Japanese Encephalitis Vaccine Research Articles

Sustainable Development Goal Halftime Project: Benefit-Cost Analysis Using Methods from the Decade of Vaccine Economics Model

AbstractIn 2023, the world will be at “halftime” with respect to the sustainable development goals (SDGs). This midline acts as an important milestone to review the progress of the SDGs and develop policies based on the most effective interventions. To estimate the remaining resources needed to achieve SDG targets for vaccines from 2023 to 2030 as well the resulting economic benefits, in this analysis, the incremental economic benefit-cost ratio (BCR) for immunization programs in 80 low- and middle-income countries targeted by the Global Vaccine Action Plan from 2023 to 2030 is calculated. Of these 80 countries, 27 are classified as low-income countries and 53 are classified as lower-middle-income countries (LMICs). The economic evaluation covers 9 vaccines employed against 10 antigens and delivered through both routine immunization programs and supplemental immunization activities. The vaccines covered in the analysis include pentavalent vaccine, human papillomavirus vaccine, Japanese encephalitis vaccine, measles vaccine, measles-rubella vaccine, meningococcal conjugate A vaccine, pneumococcal conjugate vaccine, rotavirus vaccine, and yellow fever vaccine, and correspond to the vaccines covered in the return-on-investment estimates presented in Sim et al., which covered 94 LMICs from 2011 to 2030. For these countries, we estimate program costs from the health system perspective, including vaccine costs such as costs to procure vaccines, which incorporate injection supplies and freight; and immunization delivery costs, which include nonvaccine commodity costs to deliver immunizations to target populations and incorporate labor, cold chain and storage, transportation, facilities, training, surveillance, and wastage. Economic benefits are calculated using a value of statistical life year (VSLY) approach applied to modeled cases, and deaths averted are converted into averted years of life lost using life expectancy data. BCRs are presented as the final output that compares incremental costs and benefits from the baseline of 2022 levels, assuming diminishing returns to scale. Overall, for this period, we estimate total costs of US$ 7,581,837,329.08 with VSLY benefits of US$ 762,172,371,553.54, resulting in a BCR of 100.53.

Common issues and improvement solution of vaccine hesitancy in children with underlying neurological conditions: Experience from one National Children's Medical Center in China.

Parents and healthcare providers usually defer or avoid immunization for children with neurological conditions. This study was conducted to investigate the common issues of immunization among these special children and the impact of specialists' recommendation on improving immunization practice. We included 2,221 children with underlying neurological conditions seeking vaccination consultation at the first Immunization Advisory Clinic in China during 2017-2019. The primary neurological conditions and immunization status were analyzed. All parents were informed to self-report the adverse events following catch-up immunization. For specially concerned children with hereditary disorders, immune-related encephalopathy and epilepsy, we conducted the active follow-up to monitor the compliance with recommendation and the adverse events. All counselling children were assessed as not having any contraindication of immunization. A total of 2,019 (90.9%) children with underlying neurological conditions had delayed immunization and 99 (4.5%) had non-immunization. The coverage rate of age-appropriate vaccines was 56.1%. The most concerned vaccines were diphtheria, tetanus and acellular pertussis combined vaccine, diphtheria and tetanus combined vaccine, meningococcal polysaccharide vaccine and Japanese encephalitis vaccine. Resuming immunization was recommended for the 2,048 (92.2%) children. Most of counselling children complied with the specialists' recommendation. Neither progress nor flaring of the neurological medical conditions was reported from parents. Vaccine hesitancy was a common issue for Chinese children with all kinds of neurological conditions. Specialized consultation on immunization is helpful to build vaccine confidence for the special children. Immunization for children with underlying neurological conditions is generally safe.

The Surveillance of Acute Encephalitis Syndrome in Thailand, 2003-2019: A Perspective for Prevention and Control.

