AVIAN INFLUENZAAVIAN INFLUENZA (AI)(AI)

Influenza aviumInfluenza aviumFowl PlagueFowl Plague

Summer term 2010

Influenza AInfluenza A

Multiple speciesMultiple species– HumansHumans– Avian InfluenzaAvian Influenza

Most virulent groupMost virulent group Classification by surface antigensClassification by surface antigens

into subtypesinto subtypes– Hemagglutinin (H or HA)Hemagglutinin (H or HA)– Neuraminidase (N or NA)Neuraminidase (N or NA)

Surface Antigens Surface Antigens and Subtypesand Subtypes

1166 HA and 9 NA for influenza A HA and 9 NA for influenza A– All in aquatic birdsAll in aquatic birds

Hemagglutinin (HA)Hemagglutinin (HA)– Function: Sites for attachment to infect Function: Sites for attachment to infect

host cellshost cells Neuraminidase (NA)Neuraminidase (NA)

– Function: Remove neuraminic acid from Function: Remove neuraminic acid from mucin and release from cellmucin and release from cell

Schema of influenza virionSchema of influenza virion

Name of influenza isolatesName of influenza isolates

A/turkey/England/199/79 (H7N7)A/turkey/England/199/79 (H7N7)1.1. antigenic typeantigenic type

2.2. host of originhost of origin

3.3. geographical locationgeographical location

4.4. strain reference numberstrain reference number

5.5. year of isolationyear of isolation

6.6. for typ A the H and N subtype for typ A the H and N subtype

Avian influenza (AI)Avian influenza (AI)

Great variability of clinical singsGreat variability of clinical sings

• from symptomless infection from symptomless infection

• across mild diseases of upper respiratory tracts across mild diseases of upper respiratory tracts

• to to acute generalize disease with high mortality, acute generalize disease with high mortality,

describe describe previously as “fowl plague“ previously as “fowl plague“

Avian InfluenzaAvian Influenza

Pathogenicity based on genetic Pathogenicity based on genetic features and/or severity of disease features and/or severity of disease in poultryin poultry– Low pathogenic AI (LPAI)Low pathogenic AI (LPAI)

H1 to H1H1 to H166 subtypes subtypes

– Highly pathogenic AIHighly pathogenic AI (HPAI) (HPAI) Some H5 or H7 subtypesSome H5 or H7 subtypes LPAI H5 or H7 subtypes can mutate LPAI H5 or H7 subtypes can mutate

into HPAIinto HPAI

Lance Jennings, Canterbury Health Labs

Influenza A VirusesInfluenza A Viruses

Mutate frequentlyMutate frequently– Antigenic driftAntigenic drift

Point mutations accumulated during Point mutations accumulated during virus replicationvirus replication

– Antigenic shiftAntigenic shift Hybrid virus emerges when cell infected Hybrid virus emerges when cell infected

with two different influenza viruseswith two different influenza viruses– Human, avian, swine, equineHuman, avian, swine, equine

Transfer of influenza virus to aTransfer of influenza virus to adifferent speciesdifferent species

Avian influenza (AI)Avian influenza (AI)

Antigenic variationAntigenic ‘drift´ accumulation of amino acid substitutions changes in the HA molecules are clustered in

specific surface areas, the are antigenically significant regions of the HA

these point mutations are responsible for the annual influenza epidemics

Avian influenza (AI)Avian influenza (AI)

Antigenic ‘shift’

more radical change in the HA and/or NA proteins

is generally associated with the appearance of new

influenza pandemics

genetic reassortment between human and animal viruses

is one of the molecular mechanisms causing influenza

pandemics

HistoryHistory

1878: First identified case in Italy1878: First identified case in Italy 1924-25: First U.S. cases1924-25: First U.S. cases Low pathogenic avian influenza first Low pathogenic avian influenza first

identified mid-twentieth centuryidentified mid-twentieth century 1970’s: Migratory 1970’s: Migratory

waterfowl carrierswaterfowl carriers Outbreaks in mink, Outbreaks in mink,

seals and whales seals and whales

Economic ImpactEconomic Impact

1983: U.S. outbreak (H5N2) 1983: U.S. outbreak (H5N2) – $65 million in losses$65 million in losses– Destruction of 17 million birdsDestruction of 17 million birds– 30% increase in egg prices30% increase in egg prices

1999-2000: Italy outbreak (H7N1)1999-2000: Italy outbreak (H7N1)– $100 million in compensation to farmers$100 million in compensation to farmers– 18 million birds destroyed18 million birds destroyed– Indirect losses of $500 millionIndirect losses of $500 million

Economic ImpactEconomic Impact

1997: Hong Kong outbreak (H5N1)1997: Hong Kong outbreak (H5N1)– $13 million for depopulation $13 million for depopulation

and indemnitiesand indemnities– 1.4 million birds1.4 million birds

2001: Hong Kong 2001: Hong Kong outbreak (H5N1)outbreak (H5N1)– 1.2 million birds1.2 million birds– $3.8 million$3.8 million

Economic ImpactEconomic Impact

2003: European outbreak (H7N7)2003: European outbreak (H7N7)– Over 33 million birds destroyedOver 33 million birds destroyed– ¼ of Netherlands’ poultry stock¼ of Netherlands’ poultry stock– Cost?Cost?

