No longer neglected—the story (behind the story) of the Japanese encephalitis vaccine

April 24, 2019 by PATH

Dr. Nihal Abeysinghe and Dr. Kathleen Neuzil are pioneers of a nearly two-decade effort to prevent and control Japanese encephalitis (JE).

Myanmar Japanese encephalitis vaccination campaign 2017

A health care worker in Shan State, Myanmar prepares a Japanese encephalitis vaccine in 2017. The vaccine made it to Myanmar, and other countries in need, with help from a 15-year public-private partnership, innovation, and persistence.

They were both critical in understanding the impact of the disease and identifying and scaling up an effective and affordable JE vaccine. Dr. Abeysinghe, formerly with Ministry of Health Sri Lanka and WHO South East Asia Regional Office and now with the Institute for Research & Development in Health and Social Care in Battaramulla, Sri Lanka, was one of the earliest researchers to see and understand the impact of the deadly JE virus. Dr. Neuzil, formerly with PATH and now director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, played a crucial role in bringing a largely unknown vaccine out of China and making it available to millions of children throughout Asia.

For World Immunization Week, Dr. Abeysinghe and Dr. Neuzil sat down and reflected on their JE journeys. Here is an excerpt from their conversation.

Kathy_Nihal.jpg

Success of the JE immunization program relied on big thinking, innovation, and persistence. Kathy Neuzil (left) and Nihal Abeysinghe (right) were some of the first people outside of China to work on JE control and prevention.

Kathy Neuzil: Nihal, you’ve been working on JE, in some part, for the majority of your career. When did you first encounter the disease, and what made you recognize its significance?

Nihal Abeysinghe: I encountered JE for the first time in 1985. I was a public health medical officer in the North Central Province of Sri Lanka, when there was a major outbreak of JE, sometimes known as ‘brain fever’. I graduated from medical school in 1981 and was never taught about JE as a zoonotic disease, much less how to identify or prevent it. JE was truly a neglected disease. The outbreak waned before continuing to rise in remote rural areas, where hundreds of children suffered tragic consequences—JE kills or severely disables about two thirds of the people it infects. Then, the alarms really sounded in 1988, when a JE outbreak took the lives of 24 percent of its victims.

KN: Sri Lanka immediately focused on vaccines. Why? Were there vaccines available?

NA: There is no cure for JE. Once you have the virus, there’s virtually nothing that can be done. We had to focus on prevention.

In 1988, we received 100,000 doses of an inactivated JE vaccine from the Japanese government as a donation and began vaccinating children under the age of 10. However, the inactivated vaccine required multiple doses and was quite expensive for Sri Lanka, so we began looking for a more affordable, effective option to prevent JE. As it turns out, from the other side of the world, you and PATH, Kathy, would play a crucial role in helping Sri Lanka find the vaccine it needed.

KN: During this time, the biggest hurdles were the limited number of vaccine manufacturers and the cost and quality of those vaccines. In 2004, PATH identified a live attenuated vaccine known as CD-JEV produced by the Chengdu Institute of Biological Products (CDIBP) and used in China, but little known to the rest of the world. This vaccine was a game-changer. Was that evident in Sri Lanka?

NA: Yes. Since Sri Lanka introduced the vaccine in all 25 districts in 2009, we have seen tremendous public health impact. In fact, it is no longer a major public health concern here. Only seven children under 20 years old were diagnosed with JE disease in 2018.

“The alarms really sounded in 1988, when a JE outbreak took the lives of 24 percent of its victims.”
— Nihal Abeysinghe

NA: Kathy, more than a decade ago, China’s CD-JEV vaccine was primarily for domestic use. PATH played a crucial role expanding access to endemic countries across Asia. What did it take?

KN: The JE vaccine story shows how PATH brings its experience and unique capabilities to bear for a project that has a positive impact on health and well-being. And it wasn’t just PATH. The JE experience demonstrates the power of many partners across multiple sectors working together.

After PATH identified the CD-JEV vaccine, we needed to get it into the countries that needed it. However, there was no market for a JE vaccine—in part, because most of the outbreaks were in poor, rural regions of Southeast Asia. That meant we had to work with countries to create that market through political will. We had to ensure its introduction and scale up in JE-endemic countries. Additionally, China had never distributed a vaccine outside its borders before.

NA: What would you say was the biggest challenge in distributing CD-JEV at such a large scale?

KN: Even though we identified a potential vaccine, there was still a mountain to climb. Nearly a decade passed between the time the vaccine was identified and when it received the World Health Organization’s stamp of approval, or prequalification – the first ever Chinese-manufactured vaccine to do so. Getting to that point was a journey. We worked closely with CDIBP to design, finance, and build a new manufacturing facility; navigate complex licensing and approvals processes: and ensure the safety and efficacy of the vaccine.

“This is a story of what is possible in global health.”
— Kathy Neuzil

NA: Why is it so significant that the vaccine was from China?

KN: The WHO prequalification achievement was truly historic, because it signaled China’s emergence in the global vaccine marketplace and unlocked more affordable access to CD-JEV for Sri Lanka and other countries in the region. It also opened the door for future Chinese vaccines and other developing country manufacturers to become players in global public health.

With access to a safe, affordable vaccine, PATH provided vaccine introduction assistance to endemic countries including India, Nepal, Cambodia, Myanmar, Laos, Indonesia, and Sri Lanka. Now, more than 300 million children in ten countries are immunized against JE – largely driven by PATH and partners’ persistence and dedication to saving lives.

NA: It’s remarkable. In Sri Lanka, we have seen firsthand the financial and public health value of delivering CD-JEV. It provides a glimmer of what vaccines might accomplish against other diseases that affect health and quality-of-life in low-resource countries. Do you see other possibilities?

KN: Absolutely. This is a story of what is possible in global health. The approval, pricing, and introduction for CD-JEV offers a model for harnessing ingenuity in low- and middle-income countries. Scaling this model to other diseases that disproportionally afflict people living in poor and rural areas—like dengue, typhoid, cholera, and other tropical diseases—has the potential to improve global health equity.

Learn more about how PATH and partners tackled a neglected tropical disease and saved entire generations from Japanese encephalitis on PATH.org, and join the conversation using #VaccinesWork or by sharing this story.