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Sleuthing Swine Flu
Chance Test Led CDC Investigators to Link Cases in U.S., Mexico

By Ceci Connolly
Washington Post Staff Writer
Sunday, May 3, 2009

ATLANTA Nancy Cox's phone connection to Mexico kept cutting off. Rain came down in sheets above the Centers for Disease Control and Prevention.

On the other end of the line the night of April 23, Mexican Health Ministry officials anxiously awaited results on a batch of samples they had sent to Atlanta that morning. They were trying to solve a mystery Cox's team had been wrestling with for more than a week: Was the sickness killing young Mexicans related to a strange new flu popping up in the United States?

People across the border were sick and dying, and, in the United States, a novel virus had surfaced in the San Diego area. Using samples from the California cases, the CDC was getting close to determining whether the cross-border illnesses matched.

"I could hear the cracks of thunder," recalled Cox, director of the CDC influenza division, describing the long silent minutes as she and the Mexicans waited for the results.

The answer she delivered was both satisfying and troubling to disease detectives at the CDC, the sleuths who unravel the puzzles surrounding outbreaks of illnesses in the United States and abroad. Yes, she told them, the viruses matched.

What began as a scientific anomaly in this country was now a deadly binational outbreak. And it was spreading fast. In the course of nine days, the virulent bug would jump swiftly from the Americas to Europe, New Zealand, the Middle East and Asia. It would lead to school closures across the United States, the slaughter of hundreds of thousands of pigs in Egypt, and the quarantining of 300 people in a Hong Kong hotel after the disease was diagnosed in a guest.

Although the disease detectives were operating without a health secretary in Washington or a permanent CDC director, Cox, an Iowa native with a love of science and travel, had years of intense preparation for just such an outbreak.

After hanging up the phone, she followed the pandemic playbook, notifying her bosses, who ordered the agency's Emergency Operations Center to ramp up to its highest response level. Within days, CDC would dispatch medical investigators to Mexico, ship new flu-test kits to state health laboratories in the United States and release pharmaceutical supplies from the Strategic National Stockpile to all 50 states.

Then Cox's cellphone rang again, with a call from home. There was more bad news for the soft-spoken blondvirologist who had grown the CDC's flu division from 14 people to more than 100 scientists. Her 1916 Tudor house in the Druid Hills neighborhood of Atlanta had been struck by lightning. Her husband and daughter were safe, but their lovingly restored home was burning to the ground.

A Fortuitous Test

The medical detective work that unearthed the 2009 outbreak of swine-origin influenza A (H1N1) -- more commonly known as swine flu -- began with a bit of happenstance.

On March 30, a 10-year-old boy in Southern California developed a cough and fever. Normally, doctors wouldn't have bothered testing for the flu; they would have given him medicine and sent him home.

But the Naval Health Research Center in San Diego was participating in a clinical trial of new, 30-minute flu tests, so they took a nasal swab and tested it the next day.

The boy had a flu strain that the virologists, skilled at identifying the seasonal flu, didn't recognize. Following the study protocols, they shipped the specimen to a research lab at the Marshfield Clinic in Wisconsin, which also concluded that the boy, who would become known as Patient A, was infected with an unrecognizable influenza virus. Next it was sent to the state health lab.

Since the 2003 bird flu outbreak, the public health community has been on the lookout for problematic new viruses. When the boy's nasal swab reached the Wisconsin state lab shortly after 3 p.m. on April 10, just as the office was closing for the Easter weekend, lab chief Peter Shult asked whether it was a high-risk case.

"The concern always is, could this be avian?" he said. "You are always worried that one of those might sneak in."

Once Shult learned that the specimen was from a child who hadn't been out of the country and had recovered from the mild illness, he decided the test could wait. He suspected the youngster had contracted swine flu, rare but not unheard of, he said later.

Swine flu in pigs is common, but only rarely does it spread to humans. Nationwide, health officials see a few cases each year, with the last major public health crisis occurring in 1976, when 40 million people were vaccinated after an Army recruit died of the illness in New Jersey. People cannot be infected by eating pork. Twice on April 13, Shult ran the lab tests, confirming that what he had on his hands was an influenza strain he could not pinpoint. "We sent it immediately to CDC," he said.

As that first San Diego sample made its way to Atlanta, the naval lab got its second curious case, a 9-year-old girl. Again, the scientists diagnosed influenza but couldn't be more specific. The only thing they knew: The child's flu was not the normal variety.

This time, the specimen was shipped to Atlanta, and Patrick Blair, the director of the Navy lab, alerted the CDC that something was amiss. CDC officials paid attention because Blair was known in the medical detective world, having spent much of his career as a virus hunter in Indonesia.

"That's the trick with catching something early," said Michael Shaw, the CDC's associate director for laboratory science. "You need a person in the field with a good eye and a bit of paranoid suspicion to send it along."

