In this issue:   

 

 

Vol. 10, January 2009

 

 

Greetings partners,

 

We are pleased to bring you the latest news on global efforts to control JE. Highlights from the past few months include continued development of JE vaccine candidates, as well as significant additions to scientific literature regarding JE disease burden as revealed through routine surveillance. Adding to this growing collection are updated surveillance standards for acute encephalitis syndrome. Published by the World Health Organization (WHO) and supplemented by feedback collected from field use, these guidelines will be important as efforts to determine the global toll of JE continue to expand.

 

The past few years have seen tremendous growth in global awareness of JE, and the key to this success has been the spirit of partnership. One primary partner, the Chengdu Institute of Biological Products, manufacturer of the SA 14-14-2 JE vaccine, marked its 50th­ anniversary last month, and I was honored to be on hand for the commemoration. During a tour of the institute’s campus, we came across a rock with an inscription from Dr. Chen Zhu, Minister of Health, People’s Republic of China. It read “Human Health, Our Undertaking.”

 

This mission of the Chengdu Institute is one that is shared among all who are working to eliminate clinical JE. Together, we have seen many accomplishments, and as we look ahead to carry this important work forward, the collaboration of committed partners will be essential to continued impact.

 

 

Sincerely,

Dr. John R. Wecker
Director, PATH’s JE Project
jeproject@path.org

 

JE Control by 2015 details sustainable priorities for the future

 

In anticipation of the close of the JE project in 2009, PATH has begun preliminary discussions with a wide array of partners toward development of a global control plan. Initiated in collaboration with WHO staff members in Geneva, the Western Pacific Region (WPR), and the Southeast Asia Region, partners working to develop the plan have grown to include representatives from the US Centers for Disease Control and Prevention (CDC); the Armed Forces Research Institute for Medical Sciences, Bangkok; the International Pediatric Association, vaccine manufacturers, and universities. Still more organizations continue to join.

 

The document, JE Control by 2015, will provide details on priority activities that must be sustained beyond PATH’S JE project, including improved understanding of disease burden, technical assistance for vaccine introduction, procurement support, and advocacy to keep JE on national, regional, and international agendas. A recently published letter in The Lancet Infectious Diseases summarizes the plan. A proposed JE coalition secretariat would promote the objective of JE control within seven to ten years; communicate progress and challenges; facilitate collaboration and communication among coalition members; maintain and monitor progress of the control plan; and raise funds for secretariat staff.

 

The next step is to bring the partners together to agree on the proposed coalition’s structure and function. The JE control plan is scheduled for ratification at the next JE Core Working Group meeting in late spring 2009.

 

CDIBP JE vaccine facility nears mechanical completion

 

Construction of the new manufacturing facility at the Chengdu Institute of Biological Products (CDIBP) continues to progress, with partners making extra effort to overcome delays caused by the devastating earthquake that struck Sichuan Province in May 2008. Despite this significant challenge, CDIBP is taking the necessary steps to ensure manufacturing processes for the SA 14-14-2 vaccine produced in the new facility will meet international standards.

 

To date, all employees have received training to develop the Quality Management System, a Validation Master Plan, and Good Manufacturing Practices. Additional training in 2009 will implement these standards in all departments. In partnership with engineering firm Technip, installation of equipment is under way, and mechanical completion of the new facility is expected in the first quarter of 2009. The critical next step—commissioning and equipment qualification—will start in February 2009.

 

GAVI Alliance commits to seek funding for JE vaccine introduction support

 

Upon its evaluation of country demand, resource availability, and vaccine availability, the GAVI Alliance board committed to seek funding to expand its portfolio of support to include additional vaccines against JE, cervical cancer, typhoid, and rubella. Following its October board meeting, GAVI announced that US$ 3 billion would be required to continue existing programs and expand its portfolio of offerings through 2015. This significant investment will speak to the global need for safe and affordable vaccines, illustrated by considerable uptake among countries already benefiting from GAVI vaccine introduction support and by growing demand for new vaccines.

 

IC51 vaccine nears US licensure for adult travelers 

 

At the October meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP), Dr. Marc Fischer of the JE Core Working Group presented an update regarding the status of JE vaccine for U.S. travelers. Currently, ACIP only recommends JE vaccine for travelers to Asia who will spend more than one month in endemic areas during transmission season, or those at high risk of exposure due to their activities or destination.

 

Production of JE-VAX®—an inactivated mouse brain-derived vaccine that is the only JE vaccine available in the US—has ceased. At the current rate of use, the supply of JE-VAX® will only last through the first quarter of 2009. On the horizon is an inactivated Vero cell–derived vaccine (IC51) manufactured by Intercell of Vienna, Austria—trade named Ixiaro®. In December 2007, Intercell submitted a Biologics License Application with the U.S. Food and Drug Administration for use of IC51 in adults with a two-dose primary series. In prelicensure clinical trials, IC51 demonstrated a good immunogenicity and reactogenicity profile. Because the vaccine is derived from cell culture and contains no gelatin or murine proteins, IC51 may be expected to result in fewer serious adverse events than JE-VAX®.  However, Fischer noted post-licensure studies and surveillance data will be important to further evaluate safety.

