The Worst Epidemics and Pandemics in History

Also known as the Plague of Galen, this pandemic arose after Roman troops laid siege to a Mesopotamian city. They subsequently spread the disease — whose symptoms consisted of skin eruptions, pharyngitis, diarrhea, and fever — amongst themselves and throughout the Roman empire, leading to millions of deaths.

The Justinian Plague is the first major pandemic caused by the same bacterium, Yersinia pestis, that would cause the Black Death centuries later. Egypt, the Mediterranean, Europe, and the Arabian Peninsula all saw great casualties. Constantinople, which was ravaged by the plague, recorded up to 5,000 deaths a day during the height of the outbreak.

This smallpox epidemic killed a third of Japan’s populace and led to subsequent famine as farmers died or abandoned their fields. After widespread migrations, dislocation, and the deaths of many powerful officials, the Japanese economy took years to recover.

Most likely spread by fleas as well as airborne aerosols, the world’s second known bubonic plague affected much of Eurasia as well as North Africa. The Black Death is known as the most fatal pandemic in recorded history, killing an estimated 75-200 million people on three continents, including up to 60% of the European population.

During the Spanish conquest of the Americas, Conquistadors Hernán Cortés and Pánfilo de Narváez brought the novel smallpox virus — along with their soldiers and slaves — to the New World. The disease wiped out 25-50% of the population of central Mexico, and helped Spain conquer the Aztec empire.

The first in a series of viral hemorrhagic fevers to strike Mexico in the 16th century, this epidemic killed about 80% of the native population. Symptoms included profuse bleeding from every orifice, as well as neck nodules, high fever, jaundice, thirst, headache, and diarrhea.

Affecting populations from northern Sonora down to Guatemala, the second outbreak of Cocoliztli killed up to hundreds of people a day in larger towns during the height of the epidemic. In the end, half the population of Mexico was dead, with Indigenous people suffering the highest mortality rates.

Also referred to as the Great Plague of Milan, this series of outbreaks claimed 25% of the Italian population. The disease was spread by French, German, and Venetian troops during the Thirty Years’ War and is considered to be responsible for triggering a huge decline in Italian economies.

Although the Naples plague spread from the southern Italian coast up to Genoa and inland to Umbria, its most devastating effects were on the population of Naples itself, where up to 200,000 people died. The epidemic ended after a forced quarantine.

This epidemic spread across the Persian Empire — modern-day Iran — into modern-day Iraq, Bahrain, and all the way to Mumbai, India. After thousands of deaths a day, quarantines successfully ended the spread of the disease.

The third and most deadly major cholera pandemic started in India and spread throughout Eurasia into Africa and North America. It caused one of the highest death tolls of any 19th century pandemic, with over 1 million people dying in Russia alone. Cholera is contracted by ingesting the bacterium Vibrio cholerae through contaminated food or water, and causes profuse diarrhea.

The third bubonic plague pandemic (there were also two previous bubonic plague epidemics) started in China and spread throughout the world, causing 10 million deaths in India alone. In 1894, scientists in Hong Kong identified the bacterium responsible, and in 1897 a vaccine was developed and utilized in India.

Also called the Asiatic flu, this pandemic quickly spread around the world as a result of modernized travel by railway and other means. It proliferated across the Northern Hemisphere in four months. Some virologists speculate that the offending pathogen may have been a strain of coronavirus.

This outbreak started in India and spread to other locales in Asia, Russia, Eastern Europe, North Africa, and the Middle East. Sanitation improvements in Western Europe prevented it from taking hold there, but 500,000 people died in Russia, as well as 200,000 in the Philippines and 800,000 in India.

This pandemic, caused by the H1N1 virus, infected 500 million people and killed an estimated 50 million. It first appeared at an army base in the United States, then spread to Europe with American soldiers deployed to fight in WWI. Eventually circling the globe, it occurred in distinct waves, with the deadliest being the second wave in the fall and winter of 1918.

Spreading along the Eastern Front during WWI, the Russian typhus epidemic infected over 30 million people. Typhus is caused by Rickettsia prowazekii bacteria, which spread to humans through infected body lice. Symptoms include headache, fever, abdominal pain, a full-body rash, and delirium caused by swelling of the membranes around the brain.

This new flu strain, H2N2, was a combination of avian and human flu viruses. Its mortality rate was partly due to its ability to cause pneumonia in an infected person even without a secondary bacterial infection. It emerged in China and spread throughout Asia to Europe and eventually to the rest of the world.

Various strains of the 1957 H2N2 virus recombined into a new H3N2 virus, causing the 1968 flu pandemic. The first case was reported in Hong Kong, where the disease spread quickly over the next few weeks. Multiple waves of the virus struck Europe, Australia, and Japan, with the second wave even deadlier than the first.

First reported in California in 1981, AIDS is now one of the largest pandemics in the world. HIV, the virus that causes AIDS, jumped from chimpanzees to humans in early 20th century Africa, and spreads through contact with bodily fluids. Although AIDS has killed at least 35 million people globally, current antiretroviral therapies can prevent its proliferation.

The ongoing COVID-19 pandemic, which has infected more than 762 million people worldwide, is the worst global pandemic of the last 100 years. Since the initial case in late 2019, there have been several waves of infection and near-global travel restrictions and lockdowns. Currently, 13.3 billion doses of vaccine have been administered to people around the world and about 69.9% of the world population has received at least one dose.