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The "Spanish Flu" of 1918 killed at least 25 million (and perhaps as many as 100 million) people worldwide, a pandemic in the era before air travel and with a population less than a third of today's. If Avian Flu evolved into a virus of similar infectiousness, the results could be far, far worse. Globe-spanning travel and higher-density urbanization patterns would allow the disease to spread at a rate far surpassing that of the Spanish Flu.

To get a sense of the scale of the problem, check out this map (PDF), showing the "areas of concern" for Avian Flu. The map displays locations of poultry and pig concentrations (pigs can be intermediary vectors for H5N1), along with density of reported cases of Avian Flu in animals and people. As a side-map, it also shows the typical flight paths for migratory water fowl.

But we have tools at our disposal today that medical scientists of a century ago couldn't have even imagined: rapid genome sequencing, collaborative networks for vaccine development, and -- possibly most important -- computer simulations. This week, two teams funded by the US National Institutes of Health published the results of detailed computer models of how a human-transmissible form of H5N1 could spread and the best ways to contain that spread. The results were published in Nature and Science, and have been getting abundant attention in the scientific community. Of the two pieces, the article in Nature is more useful, as the full text is available for free.

Both studies look at Thailand as the example source of an epidemic, in part because the Thai government has been more forthcoming with useful information than China and Vietnam (other locations of known human H5N1 infections), and in part because Thailand remains a hotbed of the virus. The Nature team took a case of a single rural resident of Thailand coming down with a human-transmissible form of H5N1, then calculated the patterns of infection across the nation. The results -- visible in this movie (small .mov, larger .ram), with red representing flu cases and green representing locations where the disease has "burned through" the population -- are sobering.

But swift containment efforts could effectively limit that spread (.mov, .ram -- blue is treated area), giving enough time for a vaccine to be developed that would be effective against that particular strain of Avian Flu (because of the rapid evolution of viruses, useful vaccines can't be prepared before the precise nature of a given strain is known). What would these containment efforts look like?

The first step in preventing a pandemic, Ferguson said, is for doctors to quickly recognize that the virus is something unusual and notify government health officials. Then, infected patients should be isolated from other populations. Steps such as closing schools and work places and limiting access to gathering spots should be taken to increase “social distance”—reducing opportunities for infected people to transmit the virus to others. Finally, Ferguson and his colleagues recommend that public health officials treat the 20,000 people closest to the outbreak with anti-viral drugs. It might take a stockpile of as many as 3 million doses of anti-viral treatments to eliminate an outbreak, the scientist said.

But such containment is contingent upon some important changes to how we report and handle flu infections:

Both groups agree that, for a containment strategy to have any hope of working, it must be in place within a few weeks at most of the first people being infected with a virus capable of sustained human-to-human transmission.

If such a virus arose today, that is unlikely to happen. Surveillance systems in southeast Asia are poor; recent cases have taken weeks to detect and diagnose. Whereas Cambodia has typically reported cases to the World Health Organization (WHO) within about a week, Vietnam has often reported cases after several weeks, and in some cases months.

Marc Lipsitch, an epidemiologist at Harvard University, says the papers leave him concerned that too little is being done to plan containment strategies. "We are simply not moving fast enough," he says.

For example, the WHO currently has just 120,000 courses of antivirals in its stockpile, although it is in discussions to get more. "I think the take-home message is that the current stockpile is very unlikely to be adequate to stop anything," says Lipsitch.

What's needed, says Ben Schwartz of the National Immunization Program at the Centers for Disease Control and Prevention in Atlanta, are international agreements on how to investigate and report clusters; training and resources to strengthen surveillance; and measures to ensure that the WHO has enough antiviral drugs. The countries where a pandemic is most likely to emerge need detailed plans and drills, he adds.

This does not mean that insufficient efforts have insufficient results, however. As the article in Nature notes, "even an unsuccessful containment strategy can delay widescale spread by a month or more—a potentially critical window of opportunity for accelerating vaccine production." The goal isn't simply to stop the spread in order to let the virus burn itself out in the infected population, but to allow the medical research teams enough time to develop a treatment that can prevent a pandemic and prevent further disease in the infected areas.

For many researchers, a human-transmissible version of Avian Flu is not a question of if, but of when. That the virus is predominantly located in developing nations, some of which with less-than-stellar records of government honesty when it comes to local disease outbreaks, complicates matters severely. A global H5N1 outbreak is not a world-ending scenario, but it's one that inevitably makes solutions to other, more chronic or deeply-rooted problems all the harder to find. The massive reduction in population that could result from a serious pandemic would not mean a reduction in resource footprints or environmental impact -- people who are desperate for survival do not give much thought to the long-term implications of their actions for the planet or for "nature" as a whole.

But we are not defenseless. We can stop or slow an Avian Flu pandemic. It won't be easy, it won't be cheap, and it won't be something we can pass off to someone else to handle. Transparency, collaboration and science are our best tools -- and the most worldchanging.

(Some links via Avian Flu blog and MedGadget)