In this issue:


Vol. 12, December 2009



Greetings partners,


Welcome to the final issue of JE Newsbriefs. It has been our sincere pleasure to bring you the latest news and events related to JE control over the past six years. We have been honored to highlight the unprecedented advances made possible by the commitment of national governments and the dedication of so many partners all working toward the common goal of protecting vulnerable populations from death and disability caused by JE. In addition to our organizational partners, I would like to extend a special thanks to Dr. Julie Jacobson, JE project founder and long-time director. The JE project’s achievements have been made possible by Julie’s vision and commitment, together with the financial support of the Bill & Melinda Gates Foundation. Furthermore, I would like to extend my sincere gratitude to the PATH staff spanning the globe who have served the JE project over the years, and to thank them for their ceaseless dedication and countless contributions.


Our collaborations throughout the JE project have been truly rewarding, not only in terms of the progress made in endemic countries, but also with regard to valuable lessons learned. PATH will carry this insight forward in future projects aimed at improving immunization services and accelerating access to lifesaving vaccines.


JE-endemic countries continue to achieve historic milestones, but the work is not complete. Moving forward, partners and stakeholders must continue to sustain progress and mobilize resources. It has truly been a memorable journey thus far and we look forward to seeing what lies ahead for the future of JE control through immunization.



Dr. John R. Wecker
Director, PATH’s JE project


Cambodia introduces JE vaccine through routine immunization


In October 2009, Cambodia began the small-scale introduction of JE vaccine through the public sector as part of routine immunization services in Kampong Cham, Svey Rieng, and Takeo provinces. The initial immunization program will ultimately target more than 100,000 9-month-old infants through 2010 and will be expanded nationwide to protect more than 400,000 children each year thereafter.


This exciting development is the result of the commitment since 2006 of the Cambodian Ministry of Health’s Communicable Disease Control Department, National Immunization Program, and National Institute of Public Health, in collaboration with the World Health Organization (WHO) and PATH, to establish a surveillance system for JE and meningo-encephalitis in Cambodia. The surveillance system has substantiated data on the disease burden of JE and established that it is an important, preventable public health problem in Cambodia.


Cambodia’s decision to introduce JE vaccine was informed by in-country, evidence-based knowledge of disease burden and cost-effectiveness. In addition, the Ministry of Health contributed awareness of the need not only for increased public understanding of meningo-encephalitis, but also for an established surveillance system and laboratory diagnosis and improved clinical management of JE cases.


Nepali delegation observes India campaigns


In an excellent example of cross-country cooperation and learning, a Nepali delegation observed the JE immunization campaign in Goa, India from June 28 to July 4. 2009. The team was headed by Dr. Shyam Upreti, Director of the Child Health Division of the Nepal Ministry of Health & Population, and their visit was arranged by PATH’s Dr. Pritu Dhalaria with the cooperation of the local government in Goa.


According to Dr. Upreti, the Goa visit was “very useful to help us strengthen our program in Nepal.” In a letter of thanks to Dr. Dhalaria, he noted that the Nepali team was especially impressed with the strong support for adverse events following immunization (AEFIs). Dr. Upreti reported that “Every booth I visited I found equipped with all necessary AEFI drugs and in every vaccination booth there was a medical officer for screening of children to manage AEFIs.”


Nepal’s own experiences with JE immunization in campaigns in 2007 and 2008 allowed the delegation to offer suggestions to improve immunization coverage in Goa. The team suggested focusing on educational outreach with pediatricians and the media to enhance awareness of the threat of JE and to bring accurate scientific information to the public. Dr. Upreti complimented the quality of Goa’s health care workers and their commitment to provide high-quality services to the people.

Biregional meeting on JE control looks at progress and next steps


The Fourth Biregional Meeting on Control of Japanese Encephalitis, organized by WHO and PATH, was held on June 8 and 9, 2009, in Bangkok, Thailand. This year’s meeting marked the conclusion of the current phase in JE control efforts with PATH’s JE project closeout in October of this year, and the continuation of planning for future activities to continue momentum.


Approximately 70 participants attended, including immunization officials from 11 JE-endemic countries and technical officers from WHO headquarters and regional offices; UNICEF, industry, nongovernmental organizations, research and academic institutions, and the Bill & Melinda Gates Foundation also were represented.


Objectives of the meeting were to review progress in endemic countries toward JE control through immunization; to provide updates and identify challenges of JE surveillance, laboratory diagnostics, and immunization strategies; and to summarize ongoing development of a plan for JE control by 2015, with an emphasis on the partnerships necessary to maintain progress.


Minutes of the 2009 biregional meeting will be published by the WHO Western Pacific Regional Office.


ACIP announces provisional recommendations for JE vaccine use


The United States Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) addressed the changing landscape of JE control in July 2009 when it provisionally updated its recommendations for the use of JE vaccine in travelers.


