Title Page
Copyright
Dedication
List of contributors
Foreword
Preface
Section I: Common aspects of animal influenza
Chapter 1: Influenza A virus
1. Introduction
2. Etiology
3. Virus life cycle
4. Virus genetics
5. Clinical disease in poultry
6. Antigenic drift and shift
7. Conclusions
8. References
Chapter 2: Diagnostics and surveillance methods
1. Introduction
2. Sample types
3. Sample collection, transport, and storage
4. Virus detection
5. Serological methods
6. Characterization of influenza isolates
7. Education and training
8. Conclusion
9. References
Chapter 3: The economics of animal influenza
1. Introduction
2. Benefits and costs of controlling animal influenza
3. The potential impact of human influenza
4. The globalized livestock sector
5. Market shocks
6. Food and livelihoods insecurity
7. Impacts of outbreak stamping-out measures
8. Post-outbreak rehabilitation
9. Longer-term measures for prevention and control of animal influenza
10. Conclusions
11. References
Chapter 4: Trade and food safety aspects for animal influenza viruses
1. Global production and trade of horses, pigs, poultry, and their products
2. Risk of the spread of animal influenza A virus through trade
3. Mitigation of trade risks
4. Food safety risks?
5. Conclusions
6. Acknowledgments
7. References
Chapter 5: Public health implications of animal influenza viruses
1. Introduction
2. Diagnosis of animal-origin influenza A virus infections
3. Human infections with LPAIVS
4. Human infections with HPAIVs
5. Recommended measures for responders to LPAI and HPAI outbreaks
6. Human infections by influenza A variant viruses
7. Conclusions
8. References
Section II: Influenza in animals of the class aves
Chapter 6: The innate and adaptive immune response to avian influenza virus
1. Overview of immunity
2. Innate immune responses to avian influenza virus
3. Immunological basis for vaccination of poultry
4. Immunology of antigen recognition and processing
5. References
Chapter 7: Wild bird infections and the ecology of avian influenza viruses
1. Introduction
2. Host range
3. Species susceptibility
4. Wild bird reservoirs
5. Spatial and temporal variation in AIV infection
6. Susceptibility to subsequent infections
7. Subtype diversity
8. Genetic diversity
9. Mechanisms for AIV maintenance and transmission
10. Viruses shared between poultry and wild birds: an H5N1 HPAI case study
11. Future directions
12. References
Chapter 8: The global nature of avian influenza
1. Introduction
2. General history
3. Regulatory aspects
4. Low-pathogenicity avian influenza in poultry and captive birds
5. High-pathogenicity avian influenza (1959–2015)
6. Conclusions
7. References
Chapter 9: Multi-continental panzootic of H5 highly pathogenic avian influenza (1996–2015)
1. Introduction
2. Genetic studies and nomenclature of GS/GD-lineage H5 HPAIVs
3. The history of the GS/GD-lineage H5 panzootic
4. Sources of infection and reasons for spread
5. Pathology of H5 HPAI
6. Diagnostic aspects
7. Disease control
8. Conclusions and the future
9. Acknowledgments
10. References
Chapter 10: High-pathogenicity avian influenza outbreaks since 2008, excluding multi-continental panzootic of H5 Goose/Guangdong-lineage viruses
1. Introduction
2. Ostrich HPAIV infections in South Africa during 2004–2011
3. H7N7 high-pathogenicity avian influenza in the UK in 2008
4. H7N7 high-pathogenicity avian influenza in Spain in 2009
5. Highly pathogenic avian influenza H7N3 outbreak in Mexico
6. Highly pathogenic avian influenza H7 in Australia during 2012–2013
7. H5N2 high-pathogenicity avian influenza in Chinese Taipei in 2012
8. H7N7 High-pathogenicity avian influenza in Italy in 2013
9. H7N7 high-pathogenicity avian influenza in the UK in 2015
10. H7N7 high-pathogenicity avian influenza in Germany in 2015
11. Addendum
12. References
Chapter 11: Low-pathogenicity avian influenza
1. Introduction
2. Low-pathogenicity avian influenza virus (LPAIV) in natural and agricultural host systems
3. H9N2 influenza A viruses: the paradigm of live poultry market-adapted LPAIVs
4. The contribution of H9N2 influenza A viruses to the diversity of avian influenza viruses that pose a public health risk
5. Molecular markers of the host range of H9N2 and H7N9 LPAIVs
6. The other side of the coin: perpetuation of LPAIV H5N2 in commercial poultry production systems: the experience in Mexico
7. Summary
8. References
Chapter 12: Epidemiology of avian influenza in agricultural and other man-made systems
1. History of humans and birds
2. General ecology and epidemiology of influenza A viruses
3. Concepts for understanding pathobiology
4. Infections within agricultural and other man-made systems
5. Conclusions
6. References
Chapter 13: Pathobiology of avian influenza in domestic ducks
1. Introduction
2. General concepts in avian influenza pathobiology
3. Influenza A in domestic ducks
4. Conclusions
5. References
Chapter 14: Avian influenza control strategies
1. Introduction
2. Goals of avian influenza control, and components of a control strategy
3. Economic costs
4. The role of international animal health organizations
5. Conclusions
6. References
Chapter 15: Vaccines and vaccination for avian influenza in poultry
1. Introduction
2. History of avian influenza vaccines
3. Features of the ideal avian influenza vaccine for birds
4. Immunological basis for protection
5. Laboratory criteria for assessing vaccine protection
6. Types of avian influenza vaccines
7. Field use of vaccine and special issues
8. Surveillance
9. Conclusions
10. References
Section III: Influenza in animals of the class mammalia
Section IIIA: Swine influenza
Chapter 16: The clinical features, pathobiology, and epidemiology of influenza infections in pigs
1. Introduction
2. History
3. Virology
4. Clinical disease
5. Pathology of IAV in pigs
6. Transmission and epidemiology of influenza A virus in pigs
7. References
Chapter 17: Immunity, diagnosis, and intervention strategies for influenza infections in pigs
1. Immunity
2. Diagnosis
3. Intervention strategies
4. References
Chapter 18: Global evolution of influenza A viruses in swine
1. Introduction
2. Geographic distribution of swine IAV genotypes
3. Antigenic evolution of IAV in swine
4. Swine in the ecology of IAV and interaction with other host species
5. Determinants of virulence and host range
6. Conclusions
7. References
Chapter 19: Vaccines and vaccination for swine influenza: differing situations in Europe and the USA
1. Introduction
2. A primer on SIV evolution and vaccine immunology
3. Commercial inactivated SIV vaccines
4. Novel SIV vaccines
5. Conclusions and perspectives
6. Acknowledgments
7. References
Section IIIB: Equine influenza
Chapter 20: The clinical features, pathobiology, and epidemiology of influenza infections in horses
1. History
2. Economic implications
3. Transmission to other mammalian hosts
4. Clinical features of infection and disease
5. Epidemiology
6. Diagnosis, treatment, and control
7. References
Chapter 21: Vaccines and vaccination to control equine influenza
1. Goals of vaccination
2. Criteria and models for measuring efficacy and protection
3. Tests and strategies for detecting EIV-specific immune responses to vaccines and infections
4. Correlates of protection and evaluation of vaccination success
5. Types of vaccines and methods of administration
6. Improving EIV vaccines and vaccine coverage
7. References
Section IIIC: Sporadic and miscellaneous mammalian influenza
Chapter 22: Canine influenza
1. H3N8 canine influenza virus
2. H3N2 canine influenza
3. Other influenza infections of dogs (and cats)
4. Summary
5. References
Chapter 23: Sporadic influenza A virus infections of miscellaneous mammal species
1. Introduction
2. H5N1 HPAIV infections in miscellaneous mammal species
3. Other influenza A virus infections in miscellaneous mammal species
4. References
Chapter 24: Mammalian experimental models and implications for understanding zoonotic potential
1. Introduction
2. Factors relating to choice of an appropriate model
3. Mammalian models of traditional intranasal and intratracheal inoculation
4. Variation of inoculation route and dose
5. The importance of established models for public health
6. Conclusion
7. References
Index
End User License Agreement

