21 of the Worst Epidemics and Pandemics in History

Epidemics have changed history more than many wars. They toppled empires, emptied cities, shifted borders and changed the way we work, build and care for one another. They also gave rise to quarantine, medical statistics, vaccines and the hygiene rules we follow today without a second thought.

Below you will find 21 of the worst epidemics and pandemics in history, in chronological order: what caused them, how they spread, how many lives they claimed and what lesson they left behind. Figures for older epidemics are historians' estimates and can vary widely from one source to another.

Outbreak, epidemic, pandemic: what's the difference

Timeline of the 21 epidemics

bacteriumvirusuncertain cause

1. Antiquity
2. 430–426BC
   01 · Ancient Greece

   The Plague of Athens

   uncertain cause: typhus, smallpox or typhoid fever

   It broke out in the second year of the Peloponnesian War, when the people of Attica were sheltering, crowded together, behind the walls of Athens. The historian Thucydides, who fell ill and survived, described the fever, the rashes and the agonizing thirst of the sick. Among the victims was Pericles, the city's leader.

   Deaths (estimates)

   a quarter to a third of the population of Athens

   Legacy

   the first detailed description of an epidemic and the observation that survivors did not fall seriously ill a second time

3. 165–180AD
   02 · Roman Empire

   The Antonine Plague

   virus, most likely smallpox

   Accounts from the time say it was brought back by legions returning from campaigns in the East. The physician Galen described the fever, diarrhea and skin rashes, on the basis of which researchers believe it was smallpox. It is named after the Antonine dynasty, to which Emperor Marcus Aurelius belonged.

   Deaths (estimates)

   5–10 million people, around 10% of the empire's population

   Legacy

   a Roman army and economy weakened for decades

4. 249–262AD
   03 · Roman Empire

   The Plague of Cyprian

   unknown cause

   It is named after Bishop Cyprian of Carthage, who described it as a sign of the end of the world. According to some ancient sources, at its peak it killed up to 5,000 people a day in Rome. In Luxor, Egypt, archaeologists found a burial site from that period, with bodies covered in a thick layer of lime, used at the time as a disinfectant, and the kilns where the lime was produced.

   Deaths (estimates)

   unknown; sources of the time describe entire cities depopulated

   Legacy

   one of the oldest archaeological records of lime being used against disease

5. 541–549recurrences until 750
   04 · Byzantine Empire and the Mediterranean

   The Plague of Justinian

   bacterium · Yersinia pestis

   The first documented plague pandemic. It started in Egypt and reached Constantinople in 542, carried by rats and fleas on grain ships. The historian Procopius wrote of thousands of deaths a day in the capital, and Emperor Justinian fell ill and survived. DNA analysis of victims' skeletons confirmed the plague bacterium in the 21st century.

   Deaths (estimates)

   classic estimates: 25–50 million, including recurrences; recent studies suggest the impact was smaller

   Legacy

   an empire weakened just as it was trying to reconquer the west of the former Roman Empire

6. The Middle Ages and the early modern era
7. 1346–1353Europe, Asia, North Africa
   05 · The deadliest pandemic on record

   The Black Death

   bacterium · Yersinia pestis

   The plague came from Central Asia along trade routes, reached Crimea in 1346 and, aboard Genoese ships, Messina in 1347. Within a few years it killed between a third and half of Europe's population. The labor shortage drove up wages and weakened serfdom. In 1377, Ragusa (today Dubrovnik) imposed a 30-day isolation on ships and travelers; Venice later extended it to 40, "quaranta giorni", which gave us the word "quarantine".

   Deaths (estimates)

   25–50 million in Europe alone

   Legacy

   quarantine, the first organized public health measure

8. from 1520the Americas
   06 · Mexico, Central and South America

   Smallpox in the New World

   virus · variola virus

   Brought by Spanish expeditions, smallpox struck populations that had never encountered the disease and had no immunity. In 1520 it killed Cuitláhuac, the Aztec ruler, and Tenochtitlan fell the following year. Together with measles, influenza and typhus, wars and exploitation, over the next century it led to the loss of a large part of the indigenous population, up to 90% in some regions.

