Comparative economic analysis of strategies for Japanese encephalitis vaccination of U.S. travelers.

BACKGROUND: Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories. METHODS: We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend ≥1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending ≥20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs. RESULTS: The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios. CONCLUSION: Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios.

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.

Recent and historical trends in the epidemiology of Japanese encephalitis and its implication for risk assessment in travellers.

Japanese encephalitis is a major disease in many countries in Asia often visited by both leisure and non-leisure travellers. Although reported cases of Japanese apoptosis (JE) in travellers are relatively few, there are indications that both the number of cases might be underreported and that changes in the epidemiological situation in these parts of Asia may increase the risk, especially non-leisure travellers. Although JE mainly is considered a rural disease urban cases are seen the large economic growth and urbanization of previously rural areas in many for JE high-endemic areas may further add to the risk for JE, especially for business travellers, when visiting newly established peri-urban areas. This review will address these dynamic and unpredictable risks for JE and discuss its possible implications for the traveller.

Economic evaluation of Japanese encephalitis vaccination programme in Uttar Pradesh, India: a cost-benefit study.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is a major cause of child mortality and disability in the state of Uttar Pradesh. The disease is vaccine preventable since 1941. Yet no major vaccination was available for public health intervention. After a massive breakout in 2005, the government launched vaccination programme in 11 most endemic districts and is planning to incorporate the vaccine in routine immunization with DPT (Diptheria, pertussis and tatanus) booster dose. The paper aims to estimate discounted net benefits and internal rate of return (IRR) to evaluate the economic feasibility for elimination of JE by utilizing available secondary information. METHODS: Cross-sectional data were collected from different sources to estimate societal costs and benefits from JE interventions with a 5 yr project period. Total costs are estimated based on the unit cost of inputs used for interventions. The benefits are derived from resources saved due to the reduction of JE incidence. Net benefits and IRRs are estimated based on standard procedures used in the field of economics. RESULTS: A total discounted net benefit of JE vaccination is Rs 598.52 million with 291% IRR. The result suggests that for every rupee invested in vaccination at present will yield Rs 11 benifit per person over five years. The regional benefits from the interventions will be greater than the sum of benefits gained by the individual country due to its nature of public goods. CONCLUSION: Vaccination against JE is a good investment opportunity despite all operational issues associated with it.

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.

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.

Investing in vaccines for developing countries: How public-private partnerships can confront neglected diseases.

This commentary discusses the barrier of vaccine price on sustainable immunization programs in developing countries and offers examples of new mechanisms driven by public-private partnerships to overcome issues of affordability. These mechanisms include Advance Market Commitments with vaccine manufacturers, which take a demand-pull approach to ensure increased production of available vaccines or development of new vaccines for neglected diseases. A second approach applies a supply-push mechanism, such as technology transfer to developing-country manufacturers. A public-private partnership that set long-term, maximum public-sector pricing to increase access of a Japanese encephalitis vaccine for the developing world is highlighted. Lessons learned from this experience can be applied to address common obstacles to new vaccine introduction in resource-limited countries, including issues of affordability, manufacturing capacity, equity in access and quality assurance.

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.

Immunization against Japanese encephalitis in China: a policy analysis.

This study examined the impact of Japanese encephalitis (JE) immunization policies on disease trends in China. Through a document review and key source interviews in eight provinces, the study found, JE immunizations were provided via a combination of fee-for-service and government funding. Unequal government funding and unbalanced economic development led to variation in JE incidence levels between provinces. Government support of low-fee JE immunization, has led to nationwide decline of JE incidence by >90%; however, greater reliance on user fees and market mechanisms in rural areas has limited the provision of JE and other childhood immunizations to poor rural children.

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.

Japanese encephalitis subunit vaccine composed of virus-like envelope antigen particles purified from serum-free medium of a high-producer J12#26 cell clone.

A stable cell clone, J12#26, which continuously secretes large amounts of the envelope (E) antigen of Japanese encephalitis (JE) virus (J. Virol. 77 (2003) 8745) was adapted to serum-free medium. The J12#26 antigen possessed hemagglutinating activity, as well as the viral E and M proteins. More than 10 and 1mg of the antigen quantified with the licensed JE vaccine (JE-VAX) as a standard by E-ELISA and protein determination, respectively, were recovered from 500 ml of serum-free medium by membrane ultrafiltration, Sephacryl S-300 chromatography, sucrose gradient centrifugation and Sephadex G-25 chromatography. SDS-PAGE and Western blot analyses confirmed the high yield and purity of the J12#26 E antigen, which was comprised of small spherical virus-like particles (VLP) of approximately 25 nm in diameter. This antigen induced in mice without adjuvant neutralizing antibody (NT Ab) titers, as high as or higher than the licensed JE vaccine, and complete protection against challenge with wild-type virus. These results suggest that the J12#26 antigen is a promising second-generation JE subunit vaccine.