Highlight
– A nationally representative serosurvey (n=2,938) in Bangladesh found low JEV IgG seroprevalence (3.4%) but an annual infection probability of ~0.5% (0.005), consistent with many asymptomatic infections.
– Modelled estimates suggest ~157,000 JEV infections per year in Bangladesh, producing a small number of severe cases (157) and deaths (31), reflecting a low clinical attack rate among infections.
– A spatially targeted vaccination campaign restricted to the ten highest-risk districts would be the most dose-efficient strategy; however, neither targeted nor nationwide vaccination met conventional cost-effectiveness thresholds at 3× GDP per capita.
Background
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that remains a leading cause of viral encephalitis across Asia. Most JEV infections are asymptomatic; clinical encephalitis occurs in a small fraction of infections but is associated with substantial morbidity and case fatality among symptomatic cases, particularly in children. In Bangladesh, JEV was first reported in 1977 and sporadic to regular cases have been identified since, yet the country has not implemented a national JEV vaccination programme. A key barrier to vaccine introduction has been uncertainty around the population-level burden and where vaccination would be most impactful and efficient.
Study design and methods
This investigation combined a nationally representative cross-sectional serological community study with spatially explicit statistical and transmission modelling to estimate infection risk and to evaluate vaccination strategies.
– Serosurvey: Conducted in 70 communities across Bangladesh between October 2015 and January 2016. Individuals of all ages were enrolled; 2,938 participants provided serum samples that were tested for anti-JEV IgG antibodies.
– Statistical analysis: Spatially explicit binomial regression models were used to infer the force of infection (annual probability of infection) across the country and to identify geographic risk factors associated with seropositivity.
– Transmission and policy modelling: Mathematical models projected the annual number of JEV infections, symptomatic (severe) cases, and deaths under current conditions and under alternative vaccination strategies. Strategies varied by geographic targeting (e.g., nationwide versus the ten most affected districts), target age groups (including catch-up campaigns for ages 1–15 years), and coverage levels. Cost-effectiveness was assessed using a willingness-to-pay threshold of three times GDP per capita.
Key findings
Seroprevalence and force of infection
– Of 2,938 participants, 100 were seropositive for JEV IgG, yielding an overall seroprevalence of 3.4% (95% CI 2.8–4.1). Community-level seroprevalence ranged from 0% to 28%.
– The estimated annual probability of infection (force of infection) was 0.005 (95% credible interval [CrI] 0.003–0.009), indicating ongoing low-level transmission population-wide.
Geographic pattern
– Infection risk was heterogeneous and concentrated near border regions. The spatial modelling identified the highest transmission intensity in a subset of districts, supporting the feasibility of geographically targeted interventions.
Disease burden projections
– Modelled annual infections: Approximately 157,000 JEV infections per year (95% CrI 88,000–261,000).
– Modelled clinical burden: These infections were projected to result in roughly 157 severe (symptomatic encephalitis) cases annually (95% CrI 89–253) and about 31 deaths (95% CrI 18–52). The large gap between infections and clinical cases reflects the well-documented low symptomatic ratio for JEV.
Vaccination strategy performance
– Targeted campaign: Vaccinating in the ten most-affected districts with a catch-up campaign covering 60% of the 1–15-year-old population would require approximately 5 million vaccine doses. Over 5 years, this scenario would avert an estimated 0.9 cases per 100,000 doses administered.
– Nationwide campaign: A broader nationwide vaccination strategy would use about 35 million doses and avert approximately 0.5 cases per 100,000 doses over 5 years.
– Cost-effectiveness: Under the assumed parameters and using a willingness-to-pay threshold equal to three times Bangladesh’s GDP per capita, none of the vaccination scenarios assessed achieved standard cost-effectiveness criteria.
Interpretation and clinical implications
This study provides the first nationally representative serological estimate of JEV exposure in Bangladesh combined with explicit modelling of vaccine impact. Key implications include:
– Low population seroprevalence but measurable transmission: A 3.4% IgG seroprevalence and a modest force of infection indicate ongoing JEV transmission with a large iceberg of asymptomatic infections.
