Encephalitis is a clinical neurological syndrome characterized by brain dysfunction associated with inflammation of the brain parenchyma (1). This condition is commonly triggered by infectious pathogens or induced through autoimmune processes, the latter potentially being post-infectious, paraneoplastic, or idiopathic (2). The breadth of infectious and autoimmune causes—numbering in the hundreds—shows the wide range of encephalitis presentations. Infectious etiologies typically present as acute febrile illnesses, accompanied by changes in personality, behavior, cognition, or consciousness. New-onset seizures or focal neurological deficits can also occur (3). Autoimmune encephalitis, in contrast, leads to varied symptoms such as seizures, behavioral changes, and cognitive decline. Immunosuppressive therapies are available, but many AE patients still face lasting cognitive impairment and refractory epilepsy after the acute phase, which lasts more than 3 months after diagnosis or treatment starts (4). Recently, climate change has sped up changes in vector transmission routes. Meanwhile, the growing use of immunosuppressive therapies and biologics—along with the increasing identification of autoantibodies related to autoimmune encephalitis—has made encephalitis a significant public health concern (5).

Encephalitis affects people of all ages, placing a heavy burden on patients, families, and society. Data show that both children and adults often face lasting effects after encephalitis. A review of outcomes in children found that almost half of survivors have ongoing neurodevelopmental issues, including cognitive delays, behavior changes, intellectual disability, and motor problems (6). In 26% to 62% of adult cases, serious aftereffects can significantly reduce quality of life, including seizures, memory loss, inappropriate behavior, poor social skills, fatigue, sleep disturbances, personality changes, cognitive issues, pain, sensory problems, and difficulties with daily activities (7). Encephalitis is a major public health challenge because of its frequency, death rate, and lasting complications.

The Global Burden of Disease (GBD) database provides a comprehensive set of quantitative tools designed to systematically assess the overall impact of various diseases, injuries, and their associated risk factors on the health status of global populations. This database not only supports cross-country and cross-temporal data comparisons but also possesses the capability to track the evolution of health indicators, thereby providing critical support for informed decision-making by public health policymakers. This paper systematically reviews and analyzes the development trends of the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year rate (ASDR) for encephalitis globally, regionally, and by country from 1990 to 2021. Furthermore, the data were refined through multi-dimensional categorization based on age, gender, and socio-demographic index (SDI), enabling a comprehensive quantitative assessment of the disease burden of encephalitis. This systematic analysis not only reveals complex patterns in disease distribution but also provides a robust scientific foundation and guiding principles for developing precise and effective public health intervention strategies.

This study analyzes the progress achieved in encephalitis prevention and control at global, regional, and national levels over the past three decades. It systematically incorporates key factors such as age, gender, and SDI. This approach enables a more comprehensive understanding of the disease’s overall epidemiological patterns. The goal is to develop targeted interventions that address complex public health challenges in a scientifically effective manner. This will help lay a solid foundation for safeguarding human health and continuously strengthening global public health security.

To effectively assess and monitor the disease burden of encephalitis, a thorough analysis of its epidemiological characteristics is crucial. Notably, from 1990 to 2021, the ASIR of encephalitis worldwide showed a marked downward trend, a change closely linked to significant advances in precision medicine and enhanced resource allocation and strategy optimization in public health. Furthermore, the implementation of appropriate and timely treatment protocols is crucial for enhancing patient outcomes. Among infectious encephalitis cases, viral encephalitis accounts for approximately 70% of all confirmed diagnoses, marking it as the predominant type. In immunocompetent individuals, one of the primary causative agents of sporadic viral encephalitis is herpes simplex virus type 1 (HSV-1), which typically accounts for 10 to 20% of all viral encephalitis cases (15). The introduction of acyclovir revolutionized the clinical management of HSV encephalitis. Specifically, this medication competitively inhibits HSV replication by blocking deoxythymidine triphosphate (dTMP), a substrate for DNA polymerase, thereby disrupting DNA chain synthesis (16). Before the widespread implementation of specific antiviral therapies, herpes simplex encephalitis carried a mortality rate as high as 70%, leaving many survivors at risk of severe neurological sequelae. In contrast, since the introduction of acyclovir into clinical practice, the mortality rate for this disease has significantly decreased to 28%, markedly improving patient prognosis and quality of life. Notably, prompt initiation of antiviral treatment strategies can substantially reduce annual mortality rates to 14% within a short timeframe (17). The diagnosis of encephalitis is especially complex and challenging. This is particularly true for immunocompromised patients, whose bodies host a greater variety of infectious agents. It is also difficult with emerging infectious diseases, as clinicians may not recognize specific causative pathogens. New laboratory technologies offer promise for accelerating and optimizing diagnostic workflows. The adoption of neuroimaging techniques, such as cranial magnetic resonance imaging (MRI) and computed tomography (CT) scans, has greatly improved lesion localization. Meanwhile, innovative pathogen detection methods, including polymerase chain reaction (PCR) and metagenomic next-generation sequencing (mNGS), have broadened the spectrum of detectable pathogens and increased sensitivity. Together, these advances have improved the accuracy and reliability of encephalitis diagnosis (18). Medical innovations and technological advances have greatly improved the early diagnosis and timely treatment of encephalitis. As a result, ASIR has been steadily declining worldwide. In public health, coordinating key strategies and measures has decisively reduced both the incidence and ASR of encephalitis. Public health agencies focus on accelerating vaccine development and expanding vaccination campaigns. Evidence suggests that these strategies significantly reduce the risk of viral infection and protect vulnerable populations. For example, in Nepal, a five-year vaccination program aimed at preventing Japanese encephalitis resulted in a 78% reduction in infection cases, according to project data (19). Under the 2004 German public health policy framework, a comprehensive varicella vaccination initiative was implemented for one-year-old children. The implementation of this program significantly reduced the incidence of varicella-related neurological complications, with estimates indicating a reduction of up to 60% (20). This national experience demonstrates how targeted public health interventions can have a positive impact on neurological outcomes. Similarly, on a global scale, the reduction in the burden of encephalitis has primarily resulted from breakthroughs in medical technology innovation and their application in clinical practice, as well as the careful planning and effective execution of public health strategies.

