**4. Systemic monitor and approach for a new information of epidemic and pandemic infections**

Avian influenza viral infections are wide ranges of mammalians, and it is not enough to monitor avian, swine, and humans for covering all types of avian influenza virus infection because of the rare case appearance of the LPAI outbreak in cats in the USA [74]. The World Health Organization (WHO) continuously monitors avian and other zoonotic influenza viruses closely through its Global Influenza Surveillance and Response System (GISRS) (http://www.who.int/influenza/ gisrslaboratory/en/). From this site, necessary information about occurrence of outbreaks, conditions, widespread of infections, etc. can be investigated and gathered. But insufficient monitor for zoonotic influenza infections as potential to

*Viruses and Viral Infections in Developing Countries*

**2.7 Other strains of avian influenza viruses.**

**3.1 Genes' transport of wild birds to poultry by antigenic shift**

the abilities of transferring from human to human [28–38].

**pandemic influenza viruses**

**3.2 Possibility of intermediate hosts or mixing vessels for the generation for** 

Avian has α2–3-linked sialic acids, human has α2–6-linked sialic acids, and swine has both types of receptor for HA of influenza A viruses [80]. These enable

around 2 km of affected farms.

**3. Transmission of species**

to mammals.

In Australia in 2010, an outbreak of LPAI H10N7 viruses was identified as 10–25 bird's deaths for 8–14 days, a 15% decrease of egg production, and no respiratory signs in affected flocks. Two of seven abattoirs who had conjunctivitis and minor upper respiratory tract symptoms were identified to be infected by H10N7 virus [79]. In Australia in 2010, surveillance for H10N7 viruses showed small numbers of wild waterfowl on the affected site and no infection of H10 subtypes in poultry

In addition to avian influenza strains of poultry to human infections, epidemics of avian influenza A strains are reported: H5N2, H5N5, and H5N8 viruses as HPAI viruses and H3N8, H6N6, H10N4, H10N5, H11N2, and H7N8 as occasional infection

As above, many avian influenza reasssortant viruses have emerged during viral transmission from wild birds (donor spices) to poultry (recipient species). LPAI viruses from wild birds have been reasserted with other influenza virus strains of poultry and changed virulence in poultry. If LPAI viruses could not adapt to new host of poultry, they would die out. LPAI viruses have been environmentally sustained by close contact to LPAI viruses among wild birds when avian influenza A virus infections happened in endemic countries. Host species barriers do not mean simply the biological barriers [7]. Biological barriers between wild birds and poultry are almost the same in concerning about influenza binding receptor in cell membrane (α2–3-linked sialic acids) and replication condition in host temperature [19, 53]. In addition to biological barriers, interspecific interactions between wild birds (donor) and poultry (recipient), interactions between avian influenza viruses and poultry (recipient), and interactions among individuals of poultry (recipient) are considered as environmental barriers [7]. In consequence of surmounting these barriers, LPAI viruses have been sustained by the successful onward adaptation to new hosts like H7N7 viruses, H9N2 viruses and H7N9 viruses in the present [47, 59, 64]. If humans have been in close contact to poultry affected with LPAI viruses, asymptomatic or mild illness of avian influenza A virus infections would appear in humans but rarely leads to fatal disease [45, 46]. LPAI viruses suddenly have changed virulence to HPAI viruses and caused severe disease and deaths among poultry like the emergence of H5N1 virus being in consequent to human epidemic [14]. Increased virulence from LPAI to HPAI following antigenic shift could not be predicted before the happening. Avian influenza A viruses need to acquire the abilities to transmit to new host species and replicate effectively in new host before an epidemic or pandemic [7]. Antigenic shift in avian viruses has transmitted the abilities of transferring from poultry to humans and replicating progeny in humans by accumulated mutations in HA, NA, PB2, NS1, etc. but has not transmitted

