20 of the worst epidemics and pandemics in history

• Black Death (200 million deaths)
• Latin American smallpox epidemic (56 million deaths)
• Spanish flu (40–50 million deaths)
• Plague of Justinian (30–50 million deaths)
• HIV/AIDS (25–35 million deaths)
• Plague of 1855 (12 million deaths)
• Cocoliztli (5–15 million deaths)
• Antonine Plague (5 million deaths)
• Russian typhus epidemic (3 million deaths)
• COVID-19 (at least 2 million deaths)
• Russian flu of 1889-90 (1 million deaths)
• Hong Kong flu of 1968 (1–4 million deaths)
• Japanese smallpox epidemic (1 million deaths)
• Third cholera pandemic (1846) (1 million deaths)
• Sixth cholera pandemic (1899) (at least 800,000 deaths)
• Fourth cholera pandemic (1865) (600,000 deaths)
• Encephalitis lethargica (up to 400,000 deaths)
• Swine flu outbreak (200,000–575,000 deaths)
• Yellow fever epidemic (100,000–150,000 deaths)
• West African Ebola outbreak (11,000 deaths)

For the vast majority of people, COVID-19 is the first and only pandemic of our lifetimes—but for the human race, it’s not the first or the deadliest. In Shakespeare’s time, for example, there was nothing unusual about quarantines and closures of public places during plague outbreaks. Let’s take a look at some of the deadliest pandemics in human history.

Black Death (200 million deaths)

The Black Death struck Europe in 1347, when ships manned by infected sailors docked in the Italian port of Messina, according to The History Channel. This bubonic plague pandemic is thought to have killed about 200 million people, making it the deadliest pandemic in recorded history. Caused by a bacterium, Yersinia pestis, it spread through the air and through the blood of infected fleas and rats. Germs would not be discovered for another five centuries, so staying away from others was the only way to avoid the disease: “Doctors refused to see patients; priests refused to administer last rites; and shopkeepers closed their stores,” the History Channel explains. Other “solutions” were less effective and more sinister—Jews and “heretics” were expelled from their communities, and many people turned to self-mutilation to gain divine forgiveness. While this plague had run its course by 1350, waves of plague would threaten Europe for centuries to come.

Latin American smallpox epidemic (56 million deaths)

In April 1520, according to Science Magazine, a contingent of Spanish soldiers landed in Veracruz, Mexico, unwittingly bringing smallpox to Latin America. By October of that year, the disease had ripped through the Aztec capital, Tenochtitlán, killing half the population of the city including the king, Cuitláhuac, and many of his advisors. The disease worked in the conquistadors’ favour: “By the time Hernán Cortés and his troops began their final assault on Tenochtitlán, bodies lay scattered over the city, allowing the small Spanish force to overwhelm the shocked defenders,” Heather Pringle of Science writes. Between 1492 and 1592, according to Science Direct, 90 per cent of the Indigenous population of the Americas was wiped out by various epidemics, even impacting the climate.

Spanish flu (40–50 million deaths)

The U.S. Centers for Disease Control and Prevention calls the 1918 flu pandemic “the most severe pandemic in recent history.” The first cases were reported in March 1918 at a military base in Fort Riley, Kansas, although the disease became known as the Spanish flu because it was first reported in the Spanish press. (In Spain, according to the History Channel, people “believed the virus came from France and called it the ‘French Flu’.”) The response to the pandemic was complicated by a lack of effective vaccines or treatment (the first flu shot wasn’t developed until the 1940s), the First World War (travelling soldiers brought the disease with them) and a health worker shortage. In the United States, local responses resembled today’s COVID-19 control measures: “Officials…imposed quarantines, ordered citizens to wear masks and shut down public places, including schools, churches and theaters. People were advised to avoid shaking hands and to stay indoors, libraries put a halt on lending books and regulations were passed banning spitting.” For the few remaining 1918 flu survivors around the world, COVID-19 has created an unpleasant sense of déjà vu.

