Long-term neurological and healthcare burden of adults with Japanese encephalitis: A nationwide study 2000-2015.

OBJECTIVE: To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE). METHODS: This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients' healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients. RESULTS: This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis (p<0.05). Having a four-dose JE vaccination (i.e., born after 1976) versus no JE vaccination history (i.e., born before 1963) was significantly associated with lower all-cause mortality (hazard ratio: 0.221 [95% confidence interval: 0.067, 0.725]). Comorbid diabetes and incident epilepsy/convulsion events significantly increased the mortality risk by 2.47- and 1.85-fold, respectively (p<0.05). CONCLUSION: A considerable medical burden associated with JE was observed in affected adults, even in the years following JE diagnosis. Vaccination should be considered to prevent this sporadic, but lethal, viral infection.

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013-2018.

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy. METHODOLOGY/PRINCIPLE FINDINGS: We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%). CONCLUSIONS/SIGNIFICANCE: JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.

Hospital-based surveillance for Japanese encephalitis in Bangladesh, 2007-2016: Implications for introduction of immunization.

BACKGROUND: Japanese encephalitis (JE) virus is recognized as a major cause of encephalitis in Bangladesh. The World Health Organization (WHO) recommends human immunization as the most effective means to control JE. Several WHO-prequalified vaccines are available to prevent JE but no vaccination program has been implemented in Bangladesh. METHODS: We conducted hospital-based surveillance for acute meningitis-encephalitis syndrome (AMES) to describe JE epidemiology and help inform policy decisions about possible immunization strategies for Bangladesh. RESULTS: During 2007-2016, a total of 6543 AMES patients were identified at four tertiary hospitals. Of the 6525 patients tested, 548 (8%) were classified as JE cases. These 548 patients resided in 36 (56%) out of 64 districts of Bangladesh, with the highest proportion of JE cases among AMES patients (12% and 7%) presenting at two hospitals in the northwestern part of the country. The median age of JE cases was 30 years, and 193 (35%) were aged ≤15 years. The majority of JE cases (80%) were identified from July through November. CONCLUSIONS: Surveillance results suggest that JE continues to be an important cause of meningo-encephalitis in Bangladesh. Immunization strategies including JE vaccine introduction into the routine childhood immunization program or mass vaccination in certain age groups or geographic areas need to be examined, taking into consideration the cost-effectiveness ratio of the approach and potential for decreasing disease burden.

Analysis of the Full Economic Cost for Japanese Encephalitis Under Different Risk Scenarios for Business Travelers to Asia.

OBJECTIVE: Methods for assessing the costs and benefits of administering vaccines to international business/occupational travelers, assignees, and expatriates have neglected the impact of health and treatment on work productivity. The research objective is to evaluate the benefit to cost ratio of the Japanese encephalitis (JE) vaccine for international business/occupational travelers to Asia and other endemic areas incorporating a health and productivity approach. METHODS: Costs and benefits were estimated using actuarial methods with data obtained from secondary sources describing prevalence of infection risk and health outcomes, and business traveler demographic and travel characteristics. Results assumed 2018 salaries and prices, with employee time valued according to total compensation. RESULTS: Risks contracting JE vary widely on the basis of length of trip, season, and destination. The productivity benefits of vaccinating a traveler outweigh the vaccination costs for those staying 30 days or longer in endemic areas during one or more transmission seasons ($2009 vs $750 per traveler), and for business travelers to endemic areas during the transmission season with outdoor activities for the average 2-week/15.4-day international business trip ($502 to $815 vs $500). Vaccination costs outweigh the productivity benefits for short-term travelers who remain in urban areas or travel outside of the transmission season ($10 vs $500). CONCLUSION: JE Vaccination for business travelers in the active transmission season has a net benefit under certain conditions that are not commonly considered risky, such as average-length trips to peri-urban areas, in situations where contracting disease would result in significant business disruption, or when multiple trips are anticipated over several years.

Clinical development of IMOJEV ®--a recombinant Japanese encephalitis chimeric vaccine (JE-CV).