List of Illustrations

Chapter 1: Influenza A virus
1. Figure 1.1 Diagrammatic representation of the source and movement of influenza A viruses or their genes within avian and mammalian ecological and epidemiological situations (updated from [160]). H = hemagglutinin subtype, ( ) = subtype previously common but no longer circulating.
2. Figure 1.2 Phylogenetic tree of 17 hemagglutinin subtypes. The complete amino acid sequence of representative isolates for all 16 avian HA subtypes and the H17 bat subtype are included, with a representative North American and Eurasian isolate where available. The tree was midpoint rooted using the Influenza Research Database PhyML program, version 3.0 [144].
3. Figure 1.3 Phylogenetic tree of the matrix gene. The tree is based on the complete nucleotide sequence of representative isolates for major groups of type A influenza viruses. The tree is rooted to equine/Prague/1/56, which is the most divergent type A influenza virus. CK = chickens, DK = ducks, TK = turkeys. Standard two-letter abbreviations are used for states from isolates from the USA.
Chapter 2: Diagnostics and surveillance methods
1. Figure 2.1 Swab pooling for specimens from avian species. Up to 11 oropharyngeal/tracheal swabs or cloacal swabs may be pooled per vial if they are collected from the same species and the birds are housed together as part of the same flock or at the same location or market.
2. Figure 2.2 Outline of common approaches to influenza A virus (IAV) diagnostic testing. Active virus infection may be detected from swab material, oral fluids, or tissue by antigen capture immunoassay (ACIA), which needs to be confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or virus isolation (VI), or may be directly tested by RT-PCR or VI. Positive samples and isolates are further characterized by subtype-specific RT-PCR and/or genome sequencing and, in some cases, in-vivo pathogenesis studies. Exposure to IAV may be evaluated by antibody detection by agar gel immunodiffusion (AGID) or enzyme-linked immunosorbent assay (ELISA). The subtype specificity of positive samples may then be determined by hemagglutination inhibition (HI) assay or neuraminidase inhibition (NI) assay.
Chapter 3: The economics of animal influenza
1. Figure 3.1 Poultry system continuum in 2006 with country examples. Modified from World Bank, FAO, IFPRI, and OIE. 2006. Enhancing Control of Highly Pathogenic Avian Influenza in Developing Countries through Compensation: Issues and Good Practice. World Bank: Washington, DC, USA. Available at www.fao.org/docs/eims/upload//217132/gui_hpai_compensation.pdf
2. Figure 3.2 Poultry meat market chains in Thailand, 2003, and layer market chains in Egypt, 2006. Boxes in gray show integrated systems. Modified from Rushton, J. 2006. Compensation for HPAI in Egypt. Report produced for the FAO ECTAD Socio-Economics Working Group, November 2006. FAO: Rome, Italy.
3. Figure 3.3 World poultry market prices and simulated impacts from 50% demand decline and export ban in Asia. Source: OECD-FAO. 2013. OECD-FAO Agricultural Outlook 2013. OECD Publishing. Available at 101718/agr_outlook-2013-en. Holger Matthey, Market and Trade Division. Used with permission from the FAO.
4. Figure 3.4 National pork and poultry prices in 2013 in China [12].
Chapter 5: Public health implications of animal influenza viruses
1. Figure 5.1 Geographic distribution of human H5N1 HPAI cases reported to the World Health Organization between November 2003 and December 2014. Source: World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC).
2. Figure 5.2 Epidemic curve of human H5N1 HPAI cases, by onset date and country, from November 2003 to December 2014. Source: Centers for Disease Control and Prevention (CDC).
3. Figure 5.3 Chest radiographic findings in a fatal case of clade 2.1 H5N1 HPAI virus infection in a 37-year-old woman. Bilateral lower lobe consolidation with patchy infiltrates in the upper lung fields were evident at admission on day 7 of the illness. Despite mechanical ventilation, the patient progressed to acute respiratory distress syndrome (ARDS) on day 10, and died on day 11. Source: T. Uyeki, Centers for Disease Control and Prevention (CDC).
4. Figure 5.4 Chest radiographic findings in the case of a clade 2.1 H5N1 HPAI virus infection of a 21-year-old man who survived. Infiltrates are present in the left mid-lung field at admission on day 5 of the illness. One week later, consolidation and diffuse infiltrates are present throughout all of the lung fields. The patient made a full recovery without mechanical ventilation. Source: T. Uyeki, Centers for Disease Control and Prevention (CDC).
Chapter 7: Wild bird infections and the ecology of avian influenza viruses
1. Figure 7.1 Variables that affect the host, agent, and environmental components of the AIV maintenance cycle in wild bird populations.
Chapter 8: The global nature of avian influenza
1. Figure 8.1 Numbers of avian influenza surveillance tests conducted under the National Poultry Improvement Plan in the USA for the years 2005 and 2007–2014.
Chapter 9: Multi-continental panzootic of H5 highly pathogenic avian influenza (1996–2015)
