What Will the Next Influenza Pandemic Look Like?

Predicting pandemics might still be impossible, but with millions of lives at stake, researchers are using the latest science and lessons from history to best prepare for the next big one















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The exact likelihood of an H5N1 pandemic moving into humans is still unknown, pointed out Derek Smith, a professor of infectious disease informatics at the University of Cambridge in the U.K. From a scientific perspective, he noted, "one expects that's a low probability, but it's a really high-impact thing to prepare against—it's like preparing against terrorism."

Despite all of the concern about H5N1, scientists are also keeping an eye out for other emerging varieties. With 16 known forms of influenza hemagglutinin (the "H" in the strain name), nine known varieties of neuraminidase enzyme (the "N" in the name), and different subtypes within each type, the potential for new enzymatic combinations—and recombinations—is great.

Even H1N1 is not yet in the clear. Since the 2009 outbreak in humans, H1N1 has become much more prevalent in pig populations, and, currently, "we are seeing quite large numbers of re-assortments," Malik Peiris, of the University of Hong Kong, said at ESWI. And a swine-origin triple re-assortment of the H3N2 strain had recently infected two children in the U.S., the Centers for Disease Control and Prevention in Atlanta reported earlier this month.

But the basic dynamics of how these diseases spread are still being worked out. "We don’t know enough about how they transmit from human to human—whether re-assortments in pigs makes it more likely or less likely" to spread among humans, Smith said.

In addition to shifts in virulence and method of spread, slight mutations in the virus can also lead to major changes in how easily it can be treated. A single-point mutation, for example, can render it resistant to commonly used antiviral medications, such as Tamiflu.

The body enigmatic
One of the most disconcerting things about influenza pandemics, as opposed to the seasonal flu, is their tendency to sicken—and often kill—the young and seemingly healthy. Underlying risk factors, such as heart disease and neurological conditions, have been linked to higher fatality rates. But as Maria Van Kerkhove, of the Imperial College London's (I.C.L.) School of Public Health, found in a survey of global data following the H1N1 pandemic, no chronic conditions were reported among some 40 percent of people who were hospitalized for the flu and then died.

There is a "massive difference in the way people respond" to the same strain of influenza, noted Peter Openshaw, director of the Center for Respiratory Infection at I.C.L. He and his colleagues are studying samples from hundreds of people, many of whom became severely ill from the H1N1 pandemic strain, to look for clues as to why one apparently healthy 40-year-old might wind up in intensive care whereas another will fight the virus off just fine at home. But because too little is known about these varied reactions, the team is looking everywhere: in human and viral genetics, for traces of bacterial infections, and elsewhere for hints about what might release the "cytokine storm" that kills some people, now seemingly at random, Openshaw said.

Unknown origins
The 2009 outbreak of H1N1 caught most people off guard—not in the least, those charged with tracking new flu strains and outbreaks. Especially after the 2003 emergence of SARS in Asia, most pandemic plans were centered on a Southeast Asian or Asian emergence for the next flu epidemic.

Modeling had predicted that a Southeast Asia–based strain would take some two to four months to spread extensively and arrive in Europe and North America about one to three months after that. That delay would give Western countries three to seven months to develop comprehensive treatment and vaccination plans.

When the flu emerged in Mexico, instead, North America endured the peak of the epidemic without a vaccine.

An outbreak's point of origin can also play a large role in determining how quickly a pandemic is detected. Regions such as Africa and some places in Southeast Asia are still lagging in surveillance capabilities, noted Maria Zambon, of the U.K. Health Protection Agency.

To the advantage of epidemiologists and the public, "the severity of a virus will determine how quickly we detect it," Neil Ferguson, a professor of mathematical biology of infectious diseases at I.C.L., said on Tuesday. The 2009 H1N1 virus had already been circulating in Mexico for some months before the full scope of its potential came to light. "We detected the 2009 virus as late as we did just because it was as mild as it was," he noted. And lingering immunity in the older population further reduced its spread. But if the next virus is more virulent and more rapidly transmitted, "we will detect it earlier," he said.

Subsequent analysis of the spread of the 2009 pandemic showed that it matched up with commercial air traffic from Mexico—spreading more rapidly into the U.S. and Spain, which are strongly socially connected to the Latin American country. If an outbreak were to begin in Asia, however, South America is "a great place to be," because there is very little direct air traffic from Asia to the region, Smith noted on Monday. So by the time the pandemic would arrive in force, a vaccine would likely already be available.