2003-2004: SE Asia (H5N1)2003-2004: SE Asia (H5N1)– 8 countries8 countries– >100 million birds destroyed>100 million birds destroyed– Cost?Cost?

2004-2005: SE Asia and Eurasia2004-2005: SE Asia and Eurasia– Spread to Eurasia by migratory birdsSpread to Eurasia by migratory birds

Morbidity/MortalityMorbidity/Mortality

Approaches 100%Approaches 100%in commercialin commercialpoultry flockspoultry flocks

Deaths within 2 Deaths within 2 to 12 days after to 12 days after first signs of illnessfirst signs of illness

Survivors inSurvivors inpoor conditionpoor condition

Animal TransmissionAnimal Transmission

Initial source of infectionInitial source of infection– Other poultry, migratory Other poultry, migratory

waterfowl, pet birdswaterfowl, pet birds Spread by aerosol, shared Spread by aerosol, shared

drinking water, fomitesdrinking water, fomites Virus in respiratory secretions Virus in respiratory secretions

and fecesand feces Virus present in eggs but eggs Virus present in eggs but eggs

unlikely to survive and hatchunlikely to survive and hatch

Human TransmissionHuman Transmission Previously considered non-pathogenic for Previously considered non-pathogenic for

humanshumans 1997, Hong Kong1997, Hong Kong

– 18 humans infected, 6 died18 humans infected, 6 died– H5N1 virus linked to outbreak in live H5N1 virus linked to outbreak in live

bird market and area farmsbird market and area farms 2003, the Netherlands2003, the Netherlands

– 83 confirmed cases in humans, 1 death83 confirmed cases in humans, 1 death– H7N7 strainH7N7 strain

Clinical SignsClinical Signs

Incubation period: 3-14 days Incubation period: 3-14 days Birds found deadBirds found dead Drop in egg productionDrop in egg production Neurological signsNeurological signs Depression, anorexia, Depression, anorexia,

ruffled feathersruffled feathers Combs swollen, cyanoticCombs swollen, cyanotic Conjunctivitis and respiratory signsConjunctivitis and respiratory signs

Post Mortem LesionsPost Mortem Lesions

Lesions may be absent with Lesions may be absent with sudden deathsudden death

Severe congestion of Severe congestion of the musculaturethe musculature

DehydrationDehydration Subcutaneous Subcutaneous

edema of head edema of head and neck areaand neck area

Post Mortem LesionsPost Mortem Lesions

Nasal and oral cavity dischargeNasal and oral cavity discharge Petechiae on serosal surfacesPetechiae on serosal surfaces Kidneys severely congestedKidneys severely congested Severe congestion of Severe congestion of

the conjunctivaethe conjunctivae

SamplingSampling

Before collecting or sending any samples, Before collecting or sending any samples, the the proper authorities should be contactedproper authorities should be contacted

Samples should only be sent Samples should only be sent under secure under secure conditionsconditions and to and to authorized laboratoriesauthorized laboratories to prevent the spread of the diseaseto prevent the spread of the disease

HPAI samples may be zoonoticHPAI samples may be zoonotic

DiagnosisDiagnosis

Clinically indistinguishable from Clinically indistinguishable from virulent Newcastle Diseasevirulent Newcastle Disease

Suspect with:Suspect with:– Sudden deathSudden death– Drop in egg productionDrop in egg production– Facial edema, cyanotic combs Facial edema, cyanotic combs

and wattlesand wattles– Petechial hemorrhagesPetechial hemorrhages

Virology and serology necessary for Virology and serology necessary for definitive diagnosesdefinitive diagnoses

Differential DiagnosisDifferential Diagnosis

Virulent Newcastle diseaseVirulent Newcastle disease Avian pneumovirusAvian pneumovirus Infectious laryngotracheitisInfectious laryngotracheitis Infectious bronchitisInfectious bronchitis ChlamydiaChlamydia MycoplasmaMycoplasma Acute bacterial diseasesAcute bacterial diseases

– Fowl cholera, Fowl cholera, E. coliE. coli infection infection

DiagnosisDiagnosis

Laboratory TestsLaboratory Tests– HP AI is usually diagnosed by HP AI is usually diagnosed by

virus isolationvirus isolation Presence of virus confirmed byPresence of virus confirmed by

