path s Japanese encephalitis project

Transcription

1 path s Japanese encephalitis project Collabor ation and commitment to protec t Asia s children

2 Japanese encephalitis transmission area Source: US Centers for Disease Control and Prevention ii PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

3 Introduc tion Japanese encephalitis (JE) is the leading viral cause of disability in Asia. 1 The mosquitoes that transmit JE breed in areas of standing water such as rice paddies and rural communities of Asia are particularly vulnerable. The disease primarily affects children and begins with flu like symptoms, sometimes progressing to abnormal behavior, confusion, and agitation. As the illness advances, seizures may occur, and patients often become comatose. Approximately 70 percent of those who develop JE illness either die or suffer long term neurological disabilities. 2 Immunization is the best method for prevention of JE, but control efforts have been hindered by inadequate disease surveillance, a limited and unstable vaccine supply, lack of guidance and programmatic support, and insufficient advocacy. Focused efforts from PATH and its partners over the past several years, however, have shifted the landscape of JE control. Dedicated endeavors have resulted in unprecedented progress in recording JE disease burden in endemic countries, ensuring access to safe and affordable vaccines, and advancing national programs for JE control. JE immunization is now under way in many developing countries and a priority for others in the near future. Photo: PATH/Julie Jacobson PATH s Japanese encephalitis projec t PATH first heard the call for JE control directly from within one of the countries suffering its greatest burden. In 2000, health officials in Andhra Pradesh, India, working with PATH to introduce hepatitis B vaccine and boost general immunization services, raised concerns about JE. Voices rose from several other states, weary from repeated outbreaks and in search of a solution. The JE project set its goals and carried out a broad array of activities that responded directly to the needs, priorities, opportunities, and challenges in endemic countries. Through a generous grant from the Bill & Melinda Gates Foundation, PATH s JE project was established in 2003 with the goal of eliminating clinical JE and avoiding the unnecessary death and disability caused by this disease. The project focused on providing technical support to JE endemic countries and operated according to the following objectives: Improve data for decision making. Advance the availability of an improved vaccine. Introduce vaccine to immunization systems. Expand outreach through advocacy. This report summarizes the accomplishments gained and challenges faced through the JE project s work with partners and endemic countries to meet these objectives. Fact sheets on each technical area, included with this report, provide further details and offer lessons learned to benefit future JE control efforts. PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 1

4 O b j e c t i v e 1: I m p r o v e data f o r d e c i s i o n m a k i n g Disease surveillance To consider the appropriateness and potential impact of JE vaccine introduction, decision makers need information on JE incidence, case fatality rate, age distribution, and more. Reliable, routine surveillance activities are critical to gathering these important data. Their value also extends beyond program planning. Continued surveillance reveals the ultimate results of JE immunization and helps inform program evolution and management. PATH and its partners collaborated to initiate or strengthen encephalitis surveillance in several countries, and these activities often provided crucial insights: In Indonesia, a sentinel surveillance study revealed JE throughout the country rather than just in pig rearing areas, as prevailing wisdom had held. 3 In Vietnam, hospital based surveillance showed that JE cases were persistent in areas not reached by the geographically targeted JE immunization program, and officials are now planning national expansion. 4 In Cambodia, sentinel surveillance showed clear evidence of disease burden, with children younger than 12 years of age at highest risk (see chart below). These results were pivotal to health officials decision to introduce the live, attenuated SA JE vaccine in October These and similar efforts in other countries were facilitated by the publication of the World Health Organization (WHO) JE surveillance standards, which provide a clinical case definition for acute encephalitis syndrome (AES) and criteria for laboratory confirmation of JE. A version of the surveillance standards was distributed in 2006 for field testing. Feedback from country level activities, combined with input from the JE Core Working Group an advisory group of experts in public health, clinical and laboratory issues, and other aspects related to JE disease helped refine an updated version published in August Distribution of JE cases by age group (Cambodia, May 2006 May 2007) JE diagnostics Beyond clinical case evaluation, the next step in surveillance activities is confirmation of JE through sample collection and laboratory testing. But major challenges have prevented streamlined and reliable JE diagnostic testing in developing countries. One significant obstacle is the lack of standardized JE test kits. The platform for JE virus laboratory diagnosis is the immunoglobulin M (IgM) antibody capture enzyme linked immunosorbent assay (ELISA), which detects antibody in serum and cerebrospinal fluid. PATH and its partners conducted studies to evaluate the accuracy and usability of currently available commercial kits (the Panbio JE Dengue IgM Combo ELISA by Inverness [Brisbane, Australia], the JE IgM ELISA by InBios International, Inc. [Seattle, USA]; and the JEV CheX kit by XCyton Diagnostics Ltd. [Bangalore, India]): An evaluation in partnership with the Armed Forces Research Institute for Medical Sciences (AFRIMS) found high sensitivity among all three kits but low specificity of the kits manufactured by InBios and XCyton when dengue is also present both had limited capacity to distinguish between JE and dengue infections. The Panbio kit includes both JE and dengue antigens. 7 A field evaluation of the Panbio and XCyton kits, in partnership with Nepal s National Public Health Laboratory and AFRIMS, showed that both kits had good predictive values using single serum samples from AES cases, and either kit could be used for laboratory based JE surveillance in similar epidemiologic settings. 8 Future efforts will need to ensure that evaluations of diagnostic kits are standardized and that all countries at risk of JE have access to qualified national or regional reference laboratories. Regional laboratory networks in WHO s Southeast Asia and Western Pacific regions will provide training, protocols, and technical assistance to national laboratories as they continue to build capacity in JE diagnostics. Number of cases under over 15 Age in years Disability after JE An often unrecognized burden of JE is the neurological disability it causes in more than one third of survivors, which can be as severe as paralysis or as mild as lingering learning disabilities and behavioral changes. 2 A complete definition of disease burden would include not just deaths caused by JE, but also the social and economic impact of disability on families and communities. Thus, data on JE disability comprise another important element to be considered by decision makers. 2 PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

