Explore History's Deadliest Diseases

This plague, brought back to the Roman Empire by soldiers returning from military campaigns in the Far East, was likely caused by measles or smallpox. Contemporaneous accounts estimate the death toll peaking at 2,000 people a day in Rome, with an estimated total toll of five million. The disease is believed to have originated in Seleucia (modern-day Iraq).

Some historical sources claim that as many as 5,000-10,000 people were dying a day at the peak of the Justinian Plague. Like the later Black Plague, this 6th century pandemic was likely caused by infected fleas, carried into new zones by rats.

This pandemic was contagious enough that even Byzantine Emperor Justinian I contracted it. Although Justinian survived, his name became irrevocably twinned with the plague, which would recur regularly for the next two centuries. In its first years, the Plague of Justinian was said to take the lives of 40% of the Byzantine capital, Constantinople.

The bubonic plague that ravaged Europe, Asia, and Africa in the medieval period is likely the most well-known disease in history. Its shockingly high death toll stuns to this day. The outbreak is now believed to have begun in Asia. Bubonic plague, originated in fleas, was carried by rats from merchant port to merchant port across the world.

Decimating an estimated 30-60% of the European population between the years 1347-1351, the Black Death not only killed millions, but also set back social and technological advancements. The bubonic plague returned repeatedly in Europe until the late 17th century, but never again reached such fatal heights as in the 14th.

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When Europeans first set foot in the Americas, they brought all of their germs with them. The Indigenous people, who had never been exposed to such diseases, were decimated. In 1519, Hernán Cortés landed ashore the Aztec Empire. Smallpox, by this time, had already started raging in the island of Hispaniola, but had been curtailed by geography.

Cortés brought the disease onto the mainland, where it killed as much as 40% of the Aztec population, estimated at eight million. Over the next 300 years, epidemics and pandemics continued to winnow the Indigenous population, helped along by some colonizers who resorted to such heinous tactics as purposefully giving Native Americans disease-riddled supplies.

Just 25 years after the smallpox outbreak, a cocoliztli (Aztec for pest or plague) epidemic swept through the Aztec Empire. It’s still unclear to researchers whether cocoliztli was a distinct disease or should fall under the umbrella of other diseases such as measles or typhus. Whatever its origin, the 1545 cocoliztli outbreak caused at least 12 million deaths. A further recurrence in 1576 would take another 2 million souls.

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Cholera, like the bubonic plague, was a disease that cropped up consistently during the Industrial Revolution and the Machine Age. The first major outbreak occurred in 1817, primarily limited to Asia. A second pandemic had further reach geographically—it was also more fatal, reaching outside of Asia to the United Kingdom and the U.S. and killing hundreds of thousands.

The third round of cholera was the most fatal, killing a million in Russia alone. This pandemic hit the United States in the midst of westward migration. Settlers moving west brought cholera with them, killing up to 12,000 people along the Oregon Trail and other well-worn paths to the West Coast.

Although called trench fever at the time of its highest virulence, this pandemic was actually caused by typhus. Like the Black Death, typhus is caused not just by a virus or bacterium, but by infected vermin. After World War I, the recognition of a relationship between lice and typhus brought an end to the full rage of typhus, but not before some 2.5 million died on the Eastern front in Russia. More fell victim to typhus in Serbia, Austria, and other areas, although the Western Front remained unaffected.

Just over a century ago, a particularly nasty strain of the flu broke out across the world. Before flu vaccinations were common, influenza was a fairly common cause of death. But this strain was unusual for its ability to fatally infect young adults, who are typically able to weather a flu.

Infecting about 500 million people globally, the Spanish flu’s fatality rate was between 4-10%. The reason behind its efficacy is debated to this day—some researchers believe that the strain was particularly virulent, while others point to overcrowding and malnourishment as factors in its fatality. Interestingly, the virus that caused the Spanish flu (H1N1) was the same as 2009’s infamous swine flu.

In the 1950s, an avian flu strain combined with a human flu to create an H2N2 virus that became a category 2 pandemic. After emerging in Singapore, the virus spread to Hong Kong, the United Kingdom, and then around the world. A vaccine was developed within about four months—it’s believed that the American death toll could have reached as high as one million people without the vaccination instead of the actual 70,000. Even with the vaccine, the elderly were particularly susceptible to the Asian flu.

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The third major flu pandemic of the 20th century, the Hong Kong flu was highly contagious, leading to cases around the globe within months. Although its mortality rate was lower than 1957’s flu pandemic, the rate of contagion led to more deaths than seen in the previous decade.

In 1981, the first cases of what would become known as Acquired Immunodeficiency Syndrome were noted in a CDC report. A year and a half later, it would receive its official name, by which time hundreds had already died. At first understood to only affect gay men—leading the disease being temporarily named Gay-Related Immune Deficiency—it took years for HIV/AIDS research to be fully funded and even longer for the disease to be understood.

In the 50 years since HIV/AIDS became a global pandemic, approximately 75 million people around the world have been infected with HIV. Approximately 35 million of those infected have died. Although the "crisis" is considered ended as of 1995, HIV/AIDS is an ongoing global health concern as scientists continue to seek a cure or vaccination.

Related: 11 Fascinating LGBT History Books to Read for Pride Month

Sources: Ancient History Encyclopedia; PBS; World Health Organization 

Featured photo: Wikimedia Commons