   Deaths (estimates)

   tens of millions in the Americas; in the 20th century alone, smallpox killed around 300 million people worldwide

   Legacy

   Edward Jenner's vaccine (1796) and the eradication of smallpox, declared by the WHO in 1980

9. 1545–1548Mexico
   07 · New Spain

   Cocoliztli

   bacterium, most likely Salmonella Paratyphi C

   In Nahuatl, "cocoliztli" means "pestilence". The sick had high fever, headaches and bleeding, and death came within a few days, in a population already weakened by a terrible drought. In 2018, a genetic study of victims' skeletons from Teposcolula-Yucundaa found the bacterium that causes paratyphoid fever, the strongest explanation so far.

   Deaths (estimates)

   5–15 million people, a large part of Mexico's indigenous population

   Legacy

   genetic archaeology, which today identifies centuries-old microbes

10. 1665–1666England
    08 · London

    The Great Plague of London

    bacterium · Yersinia pestis

    The last major plague outbreak in England. Those who could afford it, including King Charles II and the court, left the city. Houses with sick people were shut with the family inside and marked with a red cross. The village of Eyam, in Derbyshire, isolated itself voluntarily to keep the disease from spreading: more than 250 villagers died, but the surrounding region was spared.

    Deaths (estimates)

    around 100,000 people, nearly a quarter of London's population

    Legacy

    the example of Eyam, a community isolating itself voluntarily for the good of others

11. 1770–1772Russia
    09 · Moscow

    The Moscow Plague

    bacterium · Yersinia pestis

    Brought from the theater of the Russo-Turkish War, the plague reached Moscow in 1770. In September 1771, fear and quarantines led to the Plague Riot: Archbishop Ambrosius, who had moved a venerated icon to prevent crowds, was killed by the mob. Catherine II sent Grigory Orlov to restore order and organize hospitals, quarantines and the disinfection of homes.

    Deaths (estimates)

    50,000–100,000 people in Moscow alone

    Legacy

    a lesson about communication: measures imposed without people's trust can provoke riots

12. 1793United States
    10 · Philadelphia

    The Philadelphia Yellow Fever Epidemic

    virus, transmitted by mosquitoes

    Philadelphia was then the capital of the United States. More than 20,000 residents, including members of the government, fled the city. No one knew the disease was transmitted by mosquitoes, and the epidemic stopped only when the autumn cold killed them. Members of the Free African Society cared for the sick, based on the mistaken belief that Black people were immune; many of them died.

    Deaths (estimates)

    around 5,000 people, nearly a tenth of the city's population

    Legacy

    mosquito transmission, confirmed in 1900 by Walter Reed's team; today there is a vaccine

13. The 19th century
14. 1813–1814Wallachia
    11 · Bucharest

    Caragea's Plague

    bacterium · Yersinia pestis

    The best-known epidemic in the history of Bucharest is named after the ruling prince of the time, Ioan Gheorghe Caragea. The plague hit the capital and the surrounding villages hard, and the gravediggers who collected the dead remained in the city's memory as nightmarish figures. Many of the dead were buried in mass graves.

    Deaths (estimates)

    tens of thousands of people in Wallachia

    Legacy

    in the following decades, the Principalities set up permanent quarantine stations on the Danube

15. from 18177 pandemics
    12 · On every continent

    The Cholera Pandemics

    bacterium · Vibrio cholerae, through water and food

    The first pandemic started in 1817 in the Ganges delta, in Bengal. Six more followed, on every continent, Romania included. In 1854, in London, physician John Snow mapped the cases in one neighborhood and showed that they all led to the same water pump, on Broad Street. Removing the pump handle became the symbol of modern epidemiology. The seventh pandemic, which began in 1961, continues to this day.

