Outbreak Reports: The First Case of Serogroup Y Neisseria meningitidis and An Expanded Investigation of Healthy Carriers — Shijiazhuang City, Hebei Province, China, 2023

The patient, a 17-year-old male boarding school student, had been vaccinated with Nm A+C polysaccharide vaccine in 2009 and 2012. The onset was rapid, beginning with a high fever (40 °C) and severe headache on November 23, 2023. Other clinical symptoms included nausea, vomiting, neck stiffness, and altered consciousness. Kernig’s sign and Brudzinski’s sign were positive. A blood test revealed a leukocyte count of 15.21×10⁹/L with 79% neutrophils. His cerebrospinal fluid (CSF) sample was turbid. Analysis showed a protein level of 2,410 mg/L, a white blood cell count of 1.978×10⁴/L, a glucose level of 0.02 mmol/L, and a chloride level of 117 mmol/L. After admission, he received meropenem, vancomycin, and ganciclovir for combined anti-infective treatment. On November 27, a third-party mNGS report indicated the detection of Nm sequences in the patient’s CSF. On November 28, the case was reported online as “meningitis, confirmed case, not classified.” On December 29, the patient was discharged after clinical treatment, cured, and without sequelae.

On December 4, the patient’s CSF Nm real-time PCR test for NmY was positive, though cultures were negative. Oropharyngeal swabs were then sampled from 166 healthy individuals, including 77 close contacts (Supplementary Table S1), and these samples underwent N. meningitidis culturing and real-time PCR testing. NmY strains were isolated from 18 samples (one per individual), with a total carriage rate of 10.84% (18/166). Among them, 7 strains were isolated from close contacts, with a carriage rate of 9.09% (7/77). Eleven strains were isolated from the other 89 individuals, with a carriage rate of 12.36% (11/89).

Epidemiological investigations revealed that the school operated under a closed boarding system with monthly holidays. The school had no vaccination requirements, and the patient had no travel history within two months and had not left the school within 15 days before disease onset. A total of nine other students shared a dormitory with the patient, and three of them experienced respiratory symptoms, including fever and rhinorrhea. All three recovered after receiving medication. The patient’s class comprised 76 students, all of whom attended classes in the same classroom; no other students developed meningococcal disease. All healthy carriers of NmY had no history of leaving the school within one month before the case occurred. The patient was also diagnosed with malnutrition upon admission to the hospital. No other individuals were found to be malnourished. Following this case, during the month-end holiday, the school underwent terminal disinfection, and all students isolated at home for two weeks. No subsequent cases were identified in the follow-up epidemiological investigation.

A total of 18 carriers of group Y meningococcus were found across 8 classes. Eleven were boys living in building A (including 2 in the same class and dormitory as the case patient, and 2 in the same class but different dormitories). Seven were girls living in building B (including 3 in the same class as the case patient) (Figure 1).

Figure 1. 

Class distribution of the patient and healthy carriers.

★ Remarked the case.

Metagenomic next-generation sequencing (mNGS) of the patient’s CSF was performed on the BGI G99 platform, yielding 242,348,594 reads with a Q30 of 93.92%. Reads were aligned to the reference genome of the case’s Nm using BWA software, resulting in 541,066 Nm reads (0.22% of the total). The aligned data were assembled using the SPAdes genome assembler v3.15.5, generating 128 contigs with a total length of 2,031,385 bp (93.66% of the average length). This sequence was used for genomic comparison of all strains in this investigation.

All strains isolated in this incident underwent whole-genome sequencing on the BGI G99 and ONT platforms. Comparison with the database identified the pathogen as belonging to the CC23 clonal complex. As of 26 March 2024, the PubMLST Neisseria Database contained 2,368 Neisseria meningitidis serogroup Y (NmY) genomes (CC23) from at least 33 countries; these CC23 genomes were downloaded for comparison. A phylogenetic tree was constructed using whole-genome single nucleotide polymorphism (wgSNP) data. MUMmer3.23 software identified SNPs among all strains. To improve data quality, SNP positions within 5 bp of each other and those containing unspecified nucleotides (“N”) were removed, resulting in a 15,413 SNP matrix. FastTree, using the maximum likelihood method, constructed the phylogenetic tree based on the wgSNP multiple sequence alignment (MSA). For further analysis, 52 representative genomes were selected, including NmY previously reported in China and global strains from 1966–2024 (Supplementary Table S2). The wgSNP-based phylogenetic tree revealed that the isolated strains clustered into two phylogenetic branches. The case sequence (Nm_23CSF) and six isolates from healthy individuals (Nm_1240, Nm_1241, Nm_1254, Nm_1266, Nm_1267, Nm_1269) belonged to the ST-18108 clonal complex (CC23). This group, designated the close contact group, formed a distinct phylogenetic branch significantly divergent from other national strains. Twelve other isolates from healthy individuals (Nm_1253, Nm_1255, Nm_1256, Nm_1257, Nm_1258, Nm_1259, Nm_1260, Nm_1262, Nm_1263, Nm_1264, Nm_1265, Nm_1268) belonged to ST-1655 (CC23) and clustered into another phylogenetic branch most closely related to strains from Portugal, the USA, Japan, New Zealand, and Sweden (Figure 2).

Figure 2. 

Phylogenies of lineages of Neisseria meningitidis serogroup Y strains by wgSNPs analysis.

