Vol. 4, May 2006

JE Newsbriefs
A periodic update on Japanese encephalitis (JE) disease, JE vaccines, and PATH's JE Project

• Government of India approves licensure of SA 14-14-2 vaccine, initiates vaccine introduction
• Public-sector pricing established for live, attenuated JE vaccine
• Strategic Advisory Group of Experts addresses JE control through immunization
• WHO publishes JE surveillance standards
• JE Project activities begin in Vietnam
• Overview of JE Project-supported studies
  
• Vaccine Spotlight: Acambis’ ChimeriVax-JE
• Partner Profile: CDC
• Who’s who at the JE Project: Vanda Moniaga
• JE resources

We are pleased to bring you the latest news on advances toward the introduction of JE vaccines for some of the world’s most vulnerable populations. Exciting progress was made earlier this month, as JE vaccination began in Uttar Pradesh, the Indian state hardest hit by last year’s outbreak. Introduction in high-risk districts of four additional Indian states will continue through July, marking a significant milestone toward immunizing the largest at-risk population in the world. These monumental steps demonstrate the efforts and dedication of so many of our partners in the field, as well as the commitment of forward-thinking national bodies such as the Government of India.

This year’s introduction in India and the impending start of the outbreak season will doubtlessly bring greater attention to this often neglected disease and the families it so tragically impacts. Adding to increased awareness among the general public, new and upcoming advances are emphasizing JE control among global and national public health communities. Last month, the World Health Organization’s (WHO) Strategic Advisory Group of Experts addressed JE control through vaccination, and their follow-up recommendations will provide essential insight for our international partners working with endemic countries.

We are encouraged by this forward momentum and look forward to seeing the impact that it will have on controlling JE disease in the most vulnerable communities.

Government of India approves licensure of SA 14-14-2 vaccine, initiates vaccine introduction

The Government of India recently approved licensure of the live, attenuated SA 14-14-2 JE vaccine manufactured by the Chengdu Institute of Biological Products for introduction in high-risk districts beginning this month. The licensure was finalized and the vaccine approved for registration and marketing in India in February 2006, and the SA 14-14-2 vaccine will be provided to nearly 12 million children in 11 endemic districts this year.

Health facilities in districts of Uttar Pradesh, the state hardest hit by last year’s outbreak, initiated introduction of the vaccine on May 15, and other high-risk districts will hold JE vaccination campaigns with the SA 14-14-2 vaccine through July. India’s introduction strategy includes a one-time campaign targeting all children between the ages of 1 to 15 years, followed by incorporation of the vaccine into routine immunization in the targeted districts. The government plans to scale up immunization with this vaccine to 104 of the country’s highest-risk districts over the next five years.

The SA 14-14-2 vaccine is very safe and highly efficacious, and it has been given to more than 200 million children since its introduction in China nearly 20 years ago. The vaccine also is licensed in Nepal, South Korea, and Sri Lanka.

Public-sector pricing established for live, attenuated JE vaccine

A key element to protecting infants, children, and adolescents from JE infection in developing countries is the affordability of a vaccine, which directly impacts a government’s ability to provide it to vulnerable, at-risk populations. Following negotiations conducted through PATH, a maximum public sector price for the SA 14-14-2 vaccine has been approved and allows for this year’s vaccine import and introduction in India, Nepal, and Sri Lanka. This public sector pricing is a commitment to provide vaccine for the lower-income endemic countries in Asia (GNP
< US$1,000) for the next 20 years. Representatives from PATH traveled to the Chengdu Institute earlier this year to formalize this important agreement.

The maximum public sector pricing agreement was formalized by representatives from PATH and the Chengdu Institute of Biological Products.

Strategic Advisory Group of Experts addresses JE control through immunization

The April 2006 meeting of the WHO’s Strategic Advisory Group of Experts (SAGE) included a discussion on the control of JE through immunization, in response to a call from WHO offices in the Southeast Asia and Western Pacific regions. Regional representatives presented data to provide a snapshot of disease burden, as well as to prompt discussion on the potential impact of JE vaccine introduction.

Discussions at the meeting addressed surveillance activities in rural areas and the continued use of WHO standards for surveillance. With regards to vaccine introduction, SAGE recommended that countries planning to introduce vaccine should assure licensure and monitoring against international standards, continue monitoring acute encephalitis syndrome, and document impact and safety issues. The group supported immunization as the most appropriate method for JE control and further noted the safety and efficacy of the SA 14-14-2 vaccine, as initially acknowledged by the WHO’s Global Advisory Committee on Vaccine Safety. SAGE applauded the JE Project for its work to continue development of the product’s profile and to address safety issues in preparation of the vaccine’s file for WHO pre-qualification. SAGE also recognized the project’s work on establishing a public sector price for the vaccine. Finally, the group encouraged continued efforts to strengthen the evidence base for JE control through immunization, along with activities to ensure sustainable vaccine financing. WHO’s position paper on JE will be updated to reflect progress in vaccine development and introduction activities. Further details on the April 2006 SAGE meeting, including recommendations regarding JE are available in the May 26 issue of Weekly Epidemiological Record.