Resource-constrained countries and regions face exceptionally urgent and complex challenges, demanding innovative solutions and optimized existing systems. Our research reveals a distinct, heterogeneous relationship between the SDI and the ASR: regions with high SDI exhibit a lower ASR trend, whereas regions with low-middle SDI display higher ASR characteristics. This finding underscores the distinct impact of socioeconomic status on the distribution of health indicators. Regions with low SDI often face more complex challenges, including uneven distribution of medical resources, unequal access to healthcare information, barriers to healthcare services, inadequate implementation of medical practice standards, and ineffective public health policies. In contrast, high SDI regions allocate superior healthcare resources and deploy specialized medical teams, who provide personalized, systematic, and efficient diagnosis and treatment for encephalitis patients. These actions facilitate precise disease management and long-term control, significantly reducing the chronic health burden. Existing literature indicates that global healthcare expenditure levels and the prevalence of imaging diagnostic equipment exhibit a marked heterogeneous distribution (21). High-income and upper-middle-income countries hold a distinct advantage in diagnostic imaging equipment. They typically provide 5 to 10 CT scanners per million residents. In contrast, low-middle and low-income countries face significant shortages, with an average of 0 to 5 such devices per million residents (22). As a result, low and middle-income countries face severe limitations in implementing optimal management practices for encephalitis. These challenges arise due to a lack of specialized medical equipment needed for specific diagnostics and assessments. This equipment shortage significantly impedes effective disease prevention, control, and treatment. Encephalitis is a complex, severe clinical condition with diverse evolutionary trajectories. Accurate diagnosis and effective treatment rely heavily on advanced expertise and technical capabilities from neurological specialists. This ensures patients receive timely, precise, and appropriate interventions. In low- to middle-income or resource-constrained regions, the availability of neurological professionals falls short of clinical demand. Statistics indicate a median of 0.43 adult neurologists per 100,000 population globally. By contrast, high-income countries approach five neurologists per 100,000 residents (23). This comparison highlights a substantial gap in medical human resources in low-income and resource-constrained regions, posing significant challenges for diagnosing and treating complex diseases such as encephalitis. Taking the Philippines as an example, a survey indicates that one adult neurologist serves approximately 176,000 Filipino adults. This amounts to 0.57 adult neurologists per 100,000 adult population. Meanwhile, pediatric neurologists are even more scarce. One pediatric neurologist serves 299,581 Filipino children, or 0.33 pediatric neurologists per 100,000 children (24). These statistics reveal significant disparities in the allocation of healthcare resources. Adequate medical staffing is crucial for improving the diagnosis and treatment outcomes of patients with encephalitis. It also facilitates their recovery process. The shortage of neurologists may worsen patients’ inability to access timely and appropriate evaluation and treatment. This not only affects their health status but also increases the risk of severe complications. To improve encephalitis treatment outcomes, especially in low-income countries and regions, regional interdisciplinary collaboration is urgently needed. This includes a focus on training healthcare personnel, capacity development, and strengthening treatment strategies. Such initiatives aim to consolidate resources, optimize service delivery, and ensure effective responses to encephalitis challenges in these regions (25). At the same time, to alleviate the global public health burden caused by encephalitis, the international community should strengthen cooperative frameworks and focus resources on supporting the development of healthcare systems in affected areas. This will help ensure all patients receive timely, high-quality medical care.

