by Alan Sipress
Infectious-disease experts now debate whether the industrialized world might actually be more vulnerable today than it was in 1918. After nearly a century of medical progress, how could this be? No doubt there have been some astounding advances in hospital care. The development of antibiotics alone might save millions who would have died in 1918. Many, perhaps most, of the Spanish flu’s victims succumbed not to the virus itself but to secondary bacterial infections that are now treatable.
But consider this: In the United States, 80 percent of all prescription drugs are now produced overseas. They are delivered to drugstores just hours before they’re dispensed. In a pandemic, international shipping could come to a halt as countries impose travel bans and quarantines, companies suspend operations, and employees fall sick or stay home. Once again, pharmacy shelves would run bare. Nor would it just be flu medicine and antibiotics. Within days, medication for heart disease, high blood pressure, and depression would vanish, and insulin for diabetics would disappear. Many hospitals now maintain minimal inventories, receiving three rounds of medicine and other equipment each day. These supplies, too, could evaporate, and with them many forms of critical care.
Since the novel strain reemerged in 2003, Dr. Michael T. Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota, has been warning of the perils inherent in modern commerce. The economies of countries like the United States now more than ever depend on just-in-time supply chains and offshore sourcing of essential goods and services. “The interconnectedness of the global economy today could make the next influenza pandemic more devastating than the ones before it,” he wrote. “Even the slightest disruption in the availability of workers, electricity, water, petroleum-based products and other products or parts could bring many aspects of contemporary life to a halt.” With little surge capacity of their own, Osterholm projects that countries facing a major pandemic would run short on everything from soap and lightbulbs to gasoline and spare parts for municipal water pumps, and, of course, food.
Four days after lab tests had come back positive for bird flu in Vietnam, Klaus Stohr in Geneva convened an unpublicized conference call on January 15, 2004, with a half dozen of the world’s leading influenza specialists. He wanted to know what he was up against.
“A critical situation, unprecedented,” said Dr. John Wood, senior virologist at Britain’s national biological institute. “We have to behave as if it could go to pandemic.”
“Very, very serious,” said Dr. Masato Tashiro, head of virology at Japan’s national infectious-disease institute. The likelihood of human transmission is rising, and this, he said, “would be devastating. [Something we] have not yet experienced before.”
Just two months earlier, Dr. Robert Webster from St. Jude Children’s Hospital had coauthored an article for Science magazine warning that the world was unprepared for a flu pandemic. Now the dread scenario seemed to unfolding. But the extent of the outbreaks caught even him by surprise.
“A very unusual event,” Webster said.
These superlatives reinforced Stohr’s concern. Stohr himself was not formally schooled in flu. Trained as a veterinarian in East Germany before the Berlin Wall came down, he had established himself as a national authority on rabies. His work caught WHO’s eye, and he was recruited to the agency, where he was later tasked with restructuring an influenza operation then considered a backwater. He joined the fraternity of flu hunters.
“Klaus was very excited,” a colleague said, recalling those uncertain days in early 2004. “It’s one of the things they wait for their whole life. Pandemic, it’s the big one.”
Reared on the grinding shortages of the Eastern Bloc, Stohr was skilled at marshaling scarce resources. Now he cobbled together a global response from an agency strapped and weary. He massaged the bureaucracy, spinning out long lists of urgent tasks as he walked the halls, assigning them with dispatch. He stoked the enthusiasm and anxiety of his staff with talk of pandemic and helped position the agency to ensure it got a piece of this action.
The CDC had been eager to send in its own team and had already won a nod from senior Vietnamese officials. But WHO, flush with its triumph over SARS, didn’t want to cede control of an emerging pandemic to the big boys from Atlanta. So WHO hurriedly dispatched Dr. Hitoshi Oshitani, its senior East Asian expert on communicable diseases. He was an astute, hard-driving Japanese doctor, a former Africa hand fascinated by diseases of the developing world. He had a humble respect for flu and little patience for politics. But he’d have to tend to both. Oshitani set out to assess the extent of the outbreak and negotiate with the Vietnamese government over permission for a larger team. He insisted that his investigators be allowed into the field. But the Vietnamese health ministry, wary of outside meddling, was reluctant to oblige.
