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Influenza is an acute respiratory illness caused by influenza A, B, and C viruses.1–3 Influenza A and B cause annual or near annual epidemics of febrile respiratory illness throughout the world.4 In temperate climates, influenza epidemics follow a typical pattern, peaking annually during colder months.1 In regions with tropical or subtropical climates, influenza epidemics have more variable seasonality often associated with the rainy season and influenza can circulate for longer periods annually.4–6 In addition to annual epidemics, new influenza A subtypes can emerge during epidemic and nonepidemic periods among humans and cause a worldwide outbreak, known as a pandemic, leading to larger than usual numbers of severe disease, deaths, and societal disruption.3

Although most cases of influenza are self-limited, influenza may cause more severe illness, hospitalization, and death, particularly among young children, elderly individuals, people with underlying medical conditions, pregnant women, and people with morbid obesity.7 The public health impact of influenza is considerable; every year influenza causes an increase in absenteeism in schools and the workplace, patient visits to physicians, hospitalizations, and deaths.8,9 Influenza-related visits can overwhelm hospitals, clinics, and emergency rooms during the influenza season.10

Vaccination remains the most effective means of prevention of influenza illness. However, vaccine effectiveness is generally only moderate and varies by influenza type, subtype, and season.11 Vaccination coverage for influenza is relatively low throughout much of the world, and influenza remains a largely uncontrolled disease.12,13 Eradication of influenza is unlikely because influenza A viruses circulate among several animal species, especially wild aquatic birds, which form the primary reservoir for all influenza A virus subtypes.


Influenza viruses that infect humans were first identified in 1933, but outbreaks of rapidly spreading febrile respiratory diseases consistent with influenza have been documented as early as the twelfth century. The term “influenza” was first used in the fourteenth century, when Buonissequi described an epidemic as the “grande influenza.”14 The Italian word for “influence” was used as a collective term for various causes of widespread epidemics. Cold weather, or “influenza di freddo,” was considered a causal factor for many years.15

The first clearly described pandemic consistent with influenza occurred in 1580. Pandemics have appeared periodically since then with four pandemics occurring in the twentieth century.16–18 The first of those, the 1918 Pandemic, which is sometimes referred to as the “Spanish flu,” is estimated to have caused at least 50 million deaths worldwide, including nearly 700,000 in the United States.18,19 Deaths occurred mainly among healthy 20- to 40-year-olds, in contrast to the usual pattern in interpandemic influenza seasons, in which most deaths occur among the elderly.20 In the era of HIV and AIDS, it is often forgotten that influenza caused the most deadly pandemic in recorded history.

During the twentieth century, a series of important ...

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