1. Figure 9.1 Phylogenetic relationships of the HA gene of Gs/GD-lineage H5N1 HPAIVs over time. The WHO/OFFLU H5 Evolution Working Group has kept under continuous review the nomenclature for Gs/GD-lineage H5 HPAIVs as they have evolved since their first emergence and detection in 1996. Discrete monophyletic groups appear within a specific clade, and when those groups meet the nucleotide divergence criteria (as well as having bootstrap values greater than 60, and within-clade average pairwise distances of less than 1.5%) they are split into second-order clades (but still considered part of the first-order clade). As a second-order clade continues to evolve it may reach a similar level of genetic diversity, at which point it may be split into third-order clades, and so on. The same clade designation criteria apply to first-, second-, and any higher-order clade designations. Extinct clades that are believed to be no longer circulating are shown without color, clades that have only been reported in avian species are shown in blue, and clades that include viruses which have been detected both in humans and in avian species are shown in green. Courtesy of Todd Davis, CDC Atlanta.
2. Figure 9.2 Distribution of Gs/GD-lineage H5 HPAIV HA clades during the period 1996–2002. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category:Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
3. Figure 9.3 Distribution of Gs/GD-lineage H5 HPAIV HA clades during the period 2003–2004. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category:Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
4. Figure 9.4 Distribution of Gs/GD-lineage H5 HPAIV HA clades during the period 2005–2008. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category: Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
5. Figure 9.5 Distribution of Gs/GD-lineage H5 HPAIV HA clades during the period 2009–2012. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category:Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
6. Figure 9.6 Distribution of Gs/GD-lineage H5 HPAIV clades during the period 2013–September 2014. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category:Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
7. Figure 9.7 Distribution of Gs/GD-lineage H5 HPAIV clades during the period October 2014–April 2015. Source: Adapted from World Map centered at the Pacific Ocean, $200inaire, 4 July 2012. https://commons.wikimedia.org/wiki/Category:Blank_maps_of_the_world_without_Antarctica#/media/File:White_World_Map(Pacfic-centered)_Blank.png Used under CC BY-SA 3.0. http://creativecommons.org/licenses/by-sa/3.0/.
Chapter 10: High-pathogenicity avian influenza outbreaks since 2008, excluding multi-continental panzootic of H5 Goose/Guangdong-lineage viruses
1. Figure 10.1 Maximum likelihood trees of full gene sequences derived from South African HPAI H5N2 isolates (shown in red), other southern African wild duck and ostrich isolates (shown in orange), and Eurasian strains (shown in black). See Plate section for color representation of this figure.
2. Figure 10.2 Distribution of H5N2 LPAI-affected premises in Chinese Taipei during 2012. Courtesy of the World Organisation for Animal Health. See Plate section for color representation of this figure.
Chapter 11: Low-pathogenicity avian influenza
1. Figure 11.1 H9 HA phylogenetic tree showing major phylogenetic groups. Phylogenetic analyses were performed using online tools available at the Influenza Research Database (www.fludb.org). The unrooted tree was generated using the Archaeopteryx software tool as described elsewhere [337]. Labeling and colors were added using PowerPoint software (Microsoft, Inc.).
2. Figure 11.2 H9 HA phylogenetic tree showing major phylogenetic relationships of H9N2 viruses isolated from various animal species. Phylogenetic analyses and editing were performed as described for Figure 11.1. H9 HA position 226 in the receptor-binding site (site) with leucine is shown in red, with glutamine is shown in black, and with mixed virus populations carrying leucine and/or glutamine is shown in green. Note that a single virus isolate from a human case with methionine 226 is shown in blue. Light red box corresponds to G1-lineage viruses, and light brown box corresponds to Y280-lineage viruses.
3. Figure 11.3 H5 HA phylogenetic tree showing major phylogenetic relationships of H5N2 viruses of North American (light orange) and Eurasian (light blue) lineages. Phylogenetic analyses and editing were performed as described for Figure 11.1. The Mexican viruses (shown in light green) form an independent evolutionary path stemming from an ancestor in the North American lineage. Mexican H5N2-vaccine-derived viruses were isolated from independent outbreaks of LPAI in Japan and Taiwan. In Taiwan, Mexican-derived H5N2 surface gene segments have reassorted with Taiwanese LPAIVs, and their endemic nature remains uncertain.
Chapter 12: Epidemiology of avian influenza in agricultural and other man-made systems
1. Figure 12.1 Pathobiology concepts for understanding AI in poultry. Source: D. Swayne, U.S. Department of Agriculture/Agricultural Research Service.
2. Figure 12.2 Six means or modes by which AIVs are introduced into poultry. Source: K. Carter, University of Georgia, and D. Swayne, U.S. Department of Agriculture/Agricultural Research Service.
3. Figure 12.3 Four proven sources responsible for introduction of LPAIV into commercial turkeys within the USA from the 1960s to 2000. Source: K. Carter, University of Georgia, and D. Swayne, U.S. Department of Agriculture/Agricultural Research Service.
4. Figure 12.4 Epidemiology of LPAIVs and HPAIVs between free-living aquatic birds and poultry. Source: D. Swayne, U.S. Department of Agriculture/Agricultural Research Service.
5. Figure 12.5 Relative importance of different means of initial introduction of AIVs from free-living aquatic birds to poultry. Source: K. Carter, University of Georgia, and D. Swayne, U.S. Department of Agriculture/Agricultural Research Service.
Chapter 13: Pathobiology of avian influenza in domestic ducks