5 S h a d o w l i v e s : A h i d d e n t o l l Mahesh was a typical boy from a rural village in southern India. He went to school, played with friends, and helped with household chores. Today, he is a shadow of his former self. Image from the video Shadow Lives (PATH) Mahesh suffered long-term neurological disability as a result of JE infection and requires constant supervision and care from his family. Two years ago, Mahesh contracted JE. Although he has fared better than most he survived and has no physical disability the infection damaged his brain so badly that he no longer recognizes his own parents. Today, Mahesh attends school, but he sits passively in the back of the classroom, unable to concentrate for any stretch of time. He will never be able to work, and his illness has been emotionally and financially devastating to his family. JE vaccination is the only way to avoid such tragedy. Determined to overcome the toll of JE on children like Mahesh, the Government of India made an unprecedented commitment to spare vulnerable children. Mass vaccination campaigns were initiated in 2006, and by 2010 more than 100 million children will be protected. PATH supported the University of Liverpool s efforts to develop a tool for assessing disability after JE that would be simple, adaptable, and easy to use in resource limited settings. The Liverpool Outcome Score met these criteria, incorporating a set of questions posed to caregivers along with observation of the child performing simple tasks such as walking and grasping an object. 9 Small scale studies in several countries revealed the tool to be a valuable method for gathering data on the burden of JE disability while estimating the likelihood of a JE survivor ultimately leading an independent life: In Cambodia, among 38 survivors who were assessed, researchers applying the tool at home visits found that 11 percent had severe sequelae, 38 percent had moderate sequelae, and 45 percent had minor sequelae. 10 In Indonesia, 65 children were evaluated, and half either died or were left with serious disabilities. 3 In Vietnam, among 26 laboratory confirmed JE cases, 2 cases had severe sequelae, 5 had moderate sequelae, and 8 had mild sequelae. 4 The disability studies clearly show the devastating impact of JE. Among the cases assessed in these studies, up to one quarter died, and almost half of JE survivors suffered severe or moderate disabilities, requiring constant support from their families and communities. As few as four percent of JE survivors recovered completely. Cost effectiveness of JE immunization Immunization is one of the most cost effective health interventions available. It is universally accepted that adopting vaccines is among the very best uses of scarce health care dollars. But even though immunization is universally recognized as a good use of health resources, many countries have limited resources to invest in new vaccines. When faced with competing priorities and limited resources, economic evaluations can help determine appropriate resource allocation and design services. In 2006 in Andhra Pradesh, India, investigators compared the cost effectiveness of (1) two strategies: a one time catch up campaign or a catch up campaign combined with routine immunization, and (2) two vaccines: inactivated, mouse brain derived JE vaccine and live, attenuated SA JE vaccine. Results demonstrated that the WHO recommended JE vaccine introduction strategy (catch up campaigns plus routine immunization) using the live, attenuated SA JE vaccine is very cost effective. This same strategy using the inactivated, mouse brain derived JE vaccine was considered not cost effective. Given limited resources, immunization strategies targeting high risk areas were found to be more cost effective. 11 It is important to note that this analysis was completed prior to the availability of public sector pricing for the SA vaccine, which further improves its cost effectiveness. Similarly, PATH launched a study in 2007 to analyze cost effectiveness of JE vaccines in Cambodia, collaborating with the Communicable Disease Control Department and the National Immunization Program of the Ministry of Health. Results helped guide decision making and inform the JE immunization strategy. 5 PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 3

