H5N1 avian influenza virus (AIV) subtype causes the disease popularly known as ‘Bird Flu’ in humans, while H1N1 subtype causes ‘Swine Flu’ in humans. The AIV H5N1 subtype, earlier limited to poultry, has now been found to be lethal for migratory birds and may pose a threat to humans (Claas et al. 1994; Capua and Alexander 2007; Capua and Alexander 2009; Adams and Sandrock 2010; Chmielewski and Swayne 2011; Sakoda et al. 2012). These have also emerged in mammals and among the human population (Cheung et al. 2002). The recent reports indicate that the virus has jumped species barrier with expansion of its host range and has been implicated to infect carnivores such as dogs, tigers, cats and leopards and other mammals, besides causing high mortality in birds (Dhama et al. 2005; Brown et al. 2007; Dhama et al. 2013).

The virus is continuously evolving and becoming more and more lethal. The AI virus has yet to acquire the ability of rapid spread from human-to-human (Wainwrighta et al. 2012; Dhama et al. 2013), as has been observed recently for the swine flu virus (H1N1 subtype) (Dhama et al. 2012).

The overall structure of H5N1 bird flu virus is not different from that of the conventional influenza/flu virus. Flu in humans is normally caused by three subtypes of influenza viruses: H1N1, H1N2 and H3N2, which are found to circulate commonly among people around the world. H5 strains had formerly been detected in poultry in Scotland in 1959 (influenza A/chicken/Scotland/59) (Brownlee 2006). As far as highly pathogenic avian influenza (HPAI) viruses are concerned, they have been reported to have zoonotic importance (Swayne and Suarez 2000; Koh et al. 2008;.WHO 2010; Kalthoff et al. 2010; Dhama et al. 2013). Presently, the risk of infection is not limited to poultry workers alone, but cases of human-to-human transmission, though few have also been observed (Dhama et al. 2005; Brown et al. 2007; Dhama et al. 2013).

Worldwide, aquatic birds are considered as the natural reservoir of the avian influenza virus (AIV) wherein there is consideration of the virus to be in the evolutionary stasis. With their natural host they are therefore in equilibrium without causing any disease. There is however periodic transmission of the influenza viruses to other hosts that include mammals, whereas the other viruses cause infections of transient nature with deaths recorded occasionally. Infections at a spontaneous rate are recorded in hosts which are less frequently infected by the AIV (Guan et al. 2004; Lipatov et al. 2004).

Zoonotic potential of avian influenza (AI) virus, the ability to jump species, i.e. from birds to humans, the main cause of concern of ‘avian flu’ or ‘bird flu’ for mankind, was first observed in 1997 in Hong Kong when the world awakened to a rude shock with hospitalization of 18 people (6 died) following infection with HPAI (H5N1) (Pollack et al. 1998; Suarez et al. 1998; Shortridge 1999; Swayne 2000; Capua and Alexander 2002; Tam 2002). This infamous ‘Hong Kong flu’ provided the first evidence that the HPAI virus of chicken can adapt, multiply and even cause death in affected individuals. Depopulation and killing of nearly 1.5 million birds within 3 days of the disease outbreak probably averted a possible pandemic.

Zoonotic alarm of bird flu virus mounted again in 2003, that is currently persisting too, with the re-emergence of a fatal flu associated with H5N1 of bird origin, causing five human deaths in Vietnam (3) and China (2), with subsequently increasing number of human casualties till date (29 August, 2013), as reported in Thailand, Azerbaijan, Cambodia, China, Indonesia, Cambodia, Egypt, Iraq, Turkey, Nigeria, Pakistan, Laos and Bangladesh (Capua and Alexander 2002; Katz 2003; Peiris et al. 2004; Tran et al. 2004; Dhama et al. 2005; Perdue and Swayne 2005; Beigel et al. 2005; Yuen and Wong, 2005; Ungchusak et al. 2005; Adams and Sandrock 2010; Kalthoff et al. 2010; Dhama et al. 2013). H5N1 bird flu virus has accounted for 378 human deaths of a total of 637 confirmed human cases reported (nearly 60 % mortality rate) (Dhama et al. 2013; WHO 2013a). The highest number of human casualties has been reported from Indonesia (161), Egypt (63), Vietnam (62), China (30), Cambodia (29) and Thailand (17). The number of human cases due to HPAI (H5N1) from 2003 to August 2013 was more in Egypt (173) compared to Vietnam (125), though the death in humans in these two countries was almost the same, while in Indonesia 193 persons were infected (WHO 2013a).

