Story URL: http://news.medill.northwestern.edu/chicago/news.aspx?id=130163
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Pandemic or paranoia? Handicapping the swine flu
by Michael Scott Leonard
May 19, 2009
Michael Scott Leonard/MEDILL
Michael Scott Leonard/MEDILL
Many Chicago residents say the media hyped the threat of swine flu, which they see as a passing illness likely to be no worse than seasonal influenza.
After all, there is always a plague coming. When Cohen wrote those words, in 1988, it was the blossoming AIDS epidemic, and the years since have seen multi-drug resistant tuberculosis, SARS and anthrax, to name just a few of the diseases that have triggered widespread fear.
Today's problem pathogen is the H1N1 influenza virus, which probably evolved in pigs and leapt into the human population on or near a Mexican hog farm some time in March. And at first blush it appeared to be moving fast indeed.
By late April, when epidemiologists began untangling suspected cases of H1N1 from what Mexican authorities had initially considered an unusually virulent incidence of late-season flu, the illness formerly known as swine influenza had reportedly killed more than 150 people around Mexico City, where it had sickened thousands more, and spread to several U.S. states and countries around the globe.
As of Tuesday, swine flu had been diagnosed in 47 states and the District of Columbia, as well as 40 total countries. And Friday, a CDC official estimated that “upwards of 100,000” Americans may actually have had mild or unreported cases of swine flu.
Yet even as health departments have kicked into overdrive, the flu’s apparent mildness has jitters over the latest Public Enemy No. 1 starting to subside. Schools are reopening, and the Centers for Disease Control and Prevention has revised its guidelines so that they no longer recommend shuttering schools where swine flu is detected. H1N1 has killed only five Americans, all suffering from medical conditions that predisposed them to severe influenza complications. (A Mexican toddler who died last month in Texas became the first official U.S. fatality of six total.)
What was hyped three weeks ago as an existential threat now looks like the plain old flu — familiar foe of the frail, the sick and the elderly but hardly an apocalyptic menace.
Still, public health officials — such as acting CDC director Richard Besser, quoted in an Associated Press story — are proclaiming that we “dodged a bullet.” And with many experts still insisting it’s only a matter of time before a virulent new strain of flu emerges to ignite a pandemic, the question remains: Did we dodge a bullet — or just imagine one?
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Like the H1N1 virus currently circling the globe, the 1918 “Spanish Flu” probably arrived in March, when American soldiers stationed at Fort Riley, Kan., began coming down with flu-like symptoms. Although commercial aviation was still more than a decade away, the troop movements and international trade required to wage World War I ensured that the disease spread quickly around the globe.
By the time that flu re-emerged in August for its “second wave,” it had mutated into the deadly strain that would claim somewhere between 20 million and 100 million lives worldwide, and more than 500,000 in the United States, over a little more than two years — an outbreak Philip Alcabes, an epidemiologist and urban public health specialist at Hunter College in New York, called “the single worst short-term disease event in all of American history,” likening it to the Black Death that killed at least a quarter of Europe’s population between 1347 and 1351.
“There’s been no other event where so many have died in such a short time,” Alcabes, author of last month’s timely “Dread: How Fear and Fantasy Have Fueled Epidemics From the Black Death to Avian Flu,” said last week.
What separates serious pandemic strains like 1918’s from seasonal flu is their tendency to reshuffle the influenza death curve. Whereas seasonal flu is deadliest to the very old, the very young, the immune-compromised and those with pre-existing lung conditions, pandemic-grade influenza can kill or seriously sicken even young, robust adults.
Sometimes, as in 1918, such strains actually hit the young and healthy harder than they do the elderly. That pattern emerges when a strain of influenza is novel — different enough from any virus our bodies have encountered that our immune systems don’t recognize it. Viral novelty can lead to a response known as a cytokine storm: a massive immune reaction that may result in fatal complications such as severe pneumonia.
“Pandemics occur when a virus that human immune systems have never seen is released,” said Michael David, an infectious disease fellow at the University of Chicago and a historian of medicine. “When people get exposed to influenza, they basically gain long-term immunity, and that’s one reason why people think not as many elderly people died in 1918 — because there had been a pretty bad pandemic in 1889-90. Many people think [the virus responsible] provided at least partial immunity to people who were alive then and in 1918.”
David said novelty is a crucial pandemic prerequisite because influenza viruses require low rates of herd immunity to spread rapidly in a population: People with immunity suffer fewer severe virus-spewing symptoms such as coughing and sneezing. In effect, they become epidemiological dead ends rather than hubs of viral transit.
