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Winner of the 1998 Francis Parkman Prize from the Society of American Historians for the year's best book on American history, named in 2005 by the New York Public Library one of the 50 "most memorable" books of the preceding 50 years.
Winner of the 2005 Keck Award from the National Academies of Science for the year's outstanding book on science or medicine.
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Influenza




Below are two articles, one from the June 23, 2009, Washington Post, the other from the April 28, 2009, New York Times, which discuss different aspects of the current pandemic.

Pandemic Reality Check
What Can Be Done -- and What Can't -- To Protect Against H1N1

By John M. Barry
Tuesday, June 23, 2009



This month, the World Health Organization finally declared that the new H1N1 virus has become pandemic. Yesterday it reported a big jump in cases and fatalities since Friday. How many people this virus will sicken and kill depends, ultimately, on three things: the virus itself; the impact of what are known as "non-pharmaceutical interventions," or NPIs; and the availability and effectiveness of a vaccine.

The virus will be the most important factor. Influenza is one of the fastest-mutating organisms in existence, which makes it unpredictable, and a virus newly infecting the human population is likely to be even more unpredictable as it adapts to a new environment. There have been four pandemics that we know about in some detail: 1889-92, 1918-20, 1957-60 and 1968-70. All four followed similar patterns: initial sporadic activity with local instances of high attack rates -- just as H1N1 has behaved so far -- followed four to eight months later by waves of widespread illness with 20 to 40 percent of the population sickened. (In a normal influenza season about 10 percent of the population gets sick.) Subsequent waves followed as well.

In all four pandemics, lethality changed from wave to wave -- sometimes increasing, sometimes decreasing. It's impossible to know what will happen this time, but in 1999 the Centers for Disease Control and Prevention modeled a moderate pandemic in the United States, including a vaccine in its calculations, and concluded that the death toll would probably be 89,000 to 207,000. If the virulence of this virus does not significantly increase -- and right now there is no reason to think it will -- something close to the lower number looks probable.

What could help bring about such a best case? Again, the virus is the most important factor, and we have no control over it. But we do have non-pharmaceutical interventions and the possibility of a vaccine. Such interventions would come into play primarily in a moderate or severe pandemic. For a mild one, we may not need to take steps beyond washing hands, exercising "cough etiquette" and keeping the sick at home. But if the virus increases its virulence, other measures, such as closing schools, urging people to telecommute and even banning public meetings, could mitigate the impact.

However, the usefulness of non-pharmaceutical interventions is limited, and even if they work, their chief impact will be to flatten the pandemic's peak and stretch out the duration of a wave of illness to make it easier to handle. Consider: Those telecommuting are likely to run into Internet capacity problems, while the impact of closing schools -- aside from the burden that creates on working parents and their employers, or on children who get good meals only at school -- depends on how much kids congregate while out of school. And sustaining compliance will be both important and difficult. Scholars Bradley Condon and Tapen Sinha found that in Mexico City this spring, when the government advised wearing masks on public transportation, compliance peaked at 65 percent three days later -- but declined to 26 percent only five days after that. This decline came even as the government was taking the extreme measure of closing all nonessential services and businesses. Such behavior does not portend well for sustained compliance with any measure.

Anti-viral drugs will be of some help-- as long as the virus does not develop resistance-- but the most important human intervention is, of course, a vaccine. There are many unknowns: Because influenza mutates so rapidly, a new vaccine has to be made each year just for seasonal flu. Vaccines for most diseases approach 100 percent effectiveness, but a good flu vaccine is 70 percent effective; a great one is 90 percent effective. The vaccine in the 2007-08 flu season was only 44 percent effective. Hitting the "good" mark for a new virus that may be changing even more rapidly than seasonal flu will be difficult.

Supply is another problem. In a best case, enough vaccine for the entire U.S. population could be available by October as long as an adjuvant is used to simultaneously stimulate the immune system, which lessens the need for antigen from the virus itself. However, if the virus used to make vaccine grows slowly, or if a dose requires more antigen than seasonal flu, or if two doses are required to provide protection, producing that much vaccine could easily stretch deep into 2010. In addition, only about 30 percent of the supply will be made in the United States. The more virulent the virus, the more likely it is that foreign governments will refuse to allow export of the vaccine until their own populations are fully protected.

