Swayne, High Path AI
- 1. David E. Swayne Exotic & Emerging Avian Viral Diseases Research Unit Southeast Poultry Research Laboratory U.S. National Poultry Research Center ARS, USDA, Athens, Georgia, USA Intercontinental Spread and Strategies to Control Highly Pathogenic Avian Influenza Outbreaks
- 2. Avian Influenza • Orthomyxovirus with protein projections on the surface: – 16 hemagglutinin subtypes (i.e. H1-H16) – 9 neuraminidase subtypes (i.e. N1, N2, N3….N9) – Thus named: H5N1, H9N2, H5N2, etc. • Vary in disease production (chickens): – Low pathogenicity (LP): local - mild respiratory disease and egg drop – (H1-16) – High pathogenicity (HP): systemic - deadly disease (some H5 & H7) • Can infect a variety of poultry and wild birds species, depending on virus strain
- 3. 1. Global Control for HPAI Historical “Stamping-out” Program: •Enhanced biosecurity → prevent HPAI introduction onto naïve farms or from leaving affected farms; movement control essential •Diagnostics and surveillance → quickly find HPAI •Elimination of infected poultry (culling) → stamp- out HPAI action plan •Education → your individual responsibility and high compliance rate •Decreasing host susceptibility (vaccines/vaccination) → temporary solution (5 of 40 outbreaks) (Preventative or Management of Diseases) Eradication is historical strategy for HPAI
- 4. 1.1 AIV Ecology/Epidemiology: Dogma LPAIV (H1-16) LPAIV (H1-13) Exposure HPAIV (H5/H7) HA Mutation • Outdoor rearing • Outdoor access • Wild bird access to buildings •Environmental exposure Adaptation e.g.: H9N2 Middle East, Asia, N. Africa H5N2 Mexico & Central America e.g.: H7N8 USA 2016 H5N2 USA (1983-84) H7N3 Mexico (2012-)
- 5. 20. 2002: Chile, H7N3 21. 2003: Netherlands, H7N7 22. 2004: USA, H5N2 23. 2004: Canada, H7N3 24. 2004: S. Africa, H5N2 (ostriches) 25. 2006: S. Africa, H5N2 (ostriches) §26. 2005: N. Korea, H7N7 27. 2007: Canada, H7N3 28. 2008: England, H7N7 29. 2009: Spain, H7N7 30. 2011-3: S. Africa, H5N2 (Ostriches) 31. 2012: Chinese Taipei, H5N2 §32. 2012-present: Mexico, H7N3 33. 2012: Australia, H7N7 34. 2013: Italy, H7N7 35. 2013: Australia, H7N2 36. 2015: England, H7N7 37. 2015: Germany, H7N7 38. 2015: France, H5Nx 39. 2016: USA, H7N8 40. 2016: Italy, H7N7 §Vaccine used in the control strategy 1. 1959: Scotland, H5N1 2. 1961: S. Africa, H5N3 3. 1963: England, H7N3 4. 1966: Canada, H5N9 5. 1975: Australia, H7N7 6. 1979: Germany, H7N7 7. 1979: England, H7N7 8. 1983-84: USA, H5N2 9. 1983: Ireland, H5N8 10. 1985: Australia, H7N7 11. 1991: England, H5N1 12. 1992: Australia, H7N3 13. 1994: Australia, H7N3 §14. 1994-95: Mexico, H5N2 §15. 1995 & 2004: Pakistan, H7N3 16. 1997: Australia, H7N4 17. 1997: Italy, H5N2 §18. 1996-present: Eurasia/Afr./N. America, H5Nx (including N1, N2, N3, N5, N6, N8 reassortants) 19. 1999-2000: Italy, H7N1 1.2. 40 HPAI Disease Events
- 6. • H5 Gs/GD largest & longest running since 1920-30 • 1996-2014: 68 countries in poultry, wild birds or humans • >500m poultry died/culled by mid-2005, >$10B in losses • Focused in Old World, Northern Hemisphere
- 7. 1.3 Ecology/Epidemiology: Gs/GD HPAIV LPAIV (H1-16) LPAIV (H1-13) Exposure HPAIV (H5/H7) HA Mutation • Outdoor rearing • Outdoor access • Wild bird access to buildings •Environmental exposure Adaptation Domestic Ducks H5 Gs/GD Exposure Re-adaptation Wild Waterfowl A/goose/Guangdong/1/1996 lineage is unique in affecting domestic poultry (including waterfowl) and wild aquatic birds
- 8. – Free-ranging production creates challenges: • Minimal movement controls • Intermixing with wild waterfowl • Short window of availability for vaccination • Difficulty in giving 2 immunizations – Vaccination has become problematic – lack of consistent disease has reduced farmer support of vaccination 1.4 H5N1 Gs/GD HPAI • Triad: wild aquatic birds with smallholder and commercial integrated poultry • Asymptomatic HPAIV-infected domestic ducks have become a major player, and in some locations a reservoir of HPAIV LPM
