Less Japanese Encephalitis Antibodies May Increase Dengue Severity: Findings from Nepal

Recent research conducted by scientists at Duke-NUS Medical School, in collaboration with researchers in Nepal, has revealed a significant link between declining immunity to the Japanese encephalitis virus (JEV) and heightened risk of severe dengue illness. The study suggests that as antibodies against JEV diminish over time, individuals may become more susceptible to severe manifestations of dengue, a mosquito-borne disease that is rapidly spreading across Asia.

Published in Science Translational Medicine, the study emphasizes how waning vaccine-induced immunity to one flavivirus can unexpectedly impact the body's response to another related virus. While Japanese encephalitis (JE) is a deadly disease affecting approximately a quarter of those with severe cases and can cause long-term disabilities, dengue remains the fastest-growing mosquito-borne disease worldwide, causing severe symptoms and fatalities, with cases surging in Nepal.

The research team examined over 500 patients in Nepal over five years, a country where both JEV and dengue are actively transmitted. They found that individuals vaccinated against JEV who experienced a decline in antibody levels were more likely to suffer from severe dengue symptoms, unlike those with sustained immunity. This phenomenon is partly explained by antibody-mediated enhancement—a process where partially effective antibodies from previous infections or vaccinations facilitate the entry of dengue virus into immune cells, leading to faster viral replication and greater inflammation.

To measure disease severity, researchers looked at levels of chymase, a blood marker associated with inflammation and worse outcomes. Elevated chymase levels were observed in patients with lower JEV antibody levels, correlating with increased signs of severe dengue, such as bleeding, abdominal pain, and fluid accumulation.

Expert insights from Dr. Sidharth Malhotra, lead author of the study, highlight the importance of maintaining robust JEV immunity through timely booster vaccinations. Strengthening JEV protection not only prevents Japanese encephalitis but may also reduce the risk of severe dengue complications. This is particularly crucial as climate change and urbanization expand mosquito habitats, increasing the risk of dengue outbreaks in new regions.

Professor Patrick Tan emphasizes that Japanese encephalitis causes a heavier health burden than dengue and can be nearly eradicated with vaccination. Enhancing vaccination programs, including booster doses, could have a dual benefit in disease prevention and mitigation.

Looking ahead, the research team plans to further monitor dengue evolution in the region and optimize vaccination strategies to protect communities effectively. Their work aims to inform public health initiatives to mitigate the impact of both viruses as they continue to spread in changing environmental conditions.