The current burden of Japanese encephalitis and the estimated impacts of vaccination: Combining estimates of the spatial distribution and transmission intensity of a zoonotic pathogen

Author summary Japanese encephalitis is a vector-transmitted, zoonotic disease that is endemic throughout a large portion of Asia. Vaccination has significantly reduced the JE burden in several formerly high-burden countries, but vaccination coverage remains limited in several other countries with high JE burdens. A better understanding of both the spatial distribution and the magnitude of the burden in endemic countries is critical for future disease prevention efforts. To estimate the number of people living in areas within Asia suitable for JEV transmission we conducted a spatial analysis of the risk factors associated with JE. We estimate that over one billion people live in areas suitable for local JEV transmission. We then combined these population-at-risk estimates with estimates of the force of infection (FOI) to model the national-level burden of JE (annual cases and deaths) over the past decade. Increases in vaccination coverage have reduced JE incidence from over 80,000 cases in 2010 to fewer than 57,000 cases in 2019. We estimate that vaccination has prevented almost 315,000 cases and 115,000 deaths in the past decade. Our results also call attention to the countries, and high-risk areas within countries, where increases in vaccination coverage are most needed. Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.

Automated summary

Japanese encephalitis continues to be a significant public health concern in Asia, with over one billion people estimated to live in areas suitable for local transmission of the Japanese encephalitis virus (JEV). Increases in vaccination coverage have led to a decrease in incidence and deaths from JE over the past decade, preventing hundreds of thousands of cases and deaths. The study highlights the need for targeted efforts to improve vaccination coverage in countries with high JE burden.