Note: Phylogenetic analysis revealed that Nm_23CSF and six other strains were clustered into the CC23 cluster closest to the US and Portuguese strains, which were isolated from meningitis patients and healthy people. All strains’ PorA genotypes were determined to be P1.5-1, and the porB and fetA alleles of these strains were 10-1 and F4–1, respectively.

We investigated these 18 serogroup Y strains by whole-genome sequencing and submitted the whole-genome data to the Neisseria spp. database at https://pubmlst.org/. Among these 18 isolates, all were characterized as Y:P1.5–1,10–1:F4-1:ST-1655 (CC23), but 7 ST-18108 sequences harbored a novel gdh allele (1349). This ST-18108 has not been reported internationally. All 18 isolates from the carriers shared identical fHbp allele 25, porB allele 3-117, and nhba allele 10, indicating considerable genetic similarity. The 18 strains were divided into 3 types according to the capsular A region, and 7 ST-18108 sequences possessed csy gene number 1 (Table 1). The novel gdh allele and the novel ST sequence type were not related to vaccine antigen sites.

Nm is responsible for IMD globally, presenting primarily as septicemia and meningitis (1). Asymptomatic nasopharyngeal carriage occurs in up to 35% of individuals at any given time (2-3), but prevalence in the general population is highly variable by region, ranging from 10% to 35% (4). Nm serogroups are defined by their capsular polysaccharides, with A, B, C, W, and Y being the most pathogenic. Over the last two decades, serogroup Y IMD has increased in Europe and the United States (5–6). For example, serogroup Y was the most prevalent cause of IMD in Sweden in 2015, representing 53% of all cases (7). Recent IMD cases in China have been caused mainly by serogroups C, A, B, and W (8); serogroup Y IMD is rare. To date, only 9 cases of serogroup Y IMD have been reported in China (Table 2): 1 in Tianjin in 2015 (9), 2 in Guangdong in 2019 (10–11), 1 in Hunan (12), 1 in Shanghai (13), 1 in Hunan in 2020 (12), 1 in Guangdong in 2021 (14), 1 in Zhejiang in 2021 (15), and 1 in Guangdong in 2023 (16). These Chinese serogroup Y cases were the internationally common ST-1655 or ST-23 types, both belonging to the CC23 complex. The case in this paper is the only NmY case reported in Hebei Province in the past 10 years. Previous continuous surveillance of meningococcal infection identified serogroup B as the predominant strain, although serogroups W and Y were occasionally isolated from throat swab samples of healthy individuals.

Laboratory testing identified this case as the first serogroup Y Nm case in Hebei Province, caused by a novel sequence type (ST) within CC23. This ST represents the first reported instance of this NmY CC23 in China. Epidemiological investigation indicated this was a sporadic, locally acquired case, with no other similar cases identified during this period. While the reported NmY carriage rate among healthy individuals in China is 0.01% (17), this investigation identified 18 asymptomatic carriers among 166 individuals, resulting in a carriage rate of 10.84% (18/166). Epidemiological findings suggest that this strain established a transmission vector within the school, potentially posing a challenge to local invasive meningococcal disease (IMD) prevention and control. Increased international travel elevates the risk of NmY importation into China, potentially altering the dominant circulating strains.

Although failure to isolate the Nm strain from the patient’s CSF was likely due to the delay between sampling and testing, Nm DNA fragments were identified in the CSF, and the complete Nm genome was assembled using mNGS. Integrating sequencing data from carriers ensured the integrity and accuracy of the laboratory data.

In Europe, the age of Neisseria meningitidis serogroup Y cases exhibits a bimodal distribution. In addition to the commonly reported adolescents and young adults aged 15 to 20 years, 50% of patients are between 45 and 88 years old (6). The patient in Hebei Province was 17 years old, within the high-incidence age range.

Genetic analysis revealed that the serogroup Y N. meningitidis strains prevalent in this school belonged to two phylogenetic branches. Similar cases involving other serogroups have been occasionally reported (18). Serogroup Y Nm ST-18108, belonging to CC23, was identified in this meningitis case and has not been previously reported. Phylogenetic analysis demonstrated that ST-18108 has a distant genetic relationship with NmY cases reported in China and other countries. Within the contact group, 5 classmates (Nm_1240, Nm_1241, Nm_1266, Nm_1267, and Nm_1269) were all close contacts of the patient. Only 1 student (Nm_1254), with whom the patient had contact, did not meet the definition of close contact. The patient's malnutrition may have contributed to lowered immunity (19), predisposing them to disease.

The clustering results, based on MLST, further demonstrate that the CC23 identified in this study is distinct from previously isolated strains. This suggests the emergence of a novel clone group in Hebei Province. The initial appearance of this clone group resulted in cases that rapidly spread on a small scale within the population, leading to widespread carriage. This indicates potentially greater pathogenicity and transmissibility of this NmY clone group compared to previous NmY strains, warranting further investigation. Host factors may also have contributed to the invasiveness of the infection. Given the increasing incidence of N. meningitidis serogroup Y cases reported both domestically and internationally, enhanced surveillance of NmY is crucial. Immunization strategies should be adjusted accordingly to prevent outbreaks of serogroup Y meningococcal disease in key settings such as schools and to reduce the incidence of fatal cases.

We thank the staff of the provincial, prefectural, and county CDCs and all clinics for investigation. We thank Dr. Biao Kan, senior consultant of China CDC, for his recommendations for editing the manuscript.