltd. All rights reserved.



Although vaccination is the main strategy used to control meningococcal disease outbreaks, mass chemoprophylaxis has also been used as an immediate response to outbreaks, either to supplement vaccination or when vaccination is not possible. However, public health guidelines regarding the use of mass chemoprophylaxis for outbreak control vary by country, partly because the impact of mass chemoprophylaxis on the course of an individual outbreak is difficult to assess. We have reviewed data for the use of mass chemoprophylaxis during 33 outbreaks that occurred both in military populations and in communities and non-military organisations. In most outbreaks, no additional cases of meningococcal disease occurred after mass chemoprophylaxis, or cases occurred only in individuals who had not received prophylaxis. A delay of several weeks was common before cases occurred among prophylaxis recipients. Overall, the outbreak reports that we reviewed suggest that mass chemoprophylaxis might provide temporary protection to chemoprophylaxis recipients during outbreaks.

Keywords: Meningococcal Disease; Antibiotics; Post-exposure prophylaxis.


Immunogenicity and safety of the multicomponent #meningococcal B #vaccine (4CMenB) in #children and adolescents: a systematic review and meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: a systematic review and meta-analysis

Maria Elena Flacco, MD†, , Annalisa Rosso, MD, Carolina Marzuillo, MD, Mario Bergamini, MD, Armando Stefanati, MD, Rosario Cultrera, MD, Prof Paolo Villari, MD, Prof Walter Ricciardi, MD, Prof John P A Ioannidis, MD, Despina G Contopoulos-Ioannidis, MD

†Contributed equally

Published: 19 January 2018 / DOI: http://dx.doi.org/10.1016/S1473-3099(18)30048-3

© 2018 Elsevier Ltd. All rights reserved.




The multicomponent meningococcal serogroup B vaccine (4CMenB) has been licensed in more than 35 countries. However, uncertainties remain about the lowest number of doses required to induce satisfactory, persistent immune responses. We did a systematic review and meta-analysis to provide quantitative estimates for the immunogenicity, persistence of immunogenicity, and safety of 4CMenB vaccine in children and adolescents.


For this systematic review and meta-analyses (proportion, head to head, and network), we searched MEDLINE, Scopus, Embase, and ClinicalTrials.gov from database inception to June 30, 2017, for randomised trials that compared the immunogenicity or safety of the 4CMenB vaccine with its originator meningococcal B recombinant vaccine or routine vaccines in children or adolescents. For proportion meta-analyses, we also included single arm trials and follow-up studies of randomised controlled trials. Trials that assessed immunogenicity against at least one of four Neisseria meningitidis serogroup B reference strains (44-76/SL, 5/99, NZ98/254, and M10713) and included participants younger than 18 years who had received two or more doses of the 4CMenB vaccine were eligible for inclusion. We requested individual patient-level data from study authors and extracted data from published reports and online trial registries. We did meta-analyses to assess 4CMenB safety and immunogenicity against the four reference strains 30 days after a primary immunisation course (three doses for children, two doses for adolescents), 30 days after the primary course plus one booster dose (children only), 6 months or more after primary course, and 6 months or more after the booster dose.


736 non-duplicate records were screened, and ten randomised trials and eight follow-on extension trials on 4CMenB met the inclusion criteria. In intention-to-treat analyses, the overall proportion of children and adolescents who achieved seroconversion 30 days after the primary course of 4CMenB was 92% (95% CI 89–95 [I2=95%, p<0·0001]) for the 44/76-SL strain, 91% (87–95 [I2=95%, p<0·0001]) for the 5/99 strain, 84% (77–90 [I2=97%, p<0·0001]) for the NZ98-254 strain, and 87% (68–99 [I2=97%, p<0·0001]) for the M10713 strain. 6 months after the primary course, the immunogenicity remained adequate to high against all three tested strains (5/99, 44/76-SL, and NZ98/254) in adolescents (≥77%), and against two of four strains (5/99 and 44/76-SL) in children (≥67%): the proportion of patients who achieved seroconversion substantially declined for M10713 (<50%) and NZ98/254 (<35%). A booster dose re-enhanced the proportion of patients who achieved seroconversion (≥93% for all strains). However, immunogenicity remained high 6 months after the booster dose for strains 5/99 (95%) and M10713 (75%) only, whereas the proportion of patients who achieved seroconversion against strains 44/76-SL and NZ98/254 returned to similar proportions recorded 6 months after the primary course (62% for 44/76-SL, 35% for NZ98/254). The incidence of potentially vaccine-related, acute serious adverse events in individuals receiving 4CMenB was low (5·4 per 1000 individuals), but was significantly higher than routine vaccines (1·2 per 1000 individuals).


4CMenB has an acceptable short-term safety profile. The primary course is sufficient to achieve a satisfactory immune response within 30 days of vaccination. A booster dose is required for children to prolong the protection against strain M10713, and the long-term immunogenicity against strain NZ98/254 remains suboptimal.



Keywords: Neisseria Meningitidis; Meningococcal Disease; Vaccines.