Intercontinental Spread and Strategies to Control Highly ... · David E. Swayne Exotic & Emerging Avian Viral Diseases Research Unit Southeast Poultry Research Laboratory U.S. National

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

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

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

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-)

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

• 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

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

– 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

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

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

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)

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

• 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

H5N1 HPAI (22)Bangladesh

Bhutan

Cambodia

Canada

China

Egypt

Germany

Hong Kong

India

Indonesia

Italy

6 genetic clades1.1.2, 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

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 clades1.1.2 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

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

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

• 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

USFW

Lesser Snow

Goose (Chen

caerulescens)

Northern Shoveler

(Anas clypeata)

Ring-necked Duck

(Aythya collaris)

Cinnamon Teal

(Anas cyanoptera)

H5Nx North America

Infectivity assess: via BID50

ver09May2015

H5N2

Index

casesH5N1

H5N8

<2log10 mallards

3log10 D. ducks

4.3log10 chickens

5.0log10 turkeys

<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)

ver09May2015

269 viruses, 3 genes

(HA, M, PB2)

Pacific Flyway

Central & MS FlywaysH5Nx North America

• Initial spread by wild waterfowl

• Later, farm-to-farm human activity

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H5 HPAI H7 HPAI Me

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Asian-African-European- N. America H5Nx

• 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:

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

103715

85081

0.816 862643

0.006 35 2.8 0.068 2.2 108 425 6.3 1626

0

20000

40000

60000

80000

100000

120000

Doses of Vaccine (millions): 2002-2010 (Total >113b)

(90.99%)

(2.32%)(4.65%) (1.43%)

Swayne et al., OIE Sci Tech Rev 30(3):839-870, 2011

2.4. HPAI Vaccination Program

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

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

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

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

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

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

Conclusions

• 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

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

Merci Beaucoup!