“Avian influenza could be much worse than SARS,” he admonished the skeptical officials. “If this avian influenza becomes a pandemic, it could infect two billion people. Millions of people would die.”
It wasn’t just a line. He personally thought he could be seeing the start of a global outbreak. Oshitani had already helped the world dodge one epidemic by steering Asia’s response to SARS. “Hitoshi suddenly came alive again,” an associate in the regional headquarters recounted. “For people like him, this is what life is about: crises. He immediately understood the implications.” When Oshitani warned that avian flu could dwarf SARS, his exhortation sent shudders through his WHO colleagues. But it also had the desired effect on the Hanoi government.
With the door cracked open, Tom Grein was urgently detoured to Hanoi from a WHO mission in southern China. Grein, who would team up two years later with Uyeki to investigate the Ginting family cluster in Indonesia’s North Sumatra province, became in essence the agency’s player-coach in Vietnam. His was an all-star roster of epidemiologists, virologists, lab technicians, clinical specialists, and veterinary, logistics, and public-affairs experts that would eventually total nearly a hundred personnel. Finally, as part of this international effort, Uyeki and Fukuda were bound for Vietnam along with five CDC colleagues.
Uyeki quickly peeled off into the field. Fukuda remained in the capital, helping set up a command center in a conference room just off the entrance to WHO’s office in downtown Hanoi, and from there he helped direct the response. “We’re not sure what’s going on,” Fukuda recalled, “and we have to sift through this pretty quickly.” He pressed Vietnamese health and agriculture officials to cooperate, to share their intelligence about the outbreaks and ramp up efforts to contain them. “Don’t be lulled into a sense of false confidence about small numbers,” he urged in meeting after meeting. Though only a handful of human cases had been detected so far, the country could be at jeopardy.
Fukuda’s counsel carried weight. He had unique credentials as a veteran of the Hong Kong outbreak in 1997. Yet these dynamics were different. The Vietnamese were not open to the kind of close partnership he’d established with Hong Kong’s health director, Margaret Chan, which had been central to success. The international team itself was also different, larger and more unwieldy than the exclusively American one he’d led six years earlier. But the outbreak itself looked very similar. Again, it was mostly birds infecting humans. In urban Hong Kong, the source had been markets. Here in rural Vietnam, it was mainly farms. Still, for Fukuda, the killer was no longer a stranger but a known assailant.
The cases continued to come, the pace quickening. Healthy, mainly young victims kept turning up with breathing problems, rising fevers, and tumbling white blood counts. Many had diarrhea. Most died. By the third week of January, the virus had opened a second front in the south of Vietnam with initial cases in a young girl and teenage boy. Poultry outbreaks were also accelerating, proliferating faster than Vietnam could slaughter its afflicted birds and extending throughout the region. Under pressure from Prasert Thongcharoen, Thailand finally stopped its dissembling and confirmed both human and poultry outbreaks. By the first of
week of February 2004, four more Asian countries had reported infected flocks: Cambodia, China, Laos, and Indonesia. Most of these countries had never been struck by any strain of avian flu before. Never had a highly lethal bird flu strain sparked as many outbreaks at once.
Each evening Pascale Brudon, the WHO’s chief representative in Vietnam, gathered team members in the command center to compare notes and briefly unwind. The workload was tremendous, the days long, and the nights late. Yet it didn’t seem to be enough for Geneva. “We had all of this pressure,” Brudon said, “a lot from headquarters from Stohr, saying that this was going to be a terrible epidemic and it was going to be like Spanish flu.”
