Older adults with chronic kidney disease (CKD) or a history of stroke face a markedly higher risk of developing severe, potentially fatal illness after West Nile virus (WNV) infection, according to new research conducted by the University of California–Los Angeles (UCLA) and Johns Hopkins University, published in JAMA Network Open.
The study analyzed electronic health records from 3,064 adults across 65 U.S. healthcare organizations between 2013 and 2024, aiming to identify factors associated with neuroinvasive West Nile disease—a serious form of the infection that can affect the brain, spinal cord, and surrounding membranes, sometimes resulting in paralysis or death.
While the majority of WNV infections are mild or asymptomatic, fewer than 1% progress to neuroinvasive disease, and approximately 10% of these patients die from the infection. Currently, no vaccines or targeted therapies are available, despite WNV accounting for roughly 80% of mosquito-borne infections in the United States each year.
“West Nile virus remains the leading mosquito-borne infection in the U.S., causing significant morbidity and mortality,” the authors noted. “Updated data are essential to identify high-risk populations and guide prevention strategies.”
The patient cohort included 53% with West Nile fever (average age 55; 50% women) and 47% with neuroinvasive disease (average age 59; 61% men). Participants were distributed geographically with 35% in the West, 35% in the South, 15% in the Midwest, and 13% in the Northeast.
Key risk factors for developing neuroinvasive WNV included:
- Older age (11% increased risk per decade)
- Male sex (29%)
- CKD (21%)
- Cerebrovascular disease such as stroke (22%)
- Blood cancers (38%)
- Use of immunosuppressive medications (43%)
- Hypertension (18%)
- Alcohol-related disorders (54%)
- Multiple sclerosis (more than double the risk)
For mortality, the strongest predictors were neuroinvasive disease (2.5 times higher risk within 30 days), age (32% higher per decade), CKD (more than double the risk), and cerebrovascular disease (twice the risk). The researchers categorized these factors as either impairing the immune system or increasing central nervous system vulnerability.
“Clinicians and the public must be aware of these risk factors to better educate and protect high-risk groups,” said lead author Seth Judson, MD, MHS, of UCLA. He emphasized that as the U.S. population ages and comorbidities rise, severe WNV and related deaths could become increasingly common.
The findings also point to potential targeted prevention strategies, including vaccines if they become available. However, the authors noted that reliance on medical diagnostic codes may limit the precision of the data and that further research is needed to better understand the underlying mechanisms behind these risk factors.
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