The 3 most severe influenza pandemics of the 20th century

1. The 1918 flu pandemic

The 1918 influenza pandemic was the most severe pandemic in history. It was caused by an H1N1 virus that originated in birds. Although the source of the virus is unknown, it spread throughout the world during 1918-1919. In the United States, the virus was first detected in the military in the spring of 1918.

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An estimated 500 million people, or one-third of the world's population, have been infected with the virus. The death toll is estimated to be at least 50 million globally, with about 675,000 of those deaths occurring in the United States. The highest mortality rates are among children under 5 years of age, people aged 20-40, and people aged 65 and older. What is unique about this pandemic is the high mortality rate among otherwise healthy people, including the 20-40 age group.

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Since there is no vaccine to protect against influenza viruses and no antibiotics to treat secondary bacterial infections associated with influenza, control measures worldwide are limited to non-pharmaceutical interventions such as isolation, quarantine, good personal hygiene, use of disinfectants and restrictions on public gatherings. However, these measures have not been applied uniformly. 

2. The pandemic of 1957 - 1958

The 1957 influenza pandemic was an outbreak of influenza first identified in February 1957 in East Asia, which later spread to countries around the world. It was the second major influenza pandemic of the 20th century, following the 1918–1919 influenza pandemic and preceding the 1968 influenza pandemic. The 1957 influenza pandemic is estimated to have killed 1 to 2 million people worldwide, making it the least severe of the three influenza pandemics of the 20th century.

This flu pandemic is caused by a virus called influenza A subtype H2N2. Research has shown that this virus is a reassortant (cross-species hybrid) strain derived from avian and human influenza viruses.

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During the 1960s, the human H2N2 strain underwent a series of small genetic changes, a process known as 'antigenic drift.' These small changes caused periodic pandemics. After 10 years of evolution, the 1957 influenza virus disappeared and was replaced through a process known as 'antigenic shift' by a new influenza A subtype, H3N2, leading to the 1968 influenza pandemic.

During the first months of the 1957 flu pandemic, the virus spread throughout China and neighboring areas. By mid-summer, it had reached the United States, initially infecting only a small number of people, but over the next few months the number of infections increased rapidly, especially among young children, the elderly, and pregnant women. 

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By that time, the epidemic had also spread to the United Kingdom. By December 1957, a total of about 3,550 deaths had been reported in England and Wales. And by March 1958, an estimated 69,800 deaths had occurred in the United States.

While some people infected with the virus experience only mild symptoms such as a cough and a low-grade fever, others develop life-threatening complications such as pneumonia. Those who are not affected by the virus are thought to have developed antibodies that protect against other closely related strains of influenza.

The rapid development of vaccines against the H2N2 virus and the availability of antibiotics to treat secondary infections helped limit the spread and mortality of this pandemic.

3. The 1968 flu pandemic

The 1968 influenza pandemic was a global outbreak of influenza that began in China in July 1968 and lasted through 1969–1970. It was the third influenza pandemic of the 20th century.

The 1968 influenza pandemic is estimated to have caused 1–4 million deaths, much fewer than the 1918–1919 pandemic.

The 1968 pandemic was caused by the emergence of a virus called influenza A subtype H3N2. It is suspected that this virus evolved from the influenza strain that caused the 1957 pandemic.

The 1957 influenza virus, also known as influenza A subtype H2N2, is thought to have given rise to H3N2 through a process called "antigenic shift," in which the hemagglutinin (H) antigen on the outer surface of the virus mutated genetically to create a new H3 antigen.

Because the new virus retained the same neuraminidase (N) antigen as N2, people exposed to the 1957 virus appeared to have some immunity to the 1968 virus. This may explain why the 1968 outbreak was less severe than the 1918–1919 pandemic.

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Although the 1968 influenza pandemic had a relatively low global death toll, the virus was highly contagious, allowing it to spread rapidly across the globe. In fact, within two weeks of its appearance in July in Hong Kong, some 500,000 cases had been reported, and the virus continued to spread rapidly throughout Southeast Asia.

Within months, the virus had spread to the Panama Canal Zone and the United States. By late December, it had spread throughout the United States and to the United Kingdom and countries in Western Europe. Australia, Japan, and many countries in Africa, Eastern Europe, Central and South America were also affected. The pandemic came in two waves, and in most places, the second wave was more deadly than the first.

The 1968 influenza pandemic caused illness of varying severity in different regions. For example, while the disease appeared sporadically and affected a small number of people in Japan, it was widespread and deadly in the United States. The infection caused typical upper respiratory symptoms of influenza, including chills, fever, muscle aches, and weakness.

These symptoms typically last four to six days. The highest mortality rates are among the most vulnerable groups, including infants and the elderly. Although a vaccine has been developed to combat the virus, it is only available after the pandemic has peaked in many countries.

Isabella Humphrey

Update 12 February 2025