The boy’s mother was stumped. So was his grandmother. The thirteen-year-old had been among the very first in southern Vietnam to succumb to this new disease. Yet there had been nothing noteworthy about his habits. The women told Uyeki they didn’t keep any poultry in their home. In fact there weren’t even farms in this suburban enclave of Ho Chi Minh City, the former southern capital still known by most of its denizens as Saigon.
Uyeki had followed the outbreak south, remaining just a week in Hanoi before decamping to Ho Chi Minh. He had tracked the virus to the boy’s home, determined to find the source of infection. “They had no idea what this kid did,” Uyeki said later. “Because, like a normal kid, aside from school, they’re playing. It’s not unusual for a parent or grandmother to have no idea what this kid does after school.” Uyeki could find no evidence of exposure to birds, much less sick ones. Nor was anyone else in the family ill. Could the virus now be lurking somewhere else? Perhaps in a new, undiscovered lair?
Sometimes, on disease investigations, fortune breaks your way. As Uyeki and his colleagues filed out of the family’s home, they were an odd sight, a band of strangers in masks. Quickly, curious neighbors started congregating. They showered the investigators with questions. Then Uyeki started doing the asking.
“Oh, yeah,” one neighbor piped up. “That kid, every day after school, he participates in cockfighting.”
Uyeki’s ears perked up. “Where?” he asked.
The neighbor led them down a narrow, paved street. After a couple of hundred yards, they came upon three or four woven baskets on the roadside, each containing a rooster. A little farther they found several more roosters and then a few more beyond that. This was the staging ground for the fights.
“We found out that this kid, along with other boys, every day after school he’d actually hold the cocks,” Uyeki later reported. “So that’s pretty good contact. If you’re holding the rooster, the rear end or the feathers are pretty close to your face. That is what we believed was his risk.” With this discovery, Uyeki had become the first to identify the threat posed by cockfighting, a popular pastime that over the coming years would be repeatedly implicated in bird flu deaths across Southeast Asia.
Other times fortune breaks against you. Days later, Uyeki and his Vietnamese colleagues pulled into a rural village in Tay Ninh province, about fifty miles northwest of Ho Chi Minh City, to investigate the case of a seventeen-year-old girl who had died of bird flu in a local hospital. They parked their van down the dirt road from her home. Chickens foraged in the dust. Pigs grazed on the roadside. Then, dressed in full protective gear, including baby blue disposable aprons and pants, masks, goggles, shower caps, gloves, and rubber shoe coverings, the team got out of the van and slowly approached the house.
But as they did, they discovered they weren’t the only strangers in town. A Vietnamese television crew had also turned up to interview the family. A crowd was forming.
The girl’s mother and grandmother were sitting in the doorway of their home, little more than a shack of bamboo and metal. They spotted the TV crew. They spotted the group of what could only have looked like space aliens. And the grandmother began to shriek. She was afraid. She was resentful of the intrusion at a time when the family was grieving.
But Uyeki wondered whether there was something more. He asked his translator what the old lady was saying. She was shouting over and over that her granddaughter had died of natural causes, insisting there was nothing untoward about the death. Uyeki suddenly realized the histrionics were meant for her neighbors. “She was trying to reassure them and also trying to deflect any potential stigma,” he concluded. The family was terrified of being ostracized if fellow villagers believed they were infectious or, even worse, cursed. The investigators retreated, deciding the family should be left alone.
As long as the cases were coming one at a time, WHO felt confident that a pandemic virus had not yet broken loose. Each isolated human case was a dead end for the pathogen. Then investigators began to hear about the wedding party.
In late December 2003, a family in the northern province of Thai Binh, a verdant, rice-growing region in the Red River delta, had gathered to prepare for a marriage. On January 3 the couple wed. Four days later, the thirty-one-year-old groom started having trouble breathing. He died in the intensive care unit barely a week after his nuptials. Next his twenty-eight-year-old bride and two younger sisters came down with a cough and fever. Though the wife soon recovered, the sisters were taken to Hanoi, where they were admitted to the tropical disease institute, a six-story cream-colored building on the bustling urban campus of Bach Mai Hospital. Both ultimately tested positive for bird flu.
