Epidemiological characteristics of invasive meningococcal disease and carriage prevalence of Neisseria meningitidis in the Xinjiang Uygur Autonomous Region, China, 2004–2023: a retrospective study

Introduction

Invasive meningococcal disease (IMD) is a systemic bacterial infection caused by the gram-negative bacterium Neisseria meningitidis, leading to septicaemia and meningitis (Dubey et al., 2022; Read, 2019). It exhibits pronounced seasonality with bimodal incidence peaks clustered in late winter and early spring, consistent with respiratory pathogen transmission dynamics under cold-dry climatic conditions. Globally, the case fatality rate of IMD is as high as 20%, with a high disability rate and severe disease burden (Parikh et al., 2020; Wang et al., 2019). It is estimated that there are approximately 1.2 million cases of N. meningitidis infection worldwide each year (mainly IMD), with a high death toll of 135,000 (Jafri et al., 2013; Peterson et al., 2019a), and 5–15% of cases will still have serious sequelae after healing (Howitz et al., 2009). N. meningitidis, an opportunistic pathogen, and asymptomatically colonizes the nasopharyngeal mucosa in healthy individuals. Humans are the only hosts of this bacterium, and approximately 10% of the healthy population carries N. meningitidis, which has become the main source of infection in the current epidemic of IMD (Alemayehu, Mekasha & Abebe, 2017; Wang et al., 2019). According to the different antigen structures of capsule polysaccharides, N. meningitidis can be divided into 12 serogroups: A, B, C, X, Y, W, Z, E, L, H, I, and K. More than 95% of the cases were caused by six serogroups A, B, C, Y, W and X (Beebeejaun et al., 2020).

While global surveillance data indicate that IMD incidence has reached historically low levels since the introduction of conjugate vaccines, persistent disparities emerge across demographic and geographic strata and hyperendemic transmission persists in meningitis belt regions and marginalized populations with <50% MenACWY vaccine coverage (Alderson et al., 2022; GBD 2016 Meningitis Collaborators, 2018). After 2000, the incidence rate of IMD in European and American countries and regions remained at 0.11/100,000 to 2.00/100,000 (Zhang et al., 2016). In 2020, the incidence rate will be 0.56/100,000 in Spain and 0.17/100,000 in Brazil (Alderson et al., 2022). In 2010, after the introduction of meningococcal polysaccharide conjugate vaccine group A (MPCV-A) in Africa and the start of vaccination, the incidence rate of IMD group A decreased significantly to 0.02/100,000 (Clément et al., 2015). Since 2005, China has entered a low incidence period of IMD. From 2015 to 2019, the incidence rate of IMD in China was 0.078/100,000 people, and the case fatality rate was 11.82% (Li et al., 2019). Despite China’s national IMD incidence remaining below since 2010, Xinjiang Uygur Autonomous Region (Xinjiang) persists as the nation’s hyperendemic epicenter. The average annual incidence rate from 2005 to 2010 was 0.56/100,000, which is significantly higher than that in other provinces; additionally, there were occasional outbreaks and epidemics (Li et al., 2015).

Currently, there are many studies on N. meningitidis carriage status around the world, molecular epidemiological surveillance reveals marked temporal shifts in meningococcal carriage prevalence among asymptomatic populations (Kristinsdottir et al., 2023; Miellet et al., 2021; Ong et al., 2023). In China, several provinces and cities have carried out surveys on N. meningitidis carriage rates (He et al., 2020; Yue et al., 2022). In contrast, there is less basic information on the N. meningitidis carriage status among asymptomatic populations in Xinjiang.

This population-based study was conducted to delineate the epidemiologic characteristics of IMD and carrier status of meningococci (not IMD) in Xinjiang, to establish an evidence-based precision prevention framework of IMD in Xinjiang.

Materials and Methods

Results

Epidemiological characteristics

Time distribution

From 2004 to 2023, a total of 1,100 cases of IMD were reported in Xinjiang, and the annual incidence rate fluctuated between 0.00/100,000–1.15/100,000. Among them, with the highest incidence rate (1.15/100,000) occurring in 2007. Two peaks occurred in 2009 and 2014, with incidence rates of 0.52 per 100,000 and 0.38 per 100,000, respectively. After 2014, the IMD incidence fluctuated at a low level, with a small peak in 2016, with an incidence rate of 0.19/100,000. Since 2019, the incidence has shown a significant downward trend, with the lowest incidence (0.01/100,000) in 2020, with three cases, and no cases reported in 2021 (Fig. 1A).

