Infectious diseases with high prevalence are separately (sometimes in addition to their epidemics), such as malaria, which may have killed 50–60 million people.

Major epidemics and pandemics By death toll Ongoing epidemics and pandemics are in bold face. 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.

+Epidemics, endemics, and pandemics with at least 1 million deathsRankEpidemics/pandemicsDiseaseDeath toll (million)Percentage of population lostYearsLocation11918 "Spanish" influenza pandemicInfluenza A/H1N125–1001–5.4% of global population1918–1920Worldwide2Plague of JustinianBubonic plague15–10025–60% of European population541–549North Africa, Europe, and Western Asia3HIV/AIDS pandemicHIV/AIDS45 ()1981–presentWorldwide4Black DeathBubonic plague25–5030–60% of European population1346–1353North Africa, Europe, and Asia5COVID-19 pandemicCOVID-197.12–38 (as of 2026)0.4375% of global population (as of 2026)2019–presentWorldwide6Third plague pandemicBubonic plague12–151855–1960Worldwide7Cocoliztli epidemic of 1545–1548 Cocoliztli (caused by an unidentified pathogen)5–1527–80% of Mexican population1545–1548Mexico8Antonine PlagueSmallpox or measles5–1025–33% of Roman population165–180 (possibly up to 190)Roman Empire91520 Mexico smallpox epidemicSmallpox5–823–37% of Mexican population1519–1520Mexico10Seventh cholera pandemicCholera1.4-9.3 (as of 2026)1961–presentWorldwide111957–1958 influenza pandemicInfluenza A/H2N21–41957–1958Worldwide12Hong Kong fluInfluenza A/H3N21–41968–1969Worldwide131918–1922 Russia typhus epidemicTyphus2–31–1.6% of Russian population1918–1922Russia14Cocoliztli epidemic of 1576Cocoliztli2–2.550% of Mexican population1576–1580Mexico15Jian'an PlagueUnknown (possibly typhoid fever or viral hemorrhagic fever)2217Han dynasty16735–737 Japanese smallpox epidemicSmallpox233% of Japanese population735–737Japan171772–1773 Persian PlagueBubonic plague21772–1773Persia18Naples PlagueBubonic plague1.251656–1658Italy (Southern)191629–1631 Italian plagueBubonic plague11629–1631Italy201846–1860 cholera pandemicCholera11846–1860Worldwide211889–1890 pandemicInfluenza or human coronavirus OC431 1889–1890 Worldwide

