Bird flu, or avian influenza, might seem like a relatively new phenomenon to the general public. But the disease, technically called Highly Pathogenic Avian Influenza (HPAI), has been sickening birds since the 1800s, and likely much longer. And in humans, cases date at least as back to the 1918 flu pandemic. If scientists could have surveyed wastewater hundreds of years ago, they might have found it had been circulating for much longer.

Understanding the history of bird flu can help reveal potential risks for a future pandemic, says Catharine Paules, an infectious diseases physician at Penn State Health Milton S. Hershey Medical Center.

“I always tell people that influenza worries me the most in terms of the risk of causing a pandemic,” Paules says.

Below is a timeline of what we know about the history of HPAI, or bird flu.

In 1878, a veterinarian in northern Italy noted a significant uptick in poultry dying. With a limited understanding of viruses at the time, people called the disease “fowl plague.” At first, it was confused with “fowl cholera,” which is caused by a bacteria.

At the time, concern centered on people’s livelihoods, not on human health, explains Andrea Prinzi, a former clinical microbiologist at Children's Hospital Colorado.

In the 19th century, the disease could spell financial ruin for a poultry farmer. “They weren’t necessarily as concerned it would infect humans,” says Prinzi, who also serves as a field medical director of U.S. Medical Affairs for bioMérieux, Inc.,a biotechnology company.

Although this instance in Italy is the first known reference to the disease, avian flu had likely been sickening birds for some time.

By 1901, scientists had identified the cause of “fowl plague” as a virus. They were able to do this by observing its ability to pass through a filter (viruses are significantly smaller than bacteria and so can pass more easily).

The disease eventually spread to eastern Austria and Germany, and later to Belgium and France, likely through traveling poultry merchants.

Amid the devastation and disruption of World War I, a flu pandemic surged, claiming more lives than battles did. The first “well-described flu pandemic,” according to Paules, resulted in about 50-100 million lives worldwide.

“That strain was really good at making the healthiest people in the population the sickest; the immune response was so severe,” Prinzi says.

Technology later determined the virus to be “an avian-like” H1N1 virus.

Avian influenza caused sporadic outbreaks worldwide among bird flocks. In the United States, the disease struck live bird markets in New York City in the winter of 1924-25.

For unknown reasons, few outbreaks were reported in the 1930s and 1940s.

By the late 1950s, poultry across Europe, Russia, North America, South America, Middle East, Africa and Asia had been affected by bird flu.

The number of birds affected varied greatly, from small flocks on a single farm to tens of thousands of birds.

In 1957, a new flu virus emerged from an avian virus, beginning a pandemic that killed over a million people worldwide and 116,000 in the United States. And for the first time, a study suggested a link between people and bird flu viruses, finding a connection between the new virus and a virus in a turkey.

Around the same time, scientists started realizing that wild birds could carry flu viruses, acting as reservoirs (and confirmed it with blood tests in 1968).

In 1968, a seasonal flu virus mixed with a bird flu virus to form a new virus better able to infect humans. The resulting pandemic killed a million people worldwide and about 100,000 people in the United States.

That mixing, known as reassortment, is often what sets the stage for a pandemic.

At the April 1981 gathering of the First International Symposium on Avian Influenza in Maryland, researchers agreed to discard the term fowl plague and replace it with the more appropriate term highly pathogenic avian influenza (HPAI).

In 1996, anew strain of avian influenza, H5N1, was identified in aquatic birds in southern China.

Eighteen infections in humans result in six deaths, the first known H5N1 human fatalities.

“It was really lethal, and people started paying attention,” Prinzi said.

Increased surveillance led to the detection of various outbreaks of avian influenza among both birds and humans including new, or novel, strains. In 2009, for example, H1N1 was detected in humans. The novel virus spread from the United States around the world. It also highlighted that bird flu can be transmitted through intermediate hosts (in this case, pigs).

The disease had finally caught the attention of the public: A 2005 World Health Organization survey identified avian influenza as the biggest global health concern.

When minks fell ill with H5N1 on a farm in Spain, presumably from exposure to birds, virologists were alarmed. It was a sign that the virus could easily spread from mammal to mammal.

In early 2023, two workers from the farm tested positive for H5N1.

“That’s when I started paying a lot of attention,” Paules says.

So did Prinzi: When a virus jumps from an animal to a human, there’s a better chance it will evolve into a strain that could cause a pandemic, she says.

“Influenza is really challenging because it changes all the time,” she says.

In the spring of 2024, dairy cows on farms in Kansas and Texas were reported to have H5N1. In April, a farmworker tested positive, marking the first known cow-to-human transmission of H5N1.

By January 2025 there were 67 confirmed human cases in the United States, according to the Centers for Disease Control and Prevention, including one death. Testing suggested that the virus mutated after the person in Louisiana was infected.

These kinds of developments present a lot of red flags, Prinzi says.

Paules agrees: “Even if it’s not this particular virus," she says, "history tells us it will be an influenza virus that will cause a pandemic."