禽流感：預防和控制策略.pdf

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1、Avian Influenza:Strategies for Prevention&ControlCSingaporeOutlines Introduction Virus Biology&AIV Current Status Epidemiology&Transmission Disease,Pathology&Diagnosis Control&Prevention Strategies Human Infections EpilogueGlobal AI Situation:January 2022 March 2023Virus Biology&AIV StatusPotentiall

2、y there is possible Combination from H and N=144H and N are important in virus entry&exit from the host cell&interaction between virus&host cellsAvian Influenza VirusesImportant Avian Influenza VirusesAIV Pathotypes&Virus PathogenicityLPAI(H9)HPAI(H5/H7)HPAI Asia Situationwww.Pirbright.ac.ukCurrentl

3、y H5N1 Clade 2.3.4.4b Viruses dominate Globally(77 countries)Domestic bird outbreaks:not reported from endemic countriesMunir Iqbal (2024)Global AI(H9N2)StatusThree stable HA lineages:G1-WGroup AGroup BGroup CGroup D Beijing(BJ94/Y280)Korean-like(Y439)Few studies on AntigenicityPeacock et al.,Viruse

4、s(2019)AI subtype H9N2 is endemic in many bird species in Asia&the Middle East.Virus has occasionally crossing species barrier to mammals including human beings.H9 subtype viruses are NOT Notifiable to OIE:possible under-reporting on actual field situations.Epidemiology&TransmissionAIV can infect a

5、variety of Domestic&Wild Avian Species(including chickens,turkeys,ducks,domestic geese,quail,pheasants,psittassines,gulls,shorebirds,emu&others).The clinical manifestation of infection ranges from asymptomatic infection to rapidly fatal diseaseAquatic birds,particularly Ducks,Shore Birds&considered

6、the Natural Reservoirs These waterfowl generally do not develop disease when infected with AI viruses.Recently,investigators in Asia have shown that asymptomatically infected domestic ducks are shedding more H5N1 to domestic poultry(references:FAO/OIE/WHO 2004)Avian Influenza Virus:The HostsInfluenz

7、a A viruses have been isolated from Free-living birds of the following Families Very Diverse Order Very Diverse Gene Pool High prevalence of infection on an annual basisRecent Evidences support the Theory that H5N1 being Spread by Migrating Wild FowlsMcClure(1998)Migration&Survival of the Birds of A

8、siaShorebird Flyways Routes of bird-to-bird transmission include:Airborne transmission if birds are in close proximityDirect contact with contaminated respiratory secretions or fecal material Vertical transmission is not known to occur (possible cross contamination in hatchery)Other factors(spread w

9、ithin&between flocks):Broken contaminated eggs in incubators infecting healthy chicksMovement of infected birds between flock.Movement of formites e.g.contaminated equipment,egg flats,feed trucks,clothing&shoes of employeeContact with infected wild birds&waterfowlFecal contamination of drinking wate

10、rGarbage fliesAIV Virus Transmission Alexander(1982)reported a 53%isolation rate from pools of cloacal swabs taken from ducks at slaughter Shortridge(1982)reported a 6%isolation rate from individual ducks in Hong Kong WHO(2005)reported 76%ducks&21%chicken tested positive for H5N1 in Mekong Delta,Sou

11、th VietnamAIV in Commercial DucksEarly Spread of HPAI(H5N1)in AsiaClade 1(2003 2004)Clade 2-Subclade 1(2004 2006)Clade 2-Subclade 2(2005 2006)Clade 2-Subclade 3(2005 2006)During winter of 2020-2021,a new genotype of highly-pathogenic H5N1 avian influenza A virus emerged in Europe,comprising a(reasso

12、rtant between the epizootic HP clade 2.3.4.4b H5N8&local LP wildfowl strains).This new genotype caused record levels of infections in farmed poultry throughout Europe and quickly traveled,via waterfowl flyways,into North America,Africa and East Asia In following seasons,this panzootic genotype under

13、went further reassortment with local LP avian strains from waterfowl or seabirds-in Europe,North America&beyond;generating a diverse range of genotypes.One of these North American reassortant genotypes then entered South America and most recently,AntarcticaEpidemiology of 2024 H5N1 Avian Infleunza O

