Disease X: The unknown threat that could trigger the next pandemic

From the Black Death and Spanish Flu to Ebola and Covid-19, history shows how quickly an unfamiliar pathogen can reshape the world. Could the next threat already be emerging?

For centuries, humanity has repeatedly been caught off guard by infectious diseases that transformed societies, overwhelmed health systems and killed millions.

The Black Death swept through Europe in the 14th century, killing tens of millions. Centuries later, the 1918 influenza pandemic infected an estimated 500 million people worldwide and killed between 20 million and 50 million.

Then came HIV/AIDS, SARS, Ebola, successive influenza pandemics and, most recently, Covid-19.

Each was different. But they share one uncomfortable lesson: the next major infectious threat may not be the disease the world is currently watching.

That is where the World Health Organisation's concept of Disease X comes in.

Disease X is not a disease currently circulating in humans.

It is a placeholder for an unknown pathogen capable of causing a serious international epidemic or pandemic.

WHO uses the concept to encourage countries and scientists to prepare for threats that have not yet been identified, rather than designing preparedness systems only around pathogens already known to science. WHO's latest pathogen-prioritisation work assessed evidence across 28 viral families and one core group of bacteria, covering 1,652 pathogens.

“This represents the world’s opportunity to plan together, detect pathogens quicker, share data broadly and collectively to respond more effectively to the next Disease X or known pathogens.” WHO Director-General Dr Tedros Adhanom Ghebreyesus.

Dr Ahmed Kalebi, a Nairobi-based consultant pathologist, public-health researcher and Founder and CEO of Dr Kalebi Labs, says the concept forces the world to think beyond today's known diseases.

“Disease X is not a specific disease. Rather, it is a placeholder concept created by the WHO to represent a future epidemic or pandemic caused by a currently unknown pathogen,” Kalebi says.

Diseases that now appear familiar were once mysterious threats. Ebola itself was unknown until 1976. SARS emerged in 2003. H1N1 influenza emerged as a pandemic threat in 2009. And SARS-CoV-2 was unknown before the Covid-19 pandemic.

The next major pathogen could similarly emerge from a place, species or ecological environment scientists are not currently watching.

The Black Death remains one of humanity's most devastating disease catastrophes.

The plague pandemic of the 14th century killed tens of millions in Europe. Today, plague can be treated with antibiotics, but medieval societies had neither the microbiological knowledge nor the medical tools needed to control it.

Then came the 1918 influenza pandemic.

An estimated 500 million people were infected worldwide, with deaths estimated at between 20 million and 50 million.

It was followed by the 1957–58 Asian Flu and the 1968 Hong Kong Flu, each estimated to have caused between one million and four million deaths.

The 2009 H1N1 pandemic was less lethal but still caused hundreds of thousands of deaths globally.

The history matters because it demonstrates that pandemic risk does not disappear simply because humanity defeats one disease.

COVID-19 provided the modern demonstration of how quickly an unfamiliar pathogen can overwhelm the world.

SARS-CoV-2 spread efficiently through the respiratory route and could be transmitted by people who were mildly symptomatic or had no obvious symptoms.

That allowed transmission to continue before many infections were recognised.

Dr Maria Van Kerkhove, WHO's Director for Epidemic and Pandemic Management, has repeatedly stressed that pandemic preparedness must begin before the crisis arrives.

In WHO's pandemic influenza preparedness messaging, the central warning is blunt: another influenza pandemic is not a question of if, but when.

“Pandemic influenza happens when a new influenza or flu virus emerges,” Van Kerkhove explains in WHO's preparedness messaging, adding that such a virus can spread easily between people when populations have little or no immunity.

The response, she says, depends on how quickly countries can identify the threat and act.

“Quick actions will not only save lives, they will keep society moving,” she says.

That means surveillance systems capable of detecting unusual disease, laboratories able to identify new pathogens, clear national pandemic plans and health systems capable of protecting health workers and vulnerable populations.

WHO continues to invest in pandemic influenza preparedness, including surveillance, laboratory capacity and national preparedness planning. In 2026, WHO has continued to support countries to strengthen these systems.

Respiratory viruses remain particularly concerning because they can move rapidly through densely populated communities and across borders.

WHO's pathogen-prioritisation work reflects this broader approach: scientists are assessing entire pathogen families and identifying where research and preparedness gaps could leave the world vulnerable.

Many emerging infectious diseases begin with a spillover event, when a pathogen moves from an animal population into humans.

Deforestation, agricultural expansion, urbanisation, wildlife exploitation, climate change and increased human movement can create more opportunities for such encounters.

Bats, rodents, primates and other animals can harbour pathogens capable of infecting people.

WHO's Maria Van Kerkhove has emphasised that countries need systems capable of detecting new threats, assessing their severity and coordinating a rapid response.

“Preparedness means having disease surveillance systems to detect new threats early, clear national pandemic plans, and health systems that protect health workers and people at the highest risk,” she says.

It also means learning from previous pandemics.

The lesson from Covid-19 was that waiting for certainty can be costly.