6 O b j e c t i v e 2: Advance availabilit y of an improved vaccine Several endemic countries have successfully controlled JE with a vaccine available for over 60 years. 2 However, most manufacturers of the inactivated, mouse brain derived vaccine had decreased or halted production, as it was difficult and expensive to produce. PATH joined others in seeking a solution. Several vaccine candidates were in development, but the SA JE vaccine manufactured by the Chengdu Institute of Biological Products (CDIBP) in China offered the greatest potential. This live, attenuated vaccine had been safely used for over 20 years, 12 a reliable supply was available, and the manufacturer was willing to provide it at an affordable price for developing countries. Because the live, attenuated SA vaccine had not been widely used outside of China, international- and country level officials called for specific clinical studies. Collaborating with the manufacturer, WHO, and ministries of health, PATH conducted pivotal clinical trials to add to a growing collection of data on the vaccine. Recommendations from the WHO Global Advisory Committee on Vaccine Safety and the Strategic Advisory Group of Experts also informed research activities. Co-administration of measles and JE vaccines (Philippines) PATH and the Research Institute of Tropical Medicine initiated a study in 2005 to evaluate the safety and immunogenicity of co-administering the live, attenuated SA JE vaccine and the Expanded Programme on Immunization (EPI) measles vaccine. The WHO Global Advisory Committee on Vaccine Safety reviewed the data and concluded that the short term safety profile was acceptable. 13 With advances in plaque reduction neutralization testing (PRNT) as the emerging gold standard for antibody testing, an expert review committee in 2009 recommended re analysis of the study samples using an ELISA test comparable to PRNT. Analysis of test results will begin in late Co-administration of measles and JE vaccines (Sri Lanka) PATH and the Ministry of Healthcare and Nutrition, Epidemiology Unit, initiated a similar study in In both studies, seropositivity rates for both JE and measles were high after follow up at one year and demonstrated no interference. Safety assessments found no severe local reactions, and no severe systemic reactions were considered by the investigators to be related to vaccination. 14 Use of SA JE vaccine after administration of mouse brain derived vaccine (Sri Lanka) A second study in Sri Lanka evaluated safety and immunogenicity of the live, attenuated SA JE vaccine among 2 and 5 year old children who had previously received doses of the mouse brain derived, inactivated vaccine used in the national program. The study was completed in 2008, and results showed a booster effect of JE antibodies at one month that persisted one year after receipt of SA vaccine. 14 Adult viremia (India) Sponsored by the Indian Council on Medical Research and the National Institute of Virology with technical assistance from PATH, this study was conducted to support the licensure process and found that there was no virus shedding after 15 days in adults who received one dose of the live, attenuated SA JE vaccine. 15 Vaccine effectiveness (India) PATH is assisting the Government of India in conducting a case control study to evaluate the effectiveness of the live, attenuated SA vaccine in preventing clinical JE. Vaccine quality Data from these studies also expanded the vaccine s dossier for submission to WHO toward prequalification, which allows for medical products to be procured through United Nations agencies. This status is granted to products and/ or manufacturers that demonstrate quality, acceptability, and reliability of supply. To ensure that vaccine production at CDIBP meets these requirements, PATH is providing support and technical assistance for construction of a new facility that will help meet regional demand and produce JE vaccine according to international standards for current Good Manufacturing Practices. Photo: Chengdu Institute of Biological Products 4 PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

7 O b j e c t i v e 3: Introduce and integr ate vaccine In recent years, numerous projects and studies have demonstrated regional and national incidence of JE as never before. With this new information and with the availability and reliable supply of a safe, affordable JE vaccine comes the increasing need for strategies to control JE and protect populations at risk. Progress has been rapid; countries that were only beginning to understand their JE burden a few years ago are now implementing immunization programs. Furthermore, their experiences are being carefully documented to benefit the future planning of their neighbors. Introduction of the live, attenuated SA JE vaccine India and Nepal were among the first to introduce the SA vaccine from CDIBP through mass campaigns and routine immunization services. A severe outbreak in 2005 spanned the two countries, raised significant community demand, and accelerated plans already under way for JE vaccine introduction. PATH provided technical assistance in both countries, from strategy development through program implementation and evaluation. In India, the government committed to a five year strategy to vaccinate more than 100 million children aged 1 to 15 years in high risk districts. Areas that held campaigns would then begin providing the vaccine in routine immunization services to protect new birth cohorts. By the end of 2010, more than 100 million children will be vaccinated. 8 Nepal had conducted sporadic campaigns a few years earlier, but committed to a sustained effort after the 2005 outbreak. Campaigns beginning in 2006 aimed to protect not only vulnerable children, but also adults. Surveillance data had revealed cases of JE in new areas. Adults in these districts would most likely not have previously been exposed to JE in the environment, and thus would not have natural immunity. Following campaigns in endemic districts, JE vaccine was provided through routine immunization services as well. 8 In the Democratic People s Republic of Korea, PATH partnered with the Ministry of Health, the Academy of Medical Sciences, Christian Friends of Korea, and Global Solutions for Infectious Diseases to support JE vaccination campaigns in 2009 to immunize nearly half a million children. PATH provided supplies for safe immunization and assembled an expert team that offered technical assistance on campaign planning and monitoring. Evaluation of the campaign s success will inform the national government s future JE immunization planning. Photos: PATH/Julie Jacobson PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 5

8 vacc i n e o f h o p e West Bengal is one of India s most high risk states for JE and was among those hit hard by an outbreak in Thousands of families were affected, among them the Hansda family, who lost their oldest son to JE. Malati Hansda remembers her son s fever and severe headache, which developed into convulsions. His father brought him to the hospital by bicycle and bus, but the boy died soon after. A vaccine against JE, said Malati Hansda, definitely could have saved my son. The next year, Malati and Dasarath Hansda brought their surviving son and daughter to a local school serving as a temporary vaccination center, determined that they would be protected before the 2006 monsoon season struck. They were one of millions of families now empowered to provide lifesaving protection to their children, thanks to the national government s prompt response to the devastating JE outbreak just one year earlier. Image from the video Vaccine of Hope (Rockhopper) The Hansdas daughter Seva received JE vaccine in 2006, one year after the virus claimed her older brother. Transition to SA JE vaccine The Government of Sri Lanka first introduced phased vaccination campaigns using the inactivated, mouse brain derived JE vaccine in Surveillance data revealed the need for national expansion, but cost considerations, unreliable supply, and reports of adverse events with the inactivated vaccine prompted a search for a better alternative. Upon review of recommendations from the WHO Strategic Advisory Group of Experts, scientific literature, cost effectiveness data, evidence of impact in other countries, and local studies on safety and immunogenicity, national immunization managers suggested transitioning to the SA vaccine. PATH assisted with local studies on the vaccine s safety and immunogenicity, which bore positive results. Beginning in July 2009, the SA vaccine was introduced in routine immunization services in 18 districts. The cost savings derived from this transition will allow for program sustainability, budget for other new vaccines, expansion of childhood JE immunization nationwide and targeting of vulnerable adults in high risk areas, and the potential to add a second dose of JE vaccine, if necessary. 16 A model project on vaccine transition: Shaanxi Province, China In collaboration with the Chinese Center for Disease Control and Prevention, PATH assisted with a model project to transition from the inactivated JE vaccine to the SA JE vaccine in three counties of Baoji Prefecture, Shaanxi Province. An ancillary part of the project, conducted in 2007, helped to set up active JE surveillance and strengthen JE laboratory and diagnostic testing at the county, prefecture, provincial, and national levels. Upcoming milestones Other countries are planning or expanding JE immunization programs as well, boosted by crucial surveillance data. In Cambodia, the SA JE vaccine was introduced on a small scale in October 2009, with plans for national expansion. The Government of Vietnam plans to expand its geographically targeted JE immunization program nationwide by PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