Acute encephalitis syndrome (AES) is an infection of the central nervous system with high case-fatality rates. Japanese encephalitis virus (JEV) is the most common vaccine preventable cause of AES in Asia and part of the Western Pacific. In 2003, the JE vaccine was introduced into Thailand's National Immunization Program and expanded to all provinces. This study reviews data from the national surveillance system on the incidence of AES, including Japanese encephalitis in Thailand to guide surveillance, control, and prevention strategies. We collected data on all patients diagnosed with AES and reported to the Bureau of Epidemiology, Ministry of Public Health, Thailand, from 2003 to 2019. A total of 9566 AES patients and 266 death cases were reported during these 17 years. Six hundred and forty-two (6.7%) patients were JE with 16 deaths. The incidence of AES increased from 0.47-0.51-1.36 cases per 100,000 population with a preponderance of cases in adults. CFR reduced from 6.25% - 6.94% in 2003-2005 to 0.78% in 2019. AES cases occurred all year round in all the age groups with a male predilection JE vaccination coverage had reached 83% by 2019. The patients were mainly from the north-eastern region of Thailand. Integrated surveillance regular monitoring, strengthening, and making immunization sustainable is required to improve and maintain progress toward JE control and prevention.

Effectiveness of Japanese encephalitis vaccination among children in central India.

Japanese encephalitis (JE) disease among children continues in central India despite vaccination implemented in the routine immunization program. Therefore, we planned to estimate the JE vaccination effectiveness among children by undertaking a 1:2 individually-matched population-based case-control study from August 2018 to October 2020. The laboratory-confirmed JE cases aged 1-15 years were enrolled along with neighborhood controls without fever and encephalitis matched on the residence area, age and sex. The JE vaccination history was enquired from parents and verified independently from the vaccination cards available at home and records at health facilities. We enrolled 35 JE cases and 70 matched controls. The vaccination effectiveness of 86.7% (95% confidence interval [CI]: 30.8-94.7) was estimated on the per-protocol analysis of 31 case-control sets. The screening method provided an effectiveness of 89.5% (CI: 78.9-94.7) on using the population vaccination coverage of 90% reported earlier in the same area. In conclusion, JE vaccination offered a moderate level of protection among children in JE medium-endemic central India, similar to reports from high-endemic areas in India. The operational aspects of vaccination program implementation need to be evaluated to assess the impact of vaccination on the disease burden of JE in medium-endemic regions of India.

Duration of seroprotection of the live attenuated SA-14-14-2 Japanese encephalitis vaccine in children in India.

Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15-20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses. A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2-10years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays. Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0-2years (n = 59), 2-4years (n = 73), 4-6years (n = 65), 6-8years (n = 48) and 8-10years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively. The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas.

Improving community coverage of Japanese encephalitis vaccination: lessons learned from a mass campaign in Battambang Province, Cambodia

A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products’ live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere.

Vaccine Uptake to Prevent Meningitis and Encephalitis in Shanghai, China.

Multiple vaccines may prevent meningitis and encephalitis (M/E). In China, the meningococcal vaccine and Japanese encephalitis vaccine (JEV) have been included in the expanded program of immunization (EPI). The pneumococcal vaccine, Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine, and enterovirus 71 (EV-71) vaccine are non-EPI vaccines and are self-paid. We aim to investigate the uptake of these M/E vaccines in children and the related knowledge and health beliefs among family caregivers. A total of 1011 family caregivers with children aged 1-6 years in Shanghai, China were included in the study. The uptake of the pneumococcal vaccine, Hib-containing vaccine, rotavirus vaccine, and EV-71 vaccine remained at 44.0-48.1% in children, compared with the higher uptake of the meningococcal vaccine (88.8%) and JEV (87.1%). Moreover, family caregivers had limited knowledge on the M/E pathogens and possible vaccines. Their health beliefs were moderate to high. Then, a health belief model (HBM) and a structural equation model were established. The uptake of four non-EPI vaccines was significantly influenced by family income (β = 0.159), knowledge (β = 0.354), self-efficacy (β = 0.584), and perceived susceptibility (β = 0.212) within an HBM. Therefore, it warrants further improving the uptake rate for these non-EPI vaccines to prevent potential M/E in children. A specific health promotion may empower the caregivers' decision-making on childhood vaccination.

