Large-scale outbreaks of infectious disease have been relatively rare throughout history, but when they do occur they can be disastrous. These diseases caused millions of deaths throughout history and many of them still cause hundreds of deaths each day. Even with the advancement of medical knowledge and treatment, these epidemics are nature’s way of reminding us that despite our best efforts, nature never has been and never will be under our control.

According to the World Health Organization, a pandemic is “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people.” As humans have spread across the world, so have infectious diseases. Even in this modern era, outbreaks are nearly constant, though not every outbreak reaches pandemic level as the Novel Coronavirus (COVID-19) has.

The continued spread of the coronavirus has prompted governments to enact tough measures to combat the pandemic, such as locking down whole cities and travel restrictions.

Below are the 11 deadliest outbreaks and pandemics in history. Ask yourself—are we prepared as a nation for the next big outbreak?

A Timeline of Historical Pandemics and Death toll. (IMAGE by Visual Capitalist)

11. First Cholera Pandemics

Death Toll: 1+ million – When: 1817

Cholera has been around for centuries — the ancient Greek physician Hippocrates seems to allude to it in his work — but for a long time it was restricted to the delta region of India’s Ganges River. It wasn’t until 1817 when, carried by travelers along trade routes, the disease spread throughout the rest of India and into what is now modern-day Burma and Sri Lanka.

Referred to as “Asiatic cholera” by Britain and the U.S. (which would not be hit by the disease until the 1830s), it eventually reached the Philippines and even Iraq, where 18,000 people died during one three-week period in 1821. During the worst period, it is estimated that as many as 3,000 people were dying per day from cholera. This was the first of seven cholera pandemics that have spread throughout the globe. Between 1816 and 1923, the first six cholera pandemics occurred consecutively and continuously over time and the seventh pandemic originated in Indonesia in 1961.

10. 1968 Flu Pandemic

Death Toll: 1 million – When: 1968-1970

The flu pandemic of 1968—also called the Hong Kong Flu—was one of the famous influenza pandemics in history. Caused by an influenza A virus (H3N2), it was the third pandemic flu outbreak to occur in theC 20th century, killing one million people worldwide and about 100,000 people in the US alone. Most excess deaths were in people 65 years and older.

The first record of the outbreak in Hong Kong appeared on 13 July 1968. By the end of July 1968, extensive outbreaks were reported in Vietnam and Singapore. By September 1968, the flu reached India, Philippines, northern Australia and Europe. The H3N2 virus continues to circulate worldwide as a seasonal influenza A virus.

9. 1889–1890 Flu Pandemic

Death Toll: 1 million – When: 1889-1890

Originally the “Asiatic Flu” or “Russian Flu” as it was called, this strain was an outbreak of the Influenza A virus subtype H3N8. Originating in the Russian Empire and subsequently spreading across the Northern Hemisphere aided by the advent of modern transport infrastructure, the disease claimed one million lives. The first cases were observed in May 1889 in three separate and distant locations, Bukhara in Central Asia (Turkestan), Athabasca in northwestern Canada, and Greenland.

Rapid population growth of the 19th century, specifically in urban areas, only helped the flu spread, and before long the outbreak had spread across the globe. Though it was the first true epidemic in the era of bacteriology and much was learned from it.

8. Asian Flu

Death Toll: 1.1 million – When: 1957-1958

Asian flu of 1957, also called Asian flu pandemic of 1957, outbreak of influenza that was first identified in Singapore in February 1957, Hong Kong in April 1957, and in coastal cities in the United States in summer 1957. The estimated number of deaths was 1.1 million worldwide and 116,000 in the United States.

It originated from mutation in wild ducks combining with a pre-existing human strain. A vaccine for H2N2 was introduced in 1957, and the pandemic slowed down. There was a second wave in 1958, and H2N2 went on to become part of the regular wave of seasonal flu. In 1968, the H2N2 Asian flu disappeared from the human population and is believed to have gone extinct in the wild. Vials of H2N2 influenza remain in laboratories across the world.

7. Antonine Plague

Death Toll: 5 million – When: 165-180

Also known as the Plague of Galen, the Antonine Plague was an ancient pandemic that affected Asia Minor, Egypt, Greece, and Italy and is thought to have been either Smallpox or Measles, though the true cause is still unknown.

It’s believed to have begun in the Mesopotamian city of Seleucia (in modern-day Iraq) and spread to Rome by soldiers returning from the city’s siege. At one point during the extended pandemic an estimated 2,000 Romans died each day. The Antonine Plague was named for Roman Emperor Marcus Aurelius Antoninus, who ruled during the outbreak along with co-regent Lucius Verus. The outbreak began in 165 and lasted until 180, killing over 5 million people and decimating the Roman army. Both emperors are believed to be among its victims.