Unidentifiable Samples

As Shult ran tests in Wisconsin and Blair puzzled over the second atypical virus to pass through his lab in less than a week, Mexican authorities grappled with a late-season wave of flulike illness.

At the White House, President Obama prepared for his first trip to Mexico, on April 16, with advance teams already on the ground.

CDC analysts scour daily for early warning signs of a disease outbreak or natural disaster. With computer search tools, they scan news reports, online blogs and the data that pours into the operations center.

"We're picking up thousands of signals every day," said Scott F. Dowell, head of global disease detection at the CDC. "The challenge is in interpreting them."

On April 13, the Mexican Health Ministry sent the CDC an e-mail describing a cluster of "unexplained respiratory illness," Dowell said. But the reports were contradictory, and because the majority of respiratory illnesses are unexplained, Dowell said it was difficult to assess what was happening thousands of miles away.

The next day, the CDC lab got the specimen from Patient A, the 10-year-old boy, and a day later identified it as the new H1N1 virus.

Interesting but not stunning, thought Daniel B. Jernigan, Cox's deputy in the flu division. As the person overseeing the rapid-flu-test project in San Diego and other sites, Jernigan makes his living tracking influenza cases. He had seen a dozen swine flu cases in recent years, most often a child who had visited a petting zoo or a farmer who had come in contact with a sick pig.

"The kid gets a fever, mom doesn't feel too good, they take some medicine, and it's all over," Jernigan said. The swine influenza, in other words, typically dies out quickly.

When the second San Diego specimen arrived and it, too, was determined to be swine influenza, Jernigan's team started digging. In the lab, "we blast-sequenced it against our entire pig laboratory," he said, describing the hundreds of swine virus samples the CDC has collected over the years. "There was no match."

Despite their confidence in Blair, they wondered whether a contaminant had landed in the Navy lab.

Then came the call from Texas -- two teenage boys in Guadalupe County with an unrecognizable flu virus.

Then San Diego. Another influenza virus they couldn't identify.

By Thursday, April 16, as Obama's Air Force One landed at Benito Juarez International Airport in Mexico City, CDC officials were struggling to "connect the dots," as Cox put it. She called Mexico, requesting specimens.

"We thought there might be a possibility but not necessarily be a connection between the situation in California and what was unfolding in Mexico," she said.

Unbeknownst at the time, a member of Obama's advance team -- dispatched to Mexico on April 13 -- had contracted the swine flu and brought it home to the Washington area.

Making the Connection

Over the weekend of April 18, CDC officials began drafting an urgent public health dispatch describing a pair of novel swine flu cases in the San Diego area. In a Saturday night conference call with California health officials, they launched a gumshoe-style investigation. Although they now knew what the virus looked like, its origins remained a mystery.

With guidance from the CDC, state health investigators visited the children, their families, and their schools and friends. They took blood samples and interviewed more than 90 people.

"We were thinking there had to be some contact with pigs," said state epidemiologist Gil Chavez. They came close; the boy had visited the zoo; the little girl had been to a county fair. But no luck.

"We absolutely couldn't establish any links with swine whatsoever," Chavez said. Furthermore, the children lived 120 miles apart and had never met.

On Monday, April 20, Veratect, a private firm based in Kirkland, Wash., that conducts disease surveillance, contacted the CDC, concerned about the respiratory illness in Mexico. But in an e-mail, medical director James Wilson acknowledged, "I suspect this is probably a false alarm."

North of the border, Canada also was picking up nervous chatter. After its devastating experience with severe acute respiratory syndrome, or SARS, in 2003, Canada's public health apparatus is highly attuned to potential outbreaks. Through the international laboratory grapevine, U.S. public health workers heard that Mexico was shipping samples to Canada.

But it wasn't adding up, Jernigan said. The situation in California -- children with mild cases of swine flu who had fully recovered -- didn't match the dire picture in Mexico.

By the time Richard E. Besser, acting director of the CDC, convened the weekly pandemic flu meeting at 8:30 a.m. on April 22, CDC lab technicians had confirmed that the viruses that infected two teenagers in Texas identically matched the California bugs.

"The first case of swine flu, you think: No big deal," Besser said in an interview. "The second is a little less common. But then when the Texas cases came in, the epidemiologist in me knew the probability of those being unrelated events has gone way down."

From a polished wood conference table next to the CDC's 24-hour Emergency Operations Center, Besser said the agency would step up its pandemic preparations, increasing the center's staffing from 10 to 70.

The next day, the CDC convened a teleconference with the 50 state public health labs in the United States and urged extra vigilance.

By evening, as the rain began to fall, Cox's team was completing its analysis of the specimens from Mexico. The genes were identical to the H1N1 swine variation found in California and Texas. Finally, she recalled, "we were really putting together a couple of major pieces of the puzzle."

One mystery had been solved. But for Cox, whose house would be torn down to the studs, the marathon was just beginning.

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