Effects of artificial intelligence aibo intervention on alleviating distress and fear in children

BackgroundProcedures and actions such as injections and immobilization cause distress to children. In the pediatric field, there is a need for interventions and support to alleviate the pain and distress caused by such medical procedures. In recent years, the introduction of robots as a means of distraction has begun to be attempted.MethodsIn this study, we conducted a non-randomized controlled trial to examine the effect of intervention using ‘aibo’, a dog-like robot which has artificial intelligence (AI), to promote distraction in children after vaccination. Children between the ages of 3 and 12 years old eligible for the Japanese encephalitis vaccine, and their caregivers were assigned to intervention group or control group. Then, children evaluated their pain and children’s behavior were observed by observer. The mean values of Faces pain rating scale scores and observer pain scale scores were compared between groups using an unpaired t-test.ResultsFifty-seven children (32 in the intervention group) participated in the study. Results of a t-test with the control group showed that the intervention group using aibo had significantly less pain following the post-vaccination intervention than the control group using stuffed dog (Face Scale, t(55) = 2.582, p = .0125; Behavioral Observation Scale, t(55) = 2.772, p = .00759). The results support the hypothesis that the aibo intervention group will be less distressed and able to calm down more quickly after vaccination than the control group.ConclusionInteractive communicative play intervention by an artificially intelligent aibo before and after painful and frightening medical procedures may alleviate fear and anxiety and prevent medical trauma in children.

Japanese Encephalitis Vaccine Generates Cross-Reactive Memory T Cell Responses to Zika Virus in Humans.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are mosquito-borne flaviviruses with sequence homology. ZIKV circulates in some regions where JEV also circulates, or where JE vaccination is used. Cross-immunity between flaviviruses exists, but the precise mechanisms remain unclear. We previously demonstrated that T cell immunity induced by the live-attenuated Japanese encephalitis (JE) SA14-14-2 vaccine conferred protective immunity against ZIKV infection in mice, which could even bypass antibody-dependent enhancement. However, the role of T cell immune, especially memory T cell subsets, in cross-reactive immune responses between JE vaccine and ZIKV in humans has not been reported. We examined central and effector memory CD4+ and CD8+ T cell (TCM and TEM) responses (including degranulation, cytokines, and chemokines) in the presence of JEV and ZIKV, respectively, by using qualified peripheral blood mononuclear cell samples from 18 children who had recently received a two-dose course of JE vaccine SA14-14-2 as well as seven children without JE vaccination. Cross-reactive CD8+ TCM in response to ZIKV was characterized by secretion of IFN-γ, whereas CD8+ TEM did not show significant upregulation of functional factors. In the presence of ZIKV, IFN-γ and TNF-α expression was upregulated by CD4+ TEM, and the expression signature of CD4+ TCM is more cytotoxic potential. We profiled the cross-reactive memory T cell responses to ZIKV in JE vaccine recipients. These data will provide evidence for the mechanism of cross-reactive memory T cell immune responses between JEV and ZIKV and a more refined view of bivalent vaccine design strategy.

VALIDATION OF POTENCY TEST OF NEW GENERATION JAPANESE ENCEPHALITIS VACCINE IMOJEV BY PLAQUE FORMING UNIT (PFU) METHOD

Implementation of potency test for new generation Japanese Encephalitis vaccine (IMOJEV) is one of the functions of National Institute for Vaccines and Biologicals (NICVB) prior to market release. Potency test of IMOJEV was carried out by using Plaque Forming Unit (PFU) method for both standard and testing samples, the results was in the approved range of manufacturer. The process of validation of potency test for Japanese Encephalitis vaccine IMOJEV was built and implemented by practical validation method with following parameters: accuracy, repeatability, and intermediate precision of the potency method for Japanese encephalitis vaccine
 Results of study showed that the parameters of accuracy, repeatability and intermediate precision of potency test for Japanese Encephalitis IMOJEV were all qualified and in the approved range of manufacturer: titer of standard sample was about 4.25-5.09 log PFU/0.5 ml and titer of IMOJEV was between 4.0-5.8 log PFU/0.5ml
 Based on our study conclussion the the potency test for Japanese Encephalitis IMOJEV after validation was qualified for accuracy, repeatability and intermediate precision with coefficient of variation CV ≤ 25% so it is suitable with laboratory condition of NICVB.

Extent of disability among paediatric Japanese encephalitis survivors and predictors of poor outcome: a retrospective cohort study in North India

ObjectiveTo determine the Japanese encephalitis (JE)-associated long-term functional and neurological outcomes, the extent of reduced social participation and predictors of poor outcomes among paediatric JE survivors.DesignA retrospective cohort study.SettingLaboratory-confirmed JE-positive...

Coverage of Japanese encephalitis routine vaccination among children in central India.