“If so many people have been infected by it already, [a virus] can’t really get up and go,” David said. “It can no longer rip through a population, finding people who may be genetically predisposed.”
Novel H1N1 probably doesn’t fall into the latter category — it appears to have a substantial enough foothold in the human population that the CDC warned recently it could emerge as a new seasonal strain — but, notwithstanding the rash of early cases in Mexico, it doesn’t yet seem deadlier than seasonal influenza or as contagious as the Spanish Flu, though the CDC has said it appears more transmissible than the seasonal flu.
“It’s acting in kind of an odd way,” David said. “It hasn’t exploded on the scene like the 1918 pandemic.”
Alcabes described worries over a 1918-level body count as overblown, cautioning people against “responding to an imagined scenario as much as, maybe in some cases more than, the facts in front of them.”
“In the annals of flu, this is a mild event,” he said.”
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Swine flu’s relatively benign nature may indeed make the 1918 pandemic — often considered the “grandfather” of modern influenza — a poor analogy. Still, studying the “Great Pandemic” can be instructive for several reasons.
First, the damage it wrought — infecting by some estimates up to a third of the globe and killing about 3 percent of the sick — etched the worst-case scenario into the popular consciousness. Nearly a century later, the term “pandemic” continues to conjure the astronomical lethality associated with 1918 despite much milder events in 1957-58 and 1968-69.
Second, the 1918 flu, like the swine strain now before us, was an H1N1 virus. In this sense, the “grandfather” conception is almost literal. That flu — an avian virus that continued to circulate, with dwindling deadliness, through most of the 1920s — is the genetic ancestor of today’s H1N1 influenzas, including both the common seasonal strains and the swine flu.
Finally, the virus responsible for Spanish Flu is the earliest strain to have been isolated and identified.
“1918 is the earliest influenza for which we have retrieved genetic information from people who died of the disease,” David said. “We can say for sure that in 1918, it was the influenza virus that we know now.”
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But influenza has surely been with us far longer than for the 90 years since Spanish Flu tore through the world in the waning months of World War I. In fact, human influenza may be nearly as old as animal husbandry, though it’s impossible to trace through history with any certainty because many of its symptoms are common in other viral infections.
“Influenza may have started to become endemic in people when they started to domesticate pigs and birds,” David said. “Some people have estimated that in China and the Middle East, we’re talking about 5,000 B.C.”
Grasping the significance of livestock to the ongoing co-evolutionary arms race between humans and the flu requires some understanding of the molecular mechanisms of viral evolution, as well as of influenza’s patterns of transmission both within and between different populations.
“Outbreaks like the current one serve to remind us that nature is constantly evolving both attacking viruses and host defenses,” said Tom Slezak, associate program leader for informatics at the Lawrence Livermore National Laboratory, a Department of Energy facility in Livermore, Calif., that recently produced a paper studying the correlation between influenza genotypes and virulence. “Our sampling of both wild and domestic livestock reservoirs could be better, in terms of monitoring what must be an incredible variety of re-assortments and mutations that are being generated.”
Influenza mutates by a process known as “reassortment,” or, more colloquially, recombination. It’s an RNA virus, which means that when reproducing, influenza can borrow genetic material from other strains of flu infecting the same cell and “recombine,” a function that helps it evolve faster than simple selection of the fittest genes would allow.
David said molecular recombination of flu viruses is likely rare in humans, who usually don’t catch simple, un-mutated avian or swine influenzas. But it can occur in birds, who have evolved to carry many strains of avian flu without showing symptoms and can also contract human influenza. And it’s most common in pigs, known as “mixing vessels” for their ability to catch human, avian and swine flu — sometimes all at once.
Greg Dwyer, a University of Chicago epidemiologist who studies viral evolution, said populations of domestic pigs and birds serve as “an evolutionary laboratory in which natural selection can act on influenza strains in a way that’s unhindered.”
“Clearly, we’re going to intervene against swine flu in human populations,” Dwyer said. “We’re going to have social distancing measures, and, if we stop the spread, that’s going to be an evolutionary dead end for the disease. But we’re never going to be tracking livestock populations as closely as humans. It’s just not worth the money.”
Without close monitoring, influenza continues to evolve in animals until natural selection inevitably produces a virus that can sicken humans. And, if we’re particularly unlucky, conditions in the new flu’s first human hosts will nudge it toward both virulence and transmissibility, the two hallmarks of any pandemic virus.