 

IC51 is expected to be approved for use in adults by early 2009. However, until data are available for review on IC51's use in children, JE-VAX® will remain the only vaccine licensed for children for another two to three years. Sanofi, the US distributor of JE-VAX®, plans to stockpile the vaccine for use in children until 2010 to extend the supply.

 

SA 14-14-2 JE vaccine developer honored

 

Professor Yu Yongxin, Director Emeritus of China’s National Institute for the Control of Biological and Pharmaceutical Products, has been honored as one of two winners of this year’s Prince Mahidol Award in public health for his work in developing the SA 14-14-2 JE vaccine.

 

The award, given by the Prince Mahidol Foundation for outstanding and exemplary contributions to the advancement of the world’s medical and public health services, honors Professor Yu’s nearly three decades of research to derive the SA 14-14-2 JE vaccine.

 

Since its development in 1988, the SA 14-14-2 vaccine has been given to more than 200 million children in China, and millions more across India, Nepal, South Korea, and other Asian countries. PATH salutes Professor Yu’s contribution to the health of the nearly 50 million additional children reached during the five-year history of PATH’s JE project.

 

WHO SAGE recommends increased JE immunization

 

The November 2008 meeting of the WHO Strategic Advisory Group of Experts (SAGE) on immunization featured discussion of a variety of issues surrounding vaccine-preventable diseases. A report from the WHO Western Pacific Region (WPR) focused on control of JE. The disease remains a significant source of death and disability in the region, with as many as 20,000–40,000 cases occurring annually. As many as half of those afflicted have long-term disabilities.

 

Vaccination has proven an effective control strategy, especially where it has been integrated into the routine immunization program. Eleven WPR countries are at various stages in JE control, some simply needing expansion of existing vaccination programs while others have yet to document disease burden.

 

SAGE supported immunization for JE control, and recognized JE vaccine as an underutilized vaccine. Additionally, the group encouraged better assessment of disease burden and the identification of appropriate target populations to receive vaccination. Finally, SAGE encouraged China’s national drug regulatory authority and CDIBP to continue to work toward SA 14-14-2 prequalification.

 

Read about CDIBP’s ongoing progress toward that goal above.

WHO publishes updated acute encephalitis syndrome surveillance standards

 

WHO has published its updated surveillance standards for acute encephalitis syndrome (AES). The field test version of the standards was first published in January 2006. Over the following two years, feedback was gathered from individuals as well as from countries who had applied the standards within their internal surveillance systems. The University of Liverpool also assessed the accuracy of the case definition by applying it to a patient data set. Following WHO's review of all feedback received, the final version of the surveillance standards was published in October 2008. Click here to read the surveillance standards for JE.

 

Improved access to JE resources in PATH’s Vaccine Resource Library

 

PATH’s online JE resources were recently enhanced with the redesign of the Vaccine Resource Library (VRL). Continuing to offer high-quality, scientifically accurate documents and links, the newly designed VRL is easier to navigate, with a web-based database that provides several ways to access content. The VRL is geared for health professionals in the developing and industrialized worlds, as well as journalists, policymakers, community leaders, parents, and anyone else interested in vaccine-related resources. JE resources available include a wide variety of materials covering broad topics such as JE vaccines at a glance, as well as focused training like teaching presentations for health workers on the Liverpool Outcome Score.

 

Recent publications offer new insights into JE

 

A number of notable articles recently appeared in peer review publications, presenting research on JE in Japan, Indonesia, Malaysia, and Nepal. For nonsubscribers in developing countries, the articles may be freely accessible through the WHO’s Health InterNetwork Access to Research Initiative (HINARI).

 

Japanese encephalitis: surveillance and elimination effort in Japan from 1982 to 2004
Arai S, Matsunaga Y, Takasaki T, Tanaka-Taya K, Taniguchi K, Okabe N, et al. Japanese Journal of Infectious Diseases. 2008; 61(5):333-338.

Researchers reviewed vaccination records, seasonal and geographic case distribution, prevalence of JE antibody, and other indicators to describe control efforts. They found that while vaccination has kept the number of cases extremely low, the risk of JE infection persists, and vaccination efforts should continue.

 

Confirmation of Japanese encephalitis as an endemic human disease through sentinel surveillance in Indonesia
Ompusunggu S, Hills S, Sembiring Maha M, Moniaga V, Susilarini N, Widjaya A, et al. American Journal of Tropical Medicine and Hygiene 2008;79(6):963-970.