Standards for country surveillance of JE were released by WHO earlier this year. This important resource provides guidelines on case definitions, laboratory criteria, region-specific types of surveillance, and data analysis. The JE surveillance standards were added to the existing WHO-recommended standards for surveillance of selected vaccine-preventable diseases, and the complete document may be accessed online at http://www.who.int/vaccines-documents/ DocsPDF06/843.pdf.

JE Project activities begin in Vietnam

PATH recently initiated activities in Vietnam that will build on established JE control efforts conducted by the national Expanded Programme on Immunization (EPI). A Vietnamese-produced, inactivated, mouse-brain derived JE vaccine was introduced in high-risk districts in 1997, and the program continues to expand with the aim of nationwide coverage by 2010. PATH will provide technical assistance to the national EPI program for enhanced JE surveillance, which will be piloted in two provinces, one each in north and south Vietnam. The pilot activities will incorporate the collection of epidemiologic data to be linked with data from laboratories and will also strengthen laboratory networks, in order to enable better understanding of disease burden and planning for JE control in the country. Upon evaluation, the pilot activities will be considered for expansion. In addition to surveillance support, PATH will also provide technical assistance as Vietnamese public health officials consider future vaccine options.

Vaccine spotlight: Acambis’ ChimeriVax-JE

The JE Project is a collaborator on several clinical studies to gather essential data on the burden of JE disease and the safety and efficacy of JE vaccines, as well as to document vaccine introduction in various countries. Here is a quick overview:

• Studies conducted by the Indian Council of Medical Research are scheduled for initiation this year and will generate surveillance data on the virus among mosquitos; determine pre- and post-vaccination JE antibodies among Indian children who are immunized; and evaluate the immunologic response to vaccine in undernourished children. Additionally, India's National Vector-borne Disease Control Program will initiate intensified acute encephalitis syndrome surveillance country-wide, with additional focus in the 11 high-risk districts set to begin vaccine introduction this year.

• Vaccine manufacturer Chengdu Institute of Biological Products will partner with the Drug Controller General of India to conduct one-year post-marketing surveillance following this year’s introduction in high-risk districts.

• A study in the Philippines is evaluating the co-administration of JE and measles vaccines. Recruitment was completed in March 2006, and results are expected in the coming months.

Partner profile: CDC

Determining the risk and burden of JE for travelers to endemic areas is a priority for the US Centers for Disease Control and Prevention (CDC), and activities to this end lend important insight to PATH’s JE surveillance and diagnostic efforts. PATH and the CDC’s Division of Global Migration and Quarantine work together to monitor regional outbreaks, and the information gathered not only informs surveillance data for PATH's JE Project, but also provides essential updates to CDC-generated travel advisories. The partners also team up to standardize diagnostic and laboratory guidelines to ensure appropriate and accurate JE diagnosis and clinical care, which not only benefit travelers to high-risk countries but also enhance the level of diagnostics and care for at-risk populations who live in the region. Additionally, CDC provides technical input toward the development of JE resources, including surveillance guidelines developed by both PATH and WHO, as well as clinical tools.

Who's who at the JE Project: Vanda Moniaga

Vanda Moniaga left the lab for the field upon joining PATH in 1995. With a bachelor’s degree in microbiology and a master’s in genetics, she was working in diagnostic development for a pharmaceutical company when the simple but effective technology of PATH’s HIV diagnostic dipstick sparked her interest. Moving to public health, she thought, would provide an opportunity to achieve a broad impact and help people on a large scale while applying her skills in diagnostics to a variety of different projects.

Currently serving as technical officer for PATH's Indonesia office, Vanda has contributed to a number of projects aimed at reviewing and improving diagnostics in resource-limited settings. Her first post built upon that initial interest in HIV diagnostics. With PATH’s AIDS Initiative, Vanda was a member of the team studying HIV prevalence in Indonesia and working with partners to train health care workers on diagnostics for sexually-transmitted diseases. Her foray into immunization projects began with activities led by Dr. Anton Widjaya aimed at scaling up hepatitis B birth dose, as well as performing cold chain assessment and applying innovative interventions to reduce vaccine freezing and improve the overall quality of the cold chain. The comprehensive approaches piloted by PATH's immunization team in Indonesia resulted in a dramatic reduction of vaccine freezing and improvement in the quality of the immunization program nationwide.

JE resources