“There could be influenza strains that are infecting livestock that with one more mutation will be able to jump into humans,” Dwyer said. “Given enough time and enough bad luck, a strain will evolve that can infect both livestock and humans.”
David laid out several unlikely conditions a novel flu strain would have to meet before it could jump from an animal reservoir to spark a pandemic: It has to be novel, contagious between humans and pathogenic (disease-causing).
“And the fourth condition is that it has to arise in a place where a person is going to catch it from an animal,” he said. “That virus has to be very special.”
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Critics have been quick to blame swine flu on agribusinesses’ housing of pigs in overcrowded facilities — which David likened to “pig cities” — they say can catalyze influenza transmission and, consequently, increase the odds of virulent mutation. Alcabes called that line of attack “silly.”
“It’s naive to think eliminating factory hog farms would make life perfectly safe, flu-wise,” he said. “By that logic, we need only go back to the middle ages for perfect public health.”
The Web site of the National Pork Board, www.pork.org, prominently features a letter from its president, Steve Weaver, assuring U.S. swine farmers that no H1N1 has been detected in any U.S. pork.
But “I have stepped up the bio-security measures at my Elk Grove, Calif., farm, and I urge you to do the same at your operation,” Weaver’s letter says.
Dr. Hans Stine, an animal nutrition specialist at the University of Illinois at Urbana-Champaign, said that in his experience, “I think it’s up to the individual farmer or producer to decide what kind of bio-security they want.”
The National Pork Board Web site links to downloadable bio-security guidelines, which it calls “recommendations.” The list includes strictly enforced sick leave for flu-symptomatic employees, limiting non-employee contact with hogs, mandating showers for entering employees, conscientious hygiene on farms and flu vaccines for employees.
Spokeswomen for the National Pork Board failed to respond to calls and e-mails seeking further information about industry standards and policies.
But David, who stressed that he is “not a veterinarian and not a pig farmer,” said he thinks factory farms have too much invested in the health of their hogs to let influenza spread through their herds. And he added that for swine viruses to acquire the ability to infect and spread among humans, pigs would need enough regular contact with people to contract human influenza, a consideration he said probably makes factory hog farms less likely amplifiers of a human influenza epidemic.
“That would suggest that the ‘pig city’ issue would actually be far outweighed by the human-proximity and poverty issues leading to the potential for novel influenza viruses to arise,” he said.
Clare Narrod, senior research fellow at the International Food Policy Research Institute and former food economist for the U.S. Department of Agriculture, also fingered pervasive poverty and pre-modern agricultural techniques in the developing world as the more likely culprit than industrial farms.
“For many of these countries, there aren’t enough animal health workers to maintain surveillance and ensure disease management,” Narrod said. “In many countries, the private sector has such services in their large operations, but the poor do not always have access to such services. This is particularly a problem for smallholder flocks.”
Stine was quick to point out that the only pigs to have tested positive for H1N1 caught it from a sick employee on a hog farm in Ontario, Canada. But both David and Dwyer said that biologically speaking, H1N1 was most likely to have developed in pigs because it contained elements of swine strains, to which birds and humans are not usually vulnerable.
“Humans are capable of being infected mainly by human influenza, birds by avian and human strains,” David said. “The pig is capable of being infected by human viruses and by bird viruses and by pig viruses.”
The H1N1 virus contains contributions from all three.
View Anatomy of a pandemic? Swine flu geography in a larger map
When swine flu began its headline-making run through Mexico City, it looked fearsome. On April 24, the Friday major American news media first devoted substantial space to the story, Mexican authorities were already reporting as many as 60 deaths from the novel virus, which seemed to have materialized out of thin air. By that Tuesday, one day after the World Health Organization had raised its pandemic alert level to Phase 4, Mexican officials said they suspected the virus in 159 deaths and of sickening about 2,000 people. (That death toll has since been revised back downward, to 72 at last count.)
Meanwhile, the number of U.S. cases continued to grow. That Sunday, April 26, New York City closed two schools after confirming eight cases of swine flu in their students. (That cluster, the largest in this country at the time, jumped to more than 40 cases the next day after additional testing.) The following day, a Notre Dame student brought H1N1 to Illinois’ doorstep as the total number of confirmed U.S. cases reached 64. By April 29, swine flu had reached Chicago.
As of Tuesday, the CDC is confirming more than 5,400 cases across 47 states and the District of Columbia, including 707 in Illinois (now the second-most-infected state, after Wisconsin). WHO has reported nearly 10,000 cases in 40 countries. Schools continue to close, people continue to fall ill, and the number of dead continues to rise, slowly but steadily, as the frail and immune-compromised inevitably succumb to the new flu.
