Schoolchildren gargling as a precaution against the Influenza epidemic, circa 1935. (Credit: Imagno/Getty Images)
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The flu, or influenza, is a highly contagious viral infection that mainly affects the respiratory system. It’s usually a seasonal illness, with yearly outbreaks killing hundreds of thousands of people around the world. Though rare, completely new versions of the virus may infect people and spread quickly, resulting in pandemics (an infection that spreads throughout the world) with death tolls in the millions. Influenza has plagued humankind for centuries and, given its highly variable nature, may continue to do so for centuries to come.

Influenza is a viral respiratory infection that causes symptoms similar to, but more severe than, the common cold, such as sudden onset fever, cough, runny or stuffy nose and severe malaise (feeling unwell).

The flu can also sometimes cause vomiting, diarrhea and nausea, (particularly in young children), but the flu is primarily a respiratory disease and not a stomach or intestinal disease.

Symptoms develop 1 to 4 days after contracting the virus. Most people recover within 2 weeks without medical treatment, but the flu can cause serious complications, including pneumonia, bronchitis and sinus and ear infections.

The “flu season” typically lasts from late fall to spring. Each year, flu epidemics cause 3 to 5 million cases of severe illness and about 290,000 to 650,000 deaths around the globe, according to the World Health Organization (WHO).

During recent years in the United States, between 12,000 and 56,000 people have died annually from the flu, according to the Centers for Disease Control and Prevention (CDC).

Influenza has likely been around for millennia, though its cause was only identified relatively recently.

One of the earliest reports of an influenza-like illness comes from Hippocrates, who described a highly contagious disease from northern Greece (ca. 410 B.C.).

The word influenza, however, wasn’t used to describe a disease until many centuries later. In 1357, people called an epidemic in Florence, Italy influenza di freddo, which translates to “cold influence,” referring to the disease’s possible cause.

In 1414, French chroniclers used similar terms to describe an epidemic that affected up to 100,000 people in Paris. They said it originated from vent puant et tout plein de froidure, or a “smelly and cold wind.”

The term influenza became commonplace to describe the disease, at least in Britain, in the mid-1700s. At the time, it was thought that the influence of the cold (influenza di freddo), along with astrological influences or the conjunction of stars and planets (influenza di stelle), caused the disease.

In 1892, Dr. Richard Pfeiffer isolated an unknown bacterium from the sputum of his sickest flu patients, and he concluded that the bacteria caused influenza. He called it Pfeiffer’s bacillus, or Haemophilus influenzae.

Scientists later discovered that H. influenzae causes many types of infections—including pneumonia and meningitis—but not influenza.

Researchers finally isolated the virus that causes flu from pigs in 1931, and from humans in 1933.

Influenza viruses, which are part of the Orthomyxoviridae family of viruses, cause the flu.

Four types of the virus exist: A and B, which are responsible for seasonal flu epidemics in people; C, which is relatively rare, causes a mild respiratory illness, and is not thought to cause epidemics; and D, which primarily infects cattle and isn’t known to affect people.

Influenza A virus, which also infects including birds, swine, horses, and other animals, is further divided into subtypes based on two antigens (proteins) on the virus’s surface: hemagglutinin (H), of which there 18 subtypes, and neuraminidase (N), of which there 11 subtypes.

The specific virus is recognized by these antigens. For example, H1N1 refers to influenza A virus with hemagglutinin subtype 1 and neuraminidase subtype 1, and H3N2 refers to influenza A virus with hemagglutinin subtype 3 and neuraminidase subtype 2.

Influenza B, on the other hand, is recognized by lineages and strains. The influenza B viruses commonly seen in people belong to one of two lineages: B/Yamagata or B/Victoria.

Influenza is a constantly evolving virus. It quickly goes through mutations that slightly alter the properties of its H and N antigens.

Due to these changes, acquiring immunity (either by getting sick or vaccinated) to an influenza subtype such as H1N1 one year will not necessarily mean a person is immune to a slightly different virus circulating in subsequent years.

But since the strain produced by this “antigenic drift” is still similar to older strains, the immune systems of some people will still recognize and properly respond to the virus.

In other cases, however, the virus can undergo major changes to the antigens such that most people don’t have an immunity to the new virus, resulting in pandemics rather than epidemics.

This “antigenic shift” can occur if an influenza A subtype in an animal jumps directly into humans.

It can also occur if an intermediate host such as a pig—which is susceptible to avian, human, and swine influenza—becomes simultaneously infected by influenza viruses from two different species and the viruses exchange genetic information to acquire completely new antigens, a process called genetic reassortment.

Pinpointing pandemics from historical reports is challenging given the lack of accurate and consistent records, but epidemiologists generally agree that the 1580 influenza outbreak is the earliest known pandemic.

The 1580 pandemic began in Asia during the summer, and then spread to Africa and Europe. Within six months, influenza had spread from southern Europe all the way to the northern European countries, and the infection subsequently reached the Americas. The actual death toll is unknown, but 8,000 deaths occurred in Rome alone.

