Alan Sipress - The Fatal Strain

Hours after Captan Boonmanut died on January 26 in a nearby ward, Siriraj Hospital convened a seminar to discuss the gathering storm. Prasert was to brief his medical colleagues and review what it would take for H5N1 to spark a human epidemic. The first two conditions had been met. He wanted to discuss the third and fateful one.

Many of those at the seminar were relative newcomers to flu. Prasert reminded them there were two ways a bird flu virus could become transmissible among people. The virus could gradually undergo a series of discrete mutations making it progressively better suited to the human body. This first process was called antigenic drift . The other way, Prasert continued, was antigenic shift , in which the bird flu virus experiences genetic reassortment, swapping genes with an existing human influenza virus and creating an entirely new strain that is both highly lethal and as easy to catch as an ordinary flu bug. This latter transformation could happen overnight, he warned.

It had taken a whole lot of pushing and prodding to get the government to acknowledge that Thailand’s birds were spreading the disease. But now, Prasert told his audience, an equally acute threat could be posed by the country’s pigs. That was because swine could be what researchers called the mixing vessel, in which two flu strains exchange genetic material. Sick pigs in Asia, Europe, and Africa had repeatedly been found infected with a human strain of influenza. Prasert said he was also hearing reports, later confirmed by Chinese researchers, that pigs in China had come down with bird flu. If a pig caught both strains at the same time, the results could be catastrophic.

Over the coming months, as the scourge spread to a third of Thailand’s provinces and across a half-dozen Southeast Asian countries, flu hunters would grow haunted by the prospect that the strain had cracked the code for human transmission. Yet even as the world was reawakening to this threat, Prasert was already probing how the virus might cross this final hurdle.

The next morning, his admonitions made headlines in Thai newspapers. But the reaction was not as he’d hoped. Swine farmers were enraged, fearing for their sales, and some threatened him.

The prime minister was asked by reporters about Prasert’s warnings and brushed them off as the ranting of a mad old man, calling them overly imaginative and without basis in science. “Are the doctor and the media going take any responsibility if the virus does not spread to pigs?” Thaksin asked pointedly.

Dismissing the elderly virologist with a disparaging Thai word, ai , that can best be translated imprecisely as “goddamn,” the prime minister accused the elderly virologist of going too far this time. “It was that goddamn doctor,” he snapped, “saying it all by himself.”

The flu hit America early that year and it hit hard. It was shaping up to be the worst season in twenty-five years. That fall, in October 2003, Tim Uyeki had been summoned back to Atlanta while at an international influenza conference on the Japanese island of Okinawa. His CDC colleagues had urgently notified him about an unusual spike in severe flu cases among children. Texas and Colorado were being struck particularly hard. The culprit was a traditional strain of human flu but a new, unexpected subtype. As autumn turned to winter, the epidemic spread eastward until outbreaks were being reported in most states. The disease was taking an unusual turn in some children, resulting in neurological complications. Even worse, scores of children were dying. Uyeki, as both a pediatrician and influenza specialist, was tapped by the CDC to help run a national effort to identify and detail these fatal cases.

Now, in the waning days of December 2003, Uyeki found himself at his desk. The hallways of the CDC were depressingly empty except for a few other souls on flu duty.

He had been forced to cancel his Christmas vacation. He could have used the downtime. It had been a grueling year, much of it spent on the road. But the mounting pile of pediatric files beckoned. He had to sift them, study them, and try to divine why children were falling victim while the flu’s typical casualties, the elderly, had this time been spared.

When he logged on to his computer on Monday, December 29, he came across an e-mail from Vietnam titled “Urgent.” It was a copy of a request sent to one of Uyeki’s colleagues by a virologist at Hanoi’s National Institute of Hygiene and Epidemiology (NIHE). The Vietnamese scientist, Dr. Le Thi Quynh Mai, reported that Hanoi Hospital was treating a number of children with respiratory symptoms and doctors there were stumped. “We need to know what’s causative of it,” she appealed.

This entreaty was the first hint outside East Asia of a nascent outbreak that would soon transfix the world’s flu specialists. In nearby Thailand, Prasert Thongcharoen had already concluded earlier in the month that bird flu was sweeping his country’s poultry flocks. But he still had no inkling that it had spread to people. That would come three weeks later.

By then, global flu hunters would be streaming into Vietnam on the trail of the novel strain. Their pursuit would widen over the coming months to ever more provinces of Vietnam and then Thailand, the two countries to confirm human infections in 2004. (More countries, including Indonesia, would begin to report them in 2005.) And with each case, investigators would confront that terrible question: Had the virus been passed from one person to another? As the cases persisted and the deaths in Vietnam and Thailand mounted, it became increasingly clear there were indeed likely instances of human transmission. Yet the region’s leaders and the senior brass of WHO itself remained loath to acknowledge publicly that the virus was flirting with the third and final condition for a pandemic.

As Uyeki reviewed the e-mail, he immediately thought of two possibilities, one worrisome and the other worse. “Could the situation be similar to what we are experiencing in the U.S.?” he wondered, thinking about the unusual uptick in seasonal flu. It would hardly be unprecedented for such a strain of human flu to circle the world. “Or,” he pondered, “could these be highly pathogenic H5N1 virus infections?”

He had reason to suspect the latter. Though there was yet no public report of unusual poultry deaths in Southeast Asia, South Korea had officially disclosed a die-off two weeks earlier on a chicken farm outside the capital, Seoul. But Uyeki had little other information to go on. So he replied to the e-mail best as he could, laying out possible diagnoses, suggesting more than a half-dozen different viral infections. Topping the list were influenza of some stripe and an ailment called respiratory syncytial virus infection, or RSV, common among infants. He urged his Vietnamese counterpart to collect samples from the patients and test for those two possibilities.

Uyeki was already acquainted with the Vietnamese doctor and her colleagues in Hanoi. He had first gone to Vietnam three years earlier to collaborate with them on a study looking for evidence of bird flu in live poultry markets. He had stayed in touch, cultivating the relationship as he had with scientists across much of Asia. When SARS broke out in Hanoi in early March 2003, Uyeki returned to help contain the epidemic. He arrived just days after Vietnam’s first case was identified and stayed for a month. Later in the year, he was back yet again, advising the Vietnamese on how to monitor for flu.

When Uyeki first joined the CDC’s influenza branch in 1998, Keiji Fukuda had been on board for two years and had already helped run the investigation into Hong Kong’s H5N1 outbreak. Now the two of them would return together to Asia yet again, trying to decipher whether the new threat was also a passing scare or a harbinger of something far worse.