But apart from what appeared to be an alarming pattern of virulence in the early wave of Mexico City cases, H1N1 has not proven as deadly as first feared. Outside Mexico, only three countries — the United States, Canada and Costa Rica — have seen a total of eight swine flu fatalities out of more than 6,000 confirmed cases. And no one knows quite why.
“With the exception of the outbreak in Mexico, which is still not fully understood, the H1N1 virus tends to cause very mild illness in otherwise healthy people,” a statement on the WHO Web site reads.
David expressed some skepticism that the H1N1 fatality rate had declined at all, whether on account of viral mutation or due to externalities such as the quality of health care or water, saying “we have no idea how many people were really affected.”
Dwyer agreed that the strain was unlikely to have evolved substantially in such a short period of time and that any appearance of declining virulence probably amounted to just that — appearances.
“That kind of change, the changes that have occurred since this thing started spreading, since it became more or less worldwide — I don’t think those are going to be big enough to make a difference,” he said. “I’d be surprised if it’s changed much.”
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In policy, as in life, the don’ts are often more straightforward than the dos. Stipulating, then, that we shouldn’t overreact in harmful ways to the potential threat posed by pandemic influenza, we are left to ask how we should react — or at least how, or even whether, we should prepare for the possibility.
“A central question in public health around flu, given that 1918 was so horrible, becomes: Do you prepare for the unlikely worst-case scenario, or do you prepare for the much more likely not-so-bad thing?” Alcabes said. “That’s a real problem question. I want to recognize that dilemma for public health officials.
“But I would argue that the real dilemma for planning is that we just don’t know what’s going to happen,” he said. “A lot of flu scientists disagree with me about that.”
Count both the CDC and WHO among them. Besser, addressing the media May 6 at one of his near-daily news conferences, warned that he “would be surprised if we don’t get to” Phase 6, the WHO pandemic alert level that signifies “a pandemic is under way.”
His colleague, respiratory expert Dr. Anne Schuchat, said Monday that H1N1 could be far deadlier when it re-emerges in the fall for its second wave, whether as a pandemic or a seasonal flu.
“I think there’s a perception out there that we’re winding down, that we’re in a lull,” she said. “It’s a time when we really need to guard against complacency as we move into a new normal. We think this virus is present in our communities and it’s actively circulating, and we don’t know what will happen come the fall.”
The WHO Web site aired a few of the more troubling possibilities — for instance, that H1N1 could mutate after encountering seasonal strains of influenza during the southern hemisphere’s fall flu season, now beginning, or that too much success at containing the virus this spring could lead to dangerously low rates of herd immunity when the virus returns for a second run in the fall.
WHO also raises the specter of exactly the sort of nightmare scenario people are beginning to feel silly for having worried over when swine flu first cropped up.
“The fact that the H5N1 avian influenza virus is firmly established in poultry in some parts of the world is another cause for concern,” the statement says. “No one can predict how the H5N1 virus will behave under the pressure of a pandemic.”
To help lower the risk of a fall pandemic, research is under way — including at Baxter International Inc., the Chicago-area medical-supplies giant — into an effective H1N1 flu vaccine, which experts say could be ready in time for the northern hemisphere’s fall flu season. But no one knows exactly how effective any vaccine might prove as the virus mutates.
Dwyer said vaccines put selective pressure on influenza to evolve, though it’s impossible to predict whether it will evolve toward virulence or mildness.
“If a high fraction of people are vaccinated against a particular strain, then that strain is going to go down in frequency and some other strain is going to arise,” he said. “Whether that new strain has a stronger effect on humans is something you can’t really say a priori. But it’s worth it for people to get vaccinated, because you never really know.”
David said it’s hard to know what effect vaccines have had on influenza’s long-term evolution due to the daunting number of variables.
“Historically, it looks like there were about five or six pandemics per century,” he said. “So the 20th century, in which there was vaccination, actually saw fewer pandemics than previous centuries did on average” — just three.
“Whether that has anything to do with the fact that many people were immunized in the last half of the century — I just don’t know,” David said.
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With so much still unknown, there are no obvious silver bullets in the fight against a flu pandemic that remains, for now, unrealized. The best course of action, as we try to toe the line between overreacting and leaving ourselves vulnerable, probably involves an emotionally unsatisfying combination of vigilance, vaccination and a sense of perspective.
“We have to remember that there is no risk-free life,” Alcabes said.