9 O b j e c t i v e 4: Expand outreach through advoc ac y Throughout the lifetime of the JE project, PATH engaged stakeholders and shared information to raise awareness at national, regional, and global levels. Advocacy efforts helped prioritize JE immunization, foster collaboration, and inform country level control strategies. Vehicles for spreading the message of JE control included key conferences convened by WHO, United Nations Children s Fund (UNICEF), and others. Every two years, PATH and WHO co sponsored the Bi regional Meeting on Control of JE, bringing together country officials from the Southeast Asia and Western Pacific regions and other public health partners. National level events in endemic countries, such as annual pediatric association meetings, also featured JE. PATH also worked closely with the GAVI Alliance to collate crucial information on JE burden, cost effectiveness, and future vaccine demand. This evidence ultimately led to GAVI s inclusion of JE vaccines among those to be considered for future support (along with vaccines against human papillomavirus, rubella, and typhoid). 17 PATH s JE resources Several different types of resources helped educate various audiences about key issues in JE control. A series of training presentations adaptable to local settings addressed vaccine storage and administration, surveillance, and diagnostics (available on the Vaccine Resource Library see sidebar). Talking points and Q&As distributed to partners ensured consistent messaging, particularly regarding clinical trials, vaccine quality and safety, and vaccine pricing. PATH also developed three films for use by partners and health officials in advocacy efforts. Shadow Lives is a short film demonstrating the impact on families and communities when a child is left with severe disability after JE. Two documentaries produced in partnership with Rockhopper TV Japanese Encephalitis and Vaccine of Hope illustrated the burden of JE and the promise of vaccines and captured the first images of Indian children receiving JE vaccine. Aired on BBC World, these documentaries were broadcast in more than 200 countries. Finally, peer reviewed publications helped disseminate the scientific evidence of JE disease burden and vaccine safety gathered through the JE project s research endeavors. Publications addressed country level disease burden, cost effectiveness, characteristics of the SA JE vaccine, disability among JE survivors, and evaluation of available diagnostic kits. A complete list of these publications is available at the end of this report. O n l i n e J E r e s o u r c e s JE Newbriefs and JE Flash archives: A quarterly newsletter on the latest developments and a supplemental announcement for breaking news. Available at: encephalitis_project_newsletter.php The PATH Vaccine Resource Library: An archive of scientific documents and training materials published by PATH and its partners on surveillance and disease burden, immunization financing, vaccine safety, and more. Available at: vaccineresources/japanese-encephalitis.php The PATH Advanced Immunization Management (AIM) e-learning module: An interactive learning tool that compiles technical information on JE disease and vaccines to enable national immunization managers to plan vaccine introduction. Available at: org/en/vaccines/je/index.html Photos: PATH/Julie Jacobson PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 7

10 T h e f u t u r e o f J E c o n t r o l PATH s JE project has provided an important model for applying donor funds toward a neglected disease. Made possible by the vision and support of the Bill & Melinda Gates Foundation, this special effort has raised awareness to an unprecedented level and achieved lifesaving impact on countries burdened by JE. But the work is not complete. Moving forward, partners and stakeholders must continue to convene in order to sustain progress and mobilize resources. To ensure that recent accomplishments represent a sustainable shift in JE control, PATH convened partners to develop a strategic plan for JE control by 2015 and beyond. The plan authored in collaboration with WHO, UNICEF, the United States Centers for Disease Control and Prevention, universities, research institutions, and others emphasizes countries priorities and identifies the responsibilities necessary for international partners to maintain progress and generate resources to achieve an ambitious set of goals. 18 Although significant resources are still needed, JE endemic countries are now more aware than ever of how, why, and when to plan JE control efforts and protect populations at highest risk. Peer reviewed public ations Broad dissemination of the experiences and data gathered through PATH s JE project will ensure that lessons learned inform future efforts at JE control. The articles listed below represent the information collected to date by PATH and its partners. Additional publications will follow in late 2009 and beyond, addressing global JE disease burden, a summary of safety studies on the live, attenuated SA JE vaccine, and experiences of regional JE laboratory networks, among other topics Suraratdecha C, Jacobson J, Sivalenka S, Nahrahari D. A cost effectiveness analysis of strategies for controlling Japanese encephalitis in Andhra Pradesh, India. Journal of Pharmaceutical Finance, Economics & Policy. 2006;15(1): Jacobson JA, Hills SL, Winkler JL, et al. Evaluation of three immunoglobulin M antibody capture enzyme linked immunosorbent assays for diagnosis of Japanese encephalitis. American Journal of Tropical Medicine & Hygiene. 2007;77(1): Zhang S, Li Y, Yang J, et al. [Analysis on surveillance data for viral encephalitis of 2005 in Shaanxi Province]. Chinese Journal of Public Health. 2007;23(9): Zhang S, Yin Z, Wang L, et al. [Analysis of Japanese B encephalitis vaccination and a knowledge, attitude and practice survey in Shaanxi Province]. Chinese Journal of Vaccines and Immunization. 2007;13(4): Photos: Patrick McHern (left) and PATH/Julie Jacobson (right) 8 PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

