**Prevention of Influenza**

[14] Yakovlev AA, Zinserling VA, Esaulenko EV. Lethal outcomes in influenza: Clinicpathological approach to immediate death causes (in Russian). Journal of Infectologii.

[15] Zinserling VA, Dedov VA Influenza. In: Hofman P, editor. Infectious Disease and

[16] Zinserling VA. Immediate death causes in influenza. Virchows Archiv. 2017;**471**(S.1):s100

2017;**9**(4):53-59. DOI: 10.22625/2072-6732-2017-9-4-53-58

30 Influenza - Therapeutics and Challenges

Parasites. Berlin: Springer; 2016. DOI: 10.1007/978-3-319-300009-2

**Chapter 3**

**Provisional chapter**

**Preventing Zoonotic Influenza**

**Preventing Zoonotic Influenza**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76966

**Abstract**

Clement Meseko, Binod Kumar and Melvin Sanicas

including advances in vaccines and chemotherapeutics.

**1. Historical perspective on zoonotic influenza**

vaccines, antiviral resistance

Clement Meseko, Binod Kumar and Melvin Sanicas

DOI: 10.5772/intechopen.76966

The public health risk of influenza at the human-animal interface is dicey, due in part to continuous evolution of the virus. Influenza virus consist of 7 genera of which only influenza A is at present zoonotic, where subtypes H5, H7 and H9 of avian origin and subtype H1 and H3 of swine origin are important. The most devastating influenza pandemic in history was suspected to have emerged from avian reservoir and manifested in 1918. The first recognized direct human transmission of highly pathogenic avian influenza (HPAI) H5N1 occurred in 1997 in Hong Kong. Subsequently, many cases of varying severity have been described in people who were exposed to poultry. More recently in 2009, triple reassortant influenza A of swine origin (A/H1N1pdm09) caused the first pandemic of the twenty-first century and since 2013, H7N9 though initially benign in birds, caused fatal infection in humans who had contact with poultry. These public health threats from animal influenza virus are aggravated by increase co-mingling in shared humananimal environment. Therefore, the challenge of emerging zoonotic influenza viruses on human host immunity, efficacy of vaccines and antiviral resistance require continuous risk assessment of virological and clinical changes that have impact on control measures

**Keywords:** influenza viruses, zoonotic transmission, reassortment, immunity and

The family of influenza virus, known as *Orthomyxoviridae*, consists of 7 genera viz.: Influenza A, B, C and D. Others are *Thogotovirus*, *Quaranjavirus* and *Isavirus* which are associated with arthropods and fish [1]. Only 3, influenza A, B and C so far have been described in humans, while only Influenza A is commonly transmitted from animals to human and vice versa [2, 3]. Influenza A virus (IAV) is further divided into subtypes based on the Hemagglutinin surface

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

#### **Preventing Zoonotic Influenza Preventing Zoonotic Influenza**

Clement Meseko, Binod Kumar and Melvin Sanicas Clement Meseko, Binod Kumar and Melvin Sanicas

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76966

#### **Abstract**

The public health risk of influenza at the human-animal interface is dicey, due in part to continuous evolution of the virus. Influenza virus consist of 7 genera of which only influenza A is at present zoonotic, where subtypes H5, H7 and H9 of avian origin and subtype H1 and H3 of swine origin are important. The most devastating influenza pandemic in history was suspected to have emerged from avian reservoir and manifested in 1918. The first recognized direct human transmission of highly pathogenic avian influenza (HPAI) H5N1 occurred in 1997 in Hong Kong. Subsequently, many cases of varying severity have been described in people who were exposed to poultry. More recently in 2009, triple reassortant influenza A of swine origin (A/H1N1pdm09) caused the first pandemic of the twenty-first century and since 2013, H7N9 though initially benign in birds, caused fatal infection in humans who had contact with poultry. These public health threats from animal influenza virus are aggravated by increase co-mingling in shared humananimal environment. Therefore, the challenge of emerging zoonotic influenza viruses on human host immunity, efficacy of vaccines and antiviral resistance require continuous risk assessment of virological and clinical changes that have impact on control measures including advances in vaccines and chemotherapeutics.