- 9. H5 GS/GD HPAIV EPIDEMIOLOGY Naïve Commercial Poultry Infected Poultry (most HPAIV) Village Poultry Fomites (clothing, shoes & equipment - mechanical) Periurban birds Wild or Domestic Waterfowl
- 10. 1.5 Gs/GD HPAIV • Three episodes of transboundary H5Nx Gs/GD lineage HPAIV introduction by wild birds – 2005: Spread westward from Quinghai Lake China to Europe – 2010: Central Asia to Japan and Korea – 2014-15: China to Korea/Japan to Russia, Europe and North America • Denial of the major contribution of HPAIV spread in country from agricultural systems – Blame on wild birds for majority of HPAIV spread – Legal and illegal movement/trade of live poultry main risk factor in spread – Blame all legal trade on meat as high risk even with OIE code mitigations for risk reduction
- 11. 1.6. NDV - historical surrogate global poultry disease, but without severe public health concern 80 countries: NDV; active, suspect or unresolved July-Dec 2015 Jan-June 2015 (75 poultry or wild birds & poultry, 5 wild birds only)
- 12. Summary 1 • Traditional Stamping-out Programs have not eliminated/eradicated H5 Gs/GD HPAIV from the globe, and its “persistence” has changed all control paradigms – Some countries have eliminated/eradicated but a reservoir in other countries maintains the virus for resurgences, including reintroductions – Staging for global elimination/eradication: risk reduction and control strategies – Maintain food security – vaccination stop gap measure – Upgrading production systems or HPAIV will become as NDV has since 1920’s
- 13. • Since 1996 – H5N1 hemagglutinin gradual changes – e.g. DRIFT (like seen with human seasonal flu) 2.3.4.4 2012-… 2016 2.3.2.1 2.2.1 1.1 7.2 2.1.3 2.1 H5 Gs/GD-lineage HPAIV
- 14. H5N1 HPAI (22) Bangladesh Bhutan Cambodia Canada China Egypt Germany Hong Kong India Indonesia Italy 6 genetic clades 1.1.2, 2.1.3.2, 2.2.1, 2.3.2.1, 2.3.4.4, 7.2 Epicenter – S. Central & SE Asia, & NE Africa 2.1. Distribution of H5 Gs/GD Subclades Japan N. & S. Korea Laos Libya Nepal Netherlands Russia United Kingdom USA Vietnam
- 15. Subclade Poultry/Wild Birds Infections Human Cases 1.1.2 Cambodia, Viet Nam Cambodia (7) 2.1.3.2a Indonesia 2.2.1 Egypt, Libya Egypt (4) 2.3.2.1a Bangladesh, India Cambodia 2.3.2.1c China, Indonesia, Lao, Viet Nam Indonesia (1) 2.3.4.4 China (H5N1/N6/N8), Japan & Korea (Rep.) (H5N8); Lao (H5N6), Viet Nam (H5N6/N1), Canada Chinese Taipei, USA China (H5N6) (1) Unknown Korea (Dem. Peoples Republic) Indonesia (1) H5N1 HPAI hemagglutinin clades 1.1.2 2.1.3.2 2.2.1 2.3.2.1 2.3.4.4 7.2 Reassortment of Genes Other Avian Influenza Viruses from Wild Birds and Live Poultry Markets H5N1 (2.3.4.4) H5N2 (2.3.4.4) H5N3 (2.3.4.4) H5N5 (2.3.4) H5N6 (2.3.4.4) H5N8 (2.3.4.4) Drift Shift 2.1. One Predictable Issue About Avian Influenza Viruses – They Change Outcome: Gene reassortment (e.g. Shift) with H5N2, H5N3, H5N5, H5N6, H5N8 emerging in Asia and North America
- 16. Recent: •H5N8 HPAI outbreaks in poultry and wild birds – S. Korea & Japan, winter 2014 •Spring 2014 virus moved to Siberia and west Alaska •Fall 2014: H5N8 appeared Europe (IcA1), North America (IcA2) •Fall 2014: Reassortant H5N2 and H5N1 in North America 2.2 Intercontinental Spread 2.3.4.4 Gs/GD lineage HPAIV
- 17. Lee et al., J Virol 89:6521–6524, 2015 Winter 2014 Fall 2014 – Winter 2015 Western Russia, Europe, Japan North America, Japan Chinese Taipei Japan & Korea
- 18. • 311 detections (4 captive wild bird; 21 backyard; 211 commercial flocks, 75 wild birds) • 21 states affected (AR , CA, IA, ID, IN, KS, KY, MI, MN, MO, MT, NE, ND, NM, NV, OR, SD, UT, WA, WI, WY) • ~ 48.6 million commercial birds: Turkeys ~7.5 million (n=153), Chickens ~41.1 million (n=47) 12/8/2015 to 6/17/2015 – H5 HPAIV in wild bird, backyard poultry and commercial poultry Pacific Flyway Midwest: Central/ MS flyways
- 19. USFW Lesser Snow Goose (Chen caerulescens) Northern Shoveler (Anas clypeata) Ring-necked Duck (Aythya collaris) Cinnamon Teal (Anas cyanoptera)
