Friday, November 9, 2012

A more virulent, mutating West Nile virus

Hints of a more virulent, mutating West Nile virus emerge


Centers for Disease Control and Prevention/Reuters - West Nile virus, spread by mosquitoes, can lead to inflammation of the brain, damaging its speech, language and thinking centers.

The West Nile virus epidemic of 2012, the worst in a decade, may be notorious for yet another reason: The virus, in some cases, is attacking the brain more aggressively than in the past, raising the specter that it may have mutated into a nastier form, say two neurologists who have extensive experience dealing with the illness.
One doctor, Art Leis in Jackson, Miss., has seen the virus damaging the speech, language and thinking centers of the brain — something he has never observed before. The other, Elizabeth Angus in Detroit, has noticed brain damage in young, previously healthy patients, not just in older, sicker ones — another change from past years.

But a scientist for the Centers for Disease Control and Prevention said the federal agency has not seen any evidence that the virus is causing a different type of brain damage. He said doctors may be seeing more-serious cases this year because there are more cases overall. But he acknowledged that the CDC does not collect the granular data needed to quickly determine whether the virus is causing more-severe brain damage.

Still, Angus, who has treated West Nile patients for a decade, and Leis, who has more experience treating severe West Nile illness than perhaps any doctor in the country, both suspect the virus has changed — a view bolstered by a Texas virologist whose laboratory has found signs of genetic changes in virus collected from the Houston area.

“I’ve been struck this year that I’m seeing more patients where the brain dysfunction has been very much worse,” said Angus, of Detroit’s Henry Ford Hospital. “It makes you wonder if something’s different, if something’s changed.”
And while the virus in the past has typically invaded the brain and spinal cord only of people who have weakened immune systems, such as the elderly and transplant or cancer patients, Angus this summer treated a severely affected woman in her 20s and a man in his 40s.
Leis said he is seeing much more severe encephalitis — inflammation of the brain — than he has in the past. “It is clearly much more neuroinvasive, neurovirulent,” he said.
Four patients Leis treated this summer had lost their ability to talk or write. Another was paralyzed on one side, as often seen in strokes, not West Nile infections. Others experienced recurring seizures.
In all, 11 of the first 12 patients Leis saw this year at the Methodist Rehabilitation Center in Jackson had more severe brain damage than he had seen previously. The outlook for such patients varies, but most will face years or a lifetime of disability.
“For the first time, we have radiographic evidence, clinical evidence of the virus attacking the higher cortical areas,” said Leis, who has published 15 scientific papers describing previous West Nile patients.
Marc Fischer, a CDC epidemiologist who tracks the West Nile virus, said the agency has not noticed the ­changes described by Leis and Angus. “There’s just a lot more cases this year than anybody has seen in at least 10 years,” he said. “You’re just going to see more severe cases and probably a broader variety of manifestations.”

Last month, Leis asked a Food and Drug Administration scientist who studies the genetics of the virus whether a new, more virulent strain was circulating.
“You are absolutely right . . . that new genetic variants of WNV might have appeared this year,” the scientist replied in an Oct. 23 e-mail obtained by The Washington Post. The scientist continued that “it is not easy to correlate” the new mutations with any specific type of brain damage.
Thirty minutes after Leis ­received the message, another ­e-mail from the same scientist arrived. It said the previous message had been “recalled.”
When contacted by phone, the FDA scientist, who works at the agency’s Center for Biologics Evaluation and Research, declined to discuss the messages, saying that his superiors had instructed him not to talk to reporters.
In an e-mail, FDA spokeswoman Heidi Rebello said that the agency is studying the genetics of West Nile viruses collected from 270 blood donors this year but that “it is premature for us to draw any conclusions about new genetic variants . . . or of any possible association of new genetic variants with increased virulence.”
West Nile virus, made of error-prone RNA instead of the hardier DNA found in human cells, can evolve rapidly. In 2002, a new strain appeared that quickly churns out copies of itself inside mosquitoes. This fast-replicating version swiftly replaced the earlier dominant variety.
In 2003, another genetic variant, now dubbed the Southwestern strain, appeared in New Mexico and Arizona.
The West Nile virus, first described in Uganda in 1937, arrived in New York City in 1999, killing eight in the city. Infected birds transmit the virus to mosquitoes, which then infect people, who cannot infect one another. By 2003, the virus had crossed the country.
So far this year, health authorities have reported more than 5,000 cases of West Nile illness and 228 deaths in 48 states, with Texas, California, Illinois and Michigan having the most cases. The CDC has classified about half of the illnesses as “neuroinvasive” — meaning the virus has gotten into the spinal cord or brain, causing encephalitis or other brain ailments. That’s the most dangerous type of illness caused by West Nile virus. In the other cases, patients come down with fevers or other flulike symptoms.
As of Nov. 6, there had been eight cases reported in the District this year, 45 in Maryland and 25 in Virginia, with new cases expected to plummet with the temperature.
In Texas, the state hit hardest by the epidemic, virologist Alan Barrett said samples of the virus taken from mosquitoes and birds in the Houston area show signs of genetic changes.
“This year’s virus looks more like the virus from 2002 and 2003” than the virus seen more recently, said Barrett, of the University of Texas Medical Branch in Galveston. Given that the Houston-Galveston area is a major flyway for birds, Barrett speculated that a different virus arrived in the area this year.
But it is too early to say whether this possible new strain is more virulent than those seen in years past, Barrett said. It will also take a while to study the genetics of viruses from other parts of the country. His laboratory, one of the few studying West Nile genetics, is backlogged with samples. “We’re overwhelmed,” he said.
North Texas suffered the worst of this year’s epidemic, with 388 cases and 18 deaths in Dallas County alone. Authorities declared a public health emergency and sprayed insecticide from airplanes and helicopters for the first time since 1966.
The spraying worked, said Christopher Perkins, the county health department’s medical director. “We’re getting one or two new cases a week,” down from 20 to 30 in July and August, he said.
Neurologists in Dallas also witnessed devastating encephalitis this year, but in different areas of the brain than Leis described. Steven Vernino, a neurologist at the University of Texas Southwestern Medical Center in Dallas, said he saw damage to the lower brain stem in several patients but not to the higher language and thinking centers.
Barrett will look at the genetics of viruses from North Texas as soon he gets samples, which he expects any day. “Everybody wants to know what’s going on in Dallas,” he said.
Leis said it’s crucial to know whether the virus is mutating. “Otherwise,” he said, “we might be unprepared to deal with it in the future.”

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