HMN 2025: How Aging population faces escalating West Nile threat as chronic diseases and immunosuppression rates climb

Older people with a history of chronic kidney disease or conditions affecting blood flow to the brain such as stroke face about double the risk of developing neuroinvasive disease that can lead to paralysis and death following infection with West Nile virus, new UCLA research finds.

The study, published in JAMA Network Open, also suggests that other factors such as male sex, hematologic malignancy, immune suppressants, hypertension, alcohol-related disorders and multiple sclerosis, contribute to the higher risk of developing neuroinvasive disease, which occurs when the virus attacks the central nervous system.

“There is currently no vaccine or treatment for West Nile virus, so preventing infection is our only line of defense,” said study lead Dr. Seth Judson, assistant professor-in-residence of medicine in the division of infectious diseases at the David Geffen School of Medicine at UCLA.

“Awareness of risk factors among clinicians and the general public is important for educating and preventing infection among higher risk populations. As the population in the US continues to age and has increasing rates of comorbidities and immunosuppression, there could be greater risk for severe West Nile disease and mortality.”

Background on West Nile virus and study findings

West Nile was first detected in 1999 in the US, where it is now endemic throughout the entire country. Since then, it has been responsible for about 80% of all mosquito-borne infections each year. About 75% of infected people are asymptomatic and most of the others develop West Nile fever, which is typically mild. A subset comprising just under 1% of people can, however, develop neuroinvasive disease which has a roughly 10% fatality rate.

The researchers examined data from 2013-2024 for about 2,000 people across 65 health care organizations culled from the TriNetX Research Network. They found the following factors that raise the risk for neuroinvasive disease, which involves infection of the brain, spinal cord and meninges:

• Older age increased the risk by about 11% for every 10-year increase in age.
• High blood pressure posed an 18% higher risk.
• People with chronic kidney disease (CKD) had about a 21% higher risk.
• Cerebrovascular disease such as a history of stroke or brain aneurysm raised the risk by about 22%.
• Men face about a 29% higher risk than do women.
• Blood cancers increased the risk by 38%.
• Immune-suppressing medications increased it by about 43%.
• Alcohol-related disorders led to a 54% higher risk.
• Multiple sclerosis was linked with more than double the risk.

Mortality risks and implications for prevention

As for mortality, neuroinvasive disease was linked with 2.5 times the risk of dying within 30 days, each decade of older age was associated with a 32% risk of dying, and both chronic kidney and cerebrovascular disease led to about double the risk of dying after infection.

Overall, the risk factors the researchers identified largely fit into two groups, those that impair the immune system and those that increase vulnerability of the central nervous system, Judson said.

“Our findings reveal groups that could be at particularly high risk for severe West Nile disease, and these populations could benefit from targeted preventative measures and future vaccines, if they become available,” he said. “These risk factors may also be helpful for clinicians for monitoring and triaging patients.”

Study limitations and future research needs

The researchers based their case analyses on ICD-10 medical diagnostic codes, which do not capture the full scope of an individual patient’s condition and are subject to documentation errors and ambiguity, so more research is needed, Judson said.

“Mechanistic and causal inference studies will be needed to further determine how these risk factors contribute to neuroinvasive disease and mortality,” he said.

Dr. David Dowdy of Johns Hopkins University is the study co-author.

The content is provided for information purposes only.