Apart from H5N1, human infections with novel influenza subtypes like H7N2, H7N3, H7N7, H7N9, H9N2, H10N8 and H10N7, the strains which have jumped species barrier from birds (fowl/birds/migratory birds), and recent H1N1 virus, a novel reassortant from swine were also reported (Dhama et al. 2005; Malik Peiris 2009; Kalthoff et al. 2010; Kuiken et al. 2011; Dhama et al. 2012; Dhama et al. 2013). The isolation of the AIV subtypes H9 and H7, supported by genetic, molecular and biological studies, has raised concern that the avian influenza virus is trying to establish itself among the human population (Peiris et al. 1999, 2001; Capua and Alexander 2002; Swayne and Halvorson 2003; Koopmans et al. 2004; Tweed et al. 2004; Butt et al. 2005; Brown et al. 2007). Studies have indicated that H9N2, H7N7 and H7N3 AIV subtypes are capable of jumping to humans, getting opportunities to swap genetic material with human strains, which could result in a reassortant virus (Shortridge et al. 2003; Swayne and Halvorson 2003; Tweed et al. 2004; Chen et al. 2006). Particularly, H5N1 is of major concern with regard to public health significance and human casualties (Beigel et al. 2005; Yuen and Wong, 2005; Perdue and Swayne, 2005; Chen et al. 2006; Dhama et al. 2013).

The exact conditions for human infections are not clear, but it would appear that these mostly occur in situations of high exposure to virus during close contact with affected birds. The infection is primarily acquired by oro-nasal route, mostly through virus inhalation during handling of infected birds or their products (eggs/meat) (Beigel et al. 2005; Perdue and Swayne 2005). But, if proper cooking practices are followed there is hardly any risk of this virus infection with well cooked poultry foods products, since the virus is fragile in nature and gets killed during heating (Beato et al. 2009; Taubenberger and Morens 2010). Predominantly, the bird flu virus affects the breathing passages of the respiratory tract with a rapid onset of severe viral pneumonia and causes a fatal disease in humans (Capua and Alexander 2002; Beigel et al. 2005; Yuen and Wong 2005; WHO 2005; Zhu et al. 2006; Dhama et al. 2013) with a high fatality rate in humans.

Viruses belonging to the influenza A subtype H7 cause widespread infection without any observation of infection in humans in Asia. Illnesses of milder intensities were previously recorded in most of the human patients infected with highly pathogenic avian influenza (HPAI) A (H7) viruses. Live bird market (LBM) plays a key role in the transmission of H7N9 infection in human. There is however no evidence of sustained transmission from one person to another but several such transmissions have been suspected (Arima et al. 2013). In Asia, the H7 viruses are transmitted on rare occasions and there is no documentation of human infection with viruses belonging to the N9 subtypes. The symptoms in humans from other parts of the world are mostly fever and cough with respiratory distress of acute nature in common with rapid deterioration of the health of the patient. The H7N9 viral haemagglutinin (HA) data sequences suggest that these viruses are influenza A viruses of low pathogenecity. Therefore, whenever there is infection of wild birds as well as domestic poultry it will result in avian disease of either asymptomatic or mild in nature. This has already resulted in an epizootic of ‘silent’ nature in China causing rapid death in chicken. The animal reservoirs according to researchers are birds, but astonishingly, the virus may infect pigs as well (which is a second common reservoir for infection of zoonotic nature). Antiviral resistance to drugs like adamantanes along with susceptibility to neuraminidase inhibitors is reported on the basis of sequence data of the virus. If infection with H7N9 subtype is either suspected or confirmed in human, oselatamivir (orally) or zanamivir (inhaled) are mandatory for patients. There is always threat of secondary bacterial infection which must be taken under the consideration of clinicians along with appropriate use of antibiotic (Koopmans and de Jong 2013; Schnirring 2013; Skowronski et al. 2013).

After the first incidence of ‘bird flu’ in humans in Hong Kong (1997), several researchers have raised concern about the possibility of a human pandemic in the near future; when it will happen nobody can predict (Shortridge et al. 2003; Fleming 2005; Horimoto and Kawaoka 2005; Mermel 2005; De la Barrera and Teran 2005; Chotpitayasunondh et al. 2005). In the twentieth century, the unexpected emergence of antigenically different human flu virus strains due to antigenic shift has occurred on three occasions which have all resulted in human influenza pandemics, viz. Spanish flu’ (H1N1, 1918), ‘Asian Flu’ (H2N2, 1957) and ‘Hong Kong Flu’ (H3N2, 1968), (Reid and Taubenberger 1999; de Jong et al. 2006). Genetic analysis of these flu virus isolates revealed that the ‘new strains’ have most certainly emerged after reassortment of genes of viruses of avian and human origin with novel viruses originating as reassortants, in which one or both human-adapted viral surface proteins were replaced by proteins from AIV strain; except during the ‘1918 Spanish flu’s (Reid and Taubenberger 1999; Basler et al. 2001). Thus, the possibility of another pandemic involving influenza virus of avian origin is not merely a hypothetical risk and can occur at any point of time.

