A new analysis of more than 3,000 U.S. patients diagnosed with West Nile virus (WNV) between 2013 and 2024 has identified several demographic and clinical factors that markedly increase the odds of developing neuroinvasive disease and of dying from the infection. The findings, based on de‑identified electronic health records from the TriNetX Research Network, reinforce long‑standing observations about age and underlying health conditions while highlighting the added risk posed by kidney disease, cerebrovascular disorders and immunosuppression.
Study Findings
Researchers from UCLA and Johns Hopkins examined 3,064 adult patients who had an ICD‑10 diagnosis consistent with WNV infection. Of these, 1,206 (39 %) met criteria for West Nile neuroinvasive disease (WNND), a severe form that can cause meningitis, encephalitis or acute flaccid paralysis. Multivariable Cox proportional‑hazard models showed that each additional decade of age increased the risk of WNND by about 11 %, and men were 29 % more likely than women to develop the condition.
Chronic kidney disease (CKD) and cerebrovascular disease (CEVD) each conferred roughly a 20 % higher hazard of neuroinvasion. Blood‑cancer (hematologic malignancy) and the use of immune‑suppressing medications raised the risk by 38 % and 43 % respectively. Hypertension, alcohol‑related disorders and multiple sclerosis were also significant predictors, the latter more than doubling the risk.
When mortality was examined, WNND itself emerged as the strongest predictor of death within 30 days, with a two‑and‑a‑half‑fold increase in risk. Age, CKD and CEVD again featured as independent mortality risk factors, with CKD more than doubling the odds of dying.
Overall, the cohort represented roughly one‑fifth of all WNV cases reported to the Centers for Disease Control and Prevention (CDC) during the same period, and more than one‑third of the nation’s reported neuroinvasive cases. The study confirms that older adults and people with specific comorbidities bear the greatest burden of severe disease.
Expert Commentary
“An aging population with rising rates of chronic illness and immunosuppression is facing a heightened threat from West Nile virus,” said Dr. Seth Judson, lead author and infectious‑disease specialist at UCLA. “Identifying these high‑risk groups allows clinicians to prioritize testing, monitoring and targeted education.”
Dr. Judith M. Hess, a CDC epidemiologist who oversees arboviral surveillance, noted that the new data align with the agency’s longstanding observations that people over 60 experience the highest incidence of neuroinvasive disease. “The CDC’s 2023 arboviral report showed a case‑fatality rate of about 7 % for neuroinvasive West Nile infections, emphasizing the need for focused prevention,” she said. (Read the full CDC summary here.)
Public‑Health Implications
The study’s risk‑factor profile supports the CDC’s 2024 National Public‑Health Strategy to reduce annual WNND cases to fewer than 500 by 2035. Vector‑control measures—such as eliminating standing water, applying larvicides, and encouraging personal protective behaviors like EPA‑registered repellents—remain the cornerstone of prevention, especially for older adults, patients with CKD or a history of stroke, and those receiving immunosuppressive therapy.
Because no vaccine or antiviral treatment is currently available for WNV, public‑health officials can use these findings to refine outreach campaigns. For instance, organ‑donor and blood‑screening programs already target WNV; the new data suggest that transplant recipients with CKD or CEVD may require heightened vigilance.
From a clinical standpoint, providers should maintain a low threshold for ordering WNV IgM testing in patients presenting with fever, meningitis, or encephalitis during mosquito season, particularly when any of the identified risk factors are present. Prompt diagnosis enables supportive care and appropriate monitoring for neurological complications.
Next Steps in Research
Although the TriNetX analysis leverages a large, geographically diverse dataset, it relies on diagnostic coding, which can miss subtleties of disease severity. Prospective cohort studies that capture detailed clinical parameters—such as viral load, immune response profiles, and organ‑function metrics—are needed to clarify causality and to explore why conditions like CKD amplify neuroinvasion.
The findings also reinforce calls for accelerated vaccine development. A 2023 editorial in The Lancet highlighted that a targeted vaccination strategy for high‑risk groups could be cost‑effective once a safe vaccine becomes available. Ongoing phase‑I trials of candidate WNV vaccines should consider enrolling participants with CKD, cerebrovascular disease or immunosuppression to assess efficacy in the most vulnerable populations.
In the meantime, clinicians, public‑health agencies and patients can use the clarified risk profile to improve surveillance, allocate resources for vector control and educate those most likely to suffer severe outcomes.
This story matters because it sharpens the focus on who is most at risk for the deadliest form of a mosquito‑borne disease that causes thousands of infections each year in the United States, guiding both medical practice and public‑health policy.
Read more on Globally Pulse Health for additional coverage of emerging infectious‑disease research.
