West Nile virus running wild

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West Nile virus: Return of a killer
ENLARGE

Close up of mosquito head and thorax

Culex pipiens, the Northern house mosquito, is the primary vector of West Nile in the Midwestern United States.

For years, it’s been absent from the headlines. By now in 2012, 1,118 Americans have been diagnosed with West Nile, and 41 have died. On Aug. 22, Houston, Texas, announced it would start airborne insecticide sprays to kill mosquitoes and reduce infections.

And public health authorities are warning about the disturbing “neuroinvasive” infections — which can cause stupors, disorientation, even permanent paralysis.

So let’s put on some long pants and shirts, slather with mosquito repellent, and stay inside at dusk and dawn, when infectious mosquitoes are most active.
And then let’s ask, what accounts for the recent rise in cases and deaths from West Nile? What is the long term picture of this emerging infectious disease?

The first human cases of West Nile were identified in Israel in the 1950s; the disease has since spread throughout the Middle East, North Africa and Europe. West Nile reached the United States in 1999 with an outbreak in New York.

U.S. cases of West Nile virus

Line graph shows 4-year rise in neuroinvasive cases and fatalities.

U.S. cases of West Nile have declined since a peak in 2002-3. That uptick in fatalities and neuroinvasive cases will continue, as West Nile is usually worst in late summer and early fall. Not shown: total diagnosed cases reached 9,862 in 2003.

A variable virus

West Nile causes no symptoms in 80 percent of people. Another 20 percent of infected people have general viral symptoms like fever, headache, body aches, nausea, and perhaps swollen lymph glands or a skin rash. About one person in 150 develops the neuroinvasive variety, which can include high fever, headache, stupor, coma, convulsions, muscle weakness, vision loss, numbness and paralysis. An estimated 3 million Americans have been infected. Most did not notice the disease, but likely gained at least some immunity after recovery. Source: CDC.

This year’s upturn was not entirely shocking, says Tony Goldberg, professor of pathobiological sciences and epidemiology at the University of Wisconsin-Madison School of Veterinary Medicine. “I was surprised at how extraordinarily high the numbers are, but my colleagues and I did predict this would be a high year for West Nile. We had a perfect storm of weather events that made us think it might be a good transmission year. There was a mild winter so more of the overwintering mosquitoes survived, then wetter conditions in the early spring [which fostered mosquito reproduction] followed by hot and dry spring and summer.”

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Hand holds mosquito with tweezers over petri dish full of specimen

Courtesy Tony Goldberg, University of Wisconsin-Madison
The only good skeeter is a dead skeeter. These corpses were collected during studies of West Nile transmission in Chicago suburbs.

Culex pipiens — the northern house mosquito — is the primary vector in the Midwest, says Goldberg, who has studied West Nile near Chicago for 10 years with National Science Foundation funds. “It breeds in standing water containing fermented organic material, exactly what we see in abandoned swimming pools, unclean gutters, bird baths and storm sewers — where water accumulates in wet weather in early spring. Then, when it’s hot and dry, the water sits there, and the eggs develop.”

Ironically, the droughted spring and summer helped C pipiens, since stormwater could not wash their larvae from the storm sewers, Goldberg says.

Blame the robin

Goldberg and colleagues have just shown that the American robin is the “super-spreader” of West Nile in the Chicago suburbs. “Gabe Hamer [now at Texas A & M University] led our effort to figure out what the mosquitoes in Chicago were feeding on,” says Goldberg. “He trapped a lot of mosquitoes, picked out the ones carrying blood, and did DNA sequencing to figure out what they were eating.”

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Orange-breasted black bird stands in grass

Around Chicago, the American robin is the major source of West Nile virus in mosquitoes, which tend (ecch!) to bite around the eye.

The result, he says, was a long list of mammals, birds, and a few amphibians, “but we were able to calculate that the robin contributes more to the transmission of West Nile than any other species.” (Goldberg is quick to stress that he opposes any vendetta against an archetype of the front yard.)

There are still questions about mosquito vectors for West Nile. To transmit the virus, a mosquito must parasitize birds, not mount an immune attack on the virus, and then bite a person, and these characteristics can vary from place to place. “We are doing a lot of work on which mosquito feeds on people in Madison,” says Susan Paskewitz, a professor of entomology at University of Wisconsin-Madison, who monitors mosquitoes for health departments. “It’s hard to get C pipiens attracted to humans here; there may be subtle population differences in behavior in Madison versus Chicago, and we want to understand why.”