**102**

the human pandemic is reinforced by the information from the collaboration with the World Organization for Animal Health (OIE) (www.oie,int/) and the Food and Agriculture Organization (FAO) (www.fao.org/home/en/). In each country, the national disease center monitors its own country and internationally collaborates with the WHO. Monitoring reinforces the environmental barriers by noticing abnormal wild birds' deaths in a province to the provincial and national authorities in an early stage of an endemic. Following this information, provincial authorities would start to investigate etiology of birds' deaths and any other birds' deaths around this area and water pollution by avian influenza viruses in ponds if avian influenza viruses caused birds' deaths. Environmental barriers have three steps which are composed of a first step of transmission from waterfowl to poultry, a second step of transmission of individuals among poultry, and a third step of transmission from poultry to humans (**Figure 2**). When a first step of environmental barrier from wild birds to poultry is surmounted by avian influenza viruses, two patterns of damage in poultry (asymptomatic/mild disease or severe disease/ deaths) are recognized. It is very difficult to detect early and diagnose asymptomatic infections in poultry, but any changes in poultry including coughing and decrease numbers of egg production should not be missed. Recently rapid influenza diagnostic tests (RIDTs) are available in testing for avian influenza viruses (H5, H7, and H9), but other RIDTs for detection of more HA subtypes are desirable to be developed in demand [83]. If any doubt for avian influenza infection, RIDTs are recommended to be applied immediately within the limits of lower sensitivity than RT-PCR and other methods. A combination of RIDTs (infection of avian influenza viruses), RT-PCR (viral genes sequence and subtypes), HA inhibition test (viral subtype), ELISA (all subtypes of avian influenza viruses and widespread of viral infection), and the inoculation of isolated viruses to chicken (identification of viral pathogeny) would be adapted without any time consumption for diagnosis. These tests may provide an initial measure and further measures for control of an endemic, epidemic, and a potential pandemic infection of avian viruses. A second step of environmental barrier is reinforced by using the following measures: isolation of birds from the others, the use of personal protection equipment (PPEs)

**105**

*Adequate Monitor of Avian Influenza Viral Infections and Foresight About Possibilities of Its…*

by farm workers, and culling the affected birds. But widespread of avian viral infections among poultry is not necessary for a long time. So it is desirable to diagnose avian viral infection in the shortest time since the first notification of disease by these diagnostic tests. Vaccination of poultry has been applied for the prevention from economic damage of culling and a potential pandemic, as biological barriers [84]. But vaccines of animals for avian viral infections would be desired to high efficacy and prevalence use in the areas. Considering the negative effect for the difficulty of conducting surveillance for persistence of the virus after vaccination or insufficient immune response in birds leading to the latent viral infection in poultry, vaccination should carefully be adapted as one component of control measures [84]. Control strategies and measures including technical guidelines for pandemic potential are available from FAO and OIE [84, 85]. It is emphasized that the surveillance standards and methodology are necessary for calling rapid response for containment or mitigation of emerging infectious disease of avian influenza but not a system for rapid detection of emerging novel influenza strains or outbreaks of disease [85]. Sentinel surveillance is desired to protect poultry and humans from the threat of epidemic and/or pandemic potential in the prevalence of avian viruses among wild birds and poultry. Collapse of a third step of environmental barrier is recognized as human infection with avian influenza viruses. This condition is called as pandemic phase 2 in the WHO pandemic phase descriptions [86] (**Figure 2**). Human infection primarily may appear in direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets. And human infection also may appear concerning slaughtering, de-feathering, handling carcasses of infected poultry, and preparing poultry for consumption, especially in household settings [87]. Surveillance of avian viral infections in these persons will be done by applying combinations of diagnostic methods as soon as possible from the onset of the first poultry infections. Consumption of prepared poultry and raw egg dishes has been reported to be linked with the infection of H5N1 human cases [87]. The virus is inactivated at temperatures (at least 70°C the center of the product) in conventional cooking, and consumption of properly cooked poultry and eggs should be recommended [88]. Although human-to-human transmission of avian influenza viruses may occur in the close and/or prolonged contact with the patients, there has been no sustained human-to-human transmission of these viruses identified [89]. But in North America in 2009, influenza A (H1N1) pdm 009 virus originated from swine influenza viruses surmounted biological barriers. It took only a few months to amount to a total number of 73 affected countries and more than 26,000 laboratory-confirmed infected cases from the first case in Mexico in February of 2009 which is called as pandemic phase 6 (**Figure 2**) [90]. These suggested how fast infections had been spread in the world and how difficult to control the widespread of emerging infectious disease (EID) after the new emerging avian influenza virus had obtained the capacity of the interhuman transmission. In this phase, therapy for patients and adaptation of control measures for pandemic were necessary. Antiviral drugs for influenza viral infections except adamantanes are effective for avian influenza infections in the early stage of infection for the decrease of mortality rate [91]. Administration of neuraminidase inhibitors (NAIs) to infected persons within 48 hours of onset would be recommended, and isolation of infected people from the public would be important in a limited term. Recently baloxavir marboxil that prevents replication by inhibiting the cap-dependent endonuclease activity of the viral polymerase and is effective for seasonal influenza and avian influenza virus infections is available in Japan [92]. In addition to NAIs, it may be one of the powerful tools as antiviral therapy. In the pre-pandemic stage to the pandemic stage, network information and control measures from the national disease center, the Global Influenza Surveillance Network (GISN), Global Outbreak

