A pandemic ( pan-DEM-ik) is an epidemic of an infectious disease that has a sudden increase in cases and spreads across a large region, for instance multiple continents or worldwide, affecting a substantial portion of the human population. Widespread endemic diseases with a stable number of infected individuals such as recurrences of seasonal influenza are generally excluded as they occur simultaneously in large regions of the globe rather than being spread worldwide. Throughout human history, there have been a number of pandemics of diseases such as smallpox. The Black Death, caused by the Plague, caused the deaths of up to half of the population of Europe in the 14th century. The term pandemic had not been used then, but was used for later epidemics, including the 1918 H1N1 influenza A pandemic—more commonly known as the Spanish flu—which is the deadliest pandemic in history. The most recent pandemics include the HIV/AIDS pandemic, the 2009 swine flu pandemic and the COVID-19 pandemic. Almost all these diseases still circulate among humans though their impact now is often far less. In response to the COVID-19 pandemic, 194 member states of the World Health Organization began negotiations on an International Treaty on Pandemic Prevention, Preparedness and Response, with a requirement to submit a draft of this treaty to the 77th World Health Assembly during its 2024 convention. The WHO Pandemic Agreement was adopted at the World Health Assembly in May 2025, establishing rules on how countries should act and collaborate to prevent, prepare for and respond to pandemic emergencies and public health emergencies of international concern. It was approved with 120 votes in favour, 70 abstentions and the absence of the United States, which had already withdrawn from the WHO.