INTRODUCTION: Japanese encephalitis (JE) is a disease of the central nervous system (CNS) caused by Japanese encephalitis virus (JEV). JE is endemic in most of the South-East Asian countries and in some parts of the Western Pacific. As mosquito control is ineffective, currently vaccination is the only available control measure. A mouse brain-derived inactivated JE vaccine (MBDV) has been in use for a long time; however, it is not feasible for mass vaccination due to the ethical and safety issues. With the World Health Organization (WHO) appealing for the development of novel, safe and affordable JE vaccines, several vaccine candidates have been developed in the recent times and IMOJEV ® is one among them. AREAS COVERED: This review presents a brief account of various developmental, immunological and ethical issues related to IMOJEV® and provides an in-depth account of its clinical development and efficacy in comparison to other JE vaccines. EXPERT OPINION: IMOJEV® is a safe and efficacious vaccine. If made affordable through financial assistance from health agencies or by its production in set ups where operational costs are lower, it may become an ideal vaccine for mass vaccination in JE endemic regions.

An economic evaluation of the use of Japanese encephalitis vaccine in the expanded program of immunization of Guizhou province, China.

BACKGROUND: Historically, China's Japanese encephalitis vaccination program was a mix of household purchase of vaccine and government provision of vaccine in some endemic provinces. In 2006, Guizhou, a highly endemic province in South West China, integrated JE vaccine into the provincial Expanded Program on Immunization (EPI); later, in 2007 China fully integrated 28 provinces into the national EPI, including Guizhou, allowing for vaccine and syringe costs to be paid at the national level. We conducted a retrospective economic analysis of JE integration into EPI in Guizhou province. METHODS: We modeled two theoretical cohorts of 100,000 persons for 65 years; one using JE live-attenuated vaccine in EPI (first dose: 95% coverage and 94.5% efficacy; second dose: 85% coverage and 98% efficacy) and one not. We assumed 60% sensitivity of surveillance for reported JE rates, 25% case fatality, 30% chronic disability and 3% discounting. We reviewed acute care medical records and interviewed a sample of survivors to estimate direct and indirect costs of illness. We reviewed the EPI offices expenditures in 2009 to estimate the average Guizhou program cost per vaccine dose. RESULTS: Use of JE vaccine in EPI for 100,000 persons would cost 434,898 US$ each year (46% of total cost due to vaccine) and prevent 406 JE cases, 102 deaths, and 122 chronic disabilities (4554 DALYs). If we ignore future cost savings and only use EPI program cost, the program would cost 95.5 US$/DALY, less than China Gross Domestic Product per capita in 2009 (3741 US$). From a cost-benefit perspective taking into account future savings, use of JE vaccine in EPI for a 100,000-person cohort would lead to savings of 1,591,975 US$ for the health system and 11,570,989 US$ from the societal perspective. CONCLUSIONS: In Guizhou, China, use of JE vaccine in EPI is a cost effective investment. Furthermore, it would lead to savings for the health system and society.

[Analysis on disease burdern of Japanese encephalitis (JE) in Gansu province].

OBJECTIVE: To evaluate the disease burden of Japanese Encephalitis (JE), and provide strategy for disease control and prevention. METHODS: Firstly, analysis the incidence, mortality and fatality rate of JE in Gansu province in 2006. Then the investigation was carried out for calculating all expenditure items of the patients, including medical cost of the hospitalization, medicines, the transport costs, and other non-medical direct cost. RESULTS: In 2006, among the 27 type A and B notifiable infectious diseases in Gansu Province, JE mortality rate was at the top 3, fatality rate was at first rank. The direct cost of JE disease was 6889 RMB per case. In 2006, the direct cost of JE cases was 1,116,000 RMB in Gansu Province. CONCLUSION: JE had the high mortality, and fatality. The fatality in adult was higher than in children. JE patients had to pay high costs. JE disease burden should not be underestimated.

A cost-effectiveness analysis of Japanese encephalitis vaccine in Cambodia.

This study aimed to evaluate the cost and effectiveness of introducing a live, attenuated vaccine (SA 14-14-2) against Japanese encephalitis (JE) into the immunization program. The study demonstrated that SA 14-14-2 immunization is cost-effective in controlling JE in Cambodia compared to no vaccination. Averting one disability-adjusted life year, from a societal perspective, through the introduction of SA 14-14-2 through routine immunization, or a combination of routine immunization plus a campaign targeting children 1-5 or 1-10 years of age, costs US$22, US$34 and US$53, respectively. Sensitivity analyses confirmed that there was a high probability of SA 14-14-2 immunization being cost-effective under conditions of uncertainty.

