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The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 has been used in Nepal for catch-up campaigns and is now included in the routine immunisation schedule. Previous studies have shown good vaccine efficacy after one dose in districts with a high incidence of JE. The first well-documented dengue outbreak occurred in Nepal in 2006 with ongoing cases now thought to be secondary to migration from India. Previous infection with dengue virus (DENV) partially protects against JE and might also influence serum neutralising antibody titres against JEV. This study aimed to determine whether serum anti-JEV neutralisation titres are: 1. maintained over time since vaccination, 2. vary with historic local JE incidence, and 3. are associated with DENV neutralising antibody levels. We conducted a cross-sectional study in three districts of Nepal: Banke, Rupandehi and Udayapur. Udayapur district had been vaccinated against JE most recently (2009), but had been the focus of only one campaign, compared with two in Banke and three in Rupandehi. Participants answered a short questionnaire and serum was assayed for anti-JEV and anti-DENV IgM and IgG (by ELISA) and 50% plaque reduction neutralisation titres (PRNT50) against JEV and DENV serotypes 1–4. A titre of ≥1:10 was considered seropositive to the respective virus. JEV neutralising antibody seroprevalence (PRNT50 ≥ 1:10) was 81% in Banke and Rupandehi, but only 41% in Udayapur, despite this district being vaccinated more recently. Sensitivity of ELISA for both anti-JEV and anti-DENV antibodies was low compared with PRNT50. DENV neutralising antibody correlated with the JEV PRNT50 ≥1:10, though the effect was modest. IgM (indicating recent infection) against both viruses was detected in a small number of participants. We also show that DENV IgM is present in Nepali subjects who have not travelled to India, suggesting that DENV may have become established in Nepal. We therefore propose that further JE vaccine campaigns should be considered in Udayapur district, and similar areas that have had fewer vaccination campaigns.

Multiple logistic regression of factors associated with the incomplete immunization status of children aged 2–3 years in China.

BackgroundSporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains.Methodology/Principal FindingsA total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013–2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents ≥35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2).Conclusion/SignificancesJE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.

BackgroundThe current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported.Methods/Principal FindingsUsing in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults.Conclusions/SignificanceLow levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.

In each bootstrapped dataset we computed binomial log likelihood for each model. For each model summary statistics of the distribution of log likelihood was presented. Abbreviations: LASSO: Least Absolute Shrinkage and Selection Operator; PCR: Principal Component Regression; GBM: Gradient Boosting Machine; NN: Neural Network; MLR: Multiple Linear Regression.

BackgroundEncephalitis, an inflammatory central nervous system disease causing significant morbidity and mortality, disproportionately affects low- and middle-income countries (LMICs) due to healthcare disparities. Encephalitis has diverse etiologies—viral, autoimmune, bacterial, parasitic—each with distinct clinical and epidemiological features. Despite declining global age-standardized rates since 1990, inequities in diagnostics, vaccine coverage, and critical care persist, worsened by COVID-19 pandemic, which delayed diagnoses and disrupted vaccinations.MethodsUsing Global Burden of Disease (GBD) 2021 data, we analyzed age-standardized prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) across 204 countries (1990–2021). We used the Bayesian Age-Period-Cohort model with integrated nested Laplace approximation to predict encephalitis’ future trends, through 2040, enhancing the study’s predictive value. Sociodemographic Index (SDI) stratification and Bayesian meta-regression models assessed trends, with significance determined via 95% uncertainty intervals and estimated annual percentage change (EAPC).ResultsIn 2021, 4.64 million individuals worldwide were affected by encephalitis (1.49 million new cases; 92,000 deaths), encompassing cases spanning acute, subacute, and chronic stages of the disease. Low-middle SDI regions bore 3–5 times higher burdens than high-SDI regions. South Asia had the highest burden (age-standardized prevalence rate [ASPR]: 140.9/100,000; incidence [ASIR]: 51.3/100,000), while Australasia reported the lowest (ASPR: 1.94/100,000). High-SDI countries showed distinct patterns, such as rising incidence in Australia. COVID-19 was associated with an 18% increase in DALYs in high-burden regions. National disparities were stark: Pakistan, India, and Nepal had the highest burdens; Canada, the lowest. The encephalitis burden was greater in children than in other age groups.ConclusionThis analysis advances prior GBD research by integrating post-COVID-19 insights and future burden forecasts, filling pre-pandemic study gaps. GBD dataset does not differentiate etiological subtypes, limiting our analysis granularity given encephalitis’ clinical and epidemiological heterogeneity. Socioeconomic inequities drive encephalitis burden, necessitating targeted interventions: scaling Japanese encephalitis vaccination in South Asia, strengthening African diagnostic hubs, and integrating climate-resilient surveillance. Post-pandemic recovery must prioritize healthcare infrastructure, telehealth, and policies addressing poverty and education. Global collaboration is critical to mitigate disparities and optimize region-specific strategies.

a This article presents initial results of the surveillance conducted by the US Naval Medical Research Unit No. 2 [43]; complete results of the surveillance were not available.b This article presents the neurologic outcome of patients described by Barzaga [12].c This figure is not included in the overall total number of JE cases from articles and presentations because of substantial overlap with cases reported by Barzaga [12]ND, No data presentedCFR, case fatality ratioSummary of reports on clinical Japanese encephalitis (JE) in the Philippines, 1972–2013.

aThe incidence rate is the number of JE confirmed cases per 100,000 population at risk.bThere were two JE confirmed cases have been received 1 dose of vaccine in 2008 and one has been vaccinated with 3 doses, in 2012.

Japanese encephalitis neutralizing antibody and seropositive proportion against P3 strain for participants with two doses of JEV-L in Zhejiang, 2015–2016.

Japanese encephalitis neutralizing antibody and seropositive proportion against P3 strain for participants above 1 year old in Zhejiang, 2015–2016.

NT—Neutralization tests; HI—Hemagglutination inhibitionSerologic surveys for Japanese encephalitis in the Philippines, 1958–1993.

aHI—Haemagglutination inhibitionJapanese encephalitis studies in animals in the Philippines, 1966–2005.