1918 Influenza (H1N1) ~50M deaths globally, 500,000 in North America
1957 Influenza (H2N2) ~2M deaths globally, 100,000 in North America
1967 Influenza (H3N2) ~1M deaths globally, 100,000 in North America
2009 Influenza (H1N1) 284,000 deaths globally, 12,469 in North America


1918 Influenza (H1N1):
Lasting from January 1918 to December 1920, it infected 500 million people – about a quarter of the world's population at the time. The death toll is estimated to have been anywhere from 17 million to 50 million, and possibly as high as 100 million, making it one of the deadliest pandemics in human history.[3]

Most influenza outbreaks disproportionately kill the very young and the very old, with a higher survival rate for those in between, but the Spanish flu pandemic resulted in a higher than expected mortality rate for young adults.[4] Scientists offer several possible explanations for the high mortality rate of the 1918 influenza pandemic. Some analyses have shown the virus to be particularly deadly because it triggers a cytokine storm, which ravages the stronger immune system of young adults.[5] In contrast, a 2007 analysis of medical journals from the period of the pandemic found that the viral infection was no more aggressive than previous influenza strains.[6][7] Instead, malnourishment, overcrowded medical camps and hospitals, and poor hygiene promoted bacterial superinfection. This superinfection killed most of the victims, typically after a somewhat prolonged death bed.[8][9]

The Spanish flu was the first of two pandemics caused by the H1N1 influenza virus; the second was the swine flu in 2009.[10]

The Spanish flu infected around 500 million people, about a quarter of the world's population.[1] Estimates as to how many infected people died vary greatly, but the flu is regardless considered to be one of the deadliest pandemics in history.[51][52]

In the U.S., about 28% of the population of 105 million became infected, and 500,000 to 675,000 died (0.48 to 0.64 percent of the population).[76] Native American tribes were particularly hard hit. In the Four Corners area, there were 3,293 registered deaths among Native Americans.[77] Entire Inuit and Alaskan Native village communities died in Alaska.[78] In Canada, 50,000 died.[79]

This huge death toll resulted from an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms.[53] Symptoms in 1918 were unusual, initially causing influenza to be misdiagnosed as dengue, cholera, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred".[54] The majority of deaths were from bacterial pneumonia,[87][88][89] a common secondary infection associated with influenza. The virus also killed people directly by causing massive hemorrhages and edema in the lungs.[89]

The pandemic mostly killed young adults. In 1918–1919, 99% of pandemic influenza deaths in the U.S. occurred in people under 65, and nearly half of deaths were in young adults 20 to 40 years old. In 1920, the mortality rate among people under 65 had decreased sixfold to half the mortality rate of people over 65, but 92% of deaths still occurred in people under 65.[90] This is unusual, since influenza is typically most deadly to weak individuals, such as infants under age two, adults over age 70, and the immunocompromised. In 1918, older adults may have had partial protection caused by exposure to the 1889–1890 flu pandemic, known as the "Russian flu".[91]

Another oddity was that the outbreak was widespread in the summer and autumn (in the Northern Hemisphere); influenza is usually worse in winter.[94]

In fast-progressing cases, mortality was primarily from pneumonia, by virus-induced pulmonary consolidation. Slower-progressing cases featured secondary bacterial pneumonia, and possibly neural involvement that led to mental disorders in some cases. Some deaths resulted from malnourishment.

In a 2009 paper published in the journal Clinical Infectious Diseases, Karen Starko proposed that aspirin poisoning contributed substantially to the fatalities. She based this on the reported symptoms in those dying from the flu, as reported in the post mortem reports still available, and also the timing of the big "death spike" in October 1918. This occurred shortly after the Surgeon General of the U.S. Army and the Journal of the American Medical Association both recommended very large doses of 8 to 31 grams of aspirin per day as part of treatment. These levels will produce hyperventilation in 33% of patients, as well as lung edema in 3% of patients.[121]

After the lethal second wave struck in late 1918, new cases dropped abruptly – almost to nothing after the peak in the second wave.[59] In Philadelphia, for example, 4,597 people died in the week ending 16 October, but by 11 November, influenza had almost disappeared from the city. One explanation for the rapid decline in the lethality of the disease is that doctors became more effective in prevention and treatment of the pneumonia that developed after the victims had contracted the virus. However, John Barry stated in his 2004 book The Great Influenza: The Epic Story of the Deadliest Plague In History that researchers have found no evidence to support this position.[5] Some fatal cases did continue into March 1919, killing one player in the 1919 Stanley Cup Finals.

Another theory holds that the 1918 virus mutated extremely rapidly to a less lethal strain. This is a common occurrence with influenza viruses: there is a tendency for pathogenic viruses to become less lethal with time, as the hosts of more dangerous strains tend to die out[5] (see also "Deadly Second Wave", above).

