Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality worldwide through an epidemic or sporadic invasive infections. The epidemiology of N. meningitidis is changing and unpredictable. Certain emerging meningococcal genotypes seem to be associated with increasing unusual clinical presentations. Indeed, early symptoms may vary and are frequently non-specific. However, atypical clinical forms including abdominal presentations, septic arthritis, and bacteremic pneumonia may lead to misdiagnosis and some are usually associated with higher case fatality rates due to delayed optimal management. Improving awareness of clinicians and public health specialists about these unusual but potentially severe presentations should help establish prompt diagnoses and provide appropriate management of cases. In this review, we described unusual panels of clinical presentations of invasive meningococcal disease linked to the recent changes in meningococcal epidemiology.

Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical measures to control the COVID-19 pandemic. A rebound in IMD cases was feared upon easing these measures. We conducted a retrospective descriptive study using the French National Reference Center Database for meningococci between 2015 and 2022. We scored serogroups, sex, age groups, and clonal complexes of the corresponding isolates. Our data clearly show a decline in the number of IMD cases for all serogroups and age groups until 2021. This decline was mainly due to a decrease in IMD cases provoked by the hyperinvasive ST-11 clonal complex. However, since the fall of 2021, there has been an increase in IMD cases, which accelerated in the second half of 2022. This rebound concerned all age groups, in particular 16-24 years. The increase in cases due to serogroups B, W, and Y were mainly due to the expansion of isolates of the ST-7460, the clonal complex ST-9316 and the clonal complex ST-23, respectively. IMD epidemiology changes constantly and profound epidemiological changes have been recently observed. The surveillance of IMD needs to be enhanced using molecular tools. Additionally, vaccination strategies need to be updated to acknowledge recent epidemiological changes of these vaccine-preventable serogroups.

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.

Since January 2018, mandatory vaccination against meningococci serogroup C has been implemented in France for children <2 years with a recommended catch-up vaccination until the age of 24 years. We aimed to analyse the impact of mandatory vaccination on populations not targeted by it (2–24 years old). We used the database of the national reference centre for meningococci to collect the number of invasive meningococcal disease (IMD) cases before (2016–2017) and after (2018–2019) the mandatory vaccination. The cultured isolates were sequenced and submitted for genomic comparison. The total number of cases was 1706, including 376 cases of IMD serogroup C. Mandatory vaccination correlated with a significant decrease among the <2 years old and a decreasing trend among the 2–14 years old group but not among 15–25 years of age. This observation may be explained by the vaccine coverage that is still low among adolescents and young adults. Moreover, the genomic analysis revealed the co-circulation of two major genotypes belonging to the clonal complex ST-11 whose distribution differed across the age groups in accord with cyclic variations of genotypes. It is important to increase specific knowledge on meningococcal epidemiology and vaccination to involve them in establishing the vaccination strategy.

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.

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.