14、utbreaksRecent Spread of H5NX(Gs/GD Euroasianlineage)HPAI Virus (2.3.4.4b Clade)1.Fall 2020:virus moved from Central Asia to Europe,Eastern Asia,Middle East&Africa Bi-directional 2021 spring migrations1.Fall 2020:virus moved from Central Asia to Europe,Eastern Asia,Middle East&Africa Bi-directional

15、2021 spring migrations2.Fall 2021:Virus moved to N.AmericaWinter 2022 move down East CoastSpring 2022 NorthwardLate Summer 2022 Southward2.Fall 2021:Virus moved to N.AmericaWinter 2022 move down East CoastSpring 2022 NorthwardLate Summer 2022 Southward3.Fall 2022:Virus moved to Central America,Carri

16、bean&Northern S.America3.Fall 2022:Virus moved to Central America,Carribean&Northern S.America4.Winter 2023:Virus moved down Pacific CoastSpring 2023 detected in Southeastern&Eastern S.America4.Winter 2023:Virus moved down Pacific CoastSpring 2023 detected in Southeastern&Eastern S.AmericaGlobal(Jul

17、y 2020 to April 2023):7515 cases,14 million poultry deaths&254 million poultry culledGlobal(July 2020 to April 2023):7515 cases,14 million poultry deaths&254 million poultry culledWOAH(2024)1234Schematic depicting the phylogenetic relationships between the HA segment of the viral genomes in differen

18、t host species&when H5N1 likely spilled over into cattleSpillover of HPAI H5N1 virus to Dairy CattleCow Flu:H5N1 Clade 2.3.4.4b(2024)Worobey et al.,2024Virus Expansion to Marine AnimalsUhart et al.,Nature Communications(2024)Pathology&DiagnosisClinical Signs:Sudden,high mortality(up to 100%)Other Si

19、gns:cessation of egg-laying,respiratory,excessive lacrimation,oedema of head,subcutaneous haemorrhage.Diarrhoea,neurological signs.Mortality pattern of HPAI(H5N1)in broiler breeders(07/2003)Highly Pathogenic Avian Influenza(HPAI)HPAI:Clinical Signs&Pathology S Si ig gn ns sHPAI:Clinical&pathological

20、 signsHPAI:Clinical Signs&Pathology:C Cl li in ni ic ca al l&P Pa at th ho ol lo og gi ic ca al l S Si ig gn ns sLPAI H9N2 in PoultryVirus is spread&disseminated via air sacs&serosal route to oviduct.Course of infection:loss of appetite,reduced feed intake&egg production drop (transient yolk follicl

21、e atresia,acute necrotic inflammation of oviduct:permanent low egg production with quality issues).H9N2 is Self-limiting disease,affected birds recover after 2 weeks.Mortality observed more in older birds(55 wks)or birds with complicated secondary pathogens.AIV Diagnostics:Serology&Molecular Methods

22、HIDisease Control&Prevention StrategyAvian Influenza Control Measures Avian Influenza Control Measures Surveillance&ReportingBiosecurityControl Strategies SOPVaccination OptionControl Measures of Avian Influenzaof AIV in PoultrySurveillance&ReportingBiosecurityControl MeasuresVaccination OptionContr

23、ol of Avian InfluenzaS Su ur rv ve ei il ll la an nc ce e&R Re ep po or rt ti in ng gEarly Detection is the Key to Control AIV SpreadEarly Detection is the Key to Control AIV Spread1.Routine Submission of Eggs or Blood to Lab for testingBroilers/turkeys 10 blood samples per flock at slaughterLayers/

24、breeders 30 eggs per month2.Routine Submission to Lab for diagnosis of any Disease Problems3.Training of local poultry industry of Danger of Avian InfluenzaPrevent introduction through good biosecurityRecognition of the diseaseTesting for avian influenzaControl of Avian InfluenzaBiosecurity:Cleaning

25、&DisinfectionXBiosecurity-Biosecurity BiosecurityWe know where the virus comes from Wild water fowl Live bird markets/Sunday markets Backyard flocks/Mixed farming Pet birds Other infected commercial poultry flocksBControl of Avian Influenza&Sanitation ProtocolBiosecurity:AI Virus Inactivation1.AIV a