1. Figure 13.1 Two-week-old Pekin ducks showing severe neurological signs at 3 days after IN inoculation with A/egret/HK/757.2/02 H5N1 HPAIV. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
2. Figure 13.3 Bile-stained loose droppings from a 2-week-old Pekin ducks at 3 days after IN inoculation with A/egret/HK/757.2/02. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
3. Figure 13.4 Moderate necrotizing rhinitis, with submucosal congestion and edema, and glandular hyperplasia of the nasal epithelium of a 2-week-old duck that died 3 days after IN inoculation with A/crow/Thailand/04 H5N1 HPAIV. HE. Inset. Demonstration of viral antigen in the epithelial cells (shown in red). Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
4. Figure 13.15 Severe multifocal cellular swelling and necrosis of the pancreatic acinar epithelium with viral staining (shown in red) of a 2-week-old duck IN infected with A/chicken/Egypt/08124S-NLQP/2008.
5. Figure 13.5 AI viral antigen (shown in red) in the epithelium and pulp of feathers of a 2-week-old duck IN infected with A/duck/Vietnam/218/2005.
6. Figure 13.10 Extensive intranuclear and intracytoplasmic AI viral antigen (shown in red) in degenerated and necrotic myocytes of the heart of a 2-week-old duck IN inoculated with A/Thailand PB/6231/04 H5N1 HPAIV and found dead at 5 days after inoculation. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
7. Figure 13.13 Vacuolar degeneration and AI viral staining (shown in red) of the Harderian gland epithelia of a 2-week-old duck IN infected with A/chicken/Egypt/08124S-NLQP/2008.
8. Figure 13.7 AI viral staining (shown in red) of phagocytic cells and air capillary epithelium of the lung of a 2-week-old duck IN inoculated with A/chicken/Egypt/08124S-NLQP/2008.
9. Figure 13.6 Degeneration and necrosis of the tracheal epithelium with mucocellular exudate containing sloughed epithelial cells of the trachea of a 2-week-old duck IN inoculated with A/crow/Thailand/04 and found dead at 4 days after inoculation. HE. Inset. AI viral antigen staining (shown in red) present in the epithelial cells. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
10. Figure 13.9 Strongly positive AI viral staining (shown in red) present in neurons of the cerebrum of a 2-week-old duck IN inoculated with A/Vietnam/1203/04 H5N1 HPAIV and found dead at 4 days after inoculation. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
11. Figure 13.8 Viral staining (shown in red) in hepatocytes and Kupffer cells in the liver of a 2-week-old duck IN infected with A/chicken/Egypt/08124S-NLQP/2008.
12. Figure 13.11 AI viral staining (shown in red) of the myocytes of skeletal muscle of a 2-week-old duck IN inoculated with A/crow/Thailand/04 and euthanized at 4 days after inoculation. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
13. Figure 13.14 AI viral antigen (shown in red) in resident and infiltrating phagocytes in a bursa follicle of a 2-week-old duck IN infected with A/chicken/Egypt/08124S-NLQP/2008.
14. Figure 13.12 AI viral staining (shown in red) of the corticotrophic cells of the adrenal gland of a 2-week-old duck IN inoculated with A/Vietnam/218/05, 2 days after inoculation. Reprinted with permission from Avian Diseases. Copyright held by the American Association of Avian Pathologists, Athens, Georgia, USA. Source: USDA – M. Pantin-Jackwood [103].
Chapter 15: Vaccines and vaccination for avian influenza in poultry
1. Figure 15.1 Example of protection metrics related to egg-laying poultry using egg production (3-day average of percentage of eggs/hen/day), hen mortality (percentage); and virus-positive eggshell surface, yolk, and albumin samples (percentage positive for virus) for sham-vaccinated and once or twice H5-vaccinated chickens challenged with A/chicken/Pennsylvania/1370/83 (H5N2) HPAIV. Swayne et al., Vaccine 30(33):4964–4970, 2012 [11]. Used with permission of Elsevier.
2. Figure 15.2 Reduction in titer of HPAIV shed from the oropharynx and cloaca of vaccinated chickens 2 days post challenge. See Table 15.3 for details. Minimum limit of detection 10₁ ELD₅₀/ml. Source: David E. Swayne.
3. Figure 15.3 Summary of H5 vaccine doses used in poultry by the 15 countries that vaccinated poultry against HPAI from 2002 to 2010. Avian Diseases 56(4):818–828, 2012; [341]. Used with permission of the American Association of Avian Pathologists.
4. Figure 15.4 Concepts for application of AI vaccine in the field during an emergency vaccination program. Source: David E. Swayne.
5. Figure 15.5 Flow diagram for virological and serological surveillance of vaccinated flocks for detection of AIV infection (i.e. DIVA strategies). Source: David E. Swayne.
Chapter 16: The clinical features, pathobiology, and epidemiology of influenza infections in pigs
1. Figure 16.1 Pulmonary bronchioles during different stages of swine AIV infection. Courtesy of Juliane Deubner and University of Saskatchewan. Figure 16.1a. Normal bronchiole (A) that has a thin layer of epithelial cells (B) with apical cilia (C) and peribronchiolar lymphoid tissue (D). Figure 16.1b. Early influenza lesions of vacuolar degeneration (E) and necrosis (F) of the epithelial cells with loss of the apical cilia are seen as early as 24 hours post infection (PI). Figure 16.1c. Influenza lesions at 72 hours PI with necrotic epithelial cells sloughing, a small influx of inflammatory cells (G), attenuation of the remaining epithelial cells (H), and mild lymphoid hyperplasia (I). Figure 16.1d. Influenza lesions 5–7 days PI, showing varying degrees of epithelial hyperplasia (J), and mitotic Figure in some of the epithelial cells.
