Anatomy Of An Outbreak

As it turns out, it wasn't the ailing old folks who heralded the arrival of a deadly new contagion in New York this summer. By the time aging patients began languishing in Flushing Hospital--confused, racked by fever, weak to the point of paralysis--crows had been dying for weeks. Queens residents had been calling city wildlife manager Joseph Pane to say that birds with no visible wounds were hobbling around shaky and disoriented. Dr. Tracey McNamara of the Wildlife Conservation Society had heard similar reports from the neighborhoods surrounding the Bronx Zoo, where she works as a pathologist. And keepers were finding crow carcasses on the zoo grounds. "It was unusual to have a single species die off like that," McNamara recalls. "Something was obviously going on."

That something, we now know, was a form of viral encephalitis never before seen in the Western Hemisphere. After a month of false starts, researchers have now linked New York's strange afflictions--both human and avian--to the Kunjin/West Nile virus, a mosquito-borne pathogen rarely seen outside Africa, Australia and the Middle East. By late last week, health officials had confirmed 36 cases of West Nile fever among New York City residents and a dozen more cases in neighboring counties. Four people have died so far, and hundreds--perhaps thousands--may have survived the infection without knowing it. Fundamental questions about this epidemic--how did it start? Will it spread to other regions?--are still unanswered. But the events of the past two months hold clear lessons. If Americans thought they were safe from obscure tropical diseases, they should now know they were wrong.

For Dr. Deborah Asnis, chief of infectious diseases at Flushing Hospital, the trouble started on Aug. 12, when a 60-year-old man showed up with a collection of symptoms that didn't seem to go together. His fever and chest X-ray suggested pneumonia, while his extreme muscle weakness pointed to Guillain-Barre syndrome, an inflammation of the nerves. But unlike a Guillain-Barre sufferer, this patient still had reflexes in his paralyzed limbs. Eleven days later Asnis called the New York City Health Department to say she now had two patients with similar symptoms. She had started to think the real problem was encephalitis, a brain inflammation that can stem from various causes. But these were highly unusual cases. "People with encephalitis are usually combative, hallucinating, having seizures," she says. "These patients were just sitting there limp in bed."

On Aug. 28, two Health Department physicians--Dr. Marcelle Layton and Dr. Annie Fine--visited Flushing Hospital. The cluster of patients had grown to four, and the investigators spent the day interviewing families to find out where the patients had traveled lately and what they'd been eating. "Nothing jumped out at us," Layton recalls, "except that many of them were older adults who spent time outdoors in the evening." While Layton and Fine were encamped at the hospital, a fifth patient showed up. This one, a 58-year-old man, did show the combative behavior typical of encephalitis, and a spinal tap revealed signs of inflammation. When Layton called the Centers for Disease Control and Prevention (CDC), officials there urged her to collect serum and spinal fluid from all the patients and send it out for lab analysis. "If you see encephalitis in the late summer," says Dr. John Roehrig, chief of the CDC's Arbovirus Disease Branch in Ft. Collins, Colo., "you have to think about viruses spread by mosquitoes."

North America is home to several encephalitis viruses, but the most common is St. Louis encephalitis (SLE), a germ that mosquitoes can transmit from birds--which aren't harmed by it--to people. SLE had not been seen in the New York area since the 1970s, but outbreaks occur periodically in the Midwest and Southeast, and the victims are usually elderly. When state and federal investigators received the samples, they ran quick tests for antibodies to several encephalitis viruses. And when SLE produced positive reactions, they figured they'd solved the mystery. On Sept. 3, Mayor Rudy Giuliani announced the lab findings and said the city would start spraying malathion to kill mosquitoes. Two more patients had died by now, and a sixth case had turned up in Brooklyn, but the war was on. City workers were distributing leaflets door to door. CDC experts were setting traps to monitor the mosquito population--and FBI officials were on site to determine whether bioterrorists were behind the whole mess. The CIA studied the CDC's response time. LET US SPRAY! the tabloids howled.