    Deaths (estimates)

    millions of people in the 19th century; today, between 21,000 and 143,000 deaths a year, according to the WHO

    Legacy

    drinking water, sewage systems and oral rehydration salts, which save most patients

16. 1889–1890worldwide
    13 · The first pandemic of the industrial age

    The "Russian" Flu

    virus, most likely influenza

    The first cases were reported in Saint Petersburg, and within a few months the disease circled the globe by train and steamship, followed by the press around the world. The cause is uncertain: an influenza virus, according to the classic hypothesis, or the human coronavirus OC43, according to a newer one.

    Deaths (estimates)

    around 1 million people

    Legacy

    proof that transport networks can carry a disease around the world in a few weeks

17. The 20th century
18. 1918–1920worldwide
    14 · During and after World War I

    The Spanish Flu

    virus · influenza A(H1N1)

    It infected around 500 million people, a third of the world's population, in three waves. Unlike ordinary flu, it killed many young, healthy adults. It did not come from Spain: the Spanish press, uncensored during the war, was simply the first to write freely about it. With no vaccine and no antibiotics for the pneumonias that followed, cities defended themselves with masks, by closing schools and theaters and by banning gatherings.

    Deaths (estimates)

    at least 50 million people, according to the CDC

    Legacy

    non-pharmaceutical measures: cities that adopted them earlier had fewer deaths

19. 1916–1955peak of the epidemics
    15 · United States and Europe

    The Polio Epidemics

    virus · poliovirus

    In 1916, an epidemic that started in New York led to more than 27,000 cases and 6,000 deaths in the United States, mostly children. The virus spreads through contaminated hands, water and food and can cause paralysis, sometimes even of the respiratory muscles; the "iron lung" kept thousands of patients alive. The Salk injectable vaccine (1955) and the Sabin oral vaccine (1960s) changed everything.

    Deaths (estimates)

    in 1988 there were still around 350,000 cases of paralysis a year

    Legacy

    cases have fallen by more than 99%; the wild virus now circulates only in Pakistan and Afghanistan

20. 1957–1958worldwide
    16 · Started in China

    The Asian Flu

    virus · influenza A(H2N2)

    It appeared in China in early 1957 and within a few months reached Singapore, Hong Kong and the United States. This time, laboratories quickly isolated the virus, and a vaccine was available within a few months. A decade later, the Hong Kong flu (1968–1969, H3N2) killed around another million people.

    Deaths (estimates)

    around 1.1 million people, according to the CDC

    Legacy

    the global influenza surveillance network, which selects the vaccine strains every year

21. from 1981worldwide
    17 · Ongoing pandemic

    HIV/AIDS

    virus · HIV, through blood and sexual contact

    The first AIDS cases were described in 1981, in the United States. Genetic studies show that the virus passed from chimpanzees to humans in Central Africa, around the 1920s. In Romania, in the late '80s and early '90s, more than 10,000 children were infected, mainly through reused syringes and needles and untested transfusions. Combination antiretroviral therapy, available since 1996, turned the disease into a chronic one.

    Deaths (estimates)

    more than 40 million people since the start of the epidemic, according to UNAIDS

    Legacy

    tested blood, disposable needles and syringes, and universal precautions in hospitals

22. The 21st century
23. 2002–200329 countries
    18 · The first pandemic coronavirus

    SARS

    virus · SARS-CoV

    It started in southern China and spread to 29 countries, largely through hospitals: about one fifth of patients were healthcare workers. It was stopped in less than a year, without a vaccine, through case detection, isolation, contact tracing and protective equipment.

    Deaths

    8,096 cases and 774 deaths, according to the WHO

    Legacy

    the International Health Regulations revised in 2005 and pandemic preparedness plans

24. 2009–2010worldwide
    19 · Started in North America

    The Swine Flu

    virus · influenza A(H1N1)pdm09

    A new virus, with genes from swine, avian and human influenza, emerged in Mexico and the United States in spring 2009, and the WHO declared a pandemic in June. Unlike seasonal flu, it hit mainly children and young adults: about 80% of deaths were in people under 65.