– AGIDAGID– ELISAELISA– RT-PCRRT-PCR

Serology may be helpfulSerology may be helpful

Treatment Treatment

No specific treatmentNo specific treatment Supportive care and antibiotics for Supportive care and antibiotics for

secondary infectionssecondary infections Antivirals (amantadine) effective in Antivirals (amantadine) effective in

reducing mortalityreducing mortality– Not approved in Not approved in

food animalsfood animals– Results in Results in

resistant virusesresistant viruses

Clinical Signs in HumansClinical Signs in Humans

1997: Hong Kong (H5N1)1997: Hong Kong (H5N1)– Fever, respiratory, vomiting, diarrhea, Fever, respiratory, vomiting, diarrhea,

pain pain – Fatal cases: severe bilateral pneumonia, Fatal cases: severe bilateral pneumonia,

liver dysfunction, renal failure, septic liver dysfunction, renal failure, septic shockshock

1979: MP AI in harbor seals (H7N7)1979: MP AI in harbor seals (H7N7)– Conjunctivitis in humans in contactConjunctivitis in humans in contact

Clinical Signs in HumansClinical Signs in Humans

2003: Netherlands (H7N7)2003: Netherlands (H7N7)– ConjunctivitisConjunctivitis– Mild influenza or respiratory symptoms Mild influenza or respiratory symptoms – Fatal case: acute respiratory distress Fatal case: acute respiratory distress

syndromesyndrome 2004-2005: S.E. Asia, EurAsia2004-2005: S.E. Asia, EurAsia

Recommended ActionsRecommended Actions

Confirmatory diagnosisConfirmatory diagnosis Depopulation Depopulation

may occurmay occur– Infected premisesInfected premises– Contact-exposed Contact-exposed

premisespremises– Contiguous premisesContiguous premises

Control and EradicationControl and Eradication

Eliminate insects and miceEliminate insects and mice Depopulate flock and Depopulate flock and

destroy carcassesdestroy carcasses Remove manure down Remove manure down

to bare concreteto bare concrete High pressure spray High pressure spray

to clean equipment to clean equipment and surfacesand surfaces

Spray with residual disinfectantSpray with residual disinfectant

PreventionPrevention

Import restrictionsImport restrictions SurveillanceSurveillance Appropriate biosecurityAppropriate biosecurity

– Control human trafficControl human traffic– Introduction of new birds into flockIntroduction of new birds into flock– Avoid open range rearing in waterfowl Avoid open range rearing in waterfowl

prevalent areasprevalent areas Education of the poultry industryEducation of the poultry industry Prompt response to MP AI outbreaksPrompt response to MP AI outbreaks

VaccinationVaccination

only killed vaccineonly killed vaccine DIVA strategy DIVA strategy

Avian Flu in Czech RepublicAvian Flu in Czech Republic

wild birds wild birds 12 swan in spring 200612 swan in spring 2006

NIH web conf

( 1957: Asian flu – 1968: Hong Kong flu)( 1957: Asian flu – 1968: Hong Kong flu)

1918 Army Photo of Victims of the Spanish Flu1918 Army Photo of Victims of the Spanish Flu

Avian Influenza

Výskyt jednotlivých subtypů chřipky A v lidské populaci(zdroj: CDC)

Genesis of strain A(H5N1) a A(H9N2) Genesis of strain A(H5N1) a A(H9N2) – Hong Kong 1997-1999– Hong Kong 1997-1999

New areas affected

A(H5N1) A(H5N1) evoluce of strainevoluce of strain•Increasing circulation over several years•Many variants – reassorted with other avian viruses•Epidemic, highly virulent current strains are genotype Z

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO

From year 2003 totally 404 cases and 254 deaths From year 2003 totally 404 cases and 254 deaths

1st. Indonesia 1st. Indonesia  - totally 141 cases and 115 deaths - totally 141 cases and 115 deaths

2nd2nd. . Viet Nam – totally 107 cases and 52 deaths Viet Nam – totally 107 cases and 52 deaths

3rd3rd. . Egypt – totally 53 cases and 23 deathsEgypt – totally 53 cases and 23 deaths

Israel: Avian influenza H5Israel: Avian influenza H5 27 January, 201027 January, 2010 An outbreak of avian influenza was discovered An outbreak of avian influenza was discovered

yesterday at a broiler breeder pullet farm in Kibbutz yesterday at a broiler breeder pullet farm in Kibbutz Ein Shemer (about halfway between Tel Aviv and Ein Shemer (about halfway between Tel Aviv and Haifa), Israel. The disease was found in a broiler Haifa), Israel. The disease was found in a broiler breeder house, 15 weeks of age, than contain breeder house, 15 weeks of age, than contain 43,000 birds. The Israeli Veterinary Services 43,000 birds. The Israeli Veterinary Services ordered all birds in the farm to be culled. and a ordered all birds in the farm to be culled. and a quarantine in all poultry enclosures within a 10-quarantine in all poultry enclosures within a 10-kilometer radius.  kilometer radius. 

According to According to Haaretz.comHaaretz.com mortality started 10 days mortality started 10 days before diagnosis has been made.  before diagnosis has been made. 

Israel: Ein Shemer Leden 2010. Broiler breeders 15 weeks old.