Medical researchers know more about influenza than they did a century ago, but the devastating global pandemic of 1918 could be repeated without global vigilance, a new study suggests.

Scientists led by Caroline van de Sandt from the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, Australia, warn of modern challenges that will affect the impact of the next pandemic, among them changing population demographics, antibiotic resistance and climate change.

“Like the 1918 pandemic, the severity of any future outbreak will result from a complex interplay between viral, host and societal factors,” says van de Sandt.

“Understanding these factors is vital for influenza pandemic preparedness.”

The 1918 outbreak was the worst in recorded history, infecting a third of the world’s population and killing 50 million people. What intrigued van de Sandt and colleagues, however, was how and why many people managed to survive a severe infection and others displayed only mild symptoms.

In their latest work, published in Frontiers in Cellular and Infection Microbiology, they set out to explain its virulence and patterns of impact by reviewing previous influenza studies.

One explanation is the viral strain itself. Some studies show the 1918 virus could spread to other tissues beyond the respiratory tract, resulting in more widespread damage. It also had mutations that allowed it to be more easily transmitted between humans.

Today scientists can evaluate the pandemic potential of new viruses, in animals and, once a strain has crossed the species barrier, humans, but, as the authors point out, such surveillance efforts are required across the world – and this will become even more important with continued climate change.

“Climate changes affect animal reservoirs of influenza viruses and bird migration patterns,” explains van de Sandt. “This could spread viruses to new locations and across a wider range of bird species.”

Public health remains an important factor. In 1918, people suffering from malnutrition and disease were more likely to die from the infection. Today, obesity and antibiotic resistance are risk factors, and crop loss due to climate change could result in malnutrition, the authors suggest.

Population demographics also must be considered. Back in 1918, young adults were among the most affected, while many older people were spared – most likely because they had built up immunity from years of being exposed to a variety of viruses.

However, given that seasonal flu typically kills the very old, today’s ageing population will likely be another challenge in any future outbreak.

“Providing emergency vaccines during future pandemics should take in account different age groups, viral and host factors,” says the Doherty Institute’s Katherine Kedzierska.

The researchers also report that basic methods to reduce disease transmission, such as banning public gatherings and hand washing, helped to reduce levels of infection and death during the 1918 pandemic, but only when applied early and for the entire duration of the event.

“Until a broadly-protective vaccine is available, governments must inform the public on what to expect and how to act during a pandemic,” says van de Sandt. “An important lesson from the 1918 influenza pandemic is that a well-prepared public response can save many lives.”