2. Figure 16.2 Experimental inoculation of a 4-week-old pig with A/swine/Texas/4199-2/1998 H3N2 virus 48 hours PI. Courtesy of Susan Detmer. Figure 16.2a. Severe, necropurulent bronchiolitis with mild interstitial pneumonia; hematoxylin and eosin (H&E), 200×. Figure 16.2b. Moderate bronchiolar epithelial cell and intraluminal immunoreactivity to anti-Influenza A nucleoprotein; immunohistochemistry (IHC) with diaminobenzidine (DAB), 200×. Figure 16.2c. Necropurulent bronchiolitis with severe alveolar pneumonia (lobular consolidation); H&E, 200×. Figure 16.2d. Strong bronchiolar and alveolar immunoreactivity to anti-Influenza A nucleoprotein; IHC with DAB, 200×.
3. Figure 16.3 Macroscopic lesions in the lung of a 4-week-old pig experimentally inoculated with A/swine/Illinois/02450/2008 H1N1 virus 5 days PI. The depressed, dark red, multifocal to coalescing lobular lesions are in the cranioventral portions of the lungs, and reflect the microscopic lesions (shown in inset) of atelectasis. Courtesy of Susan Detmer.
Chapter 18: Global evolution of influenza A viruses in swine
1. Figure 18.1 The number of hemagglutinin (HA) gene sequences available in the public database GenBank is not consistent with the geographic distribution of live pig populations. Although Asia currently has around 60% of the world's live pig population, only 10% of the HA gene sequences available from IAVs isolated from swine during 2012–2013 were from this region. In contrast, North America has approximately 10% of the world's pig population, but reported around 90% of the global IAV HA sequences from swine. Relatively few sequences were available from pigs in Central and South America, Europe, and Africa. The Oceania region has few pigs and very few sequences from IAVs from pigs.
2. Figure 18.2 The major H1 and H3 genetic lineages and their geographic distribution in swine. (a) The phylogenetic relationships of H1 sequences. (b) H3 sequences are depicted in respective trees and color coded by lineage. In Europe, the HA genes are derived from Eurasian avian-like H1N1 (shown in blue), a human-like H3N2 (shown in green), or a human-like H1N2 (shown in yellow). Classical H1 (shown in brown), human-like H1 (shown in yellow), and human-like H3-TRIG (shown in purple) co-circulate. In Asia, the predominant HA lineages reflect the dynamics observed in North America and Europe, with co-circulating viruses classified as a classical swine lineage, human-like H3, or Eurasian avian-like H1. The H1N1pdm09 arose from the classical swine-lineage H1 (shown in red), and underwent global dissemination through human-to-swine transmission. Used with permission from Vincent, A. L., K. M. Lager, and T. K. Anderson. 2014. A brief introduction to influenza A virus in swine. Methods in Molecular Biology 1161:243–258.
3. Figure 18.3 Putative generation of H3N2 variant in pigs. Pigs infected with two strains of IAV—H3N2-TRIG (shown in blue) and H1N1pdm09 (shown in pink)—allowed for reassortment of each parent virus's specific whole-genome constellation to generate novel progeny virions. One virus resulting from the potential reassortment patterns contained seven gene segments derived from the H3N2-TRIG and a single gene segment derived from H1N1pdm09 (the M gene shown in light green). An H3N2 with the genome constellation depicted here has been found in almost 350 human cases in the USA since 2010, termed H3N2 variant (H3N2v). Reassortants between endemic swine viruses and the H1N1pdm09 have been detected frequently in pig populations around the world since 2009.
Chapter 20: The clinical features, pathobiology, and epidemiology of influenza infections in horses
1. Figure 20.1 Phylogenetic tree of EIV H3N8 HA1 nucleotide sequences. This maximum-likelihood tree was generated using PhyML version 3. Bootstrap values obtained after 100 replicates are shown at major nodes. Amino acid substitutions are shown in parentheses or indicated at branch points. Phylogenetic groups (Pre-divergence, American lineage, Eurasian lineage, and Florida sub-lineage clades 1 and 2) are shown on the right. Sequences are color coded by date of isolation for the years 2010 (green), 2011 (red), and 2012 (blue), with the older isolates shown in black. The present OIE-recommended representative vaccine strains A/eq/Richmond/1/07 and A/eq/South Africa/4/03 are shown in bold. Reassortant strains that were identified containing HA from one Florida clade and NA from the other are highlighted in yellow. Reprinted from Woodward A. L. et al., Development of a surveillance scheme for equine influenza in the United Kingdom and characterisation of viruses isolated in Europe, Dubai and the USA from 2010–2012. Veterinary Microbiology 169:113–127, 2014, with permission from Elsevier. We thank Dr. Adam Rash for providing the figure.
2. Figure 20.2 Equine influenza virus-infected horse exhibiting typical mucopurulent nasal discharge. Experimental infection with A/equine/Ohio/2003 (H3N8) virus, 5 days post infection. The horse was not febrile at this point, but had a cough and was still shedding detectable virus. Some horses in this study developed secondary spikes of pyrexia, and mucopurulent nasal discharge persisted as late as 9 days post infection. Photo courtesy of Thomas Chambers.
3. Figure 20.3 Acute severe bronchointerstitial pneumonia with edema and hemorrhage in a horse with equine influenza A virus infection and secondary bacterial infection. Photo from Noah's Arkive, University of Georgia.
Chapter 22: Canine influenza