Cost-effectiveness of Japanese encephalitis (JE) immunization in Bali, Indonesia.

Two hypothetical birth cohorts in Bali, each consisting of 100,000 newborns, one immunized with live, attenuated JE vaccine and the other un-immunized, were modeled for JE risk over 11 years. Cumulative JE incidence before JE vaccine introduction was used to represent JE risk in the unvaccinated cohort. Data on vaccine efficacy, vaccination and treatment costs were taken from published papers and surveys. The potential immunization program averted 54 cases, 5 deaths and saved 1,224 disability adjusted life years (DALYs) at a net cost of USD 700 per JE case averted and USD 31 per DALY saved and thus was highly cost-effective.

A chimeric live attenuated vaccine against Japanese encephalitis.

Japanese encephalitis is a disease of the CNS, endemic in Asia and Oceania. The disease is refractory to drug treatments and whilst the rural economies remain heavily dependent on agriculture, conditions for propagation of the disease will persist. Thus, there is a need for effective vaccines. Although some currently exist, they have their shortcomings. ChimeriVax-JE (Acambis Inc.) is a chimeric, live attenuated vaccine which expresses protective Japanese encephalitis antigens and to date has proven to be safe, effective and well-tolerated in clinical trials. It therefore appears to be a cost-effective prophylactic vaccine against this debilitating disease.

Cost-effectiveness of routine immunization to control Japanese encephalitis in Shanghai, China.

OBJECTIVE: To assess the cost-effectiveness of inactivated and live attenuated Japanese encephalitis (JE) vaccines given to infants and children in Shanghai. METHODS: A decision-analytical model was constructed in order to compare costs and outcomes for three hypothetical cohorts of 100,000 children followed from birth in 1997 to the age of 30 years who received either no JE vaccine, inactivated JE vaccine (P3), or live attenuated JE vaccine (SA 14-14-2). Cumulative incidences of JE from birth to 30 years of age in the pre-immunization era, i.e. before 1968, were used to estimate expected rates of JE in the absence of vaccination. The economic consequences were measured as cost per case, per death, and per disability-adjusted life year (DALY) averted for the two JE immunization programmes. FINDINGS: In comparison with no JE immunization, a programme using the P3 vaccine would prevent 420 JE cases and 105 JE deaths and would save 6456 DALYs per 100,000 persons; the use of the SA 14-14-2 vaccine would prevent 427 cases and 107 deaths and would save 6556 DALYs per 100,000 persons. Both kinds of immunization were cost saving but the SA 14-14-2 vaccine strategy resulted in a saving that was 47% greater (512,456 US dollars) than that obtained with the P3 vaccine strategy (348,246 US dollars). CONCLUSION: Both JE immunization strategies resulted in cost savings in comparison with no JE immunization. This provides a strong economic rationale for vaccinating against JE in Shanghai and suggests that vaccination against JE might be economically justifiable in other parts of China and in certain other developing countries of Asia where the disease is endemic.

Cost benefit analysis of Japanese encephalitis vaccination program in Thailand.

Using decision analysis, we estimated benefits, risks, and costs of implementing the Japanese encephalitis (JE) vaccination program in children aged 18 months and 6 years in Thailand. The costs for inclusion of JE vaccine into the routine immunization program at 18 months and 6 years are $2.16 and $3.68 per person, respectively. In the baseline model, the JE vaccination program will prevent 124 JE cases in the program for 18 months old children and 153 JE cases in the program for 6 years old children. The 18 month child program is more cost-effective than the 6 year child program. The cost-effectiveness ratio in the 18 month child program is $15,715 compared with $21,661 in the 6 year child program. The benefits of the JE vaccination program are the savings in treatment cost, disability care, and the future lifetime earnings from JE prevented. The 18 month child program will save $72,922 per one prevented JE compared with $66,197 in the 6 year child program. The JE vaccination program is cost-beneficial under the base-case assumption. Sensitivity analysis which alters various assumptions indicates that the JE vaccination program is worth implementing unless the incidence of JE is less than 3 per 100,000 population. Otherwise, the cost of vaccine has to be reduced.