Meanwhile, the emergence of the H1N1 virus in no way lessens the threat from H5N1, more commonly known as bird flu. And the same day the World Health Organization declared H1N1 a pandemic, Egypt announced 25 new human cases of H5N1 -- the largest number yet identified in a single day.

The bottom line? Little can be done in the short term beyond exerting diplomatic pressure to guarantee that foreign governments allow manufacturers to honor contracts to export vaccine. In the medium term, sustained investment in vaccine production technologies -- especially recombinant ones -- could make it possible to produce massive amounts of vaccine in a few weeks. In the long term, we need a vaccine that works against all influenza viruses. Enough work has been done to suggest that this Holy Grail is achievable. Had influenza been taken seriously for the past 30 years, we would probably have one by now. No matter what happens over the next year or two, that's one history lesson we need to learn.









April 28, 2009, New York Times

Where Will the Swine Flu Go Next?

By JOHN M. BARRY
New Orleans

AS the swine flu threatens to become the next pandemic, the biggest questions are whether its transmission from human to human will be sustained and, if so, how virulent it might become. But even if this virus were to peter out soon, there is a strong possibility it would only go underground, quietly continuing to infect some people while becoming better adapted to humans, and then explode around the world.

What happens next is chiefly up to the virus. But it is up to us to create a vaccine as quickly as possible.

Influenza viruses are unpredictable because they are able to mutate so rapidly. That capacity enables them to jump easily from species to species, infecting not only pigs and people but also horses, seals, cats, dogs, tigers and so on. An avian virus responsible for the 1918 pandemic jumped first from birds to humans, then from humans to swine (as well as other animals). Now, and not for the first time, pigs have given a virus back to humans.

Mutability makes even existing, well-known flu viruses unpredictable. A new virus, formed by a combination of several existing ones as this virus is, is even less predictable. After jumping to a new host, influenza can become more or less virulent — in fact, different offshoots could go in opposite directions — before a relatively stable new virus emerges.

Influenza pandemics have occurred as far back in history as we can look, but the four we know about in detail happened in 1889, 1918, 1957 and 1968. The mildest of these, the so-called Hong Kong flu in 1968, killed about 35,000 people in the United States and 700,000 worldwide. Ordinary seasonal influenza, in comparison, now kills 36,000 Americans a year, because the population has a higher proportion of elderly people and others with weak immune systems. (If a virus like the Hong Kong flu hit today, it would probably kill more people for the same reason.)

The worst influenza pandemic, in 1918, killed 675,000 in the United States. And although no one has a reliable worldwide death toll, the lowest reasonable number is about 35 million, and some scientists believe it killed as many as 100 million — at a time when the world’s population was only a quarter of what it is today. The dead included not only the elderly and infants but also robust young adults.

What’s important to keep in mind in assessing the threat of the current outbreak is that all four of the well-known pandemics seem to have come in waves. The 1918 virus surfaced by March and set in motion a spring and summer wave that hit some communities and skipped others. This first wave was extremely mild, more so even than ordinary influenza: of the 10,313 sailors in the British Grand Fleet who became ill, for example, only four died. But autumn brought a second, more lethal wave, which was followed by a less severe third wave in early 1919.

The first wave in 1918 was relatively mild, many experts speculate, because the virus had not fully adapted to humans. And as it did adapt, it also became more lethal. However, there is very good evidence that people who were exposed during the first wave developed immunity — much as people get protection from a modern vaccine.

A similar kind of immune-building process is the most likely explanation for why, in 1918, only about 2 percent of those in the developed world who contracted the flu died. Having been exposed to other influenza viruses, most people had built up some protection. But even in the west, some population sub-groups suffered disproportionately. Metropolitan Life Insurance Company suggests that case mortality for industrial workers ranged from 8% to 12%. People in less developed regions of the world, but also including such isolated parts of the U.S. as American Indian reservations and Alaskan Inuit villages, had even higher case mortality — presumably because they had less exposure to influenza viruses.

The 1889 pandemic also had a well-defined first wave that was milder than succeeding waves. The 1957 and 1968 pandemics had waves, as well, though mortality differences between the waves were less well defined.

In all four instances, the gap between the time the virus was first recognized and a second, usually more dangerous wave swelled was about six months. It will take a minimum of four months to produce vaccine in any volume, possibly longer, and much longer than that to produce enough vaccine to protect most Americans. The race has begun.

John M. Barry, Distinguished Scholar at the Center for Bioenvironmental Research at Tulane and Xavier Universities, is the author of “The Great Influenza.”