*DOI: http://dx.doi.org/10.5772/intechopen.86551*

#### *Adequate Monitor of Avian Influenza Viral Infections and Foresight About Possibilities of Its… DOI: http://dx.doi.org/10.5772/intechopen.86551*

by farm workers, and culling the affected birds. But widespread of avian viral infections among poultry is not necessary for a long time. So it is desirable to diagnose avian viral infection in the shortest time since the first notification of disease by these diagnostic tests. Vaccination of poultry has been applied for the prevention from economic damage of culling and a potential pandemic, as biological barriers [84]. But vaccines of animals for avian viral infections would be desired to high efficacy and prevalence use in the areas. Considering the negative effect for the difficulty of conducting surveillance for persistence of the virus after vaccination or insufficient immune response in birds leading to the latent viral infection in poultry, vaccination should carefully be adapted as one component of control measures [84]. Control strategies and measures including technical guidelines for pandemic potential are available from FAO and OIE [84, 85]. It is emphasized that the surveillance standards and methodology are necessary for calling rapid response for containment or mitigation of emerging infectious disease of avian influenza but not a system for rapid detection of emerging novel influenza strains or outbreaks of disease [85]. Sentinel surveillance is desired to protect poultry and humans from the threat of epidemic and/or pandemic potential in the prevalence of avian viruses among wild birds and poultry. Collapse of a third step of environmental barrier is recognized as human infection with avian influenza viruses. This condition is called as pandemic phase 2 in the WHO pandemic phase descriptions [86] (**Figure 2**). Human infection primarily may appear in direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets. And human infection also may appear concerning slaughtering, de-feathering, handling carcasses of infected poultry, and preparing poultry for consumption, especially in household settings [87]. Surveillance of avian viral infections in these persons will be done by applying combinations of diagnostic methods as soon as possible from the onset of the first poultry infections. Consumption of prepared poultry and raw egg dishes has been reported to be linked with the infection of H5N1 human cases [87]. The virus is inactivated at temperatures (at least 70°C the center of the product) in conventional cooking, and consumption of properly cooked poultry and eggs should be recommended [88]. Although human-to-human transmission of avian influenza viruses may occur in the close and/or prolonged contact with the patients, there has been no sustained human-to-human transmission of these viruses identified [89]. But in North America in 2009, influenza A (H1N1) pdm 009 virus originated from swine influenza viruses surmounted biological barriers. It took only a few months to amount to a total number of 73 affected countries and more than 26,000 laboratory-confirmed infected cases from the first case in Mexico in February of 2009 which is called as pandemic phase 6 (**Figure 2**) [90]. These suggested how fast infections had been spread in the world and how difficult to control the widespread of emerging infectious disease (EID) after the new emerging avian influenza virus had obtained the capacity of the interhuman transmission. In this phase, therapy for patients and adaptation of control measures for pandemic were necessary. Antiviral drugs for influenza viral infections except adamantanes are effective for avian influenza infections in the early stage of infection for the decrease of mortality rate [91]. Administration of neuraminidase inhibitors (NAIs) to infected persons within 48 hours of onset would be recommended, and isolation of infected people from the public would be important in a limited term. Recently baloxavir marboxil that prevents replication by inhibiting the cap-dependent endonuclease activity of the viral polymerase and is effective for seasonal influenza and avian influenza virus infections is available in Japan [92]. In addition to NAIs, it may be one of the powerful tools as antiviral therapy. In the pre-pandemic stage to the pandemic stage, network information and control measures from the national disease center, the Global Influenza Surveillance Network (GISN), Global Outbreak