DOI: 10.5772/intechopen.76966

**Keywords:** influenza viruses, zoonotic transmission, reassortment, immunity and vaccines, antiviral resistance

#### **1. Historical perspective on zoonotic influenza**

The family of influenza virus, known as *Orthomyxoviridae*, consists of 7 genera viz.: Influenza A, B, C and D. Others are *Thogotovirus*, *Quaranjavirus* and *Isavirus* which are associated with arthropods and fish [1]. Only 3, influenza A, B and C so far have been described in humans, while only Influenza A is commonly transmitted from animals to human and vice versa [2, 3]. Influenza A virus (IAV) is further divided into subtypes based on the Hemagglutinin surface

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

glycoproteins (HA1-18) and Neuraminidase (NA1-11), HA1-16 and NA1-9 are those that are up till date identified to occur naturally in avian host, mostly waterfowls where they exist in benign form (low pathogenic) [4, 5]. Two additional subtypes (HA 17 and 18, NA 10 and 11) were identified in bats [6]. Genetic mutations and reassortment may occur spontaneously or over a long period in reservoir hosts. These result in the emergence of novel subtypes, reassortants, strains or variants from the Low Pathogenic Avian Influenza (LPAI) precursors. These phenomena that have been described as antigenic shift and drift also contribute to the evolution, adaptation and inter-species transmission of influenza viruses and provide opportunities for gain of function in nature including molecular and or biological properties that may enhance zoonotic transmission. Sometimes a strain may arise in animals with adaptations of fitness to cause fatal infection or increase transmission and potentials to cause pandemics in human population [7, 8].

Aquatic birds are the most important group of animals in the ecology and epidemiology of influenza virus. Almost all naturally circulating subtypes of influenza virus in birds and mammals (including human) can be traced to avian descendants including earlier description in literature by Perroncito in 1878 [4, 9]. The first pandemic of influenza virus that occurred in 1918 (Spanish flu) was caused by an avian influenza virus, as revealed by sero-archeology and molecular characterization [10, 11]. The 1918 influenza pandemic killed over 50 million people and about one third (500 million persons) of the world's population had clinically apparent illnesses. The Case-fatality rate was greater than 2.5% in comparison to less than 0.1% in other influenza pandemics. Nearly half of influenza-related deaths were observed in young adults between the ages of 20–40 years, an indication that the virus was newly introduced possibly from animal reservoir to naive human population [12].

zoonotic and potentially pandemic influenza A virus infections has therefore attracted global concern since the identification of avian and swine influenza viruses that can (with or without biological or molecular adaptations) be transmitted directly, and cause severe disease in humans and other mammals. This was notable with the advent of A/Goose/Guangdong/96 lineage of H5N1, which had infected 860 people and killed 454 (52% case-fatality rate) up till December 2017 [19]. Continuous circulation of H5N1 in birds and zoonotic transmission to human may cause influenza virus to acquire adaptive genetic features for efficient human to human transmission through mutations (insertions/deletions), reassortment or emergence of immune or antiviral resistant strains. Those may likely be precursors of emerging influenza virus with pandemic potential. Global surveillance for influenza diversity in animals and human may therefore greatly improve our ability for early detection, to identify and antici-

**Figure 1.** Illustration of cross-species transmission of avian, swine and human influenza viruses. Waterfowls as natural reservoirs, pigs serve as 'mixing vessels', viruses from humans seed pH1N1 in swine populations, reassortment between

Preventing Zoonotic Influenza

35

http://dx.doi.org/10.5772/intechopen.76966

pH1N1 viruses and co-circulating triple reassortant H3N2 viruses in pigs generate novel reassortant H3N2v.

The first human transmission of Highly Pathogenic Avian Influenza (HPAI) subtype H5N1 occurred in 1997 in Hong Kong. It became a global public health concern, knowing that pandemic influenza viruses in the past originated from animals [20]. The H5N1 was thus considered a potential pandemic threat [21]. The HPAI H5N1 lineage (A/Goose/Guangdong/1/96) was initially isolated from a goose farm in Guangdong Province, China in 1996. In the following

pate which strains are more likely to evolve and be better prepared [18].

**2. Human infections with avian influenza virus**

The causative virus of the 1918 pandemic, following human transmission, was concurrently transmitted to pigs in America, Europe and China. This was to play out again in 2009 when A/ H1N1pdm09 virus was also transmitted via anthropogenic means to swine. In both scenarios, the causative virus was eventually isolated in pigs [2, 13]. More epidemics and pandemics arising from descendants of the 1918 virus were subsequently recorded in 1957 Asian flu (H2N2), 1968 Hong Kong flu (H3N2) and the more recent H1N1 2009 influenza pandemic that originated in Mexico (Mexican flu). The common precursor of these viruses appeared to be an avian influenza virus that entered the human population directly or indirectly through intermediate hosts probably at some points involving pigs as enunciated by Nelson et al. [14] and in **Figure 1**. Exceptionally, the 1918 pandemic virus appeared to have been wholly derived from avian-like influenza virus from an unknown source [15]. Thus zoonotic influenza transmission seems to be the foundation of influenza virus infection in human including previous pandemics, contemporary and more recent transmissions and fatal human infections caused by avian H5, H7 and H9 in many countries [16, 17].