11 2008 Gatchalian S, Yao Y, Zhou B, et al. Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA vaccine in Philippine infants. Vaccine. 2008;26(18): Fischer M, Hills S, Staples E, et al. Japanese encephalitis prevention and control: advances, challenges, and new initiatives. In: Scheld WM, Hammer S, Hughes JM, eds. Emerging Infections. Vol. 8. Washington DC: American Society for Microbiology. 2008: Ompusunggu S, Hills SL, Sembiring Maha M, et al. Confirmation of Japanese encephalitis as an endemic human disease through sentinel surveillance in Indonesia. American Journal of Tropical Medicine and Hygiene. 2008;79(6): Touch S, Grundy J, Hills S, et al. The rationale for integrated childhood meningoencephalitis surveillance: a case study from Cambodia. Bulletin of the World Health Organization. 2009;87(4): Wang H, Fu S, Wang L, et al. [Confirmed diagnosis for Japanese encephalitis reported cases in Shaanxi Province during ]. Chinese Journal of Vaccines and Immunization. 2008;14(2): Zhang S, Yin Z, Suraratdecha C, et al. [Analysis on data from the clinical acute viral encephalitis surveillance system in three prefectures in Shaanxi during ]. Chinese Journal of Epidemiology. 2008;29(9): Elias C, Okwo Bele JM, Fischer M. A strategic plan for Japanese encephalitis control by Lancet Infectious Diseases. 2009;9(1):7. Hills S, Phillips D. Past, present, and future of Japanese encephalitis. Emerging Infectious Diseases. 2009;15(8):1333. Maha MS, Moniaga VA, Hills SL, et al. Outcome and extent of disability following Japanese encephalitis in Indonesian children. International Journal of Infectious Diseases. 2009;13(6):e Touch S, Hills S, Sokhal B. Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance. Tropical Medicine & International Health [Epub] Yaïch M. Investing in vaccines for developing countries: How public private partnerships can confront neglected diseases. Human Vaccines. 2009; 5(6): Photos: PATH/Julie Jacobson (left) and Jacques Bablon (right) PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 9

12 Country ac tivities with support from PATH s je projec t N e pa l Sustained JE vaccine campaigns and routine immunization were introduced in high-risk districts in Diagnostic assessments provided information on the accuracy of commercial ELISA kits. I n d i a JE vaccine campaigns were introduced in high-risk districts, beginning in JE vaccine was then added to routine immunization services in campaign districts. Reporting of adverse events following immunization was enhanced. S r i L a n k a Clinical studies evaluated co-administration of JE and measles vaccines and use of the live, attenuated SA JE vaccine for children who previously received doses of the inactivated vaccine. After reviewing preliminary study results, the Government of Sri Lanka transitioned from the inactivated vaccine to the SA vaccine in C o u n t r y pa r t n e r s Cambodia: Department of Communicable Disease Control, National Institute of Public Health, National Immunization Program China: Center for Disease Control, Chengdu Institute of Biological Products, China National Biotec Group India: Indian Council on Medical Research, Ministry of Health & Family Welfare, National Vector-borne Disease Control Programme, National Institute of Virology Indonesia: Center of Biomedical and Pharmaceutical Research and Development, National Institute of Health Research and Development Nepal: Ministry of Health and Population North Korea: Democratic People s Republic of Korea Ministry of Health, Academy of Medical Sciences Sri Lanka: Ministry of Healthcare & Nutrition, Epidemiology Unit Vietnam: National Institute of Hygiene and Epidemiology, National Expanded Programme on Immunization 10 PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

13 N o r t h K o r e a JE vaccination campaigns in 2009 reached nearly half a million children. C h i n a AES surveillance in Baoji Prefecture, Shaanxi Province ( ), found that more than 7% of cases diagnosed clinically as non-je were laboratoryconfirmed as JE. Evaluation of knowledge, attitudes, and practices and lessons learned from transition from the mouse brain derived to the live, attenuated SA JE vaccine in three counties identified best practices for effective vaccine delivery. PATH s partnership with the Chengdu Institute of Biological Products fostered affordability of the SA JE vaccine and construction of a new production facility to meet international manufacturing standards. V i e t n a m Enhanced surveillance in 2007 showed persistent JE cases in areas not covered by routine JE immunization. A disability study found that 8% of JE patients had severe sequelae incompatible with independent living. C a m b o d i a Surveillance (June 2006 May 2008) found that JE comprised 19% of all meningoencephalitis cases; children under 12 were at highest risk. A disability study showed that 1 in 4 children with clinical JE either died or had severe sequelae. Data on treatment costs associated with hospitalized JE cases helped guide decision-making on JE vaccine introduction. JE vaccine was introduced in I n d o n e s i a Surveillance (January 2005 December 2006) demonstrated JE disease across the country. Follow-up assessments found that half of JE survivors had died or were left with severe disabilities. The JE project also supported WHO regional offices for JE surveillance in the following countries: Bangladesh Bhutan Cambodia China India Laos Nepal Papua New Guinea Philippines Timor L este Vietnam Source: US Centers for Disease Control and Prevention PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children 11

