Table 1.

Details of significant influenza pandemics since the late 1800’s.

Name of pandemic	Year	Strain	Disease burden	Additional information
Russian influenza pandemic	1889	A(H2N2)	132,000 deaths in England, Wales, and Ireland alone (Smith, 1995).	The 1889 ‘Russian Flu’ as the name suggests started in Russia and spread across Europe reaching North America in 1890. In only 4 months the infection had spread across all of Europe and the United States. The United Kingdom encountered four waves of disease and it is thought that at least one third of the adult population in England and Ireland suffered at least one bout of disease (Smith, 1995; Valleron et al., 2010).
Spanish influenza pandemic	1918	A(H1N1)	Caused 40–50 million deaths worldwide. India alone suffered 7 million deaths (Potter, 2001; Hilleman, 2002; Brundage, 2006; Michaelis et al., 2009).	Considered the most devastating influenza pandemic ever recorded, infecting 50% of the world’s population. The origin of this pandemic is unclear as it appeared in North America, Asia, and Europe at roughly the same time (Taubenberger et al., 2001; Hilleman, 2002). Reports of disease and mortality were initially suppressed in many countries, included the United Kingdom, France and the United States, to ensure wartime efforts and morale weren’t negatively affected. In Spain the press were able to print freely, meaning the first publicized cases were reported from Spain facilitating the nickname ‘the Spanish flu’ (Johnson, 2016; Peckham, 2016). In contrast to its name, it has been suggested that the pandemic started in France/mainland Europe and that it reached Spain from France (Reid et al., 2001; Trilla et al., 2008) although more recent papers suggest New York as the origin due to evidence of a pre-pandemic wave of the H1N1 virus (Olson et al., 2005). What is remarkable is how far the pandemic spread; the pandemic reached as far as the Alaskan wilderness to remote Pacific islands (Burnet and Clark, 1942; Taubenberger et al., 2001). The pandemic experienced a couple of waves; the first of which was relatively mild. The second wave, however, was far more lethal (Hilleman, 2002). The first outbreaks were reported in military camps as males responded to the call for troops in the spring and summer of 1918. A period of dormancy was then recorded toward the end of summer in America, but this was short lived as transmission picked up as schools reopened in September after the summer holidays (Glezen, 1996).
Asian influenza pandemic	1957–1958	A(H2N2)	Although global death toll estimates vary [between 1.5 million (Gatherer, 2009) and 2–4 million (Michaelis et al., 2009)], the death toll in the United States is accurately reported to have been 69, 800 (Klimov et al., 1999; Hilleman, 2002).	The pandemic affected 40–50% of people worldwide (Potter, 2001), however, resulted in lot less mortality than the previous pandemic. This Asian influenza pandemic started in March 1957 in Southern China, where pigs, ducks, and humans live together closely. It reached Hong Kong in April, and then spread to Singapore, Taiwan, and Japan (Fukumi, 1959; Potter, 2001; Hilleman, 2002). The pandemic reached India, Australia, and Indonesia by May, Pakistan, Europe, North America, and the Middle East by June, South Africa, South America, New Zealand, and the Pacific Islands by July, and Central, West and East Africa, Eastern Europe, and the Caribbean by August (Dunn, 1958; Payne, 1958; Potter, 2001).
Hong Kong influenza pandemic	1968–1969	A(H3N2)	1–2 million people died worldwide (Michaelis et al., 2009). Overall 33,800 people died in the United States (Klimov et al., 1999) and England and Wales saw a 55% increase in respiratory deaths in 1969 (Tillett et al., 1983).	The 1968 Hong Kong pandemic started in July 1968 in Hong Kong and spread to the Southern hemisphere by June 1969 (Biggerstaff et al., 2014). The H3N2 virus was isolated and identified too late in the pandemic for vaccine intervention (Nakajima et al., 1978; Hilleman, 2002) so it was fortunate that in most countries, apart from the United States, the disease was mild (Cockburn et al., 1969). There are several proposed reasons for the reduced mortality of this compared to the Asian Flu. Firstly the N2 was seen in the Asian Flu so may have contributed some cross-reactive immunity to this H3N2 strain (Glezen, 1996). Although antibodies to NA do not prevent infection, they help to reduce the amount of newly formed virus released from infected cells (Couch et al., 1974; Glezen, 1996). Secondly, during the initial wave of this pandemic, the number of cases started to grow exponentially in December, at this point the school Christmas holidays began; it has been speculated that this removed an important susceptible population (Glezen, 1996).
Russian Flu influenza pandemic	1977–1978	A(H1N1)	Approximately 700,000 deaths globally (Michaelis et al., 2009).	This pandemic was caused by a reappearance of H1N1, identical to that of the Spanish flu virus (Michaelis et al., 2009). The disease mainly affected those born after the late 1950’s, so those who had not been exposed to the pandemic H1N1 strain that had circulated previously (Hilleman, 2002).
Swine influenza pandemic	2009	A(H1N1)	By the end of the pandemic it is thought that there were 284,000 deaths worldwide (Chertow and Memoli, 2013).	In early 2009, an influenza A H1N1 virus outbreak was initially identified in Mexico and then the United States (Michaelis et al., 2009). In June 2009 the WHO declared the outbreak a pandemic. Within 4 weeks the outbreak had spread to 41 countries, resulting in 11,034 confirmed cases and 85 deaths (Michaelis et al., 2009; Wang and Palese, 2009). Disease/symptoms were generally mild (Peiris et al., 2009) however, complications of the disease did result in hospitalization, particularly in at risk groups (Wang and Palese, 2009).
				Unlike other pandemics and yearly epidemics, during this pandemic it was predominantly children and young adults that were affected, particularly those aged 12–22 (Gill et al., 2010). Overall this pandemic was relatively mild. It is thought that morbidity and mortality rates were reduced due to three main factors. Firstly, the quick responses of various governments in terms of school closures helped reduce the spread of the virus. Thousands of schools were shut worldwide, including the United States and Mexico. Japan alone closed almost 2000 schools (Wang and Palese, 2009; Jackson et al., 2014). Secondly, influenza A H1N1 strains have been circulating amongst the human population for decades, therefore prior exposure could have provided some degree of immunity against the 2009 pandemic strain. Lastly an important pathogenicity factor, PB1-F2, was not present making the strain milder than those present in previous pandemics (Wang and Palese, 2009).