Influenza, commonly known as flu, is an infectious disease of birds as well as some mammals including human beings and is caused by a variety of species and strains of influenza viruses (Stack et al. 2013). Generally, two flu seasons (one per hemisphere) occur per year, leading to 3–5 million cases of severe illness and 0.25–0.50 million deaths all over the world (WHO 2009), which may reach up to millions in some pandemic years. According to a study conducted on Scottish people by Riggs and Cuff (2013) it was found that men who were in utero between 1889 and 1893 were slightly stunted, “marked for life” by repeated encounters with the Russian influenza. Influenza viruses are highly contagious and cause respiratory disease in humans, animals and poultry. Some of these viruses can cause generalized disease in fowl in which, besides respiratory symptoms, diarrhoea, paralysis and decreased egg production in layer birds are also observed. Influenza viruses on rare occasions can become zoonotic. The avian and swine influenza A virus has zoonotic potential (van Reeth 2007; Dhama et al. 2005; Pawaiya et al. 2009; Nagrajan et al. 2010). These virus evolve in animals and poultry and ultimately jump species to cause epidemics and even pandemics in human (Kawaoka 2006; Klenk 2008; To et al. 2012). Four types of influenza virus, viz. types A, B, C and Thogotovirus (influenza D) have been recognized in family Orthomyxoviridae (Koparde and Singh 2011). Influenza A virus are associated with diseases in humans, poultry, pigs, horses and other mammals such as mink, seals, dogs (Mancini et al. 2012), cats (Rahman 2012) and whales (Swayne and King 2003). Influenza B virus has been isolated from human beings only and Influenza C virus can infect humans and, in some instances, swine and seals also (Swayne and Halvorson 2003). The exchange of genetic information through reassortment can occur among members within any of the three types of influenza viruses but has never been reported between members of different types. Influenza virus are named according to their type, host from which the virus was isolated (omitted if human), location where isolated, the successive isolate number from the location and year of isolation. The virus subtype may also be included (e.g. Influenza A virus/Hong Kong/1/68[H3N2] is the first isolate of influenza A virus, subtype H3N2 isolated from human in 1968; and Influenza A virus/Chicken/Hong Kong/59/97[H5N1] is the 59th influenza virus Type A, subtype H5N1, isolated from chickens in Hong Kong in 1997). This chapter will focus mainly on influenza type A virus.

The word Influenza is from the Italian language and was initially used to associate the cause of the disease with some astrological influences. But with advance in medical science, this concept was changed and ultimately influenza del freddo, meaning ‘influence of the cold’. The use of the word influenza for the first time in English language was in 1743, to report the disease outbreak in Europe (Vyshnavi et al. 2010). Influenza epidemics in humans have been regularly reported throughout the recorded history. Severe, widespread, global outbreaks of influenza called pandemics have occurred occasionally. The first authentic influenza pandemic was recorded in 1580, which started in Russia and spread to Europe via Africa. After that sporadic outbreaks of influenza continued to occur throughout the seventeenth and eighteenth centuries. Pandemic outbreaks are the most dramatic manifestations of influenza, causing morbidity in 20 to 40 % of the world population and resulting in significant mortality. Five pandemics, [Asian (Russian) flu pandemic ‘H2N2’ (1889–1890); Spanish influenza pandemic ‘H1N1’ (1918–1920); Asian pandemic ‘H2N2’ (1957–1958); Hong Kong pandemic ‘H3N2’ (1968–1969); Swine flu pandemic ‘H1N1’ (April, 2009–December, 2009)], based on virus isolation and nucleotide sequencing, have occurred so far (Pyle 1986; Beveridge 1991; Zeitlin and Maslow 2005; Horimoto and Kawaoka 2005; Kilbourne 2006; Bautista et al. 2010; Koparde and Singh 2011). It is estimated that one million people died due to ‘Asian (Russian) flu’, 50 million people died due to ‘Spanish influenza’, 1–2 million human deaths occurred in each of the subsequent ‘Asian pandemic’ and ‘Hong Kong pandemic’ and many human deaths continue to occur due to H1N1, S-OIV (Koparde and Singh 2011). The devastating effects of ‘Spanish flu’ led to the formation of a World Health Organization (WHO) surveillance network for influenza, which was ultimately developed into the WHO Global Influenza Programme (Stohr 2003). It has been estimated that the U.S. alone has to bear an annual burden of over $10 billion from the annual/seasonal human influenza outbreaks causing deaths and requiring hospitalizations (www.​whitehouse.​gov). The endemic infection of pigs in southern China with H3N2 influenza virus subtype of human poses another threat as it raises the potential of reassortment with avian H5N1 viruses in pigs that can act as the intermediate host due to the presence of receptors for both these viruses (Daum et al. 2005). A fresh multidisciplinary approach and analysis on current and archival data on the origins and dissemination of the 1918 flu within the perspective of global war has divulged that the 1918 flu virus and the resultant disease most probably emerged first in the winter of 1917–1918 in China. Subsequently, from China it dispersed throughout the globe when the battlefields of Europe became a common ground for the previously isolated populations to come into contact with one another. The sustenance of the war effort on the Western Front further helped in the disease dissemination along various global military pathways (Humphries 2014).

