Alan Sipress - The Fatal Strain

“We thought that it appeared there really could be some changes going on,” Fukuda said. “We were in that sort of gray area of understanding. Even if you have enough data to suggest, you don’t have enough data to tell you really what’s going on, and you need help interpreting.”

Fukuda and his colleagues pressed for a wider review of the evidence, and WHO scheduled a private conference for the first week of May, just ten days after the mission left Hanoi. It was to be held in Manila, the Philippine capital and home of the agency’s regional headquarters. WHO summoned staff from Geneva and across Asia. Senior government health officials from Vietnam, Thailand, and Cambodia were pulled in, as were outside specialists from the United States, Japan, Britain, and Australia. Leading laboratories, in particular the CDC in Atlanta and the National Institute of Infectious Diseases in Tokyo, were also asked to prepare genetic analyses of H5N1 specimens so these could be compared with the pattern of cases in the field.

“We called for the consultation knowing that it was a lot of trouble to bring a lot of people in rather quickly, but on the other hand these weren’t academic questions,” Fukuda recounted. “If there really was a change going on, we really wanted to try to come to grips with that as quickly as possible.”

For two days, the experts cloistered in Manila and sifted the evidence. Afterward the agency issued a report that cited the shifting patterns of infection in northern Vietnam, including a wider age range of victims, more and larger clusters involving cases over a longer period of time, cases without symptoms, and a declining mortality rate. The document said this was all consistent with the possibility of human transmission and greater infectiousness.

It also detailed genetic changes in viruses isolated in northern Vietnam. One mutation involved the place on the virus where it binds to either human or animal cells and could make it easier for the pathogen to infect people. Another change was near a site related to the lethality of the virus. The report also revealed that a sample from Nguyen Thi Ngoan, the mischievous teen from Thai Binh, showed a mutation that could cause resistance to the antiviral drug Tamiflu. If that change became widespread, it could rob doctors of a vital weapon.

“While the implications of these epidemiological and virological findings are not fully clear,” the report concluded, “they demonstrate that the viruses are continuing to evolve and pose a continuing and potentially growing pandemic threat.”

In the United States concern was mounting. Just three days after the Manila conference, the Central Intelligence Agency sponsored an exercise to model the global impact of a pandemic strain erupting out of an unnamed Southeast Asian country. Participants were drawn from five federal departments, including Defense and Commerce. The conclusions were sobering: economic downturns, international tension, and political instability.

On May 26, two weeks after Nguyen Sy Tuan was finally discharged from Bach Mai Hospital, WHO’s senior communicable disease officer in East Asia, Hitoshi Oshitani, got an alarming e-mail. It was from an epidemiologist in the agency’s Hanoi office. Vietnamese researchers at NIHE had been testing specimens taken randomly at health-care facilities in Thai Binh province. The sampling had not specifically targeted suspected bird flu cases. But 10 percent of the 170 specimens had come back positive for the virus, an exceptionally high proportion.

The results seemed to underscore the frightening scenario mooted in Manila. Even worse, the data lent credibility to separate tests conducted by Canadian scientists in Vietnam, which Oshitani had been hearing about.

Without a word to WHO headquarters in Geneva, he flew to Hanoi to see the Canadian microbiologist responsible for the research, Dr. Yan Li. WHO’s flu hunters in Asia were trying to keep the startling information from leaking out prematurely. “We didn’t want a huge panic with unverified information,” explained Peter Horby, the agency’s lead flu investigator in Vietnam.

Based on their briefings in Hanoi, Oshitani and Horby drafted a confidential report and on Tuesday, June 7, shared its contents with Geneva. They reported that Li, a Beijing-born scientist based at the Canadian health department’s National Microbiology Laboratory in Winnipeg, had begun a project earlier in the spring to help train Vietnamese scientists responsible for flu research in testing and laboratory techniques. As part of the work, the Canadians had sent in their own mobile lab. They began testing nearly two hundred samples previously collected by the Vietnamese. These were blood samples, or more accurately serum, the clear liquid that remains in blood once red and white cells and platelets are removed. The Canadians were using a technique called Western blot that could detect the antibodies that the human immune system produces in response to a bird flu infection. Though the Western blot technique was not entirely reliable, it did not require advanced lab safeguards like other antibody tests and could be done under local conditions in Vietnam.

According to the confidential report, the researchers tested 86 specimens from people with suspected cases of bird flu. About two-thirds came back positive for the telltale antibodies, indicating the patients had caught the bug. Another 101 samples were from people who had had contact with confirmed cases or infected birds. Nearly as many of these, about three-fifths, were also positive.

Separately, the Vietnamese had run tests using a different technique on the samples from the Thai Binh health facilities. Scientists at NIHE had established that 10 percent were positive by using a method that looked for genetic evidence of the virus itself rather than for antibodies. This technique, called polymerase chain reaction or PCR for short, uses special strands of highly sensitive genetic material called primers. Scientists would combine these with the sample and, if they matched, the primers would cause the virus’s own genetic material to rapidly reproduce until there was enough of it to identify.

Finally, the Canadians and their Vietnamese counterparts had conducted an analysis of thirty-eight samples and found that many had specific mutations in the surface proteins of the virus, strongly suggesting it was becoming less deadly. These mutations could help explain some of the milder and asymptomatic cases in Thai Binh and elsewhere in northern Vietnam, such as those of Nguyen Sy Tuan’s sister and grandfather.

The report concluded that the disease could be spreading among people more readily than anyone had thought. Moreover, if most cases were mild or lacked symptoms altogether, identifying those who were infected would prove nearly impossible. Even in hospitals, it would be challenging to recognize bird flu patients and segregate them from others. “Extinguishing a pandemic strain by early identification and targeted use of anti-viral [drugs] and public health measures is not going to be successful,” the document warned.

Klaus Stohr, the influenza chief, was taken aback. But at the same time, there was something about the results that struck him as not quite right. If the virus was already racing across Vietnam, shouldn’t the hospitals be flooded with patients? They weren’t. “It should stick out like a sore thumb,” he thought.

Calling his staff into his fourth-floor office at WHO headquarters on the morning of Thursday, June 9, Stohr said he planned to urgently convene an outside panel of experts to evaluate the information. “We’ll never have perfect data,” responded one of his lieutenants, but added, “We have data sufficient to consider raising the pandemic alert level.”

Stohr began drafting a memo to Lee Jong Wook, the agency’s director general, outlining the arguments pro and con for sounding the global alarm. Raising the alert level would immediately activate steps to contain the outbreak. Stockpiles of antiviral drugs could be rushed to Vietnam and the surrounding region. A warning against travel to Vietnam and nearby countries might follow. Every day mattered. Any delay could hand the disease an even larger head start, potentially costing the lives of untold masses of people.