    Deaths (estimates)

    between 151,700 and 575,400 deaths in the first year, according to the CDC

    Legacy

    the virus is now part of the annual flu vaccine

25. 2014–2016West Africa
    20 · Guinea, Liberia, Sierra Leone

    Ebola

    virus · Ebola, through blood and body fluids

    It began in Guinea in late 2013 and spread to Liberia and Sierra Leone, with exported cases in Europe and the United States as well. It is transmitted through direct contact with the blood and body fluids of sick or deceased people, which is why patient care and burial rituals were at the center of the epidemic. More than 500 healthcare workers died.

    Deaths

    28,600 cases and 11,325 deaths, according to the CDC

    Legacy

    strict donning and doffing protocols and a vaccine approved in 2019

26. from 2019worldwide
    21 · The most recent pandemic

    COVID-19

    virus · SARS-CoV-2

    The first cases were reported in Wuhan in December 2019, and the WHO declared a pandemic on March 11, 2020. The virus spreads mainly through the air, via respiratory particles, including from people without symptoms. Vaccines were developed and authorized in less than a year, and the public health emergency of international concern ended on May 5, 2023.

    Deaths

    more than 7 million deaths reported to the WHO; estimated excess mortality for 2020–2021 was nearly 15 million

    Legacy

    masks, hand hygiene, ventilation and telemedicine, now part of everyday routine

There were other serious epidemics that did not make the list: the Great Plague of Marseille (1720–1722), MERS (since 2012, nearly 2,600 confirmed cases and more than 900 deaths), the 2015–2016 Zika epidemic, with thousands of children born with microcephaly, and mpox in 2022.

What they taught us, in order of discovery

1. 1377 · QuarantineRagusa isolates ships and travelers for 30 days, and Venice extends the period to 40. The principle is still used today, from isolating the sick to quarantining contacts.
2. 1796 · The first vaccineEdward Jenner shows that inoculation with cowpox protects against smallpox. The word "vaccine" comes from the Latin "vacca" (cow).
3. 1847 · Hand hygieneIn Vienna, Ignaz Semmelweis requires handwashing with chlorinated lime solution before deliveries, and deaths from puerperal fever drop dramatically.
4. 1854 · EpidemiologyJohn Snow links cholera cases to a contaminated water pump and shows that data and a map can stop an epidemic.
5. 1880s · GermsLouis Pasteur and Robert Koch prove that infectious diseases are caused by microorganisms. Koch identifies the tuberculosis bacillus (1882) and the cholera vibrio (1883).
6. 1928 · AntibioticsAlexander Fleming discovers penicillin, widely used from the 1940s. Bacterial diseases such as plague become treatable.
7. 1980 · Smallpox eradicationAfter a global vaccination campaign, the WHO declares smallpox eradicated, the first and only human disease completely eliminated.
8. 2020 · Vaccines in less than a yearNew technologies, including mRNA vaccines, make it possible to develop and authorize a COVID-19 vaccine within months.

How they spread and how we protect ourselves today

Almost all the epidemics on the list fall into a few routes of transmission. For each one there are clear measures, and many of them require nothing more than discipline and the right equipment.

Today's epidemics are stopped with the same principles as centuries ago, only now we have much better tools. In healthcare facilities, pharmacies and anywhere with lots of people, a few gestures repeated correctly make the difference.

Medical face mask or FFP2?

• PRIMA type IIR surgical masks, 3-ply with a meltblown filter layer, compliant with EN 14683, and Abena IIR medical face masks, compliant with EN 14683:2019. For children: children's medical face masks.
• PRIMA face shield, reusable, with 10 replacement visors, or indirect-vent safety goggles, for procedures with a risk of splashing.
• PRIMA hooded coverall, made of nonwoven fabric, and visitor protective gowns, for isolation areas.
• For fever screening: the Microlife NC150 non-contact thermometer, the PRIMA ear and forehead thermometer and, for oxygen saturation, the fingertip pulse oximeter.

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