Plague of Justinian (30–50 million deaths)

The Plague of Justinian was caused by the same rat-borne bacterium, Yersinia pestis, that unleashed the Black Death on medieval Europe. According to the Ancient History Encyclopedia, it was first detected in Constantinople in 542 CE, during the reign of Justinian I, accompanied by some unusual climatic phenomena that helped its spread: “Colder than usual weather affected crop harvests, leading to food shortages that resulted in the movements of people throughout the region. Accompanying these reluctant migrants were plague-infected, flea-ridden rats.” As with other pandemics, war, trade and travel helped the disease spread far and wide. The initial outbreak in Constantinople lasted only four months, according to the encyclopedia, but periodic flare-ups would occur for the next 200 years. According to Smithsonian Magazine, the plague is “widely believed to have culled the era’s Mediterranean populations by up to 60 percent,” although recent archaeological evidence suggests it may not have been as transformative as previously thought.

HIV/AIDS (25–35 million deaths)

In 1981, doctors were baffled when rare forms of pneumonia and skin cancer began appearing in young gay men in the United States. Over the next year, the diseases also appeared in drug users and in blood transfusion recipients. French scientists were the first to isolate the human immunodeficiency virus (HIV) which caused acquired immunodeficiency syndrome (AIDS). The virus is believed to have made the leap from infecting chimps to infecting humans sometime in the early 20th century, in central Africa; it went on to ravage every continent. There is still no cure for AIDS. Citizens’ groups like ACT-UP (pictured) in North America and Europe lobbied for increased investment and research. Although the development of antiretroviral drugs starting in the mid-1990s turned it into a manageable chronic condition for many patients, particularly in wealthier countries, AIDS still killed nearly 700,000 people in 2019.

Plague of 1855 (12 million deaths)

The third plague pandemic emerged in China in 1855 and later spread to India and Hong Kong. It was mainly spread by fleas, at least at first. The History Channel states that the pandemic “was considered active until 1960, when cases dropped below a couple hundred.” Bubonic plague outbreaks are still a public health threat in some countries today, notably in remote parts of Madagascar, where small flare-ups are frequent. The disease which once killed millions and threatened the survival of nations is now easily treatable with antibiotics.

Cocoliztli (5–15 million deaths)

In 1545, a mysterious disease called cocoliztli first surfaced among Indigenous people in Mexico. The cause of the disease has never been clearly identified, although DNA recovered from the teeth of victims has “revealed a surprising new candidate,” according to a recent story in The Atlantic. “Dental pulp—the soft, living tissue inside teeth—is full of blood vessels and thus any pathogens that once circulated in the blood,” Sarah Zhang writes. “And hard enamel on the outside protects the DNA of those pathogens for centuries.” Scientists concluded that Salmonella enterica, a bacterium that spreads through contaminated food or water, was present in many of the teeth, making it a prime suspect—although by no means the only possible cause of the disease. A similar epidemic struck Mexico in 1576, but no S. enterica epidemics of similar scale have been recorded since, making some researchers wonder if another pathogen may be the real culprit.

Antonine Plague (5 million deaths)

The Antonine Plague was a smallpox epidemic which swept through much of the Roman Empire around 165 CE, killing as much as 10 per cent of the population. At the plague’s peak in the year 189 CE, according to Smithsonian Magazine, as many as 2,000 people died per day in Rome, and the empire was shaken to its core: “The plague so ravaged the empire’s professional armies that offensives were called off. It decimated the aristocracy to such a degree that town councils struggled to meet [and] abandoned farms and depopulated towns dotted the countryside from Egypt to Germany.” However, Romans found ingenious ways to keep the structures of society afloat, including making the sons of freed slaves eligible for local office, and the empire endured for another two centuries. Roman historian Cassius Dio believed “the trauma of living through plague can be overcome if a well-governed society works together to recover and rebuild, and the society that emerges from those efforts can become stronger than what came before.”

Russian typhus epidemic (3 million deaths)

The Spanish flu and bullets were not the only potentially lethal threats faced by soldiers in the First World War. Between 1918 and 1922, typhus, a bacterial disease spread by body lice, “swept from Serbia through Russia and surrounding countries—the Eastern Front of The Great War—causing an estimated 30,000,000 cases and 3,000,000 deaths,” medical historian Frederick Holmes writes. “Living in close quarters, huddling together for warmth, soldiers made it easy for lice to move from man to man, living comfortably in the seams of their uniforms and enjoying blood meals. […] The War to End All Wars would have ended sooner had Russia managed to conquer the louse.” According to the U.S. Centers for Disease Control, typhus is considered a rare disease today, although the lice which cause it still thrive in areas where people are unable to wash regularly.

