7 of history’s deadliest plagues and the science behind their spread

Long before scientists could identify bacteria or sequence viruses, infectious diseases traveled with soldiers, merchants, and ships. While some outbreaks overwhelmed cities within months, others spread across continents and continued killing for generations.

The deadliest plagues in history reveal how closely disease follows human movement. They also show why comparing death tolls is difficult: ancient records are incomplete, estimates vary, and some pandemics remain ongoing.

These seven events are presented without a strict ranking because their durations and death estimates differ considerably.

1. Black Death

The Black Death swept through Europe during the mid-14th century, devastating communities and disrupting trade, farming, and everyday life.

Widely cited estimates place death toll across affected regions between 75 million and 200 million, although the true total remains uncertain. The disease was caused by Yersinia pestis, the bacterium responsible for plague.

Modern researchers have traced part of its history through DNA preserved in human remains.

A 2022 study recovered plague genomes from burials dated to 1338 and 1339 in present-day Kyrgyzstan. The findings linked those infections to the bacterial lineage behind the Black Death, providing evidence of its origins in Central Asia.

2. The 1918 influenza pandemic

The 1918 influenza pandemic infected an estimated one-third of the world’s population and killed at least 50 million people, including approximately 675,000 in the United States.

Although commonly called the Spanish flu, its geographical origin remains unresolved. One particularly striking feature was its high mortality among otherwise healthy adults aged 20–40.

The virus spread during World War I, when troop movements and crowded living conditions helped carry infections between communities. Doctors lacked influenza vaccines and antibiotics to treat secondary bacterial infections.

Decades later, scientists recovered genetic material from preserved tissues and reconstructed the virus under tightly controlled laboratory conditions to investigate what made it so dangerous.

3. The HIV/AIDS pandemic

First recognized in 1981, the HIV/AIDS pandemic developed over decades rather than as a single, short outbreak.

WHO estimates available for 2024 put cumulative deaths from HIV-related causes at approximately 44.1 million since the epidemic began. That total reflects a continuing global burden, with the WHO African Region remaining the most severely affected.

HIV attacks the immune system, leaving untreated individuals vulnerable to serious infections and certain cancers. Antiretroviral therapy changed that outlook by suppressing the virus and protecting immune function.

4. The COVID-19 pandemic

COVID-19 emerged in late 2019 and spread internationally within months. Its death toll illustrates how much the method of counting matters.

WHO estimated approximately 14.9 million excess deaths associated with the pandemic during 2020 and 2021 alone, substantially exceeding the deaths officially reported as directly caused by COVID-19 during that period.

Excess mortality compares the number of people who died with the number expected without the crisis. It captures both direct deaths and indirect losses, including those associated with disrupted healthcare.

The estimate is therefore neither a count of laboratory-confirmed COVID-19 deaths nor the pandemic’s complete lifetime toll. It provides a broader measure of its impact during those two years.

5. The Justinianic plague

The Justinianic plague reached Constantinople in 541, during the reign of Byzantine Emperor Justinian I. Historical accounts describe a severe outbreak that overwhelmed the city.

Popular summaries frequently cite tens of millions of deaths, but researchers continue to debate how extensive the mortality was and how strongly the pandemic affected the wider Mediterranean world.

Scientific evidence has identified Yersinia pestis as the pathogen involved. Establishing the bacterium’s presence, however, does not establish a precise death toll. Researchers examining historical and environmental evidence have challenged sweeping claims about population collapse.

6. The third plague pandemic

The third plague pandemic began in southwestern China in 1855 and spread worldwide, reaching ports and inland communities across inhabited continents.

A University of St Andrews research project places its death toll at approximately 12 million through 1959. International shipping helped connect outbreaks in widely separated places.

This pandemic also brought a major scientific breakthrough. Alexandre Yersin isolated the plague bacterium in 1894 during the Hong Kong outbreak.

Understanding the pathogen and its transmission through infected fleas helped turn an apparently mysterious catastrophe into a disease that could be investigated and controlled.

7. Smallpox epidemics in the Americas

Smallpox devastated Indigenous communities following European arrival in the Americas. An outbreak reached present-day Mexico in 1520, followed by repeated waves of disease.

Communities with no previous exposure to the virus suffered catastrophic losses, while other introduced infections, including measles and influenza, compounded the destruction.

The death toll requires particular care. Large estimates for Indigenous population decline encompass multiple diseases and the wider effects of colonization, rather than smallpox alone.

Presenting those losses as one smallpox outbreak creates a misleading comparison. This was a succession of epidemics across different regions and decades, whose combined consequences reshaped societies throughout the Americas.

What these outbreaks reveal

These outbreaks differed in their pathogens, transmission routes, and duration. Their histories also reflect the changing tools available to study disease, from written observations to laboratory testing and ancient DNA.

Death estimates help convey their scale, but understanding how those figures were produced matters just as much. A precise-looking number can conceal incomplete records, disputed assumptions, or several different causes of death.

Source: https://interestingengineering.com/lists/deadly-plagues-that-swept-continents