By Steve Lundeberg
As World War I headed into its bloody homestretch a century ago, an even deadlier event was ramping up: A full third of the Earth’s population was on its way to contracting influenza. Of the 500 million people who got sick during what was to become known as the Spanish flu pandemic, at least one in 10 perished — making it a medical catastrophe of almost unrivaled proportions.
A century later, research spearheaded by Benjamin Dalziel, an assistant professor at Oregon State University’s College of Science, is paving the way toward city planning and management that takes influenza outbreak control into account. The more residents a city has and the more organized their movement patterns, the longer its flu season is apt to last, his work has shown.
The findings are an important step toward predicting outbreak trends for a viral infection that continues to sicken millions of Americans annually, sending hundreds of thousands to the hospital and killing tens of thousands. To put the flu’s havoc-wreaking potential in perspective, World War I, one of the deadliest conflicts in human history, needed four years to amass a death toll of approximately 17 million. In just over a year, the Spanish flu pandemic killed at least three times that many.
Some death toll estimates for the pandemic — which earned its name because Spain, neutral in the war, reported freely on the disease, whereas the combatants censored media coverage — range as high as 100 million. By comparison, the top-of-mind epidemic among many people — HIV — has claimed 35 million since the virus’s discovery in the early 1980s.
The U.S. was also hard hit by the Spanish flu. “The influenza pandemic killed 675,000 people in the U.S.,” says Jeff Bethel, an epidemiology researcher in the College of Public Health and Human Sciences. “One unusual aspect of that pandemic was that there was not only increased mortality among young and elderly people but also high mortality among healthy 20- to 40-year-olds.”
Dalziel, a population biologist, worked with an international collaboration to analyze weekly flu incidence data from 603 cities of varying size and “structure.” They examined the patterns people follow regarding where they live and work, along with the role a key weather metric — specific humidity — played in flu epidemics. Specific humidity is defined as the ratio of the mass of water vapor in air to the total mass of air and water vapor.
Flu is transmitted by virus-bearing moisture droplets that people exhale, cough or sneeze out, creating a “cloud of risk” that emanates from an infected person and is breathed in by those around him or her.
“As specific humidity decreases, the virus remains viable in the air for longer, effectively expanding that cloud,” says Dalziel. “However, if an infected person is right beside you, it matters less what the specific humidity is.”
Humidity, coincidentally, played a key role in the war, whose end coincided with the Spanish flu pandemic’s beginning: The blister-causing terror of mustard gas was at its worst during hot, humid conditions.
As for the flu, if a city has a large population with transportation patterns that frequently draw them together, flu viruses can find new hosts even when climatic conditions aren’t at their most favorable. “One thing that distinguishes urban centers from small towns is the presence of localized pockets of high population density that are connected by organized movement patterns,” says Dalziel. “We found that makes a difference for how influenza spreads at different times of the year.”
The researchers discovered that in metropolises, flu cases are more spread out through the winter months, including early and late in the season, when the weather is not optimal for transmission. By contrast, in smaller cities, more cases will be tightly grouped in a short period, during peak season, when climate conditions are best for transmission.
“We found that as cities become larger and mobility patterns become more highly organized, climatic conditions play a relatively smaller role in influenza transmission,” adds Dalziel.
Flu is an immunizing infection — once a particular strain has infected people, they’re unlikely to become infected again, at least not right away, because their immune system recognizes it and typically can deal with it efficiently. “From the flu’s perspective, it’s facing a limited resource each season — the fraction of the population susceptible to a given strain declines as it spreads,” says Dalziel.
Counterpunching the response of the immune system, flu viruses are constantly evolving. They switch up the proteins that the immune system responds to, shuffling in new ones that aren’t recognized right away.
“Forecasting and controlling influenza is important for public health,” notes Dalziel. “And there is another reason to study the flu: It’s a classic example of a complex system on Earth. To predict flu outbreaks, you need to look at a variety of processes from urbanization to climate. What’s more, flu spreads and evolves in a range of animal species, and in these senses, it is deeply integrated with the biosphere.”
There are four genera of influenza viruses, labeled influenza A, B, C and D. Influenza A viruses are the most dangerous for humans, and varieties of it were the pathogens behind the 1918 — 19 pandemic (H1N1 virus). Lesser but still deadly pandemics in 1957 (H2N2), 1968 (H3N2), 2004 (H5N1) and 2009 (also H1N1) were caused by Type A.
During the Spanish flu pandemic, H1N1 received an assist from the troop movements and close quarters required by the war. Unusually high flu incidence in the U.S. was first detected in military camps, as well as some cities, in spring 1918, as Germany attacked on the Western Front.
In four months of fighting in Europe, 1 million German soldiers were killed. Meanwhile, the pandemic was claiming an estimated 1 million per week for 25 weeks.
“Influenza pandemics have been reported for at least 500 years, and we experience one typically every 30 or 40 years,” Bethel says. “The 1957 ‘Asian flu’ affected nearly half of the world’s population in two waves and resulted in over 1 million deaths. The 1968 pandemic caused an estimated 1 million deaths worldwide and about 100,000 in the U.S., mostly among the elderly.”
Even in nonpandemic years, the burden of seasonal influenza on the health of the population is “quite large,” Bethel adds. “Many people think the flu is not a big deal, and while it is usually self-limiting, lasting three to five days, they are a very uncomfortable three to five days with extreme fatigue, intense muscle aches and headaches, high fever and runny or stuffy nose,” he says. “It’s not fun.”
Cecile Viboud of the National Institutes of Health, a co-author with Dalziel on the study, says the start of the flu season can vary widely from year to year and place to place. “It can start as early as November or as late as March,” she notes. “We think city-to-city variation in flu timing is linked to differences in the arrival of influenza viruses — a function of connectivity and geography, possibly moderated by humidity and population immunity.”
In nonpandemic seasons, Viboud adds, epidemics tend to have earlier onsets in the South, although not always in the same city, and then move north. “Locales that experience earlier flu activity could be tempted to vaccinate earlier, but that urge has to be balanced with the waning of vaccine-induced immunity within the season — if you vaccinate too early, you lose effectiveness by the end of the season,” she says.
While Dalziel is excited about what he, Viboud and the other collaborators learned about flu outbreaks, he stresses a few caveats. “Our research does not show that some cities are safer than others for flu — rather it shows relative differences in when the cases are likely to occur,” he says. “Also, our model is not designed to predict what will happen with flu epidemics under climate change — there’s still a lot of uncertainty about what will happen to specific humidity as a result of global climate change. And finally, while flu vaccination is an important topic, our analysis was focused on other potentially important factors — city size and structure. Our findings showed that city size and structure could play a role in determining how climate, and other factors such as vaccination coverage, affect influenza epidemics.”
And for people who want to avoid the flu — which means everyone — the recommendations are the same regardless of where someone lives. “Wash your hands often, cover your cough and get a flu shot,” Dalziel adds. “Another way to think about it is that our results on city size and flu spread cut both ways in terms of protective action: If you live in a big city and the thought of more efficient flu transmission in metropolises spurs you to take these protective actions, great. If you live in a small town and the thought of a more explosive flu season spurs you to take these protective actions, also good.”