1. Figure 22.1 Phylogenies showing the origins of the widely circulating CIVs, namely the H3N8 virus that emerged in North America around 2000 as a variant of EIV, and the H3N2 virus that emerged in China and Korea around 2005 as a variant of an avian virus. (A) The H3N8 CIV HA and (C) the MP sequences, compared with the H3N8 EIV sequences from viruses collected from horses at various times after that virus emerged around 1963. Equine viruses are shown in black, and canine isolates in blue. (B) The H3N2 HA and (D) the MP sequences, compared with the sequences of different avian influenza viruses that are in the databases. The CIV sequences are shown in red, the Eurasian avian viruses are shown in green, and the American viruses are shown in blue. Modified from Figure 1 of Hayward, J. J., E. J. Dubovi, J. M. Scarlett, S. Janeczko, E. C. Holmes, and C. R. Parrish. 2010. Microevolution of canine influenza virus in shelters and its molecular epidemiology in the United States. Journal of Virology 84:12636–12645, and Figure 1 of Zhu, H., J. Hughes, and P. R. Murcia. 2015. Origins and evolutionary dynamics of H3N2 canine influenza virus. Journal of Virology 89:5406–5418.
2. Figure 22.2 The time course of H3N2 canine virus replication in dogs. Virus shedding and the serological response of beagles after experimental contact transmission of H3N2 CIV in dogs. EID, egg infectious dose; PI, percentage inhibition. Source: Figure 1 from Song, D., C. Lee, B. Kang, K. Jung, T. Oh, H. Kim, B. Park, and J. Oh. 2009. Experimental infection of dogs with avian-origin canine influenza A virus (H3N2). Emerging Infectious Diseases 15:56–58, with permission.
3. Figure 22.3 Infection and replication of the H3N8 CIV in dogs after natural or experimental infection. (A) Bronchus from greyhound spontaneously infected with canine influenza virus. There is focal epithelial erosion of the surface epithelium. The epithelial cell cytoplasm and luminal macrophage cytoplasm are positive for hemagglutin antigen (arrows). Immunohistochemistry staining is for H3 viral antigen. (B) Trachea from a dog 5 days after inoculation with canine influenza virus. Viral hemagglutinin antigen is present in the cytoplasm of ciliated and non-ciliated cells as well as basal cells. Immunohistochemistry for H3 viral antigen. Derived from Figure 3 and 7 of Castleman, W. L., J. R. Powe, P. C. Crawford, E. P. Gibbs, E. J. Dubovi, R. O. Donis, and D. Hanshaw. 2010. Canine H3N8 influenza virus infection in dogs and mice. Veterinary Pathology 47:507–517, with permission of Sage.
Chapter 23: Sporadic influenza A virus infections of miscellaneous mammal species
1. Figure 23.1 Natural infection of tigers with H5N1 highly pathogenic avian influenza virus in Sri Racha, Thailand, in 2004. Affected animals had high fever, respiratory distress, and (in some cases) nervous signs, and died with serosanguinous nasal discharge. Photograph courtesy of Dr. Roongroje Thanawongnuwech, Chulalongkorn University, Thailand.
2. Figure 23.2 Systemic histological lesions in domestic cats after experimental HPAIV H5N1 infection. The left-hand column shows necrotizing inflammatory foci present in multiple tissues stained with hematoxylin and eosin. The right-hand column shows influenza virus antigen (red-brown staining) present in serial sections of the same tissues, stained for nucleoprotein by immunohistochemistry. Reprinted from The American Journal of Pathology, January 2006, Vol. 168, No. 1, pp. 176–183, Rimmelzwaan G. F., van Riel D., Baars M., Bestebroer T. M., van Amerongen G., Fouchier R.A., Osterhaus, A. D., Kuiken, T. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts, with permission from Elsevier.
3. Figure 23.3 Low pathogenic avian influenza A virus (H7N7), human seasonal influenza A virus (H3N2), and human influenza B virus show different degrees of attachment to the trachea and bronchiole of a harbor seal (Phoca vitulina). Red staining indicates virus attachment to the epithelial cell surface. Reprinted from Ramis A. J., van Riel D., van de Bildt M. W. G., Osterhaus A., Kuiken T. Influenza A and B virus attachment to respiratory tract in marine mammals. Emerging Infectious Diseases [serial on the Internet]. 2012 May [date cited]. Available from 10.3201/eid1805.111828. With permission of EID.
4. Figure 23.4 Phylogenetic trees displaying the hemagglutinin (HA) and neuraminidase (NA) genes of bat-derived H17N10 and H18N11 influenza viruses (denoted by asterisks) compared with the relative distance of HAs and NAs of all previously known influenza A virus subtypes. Reprinted from Trends in Microbiology, April 2014, Vol. 22, No. 4, pp. 183–191, Wu Y., Wu Y., Tefsen B., Shi Y., Gao G. F. Bat-derived influenza-like viruses H17N10 and H18N11, with permission from Elsevier.
Chapter 24: Mammalian experimental models and implications for understanding zoonotic potential
1. Figure 24.1 Laboratory modeling of influenza virus infection in mammals. Examples of different research platforms that can contribute towards a greater understanding of influenza virus pathogenicity, transmissibility, and tropism. In spiritus = in breath.
2. Figure 24.2 Advantages and disadvantages of mouse, ferret, and guinea pig models for use in influenza virus research.
3. Figure 24.3 Binding of influenza virus to host epithelial cell. The influenza hemagglutinin (HA) binds to sialic acids present on the epithelia of host cells in the respiratory tract. Source: Dan Higgins/PHIL CDC.
4. Figure 24.4 Use of the ferret model to study H5N1 virus pathogenesis. Numerous virus and host features studied in the laboratory in ferrets following infection with avian influenza viruses such as H5N1 are shown. Many LPAI viruses exhibit similar features to the low virulent H5N1 viruses depicted in the top panel. Illustration by Alissa Eckert. From Belser, J. A. and T. M. Tumpey. 2013. H5N1 pathogenesis studies in mammalian models. Virus Research 178:168–185, with permission of Elsevier.

