Overall characteristics of IMD clinical presentations between 2015 and 2022
Characteristics of this database for the number of cases, average age and sex ratio were previously reported in another study [12]. It includes 2,719 cases of IMD between 2015 and 2022 with no significative variation of the average sex ratio and the average median age [12].
The bacteriemia/shock clinical presentation remained the main presentation of IMD during the studied period. Its percentage remained stable during the whole study period, varying non-significantly (p = 0.94) between 44.7% (318 cases in 2021) and 50.3% % (71 cases in 2022) (Fig. 1). This 2022 bacteremia/shock increase was significantly associated with serogroups W and Y (p < 0.0001) (Supplementary Fig. 1). Consequently, bacteremia/shock was significantly more frequent with isolates of the clonal complex 11 as it represented 65% of identified IMDW cases between 2015 and 2022 (p < 0.0001). However, bacteremia/shock was also linked to isolates that were non-assigned to known clonal complexes (p < 0.0001) and to older adults of ≥ 65 years of age (p < 0.0001) (Fig. 2A and 2B).
The meningeal presentation was significantly more frequent in proportion before the COVID-19 pandemic and decreased from 44.1% (240 cases in 2015) to 32.7% (in 156 cases in 2022) but this reduction remained non-significant (p = 0.03 with a threshold at 0.01 for 5 comparisons) (Fig. 1). Meningeal presentation was significantly associated with serogroup B (p < 0.0001) (Supplementary Fig. 1), with clonal complex 32 (p < 0.0001), 41/44 (p < 0.0001), and 213 (p = 0.001) which are all related to IMDB. Meningeal form was also prevalent among the less than 5-year-olds (p < 0.0001) (Fig. 2A and 2B).
There was an increase of bacteriemic meningococcal pneumonia increasing from 2.6% of all clinical forms in 2015 up to 8.2% in 2021 and 6.1% in 2022 but these variations remained at the level of significance (p = 0.01) (Fig. 1). Bacteriemic meningococcal pneumonia was significantly associated with serogroups W and Y (p < 0.0001) (Supplementary Fig. 1), to clonal complexes 11 and 23 (p < 0.0001), and among older adults of ≥ 65 years of age (p < 0.0001) (Fig. 2A and 2B).
Abdominal presentations significantly increased during the study period and particularly in 2022 (p = 0.0001), increasing from 2% in 2015 to 5.7% in 2021 and 8% in 2022 (Fig. 1). They were significantly associated with serogroup W (p < 0.0001) (Supplementary Fig. 1), to clonal complex 11 (p < 0.0001), and were more frequent among the 20–24 years-olds (p = 0.005) (Fig. 2A and 2B). It is noteworthy abdominal presentations that provoked by W/cc11 isolates dropped over the study period from 49.5% between 2015 and 2019 to only 15.3% from 2020 to 2022, without significant changes in the number of non-cc11 abdominal forms between these two periods (56 and 50 cases respectively).
Conversely, meningococcal arthritis did not significantly change during the study period and varied between 5.6% and 2.9%. Meningococcal arthritis was significantly associated with serogroup C and W (p < 0.0001) (Supplementary Fig. 1), to clonal complex 11 (p < 0.0001), but wasn’t significantly associated with a specific age group (Fig. 2A and 2B).
Early IMD mortality, as defined in the Methods section, was 7.6% and varied non-significantly between 6.25% in 2022 to 8.8% in 2015.
Meningeal and arthritis presentations were significantly associated with fewer early deaths (p = 0.001 and p = 0.0002 respectively). Particularly, there was no death between 2015 and 2022 linked to meningococcal arthritis.
Conversely, bacteriemic meningococcal pneumonia and abdominal presentations were significantly linked with more early deaths (p = 0.0015 and p < 0.0001 respectively), with an early mortality rate of 13.5% and 15.1% respectively (Fig. 3). Bacteriemia/shock was also significantly associated with more early deaths (p < 0.0001).