*Viruses and Viral Infections in Developing Countries*

the human pandemic is reinforced by the information from the collaboration with the World Organization for Animal Health (OIE) (www.oie,int/) and the Food and Agriculture Organization (FAO) (www.fao.org/home/en/). In each country, the national disease center monitors its own country and internationally collaborates with the WHO. Monitoring reinforces the environmental barriers by noticing abnormal wild birds' deaths in a province to the provincial and national authorities in an early stage of an endemic. Following this information, provincial authorities would start to investigate etiology of birds' deaths and any other birds' deaths around this area and water pollution by avian influenza viruses in ponds if avian influenza viruses caused birds' deaths. Environmental barriers have three steps which are composed of a first step of transmission from waterfowl to poultry, a second step of transmission of individuals among poultry, and a third step of transmission from poultry to humans (**Figure 2**). When a first step of environmental barrier from wild birds to poultry is surmounted by avian influenza viruses, two patterns of damage in poultry (asymptomatic/mild disease or severe disease/ deaths) are recognized. It is very difficult to detect early and diagnose asymptomatic infections in poultry, but any changes in poultry including coughing and decrease numbers of egg production should not be missed. Recently rapid influenza diagnostic tests (RIDTs) are available in testing for avian influenza viruses (H5, H7, and H9), but other RIDTs for detection of more HA subtypes are desirable to be developed in demand [83]. If any doubt for avian influenza infection, RIDTs are recommended to be applied immediately within the limits of lower sensitivity than RT-PCR and other methods. A combination of RIDTs (infection of avian influenza viruses), RT-PCR (viral genes sequence and subtypes), HA inhibition test (viral subtype), ELISA (all subtypes of avian influenza viruses and widespread of viral infection), and the inoculation of isolated viruses to chicken (identification of viral pathogeny) would be adapted without any time consumption for diagnosis. These tests may provide an initial measure and further measures for control of an endemic, epidemic, and a potential pandemic infection of avian viruses. A second step of environmental barrier is reinforced by using the following measures: isolation of birds from the others, the use of personal protection equipment (PPEs)

**104**

**Figure 2.**

*Comparison WHO Pandemic Phase and biological and environmental barriers step ladder.*

and Alert Network (GOARN), and the original network for influenza viral infection in province. In usual diagnosis and treatment of influenza viral infection, RIDTs are a useful step-up strategy for the treatment of influenza viral infections regardless of limiting sensitivity. RIDTs for seasonal influenza viral infection can only detect A type and/or B type of viral HA but not subtypes of HA strains. But these tests recognize human and avian influenza viral strains (H1N1, H2N3, H3N8, H4N6, H5N2, H6N2, H7N7, H8N4, H9N2, H10N7, H11N6, H12N6, H13N6, H14N5, H15N8, H16N3, H5N1, H5N6, H5N8, H7N1, N7 N7, and H7N9) as influenza type A viral infections (Tauns Inc.). By the results of these tests, and then if an antiviral therapy for influenza viral infection would be applied to patients. And then if an antiviral therapy is judged as not to be effective by the evaluation for the time of alleviation of fever in humans with influenza viral infections, further investigation for complications of viral infections, a new emerging viral infection using RIDTs for HA sub-strains, RT-PCR and/or viral cell culture, or mutant viruses resistant to antiviral drugs [13, 93]. In the pandemic phases 4–6, there may be many patients with influenza viral infection. It is very important to minimize the severe fatal disease from HPAI or LPAI infections and to select and send the patients with severe disease to the hospitals under the capacities for admission effectively by the triage between mild disease and severe disease. So this system may enable an early intervention of viral infections within 48 hours from onset and less numbers of patients with severe disease. It is not necessary to divide seasonal viral infection treatment from LPAI infection treatment except the necessity of special training and area for protection of widespread of EID using PPE. Like in the case with LPAI H6N1 virus in Taiwan [77], LPAI viral infections may be treated without identification in the circumstance of avian viral widespread among domestic birds. As one of the control points for pandemic preparedness, the candidate pandemic vaccine is desired and planned to be developed for prophylaxis and the most effective one of the control measures. The WHO has developed the influenza candidate vaccine viruses (CVVs) which are planned to be supplied to national authorities for pilot lot vaccine production, clinical trials, and other pandemic preparedness purposes based on their assessment of public health risk and need (contact at gisrs-whohq@who.int) [94]. Effective pandemic vaccines may be the most powerful measures for pandemic.
