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This is a list of the largest known epidemics and pandemics caused by an infectious disease in humans. Widespread non-communicable diseases such as cardiovascular disease and cancer are not included. An epidemic is the rapid spread of disease to a large number of people in a given population within a short period of time; in meningococcal infections, an attack rate in excess of 15 cases per 100,000 people for two consecutive weeks is considered an epidemic. Due to the long time spans, the first plague pandemic (6th century – 8th century) and the second plague pandemic (14th century – early 19th century) are shown by individual outbreaks, such as the Plague of Justinian (first pandemic) and the Black Death (second pandemic). Infectious diseases with high prevalence are listed separately (sometimes in addition to their epidemics), such as malaria, which may have killed 50–60 billion people throughout history, or about half of all humans that have ever lived. On 6 May 2024, the White House released an official policy to more safely manage medical research projects involving potentially hazardous pathogens, including viruses and bacteria, that may pose a risk of a pandemic. Major epidemics and pandemics By death toll Ongoing epidemics and pandemics are in boldface. For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population. Depopulation of the Americas Not included in the above table are many waves of deadly diseases brought by Europeans to the Americas and Caribbean. Western Hemisphere populations were ravaged mostly by smallpox, but also typhus, measles, influenza, bubonic plague, cholera, malaria, tuberculosis, mumps, yellow fever, and pertussis. The lack of written records in many places and the destruction of many native societies by disease, war, and colonization make estimates uncertain. Deaths probably numbered in the tens or perhaps over a hundred million, with perhaps 90% of the population dead in the worst-hit areas. Lack of scientific knowledge about microorganisms and lack of surviving medical records for many areas makes attribution of specific numbers to specific diseases uncertain. Infectious diseases with high prevalence There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll. Malaria has had multiple documented temporary epidemics in otherwise non-affected or low-prevalence areas, but the vast majority of its deaths are due to its constant prevalence in affected areas. Tuberculosis (TB) became epidemic in Europe in the 18th and 19th century, showing a seasonal pattern, and is still taking place globally. The morbidity and mortality of TB and HIV/AIDS have been closely linked, known as "TB/HIV syndemic". According to the World Health Organization, approximately 10 million new TB infections occur every year, and 1.5 million people die from it each year – making it the world's top infectious killer (before COVID-19 pandemic). However, there is a lack of sources which describe major TB epidemics with definite time spans and death tolls. Hepatitis B: According to the World Health Organization, as of 2019 there are about 296 million people living with chronic hepatitis B, with 1.5 million new infections each year. In 2019, hepatitis B caused about 820,000 deaths, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer). In many places of Asia and Africa, hepatitis B has become endemic. In addition, a person is sometimes infected with both hepatitis B virus (HBV) and HIV, and this population (about 2.7 million) accounts for about 1% of the total HBV infections. Hepatitis C: According to the World Health Organization, there are approximately 58 million people with chronic hepatitis C, with about 1.5 million new infections occurring per year. In 2019, approximately 290,000 people died from the disease, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer). There have been many hepatitis C virus (HCV) epidemics in history. Chronology Events in boldface are ongoing. See also Globalization and disease – Overview of globalization and disease transmission History of smallpox – Impact of smallpox on world history List of Ebola outbreaks – Cases and outbreaks of Ebola virus disease List of infectious diseases List of natural disasters by death toll#Deadliest epidemics Timeline of plague – Human and animal diseasePages displaying short descriptions of redirect targets Explanatory notes References Further reading Eisenberg, Merle, and Lee Mordechai. "The Justinianic Plague and Global Pandemics: The Making of the Plague Concept." American Historical Review 125.5 (2020): 1632–1667. Hunter, Philip (2007). "Inevitable or avoidable? Despite the lessons of history, the world is not yet ready to face the next great plague". EMBO Reports. 8 (6): 531–534. doi:10.1038/sj.embor.7400987. PMC 2002527. PMID 17545992. Snowden, Frank M. (2019). Epidemics and Society: From the Black Death to the Present. Yale University Press. ISBN 978-0300192216. 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