From 2004 to 2023, a total of 102 IMD deaths were reported in Xinjiang, with a fatality rate of 9.27%. The annual mortality rate fluctuated between 0.00/100,000–0.09/100,000, and the annual case fatality rate was 0–20%. The death rate in 2007 (0.09/100 000) was the highest, with 19 deaths (8.02%), followed by 2009 (0.05/100 000), with 15 deaths (12.71%). Since 2010, there has been a downward trend in deaths, with a small peak in 2016, and no deaths have been reported since 2020 (Fig. 1B).

The incidence shows obvious seasonality, with a peak from February to May, accounting for 61.73% (679/1,100) of the total incidence. Among them, April had the highest incidence, accounting for 22.91% (252/1,100) of the total incidence. The number of cases in September and October was the lowest, with 22 and 21 cases, respectively, showing an increasing trend from November to December (Fig. 1C).

Regional distribution

From 2004 to 2023, cases of IMD were reported in all 14 prefectures (states and cities) under the jurisdiction of Xinjiang, with the three highest annual average incidence rates being 0.58/100,000 in Hotan Prefecture, 0.46/100,000 in Kashgar Prefecture and 0.37/100,000 in Urumqi city. The bottom three annual average morbidity rates were 0.02/100,000 in Tacheng, 0.03/100,000 in Karamay/Mongolia Autonomous Prefecture of Bortala (Bortala) and 0.04/100,000 in Changji Hui Autonomous Prefecture (Changji). The three highest annual average mortality rates were 0.06/100,000 in Urumqi city, 0.05/100,000 in Turpan city and 0.05/100,000 in the Hotan region. No fatal cases were reported in the three regions of Changji, Bortala and Altay. The three regions with the highest case fatality rates were 50% in Karamay city, 20% in the Tacheng region and 17.65% in Urumqi city. Of the total number of reported cases, 66.45% (731/1,100) were reported in the southern Xinjiang region, and 33.55% (369/1,100) were reported in the northern Xinjiang region (Fig. 2).

Population distribution

Of the 1,100 cases of IMD reported in Xinjiang from 2004 to 2023, 687 were male and 413 were female, with a male-to-female sex ratio of 1.66:1 (Fig. 3).

From 2004 to 2023, the incidence population in Xinjiang was mainly concentrated in people under 20 years of age, accounting for 80.36% (884/1,100) of the total number of cases. 10–15 years of age had the highest number of incidence cases, accounting for 16.09% (177/1,100) of the total number of cases, followed by 15–20 years of age, accounting for 15.82% (174/1,100) of the total number of cases. The number of reported cases in the age group above 25 years showed a decreasing trend with increasing age (Fig. 3).

The top three cases were scattered children, students and farmers, accounting for 34.18% (376/1,100), 33.27% (366/1,100) and 17.00% (187/1,100) of the total number of cases, respectively. Teachers, laborers and businessmen were the last three with the lowest number of cases, with two, five and five cases, respectively (Fig. 4).

Discussion

In recent years, the incidence of IMD in Xinjiang has reached a relatively high level in the country, and some areas have even experienced an explosive epidemic (Li et al., 2015). Therefore, this study investigated the epidemiological characteristics of IMD in Xinjiang from 2004 to 2023 and the carriage situation of N. meningitidis among the healthy population. Epidemiological transition analysis revealed that Xinjiang Uygur Autonomous Region (Xinjiang)—China’s meningitis hyperendemic frontier bordering Central Asia—underwent a paradigm shift from cyclical epidemic patterns to sustained hypoendemic transmission, yet still maintaining higher disease burden compared to Europe and the United States (Parikh et al., 2020; Sohn et al., 2022). Since the 1980s, China has successfully developed a polysaccharide vaccine for group A IMD and has conducted extensive vaccination, resulting in a decreasing trend in the incidence of IMD annually (Shao et al., 2006). However, epidemiological surveillance data reveal persistent reporting of laboratory-confirmed IMD cases across Xinjiang, and this study revealed that these cases were mainly distributed in southern Xinjiang (Hotan and Kashgar), which was consistent with the results of carrier rate among healthy individuals. Based on practical considerations, the economic development level of northern Xinjiang was significantly higher than southern Xinjiang (Abulimiti et al., 2022). Beyond socioeconomic determinants and healthcare access barriers, regional climate characteristics and vaccination conditions were also the main factors (Xie et al., 2021). The southern Xinjiang region, characterized by a temperate continental arid climate with annual precipitation <100 mm, experiences frequent dust-laden winds that exacerbate respiratory pathogen transmission. Therefore, in addition to improving medical facilities and strengthening public education, it is necessary to enhance laboratory monitoring capabilities and facilitate cooperation between medical institutions and disease control departments to establish a monitoring system for IMD cases. Given Xinjiang’s climate, targeted prevention and control measures should be implemented during the peak incidence seasons of winter and spring, along with initiatives to popularize personal protection knowledge, effectively reducing the transmission risk of respiratory pathogens such as those causing IMD.