14 R e f e r e n c e s 1 World Health Organization (WHO). Japanese encephalitis vaccines. Weekly Epidemiological Record. 2006;81(34/35): Halstead SB, Jacobson J. In: Chambers T, Monath T, eds. The Flaviviruses: Detection, Diagnosis and Vaccine Development, San Diego: Elsevier Academic Press; 2003: Maha MS, Moniaga VA, Hills SL, et al. Outcome and extent of disability following Japanese encephalitis in Indonesian children. International Journal of Infectious Diseases. 2009;13(6):e Cuong N. Japanese encephalitis surveillance in Vietnam. Presented at: 4th Biregional Meeting on the Control of Japanese Encephalitis, 8 9 June 2009; Bangkok, Thailand. 5 Sarath S. JE vaccine introduction plan in Cambodia. Presented at: 4th Biregional Meeting on the Control of Japanese Encephalitis, 8 9 June 2009; Bangkok, Thailand. 6 WHO. WHO Recommended Standards for Surveillance of Selected Vaccine Preventable Diseases. WHO/V&B/ Geneva: WHO; Available at: WHO_JE_surveillancestandards.pdf. 7 Jacobson JA, Hills SL, Winkler JL, et al. Evaluation of three immunoglobulin M antibody capture enzyme linked immunosorbent assays for diagnosis of Japanese encephalitis. American Journal of Tropical Medicine & Hygiene. 2007;77(1): WHO. Meeting Report: Third Biregional Meeting on Control of Japanese Encephalitis. RS/2007/GE/06(VTN). Manila; WHO Regional Office for the Western Pacific: Available at: who.int/nr/rdonlyres/50129d1d E9B A62E 0A541DBC3032/0/ MTGRPT_JEBireg3.pdf. 9 University of Liverpool Brain Infections Group. Liverpool outcome score for assessing children at follow up. Liverpool, UK: University of Liverpool Brain Infections Group; Available at: path.org/vaccineresources/details.php?i= Cambodia Ministry of Health, PATH. Report on the Japanese encephalitis disability assessment. Phnom Penh, Cambodia: Ministry of Health; Suraratdecha C, Jacobson J, Sivalenka S, Nahrahari D. A cost effectiveness analysis of strategies for controlling Japanese encephalitis in Andhra Pradesh, India. Journal of Pharmaceutical Finance, Economics & Policy. 2006;15(1): Benli Z, Min Z, Pinquan C, et al. An 11 year follow up of epidemiological effect Japanese encephalitis vaccine, live (SA ). Chinese Journal of Biologicals. 2001;14(3). 13 WHO. Global Advisory Committee on Vaccine Safety, December Weekly Epidemiological Record. 2008;83(4): Yaïch M. Results from recent clinical studies. Presented at: 4th Biregional Meeting on the Control of Japanese Encephalitis, 8 9 June 2009; Bangkok, Thailand. 15 Yaïch M. Japanese encephalitis vaccines. Presented at: International Center for Diarrhoeal Disease Research 12th Annual Scientific Congress, February 10 12, 2009; Dhaka, Bangladesh. 16 Wijesinghe PR. Transition from mouse brain derived vaccine to SA Presented at: 4th Biregional Meeting on the Control of Japanese Encephalitis, 8 9 June 2009; Bangkok, Thailand. 17 New vaccine strategy prioritises deadly diseases. [press release]. Geneva: GAVI Alliance; June 25, Available at: releases/2008_06_25_en_pr_nvi_strategy_7_diseases.php. 18 PATH, AFRIMS, Biken, et al. Japanese encephalitis morbidity, mortality, and disability: reduction and control by Seattle: PATH; Available at: details.php?i= PATH s JAPAnese EncePHAlitis Project: Collaboration and Commitment to Protect Asia s Children

15 About PATH PATH is an international nonprofit organization that creates sustainable, culturally relevant solutions, enabling communities worldwide to break longstanding cycles of poor health. By collaborating with diverse public- and private sector partners, PATH helps provide appropriate health technologies and vital strategies that change the way people think and act. PATH s work improves global health and well being. For more information, please visit Copyright 2009, Program for Appropriate Technology in Health (PATH). All rights reserved. The material in this document may be freely used for educational or noncommercial purposes, provided that the material is accompanied by an acknowledgment line. Suggested citation: PATH. PATH s Japanese Encephalitis Project: Collaboration and Commitment to Protect Asia s Children. Seattle: PATH; December 2009

16 S t r e e t A D D r E S S 2201 Westlake Avenue, Suite 200 Seattle, WA 98121, USA M a i l i n g A D D r E S S PO Box Seattle, WA 98109, USA Tel: Fax:

17 PAT H S J A PA N E S E E N C E P H A L I T I S P R O J E C T: A C C O M P L I S H M E N T S A N D L E S S O N S L E A R N E D A D V O C AC Y F O R J A PA N E S E E N C E P H A L I T I S Japanese encephalitis (JE), a mosquito borne viral brain infection, afflicts an estimated 35,000 to 50,000 inhabitants of Asia and the western Pacific annually. 1 The disease most often strikes children, who have not yet built up a natural immunity. One third of JE infections are fatal, and another third leave survivors with severe neurological sequelae. There is no treatment for JE; vaccination is the only defense. Funded by the Bill & Melinda Gates Foundation, PATH s JE project ( ) worked with international partners and developing countries to increase the information available for understanding the extent of the disease and how best to control it. Background PATH s advocacy work raised the prominence of JE within the global health dialogue. Efforts at regional and national levels also helped prioritize JE immunization, fostering collaboration and country level control strategies. The importance of advocacy was revealed in the early stages of the PATH JE project. In Andhra Pradesh, India, officials working with PATH to support routine immunization and hepatitis B vaccine introduction voiced concerns about JE. Voices rose from several other states, citing repeated outbreaks and seeking a solution. By 2003, PATH had secured a grant from the Bill & Melinda Gates Foundation to tackle JE not just in one state in India, but in the entire Southeast Asia and Pacific region. Since then, focused advocacy has sensitized stakeholders and raised awareness among decision makers so they may set appropriate policies in support of JE control efforts. Local conversations and global outreach Information sharing was a key element of the JE project s accomplishments in all technical areas. To disseminate data on surveillance studies and clinical trials or to discuss country experiences using JE vaccine, PATH presented at international meetings and local workshops. Conversations with ministries of health identified information gaps, such as details on the safety of JE vaccines, and guided the JE project s communications and outreach efforts. PATH raised awareness of JE control at key conferences, ensuring it was included on the agendas of various meetings, including the World Health Organization (WHO) Global Vaccine Research Forum, the United Nations Children s Fund Global Immunization Meeting, and the WHO Global Meeting on New and Underutilized Vaccines Implementation. Presentations to WHO s Strategic Advisory Group of Experts and Global Advisory Committee on Vaccine Safety brought new data for review by experts setting global recommendations. Every two years, PATH and WHO co sponsored a Bi regional Meeting on Control of JE, bringing together country representatives, officers from the WHO s Southeast Asia and Western Pacific regions, and other partners to share lessons learned and set priorities for the coming years. Established as a primary resource for information on JE disease and vaccines, PATH was a major contributor to an effort initiated by the GAVI Alliance to identify vaccines for future support. PATH and its partners compiled crucial information that informed GAVI s evaluation and eventually led to the designation of JE vaccines as a future funding priority (along with vaccines against human papillomavirus, rubella, and typhoid). 2 Laying a foundation for continued advocacy, PATH assembled a coalition of partners to develop a JE global control plan with communications and advocacy as primary components. Japanese Encephalitis Morbidity, Mortality, and Disability: Reduction and Control by 2015 outlines priority activities that must be sustained, including improved understanding of disease burden, technical assistance for vaccine introduction, procurement support, and advocacy. 3 Multiple organizations including PATH, WHO, UNICEF, the US Centers for Disease Control and Prevention, research institutions, universities, and others helped develop the plan and have committed to working together to maintain progress, catalyze fundraising, and provide assistance to countries in need. Multiple channels to reach multiple audiences To raise awareness of clinical information about JE, PATH created training presentations on vaccine storage and administration, surveillance, and diagnostics (available on the Vaccine Resource Library see sidebar). Provided in a generic format, these materials allow for adaptation according to local settings. Other training materials produced by the University of Liverpool with funding from the JE Project focus on clinical evaluation of patients at hospital admission and follow up important tools to assess the burden of JE disability. Talking points and Q&As distributed to partners ensured consistent messaging, particularly regarding clinical trials, vaccine quality and safety, and public sector pricing. In 2006, the importance of clear and accurate messaging was illuminated by inaccurate press reports that questioned the safety of the SA JE vaccine and threatened mass campaigns in India. With clear and thorough responses already prepared, PATH and the Government of India were able to quell rumors and provide accurate information.

18 O N L I N E R E S O U R C E S JE Newbriefs archives: A quarterly newsletter on the field s latest developments, supplemented by JE Flash, a timely announcement to distribute breaking news. project_newsletter.php The PATH Vaccine Resource Library: An archive of scientific documents published by PATH and partners on surveillance and disease burden, immunization financing, vaccine safety, and more. The PATH Advanced Immunization Management (AIM) e-learning module: An interactive learning tool that compiles technical information on JE disease and vaccines to enable national immunization managers to plan vaccine introduction. Key lessons learned Advocacy efforts must highlight the impact of regional diseases, which may be underappreciated by funding agencies and global health bodies. The total disease burden of JE may be less overall than for diseases found around the world, but the impact of JE on an individual country can be catastrophic. Close attention must be paid to media reports and communications outlets within the global public health community. Inaccurate and/or incomplete news reports from even local publications can quickly become available on the Internet. It is crucial to develop a crisis communications plan to ensure immediate clarification and responses when appropriate. The decision of a national government to introduce a new vaccine can significantly influence decisions in other countries of the region. Vaccine introduction experiences can be valuable in a regional and global context, and it is important to document these experiences and support the sharing of lessons learned and best practices. Shadow Lives, a film produced by the JE project in 2005, demonstrated the impact of JE on families and communities and is a powerful advocacy tool. Two additional films produced in partnership with Rockhopper TV Japanese encephalitis and Vaccine of Hope documented the burden of JE and the promise of vaccines and captured the first images of Indian children receiving JE vaccine. Aired on BBC World, these documentaries were broadcast in more than 200 countries. Finally, peer reviewed publications were a priority for the JE project, with clinical trials and surveillance studies generating new information. Publications addressed cost effectiveness, co-administration of JE and measles vaccines, country level disease burden, disability among JE survivors, and evaluation of available diagnostic kits. E N D N O T E S 1 Solomon T, Dung NM, Kneen R, Gainsborough M, Vaughn DW, Khanh VT. Japanese encephalitis. Journal of Neurology, Neurosurgery, and Psychiatry. 2000;68(4): New vaccine strategy prioritises deadly diseases. [press release]. Geneva: GAVI Alliance; June 25, Available at: centre/press_releases/2008_06_25_en_pr_nvi_strategy_7_diseases.php. 3 PATH, AFRIMS, Biken, et al. Japanese Encephalitis Morbidity, Mortality, and Disability: Reduction and Control by Seattle, WA: PATH; Available at: PO Box Seattle, WA USA December 2009 PATH is an international nonprofit organization that creates sustainable, culturally relevant solutions, enabling communities worldwide to break longstanding cycles of poor health. By collaborating with diverse public- and private-sector partners, PATH helps provide appropriate health technologies and vital strategies that change the way people think and act. PATH s work improves global health and well-being.