JE vaccine is recommended for travelers who plan to spend a month or longer in endemic areas during the JE virus transmission season. Clinicians are asked to consider vaccinating even short-term travelers who visit endemic areas during the transmission season if they will have an increased risk of exposure to JE virus, such as spending “substantial time outdoors in rural or agricultural areas, especially during the evening or night.”


Since the previous guidelines for JE vaccination were adopted in 1993, new vaccines have been in development while supplies of JE-VAX® have dwindled. ACIP’s recommendations encompass both US-licensed JE vaccines. With the US Food and Drug Administration’s 2009 approval of the Ixiaro vaccine (manufactured by Intercell Biomedical and distributed in the US by Novartis) for adults 17 years of age or older, remaining stockpiles of JE-VAX® have been restricted to children between the ages of 1 and 16 years.


ACIP’s final recommendations are expected to be published by the end of the year in Morbidity & Mortality Weekly Report.


Sanofi Pasteur files for approval in Australia and Thailand


Sanofi Pasteur has filed applications with Australia’s Therapeutic Goods Administration and the Thailand Food and Drug Administration (TFDA) to request marketing authorization for IMOJEV, its single-dose JE vaccine targeted to both children and adults in JE-endemic countries.


TFDA has agreed to a fast-track review of IMOJEV, bolstered by the country’s experience in the vaccine’s clinical trials, which were also conducted in Australia, the Philippines, and the US. In studies of adults and children, a single dose of IMOJEV was as immunogenic as the three-dose regimen of the inactivated, mouse brain–derived JE-VAX®, and was well tolerated.


JE vaccination expands in Sri Lanka


The Epidemiology Unit of Sri Lanka’s Ministry of Healthcare and Nutrition announced the introduction of the live, attenuated SA-14-14-2 JE vaccine into its national immunization program starting July 1, 2009. Previously, Sri Lanka used inactivated, mouse brain–derived vaccine for a geographically targeted routine JE immunization program.


The disease has been contained in endemic areas due to high immunization coverage. However, sporadic JE outbreaks have occurred in previously unaffected areas without immunization, underlining the need for national expansion of the program.  The annual cost of JE vaccination with inactivated, mouse brain–derived vaccine comprised three quarters of the national vaccine budget, and the projected cost of expanding routine JE vaccination threatened the sustainability of the entire program. The AEFI surveillance system also has recorded a growing trend of AEFIs with the inactivated vaccine. Given all these factors, a safe, immunogenic, and cheaper alternative to the inactivated vaccine was required.


The Epidemiology Unit’s suggestion to shift to SA 14-14-2 vaccine was approved by the Advisory Committee on Communicable Diseases after review of the recommendations of the WHO Strategic Advisory Group of Experts; scientific literature; safety and cost-effectiveness data; and the experiences of China, India, and Nepal. Results of local safety and immunogenicity studies of the vaccine were the final deciding factor.


The significant cost-savings from the switch to SA 14-14-2 vaccine will not only allow sustainability of the JE immunization program already in place, but also expansion of the program to vulnerable adults in high-risk areas.


PATHs JE project closes, JE control continues


After six years of helping JE-endemic countries better understand and reduce the toll of JE on their children, families, and communities, PATH’s JE project came to an official close on October 31, 2009. From its inception in 2004, the project conducted activities that contributed to its vision of eliminating clinical JE in endemic countries by improving disease surveillance and diagnostic testing, accelerating the availability of JE vaccine, assisting with vaccine introduction, and increasing global and national awareness and support of JE-endemic countries.


PATH will continue to support access to an efficacious, safe, and affordable vaccine through assistance to the Chengdu Institute of Biological Products for the preparation and submission of the SA 14-14-2 vaccine dossier for WHO prequalification, furthering the project’s long-term goal of securing affordability and vaccine financing for endemic countries.


After PATH’s exit, the JE Control Working Group will continue its long-term guidance for JE control in the Southeast Asia and Western Pacific regions. Slated to be hosted by the WHO, the JE Control Working Group will help maintain the momentum of JE control into the future.


Final reports are under way to document the compelling work of the JE project. The success of PATH’s JE project reflects the success of its many partner countries and organizations in identifying needs, developing capacity, and acting to bring lifesaving interventions to at-risk children in JE-endemic areas.


Recent publications address history and future of JE


Recent articles present a wide range of topics from country research on JE in Cambodia and Indonesia to a new JE vaccine and how partnerships can address global immunization needs. For nonsubscribers in developing countries, the articles may be freely accessed through the WHO’s Health InterNetwork Access to Research Initiative (HINARI).


Gilden, D. Faster, better, cheaper: new vaccine promises to control Japanese encephalitis. In Case Studies for Global Health: Building relationships. Sharing knowledge. Alliance for Case Studies in Global Health: Deerfield, IL; 2009.

