Samy Taha

Background/Objectives: Re-emergence of Haemophilus influenzae serotype b (Hib) was reported in several European countries. We aimed to characterize the age distribution of H. influnezae carriage before and after Hib vaccination. Methods: We conducted a systematic review and meta-analysis to reassess H. influenzae carriage dynamics in the pre- and post-Hib vaccination eras, focusing on age-specific patterns in childhood. Searches were performed with no date restriction and included PubMed/MEDLINE, Scopus, Web of Science, WHO Global Index Medicus, and the Cochrane Library. Eligible studies reported nasopharyngeal and/or oropharyngeal carriage prevalence and serotype distribution. Pooled estimates with 95% confidence intervals (CIs) were calculated using random-effects models, with age-stratified analyses. Results: Twenty-two studies were included (12 pre- and 10 post-Hib vaccination). Pre-vaccination, pooled H. influenzae carriage prevalence was 24.3% (95% CI, 18.9–30.7%), including 6% (95% CI, 3.4–12.8%) for Hib and 17.5% (95% CI, 12.6–23.9%) for non–type b strains. Post-vaccination, overall carriage remained similar (21.8%; 95% CI, 14.6–31.2%), but Hib carriage declined markedly to 0.67% (95% CI, 0.26–1.71%), while non–type b strains predominated (16.7%; 95% CI, 10.4–25.6%). Meta-analysis showed that carriage peaked around 4–5 years of age and persisted into later childhood. Conclusions: Hib vaccination has reduced Hib carriage, but overall H. influenzae carriage persists due to non–type b strains. Age-related persistence of carriage may have implications for herd protection, particularly in the context of evolving vaccination schedules with early childhood boosters. Continued surveillance integrating carriage and immunological data is needed to inform optimization of vaccination strategies.

Haemophilus influenzae type b (Hib) conjugate vaccines have markedly reduced global invasive Hib disease. However, surveillance in France has shown a resurgence of Hib infections in children despite >90% vaccination coverage, coinciding with the shift from a 3 + 1 to a 2 + 1 schedule. All laboratory-confirmed Hib cases reported to the French National Reference Centre for Meningococci and Haemophilus influenzae (NRCMHi) between 2017 and 2024 were analysed. Vaccine failure was defined as invasive Hib disease at least 2 weeks after completion of the age-appropriate schedule. Clinical, microbiological, and immunological data were collected, including whole-genome sequencing (WGS), anti-polyribosylribitol phosphate (PRP) IgG levels, and complement deposition assays. Among 1663 invasive H. influenzae cases, 268 (16.1%) were due to Hib, with annual proportions rising from 6.9% in 2017 to 16.8% in 2024. Of 197 cases in children under 5 years, 174 had known vaccination status; 55 (31.6%) met criteria for vaccine failure after completing the 2 + 1 schedule. All isolates were ST-6 clonal complex, without genotype linked to failure. Capsule locus duplication was found in 37% of isolates but unrelated to vaccination status. Acute-phase sera from failure cases showed anti-PRP IgG < 1 µg/mL, with convalescent titres rising above1 µg/mL; complement C3b and C5b-9 deposition correlated with antibody levels. The resurgence of Hib among fully vaccinated children highlights the need to reassess the 2 + 1 schedule and strengthen serological monitoring to sustain herd protection.