- 21. H5Nx North America Infectivity assess: via BID50 ver09May2015 H5N2 Index cases H5N1 H5N8 <2log10 mallards 3log10 D. ducks 4.3log10 chickens <2log10 mallards 3log10 D. ducks 5.7log10 chickens 5.0log10 turkeys 3.3log10 EID50 chickens 5.1 log10 EID50 chickens 3 genes (HA, M, PB2)
- 22. ver09May2015 269 viruses, 3 genes (HA, M, PB2) Pacific Flyway Central & MS Flyways H5Nx North America • Initial spread by wild waterfowl • Later, farm-to-farm human activity
- 23. • 35 epizootics used stamping-out alone, but 5 epizootics added vaccination as a additional control component • Vaccination - immediate positive impact on HPAI prevention & management (disease & mortality) • But stamping-out alone was associated with shorter eradication times than stamping-out + vaccination programs (Pavade et al. OIE Sci Tech Rev 30:661-671, 2011) • HPAI vaccination can be associated with complacency Traditional stamping-out (35) Vaccination included (5) 2.3. HPAI Control Metrics Timeline HPAI:
- 24. 14 countries vaccinated poultry against HPAI (2002-2010) • Preventive (<0.2%): Mongolia, Kazakhstan, France, The Netherlands • Emergency (<0.8%): Cote d’Ivoire, Sudan, PDR Korea, Israel, Russia, Pakistan • National/routine (>99%): China (including HK), Egypt, Indonesia and Vietnam, plus added Bangladesh and Mexico Swayne et al., OIE Sci Tech Rev 30(3):839-870, 2011 2.4. HPAI Vaccination Program
- 25. What Can Vaccines Do? Increase resistance to AIV infection Reduce replication of AIV in respiratory & GI tract Prevent illness and death in poultry Reduced environmental contamination Reduced transmission to birds Maintained livelihood and food security of rural poor Result: Vaccines manage disease Negative: Makes diagnosis and surveillance difficult
- 26. What is needed to have effective LPAI or HPAI vaccination program? 1)High potency vaccine 2)Antigenically relevant vaccine seed strains 3)Proper vaccination program 4)Adequate number of vaccinations 5)Monitor vaccinated populations for protective titers 6)Survey vaccinated populations to find vaccine resistant AIV (‘DIVA’) Vaccines/Vaccination
- 27. OIE Performance of Veterinary Services (PVS) tool: Higher critical competencies associated with better HPAI control: •Staffing of veterinarians and paraveterinarians •Professional competencies & continuing education of vets •Emergency funding •Veterinary laboratory diagnosis •Epidemiological surveillance •Availability of veterinary medicines and biologicals •Transparency •Disease prevention, control and eradication measures Outcome: • Higher PVS scores were associated with shorter time to eradication, fewer outbreaks, lower mortality rate, and higher culling rate Risk Factors for Delayed Eradication
- 28. Summary 2 • What is limiting elimination/eradication – Low biosecurity/movement control of small holder/live poultry market system – Lack transparency & lapses in biosecurity of commercial integrated production system – Lack of effective compensation system – Inadequate national, Provincial/State and/or local veterinary services – Limited outside resource funding long term: e.g. donor fatigue – Need for effective restructuring of national poultry production systems (long-term) – Inadequate/inflexible vaccination programs
- 29. Global Improvements in Last 10 Years • Rapid Diagnosis – RRT-PCR accelerated speed and accuracy • Increased usage of indemnification • Rapid depopulation – CO2 (whole house and plastic tent methods) and foam • Safe Disposal – composting or burial • Re-invigorated veterinary infrastructure • Partnerships (trust): government/academia/industry • Improved surveillance methods (poultry & wild birds) • Emergency response plans and exercising • Regionalization of poultry trade
- 30. Challenges for Future • Consistent practice of biosecurity: Are we doomed to repeat the mistakes of the past? – Economics – Social structure – Low education of workers and farmers • Vaccines for emergency verses routine use – when & how • Resurgence of outdoor rearing in developed and developing countries: Partnership, trust and education in outdoor rearing systems for risk reduction and early detection • Movement controls and LPM system • Early warning system in wild bird detections