– Focal risk supports targeted approaches: Because risk clusters geographically, limited vaccine supply or constrained budgets could be used more efficiently via spatially targeted campaigns focusing on high-transmission border districts.
– Low clinical incidence per infection reduces cost-effectiveness: The small number of symptomatic cases and deaths relative to total infections means that, at current vaccine prices and programmatic costs, vaccination programmes do not meet conventional cost-effectiveness thresholds in Bangladesh as modelled.
– Policy trade-offs: Decisions should weigh economic metrics against other priorities—preventing severe neurological disease in children, equity, health-system strengthening, and potential future reductions in vaccine cost or changes in transmission that could alter cost-effectiveness.
Expert commentary and limitations
Strengths
– Nationally representative sampling across age groups provides robust seroprevalence estimates and allows spatial modelling of transmission.
– Integration of serology with transmission and economic modelling gives a comprehensive picture of both epidemiology and policy-relevant outcomes.
Limitations
– Serology and cross-reactivity: JEV IgG assays can cross-react with antibodies to other flaviviruses (for example dengue), potentially biasing seroprevalence estimates. The study methods and laboratory controls are critical; interpretation should consider possible cross-reactivity.
– Assumptions in clinical ratio: The projected number of symptomatic cases depends on the assumed infection-to-encephalitis ratio. If local clinical attack rates differ from those assumed, burden estimates would change.
– Economic model inputs: Cost-effectiveness is sensitive to vaccine price, delivery costs, disability weights, and chosen willingness-to-pay threshold. Using alternative thresholds, lower vaccine prices, or valuing prevention of catastrophic disability differently could change conclusions.
– Temporal representativeness: The serosurvey captures a snapshot (Oct 2015–Jan 2016). JEV transmission can vary seasonally and interannually; longer-term surveillance would refine estimates.
Context with existing guidance
– WHO recommends inclusion of JE vaccination in national immunization programmes where JE is a public health problem, with options for routine infant immunization plus campaigns in high-risk areas (WHO position paper on Japanese encephalitis vaccines, 2015). This study provides country-specific data to inform whether and where Bangladesh might meet that definition.
Conclusions and research priorities
This combined serological and modelling study suggests that although JEV transmission in Bangladesh leads to many infections annually, relatively few symptomatic cases occur, meaning vaccine programmes—even when geographically targeted—are unlikely to be cost-effective under current assumptions. A spatially targeted campaign focusing on the highest-risk districts provides the best dose efficiency and should be considered if policy priorities favor concentrated prevention in those areas.
Research and policy priorities include:
– Strengthening acute encephalitis surveillance and laboratory confirmation to better quantify symptomatic burden and temporal trends.
– Improving serological tools and using virus-neutralization assays in subsamples to reduce misclassification from cross-reactivity.
– Conducting updated cost-effectiveness analyses incorporating potential lower vaccine prices, integration with routine immunization platforms, and broader societal benefits of preventing neurological disability.
– Evaluating programmatic feasibility of targeted campaigns and exploring combining JE vaccination with other public health interventions in high-risk districts.
Funding
This work was funded by the Gates Cambridge Trust (as reported in the source publication).
Selected references
– Duque MP, Paul KK, Sultana R, Ribeiro Dos Santos G, O’Driscoll M, Naser AM, Rahman M, Alam MS, Al-Amin HM, Rahman MZ, Hossain ME, Paul RC, Krainski E, Luby SP, Cauchemez S, Vanhomwegen J, Gurley ES, Salje H. National burden of and optimal vaccine policy for Japanese encephalitis virus in Bangladesh: a seroprevalence and modelling study. Lancet Infect Dis. 2025 Nov 18:S1473-3099(25)00590-0. doi: 10.1016/S1473-3099(25)00590-0 . Epub ahead of print. PMID: 41270761 .
– World Health Organization. Japanese encephalitis vaccines: WHO position paper — February 2015. Weekly Epidemiological Record. 2015;90(9):69–88.
– Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ. 2011;89(10):766–774, 774A.
(Additional primary surveillance and modelling literature should be consulted when developing national policy.)