Prudent measures, to be sure, even if they were aimed at the wrong virus. As trucks and helicopters started showering the region with pesticide, McNamara (the Bronx Zoo pathologist) and Pane (the city wildlife manager) were still puzzling over the onslaught of sick crows. In dissecting carcasses, they had found that many of the birds suffered from heart lesions and brain hemorrhages. Both scientists had been shipping dead crows to New York state wildlife pathologists in Albany. But McNamara's concern turned to alarm over the Labor Day weekend, when the zoo's rare birds started dying. In just a few days' time, she lost a cormorant, three Chilean flamingos and an Asian pheasant. Pathology tests revealed the same heart-and-brain lesions that the crows had suffered.

Now convinced that an infectious agent was on the loose, McNamara alerted the U.S. Department of Agriculture's National Veterinary Services Laboratories, in Ames, Iowa. NVSL researchers confirmed that the bird tissue was infectious, but when further tests ruled out the most likely bird maladies (avian influenza and Newcastle disease), things got confusing. The tissue tested negative for the most plausible encephalitis viruses (eastern, western and Venezuelan equine encephalitis). There was less reason to pursue St. Louis encephalitis, the ostensible culprit in the human epidemic, since birds are not normally harmed by it. But on Sept. 16, NVSL researchers called McNamara with an intriguing bit of news. Using an electron microscope, they had identified viral particles that measured 40 nanometers in diameter. And that suggested that the bird virus belonged to the same genus as SLE, the Flavivirus genus.

Though no one yet realized it, the two investigations were starting to converge. Health officials were still identifying human encephalitis cases in and around New York City, and they were now sending samples of deceased patients' brain tissue to two labs--the CDC's arbovirus lab in Ft. Collins and the Emerging Diseases Laboratory at the University of California, Irvine--for closer analysis. By Sept. 23 the California team had found virtually identical strings of viral DNA in the brain tissues of two patients. And as lab director Dr. Ian Lipkin told New York state health officials the next morning, it didn't belong to SLE. It bore more resemblance to SLE's flavivirus cousin: the Kunjin/West Nile virus.

CDC researchers were reanalyzing human serum samples and reaching the same conclusion. "We realized that, yes, those patients were reactive with [antibody tests for] St. Louis encephalitis," says the CDC's Roehrig, "but they were far more reactive with West Nile encephalitis." That wasn't all his team had learned. By now, Roehrig's group was also analyzing tissue samples from the dead birds that McNamara had sent to Iowa. Like the human tissues, they contained genetic sequences resembling those of the SLE virus. But when the bird tissues were tested for the West Nile virus, the match was nearly perfect. That's when everything fell into place. The two outbreaks were really one.

The mosquito season is now ending in the Northeast, and the birds are heading south. It's conceivable that a few infected bugs will survive the winter in basements or subways and cause more trouble in the spring. But mosquitoes aren't the only variable in the equation. Experts believe this summer's drought conditions helped fuel the outbreak, by leaving unflushed ponds, pools and storm drains for mosquitoes to breed in. Under different conditions, the Kunjin/West Nile virus might simply die out. The more immediate concern is that infected birds will carry the virus down the East Coast this fall.

Fortunately, most Southeastern states are savvy about the potential for trouble. Instead of doing battle with swarms of winged adults, mosquito-control experts combat them at the larval stage, when they're confined to water and easily killed. The aerial spraying now underway in New York is the right move, says Wayne Crans of Rutgers University, "but an admission that other proper steps weren't taken."

How did the Kunjin/West Nile virus find its way to New York City? We may never know. Maybe an infected bird, blown off course in North Africa, crossed the Atlantic and passed the virus to a mosquito. That's unlikely, since birds are contagious for only a few days. It's also unlikely that legally imported birds introduced the virus (they're quarantined for at least a month upon arrival) or that an infected person brought it over (human blood may not carry enough virus to arm a biting mosquito). Smuggled birds are a likelier source, since they fly at jet speed and bypass quarantine. In any case, no one should assume that Kunjin/West Nile is the last exotic pathogen we'll see on this continent. There are more out there, and as the events of this summer make clear, they've got wings.

 

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