- 31. ConclusionsConclusions • Biosecurity is critical in control and eradication • Eradication requires strong veterinary services, movement controls, and high level of buy-in and observance by growers • Eradication HPAI is not achievable in immediate future in developing world – Large number of small producers – Lack of fair and fast compensation system – Live market systems disfavors movement control system and biosecure production • Prevention is critical in non-affected countries
- 32. Conclusion • Enhance biosecurity on farms after audits on each farm to prevent introduction • Movement controls/restrictions • Increased surveillance for earlier detection, quarantine and stamping-out • Quick depopulation of infected premises (24hr) • Safe disposal of carcasses and litter • Vaccine bank for high risk areas Prevention
- 33. Merci Beaucoup!
Editor's Notes
- #2: 45 minutes
- #3: LPAI Virus - resp and GI tracts HPAIV – everywhere (all tissues)
- #4: Comprehensive strategies with 5 basic components
- #6: To find similar endemic, widespread multi country infection – have to look back to 1920-1930s in EU, Asia, N and S America
- #7: Delete Canada and USA for better flow
- #9: LPAI Virus - resp and GI tracts HPAIV – everywhere (all tissues)
- #11: LPAI Virus - resp and GI tracts HPAIV – everywhere (all tissues)
- #12: Suspect or clinical disease
- #13: LPAI Virus - resp and GI tracts HPAIV – everywhere (all tissues)
- #14: Diversification has given rise to numerous clades, which have distinct antigenic properties and virulence. In particular, clade 2.3.2.1 that dominates in Vietnam has evolved these past years into subgroups A, B, and C, which not necessarily share cross-protection. In fact, new variants can escape immunity with vaccines based on classic strains, which rises the need for vaccine update. For example, in Vietnam commercial vaccines Re-1 and Re-5 no longer provide protection against the new antigenic variants.
- #16: Check internet for clades of H5N5, H5N6 and H5N2
- #18: The median-joining network was constructed from the HA-encoding gene. This network includes all of the most parsimonious trees linking the sequences. Each unique sequence is represented by a circle whose size reflects the frequency of the sequence in the data set. Branch length is proportional to the number of mutations. Isolates are colored according to the origin and season of the sample as follows: red inner circle, poultry farm isolates; purple inner circle, wild-bird isolates; black outer circle, early 2014 isolates; blue outer circle, late 2014 isolates.
- #19: Recheck outbreaks to see
- #21: Pacific flyway – dominated by WB cases, but some contact cases with Bkyd poultry, and 2 commercial cases Midwest – dominated by poultry outbreaks
- #22: HA, PB2 and M: Network Analysis Translation: Pathobiology and Network analysis Red star= chicken BC H5N2 Green star = index H5N8 gyrfalcon Yellow star = H5N2 NOPI Blue circle – expansion of poultry with S141P at antigenic site A with evidence of the change in wild birds – (21/28 with ≥1 AA change to gyr)
- #23: long branches suggest point source introductions
- #24: Staffing of veterinarians and paraveterinarians Professional competencies & continuing education of vets Emergency funding Veterinary laboratory diagnosis Epidemiological surveillance Availability of veterinary medicines and biologicals Transparency Disease prevention, control and eradication measures
- #27: Many of the first doses were acquired in 2006 when risk of H5N1 HPAI virus introduction from migratory wild birds was perceived as highest. Since then, some countries have opted out of vaccine banks perceiving the cost to high and maintenance is difficult when the risk has declined.
- #29: LPAI Virus - resp and GI tracts HPAIV – everywhere (all tissues)