This year marks the 100th anniversary of the global influenza pandemic of 1918 that killed at least 50 million people worldwide, yet it’s something that remains with us to this day—and not figuratively. It is literally, biologically, present.

“All of the influenza A viruses, all of the ones we get vaccinated for every year, contain genes that are descended from the 1918 virus in one way or another,” said David Morens of the National Institutes of Health, who offered a detailed review on Tuesday at TropMed18 of the catastrophic outbreak disease experts refer to as “the Big One.”

Of the two types of influenza viruses humans contend with every year, influenza A strains tend to be much more dangerous and deadly than influenza B strains.

Morens said the descendants of the 1918 A strain have become steadily less lethal, but they continue to inflict considerable damage. In fact, Morens said that in the United States, if you add up all the flu deaths that have occurred in the 100 years since the 1918 pandemic, “three to four times as many people have died of seasonal” influenza A viruses than died in the US during the 1918 pandemic.

For infectious disease experts, a global outbreak of a very lethal strain of influenza remains at the top of the list of dangerous pathogens capable of causing a global health emergency. An influenza pandemic occurs when a new strain of influenza A emerges that is sufficiently different from previous strains to allow it to spread rapidly around the world.

The last influenza pandemic involved the H1N1 strain from 2009. And while it turned out to be not as deadly as feared, it still rattled disease experts by its ability to quickly circle the globe. Also, despite the many advances in disease surveillance that have occurred since 1918, H1N1’s sudden appearance—in Mexico, where the first infections were traced to pigs—took many flu hunters by surprise.

Morens said another pandemic strain is “inevitable” because different segments of the influenza virus genome are constantly circulating in wild birds.

“They re-assort. They get into mammals and people. They will come back again,” he said.

Tim Uyeki, with the US Centers for Disease Control and Prevention, said the world is “better prepared” for the next pandemic but not “fully prepared.”

He said the concern today remains focused on strains of avian influenza that have infected humans and proven to be especially deadly.

The one getting the most attention right now is known as H7N9. The disease was first reported in humans in March of 2013 in China. Uyeki said there have been 1567 cases documented so far, and 39 percent of those infected died.

Almost all of the known infections of H7N9 have been traced to contact with infected birds. Uyeki said there is evidence of very limited human-to-human transmission, but “then it stops” and does not continue hopping from person to person. Still, he said H7N9 “really alarms us” because health experts worry that transmission eventually could “become sustained” and produce a terrible pandemic.

But Uyeki said the difference between now and 1918 is that there are numerous advances that could help countries fight back. They include anti-viral medications, those existing and new ones that soon could be available; new vaccines under development, including a “universal” vaccine that could provide protection against any flu strain; and a much better global surveillance network that could help guide strategies to contain an outbreak.

Uyeki said that while “everyone focuses on a pandemic,” there should also be increased attention to the dangers of seasonal influenza. For example, in the United States, the 2017 influenza season produced a particularly high number of deaths in children.

Moreover, Uyeki said that “improving our response to seasonal influenza will improve our response to the next pandemic.”