In the current study, we found that the seasonal peak of IMD cases in Xinjiang was from February to May, with the highest number of cases occurring in April, which was similar to findings in other Chinese provinces (Chen et al., 2018; Li et al., 2015). This may be related to climatic factors, for example, during the peak season of influenza in China, there is a seasonal difference between the north (January) and the south (June to July), and the climate in the south is warm and humid (Shu et al., 2010), which also suggests that the climate has a certain influence on the prevalence of infectious diseases. The Xinjiang region is in the northwestern region of China, and the climate is different from other regions. The climate in the southern Xinjiang region is an extreme continental climate of the tropics, with hot and dry summers, low rainfall, and abundant sunshine. The results of the study by Jusot et al. (2017) showed that high temperatures and low visibility were identified as important risk factors for bacterial meningitis. Therefore, climate surveillance is used to predict the prevalence of IMD, in order to prevent and control outbreaks of IMD. In addition to climatic factors, national social factors should also be considered. China’s Spring Festival migration (January–March) represents the planet’s largest annual human migration event, with >200 million interregional travelers generating transient population density increases of 3–5 fold in receiving communities (Wang et al., 2013). Mass population mobility during holiday periods generates two synergistic risk amplifiers for meningococcal transmission: prolonged close contact (<1 m interpersonal distance for >4 h) in overcrowded transport nodes (airports/railway stations reaching 6–8 persons/m²), and aerosol dispersion efficiency increases in enclosed vehicles, these findings underscore the critical need for time-sensitive meningococcal prevention strategies during mass migration periods.

The results of many studies showed that cases of IMD have been reported in people of all age groups, mainly occurring among those under 15 years old (Flountzi et al., 2019; Li et al., 2018; Yue et al., 2022). From 2004 to 2023, the reported cases of IMD in Xinjiang were mainly in people under 20 years of age, with the highest number of cases occurring in the 10–15-year-old age group, which was similar to the results of this healthy population carrier rate survey. The highest carrier rate was found in the ≥21 years age group, followed by the 16–20 years age group. Some researchers had shown that 40% of N. meningitidis usually colonize the nasopharynx of adults and occasionally cause IMD disease (Borrow, 2012). Adolescents aged 15–20 years—primarily school and university students—represent a high-risk demographic for IMD, which is more likely to lead to aggregated IMD outbreaks. This has been similarly reported in many investigations (Borrow et al., 2017; Coronell-Rodriguez et al., 2023; McMillan et al., 2024; Peterson et al., 2019b; Tefera et al., 2020). In particular, students in group accommodations at school are at high risk of contracting N. meningitidis (Miellet et al., 2021). Therefore, the prevention and control of IMD in schools should be given high priority. It is crucial to remain vigilant about the transmission of carriers among students, strengthen sanitation and cleaning in classrooms and dormitories, and conduct targeted catch-up vaccination campaigns for IMD to prevent outbreaks on campus.

The N. meningitidis carrier status of healthy people is closely related to the prevalence of IMD epidemics (The MenAfriCar Consortium, 2015; Steurer et al., 2020). Therefore, it is important to investigate the N. meningitidis carrier status of healthy populations for the prediction of IMD epidemics and the formulation of immunization strategies. In the present study, a survey of N. meningitidis carriage status was carried out among 3,075 healthy people in Xinjiang, and 411 N. meningitidis strains were detected, with an overall carriage rate of 13.37%, which was significantly greater than the upper respiratory N. meningitidis carriage status of university students in Kampar, Malaysia, which was 5% (Ong et al., 2023); and in Iceland from 2019 to 2021, which was 6.50% (Kristinsdottir et al., 2023) and mainly involved adolescent groups. This may be related to the vaccination situation. In some countries, vaccination is provided to teenagers to reduce the carriage rate and the incidence of IMD among the whole population. The available vaccines differ across the countries, including both conjugate vaccines and polysaccharide vaccines, but the use of only conjugate vaccines could interrupt the acquisition of carriage (Bai et al., 2019). Currently, countries such as the United States and the United Kingdom have implemented the MenACWY conjugate vaccine in adolescent populations, resulting in effective control of both N. meningitidis carriage rates and the incidence of IMD (Dretler, Rouphael & Stephens, 2018; Vetter et al., 2016). However, in most countries, N. meningitidis vaccines are only provided to high-risk groups. In China, only polysaccharide vaccines are included in the expanded programme on immunisation. Given the increasing carriage rate among the adolescent population, it is important for China to consider following the example of other countries and modifying the immunisation strategy to use conjugate vaccine against IMD-related serogroups in teenagers.