List of Tables

Chapter 1: Influenza A virus
1. Table 1.1 Hemagglutinin subtype distribution^a of influenza A viruses between different birds (class: Aves) and mammals (class: Mammalia)
2. Table 1.2 Examples of genetic mechanisms for LP to HP change based on deduced amino acid sequence of HA proteolytic cleavage sites in H5 and H7 AIV
Chapter 2: Diagnostics and surveillance methods
1. Table 2.1 Characteristics of selected IAV diagnostic assays
Chapter 3: The economics of animal influenza
1. Table 3.1 Influenza A virus subtypes that circulated in birds and were found sporadically in people [26, 54, 82]
2. Table 3.2 Phases of disease and socio-economic issues for notifiable animal influenza outbreaks
3. Table 3.3 Production and international trade of pig and poultry meat during the period 2002–2011
4. Table 3.4 Yellow broiler wholesale market prices (in yuan/kg) in different provinces in China
5. Table 3.5 Timeline for an H5N1 HPAI outbreak in Turkey
Chapter 4: Trade and food safety aspects for animal influenza viruses
1. Table 4.1 Global production and export of agricultural animals and their derived products for species that have endemic or high susceptibility to influenza A viruses (FAO statistics)
2. Table 4.2 Data for specific-pathogen-free chickens vaccinated subcutaneously at 1 day of age with either a recombinant fowl poxvirus containing an H5 AI gene insert (rFP-AI-H5) or inactivated H5N9 AI oil-emulsified vaccine (A/turkey/Wisconsin/68), and challenged intranasally 3 weeks later with H5N1 HPAIV (A/chicken/South Korea/ES/03). Meat samples were taken on day 2 after inoculation from euthanatized (vaccine) or dead (sham) chickens
3. Table 4.3 Time predicted for an 8.7-log₁₀ reduction of Korea/03 HPAIV titer in chicken meat at a given internal temperature, and number of log₁₀ reductions of Korea/03 HPAIV titer achieved in chicken meat cooked according to minimum current USDA FSIS time–temperature guidelines for a 7-log₁₀ reduction in Salmonella [91]
4. Table 4.4 Estimated pasteurization times for eggs contaminated with HPAIV, and estimated number of log₁₀ reductions in HPAI achieved by industry pasteurization standards
5. Table 4.5 Estimated pasteurization times for eggs artificially contaminated with H5/H7 LPAIV^a and estimated number of log₁₀ reductions in H5/H7 LPAIV achieved by industry pasteurization standards
Chapter 5: Public health implications of animal influenza viruses
1. Table 5.1 Subtypes of animal influenza A viruses causing zoonotic infections and subtypes causing influenza pandemics since 1900
2. Table 5.2 Infections with LPAIVs reported to cause human illness (from data up to December 2014^a)
3. Table 5.3 Infections with HPAIV subtypes reported to cause human illness (from data up to December 2014)
4. Table 5.4 Gene composition of influenza A H3N2v viruses, 2011–2014
Chapter 7: Wild bird infections and the ecology of avian influenza viruses
1. Table 7.1 Free-living species from which low-pathogenic avian influenza viruses have been isolated
2. Table 7.2 Predominant HAs and HA/NA combinations reported from ducks, gulls, and shorebirds. The three predominant HA subtypes detected in each study are highlighted
Chapter 8: The global nature of avian influenza
1. Table 8.1 Details of the 37^a documented pandemics, epidemics, or limited outbreaks of HPAI since the discovery of AIVs as the cause of fowl plague in 1955
Chapter 9: Multi-continental panzootic of H5 highly pathogenic avian influenza (1996–2015)
1. Table 9.1 Variability in HA0 cleavage site motifs of selected H5 HPAIVs
Chapter 10: High-pathogenicity avian influenza outbreaks since 2008, excluding multi-continental panzootic of H5 Goose/Guangdong-lineage viruses
1. Table 10.1 Summary of ostrich HPAI infections in South Africa during the period 2004–2011
2. Table 10.2 Summary of H7N7 HPAI infections in the UK in 2008
3. Table 10.3 Summary of laboratory results of serological, PCR, and sequencing analyses on samples from the infected premises
4. Table 10.4 Summary of H7N7 HPAI infections in Spain in 2009
5. Table 10.5 Summary of high-pathogenicity avian influenza H7N3 outbreak in Mexico
6. Table 10.6 Summary of H7 HPAI infections in Australia during the period 2012–2013
7. Table 10.7 Summary of H5N2 HPAI infections in Chinese Taipei in 2012
8. Table 10.8 Summary of H7N7 HPAI infections in Italy in 2013
Chapter 12: Epidemiology of avian influenza in agricultural and other man-made systems
1. Table 12.1 Pathobiological terms
Chapter 13: Pathobiology of avian influenza in domestic ducks
1. Table 13.1 Variability in intranasal infectivity of several LPAIVs and HPAIVs for domestic ducks as mean bird infectious dose (BID₅₀) and lethal infectious dose (LID₅₀)