Invasive meningococcal disease (IMD) is classically associated with meningitis and septic shock, but an increasing proportion of cases present with atypical, extra-meningeal manifestations. Following the COVID-19 pandemic, major epidemiological shifts have occurred in France, including a rebound in IMD incidence and changes in circulating serogroups and clonal complexes. We conducted a nationwide retrospective study including all laboratory-confirmed IMD cases analysed by the French National Reference Centre between July 2014 and June 2025. Clinical presentations were coded as non-exclusive entities. Associations with age, serogroup, clonal complex, antimicrobial susceptibility and early mortality (≤72 h) were assessed using descriptive analyses and multivariable logistic regression models. Among 4328 IMD cases, sepsis/shock (61.1%) and meningeal involvement (54.9%) predominated, while atypical forms were frequent, including bacteraemic pneumonia (7.7%), abdominal presentations (8.0%) and arthritis (6.0%). Bacteraemic pneumonia was strongly associated with older age and serogroups W and Y, whereas abdominal forms predominated in adolescents and young adults and were independently associated with serogroups W and Y and clonal complex (cc) cc11. Abdominal presentations were independently associated with early mortality (adjusted odds ratio [aOR] 2.40) but not meningococcal pneumonia. Abdominal presentations were associated with serogroup W (aOR 2.27; 95% CI 1.35–3.83) and serogroup Y (aOR 2.92; 95% CI 1.79–4.75) and with cc11 (aOR 1.77; 95% CI 1.07–2.94). In contrast, cc23 was associated with lower odds of abdominal involvement (aOR 0.42; 95% CI 0.25–0.70). Overall, atypical presentations now represent a substantial proportion of IMD in France and are strongly shaped by age and meningococcal lineage. These findings highlight diagnostic challenges, prognostic heterogeneity and the need for continued integrated clinical, microbiological and genomic surveillance in the context of evolving vaccination strategies.

Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about an “immunity gap” due to reduced circulation of the bacteria. During the study period, vaccination against MenC was mandatory from 2018, and vaccination against MenB has been recommended since 2022. Methods: We conducted a retrospective seroepidemiological study using 166 normal sera collected between 2016 and 2024. Anti-Neisseria meningitidis IgG levels were quantified by ELISA using purified capsular polysaccharides for serogroups B, C, W, Y, and X. Samples were categorized into three periods: pre-NPIs (n = 72), during NPIs (n = 33), and post-NPIs (n = 61). Statistical comparisons were performed using Kruskal–Wallis tests for non-parametric data. Results: Our results show a significant decline in anti-serogroup B IgG antibody levels after the lifting of NPIs (p < 0.0001) in line with reduced circulation. Anti-serogroup C IgG antibody levels increased incrementally (p = 0.0003), particularly in those aged 1–4 years, likely reflecting a catch-up in anti-meningococcal C vaccination coverage. Anti-serogroup W IgG antibody levels remained stable, suggesting sustained circulation, but shifted to young children in the post-NPI period, potentially due to a genotypic shift. Anti-serogroup Y IgG antibody levels transiently increased significantly (p < 0.0001) during the NPI period but then decreased back after their lifting. Anti-serogroup X IgG antibody levels remained stable, consistent with its low prevalence and the absence of targeted vaccination.

Most cases of invasive meningococcal disease (IMD) in Europe are caused by isolates of the Neisseria meningitidis serogroups B, C, W, and Y. We aimed to explore cases caused by other unusual serogroups. We retrospectively screened IMD cases in the databases of the National Reference Center for Meningococci and Haemophilus influnezae in France between 2014 and 2023. Age, sex, serogroups, and genetic lineage distributions were analyzed. We also measured complement deposition on the bacterial surface and tested coverage by vaccines against serogroup B. Cases due to isolates of serogroups other than B, C, W, and Y represented 1.6% of all 3610 IMD cases during the study period with 59 cases and a median age of 21.5 years of age. The corresponding isolates were non-groupable (26 cases), serogroup X (21 cases), serogroup E (11 cases), and one isolate belonged to serogroup Z. Only a low proportion (7.4%) belonged to the hyperinvasive genetic lineages. Isolates of serogroup E bound a significantly higher amount of complement on their surface and were mainly detected in patients with terminal complement pathway deficiencies. Isolates of these unusual serogroups were shown to be covered by vaccines licensed against meningococci B. Surveillance of these isolates needs to be enhanced.

Neisseria meningitidis can be surrounded by a polysaccharide capsule that defines one of the 12 meningococcal serogroups, of which 6 (A, B, C, W, X and Y) are the most frequent among invasive meningococcal disease (IMD) cases. Unencapsulated or non-serogroupable (NG) isolates are usually encountered in carriers, although IMD cases are sometimes reported with NG isolates. Isolates are also characterized based on DNA sequences that classify isolates into MLST STs according to homologies of gene fragments of seven housekeeping genes. Related STs are further grouped into clonal complexes.¹ IMD is dominated by meningitis and septicaemia, which leads to a severe disease burden. As such, it requires prophylactic measures including antibiotic prophylaxis and vaccination. N. meningitidis is still susceptible to most antibiotics that are used for treatment and prophylaxis.² Ciprofloxacin is recommended for antibiotic prophylaxis. Resistance to this antibiotic in N. meningitidis (MIC > 0.016 mg/L) was previously extremely rare in Europe and was reported only from sporadic cases.³ However, several recent reports from India and China have described increased ciprofloxacin resistance.² Moreover, recent reports have described meningococcal isolates among travellers or migrants in Europe.^4,5 Here we describe four cases of IMD due to ciprofloxacin-resistant N. meningitidis isolates in 2023 in France.

