Global epidemiology and pathogen spectrum of enterovirus-associated encephalitis and meningitis outbreaks from 1960 to 2025: A systematic review and meta-analysis.

BACKGROUND

Enteroviruses (EVs) are the major pathogens causing viral encephalitis and meningitis and frequently drive outbreaks in high-risk settings such as schools and healthcare facilities. We analyzed outbreaks reported from 1960-2025 to map epidemiology, clinical manifestations, and serotypes, informing prevention and control.

METHODS

We systematically searched Web of Science, PubMed, CNKI, and Wanfang from 1960 to July 1, 2025 using the keywords of enterovirus, encephalitis, meningitis and outbreak to assemble a global dataset of enterovirus encephalitis and meningitis outbreaks. Eligible studies must report outbreaks of laboratory-confirmed enterovirus meningitis or encephalitis, while those with unclear outbreak definitions or no laboratory confirmation were excluded. Standardized forms were used to extract information on outbreak characteristics, case demographics, and etiology data. A random-effects model was employed to derive combined estimates of attack rates, hospitalization rates, clinical manifestations and serotype distribution, with subgroup analyzes by geographic region, temporal period, and age group. This research was registered in PROSPERO (CRD420251140412).

RESULTS

A total of 56 outbreaks (28,622 cases) across 20 countries were included. Outbreaks were most prevalent in the Western Pacific and Europe, exhibiting seasonal peaks in June-July (Northern Hemisphere) and April-May (Southern Hemisphere), with a median size of 90 cases. Schools and medical institutions were the major outbreak settings. EV-B was the dominant species (94.6%, 53/56), with E30 being the most prevalent serotype. Two decades, 2000-2009 and 2010-2019, saw the highest number of reported outbreaks. The overall attack rate was estimated at 13.2% (95% CI 6.1-22.3). Notably, the pooled hospitalization rate was exceptionally high at 94.0% (95% CI 85.9-99.2). The most frequently reported symptoms were fever, headache, and vomiting.

CONCLUSIONS

Enterovirus encephalitis and meningitis outbreaks remain a persistent global concern, marked by high hospitalization rates, summer-autumn peaks and regional patterns. They primarily affect children under 15 years old, with multiple serotypes in circulation. Shifting toward active syndromic and genomic surveillance, alongside targeted prevention in high-risk settings, is urgently needed.

FUNDING: This work was supported by the Beijing Natural Science Foundation (L242052) and National Key R&D Program of China (2024YFC2310403); Jiangsu Province 333 Project.