Nearly 150 years later, another influenza pandemic arose. It began in 1729 in Russia and spread throughout Europe within 6 months and all the world within 3 years. King Louis XV was reportedly infected and stated that the disease spread like a foolish little girl, or follette in French.

Only 40 years later, in 1781, another pandemic struck. It arose in China, spread to Russia, and then encompassed Europe and North America over the next year. At its peak, the infection struck 30,000 people each day in St. Petersburg and affected two-thirds of the population in Rome.

The pandemic of 1830–1833 began in China, and then spread by ships to the Philippines, India, and Indonesia, and finally across Russia and into Europe, which experienced two recurrences over the span of the pandemic.

Outbreaks appeared in North America from 1831–1832. Before it ended, the pandemic may have affected 20 to 25 percent of the world’s population.

The first “modern” flu pandemic occurred in 1889 in Russia, and its sometimes known as the “Russian flu.” It reached the American continent just 70 days after it began and ultimately affected approximately 40 percent of the world’s population.

The flu pandemic of 1918 is sometimes known as the “mother of all pandemics.” The so-called Spanish flu pandemic was the deadliest in history, affecting one-third of the world’s population and killing up to 50 million people.

The Spanish flu, the first known pandemic to involve the H1N1 virus, came in several waves and killed its victims quickly, often within a matter of hours or days. More U.S. soldiers in World War I died from the flu than from battle.

The 20th century saw two other flu pandemics: the 1957 Asian flu (caused by H2N2), which killed 1.1 million people worldwide, and the Hong Kong flu of 1968 (H3N2), which killed 1 million people worldwide. Both of these flu strains arose from a genetic reassortment between a human and an avian virus.

In 2009, a new influenza A H1N1 virus emerged in North America and spread throughout the world. The “swine flu” pandemic primarily affected children and young adults who had no immunity to the new virus, while nearly one-third of people over the age of 60 had antibodies against the virus due to prior exposure to a similar H1N1 virus strain.

Compared with previous pandemics, the 2009 swine flu was relatively mild, despite killing up to 203,000 people worldwide.

Shortly after scientists identified the influenza A virus, researchers began work on creating a flu vaccine, with the first clinical trials commencing in the mid-1930s.

Given the high death toll of World War I soldiers to the flu, the U.S. military was highly interested in a flu vaccine. During World War II, U.S. soldiers were part of field tests on the safety and efficacy of the new vaccine.

But during these 1942–1945 tests, scientists discovered influenza type B, necessitating a new bivalent vaccine that protects against both H1N1 and the influenza B virus.

After the Asian flu pandemic arose in 1957, a new vaccine protecting against H2N2 was developed. WHO monitored the circulating influenza virus strains in various countries to determine which flu vaccine would be needed in an upcoming season.

During the 1978 pandemic, scientists developed the first trivalent flu vaccine, which protected against one strain of influenza A/H1N1, one strain of influenza virus A/H3N2 and a type B virus. Most U.S.-licensed seasonal flu vaccines since then have been trivalent.

In 2012, the first quadrivalent flu vaccine that protects against an additional influenza B virus was approved for use.

Scientists at WHO and its collaborating centers determine which strains to vaccinate against based on how the viruses have mutated in the past year and how they are spreading, with different vaccines needed for the Northern and Southern hemisphere.

But given the uncertainties involved in these estimates, vaccine effectiveness can vary widely—the 2004–2005 vaccine was only 10 percent effective in the United States, while the 2010-2011 vaccine was 60 percent effective, according to the CDC.

The 2017–2018 flu vaccine was only 10 percent effective in Australia and about 25 percent effective in the United States against the H3N2 strain that caused most illnesses and deaths.

Lina B. (2008). “History of Influenza Pandemics.” In: Raoult D., Drancourt M. (eds) Paleomicrobiology. Springer, Berlin, Heidelberg.
Potter, C.W. (2001). “A history of influenza.” Journal of Applied Microbiology.
Sophie Valtat et al. (2011). “Age distribution of cases and deaths during the 1889 influenza pandemic.” Vaccine.
Lone Simonsen et al. (2013). “Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study.” PLOS ONE.
Barberis, I. et al. “History and Evolution of Influenza Control through Vaccination: From the First Monovalent Vaccine to Universal Vaccines.” Journal of Preventive Medicine and Hygiene 57.3 (2016): E115–E120. Print.
Paules et al. (2018). “Chasing Seasonal Influenza—The Need for a Universal Influenza Vaccine.” The New England Journal of Medicine.
Seasonal Influenza Vaccine Effectiveness, 2005-2018; CDC.
The Flu Vaccine Is Working Better Than Expected, C.D.C. Finds; NYTimes.
Seasonal Influenza, More Information; CDC.
How the Flu Virus Can Change: “Drift” and “Shift”; CDC.
Estimating Seasonal Influenza-Associated Deaths in the United States. CDC.