Courtesy Tony Goldberg
This innocent-looking storm drain in the western suburbs of Chicago hides a breeding-ground nightmare for West Nile vectors. Rollover: Notice the soggy, decaying organic crud? That’s home sweet home to C pipiens mosquitoes!

Turning up the heat on infection

Like drought, heat plays a direct role in mosquito transmission, says Edward Walker, a professor of microbiology and entomology at Michigan State University. Newly hatched mosquitoes must be infected by drinking blood from an infected animal and so cannot harbor West Nile.

Even then, the bug cannot immediately spread the infection. “The virus has to incubate in the mosquito’s body and spread from the stomach to the salivary glands,” says Walker. “A mosquito spits on you before biting, and its saliva carries the virus.”

The incubation period depends on environmental temperatures, Walker adds. As insects are cold blooded, the movement into the salivary glands happens more quickly in hot weather, which helps explain why West Nile infection rates peak in late summer, and why the record heat of the last year may be propelling infection rates. (In land in the Northern Hemisphere, July 2012 was the warmest July on record, 1.19°C above average.)

One persistent virus

To slither back to the slimy subject of mosquito spit: Kristen Bernard, an associate professor of pathobiological sciences at the University of Wisconsin-Madison, has found a higher level of West Nile virus among mice that were infected by Nile mosquitoes, compared to infection through injection. She suspects that the saliva carries a chemical that hobbles the host immune system.

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Mosquito next to 5 mm scale; its legs are at least twice as long as its body

Credit: Pete DeVries
Culex pipiens, the Northern house mosquito, is a key vector of West Nile in parts of the United States.

Considering the high number of neuroinvasive West Nile cases this year, we were disturbed to hear that West Nile isn’t always “cleared” by the body as once thought. Bernard found West Nile in mice up to six months after the symptoms ended — although the virus did eventually disappear.

Bernard did find immune cells that target West Nile in these mice, but they were dormant. The immune system must be tightly controlled to prevent auto-immune disease, she notes, and “I think for some reason the immune cells are being kept in check a little too much.”

In people, West Nile can persist and cause disease in the kidney, and has been detected six years after infection in the urine of people who think they have recovered, says Bernard. “There is a lot of data showing long term consequences years later, with cognitive problems, memory loss, weakness, malaise. People just don’t feel right.”

It’s unclear if these problems result from the initial damage, or from continued viral activity, Bernard says. “There is a good chance that there could be some persistence in the human central nervous system, but we don’t have evidence.”

Texas blues

Why are Texas and nearby states the epicenter of infection this year? An epidemic of infectious disease is often most intense at first, when it confronts an immune system that has never mounted a defense against it.

That surge-and-decline pattern surfaced when West Nile reached New York in 1999, and was repeated as it marched across the country. But Texas “is such a weird anomaly” because it had already seen West Nile, says Hamer, a clinical assistant professor of entomology at Texas A&M. “After West Nile has been here so long, to have such a big epidemic is just strange.”

West Nile by county, August 21, 2012

Map of cases shows hot spots in Texas, California, Upper Midwest

Credit: CDC
A cluster of reports from Texas, Louisiana and Mississippi are the epicenter of the 2012 West Nile epidemic. A county is shaded if it has any reports of West Nile.

Why the difference?

✘ Mosquito control practices: larva-killing chemicals are used less commonly in the South than in the Midwest and East.

✘ The immune situation in birds: With few people infected in Texas in 2011, it’s unlikely that many birds were exposed that year, either. If few birds now have antibodies against West Nile, they would be more susceptible to the virus.

✘ The weather in Texas: “Last summer, Texas was extremely hot and dry, it broke a lot of records,” Hamer says. After a mild winter, spring 2012 brought “a ton of rain, and now it’s a typically hot and dry summer. This combination of conditions that has never occurred in the last 10 years was conducive to West Nile.”

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Three men stand over open sewer in road with tools and petri dishes

Courtesy Susan Paskewitz and Karli Reifschneider
Introducing fish and small animals called copepods could biologically control the mosquitoes that carry the West Nile virus. Here, University of Wisconsin-Madison students check Madison sewers for copepods and mosquito larvae.

Praying for spraying

Vaccines can defeat many viruses, and one already protects horses from West Nile. However, “vaccinating the human population is not considered the most effective way to control West Nile,” says Goldberg. “The vast majority of infections are asymptomatic. There are cost issues and side effects, and the people who are most susceptible to West Nile tend to be elderly or immuno-compromised, and might not respond well to the vaccine.”