In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the 1918 flu pandemic strain.[148]

In 2013, the AIR Worldwide Research and Modeling Group "characterized the historic 1918 pandemic and estimated the effects of a similar pandemic occurring today using the AIR Pandemic Flu Model". In the model, "a modern day 'Spanish flu' event would result in additional life insurance losses of between US$15.3–27.8 billion in the United States alone", with 188,000–337,000 deaths in the United States.[150]

1957 Influenza (H2N2):
It may have infected as many or more people than the 1918 Spanish flu pandemic, but the vaccine, improved health care, and the invention of antibiotics contributed to a lower mortality rate.[1] Overall, the pandemic caused 1 to 2 million deaths worldwide[2] or 2 to 4 million.[1] The CDC estimates 1.1 million deaths worldwide.[12] According to a study in the Journal of Infectious Diseases, the highest excess mortality occurred in Latin America.[13]

About 70,000[1][11] to 116,000 people died in the United States.[14] In early 1958, it was estimated that 14,000 people had already died of the flu in the United Kingdom of the 9 million who became sick.[3] It caused many infections in children, spreading in schools and leading to many school closures, but was rarely fatal in children. The virus was most deadly in pregnant women, the elderly, and those with pre-existing heart and lung disease.[1]

1967 Influenza (H3N2):
The first record of the outbreak in Hong Kong appeared on 13 July 1968. By the end of July 1968, extensive outbreaks were reported in Vietnam and Singapore. Despite the lethality of the 1957 Asian Flu in China, little improvement had been made regarding the handling of such epidemics. The Times newspaper was the first source to sound alarm regarding this new possible pandemic.

By September 1968, the flu reached India, the Philippines, northern Australia, and Europe. That same month, the virus entered California from returning Vietnam War troops but did not become widespread in the United States until December 1968. It would reach Japan, Africa, and South America by 1969.[5] The outbreak in Hong Kong, where population density is greater than 6,000 people per square kilometre, reached maximum intensity in two weeks, lasting six months in total from July to December 1968. However, worldwide deaths from this virus peaked much later, in December 1968 and January 1969. By that time, public health warnings[6] and virus descriptions[7] were issued in the scientific and medical journals. In comparison to other pandemics, the Hong Kong flu yielded a low death rate, with a case-fatality ratio below 0.5% making it a category 2 disease on the Pandemic Severity Index. The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population.[5]

This pandemic struck in two waves with the second wave being deadlier than the first in most places.[8] The same virus returned the following years: a year later, in late 1969 and early 1970, and in 1972. The CDC currently estimates that, in total, the virus killed 1 million people worldwide and around 100,000 people in the U.S.[9] Fewer people in the U.S. died during this pandemic than in previous pandemics for various reasons:[10]

some immunity against the N2 flu virus may have been retained in populations struck by the Asian Flu strains which had been circulating since 1957;

the pandemic did not gain momentum until near the winter school holidays, thus limiting the infection spreading;

improved medical care gave vital support to the very ill;

the availability of antibiotics that were more effective against secondary bacterial infections.

vitamins were fashionable. Linus Pauling's ideas about Vitamin C were at their peak.

2009 Influenza (H1N1) 284,000 deaths globally, 12,469 in North America
The 2009 swine flu pandemic was an influenza pandemic that lasted from January 2009 to August 2010, and the second of the two pandemics involving H1N1 influenza virus (the first being the 1918–1920 Spanish flu pandemic), albeit a new strain.

Some studies estimated that 11 to 21 percent of the global population at the time—or around 700 million to 1.4 billion people (of a total 6.8 billion)—contracted the illness. This was more than the number of people infected by the Spanish flu pandemic,[12][13] but only resulted in about 150,000 to 575,000 fatalities for the 2009 pandemic.[14

Unlike most strains of influenza, the Pandemic H1N1/09 virus does not disproportionately infect adults older than 60 years; this was an unusual and characteristic feature of the H1N1 pandemic.[16] Even in the case of previously healthy people, a small percentage develop pneumonia or acute respiratory distress syndrome (ARDS). This manifests itself as increased breathing difficulty and typically occurs three to six days after initial onset of flu symptoms.[17][18] The pneumonia caused by flu can be either direct viral pneumonia or a secondary bacterial pneumonia. A November 2009 New England Journal of Medicine article recommended that flu patients whose chest X-ray indicates pneumonia receive both antivirals and antibiotics.[19] In particular, it is a warning sign if a child seems to be getting better and then relapses with high fever, as this relapse may be bacterial pneumonia.[20]

The symptoms of H1N1 flu are similar to those of other influenzas, and may include fever, cough (typically a "dry cough"), headache, muscle or joint pain, sore throat, chills, fatigue, and runny nose. Diarrhea, vomiting, and neurological problems have also been reported in some cases.[59][60] People at higher risk of serious complications include people over 65, children younger than 5, children with neurodevelopmental conditions, pregnant women (especially during the third trimester),[17][61] and people of any age with underlying medical conditions, such as asthma, diabetes, obesity, heart disease, or a weakened immune system (e.g., taking immunosuppressive medications or infected with HIV).[62] More than 70% of hospitalizations in the U.S. have been people with such underlying conditions, according to the CDC.[63]

The virus was found to be a novel strain of influenza for which extant vaccines against seasonal flu provided little protection. A study at the U.S. Centers for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain but that adults, particularly those older than 60, had some degree of immunity. Children showed no cross-reactive antibody reaction to the new strain, adults aged 18 to 60 had 6–9%, and older adults 33%.[79][80]

The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75.[89] A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms.[90] The H1N1 virus has been transmitted to animals, including swine, turkeys, ferrets, household cats, at least one dog, and a cheetah.[91][92][93][94]

On 8 December 2009, the Cochrane Collaboration, which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza.[167][168]