2. Table 13.2 Mortality, mean death time (MDT), and viral replication titers from oropharyngeal and cloacal swabs of 2-week-old ducks inoculated intranasally with 10⁶ EID₅₀ of Gs/GD-lineage H5N1 HPAIVs. Data from previously published and unpublished experiments [78, 94, 103, 106, 107, 147, 153]
3. Table 13.3 Morbidity, mortality, mean death time (MDT), and viral shedding in ducks inoculated with Gs/GD-lineage H5N1 HPAIVs
Chapter 15: Vaccines and vaccination for avian influenza in poultry
1. Table 15.1 Properties of ideal avian influenza vaccines and vaccination methods for poultry (modified from Swayne and Spackman [339])
2. Table 15.2 AI vaccine protection as measured by prevention of clinical signs (morbidity) and death (mortality) of vaccinated chickens following challenge with different doses of HPAIV (mean embryo infectious [EID₅₀] and mean chicken lethal [CLD₅₀] doses)
3. Table 15.3 AI vaccine protection as measured by reduction in the number of vaccinated chickens shedding HPAIV from the oropharynx and cloaca
4. Table 15.4 AI vaccine protection as measured by interruption of contact transmission
5. Table 15.5 Compiled information on AI experimental and field vaccine studies in poultry and other birds
6. Table 15.6 Current vaccines technologies licensed and used in the field for H5 and H7 avian influenza vaccines (compiled from available information [81, 82, 118–120, 133, 157, 158, 179, 180, 186, 285, 296, 311, 346] (www.nibsc.org/documents/ifu/07-252.pdf, http://onehealth.org.vn/influenza-vaccine-manufacturing-in-viet-namreport-on-the-apaci-satellite-session.new, www.fao.org/3/a-ai326e.pdf, www.navetco.com.vn/vi/sanpham/navet-vifluvac)). Information on seed strains for other subtypes was unavailable
7. Table 15.7 Positive serological results against specific AI viral proteins following AIV infection or vaccination with different types of AI vaccines
Chapter 19: Vaccines and vaccination for swine influenza: differing situations in Europe and the USA
1. Table 19.1 Major SIV lineages in Europe and North America
2. Table 19.2 Major commercially available SIV vaccines in Europe in 2015
3. Table 19.3 Major commercially available SIV vaccines in North America in 2011
Chapter 21: Vaccines and vaccination to control equine influenza
1. Table 21.1 Licensed commercial EIV vaccines available throughout the world
Chapter 23: Sporadic influenza A virus infections of miscellaneous mammal species
1. Table 23.1 Virological evidence of natural influenza A virus infection in mammals of the suborder Caniformia (dog-like carnivores). Only reports where the virus was detected by virus isolation or RT-PCR are listed
2. Table 23.2 Virological evidence of natural influenza A virus infection in mammals of the suborder Feliformia (cat-like carnivores). Only reports where the virus was detected by virus isolation or RT-PCR are listed
3. Table 23.3 Virological evidence of natural influenza A virus infection in mammals of the orders Perissodactyla (Equidae), Artiodactyla (Bovidae, Camelidae, and Cervidae), and Cetacea (Balaenopteridae and Delphinidae). Only reports where the virus was detected by virus isolation or RT-PCR are listed
4. Table 23.4 Serological evidence of natural influenza A virus infection in marine mammals of the order Carnivora, clade Pinnipedia (Phocidae, Otariidae, and Odobenidae), and of the order Cetacea (Balaenopteridae and Delphinidae). Only reports where antibody to influenza A virus in serum was detected are listed
5. Table 23.5 Virological evidence of natural influenza A virus infection in mammals of the order Primates (Cercopithecidae and Hylobatidae) and Chiroptera (Vespertilionidae and Phyllostomidae). Only reports where the virus was detected by virus isolation or RT-PCR are listed
6. Table 23.6 Serological evidence of natural influenza A virus infection in mammals of the order Primates (Homidae, Hylobatidae, and Cercopithecidae). Only reports where antibody to influenza A virus in serum was detected are listed
Chapter 24: Mammalian experimental models and implications for understanding zoonotic potential
1. Table 24.1 Differential virulence of closely related influenza viruses in different species

Animal Influenza

Second Edition

Edited by

David E. Swayne DVM, MSc, PhD, Dipl ACVP, Dipl ACPV

Exotic and Emerging Avian Viral Diseases Research Unit

Southeast Poultry Research Laboratory

US National Poultry Research Center

Agricultural Research Service

United States Department of Agriculture

Athens, Georgia, USA

The following chapters remain with the US Government: 1, 2, 4, 5, 6, 8, 10, 12, 13, 14, 15, 18, 19, 24

Editorial offices: