1887

Abstract

We studied population genomics of 486 isolates causing meningitis in the Netherlands during the period 1979–2003 and 2006–2013 using whole-genome sequencing to evaluate the impact of a hyperendemic period of serogroup B invasive disease. The majority of serogroup B isolates belonged to ST-41/44 (41 %) and ST-32 complex (16 %). Comparing the time periods, before and after the decline of serogroup B invasive disease, there was a decrease of ST-41/44 complex sequences (=0.002). We observed the expansion of a sub-lineage within ST-41/44 complex sequences being associated with isolation from the 1979–2003 time period (=0.014). Isolates belonging to this sub-lineage expansion within ST-41/44 complex were marked by four antigen allele variants. Presence of these allele variants was associated with isolation from the 1979–2003 time period after correction for multiple testing (Wald test, =0.0043 for FetA 1–5; =0.0035 for FHbp 14; =0.012 for PorA 7–2.4 and =0.0031 for NHBA two peptide allele). These sequences were associated with 4CMenB vaccine coverage (Fisher’s exact test, <0.001). Outside of the sub-lineage expansion, isolates with markedly lower levels of predicted vaccine coverage clustered in phylogenetic groups showing a trend towards isolation in the 2006–2013 time period (=0.08). In conclusion, we show the emergence and decline of a sub-lineage expansion within ST-41/44 complex isolates concurrent with a hyperendemic period in meningococcal meningitis. The expansion was marked by specific antigen peptide allele combinations. We observed preliminary evidence for decreasing 4CMenB vaccine coverage in the post-hyperendemic period.

Funding
This study was supported by the:
  • Arie van der Ende , Rijksinstituut voor Volksgezondheid en Milieu
  • John A Lees , Medical Research Foundation , (Award 1365620)
  • Stephen D Bentley , Wellcome Trust , (Award 098051)
  • Diederik van de Beek , ZonMw , (Award 016.116.358)
  • Diederik van de Beek , H2020 European Research Council , (Award 281156)
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2020-08-10
2020-10-22
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