6. The Third Plague

Death Toll: 12 million – When: 1855

The first two major plague pandemics began with the Plague of Justinian and the Black Death. The most recent, the so-called “Third Pandemic,” erupted in 1855 in the Chinese province of Yunnan. The disease traversed the globe over the next several decades, and by the beginning of the 20th century, infected rats traveling on steamships had carried it to all six inhabited continents.

The worldwide outbreak would eventually claim more than 12 million deaths, with about 10 million killed in India alone. However, it occurred at a time when scientific understanding of diseases was developing, giving doctors and scientists a perfect empirical test case for germ theory and new medicines. This has been a large part of why we haven’t seen a fourth pandemic.

Scientists use a basic measure to track the infectiousness of a disease called the reproduction number — also known as R0 or “R naught.” This number tells us how many susceptible people, on average, each sick person will in turn infect. (IMAGE by Visual Capitalist)

5. HIV/AIDS

Death Toll: 25-35 million – When: 1980-present

Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) were first discovered in the early 1980s. AIDS was first identified in the Republic of Congo in 1976 and it’s thought to have developed from a chimpanzee virus from Africa in the 1920s. Now, according to the most recent data from the CDC from 2006, it’s grown to pandemic proportions, with an estimated 70 million infections and 25-35 million deaths worldwide.

Though we now know that anyone can get AIDS, as the disease is spread through unprotected sex, the sharing of needles and through birth, it was first believed to only affect gay men. Scientific advancements have been made in recent years to extend the lives of those infected.

4. The Plague of Justinian

Death Toll: 30-50 million – When: 541-542

Thought to have killed perhaps half the population of Europe, the Plague of Justinian was an outbreak of the bubonic plague that afflicted the Byzantine Empire and Mediterranean port cities, killing up to 30-50 million people in its year long reign of terror. Even the emperor himself—Justinian I, for whom the plague was named—contracted the disease. While he lived, many didn’t, with modern scholars estimating that at one point as many as 5,000 people died per day in Constantinople, the empire’s capital.

By its end, about 40 percent of the city’s population was dead—so many and so quickly that bodies were left in piles—joined by about one-fourth of the eastern Mediterranean. For about 200 years after this epidemic, outbreaks of the disease manifested occasionally throughout Europe and Asia, but these epidemics were never to reach the level of the one that plagued Constantinople.

3. Spanish Flu

Death Toll: 40-50 million – When: 1918-1919

The influenza pandemic that claimed the lives of tens of millions of people during the course of a single year was one of the deadliest pandemics in recorded history. It was caused by an H1N1 virus, with an avian (bird) origin, though it’s unclear exactly where the virus originated. It is estimated that about 500 million people (or one-third of the world’s population) became infected with the virus. It ultimately caused least 50 million deaths worldwide.

This outbreak was spread globally due to WWI soldiers returning to their home countries, many of whom had become infected with the disease during the war. This global pandemic caused businesses to close, schools to shut down, and left thousands of children orphaned. This particular strain of influenza is similar to strains we see today, but was characterized by an excess buildup of fluid in the victims’ lungs.

2. Smallpox

Death Toll: 56 million – When: 1520 – onwards

Though the exact origin of smallpox is unknown, the disease is believed to have originated in Ancient Egypt, as smallpox-like scars were found on three mummies. The greatest spreads of smallpox are attributed to world exploration and growing trade routes. As soon as the New World was discovered by European explorers, the smallpox quickly swept through the continent and wiped out countless tribes of Native Americans.

During the 18th century, over 400,000 people died annually in Europe from smallpox. Overall fatality rates were around 30%; however, rates were much higher in infants (80-98%), and one third of all survivors went blind. A vaccine for smallpox was eventually created in 1796, but we still witness occasional breakouts of the disease today.

1. The Black Death

Death Toll: 75 to 200 million – When: 1346–1353

The Black Death ravaged most of Europe and the Mediterranean from 1346 until 1353. At least 75 million are believed to have perished throughout the pandemic, with some estimates as high as 200 million. As much as half of Europe may have died in a span of only four years.

Thought to have originated in Asia, the Plague most likely jumped continents via the fleas living on the rats that so frequently lived aboard merchant ships. Ports being major urban centers at the time, were the perfect breeding ground for the rats and fleas, and thus the insidious bacterium flourished, devastating three continents in its wake.