What does it mean for a disease to be “endemic”?

It doesn’t mean the disease disappeared. When epidemiologists use the word “endemic,” they mean that a disease is occurring “at an expected level in a location during a period of time,” explains epidemiologist René Najera, editor of The History of Vaccines, an online resource by The College of Physicians of Philadelphia.

“Endemic” also doesn’t mean that a disease has ceased to be harmful. Malaria, tuberculosis and influenza are all serious and potentially fatal endemic diseases that occur every year. Since the 1940s, countries have built robust international health networks that identify flu strains in order to keep them under control, and avoid the kind of devastation that happened during the 1918 pandemic. This is something epidemiologists and virologists have argued is necessary for COVID-19, and will continue to be necessary if and when the virus becomes endemic.

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In 1946, the United States established the Communicable Disease Center, or CDC, in Atlanta, Georgia. Now known as the Centers for Disease Control and Prevention, the CDC’s initial focus was preventing the spread of malaria. Two years later, the newly-formed United Nations—created as a result of World War II—established the World Health Organization, whose constitution asserts that “Governments have a responsibility for the health of their peoples.”

An early concern of the World Health Organization, or WHO, was the flu, says Wenqing Zhang, director of the WHO’s Global Influenza Program. The 1918 influenza pandemic had led to an estimated 50 million deaths worldwide. During World War II, the U.S. Army, remembering how the flu had devastated troops during World War I, began funding research into a flu vaccine. In the early 1940s, an Army-supported research team at the University of Michigan led by Thomas Francis Jr. and Jonas Salk (of the polio vaccine) developed the first viable flu vaccine. In 1945, flu vaccines became available for civilians.

In 1952, the WHO ​​established the Global Influenza Surveillance and Response System in order to collect flu data from different countries and coordinate global efforts to combat the flu. This was a period in which the U.S. military—which was stationed all over the world—and other countries’ militaries were monitoring infectious disease outbreaks, and the WHO’s flu program attempted to use countries’ monitoring stations to look at the big picture. Within a few years, the CDC’s Influenza Division became a collaborating center with the WHO program.

Initially, the WHO’s flu program looked for signs and symptoms of influenza and apparent spikes in flu cases, Najera says. Finding the right vaccine to treat those cases was a more difficult matter. Bivalent flu shots could vaccinate against two strains of flu at a time, but discovering what type of flu strains were circulating, and what type of vaccine composition would best treat an outbreak, was still something scientists were learning to do. During the 1950s and ‘60s, they began to make some headway.

The first post-World War II flu pandemic occurred relatively early in the WHO’s flu program’s existence. Yet, according to Maurice Hilleman, the microbiologist who sounded the alarm about the outbreak, the WHO missed the pandemic’s early signs. In April 1957, Hilleman read about a flu outbreak in Hong Kong that had started a couple of months before in East Asia. After obtaining samples of the virus from a U.S. Army Medical General Laboratory in Zama, Japan, he realized that it was a new strain capable of turning into a pandemic.

Which is what it did. The 1957 pandemic killed an estimated 1.1 million people around the world, and very likely would’ve killed many more if not for Hilleman, who jump-started work on a vaccine that became available that year. Hilleman went on to develop more than 40 vaccines and receive the National Medal of Science for his contributions to public health.

When the next flu pandemic hit in 1968, the WHO’s flu surveillance program was more effective at detecting it. In July 1968, the National Influenza Center at the University of Hong Kong identified a flu strain that was spreading in the region. Scientists at the World Influenza Center in London and the CDC in Atlanta received samples of the virus. The scientists who analyzed it found that the virus, like the 1957 one, was a unique strain that could cause a pandemic. They relayed this information to the WHO, which in August issued a warning that a new flu pandemic was starting.

With this information and warning, vaccine-makers were able to develop vaccines specific to this virus strain. Like all pandemics, the 1968 one left a devastating toll, killing an estimated one million people. Still, the sharing of information globally led to the development of strain-specific vaccines that helped prevent infection and severe illness in many people.

During the 1970s and ‘80s, scientists started to gain a better understanding of the flu. They could see that different strains were prominent during different flu seasons, meaning that vaccines should specifically target the strains in circulation in order to be effective. In 1973, the WHO made its first formal recommendation for which strains new flu vaccines should target, Zhang says.

In 2007, an international resolution gave the WHO more authority to tell collaborating countries which flu vaccines they should distribute for that year based on circulating strains, and also what to do if the WHO detected a growing flu pandemic—things like increasing vaccine production, increasing testing, enforcing of travel restrictions, etc. (Zhang notes, however, that the WHO cannot force a country to use certain vaccines).

The H1N1 outbreak in 2009 “was the first test of these international health regulations,” Najera says. Although ​​the virus killed an estimated 151,700 to 575,400 people, early detection and the relative availability of tests and vaccines helped prevent the pandemic from becoming worse. (In comparison, the WHO estimates there are 290,000 to 650,000 influenza-related respiratory deaths each year.) Ironically, many people who avoided the flu that year may not have realized how they benefited from global health systems doing their job.

“That is the issue with public health,” Najera says. “When things go right, nobody notices.”