The lessons from the past need to be kept in mind and the infections that has recently resulted in person to person transmissibility should be given due attention so as to avert a possible threat of an imminent pandemic (Shortridge et al. 2003; Horimoto and Kawaoka 2005; Dudley 2006). History has evidenced that every 30 years or so the pandemics have occurred with the last pandemic occurring in 1968, so the researchers all over the world have warned about the probability of the emergence of a new avian influenza virus strain in the near future at any time that can trigger a devastating pandemic, if given the right conditions (Mermel 2005, De la Barrera and Teran 2005; Horimoto and Kawaoka 2005). Avian species harbour a large reservoir of influenza viruses, which can contribute genes to potential new pandemic human strains. Added to this, the reports of mammalian infections with H5N1 AI viruses and, in particular, mammal-to-mammal transmission in humans and tigers are unprecedented. Of paramount importance is the threat emanating from the combination of wild bird reservoirs, backyard poultry and pig rearing in the vicinity. The regions which could form an influenza epicentre are those, like South-East Asia, where birds, other animals and humans live in close proximity and under such conditions influenza viruses have the greatest opportunity to pass from one species to another, which could result in a virus with pandemic threat and potential.

Fully aware of the risk of avian influenza the plan of pandemic preparedness has been activated by World Health Organization (WHO). Along with this there is alertness in the network laboratories and there has also been placement of response teams. The response plan laid down by WHO consists of mainly three objectives: averting a pandemic; controlling the human outbreak of avian influenza; preventing further cases; conducting the required research activities for monitoring the situation and for improving preparedness. Improving the preparedness includes the vaccine development immediately (Morens et al. 2004; Weiss and McMichael 2004).

The economically important disease of pigs, ‘swine flu’ is caused mainly by H1N1, HNN2 and H3N2 viruses which are responsible for causing pandemic threat. Human and avian influenza viruses can also infect pigs which thereby act as mixing vessel for the evolution of new reassortant virus (Pawaiya et al. 2009).

From the first report of swine flu H1N1 human pandemic in April 2009 (Zhang and Chen 2009), within a year more than 208 countries were affected with at least 13,554 deaths (Pawaiya et al. 2009; Koparde and Singh 2011; Dhama et al. 2012). In August 2010, the World Health Organization declared the swine flu pandemic to be over. The swine influenza H1N1 strain is an H1N1 human-swine-avian reassortant strain (Zhang and Chen 2009) of avian H1N1, H1N1 classical swine virus (Eurasian and North American) and H3N2 seasonal flu virus (Smith et al. 2009). The sequence of this swine flu virus was reported to be evolutionarily widely different from the past few year sequences but had close similarity with the ancient (1918) viral sequences reported (Sinha et al. 2009). The H1N1, H1N2 and H3N2 subtypes of influenza A viruses of swine origin can be transmitted between humans and animals. Detection of a novel reassortant influenza virus in swines in the year 2010, having genes encoding internal proteins from H1N1 pandemic (2009) virus and haemagglutinin and neuraminidase genes from H1N2 swine influenza virus during the influenza virus surveillance in the United Kingdom, reflects the heterogeneity of the virus and its potential to get transmitted to human. In comparison to other reported reassortants, human-like host restrictive and putative antigenic sites were preserved in HA and NA genes of both viruses (Howard et al. 2011). In the US, two cases of H3N2 swine-origin influenza A virus infection were reported in two children of 5 years age in August 2011 with a history of recent contact with pigs, and both had received seasonal influenza vaccine containing the pandemic H1N1 swine flu virus strain in the previous year. In August 2012, the confirmed human cases primarily in children of H3N2 virus, was reported in the US (Skowronski et al. 2012) with history of exposure to pigs.

The reassortment events of swine flu viruses with the pandemic H1N1 virus and interspecies transmission abilities of such reassortants from pig to human and other species highlights the significance of heightened surveillance systems of the swine population to establish the origin of such viruses, to know the prevalence of similar reassortants and their impact on both swine production and public health in the US (Ali et al. 2012). It is good that the swine flu did not acquire the lethality as that of bird flu virus having nearly 60 % case fatality rates, in which case a deadly pandemic would begin and would create a threat to human survivability.

In the context of the concept of ‘original antigenic sin’ it has been postulated that on exposure to the swine influenza virus for the first time during childhood there is development of strongest immunity in the following years. Thus there is development of natural immunity at the greatest to the A/H1N1 pdm pandemic virus in circulation at present (Chowell et al. 2011; Rifkin and Schaal 2012).