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. Malaria is commonly spread by mosquitoes. 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. Its symptoms include coughing up blood. It can generally be treated with strong antibiotics; untreated TB can be fatal. An opportunistic infection, TB is the leading cause of death of those with HIV/AIDS, and is considered an AIDS-defining clinical condition. The association between HIV/AIDS and TB has been described as the "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, 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 Pre-1500s +Chronological table of epidemic and pandemic events before the 1500s Event Years LocationDisease Death toll (estimate) Ref. 1350 BC plague of Megiddo1350 BC (circa) Megiddo, land of Canaan Unknown. In the Amarna letters EA 244, Biridiya, the mayor of Megiddo complains to Amenhotep III of his area being "consumed by death, plague and dust" data-sort-value="0" Amarna Tablet 244 .Hittite Plague/"Hand of Nergal"1330 BC (circa)Near East, Hittite Empire, Alashiya, possibly EgyptUnknown, possibly Tularemia. Mentioned in Amarna letter EA 35 as the "Hand of Nergal", cause of death of Šuppiluliuma I. data-sort-value="0" Plague of Athens430–426 BC Greece, Libya, Egypt, Ethiopia Unknown, possibly typhus, typhoid fever or viral hemorrhagic fever75,000–100,000 412 BC epidemic412 BC Greece (Northern Greece, Roman Republic) Unknown, possibly influenza473,000 (10% of the Roman Population) Antonine Plague165–180 (possibly up to 190) Roman Empire Unknown, possibly smallpox5–10 million "Past pandemics that ravaged Europe", BBC News, 7 November 2005 Jian'an Plague 217 Han dynasty Unknown, possibly typhoid fever or viral hemorrhagic fever2 million Plague of Cyprian249–262 Europe Unknown, possibly smallpox or viral hemorrhagic fever310,000 D. Ch. Stathakopoulos Famine and Pestilence in the late Roman and early Byzantine Empire (2007) 95 Plague of Justinian (beginning of first plague pandemic)541–549 Europe and West Asia Bubonic plague15–100 million 580 Dysentery Epidemic in Gaul580 Gaul Dysentery or possibly smallpox450,000 (10% of the Gaul population) Gregory of Tours. A History of the Franks. Pantianos Classics, 1916 Roman Plague of 590 (part of first plague pandemic)590 Rome, Byzantine Empire Bubonic plague data-sort-value="0" Plague of Sheroe (part of first plague pandemic)627–628 Bilad al-Sham Bubonic plague25,000+ Plague of Amwas (part of first plague pandemic)638–639 Byzantine Empire, West Asia, Africa Bubonic plague25,000+ Plague of 664 (part of first plague pandemic)664–689 British Isles Bubonic plague data-sort-value="0" Plague of 698–701 (part of first plague pandemic)698–701 Byzantine Empire, West Asia, Syria, Mesopotamia Bubonic plague data-sort-value="0" 735–737 Japanese smallpox epidemic735–737 Japan Smallpox2 million (approx. of Japanese population) Plague of 746–747 (part of first plague pandemic)746–747 Byzantine Empire, West Asia, Africa Bubonic plague data-sort-value="0" Black Death (start of the second plague pandemic) 1346–1353 Eurasia and North Africa Bubonic plague25–50 million (30–60% of European population and 33% percent of the Middle Eastern population) Sweating sickness (multiple outbreaks) 1485–1551 Britain (England) and later continental Europe Unknown, possibly an unknown species of hantavirus10,000+ 1489 Spain typhus epidemic 1489 Spain Typhus17,000

1500s +Chronological table of epidemic and pandemic events that started in the 1500s Event Years LocationDisease Death toll (estimate) Ref. 1510 influenza pandemic 1510 Asia, North Africa, Europe InfluenzaUnknown, around 1% of those infected 1520 Mexico smallpox epidemic 1519–1520 Mexico Smallpox 5–8 million (40% of population) Cocoliztli epidemic of 1545–1548 1545–1548 Mexico Possibly Salmonella enterica 5–15 million (80% of population) 1557 influenza pandemic 1557–1559 Asia, Africa, Europe, and Americas Influenza Unknown (10% of the infected) 1561 Chile smallpox epidemic 1561–1562 Chile Smallpox120,000–150,000 (20–25% of native population) Alonso de Góngora Marmolejo Historia de Chile desde su descubrimiento hasta el año 1575 . Cervantesvirtual.com. Retrieved on 2011-12-06. 1563 London plague (part of the second plague pandemic) 1563–1564 London, England Bubonic plague 20,100+ Cocoliztli epidemic of 1576 1576–1580 Mexico Possibly Salmonella enterica 2–2.5 million (50% of population) 1582 Tenerife plague epidemic (part of the second plague pandemic) 1582–1583 Tenerife, Spain Bubonic plague 5,000–9,000 1592–1596 Seneca nation measles epidemic 1592–1596 Seneca nation, North America Measles data-sort-value="0" 1592–1593 Malta plague epidemic (part of the second plague pandemic) 1592–1593 Malta Bubonic plague 3,000 1592–1593 London plague (part of the second plague pandemic) 1592–1593 London, England Bubonic plague 19,900+ 1596–1602 Spain plague epidemic (part of the second plague pandemic) 1596–1602 Spain Bubonic plague 600,000–700,000 Stanley G. Payne: A History of Spain and Portugal Volume 1, Ch 15 The Seventeenth-Century Decline THE LIBRARY OF IBERIAN RESOURCES ONLINE, accessed 26 May 2020

1600s