The use of vaccines has a significant effect on controlling the prevalence and distribution of IMD diseases (Pizza, Bekkat-Berkani & Rappuoli, 2020). The most prevalent strains of IMD in China in the past were Group A and Group C. After the 1980s, with the use of group A vaccines, the incidence of group A IMD cases in China showed an overall decreasing trend (Abio, Neal & Beck, 2013). The serotype and flora distribution of N. meningitidis changed accordingly (Peterson et al., 2019b). Recent research in China showed that the proportion of IMD patients with Group A continued to decrease, the number of patients with Group B increased significantly, accounting for more than half of the total number of IMD patients (Parikh et al., 2020). This finding was basically consistent with the results of this study. Serogroup B emerged as the predominant Neisseria meningitidis carriage strain among asymptomatic populations in Xinjiang. The results of this study were basically consistent with those of Peterson et al. (2019a), Yue et al. (2022), Sofer-Sali et al. (2022) and others abroad. Both polysaccharide- and protein-bound vaccines have been developed that can be used against serogroup A, C, W, and Y, with direct and indirect (population) protection, but cannot provide cross-protection against other N. meningitidis serogroup (Borrow, 2012). However, polyglycoprotein-binding vaccines against group B are difficult to develop, because their structure is similar to that of polysialic acid on human nerve cells, resulting in the low immunogenicity and difficulty in generating effective antibodies. Therefore, the development of such vaccines against group B meningococcal has been challenging (Ladhani et al., 2020). At present, some developed countries have obtained licenses for group B meningococcal vaccines (Borrow, 2012; Ladhani et al., 2020), notably, China presently lacks nationally licensed vaccines targeting Neisseria meningitidis serogroup B (MenB) strains. In this study, nongenogroup bacteria accounted for 38.44% of all detected strains. Many studies have shown that nongenogroup strains were carried by healthy people and rarely pathogenic (Coch Gioia et al., 2015), but there have been cases of IMD caused by nongenogroup strains in China (Zhang et al., 2019). Therefore, the monitoring of nongenogroup N. meningitidis should not be ignored, the monitoring and related research of nongenogroup strains should be strengthened, which has important public health significance.

A survey on the rate of N. meningitidis infection among healthy people revealed that the rate of N. meningitidis infection in other years differed from that in 2022 and 2023. The results were consistent with the incidence data from this study. Since 2019, there has been a significant downward trend in the incidence rate, with the lowest rate recorded in 2020 and no cases reported in 2021. This might be attributed to the impact of the COVID-19 pandemic, people generally took personal protective measures such as wearing masks, reducing going out and gathering, frequent hand washing and ventilation. This effectively reduced the possible transmission of respiratory infectious diseases such as IMD (Alderson et al., 2022; Liu et al., 2021).

In this study, relevant factors such as age, sex, year, region and vaccination status were significantly correlated with N. meningitidis carrier status. These factors were significantly related to risk factors according to different studies (Coch Gioia et al., 2015; Ong et al., 2023; Tefera et al., 2020). There was a significant positive correlation between N. meningitidis carriage prevalence in healthy populations and IMD incidence rates.

This study has several limitations. Firstly, there is a potential risk of bias in vaccination information among healthy adult populations. For older age groups, vaccination records lack systematic electronic archiving, and their immunization history was primarily collected through personal recall or family oral descriptions. To address this issue, future research could employ multi-source data verification and supplement biological indicators to reduce information bias caused by subjective recollection. Additionally, expanding the inclusion of samples from recently vaccinated populations would enhance analytical precision. Secondly, there are gaps in serogroup distribution characteristics data of case strains. To improve this limitation, subsequent studies will establish a real-time strain sharing mechanism to ensure timely sample collection during case occurrences. Through molecular biology techniques, we will systematically analyze strain serogroup distribution, antimicrobial resistance profiles, and clonal transmission chains. These efforts will accumulate critical data for accurately assessing vaccine protection effectiveness and formulating regional prevention and control strategies.

Conclusion

Longitudinal surveillance (2004–2023) revealed a significant decline in IMD incidence across Xinjiang, transitioning from cyclical epidemic patterns to sustained hypoendemic transmission. Notwithstanding declining IMD incidence, N. meningitidis carriage persisted at elevated levels, with multilevel logistic regression identifying key determinants of regional heterogeneity. We recommend expanding the surveillance network for IMD and conducting annual population-based surveys of N. meningitidis carriage during early IMD outbreaks. This dual approach will enhance predictive capability for regional IMD trends, enabling timely adjustments to prevention and control strategies—ultimately strengthening evidence-based IMD management in Xinjiang.

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