Instead, Goldberg favors a traditional tactic against mosquito-borne illness: Vector control; killing carrier mosquitoes. “An ounce of prevention is worth a pound of cure,” he says. “If we could get rid of breeding habitat, that would solve the West Nile problem. Everybody knows where the mosquito likes to breed, C. pipiens breeds in standing water with organic material. They can breed in very small puddles, gutters and abandoned swimming pools.”

Here, public health meets economics: the moribund housing market has converted thousands of homes — together with their swimming pools — into mosquito factories. “The foreclosure crisis has led to a disease emergence problem,” Goldberg says.

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Equipment including a large green sprayer in back of white pickup truck

Photo: 2005, Pelham Bay Park, Bronx, New York, Kyrion
New York City responded to a West Nile epidemic by killing mosquitoes that transmit the virus by spraying insecticide from trucks.

The classic anti-mosquito tactic is to drain wet spots, and spread larvacide to kill mosquito larvae on marshes and other wet places that can’t be drained. But faced with West Nile, authorities are spraying adult mosquitoes, especially in Texas, site of roughly half of U.S. West Nile infections.

The logic of killing adults emerges from the biology of vector and virus, says Walker. “Spraying adults with insecticide is a highly rational approach, as it kills the older mosquitoes on the wing, and the older ones are more likely to have the virus infection.”

A spray program in Dallas, during a 1966 outbreak of St. Louis encephalitis, cut the infection rate from one mosquito in 167 to one in 28,000, says Walker.

A 2002 study in Michigan found that the risk of West Nile was 10 times higher outside a five-county mosquito-control area. But in general, it’s difficult to prove that mosquito controls reduce the West Nile rate, Walker says. “Epidemiologically there is some evidence that spraying reduces human infections,” but a careful study would be forced to test many people for West Nile for several years.

“Passive case detection,” asking public health authorities to report illness, is unlikely to prove that spraying works, he says, just as it is unlikely to show that bed nets prevent malaria. Lengthy studies that actively monitor blood samples do prove the benefit of bed nets, however.

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Critter looking like 3-leaf clover has antennae at 1 end, 2 featherlike structures at other.

Photo: Wikipedia
Macrocyclops albidus, a copepod, is a ferocious consumer of mosquito larvae.

The big picture

July 2012: warmest month in U.S. history

ottest area is a triangle from Tex. to Ohio to Canadian border to Wash. State. Almost all states above average.

Credit: National Climatic Data Center, NOAA
The average temperature for the contiguous United States during July was 77.6°F, 3.3°F above the 20th-century average.

If you’re old enough to remember the days before AIDS, you may be wondering about the steady, deadly parade of new diseases. Viruses are a particularly rich category, and it’s not just West Nile: the list of emerging infectious diseases includes SARS, Ebola, and new strains of influenza and hepatitis.

What accounts for the dramatic increase in new pathogens? Goldberg, who is associate director for research at the Global Health Institute at UW-Madison, says better surveillance and diagnostics make it easier to identify new diseases, “but the majority view is that certain imbalances are the cause. A higher human population is encountering more wildlife, urbanization has created higher density, allowing more transmission, globalization has allowed opportunities for pathogens to escape.”

All these factors, propelled by climate change, are hastening the evolution and emergence of pathogens from the ends of the Earth.

The recurrent outbreak of West Nile shows that viral diseases “are very unpredictable,” says Goldberg. “They can change due to the virus mutating or a change in ecological conditions. We can get new outbreaks of an old disease as soon as we let our guard down.”

With few drugs available to treat West Nile, Goldberg says scientists are gaining the ability to predict the intensity of the epidemic in advance. “In Chicago, we can already predict the size of the epidemic, using early-season data on weather, mosquito population and robin breeding. But extrapolating to new places is very difficult. We really need a universal predictive model of West Nile outbreaks.”

Such a model, he adds, must account for the abnormal weather that is becoming normal with a changing climate. “Everyone has a strong sense that the unusual weather patterns we have seen are responsible for the high transmission rates.”

– David Tenenbaum

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Terry Devitt, editor; S.V. Medaris, designer/illustrator; Molly Simis, project assistant; David J. Tenenbaum, feature writer; Amy Toburen, content development executive

Bibliography

  1. Mosquito repelling plants
  2. Mosquito repelling phone app
  3. History of West Nile Virus
  4. Mosquitoes and disease
  5. Zimmer on WNV
  6. Preventing bird-borne diseases
  7. Immune system overview