Since its initial recognition, autoimmune encephalitis (AE) has been established as a dynamically evolving neurological disorder (26). Over the past decade, research on AE has advanced rapidly. This progress is driving continuous changes in clinical diagnosis and treatment approaches (27). Recent advances in autoantibody detection technologies have revealed that its prevalence now rivals that of infectious encephalitis. This dramatic increase demands corresponding efforts from clinicians to keep pace with emerging knowledge. However, disparities in access to medical information remain particularly pronounced. This is especially true in low and middle-income countries, where conducting high-quality research is often hindered by insufficient capacity. Most patients with AE respond positively to immunotherapy. In some cases, however, prolonged hospitalization and intensive care support may be required to manage their complex conditions. At the same time, the medical burden of patients exhibiting encephalitis-induced behavioral disturbances and resulting long-term disabilities inevitably places significant strain on social welfare systems and family finances. Therefore, quantifying the economic costs associated with the rational allocation of healthcare resources is a critical consideration (28–31). From a long-term perspective, strengthening capacity building in AE research within low and middle-income countries significantly improves patients’ quality of life. It also helps alleviate the economic burdens on society and families. This process requires collaboration among multiple stakeholders and systematic planning. International organizations and philanthropic foundations should prioritize funding and technical guidance to support AE research in these countries. Establishing close partnerships and training local researchers can enhance their professional skills and research standards. This enables them to join the global scientific community and supports international knowledge sharing and collaboration. Secondly, high-income countries should regularly host international academic conferences and symposiums. These events facilitate knowledge exchange among global research communities, promoting the sharing of practical experiences and expertise. Such gatherings offer researchers from low- and middle-income countries the opportunity to meet with leading international experts. They can learn cutting-edge research techniques and gain new insights, which enhances their own research skills and sparks innovation.

Vaccination plays a crucial role in pre-exposure prophylaxis against specific viral encephalitis, particularly for viruses such as tick-borne encephalitis, rabies, and Japanese encephalitis. However, vaccine development and production are time-consuming and complex, requiring advanced technological support and substantial government funding (32). Despite effective vaccines existing, low and middle-income countries face several key challenges in implementing vaccination programs: (1) low levels of education result in limited vaccine knowledge and skepticism; (2) severe economic constraints and insufficient healthcare infrastructure mean fewer accessible vaccination sites, especially in rural areas; (3) the high cost and multiple doses of vaccines place additional strain on healthcare systems. These barriers significantly hinder vaccination uptake in these settings (33). Secondly, for low and middle-income countries, major challenges in vaccine supply include, but are not limited to, the lack of clinical trial infrastructure, deficiencies in the effectiveness of the regulatory system, and the absence of sustainable financing channels (34). These systemic barriers not only limit the widespread adoption of vaccines but also impose enduring constraints on vaccine program development, severely undermining their long-term sustainability. We must urgently implement comprehensive and targeted public health interventions in low and low-middle SDI regions to reduce key risk factors that exacerbate the burden of encephalitis. We should strengthen health education and awareness campaigns on vaccination in these regions to improve public understanding, dispel misconceptions, and increase vaccine acceptance. This will create a more favorable environment for vaccination. Additionally, systematic investment and optimization of basic health infrastructure in low-income countries are vital. Measures such as increasing vaccination sites and offering mobile services help ensure timely access to vaccinations. Furthermore, increased investment in global health, especially vaccine research and development for low-income countries, is crucial for advancing health equity. By promoting vaccines tailored to regional needs, every country can access products that are specifically suited to address its unique health challenges. These actions optimize limited resources and systematically enhance encephalitis prevention, ultimately upgrading public health systems.