Characteristics of serogroup B IMD clinical presentations between 2015 and 2022
IMD due to serogroup B (IMDB) isolates remained the most prevalent (n = 1354) between 2015 and 2022, representing an average of half of IMD cases.
Typical presentations (bacteriemia/shock and meningeal) represented an average of 93% of all IMDB forms. However, the proportion of abdominal presentations significantly increased from 4 to 7.8% in 2022 (p = 0.0006) (Supplementary Fig. 1).
IMDB bacteriemic meningococcal pneumonia presentation was significantly more prevalent among the 65 and older age group (p < 0.0001) (Fig. 4). But no IMDB clinical presentation is significantly associated with a specific clonal complex.
Characteristics of serogroup C IMD clinical presentations between 2015 and 2022
IMDC cases evolved in a particular way before the COVID-19 pandemic, due to multiple factors: mainly the modification of the vaccination recommendations against MenC in 2017, the mandatory vaccination in 2018, and the modification of the circulating strains [14]. The proportion of IMDC cases drastically decreased from 27% of all cases in 2015 to 12.5% in 2019 and then further to 3% in 2021 and 2022, with a very marginal rebound that year [12].
Typical presentations (bacteriemia/shock and meningeal) also represented an average of 86% all IMDC forms during the study period. This proportion did not significantly vary but the low number of cases makes the statistical analysis less relevant (Supplementary Fig. 1).
When all IMDC were considered, bacteriemic pneumonias were significantly more prevalent among the 65 and over age group (p < 0.0001) (Fig. 5). Clonal complex 11 represented 91% of identified IMDC cases across the study period but clinical presentations associated with this clonal complex did not vary significantly when compared with the other CCs.
Characteristics of serogroup W IMD clinical presentations between 2015 and 2022
IMDW have been increasing since 2015 in France, modifying their clinical presentations. Serogroup W was identified in 35% of all IMD abdominal presentations between 2015 and 2022, compared with only 16% between 1991 and 2016 [7].
IMDW decreased during the pandemic but rebounded sharply since 2022 across all age groups, exceeding pre-pandemic levels [12]. However, there was no significant variation in the distribution of clinical presentations from one year to another between 2015 and 2022.
IMDW significantly varied from one age group to another since 2015 (Supplementary Fig. 1).
Meningeal presentations were significantly more prevalent among the less than 1 year of age (p < 0.0001) and the 1–4-year-olds (p = 0.0035). Abdominal presentations were significantly more present among the 15–19-year-olds and 20-24-years-olds (p = 0.0007). Bacteriemic pneumonia presentations were again significantly more prevailing among the 65 and older age group (p < 0.0001) (Fig. 6).
As for serogroup C, the hyperinvasive clonal complex 11 represented 63% of all IMDW cases during the study period. But when compared with the other clonal complexes, it wasn’t associated with a particular clinical form.
Characteristics of serogroup Y IMD clinical presentations between 2015 and 2022
Unlike the other serogroups, IMDY were uncommon before the age of 15 and occurred mainly among the 65 and older. But since the COVID-19 pandemic, IMDY increased from 12% in 2019 and 2020 to 25% in 2022, becoming the second most prevalent serogroup in France and rebounding even across younger age groups that year [12].
Despite this sharp rebound, IMDY clinical presentations did not vary significantly on the studied period from one year to another.
Bacteriemic meningococcal pneumonia due to serogroup Y was significantly more prevalent among the 65 and older year-olds (p < 0.0001) (Fig. 7). Serogroup Y was associated with 42% of all bacteriemic pneumonia presentations between 2015 and 2022 and 46% of bacteriemic pneumonia presentations among the 65 and older age group (Fig. 1 and Fig. 7).
Clonal complex 23 represented 70% of all IMDY during the study period. But it was not associated with a specific clinical form when compared with the other clonal complexes of serogroup Y (Fig. 2B).