In the last 100 years, influenza virus in human are generally manifested as seasonal, zoonotic and pandemic with clinico-pathological manifestation that vary from mild, severe to fatal. However, the most threatening influenza infections are those caused by zoonotic and/or pandemic strains following their introduction usually from animal reservoir into human population that has little or no pre-existing specific or cross protective immunity [18]. The burden of

glycoproteins (HA1-18) and Neuraminidase (NA1-11), HA1-16 and NA1-9 are those that are up till date identified to occur naturally in avian host, mostly waterfowls where they exist in benign form (low pathogenic) [4, 5]. Two additional subtypes (HA 17 and 18, NA 10 and 11) were identified in bats [6]. Genetic mutations and reassortment may occur spontaneously or over a long period in reservoir hosts. These result in the emergence of novel subtypes, reassortants, strains or variants from the Low Pathogenic Avian Influenza (LPAI) precursors. These phenomena that have been described as antigenic shift and drift also contribute to the evolution, adaptation and inter-species transmission of influenza viruses and provide opportunities for gain of function in nature including molecular and or biological properties that may enhance zoonotic transmission. Sometimes a strain may arise in animals with adaptations of fitness to cause fatal infection or increase transmission and potentials to cause pandemics in

Aquatic birds are the most important group of animals in the ecology and epidemiology of influenza virus. Almost all naturally circulating subtypes of influenza virus in birds and mammals (including human) can be traced to avian descendants including earlier description in literature by Perroncito in 1878 [4, 9]. The first pandemic of influenza virus that occurred in 1918 (Spanish flu) was caused by an avian influenza virus, as revealed by sero-archeology and molecular characterization [10, 11]. The 1918 influenza pandemic killed over 50 million people and about one third (500 million persons) of the world's population had clinically apparent illnesses. The Case-fatality rate was greater than 2.5% in comparison to less than 0.1% in other influenza pandemics. Nearly half of influenza-related deaths were observed in young adults between the ages of 20–40 years, an indication that the virus was newly introduced possibly

The causative virus of the 1918 pandemic, following human transmission, was concurrently transmitted to pigs in America, Europe and China. This was to play out again in 2009 when A/ H1N1pdm09 virus was also transmitted via anthropogenic means to swine. In both scenarios, the causative virus was eventually isolated in pigs [2, 13]. More epidemics and pandemics arising from descendants of the 1918 virus were subsequently recorded in 1957 Asian flu (H2N2), 1968 Hong Kong flu (H3N2) and the more recent H1N1 2009 influenza pandemic that originated in Mexico (Mexican flu). The common precursor of these viruses appeared to be an avian influenza virus that entered the human population directly or indirectly through intermediate hosts probably at some points involving pigs as enunciated by Nelson et al. [14] and in **Figure 1**. Exceptionally, the 1918 pandemic virus appeared to have been wholly derived from avian-like influenza virus from an unknown source [15]. Thus zoonotic influenza transmission seems to be the foundation of influenza virus infection in human including previous pandemics, contemporary and more recent transmissions and fatal human infections caused

In the last 100 years, influenza virus in human are generally manifested as seasonal, zoonotic and pandemic with clinico-pathological manifestation that vary from mild, severe to fatal. However, the most threatening influenza infections are those caused by zoonotic and/or pandemic strains following their introduction usually from animal reservoir into human population that has little or no pre-existing specific or cross protective immunity [18]. The burden of

human population [7, 8].

34 Influenza - Therapeutics and Challenges

from animal reservoir to naive human population [12].

by avian H5, H7 and H9 in many countries [16, 17].

**Figure 1.** Illustration of cross-species transmission of avian, swine and human influenza viruses. Waterfowls as natural reservoirs, pigs serve as 'mixing vessels', viruses from humans seed pH1N1 in swine populations, reassortment between pH1N1 viruses and co-circulating triple reassortant H3N2 viruses in pigs generate novel reassortant H3N2v.

zoonotic and potentially pandemic influenza A virus infections has therefore attracted global concern since the identification of avian and swine influenza viruses that can (with or without biological or molecular adaptations) be transmitted directly, and cause severe disease in humans and other mammals. This was notable with the advent of A/Goose/Guangdong/96 lineage of H5N1, which had infected 860 people and killed 454 (52% case-fatality rate) up till December 2017 [19]. Continuous circulation of H5N1 in birds and zoonotic transmission to human may cause influenza virus to acquire adaptive genetic features for efficient human to human transmission through mutations (insertions/deletions), reassortment or emergence of immune or antiviral resistant strains. Those may likely be precursors of emerging influenza virus with pandemic potential. Global surveillance for influenza diversity in animals and human may therefore greatly improve our ability for early detection, to identify and anticipate which strains are more likely to evolve and be better prepared [18].