Hospital-based sentinel surveillance of AES and JE in children 15 years of age and younger from 2005 to 2006 revealed confirmed JE cases with varying rates among all provinces. The researchers concluded that JE is endemic across Indonesia.

 

The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in central Sarawak, Malaysia, 1997-2005 (abstract)
Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, Lim L, et al. Clinical Infectious Diseases 2008; 47(4):458-468.

Researchers evaluated Malaysian children with confirmed JE over an 8.3-year period, assessing and grading outcomes with a functional outcome score and found that an assessment at hospital discharge did not predict the child’s long-term outcome.

 

Laboratory-based Japanese encephalitis surveillance in Nepal and the implications for a national immunization strategy (abstract)

Wierzba TF, Ghimire P, Malla S, Banerjee MK, Shrestha S, Khanal B, et al. American Journal of Tropical Medicine and Hygiene 2008; 78(6):1002-1006.

A total of 4,652 encephalitis patients were evaluated from the southern plains and western districts of Nepal. The researchers concluded that targeted immunization may have reduced JE cases by 84 percent, and deaths by 92 percent, nationally.

 

Partner profile: Indian Council for Medical Research

 

The Indian Council for Medical Research (ICMR) has been at the forefront of medical research sponsorship in India from its inception in 1911 as the Indian Research Fund Association. Since 1949, with a broadened scope and new name, ICMR has supported research to reduce India’s disease burden and promote the health of the country’s population.

 

The council played a pivotal role in the decision to introduce JE vaccine in India, as well as the subsequent approval process. ICMR’s partnership with PATH’S JE project began in October 2004 with the assembly of the India JE Working Group, formed with members from WHO, the United Nations Children’s Fund, ICMR, and PATH. ICMR helped raise awareness of JE through a better understanding of disease burden in the country and intensified AES surveillance to identify and map high-risk areas for targeted vaccination campaigns.

 

ICMR’s own Director General served as chairman of a committee that considered the scientific evidence for the introduction of JE vaccine in India, providing guidance on its use. The council took the lead in advising the Drug Controller General of India on the process for registering the SA 14-14-2 JE vaccine for marketing. ICMR’s recommendation eventually allowed the import of the vaccine.

 

Following the introduction, ICMR has continued to play a key role in monitoring and evaluation, including investigation of adverse events following immunization. Their efforts in support of the JE vaccine include a postmarketing surveillance study to collect safety and immunogenicity data, sponsorship of an adult viremia study, and partnership with PATH and WHO to conduct a case control study to demonstrate vaccine effectiveness.

 

In a complex and demanding public health environment, ICMR has exhibited consistent leadership that has improved the health and quality of life of India’s citizens. The council’s partnership with PATH has facilitated the introduction of life-saving protection against JE to more than 44 million Indian children to date. 

 

Who’s who at PATH’S JE project: Jean-Marie Préaud

 

A brief conversation with Jean-Marie Préaud is all it takes to hear the excitement and enthusiasm he brings to his work at PATH. Since joining the team in August 2004 as a senior technical officer for PATH’S JE project, Jean-Marie has focused on helping the Chengdu Institute of Biological Products implement improvements to its manufacturing processes and facilities— critical steps toward gaining what would be a first among Chinese vaccine manufacturers: WHO prequalification for the SA 14-14-2 JE vaccine.

 

Originally a student of food science and technology, Jean-Marie characterizes his entrance into the world of vaccines as accidental; it came through the technology of lyophilization. However, his career has featured numerous contributions to veterinary and human vaccine development and manufacturing, including the raw materials supply chain, scaling up of production processes, industrial production, design of new facilities, international regulatory standards, stability programs, and cold chain maintenance.

 

Jean-Marie speaks with pride about the eight technology transfers he has been associated with during his career, between diverse countries like France, Australia, Thailand, Vietnam, Spain, and Poland. His most recent transfer—from the US and the Netherlands to India—was with PATH’s Meningitis Vaccine Project. It is this rich, multinational environment that provides Jean-Marie the most satisfaction. The most important thing, he says, is “to help people work together and respect each other.”

 

Although he has a realistic appreciation of the challenges inherent in his work, Jean-Marie maintains an optimistic view of the opportunities emerging for the vaccine manufacturers with whom he works. Jean-Marie’s ability to bring people together from different cultures, languages, and backgrounds to solve complex technical issues makes him an invaluable member of PATH’s JE project team.

 

JE resources


JE project web page   
www.path.org/je

 

JE on PATH’s Vaccine Resource Library
www.path.org/vaccineresources/japanese-encephalitis.php   

Japanese encephalitis online training module (AIM series)
http://aim.path.org/en/vaccines/je/index.html

 
WHO position paper on JE

www.path.org/vaccineresources/files/WHO_JE_position_paper_2006.pdf

 

Masthead photo: Richard Lord