This case study provides a helpful overview of the multifaceted partnership between the JE project and the Chengdu Institute of Biological Products to provide an affordable and effective JE vaccine.


Buhl MR, Lindquist L. Japanese encephalitis in travelers: review of cases and seasonal risk. Journal of Travel Medicine. 2009;16(3):217–219.

Authors review cases of JE among travelers and expatriates visiting Southeast Asia for varying lengths of time. They conclude that the duration of stay is not a good predictor of JE transmission, and that in light of new cell culture–derived vaccines, JE vaccination recommendations for travelers should be revised.


Dhillon GP, Raina VK. Epidemiology of Japanese encephalitis in context with Indian Scenario. Journal of the Indian Medical Association. 2008;106(10):660–663.

This article provides a historical overview JE in India since the first detection of JE virus activity in 1952 to the 2006 introduction of JE vaccine in high-risk states and expansion of vaccination efforts in 2007 and 2008.


Kollaritsch H, Paulke-Korinek M, Dubischar-Kastner K. IC51 Japanese encephalitis vaccine. Expert Opinion on Biological Therapy. 2009;9(7):921–931.

This article describes Intercell’s new JE vaccine, Ixiaro™, which was approved this year in Australia, the European Union, and the United States. Recently published Phase 3 immunogenicity and tolerability studies are addressed and authors discuss the benefits of next-generation, cell-culture–based vaccines.


Touch S, Hills S, Sokhal B, Samnang C, Sovann L, Khieu V, et al. Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance. Tropical Medicine and International Health. 2009;14(11):1365–1373. Epub 2009 Sep 11.

A report on two years of JE surveillance integrated in to routine meningo-encephalitis surveillance in six sentinel hospitals, this study demonstrates that JE is an important cause of meningo-encephalitis in Cambodian children and suggests immunization would reduce JE morbidity and mortality.


Partner Profile: Walter Reed/AFRIMS Research Unit Nepal


The Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok and its field unit in Kathmandu, the Walter Reed/AFRIMS Research Unit Nepal (WARUN), have partnered with PATH’s JE project from its inception to conduct research on diagnostics assays for JE.


A validation study in 2005 evaluated the performance of three commercially available diagnostic kits for JE against AFRIMS’ own JE IgM antibody-capture, enzyme-linked immunosorbent assay. Results from this study have informed the use of these kits by WHO and JE-endemic countries. In 2007, WARUN assisted Nepal’s National Public Health Laboratory (NPHL) with a JE diagnostic kit evaluation study to determine the positive predictive value of two of the commercial kits.  WARUN and AFRIMS were instrumental in data and sample management, quality control, specimen maintenance, and overall technical support to NPHL.


In addition to their research contributions, AFRIMS senior virologists also serve on the WHO JE Laboratory Working Group of experts, providing advice on lab and diagnostic issues, kit recommendations, and technical assistance and training to WHO and JE-endemic countries undertaking laboratory-based surveillance of JE. The technical expertise of AFRIMS and WARUN has helped bring more accurate laboratory confirmation of JE cases to endemic countries, giving their governments clearer understanding of disease burden.


Who’s who in the JE project: John (Chris) Victor


Chris Victor knows clinical trials—his first vaccine trial was as a doctoral student leading a 4,500-person study in Kazakhstan. “I got on a plane with a suitcase and a protocol and had to go make it happen.” As Clinical Trials Advisor to the JE project since 2006, Chris has brought his experience and special insights to JE vaccine trials. “Leading a trial as an on-the-ground investigator teaches you a lot.” Chris also splits his time with other PATH projects, including directing a cluster-randomized influenza vaccine effectiveness study in Senegal and working on the Rotavirus Vaccine Program’s developing-world trials in Africa and Asia.


Chris entered epidemiology and vaccinology in 1995 for the science. Given the frequently long timelines of clinical research, he says “one of the challenges inherent to the work is that the science often progresses during the time between designing of a trial and when results are obtained.” Reconciling trial results with the current state of knowledge can be complex, but this problem is also what makes the work interesting. “You are always trying to generate the best data you can to move the science and decision-making forward; it’s often not that straightforward, but it’s almost always fun!”


Chris realized early that he would need to go where the burden of disease is greatest to have impact; he really values being able to play a part in helping developing countries generate their own data for local decision-making. Chris has always been impressed with the exceptional potential of developing-country researchers. The capacity for high quality is there, he says, “it only takes some training and a little supervision.” His overarching goal is to “support the local investigator in taking ownership and leadership of the study.” One of the greatest rewards of his work is seeing local field researchers strengthening their expertise in conducting clinical research and independently leading studies.


JE resources

JE project web page


JE on PATH’s Vaccine Resource Library

Japanese encephalitis online training module (AIM series)

WHO position paper on JE


Masthead photo:Richard Lord