View inspirational photography from India's landmark campaign in this slideshow. Photo: PATH.
PATH’s work on Japanese encephalitis helps millions get access to a lifesaving vaccine
The historic announcement came on October 9, 2013: the World Health Organization (WHO) gave a critical stamp of approval for a vaccine against Japanese encephalitis (JE). In a decade of milestones for JE control—from locating the desperately needed vaccine to a massive immunization campaign in India—the approval, known as prequalification, marks a turning point. It means millions more children will be protected from a truly devastating disease.
The WHO decision allows United Nations procurement agencies to purchase the vaccine. It also opens the door for the vaccine’s inclusion in the GAVI Alliance portfolio, which provides vaccine financing for low-income countries where the burden of JE is especially high. Further, the prequalification represents China’s entrance into the global vaccine marketplace—which could fundamentally shift how vaccines are made, delivered, and priced for the developing world.
This is the story of how PATH and our many partners put JE vaccine on the fast track—redefining what is possible in global health and saving thousands of lives.
Prevention through vaccination
Nicknamed “brain fever,” JE begins like the flu, progresses to a brain infection, and ends by killing up to 30 percent of its victims and leaving thousands more with permanent brain injuries. The virus is hosted by wading birds like herons and egrets, which flock to rice paddy fields, and by the pigs commonly raised in rural areas. It’s transmitted to humans by mosquitoes, which breed by the tens of thousands in rice paddies.
There is no treatment for JE. The only viable solution is prevention through vaccination. But until PATH launched our work in JE in 2003, tens of thousands of children died or were disabled each year for lack of an accessible, affordable, and reliable vaccine.
“Neither alive nor dead”
Because JE mainly strikes poor rural communities in Southeast Asia and the Western Pacific and is virtually unheard of in the Western world, it has historically received little attention. Yet approximately four billion people live in areas at risk for JE, and up to 70,000 cases are reported annually. The WHO estimates that JE claims 10,000 to 15,000 lives a year, but because awareness of the disease is low and it’s difficult to diagnose, these figures may significantly underestimate its impact.
Even less understood is the lifelong toll that JE takes on its survivors. Up to half suffer permanent neurological damage, such as paralysis, recurrent seizures, or the inability to speak. It affects boys like Mahesh, who was once among the brightest in his school in India and now sits in the back of the classroom barely aware of his surroundings, and girls like Shekaramma, described by her grief-stricken mother as “neither alive nor dead.” “Questions about Japanese Encephalitis” has more information on the disease and its effects.
A growing awareness
In the early 2000s, PATH was strengthening immunization services in the state of Andhra Pradesh, India, when we began to suspect that JE was a bigger problem than previously realized. Health workers in Andhra Pradesh routinely voiced concerns about JE, and improved surveillance of disease outbreaks suggested a high incidence.
In 2003, we secured a grant from the Bill & Melinda Gates Foundation to tackle JE not just in one state in India, but across the entire Southeast Asia and Pacific Region. Our goal was to understand the disease, determine the health and economic burden it placed on countries, and prepare the way for a vaccine that would safely and affordably prevent it. A “Timeline of the Japanese Encephalitis Project” gives a succinct overview of our work.
We began by establishing reliable methods of diagnosing and tracking JE. We helped private-sector partners develop standard diagnostic tests, and we worked with WHO and governments to set up surveillance systems and a web-based platform for sharing data about JE incidence. These efforts allowed countries to understand the extent of JE, prioritize it, and focus prevention efforts on the regions and people most needing protection.
Hope from a hidden vaccine
Then, in 2005, a devastating outbreak of JE killed nearly 2,000 people in India and Nepal, mostly children. Media coverage focused international attention on JE, while governments strengthened their resolve to protect their young people.
With JE finally getting the attention it deserved, there was still the matter of how to control it. The consensus among global health experts was that controlling the virus was impractical—a vaccine was the only hope. However, affected countries didn’t have the resources to develop the needed vaccine, and wealthy countries didn’t have the incentive.
In truth, vaccines against the disease actually existed, and international travelers to Asia were routinely vaccinated against JE. But the commonly used vaccine had significant drawbacks—three doses were required and it was extremely time-consuming and expensive to produce. There simply wasn’t enough funding or vaccine for all the children who needed it.
In search of a solution, PATH surveyed the field for a better JE vaccine. We discovered that one JE-affected country had already developed an affordable vaccine—China. In fact, China had vaccinated more than 200 million children with its vaccine, known as SA 14-14-2. The vaccine, made from active but weakened virus, was safe, effective, and required only one dose. But it was virtually unknown outside the country—and might have stayed that way had PATH not infused innovative thinking into JE control and played a bridging role between partners around the world.
With the vaccine identified, PATH collaborated with international partners and ministries of health in Asia to accelerate its introduction. Because SA 14-14-2 had not been used widely outside of China, international officials called for specific clinical studies. PATH collaborated with the manufacturer, WHO, and ministries of health on pivotal clinical trials to add to a growing collection of data proving the vaccine was safe and effective.
We also supported clinical trials to confirm that the vaccine can be given at the same time infants get their measles shots, which would make it easier to fit into existing immunization programs. To help countries plan for the vaccine’s introduction, we modeled the cost-effectiveness of immunization strategies—either integrating JE vaccine into immunization programs or combining routine vaccination with mass campaigns to vaccinate at-risk children and adolescents.
The vaccine also needed to be affordable for use in low-income countries, so PATH negotiated with the vaccine manufacturer—Chengdu Institute of Biological Products (CDIBP )—to establish a special public-sector price.
India and beyond
In the hot summer sun of 2006, just a year after the deadly JE outbreak, millions of Indian children lined up outside village clinics, schools, and community centers for the lifesaving protection of the new vaccine. India and Nepal were the first countries outside of China to introduce the SA 14-14-2 vaccine through mass campaigns and routine immunization services. They were soon followed by Cambodia, Sri Lanka, and the Democratic People’s Republic of Korea (North Korea).
Over the next seven years, India’s unprecedented immunization campaigns reached more than 88 million children. Millions more in Southeast Asia—from Nepal to Cambodia to Sri Lanka—were also vaccinated. By 2013, the vaccine had been supplied to 11 countries outside China for one-time campaigns and routine use, and the vaccine had reached more than 200 million people. Throughout this period, PATH and our partners provided technical assistance to countries—from developing introduction strategies to implementing and evaluating immunization programs.
A leap forward
We were also helping the vaccine manufacturer, CDIBP, pursue WHO prequalification as the critical next step in expanding access. Both the vaccine and CDIBP underwent rigorous inspections to ensure they met international standards of quality, safety, and efficacy. PATH provided CDIBP with technical and financial support to meet these standards. We also assisted in the design and financing of a new manufacturing facility to ensure high-quality, adequate, stable, and affordable vaccine supply.
The JE vaccine is the first vaccine ever produced in China to receive WHO prequalification—a first that has the potential to shift China’s role in global health. The growing capacity of China’s biotechnology sector and its emergence as an important vaccine supplier could help to foster a more competitive vaccine manufacturing market.
PATH continues to be intimately involved with JE control, serving as a technical resource, advocating for use of the vaccine, and leading a multicountry project that builds on the best practices we developed to introduce and scale up JE vaccination in endemic countries.
The day when all children at risk of JE are protected by a safe, effective, and affordable vaccine is now within reach.