The importance of the highly pathogenic influenza virus has also increased due to its potential to be used in bioterrorism (WHO 2004). Besides causing heavy mortality, trade embargoes and barriers can be imposed on poultry and poultry products from a region/country in which Highly Pathogenic Avian Influenza (HPAI) has been detected. Ever since the first incidence of ‘bird flu’ in humans in Hong Kong in the year 1997, researchers have raised concern about the possibility of a human pandemic in the near future (Shortridge et al. 2003; Fleming 2005; Horimoto and Kawaoka 2005; De la Barrera and Teran 2005; Sellwood et al. 2007; OIE 2011; Rios-Soto et al. 2011; van Kerkhove et al. 2011; WHO 2011). The functions and responsibilities of WHO, and the recommendations for national measures to be taken before and during pandemics have been outlined in ‘WHO Global Influenza Preparedness Plan’ (WHO/CDS/CSR/GIP/2005.5).

A novel and unique flu virus of influenza A H1N1 subtype of swine origin was identified in April 2009. This virus infected humans and spread from person-to-person, causing large number of outbreaks with an increasing number of diseased cases in the US and other countries. Before April 2009, sporadic infections of humans with swine influenza have occurred. Most of these cases were observed in people who were directly exposed to pigs, and only in a few instances the disease was reported due to human-to-human transmission of the swine influenza virus. However, in the current swine flu outbreak, WHO has reported that the virus is spread from human to human, and not from contact with infected pigs.

Outbreaks of A (H1N1, H3N2) swine influenza were reported worldwide from countries far apart from each other. Also, the observation of human-to-human transmission of these viruses and the ability of the virus to cause community-level outbreaks raises an important question on the chances of its prolonged transmission from human-to-human. The phylogenetic ancestry of the classical swine viruses and avian-like H1N1 swine viruses is quite discrete (Olsen et al. 2000). The detection of viruses with classical swine HA from turkeys and subsequent comparative sequence analysis on the haemmagglutinin of turkey and swine viruses shows high similarity (Altmuller et al. 1992; Suarez et al. 2002). The isolation of H3N2 swine viruses with human-like haemmagglutinin from turkeys has also been reported (Choi et al. 2004). Swine influenza infection in pigs can occur as an acute outbreak with epidemic spread to an endemic situation (Simon-Grife et al. 2012). The potential of this strain to cause pandemic was reported (Fraser et al. 2009). In response to escalating outbreaks in the United States and other countries of the world, caused by a new influenza virus of swine origin (S-OIV), the World Health Organization on 11 June 2009, declared the present swine flu ‘H1N1’ a pandemic in humans by raising the pandemic phase to level #6. One cannot be complacent about the influenza virus as shown by the emergence of influenza A virus H7N9 subtype in the year 2013. This subtype caused mortality in 43 humans in China in the first 8 months of 2013 (Parry 2013; Wiwanitkit 2013). Avian influenza A (H10N8) virus for the first time was found to infect humans in December 2013 (To et al. 2014). Two new subtypes, H17N10 and H18N11, isolated from bats have been identified during the last 1 year (Tong et al. 2012, 2013).