Aging Populations and Chronic Illness Are Increasing the Risk of Severe West Nile Virus Disease

West Nile virus has been part of the public health landscape in the United States for more than two decades, but new research suggests that its most dangerous effects may become more common as the population ages and rates of chronic illness rise. A large new study from researchers at the University of California, Los Angeles sheds light on exactly who is most at risk of developing neuroinvasive West Nile disease, a severe and sometimes fatal complication that affects the brain and nervous system.

The findings, published in JAMA Network Open, point to a growing concern: people who are older or living with certain medical conditions face a significantly higher risk of serious illness and death after a West Nile virus infection. With no approved vaccine or specific treatment available, understanding these risk factors is critical for prevention and early medical response.

Understanding West Nile Virus in the United States

West Nile virus was first detected in the U.S. in 1999 and has since become endemic across the entire country. It is now responsible for roughly 80% of all mosquito-borne infections reported each year in the U.S. The virus is primarily spread through the bite of infected mosquitoes, most commonly during warmer months.

For most people, infection is either silent or mild. About 75% of infected individuals show no symptoms at all, while many others develop West Nile fever, which typically includes flu-like symptoms such as fever, headache, body aches, and fatigue. These cases usually resolve without long-term complications.

However, a small but important fraction of infections take a much more serious turn. Just under 1% of infected individuals develop neuroinvasive disease, where the virus attacks the central nervous system, including the brain, spinal cord, and surrounding tissues. This form of the illness can cause encephalitis, meningitis, paralysis, long-term neurological damage, and death, with a fatality rate of around 10%.

How the UCLA Study Was Conducted

To better understand who is most vulnerable to severe outcomes, UCLA researchers analyzed medical data from 2013 to 2024 using the TriNetX Research Network, a large database that aggregates health records from multiple institutions. The study included about 2,000 adults diagnosed with West Nile virus across 65 health care organizations in the United States.

The researchers focused on identifying factors that increased the likelihood of developing neuroinvasive disease and the risk of death following infection. Diagnoses and conditions were identified using ICD-10 medical codes, which allowed the team to evaluate patterns across a large and diverse population.

Key Risk Factors for Neuroinvasive West Nile Disease

The study revealed several clear and measurable risk factors that increase the chance of West Nile virus progressing to its most dangerous form. Age stood out as one of the strongest predictors.

For every 10-year increase in age, the risk of developing neuroinvasive disease rose by about 11%. This finding reinforces long-standing concerns that older adults are more vulnerable to severe mosquito-borne infections.

Several chronic medical conditions were also linked to higher risk:

High blood pressure was associated with an 18% increased risk of neuroinvasive disease.
Chronic kidney disease raised the risk by approximately 21%.
Cerebrovascular disease, including conditions such as prior stroke or brain aneurysm, increased risk by about 22%.

Sex also played a role. Men were found to have a 29% higher risk of developing neuroinvasive disease compared with women.

Certain immune-related conditions and treatments significantly amplified risk as well:

Hematologic (blood) malignancies, such as leukemia or lymphoma, increased risk by 38%.
Use of immune-suppressing medications raised the risk by around 43%.
Alcohol-related disorders were associated with a 54% higher risk.
Multiple sclerosis stood out as one of the strongest risk factors, with affected individuals facing more than double the risk of developing neuroinvasive disease.

Overall, the researchers noted that these risk factors fall into two broad categories: those that weaken the immune system and those that increase vulnerability of the central nervous system.

Mortality Risk After Infection

The study also examined what factors influence the risk of death following West Nile virus infection, particularly in the short term. The results underscore just how dangerous neuroinvasive disease can be.

People who developed neuroinvasive West Nile disease had 2.5 times the risk of dying within 30 days compared with those who did not. Age again played a major role, with each additional decade of life linked to a 32% higher risk of death after infection.

Two chronic conditions stood out as especially concerning when it came to mortality:

Chronic kidney disease roughly doubled the risk of death following infection.
Cerebrovascular disease also led to about a twofold increase in mortality risk.

These findings suggest that the same conditions that make people more likely to develop severe disease also make recovery more difficult once the virus affects the nervous system.

Why Aging and Chronic Disease Matter More Than Ever

One of the most important implications of this research is how it intersects with broader demographic trends. The U.S. population is aging rapidly, and rates of chronic illnesses such as kidney disease, hypertension, and conditions requiring immune suppression are increasing.

As a result, a larger share of the population may now fall into high-risk categories for severe West Nile virus outcomes. This raises concerns that, without improved prevention strategies, cases of neuroinvasive disease and related deaths could become more common in the coming years.

Prevention Remains the Only Defense

At present, there is no approved vaccine or antiviral treatment for West Nile virus. Care for infected patients is largely supportive, focusing on managing symptoms and complications. This makes prevention the most effective strategy for reducing illness and death.

Public health experts emphasize mosquito control measures, such as reducing standing water, using insect repellents, wearing protective clothing, and ensuring window screens are intact. For clinicians, awareness of high-risk groups can help guide early monitoring, triage, and supportive care when West Nile infection is suspected.

The study’s authors also note that identifying high-risk populations could help shape future vaccine strategies, should a vaccine become available.

Study Limitations and Future Research Needs

While the findings are robust, the researchers acknowledged several limitations. The study relied on ICD-10 diagnostic codes, which may not fully capture the complexity of individual patients’ health conditions and can be affected by documentation errors.

The authors emphasized the need for mechanistic and causal studies to better understand how these risk factors contribute to neuroinvasive disease and mortality. Such research could eventually lead to improved prevention strategies or targeted therapies.

Final Thoughts

This study offers one of the most detailed looks to date at who is most vulnerable to the worst outcomes of West Nile virus infection. As the population continues to age and chronic diseases become more common, these findings highlight a growing public health challenge that deserves attention from clinicians, policymakers, and the public alike.

Understanding risk is not about causing alarm, but about being informed. With no vaccine and limited treatment options, knowledge remains one of the most powerful tools we have to reduce the impact of West Nile virus.

Research paper:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2025.48229