19 PAT H S J A PA N E S E E N C E P H A L I T I S P R O J E C T: A C C O M P L I S H M E N T S A N D L E S S O N S L E A R N E D C O S T E F F E C T I V E N E S S O F J A PA N E S E E N C E P H A L I T I S VACC I N AT I O N Japanese encephalitis (JE), a mosquito borne viral brain infection, afflicts an estimated 35,000 to 50,000 inhabitants of Asia and the western Pacific annually. 1 The disease most often strikes children, who have not yet built up a natural immunity. One third of JE infections are fatal, and another third leave survivors with severe neurological sequelae. There is no treatment for JE; vaccination is the only defense. Funded by the Bill & Melinda Gates Foundation, PATH s JE project ( ) worked with international partners and developing countries to increase the information available for understanding the extent of the disease and how best to control it. Background Immunization is one of the most cost effective health interventions: most childhood vaccines are inexpensive and so effective that vaccination can be cost saving to health systems. However, in countries with limited resources and competing public health priorities, it is important to determine whether new vaccine introduction is an appropriate financial investment. Economic evaluations, including cost effectiveness analyses, can help in decision making by comparing resource costs to public health outcomes when choosing one health intervention over another. Cost effectiveness analysis Cost effectiveness analysis is often used to inform decisions about the use of health care resources, including those related to vaccines and immunization strategies. In simple terms, cost effectiveness analysis helps determine how much will be spent on an intervention to gain health improvement, such as saving one life or other measures of health outcomes, as compared with existing or other interventions. Epidemiology patterns and vaccine characteristics determine both the inputs (costs) and the outcomes (e.g., cases, deaths, sequelae, or disability adjusted life years averted) for a cost effectiveness analysis associated with any intervention. Outcomes of cost effectiveness analysis of new vaccines can vary according to the characteristics of the country health system as well as vaccine characteristics. Cost effectiveness analysis of JE vaccines Studies on cost effectiveness of JE vaccination were undertaken throughout the life of the JE project. In 2006, PATH and local investigators studied cost effectiveness of JE immunization in Andhra Pradesh, India, by (1) comparing implementation of a one time vaccination campaign with an intervention that combined campaign plus routine immunization, and (2) comparing use of either the inactivated, mouse brain derived JE vaccine or the SA JE vaccine. Results demonstrated that the World Health Organization (WHO) recommended combined JE vaccine introduction strategy (catch up campaigns plus routine immunization) using the live, attenuated SA JE vaccine was very cost effective. This same strategy using the inactivated, mouse brain derived JE vaccine was considered not cost effective. Given limited resources, immunization strategies targeting high risk areas also were found to be more cost effective. 2 (It is important to note that this article was completed prior to the availability of SA vaccine with a public sector price. Introducing the lower public sector price will further improve its cost effectiveness.) In 2007, the National Institute of Health Research and Development of the Indonesia Ministry of Health, the Directorate General of Communicable Disease Control and Environmental Health, and PATH linked an assessment of the economic burden of JE with a study on hospital based surveillance in six Indonesian provinces, collecting data on hospital costs associated with JE infection and financial implications for families. Similarly, PATH and investigators from the China Center for Disease Control gathered information on costs associated with JE illness in Shaanxi Province in order to perform an economic evaluation of the JE vaccination program and identify strategies to improve JE immunization. Additionally, the Communicable Disease Department of Cambodia launched a study to analyze cost effectiveness of JE vaccine in 2007, collaborating with the National Immunization Program, National Institute of Public Health, PATH, and WHO. Five hospital sentinel sites collected data on treatment costs associated with JE cases identified through the meningo encephalitis syndromic surveillance system. Results helped guide decision making and inform immunization policy. 3 Future directions Studies have demonstrated that JE imposes a significant economic burden on households and JE vaccination is considered a cost effective intervention for endemic populations. The public-sector price set by the manufacturer of the SA JE vaccine also increases affordability and access for countries that must allocate limited public health resources. As countries continue to introduce vaccine, data on immunization program impact also will be important in refining cost effectiveness analyses and planning future immunization strategies.