Bach Mai was already associated with tragedy. In the waning days of 1972, U.S. B-52s had leveled the hospital during a withering aerial campaign against North Vietnam that came to be known as the Christmas bombing. At least thirty people inside Bach Mai were killed in an attack emblematic of the war’s excesses. After the conflict subsided, the hospital was slowly rebuilt, an inch at a time because of unexploded ordnance. Now, a generation later, Bach Mai again commanded the world’s uneasy attention.
Peter Horby went to visit the sisters the day after they were admitted. “They were well,” he recalled. They were walking around and taking the antiviral drug Tamiflu. But soon they started to deteriorate and within nine days were dead.
Horby set out for Thai Binh to learn more about the cluster of cases. “This was the first time we could investigate something like this,” he said. “Everyone was wondering whether it was human-to-human.” He interviewed the mother of the three victims. It was a tough conversation. She was distraught. He questioned neighbors. He tried to reconstruct the chain of events and scrutinized the timing of the cases to see whether everyone could have conceivably contracted the disease from the same, single source.
He learned that one sister had handled a duck while cooking. But she had not personally butchered the bird, considered a practice with a high risk of infection, and in any case the duck had seemed healthy. The bride and the other sister had no such exposure at all. There were no birds around their house or, for that matter, in their immediate neighborhood. They lived in town, not on a farm. But the sisters had cared for their ailing brother who, though never tested, almost certainly died from the disease. Horby deduced that the sisters had likely caught the virus directly from him.
Horby drove back to Hanoi and presented his report. The findings were explosive, especially because WHO had been reassuring the world’s media there was no reason to panic as long as there was no human-to-human transmission.
“We really have to be sure,” Brudon told the team members. “We must be really, absolutely sure.”
For several long evenings, they cloistered in the Hanoi command center scrubbing the evidence. The conclusion was clear. “The team was quite convinced after the careful epidemiological investigations done by some members of the team,” Brudon later wrote, “that we were in front of cases of H to H transmission.” She agreed to release the findings.
Almost instantly, Horby said, “the shit hit the fan.” The agency’s upper echelons had not seen the disclosure coming. The next day WHO’s director general, Dr. Lee Jong Wook, called Brudon. He was furious. He castigated her for endorsing what he thought an ill-considered statement. He said she
had rattled the world for no reason.
Team members in Vietnam were stunned by Lee’s response. They were sure their hard work had uncovered a fateful twist in the evolution of a killer virus, and this was their reward? They concluded that Lee had buckled under pressure from some of WHO’s member countries, notably the Thais. With the virus also circulating in Thailand, that country’s government was sensitive about any suggestion that the strain could become epidemic, fearful of the toll this could take on the economy. Thai Prime Minister Thaksin publicly attacked WHO’s statement about human transmission, calling it bad science. “Normally, the ethics of researchers is such that if there is only a slight possibility of something happening, then they will discuss it among themselves. They will not say anything to the public to raise concern,” Thaksin told reporters, assuring them that “the possibility of human-to-human transmission is 0.00001 percent.”
In subsequent statements WHO adopted a far more reassuring tone, minimizing the significance of what the team in Vietnam had discovered. Three leading researchers based in Vietnam, including the director of its National Institute of Hygiene and Epidemiology, later cited the episode, recounting that “temperatures were running high, and any mention of person-to-person transmission of H5N1 was thought by some to be reckless.” They added, “An air of tension . . . surrounds this disease, particularly in the corridors of power within the international health and political communities.”
WHO would later clarify that “limited” human transmission was not a threat. The concern was “sustained” and “efficient” transmission. But the novel strain had now crossed another barrier. In 1997, it had demonstrated it could jump from animals to people. Back then, investigators in Hong Kong had also suspected that the virus could hop from person to person but never had conclusive proof. Now, nearly seven years later, it had shown convincingly that it could.