We aimed to estimate the coverage of Japanese encephalitis (JE) vaccination in central India to help explain the continued occurrence of JE disease despite routine vaccination.We implemented a 30-cluster survey for estimating the coverage of JE vaccination in the medium-endemic areas implemented with JE vaccination in central India. The parents were enquired about the uptake of the JE vaccine by their children aged 2-6 years, followed by verification of the immunization cards at home along with reasons for non-vaccination. Vaccination coverage was reported as a percentage with 95% confidence intervals (CI).We estimated high coverage of live-attenuated SA 14-14-2 JE vaccination in Maharashtra (94.8%, 95% CI: 92.7-96.3) and Telangana (92.8%, 95% CI:90.0-94.9). The vaccination card retention was 90.3% in Maharashtra and 70.4% in Telangana state. There were no gender differences in coverage in both states. A similar level of JE vaccination coverage was observed during the year 2013-2021 in both states. In Maharashtra, the maximum age-wise coverage was 96.6% in the >60 months age category, whereas in Telangana it was in the <24 months age category (97.2%). The timeliness of JE vaccination was appropriate and similar in both states. We found a very good agreement between JE and measles-rubella vaccinations administered simultaneously. The reasons for non-vaccination were the shortage of vaccines and the parental migration for work.The coverage of JEvaccination was high in medium-endemic regions in central India. Vaccination effectiveness studies may help further explain the continued incidence of JE.

Detection of Polyfunctional T Cells in Children Vaccinated with Japanese Encephalitis Vaccine via the Flow Cytometry Technique.

T cell-mediated immunity plays an important role in controlling flavivirus infection, either after vaccination or after natural infection. The "quality" of a T cell needs to be assessed by function, and higher function is associated with more powerful immune protection. T cells that can simultaneously produce two or more cytokines or chemokines at the single-cell level are called polyfunctional T cells (TPFs), which mediate immune responses through a variety of molecular mechanisms to express degranulation markers (CD107a) and secrete interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, or macrophage inflammatory protein (MIP)-1α. There is increasing evidence that TPFs are closely related to the maintenance of long-term immune memory and protection and that their increased proportion is an important marker of protective immunity and is important in the effective control of viral infection and reactivation. This evaluation applies not only to specific immune responses but also to the assessment of cross-reactive immune responses. Here, taking the Japanese encephalitis virus (JEV) as an example, the detection method and flow cytometry color scheme of JEV-specific TPFs produced by peripheral blood mononuclear cells of children vaccinated against Japanese encephalitis were tested to provide a reference for similar studies.

Interventions for the Prevention and Treatment of Japanese Encephalitis.

Purpose of ReviewJapanese encephalitis (JE), a clinical indication of JE virus–induced brain inflammation, is the most prevalent cause of viral encephalitis in the world. This review gives a comprehensive update on the epidemiology, clinical features, therapeutic trials and approaches for preventing the spread of JE. It also outlines the different JE vaccines used in various countries and recommendations for administration of JE vaccines.Recent FindingsAccording to the WHO, annual incidence of JE is estimated to be approximately 68,000 cases worldwide. It is widespread across Asia–Pacific, with a potential for worldwide transmission. In endemic locations, JE is believed to affect children below 6 years of age, but in newly affected areas, both adults and children are at risk due to a lack of protective antibodies. Various vaccines have been developed for the prevention of JE and are being administered in endemic countries.SummaryJE is a neuroinvasive disease that causes symptoms ranging from simple fever to severe encephalitis and death. Despite a vast number of clinical trials on various drugs, there is still no complete cure available, and it can only be prevented by adequate vaccination. Various nanotechnological approaches for the prevention and treatment of JE are outlined in this review. Supplementary InformationThe online version contains supplementary material available at 10.1007/s11908-022-00786-1.

Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis

BackgroundWe aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968–1987], the SA 14-14-2 live-attenuated vaccine strategy [1988–2007], and the Expanded Program on Immunization [EPI, 2008–2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. MethodsThe JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. ResultsAfter the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). ConclusionsEach vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

Japanese Encephalitis DNA Vaccines with Epitope Modification Reduce the Induction of Cross-Reactive Antibodies against Dengue Virus and Antibody-Dependent Enhancement of Dengue Virus Infection