COVID-19 (at least 2 million deaths)

On Dec. 31, 2019, health officials in the Chinese city of Wuhan confirmed “dozens of cases of pneumonia from an unknown cause.” A week later, the source of the outbreak was identified as a new coronavirus. On Jan. 20, 2020, the first cases outside of China were confirmed; by March, the disease had spread around the world, cancellations of major international events began, and countries closed their borders to non-citizens; several nations imposed stay-at-home orders. The World Health Organization estimated that as many as 1.6 billion people were at risk of losing their livelihoods due to the pandemic’s economic impact. As of this writing, the World Health Organization has reported 6.5 million deaths worldwide from coronavirus, over 1 million in the United States alone. The development of multiple vaccines has raised hope that the pandemic may be under control in some countries within a few years, but the way we travel, work and socialize may never be the same.

Russian flu of 1889-90 (1 million deaths)

In fall 1889, a flu pandemic “struck with a vengeance in the Russian capital of St. Petersburg, infecting as much as half the population,” according to the History Channel. Within a few months, it had spread to much of the world, following major roads, rivers and railway lines. It is often considered the first modern pandemic—the first one in the era of rail and steamship travel. “As long as people could move with ease from city to city and country to country, stopping its spread would be all but impossible,” the History Channel observes. The pandemic had largely burned out in the U.S. by February 1890.

Hong Kong flu of 1968 (1–4 million deaths)

The 1968 flu pandemic was caused by a highly contagious flu strain that emerged in Hong Kong in summer 1968, according to Encyclopedia Britannica. Close to 500,000 cases were already reported within two weeks of the strain’s emergence. Soldiers returning from Vietnam spread the disease to the United States. “The highest levels of mortality were associated with the most susceptible groups, namely infants and the elderly,” the encyclopedia explains. “Although a vaccine was developed against the virus, it became available only after the pandemic had peaked in many countries.” The strain which caused the 1968 pandemic is still in circulation today.

Japanese smallpox epidemic (1 million deaths)

Smallpox first emerged in Japan in 735 CE; that epidemic is thought to have killed as much as one-third of the population of the country. Like the smallpox epidemic that would hit Central America centuries later, this was a virgin-soil epidemic, ravaging a population which had no previous exposure to it. After the initial epidemic, outbreaks returned every 10-15 years for several centuries. On average, three out of 10 people who caught smallpox died. Smallpox eventually became endemic in most of the country. Mass vaccination campaigns starting in the late 1950s led to the eradication of the disease from Asia in 1975 and from the world in 1980.

Third cholera pandemic (1846) (1 million deaths)

There have been seven major cholera pandemics in the past 200 years. Cholera is caused by the Vibrio cholerae bacterium, and spread through food or water contaminated with fecal matter. According to the Centers for Disease Control, cholera “is most likely to occur and spread in places with inadequate water treatment, poor sanitation, and inadequate hygiene.” The third pandemic, generally considered the most deadly, originated in India. During the worst year of the pandemic, in 1854, 23,000 people died in Britain alone. British doctor John Snow traced the source (pictured) of a particularly deadly London outbreak to a contaminated water pump. “After [Snow convinced] officials to remove the pump handle, the number of cholera cases in the area immediately declined,” according to CBC.

Sixth cholera pandemic (1899) (at least 800,000 deaths)

The sixth cholera pandemic originated in India and hit hard there, killing 800,000 people. It eventually spread into the Middle East, North Africa and parts of Europe, according to CBC. Although subsequent cholera outbreaks have not been nearly as devastating, the disease still circulates—most recently, 500 people died in an outbreak in Zimbabwe in 2008, and an outbreak in Haiti that began in 2010 and ended in 2019 killed 10,000 people.

