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West Nile may be fatal years after infection and recovery, according to a new study.

Mike Blake/REUTERS

West Nile virus may be deadlier than thought

ATLANTA—Since West Nile fever first appeared in the United States in 1999, more than 45,000 people have been infected, and nearly 2000 of them are known to have died, for a roughly 4% fatality rate. But a new study, reported today here at the annual meeting of the American Society of Tropical Medicine and Hygiene, suggests that the fatality rate may be much higher. That’s because people infected with the virus may still die years after recovery, because it leaves them more vulnerable to other infectious diseases and kidney problems like renal failure. “This is exciting work,” says Gregory Ebel, a virologist at Colorado State University in Fort Collins, who was not involved in the study. “It’s really strong support for a case that has been building for almost 10 years now.”

West Nile fever was long thought to be a manageable public health problem. The mosquito-borne virus—a relative of the Zika and yellow fever viruses—causes symptoms in just one out of every five infected people. Most of those experience fever and a flulike illness. But in some patients, the virus also infects the central nervous system, which can be fatal. Patients who survive tend to do worse later in life, according to some anecdotes. What’s more, two small studies, one in Israel in 2005 and one in Colorado in 2012 also suggested that overall mortality might be higher than acute cases suggest. But good data have been lacking.

In an effort to change that, Kristy Murray, a researcher at the Baylor College of Medicine in Houston, Texas, and her colleagues went through all 4162 cases of West Nile virus reported to the Texas Department of State Health Services for the more than 10 years between July 2002 and December 2012. They found that 557 patients had died: 289 of them in the first 90 days after infection, and 268 people after. Not all the later deaths resulted from West Nile. But patients who had neurological infections had a higher risk of dying of some other diseases than the general population. For instance, they were almost five times as likely to die of kidney problems and more than twice as likely to die from an infectious disease, Murray found. The effect was particularly pronounced in patients younger than 60. “This shows in a large population size that mortality does increase greatly in the first 6 years after infection,” Murray says.

How exactly the virus leads to longterm health problems is still unclear. It may simply persist in the kidney after the patient has recovered, says Murray, barely replicating but slowly damaging the organ. And other viruses like measles are also known to make the immune system less able to defend against other infections for years. The neurological symptoms may simply be a marker of a particularly severe infection.

The researchers can’t rule out that the patients who died earlier than expected had underlying diseases that might explain both their early deaths and why they fell ill from West Nile fever in the first place. Still, the work is the strongest evidence yet that the virus is deadlier than was thought, Ebel says. “This shows that if you have younger West Nile patients with neuroinvasive disease you better be watching them.” Murray says her finding also underscores the need to fight the virus, which continues to infect thousands of people in the United States annually. “We really need to push for a vaccine.”