Meanwhile, our research reveals that encephalitis cases are particularly concentrated in Asian countries such as Pakistan, India, Bhutan, and Nepal, where public health systems face severe challenges. This is manifested in high prevalence, incidence, and mortality, as well as a significant increase in DALYs. Therefore, these nations should be regarded as key focal areas for future monitoring of the encephalitis disease burden. Persistently high incidence and mortality rates in South and Southeast Asian countries likely result from factors such as high population density, inadequate public health infrastructure, and limited vaccine coverage (10). Japanese Encephalitis (JE), a mosquito-borne viral disease caused by the Japanese Encephalitis Virus (JEV), is primarily endemic in Southeast Asia, India, Indonesia, and parts of Australia (35). Currently, there is no specific treatment for Japanese encephalitis, so existing strategies focus on supportive and symptomatic care. Clinically validated, safe, and effective vaccines exist and have been approved to prevent Japanese encephalitis virus infection. Widespread vaccination has significantly reduced disease incidence and mortality, particularly among high-risk groups, such as children, underscoring the importance of vaccines in public health strategies. However, in recent years, the geographic distribution of Japanese encephalitis in Nepal has expanded, accompanied by complex challenges. Key factors behind its emergence and recurrence include low vaccination coverage, unvaccinated swine populations, limited public health awareness, inadequate mosquito control, vector spread facilitated by climate change, poor sanitation, and the use of irrigated rice farming systems (36). Notably, since China incorporated the Japanese encephalitis vaccine into its immunization program in 2008, a two-dose regimen for children under 15 years of age has led to a decline in disease incidence, from 1.63 per 100,000 in 2004 to 0.16 per 100,000 in 2018 (37). China’s rapid economic growth and major improvements in public health have positively influenced living conditions. Key measures include purifying sewage to reduce mosquito breeding, optimizing pig farming to minimize the transmission of Japanese encephalitis virus, and relocating pigsties away from homes to lower risks (38). These steps have helped curb the spread of Japanese encephalitis. Asian nations like Pakistan, India, Bhutan, and Nepal can learn from China’s success. By boosting vaccination rates and implementing targeted public health strategies, they can reduce disease transmission and mitigate its socioeconomic impact. Expanding access to water, sanitation, and hygiene (WASH) services also remains central to effective disease prevention (39). In South Asia, particularly in Afghanistan, Bangladesh, Nepal, and Pakistan, significant improvements have been observed in enhancing access to water and sanitation services. However, over 134 million people in the region still lack access to safe drinking water, with contamination levels ranging from 68 to 84% (40). Statistical data indicate that approximately 52% of households in rural Pakistan lack sanitation facilities, while this proportion drops significantly to 8% in urban areas (41). This contrast reveals substantial disparities in basic infrastructure coverage between urban and rural areas.

Our analysis reveals significant variations in disease burden across different age groups. This underscores not only the importance of personalized intervention strategies but also the need for precision medicine measures tailored to specific age cohorts. In statistical analyses spanning 1990 to 2021, we found that the older adult consistently ranked highest in ASMR. In contrast, children exhibited markedly higher ASIR and ASDR. These findings illustrate disparities in health and quality of life across different life stages. Furthermore, multiple studies have validated age as a key independent risk factor, revealing its significant impact on fatal outcomes associated with encephalitis. In particular, the higher mortality rate among the older adult is typically attributed to the aging of the immune system and the interaction of multiple comorbidities (42). The incidence of cardiovascular and cerebrovascular diseases rises significantly in the older adult, along with a marked decline in immune function. When pathogens invade the nervous system, the older adult struggle to activate mechanisms that secrete cytokines, chemokines, and specific antibodies. These responses are crucial in regulating inflammation. As a result, the older adult are at a disadvantage in fighting neurological infections. Additionally, cerebrospinal fluid changes in the older adult lack specificity, and imaging tests such as cranial MRI and Electroencephalogram (EEG) have low detection rates. These factors can lead to missed diagnoses and affect disease progression. Encephalitis is also common in children. An Australian multicenter study found acute encephalitis to be more prevalent in young children, with a median age of 1.7 years (43). The higher incidence and mortality rates in children stem from their fast metabolism and immature internal buffering and neuroendocrine systems. Children resist external environmental stimuli less, making them more susceptible to internal imbalances that can exacerbate disease progression and impede recovery. This likely connects to their underdeveloped blood–brain barrier and atypical clinical symptoms. Regular health monitoring and rapid identification of infection signs in vulnerable groups are key to protecting health. Current encephalitis research shows males have a higher incidence of encephalitis than females. Further analysis using Anti-NMDA receptor encephalitis criteria reveals that females comprise 64% of cases (44), underscoring their predominance in this disease. Another French study on HSV encephalitis enrolled 1,425 patients with a male-to-female ratio of 1.07 (736/689), indicating a slight predominance of males (45). These observations suggest that clinical manifestations of encephalitis may exhibit significant heterogeneity across different subtypes, a phenomenon potentially linked to the complex diversity of genetic backgrounds or intrinsic differences in disease pathogenesis.

This study provides valuable data on encephalitis diseases, which have significant implications for global public health. To mitigate the impact of encephalitis at the global, regional, and national levels, it is essential to develop targeted intervention policies for high-risk areas and populations, with a focus on prevention and treatment. As the world’s population continues to grow, more attention must be given to addressing this urgent issue.