Long-term neurological and healthcare burden of adults with Japanese encephalitis: A nationwide study 2000-2015

Abstract

Objective

To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE).

Methods

This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients’ healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients.

Results

This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis ( p<0.05). Having a four-dose JE vaccination (i.e., born after 1976) versus no JE vaccination history (i.e., born before 1963) was significantly associated with lower all-cause mortality (hazard ratio: 0.221 [95% confidence interval: 0.067, 0.725]). Comorbid diabetes and incident epilepsy/convulsion events significantly increased the mortality risk by 2.47- and 1.85-fold, respectively ( p<0.05).

Conclusion

A considerable medical burden associated with JE was observed in affected adults, even in the years following JE diagnosis. Vaccination should be considered to prevent this sporadic, but lethal, viral infection.

Author summary

The epidemiology of adulthood Japanese encephalitis (JE) remains limited, and data on the economic burden associated with JE is lacking. This study is the first to comprehensively examine the healthcare burden (i.e., healthcare utilization and costs, neurological complications, all-cause mortality) of an adult population with JE, utilizing a nationwide cohort of JE-infected adults with up to 16 years of follow-up. In the first 6 months following JE diagnosis, a higher rate of neurological disorders was found, compared to the years after the diagnosis, with stroke being the most common neurological complication, followed by epilepsy/convulsions. The healthcare utilization of JE patients was higher in the first 6 months after the diagnosis compared to the years following the diagnosis. Medical costs increased considerably at JE diagnosis and subsequent-year costs after diagnosis remained higher than the cost before diagnosis. Having comorbid diabetes or incident epilepsy/convulsion events was a significant risk factor for mortality of adults with JE. Being born after 1976 in Taiwan, and thus likely receiving a four-dose schedule of vaccination, was associated with reduced mortality. Therefore, special attention is required for JE patients with comorbid diabetes or incident epilepsy/convulsion events, and JE vaccination should be considered to prevent this sporadic but lethal viral infection.