Asia is still at the focus of pandemic watchfulness, especially for hints of H5N1 spread. The virus is relatively common among migratory birds, which it usually does not sicken. As Osterhaus noted, "dead birds don't fly," so the well ones that still carry the disease are free to travel, infecting other flocks—and domestic poultry as well. It can also be spread via human activity, with exports of birds, feathers and other related products.

A recent study of the H5N1 virus in Laos found that some 0.6 percent of ducks sampled showed traces of the infection. And in places like Laos, where local poultry markets facilitate the movement of fowl around the country, the spread of the infection is of great concern to local and foreign health officials. The country has seen a documented outbreak of H5N1 every year since 2006.

Surveillance of the virus has been ramping up throughout Southeast Asia. In Bangladesh, for example, backyard farms predominate, putting fowl in close contact with both humans and migratory birds, so spread to the dense human population is of particular concern. "Bangladesh is in the front line now," explained Syed Ahmed, of the University of Southern Denmark.

Preparing for the unpredictable
With the virus mutating in the dark, hidden cells in billions of birds, pigs and other animals, tracking their changes might seem impossible. "If we're going to [create] the best interventions that we can, we need to understand how they circulate around the world," Smith said of flu viruses. Surveillance of animal populations worldwide has improved vastly in the past decade, boosting the chance that scientists will spot new potentially dangerous mutations early.



9 Comments

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  1. 1. Torchlake 12:58 PM 9/19/11

    Wouldn't it be prudent to keep the pressure on the public to be repaired as best we can. Example..Does a hepa-filter in a confined area be effective in creating a somewhat safe area? Should the public have face masks? The CDC has a nice web-page on these matters? Try reading "The Great Influenza" This is a real eye opener as to what will occur....! not IF...WHEN!






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  2. 2. ASHIK 01:14 PM 9/19/11

    It is a never ending fight with mutating viruses for sure.Preparation to fight against next flu attack could only be possible if scientists can predict it accurately and in advance.Lets hope we win every single time virus attacks in the future.

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  3. 3. mr2sheds 01:46 PM 9/19/11

    I think you are missing the real story here...FERRETS?

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  4. 4. biomedical 06:04 PM 9/19/11

    Health experts and CDC scientists seem to all agree that "it is not if, but when a real, large scale pandemic will occur," and Public Health officials are realizing that front-line respiratory protection is critical. I keep hearing people as … "will we be prepared?" Bio-Medical, http://www.maxair-systems.com

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  5. 5. rumyan 10:17 AM 9/20/11


    The 2009 pandemic of influenza A H1N1 has been relatively mild. It killed about one in 10,000 people who came down with it. The pandemic claimed near14,000 lives across the globe i.e. less than 0.0002% of world population. The most basic question that arises immediately - why 0.0002% of healthy people died of the flu and others 99, 999% did not. This question is most basic and it must be answered first of al. Unfortunately, the experts cited in the discussed letter don’t focus their attention on relevant traits of most susceptible human individuals. They continue to exploit infertile idea of prevalent value of virus mutations. What is more, they ignore the observations and technologies evidenced genetic nature of individual differences in human susceptibility to influenza has been published in the article “Genetic immunity and influenza pandemics” (FEMS immunology and medical microbiology 2006;48:1-10) and in the book “Hereditary Immunity: Fundamental Principles and Exploitation in Life Study and Health Care” (New York: Nova Biomedical Books, 2008).
    .

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  6. 6. bucketofsquid 04:17 PM 9/23/11

    So out of curiosity this guy weaponized H5N1 virus and he only had to do a handful of variety combinations and then spread it through 10 hosts before it became airborn and thus weapon suitable. An airborn virus with a 60% fatality rate of infected persons is pretty impressive. I wonder how much he is selling it for.

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  7. 7. rumyan 05:07 PM 9/23/11

    Dear "bucketofsquid”, the answer to your questions you can find inside of the book entitled "Is Bioterrorism Idea a Delusion or Skillful Swindling?" Puurs, Belgium: UniBook, 2010.


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  8. 8. Wayne Williamson in reply to bucketofsquid 08:25 PM 9/29/11

    reminds me of the movie 12 monkeys....

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  9. 9. JamesRoday in reply to mr2sheds 11:14 PM 1/23/12

    Would you rather... HUMANS?

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