Background: Meningococcal disease caused by Neisseria meningitidis (Nm) varies substantially by geography and time. In Nigeria's meningitis belt, serogroup C (NmC) has historically dominated outbreaks; however, serogroup X (NmX) is capable of causing epidemics with high case-fatality rates. The recently introduced pentavalent meningococcal conjugate vaccine (Men5CV), which protects against NmX, remains inaccessible across much of the African meningitis belt. Genomic characterisation of circulating NmX strains is critical to understanding transmission dynamics and informing evidence-based vaccine policy.
Methods: All 1,192 cerebrospinal fluid (CSF) samples collected from suspected meningitis cases during outbreak surveillance in Nigeria (2017–2021) were tested by multiplex polymerase chain reaction (PCR) targeting sodC, lytA, and hpd. Sixty-six samples positive for NmX underwent targeted whole-genome sequencing (WGS; n=24) at University College London, using RNA-bait capture for bacterial enrichment followed by Illumina sequencing. Sequence quality control and N. meningitidis characterisation were performed using a Galaxy-hosted pipeline (galaxy.sciensano.be) with the PubMLST Neisseria database for multilocus sequence typing (MLST), fine-typing, and maximum-likelihood phylogenetic analysis.
Results: Of 1,192 CSF samples, 340 (28.5%) were confirmed meningococcal. NmC was the dominant serogroup (253/340; 74.4%), followed by NmX (66/340; 19.4%) and non-groupable strains (21/340; 6.2%). Other pathogens included Streptococcus pneumoniae (85; 7.1%) and Haemophilus influenzae (43; 3.6%). Of 24 sequenced samples, N. meningitidis was confirmed in 19/24 (79.2%); five yielded low-quality sequences or non-meningitidis species. MLST was resolved for 13/19 (68.4%): 11/13 (84.6%) were CC181:ST181 with antigen profile PorA:P1.5-1,10-1; PorB:231; FetA:F1-31; fHbp:61; NadA:null; NHBA:75 — serogroup X capsule was confirmed in 1/11 (9.1%), with the remainder inconclusive at the capsule locus. Two samples (2/13; 15.4%) belonged to CC10217:ST9367 with a serogroup C capsule locus (PorA:P1.21-15,16 and P1.5-11,16; PorB:506; FetA:F1-7).