Fourth cholera pandemic (1865) (600,000 deaths)

The fourth cholera pandemic, like the one before it, originated in India. It began in 1863 in the Ganges Delta, and “travelled with Muslim pilgrims to Mecca and then to Russia, Africa, North America and Europe,” according to The Guardian. In 1866, it spread further with the Austro-Prussian War. “Although [cholera] gathers and is intensified in unhealthy places, it moves along the lines of human intercommunication,” The Guardian observed. “There are two modes of dealing with contagious diseases. One is to bar them out by means of a rigid quarantine; the other is to establish such a degree of cleanliness and careful observance of sanitary laws as to reduce to a minimum any predisposition to disease.”

Encephalitis lethargica (up to 400,000 deaths)

A mysterious pandemic of “sleepy sickness,” also known as encephalitis lethargica or epidemic encephalitis, sickened up to 1 million people around the world between 1916 and 1926. According to Scientific American, the disease “emerged from the cold, wet plains and trenches of northern France and Belgium, the battlefields of World War I… a landscape crowded with millions of young men living under…unsanitary conditions at close quarters.” In people who caught the disease, flu-like symptoms gave way to uncontrolled eye movements, and later “an irresistible need to sleep. This lethargy lasts for weeks, in some cases even a year or more. […] Mortality in this acute phase of the disease was as high as 30 or 40 percent.” Of those who survived, many developed Parkinson’s disease. The epidemic disappeared as quickly as it had arisen, about 10 years later. Scientists have not been able to pinpoint a single cause for this disease, “leaving the culprit unknown, and presumably at large.”

Swine flu outbreak (200,000–575,000 deaths)

In June 2009, nearly two months after two human cases of a flu strain common in pigs were found in California, the World Health Organization declared that the H1N1 flu virus had brought about a pandemic. By 2019, H1N1 had infected 100 million people in the United States, leading to more than 900,000 hospitalizations and 75,000 deaths. Worldwide, it killed as many as 575,000 people (although estimates of the total death toll vary widely). The people H1N1 killed were younger, on average, than those at risk of death from seasonal flu. (“The elderly, whose immune systems had seen viruses similar to this one long ago, weathered the pandemic pretty well,” medical news website StatNews observes.) The international response to the H1N1 pandemic was later criticized as overblown—raising questions about what the world learned from the experience. “The 2009 H1N1 pandemic should have been a warning sign,” Steffanie Strathdee, the associate dean of Global Health Sciences at the University of California San Diego’s department of medicine, told LiveScience. “It didn’t end up being a pandemic that killed millions of people as we feared it would, but it should have been a wake-up call.”

Yellow fever epidemic (100,000–150,000 deaths)

Yellow fever is a mosquito-borne virus with a mortality rate as high as 50 per cent. A series of epidemics between 1793 and 1905 in the southern and eastern United States killed thousands. By all accounts, it wasn’t a pleasant way to die: “Victims would experience a host of unpleasant symptoms: jaundice, chills, nausea, headaches, fever, convulsions, delirium. Then, there was the blood.” In the later stages of the illness, victims bled through their eyes, noses and ears. People who survived the disease were immune. In 19th-century New Orleans, according to NPR, survivors were referred to as “acclimated,” and unacclimated people struggled to find jobs and housing. Starting in the early 20th century, a series of vaccines were developed, at a heavy cost—several vaccine researchers accidentally contracted the disease and lost their lives. The disease still kills about 30,000 people per year, mainly in Africa. Proof of vaccination is required for international travel to many African countries.

West African Ebola outbreak (11,000 deaths)

The Ebola virus was first discovered in 1976 along the Ebola River in the Democratic Republic of Congo. It is spread by contact with the blood or bodily fluids of infected animals or people. The world’s largest Ebola outbreak to date began in December 2013, when a two-year-old in the West African country of Guinea died from the disease. By September 2014, over 3,000 people had died, mainly in hard-hit Liberia, Guinea and Sierra Leone; neighbouring Nigeria and Senegal were better able to contain the disease. There were also isolated cases in the United States and several European countries. Guinea, the last affected country to stamp out the virus, was declared Ebola-free in June 2016. The West African outbreak eventually led to the development of effective Ebola vaccines and treatments.