Most of the invasive meningococcal disease (IMD) in Europe are caused by isolates of Neisseria meningitidis serogroups B, C, W and Y. We aimed to explore cases caused by other, unusual serogroups. We retrospectively screened IMD cases in the databases of the National Reference Center for Meningococci and Haemophilus influnezae in France between 2014-2023. Age, sex, serogroups, and genetic lineages distributions were analyzed. We also measured complement deposition on the bacterial surface and tested coverage by vaccines against serogroup B. Cases due to isolates of serogroups other than B, C, W, and Y represented 1.6% of all 3610 IMD cases during the study period, with 59 cases and a median age of 21.5 years of age. The corresponding isolates were non-groupable (26 cases), serogroup X (21 cases) serogroup E (11 cases) and one isolate belonged to serogroup Z. Only a low proportion (7.4%) belonged to the hyperinvasive genetic lineages. Isolates of serogroup E bound a significantly higher amount of complement on their surface and were mainly detected in patients with terminal complement pathway deficiencies. Isolates of these unusual serogroups were shown to be covered by vaccines licensed against meningococci B. Surveillance of these isolates needs to be enhanced.

Background: Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical interventions (NPI) (social distancing and mask wearing) to control the COVID-19 pandemic but rebounded in 2022 in numbers with genotypical changes of the strains. We explored here associated modifications in the clinical presentations of IMD. Methods: We conducted a retrospective descriptive study using the Database of the French National Reference Centre for meningococci and Haemophilus influnezae for IMD cases between 2015 and 2022. We scored serogroups, sex, age groups, clinical presentations and clonal complexes of the corresponding patients and isolates. Findings: Non-meningeal forms of IMD increased significantly upon easing of NPI, such as bacteremic meningococcal pneumonia and bacteremic abdominal forms. They represented 6% and 8% of all IMD forms and were significantly linked to serogroups Y and W respectively, to older adults for bacteremic pneumonia and to young adults for bacteremic abdominal presentations. These forms were significantly associated with more early mortality and clonal complexes 23, 11 and 9316. Interpretation: The increase in atypical IMD forms may lead to higher burden of IMD due to delayed diagnosis and management. Updating prevention may be needed through by adapting the current vaccination strategies to epidemiological changes.

Background: Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical interventions (NPI) to control the COVID-19 pandemic but rebounded since the second half of 2022 in numbers with genotypical changes of the strains. We explored in this report associated modifications in the clinical presentations of IMD. Methods: We conducted a retrospective descriptive study using the French National Reference Centre Database for meningococci between 2015-2022. We scored serogroups, sex, age groups, clinical presentations and clonal complexes of the corresponding isolates. Findings: Non-meningeal atypical forms of IMD increased significantly upon easing of NPI, such as bacteriemic meningococcal pneumonia and abdominal forms. They represented 6% and 8% of all IMD forms and were significantly linked to serogroups Y and W respectively, to older adults for bacteriemic pneumonia and to young adults for abdominal presentations. These atypical forms were also significantly associated with more early mortality. Interpretation: An upsurge of atypical forms in France since the lifting of COVID-19-related NPI accompanied the rebound of IMD cases. An increase in IMD burden may be expected and urge to enhance preventive strategies against IMD by adapting current vaccination strategies to epidemiological changes.

The rebound of invasive meningococcal disease cases in France since the fall of 2022 was accompanied by an increase in adult epiglottitis. These cases were provoked mainly by isolates of serogroup W belonging to the clonal complex 11 of Neisseria meningitidis. Awareness and surveillance should be reinforced.