Infection with viruses belonging to the genus Flavivirus, such as Japanese encephalitis virus (JEV) and dengue virus (DENV), is a worldwide health problem. Vaccines against JEV and DENV are currently available. However, the dengue vaccine possibly increases the risk of severe dengue due to antibody-dependent enhancement (ADE). Moreover, the Japanese encephalitis (JE) vaccine reportedly induces cross-reactive ADE-prone antibodies against DENV, potentially leading to symptomatic dengue. Therefore, it is necessary to eliminate the risk of ADE through vaccination. In this study, we attempted to develop a JE vaccine that does not induce ADE of DENV infection using an epitope modification strategy. We found that an ADE-prone monoclonal antibody cross-reactive to DENV and JEV recognizes the 106th amino acid residue of the E protein of JEV (E-106). The JE DNA vaccine with a mutation at E-106 (E-106 vaccine) induced comparable neutralizing antibody titers against JEV to those induced by the wild-type JE DNA vaccine. Meanwhile, the E-106 vaccine induced 64-fold less cross-reactive ADE-prone antibodies against DENV. The mutation did not compromise the protective efficacy of the vaccine in the lethal JEV challenge experiment. Altogether, the modification of a single amino acid residue identified in this study helped in the development of an ADE-free JE vaccine.

Evaluation of the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province-based on interrupted time series

Objective: To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province. Methods: Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design. Results: The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 (t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 (t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 (β1+β3=0.071). Conclusions: The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

Viral Etiology in Acute Encephalitis Syndrome in North Indian Children

Background and Objective: Acute Encephalitis Syndrome (AES) leads to significant mortality and morbidity in children. This study was undertaken to identify the viral causes of AES and its correlation with clinicodemographic profile. Methods: This cross-sectional study included 100 children aged 1 to 12 years presenting with fever of &lt;14 days duration and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) [1]. Cerebrospinal Fluid (CSF) was collected aseptically by lumbar puncture for biochemical and cytological analysis, and for bacteriological culture. Multiplex PCR for the viruses HSV1, HSV2, Varicella zoster virus, Enterovirus, Mumps and Parecho virus was carried out. Serology for Japanese Encephalitis (JE) was done in blood and CSF by ELISA method. Dengue NS1 antigen and IgM ELISA was carried out in both blood and CSF samples. Serum IgM antibody for scrub typhus was done by ELISA method. Results: Out of 100 children viral cause was detected in 21 patients (Japanese encephalitis -16, Dengue – 4, Varicella zoster virus, Enterovirus and Mumps virus – 1 each). Serum IgM ELISA for scrub typhus was positive in 6 patients. Multiple viral etiology was seen in 2 patients. Mortality was significantly more in females (p=0.021), GCS &lt;8 (p &lt;0.001). Mortality was significantly more with higher CSF neutrophils and higher proteins (p&lt;0.05). Interpretation and Conclusion: This study concludes that viral causes specially JE contributed in AES in North India. Hence viral pathogens including JE needs to be considered as one of major causative agents while treating patients of AES and further emphasis has to be given for JE vaccination in this region.

Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis

In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, β1 and β1+β3 represented the slope or trend of the JE incidence before and after the EPI, respectively; β2 was the level change of the JE incidence immediately after the EPI; β3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (β1<0.000, P<0.05). The JE incidence in Mainland China (β2=−7.669, P<0.05), East China (β2=−9.791, P<0.05), Central China (β2=−10.695, P<0.05), South China (β2=−6.551, P<0.05) and Southwest China (β2=−2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (β3=0.272, P<0.05), East China (β3=0.337, P<0.05), Central China (β3=0.381, P<0.05), South China (β3=0.254, P<0.05) and Southwest China (β3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (β1+β3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.

Review of Japanese Encephalitis Vaccines in India

Japanese encephalitis virus belongs to the genus Flavivirus. Case fatality averages 30% and almost 50% of the survivors are left with permanent neuropsychiatric sequelae. Japanese encephalitis occurs in nearly all Asian countries including India. Patterns of JE transmission vary within individual countries and from year to year. In endemic areas, sporadic cases occur throughout the year. Japanese encephalitis or AES has been reported from 231 districts of 23 states. The best way to control JE in humans is through vaccination. Currently available vaccines in India are live attenuated, cell culture-derived SA 14-14-2, inactivated SA 14-14-2 vaccine (IC51; IXIARO® by Intercell and JEEV® by Biological Evans India Ltd.) and inactivated Vero cell culture-derived Kolar strain, 821564XY, JE vaccine (JENVAC® by Bharat Biotech). As 2006 position paper of WHO stated that mouse brain derived vaccines should be withdrawn and replaced by newer vaccines due to safety profile and as it is not available in our country now, this vaccine will not be discussed henceforth.