26、re not very hardy,killed or inactivated by heat,drying,UV light&common chemical disinfectants e.g.sodium hypochlorite,phenolic compounds,quarternary ammonium compounds,iodine compounds,formalin&other aldehydes.2.AIV inactivated within 6 days with field manure at an ambient temp(approx.15oC)condition

27、(Lu et al.,2003).3.AIV(H7N2)loss infectivity in 24 hrs under 30 37oC&less than a week under 15 20oC temperatures(Lu at al.,2003).Effect of One hour Exposure of Different Disinfectants on the ability to inactivate AIV All 5 disinfectants are effective at inactivating AIV recommended concentrations.On

28、ly the Chlorine&Peroxygen compounds damaged the RNA(could not be detected by RT-PCR).ANT=not tested.B(-)=negativefor RT-PCR.C(-)=negative by virus (Suarez et al.,2003)Sodium hypochlorite*PhenolicLysolQuaternary ammoniaPeroxygen compound*Peroxygen Compound(10 day old)Environmental Challenges:Biofilms

29、New Idea in Air Sanitation:In-housing Fogging&DisinfectionContaminated air is one way that diseases and viruses like HPAI can be transmitted into a facilityAvian Influenza Virus Shedding Avian influenza viruses are shed in the saliva,mucous,feces,&respiratory secretions of infected birdsThe virus ca

30、n also be found in the body fluids of other infected animals,such as cow milkLPAI viruses can be shed in asymptomatically infected or minimally affected flocksAn Indication of AIV shedding length in days in multiple poultry speciesMean shedding(log10EID50/mL)in respiratory&cloacal swabsHPAIVLPAIVGer

31、meraad et al.,(2019)Reduce Virus Shedding&Contamination by Aerosol FoggingHouse&Environment DecontaminationWashing with surfactant,disinfectant spraying,thermal foggingConsider Foaming disinfection in severe outbreak caseContinuous use of water sanitizerApplication of FoggersMicroaerolized H2O2on Ba

32、cterial&Viral Poultry PathogensUse of AI VaccinesCountries officially vaccinating against LPAI&HPAIAvian Influenza Poultry VaccinesInactivated“Whole virus”vaccines Inactivated“Reverse Genetic”vaccinesRecombinant vaccinesBaculovirus as the vectorPoxvirus as the vectorNewcastle Disease virus as the ve

33、ctorHerpesvirus of Turkey(HVT)as vectorExample:Inactivated“Whole Virus”Vaccine Response(H9 HI titers)Example:Inactivated Recombinant Vaccine against AIV H5(B.E.S.T.Technology)Stephane Lemiere(2024)Example:HVT-vectored H5 VaccineHVT-H5 vaccine was constructed by inserting a recombinant HA-H5 gene int

34、o the genome of HVT FC126.The recombinant HA-H5 was derived from a compilation of HPAI H5N1,clade 2.2,2005 strains(GenBank:MW310457).Insertion of HA-H5 geneRecent Focus on Avian Immune System under Virus Challenge Situation Feed Sanitation&Water Hygiene Nutrient Uplift&Consider Micro-nutrient Suppor

35、tApply Immune Modulating Agents Role of Cell-mediated Immunity in Support of Inactivated VaccinationThiery van den Berg(2014)Guillermo Zavala(2020)Use of Antioxidants,Probitoics,Immuno-modulators,Organic Minerals&Vitamins Example:Organic Zinc&Selenium reduce symptoms of vaccination stress by support

36、ing the Immune systemVirucidal Effect of Medium Chain Fatty Acids HA&N plays a vital role in the attachment and release of AIV during infection:HA in virus envelope plays a critical role in viral binding,fusion&entry processes.1-Monocaprin*docks with H5N1 HA(5 amino acids)of Avian influenza virus,ex

37、hibiting inhibitory effects against H5N1 HA(Maheswaran&Revathi,2017).HA ProteinAntiviral Effect of Medium Chain Fatty Acid(MCFA)Application through Feed/drinking water Michelles from MCFA(Caprylic acid,Monocaprylin)interact with virus membranes,causing buds or tubules formation which will rupture,le

38、aving holes in the membrane,killing microbial pathogens&inactivating virus particles.Supplementation of MCFA Caprylic acid through feed or water could kill the virus in live birds.MCFA&MCMG are potent antimicrobials&antiviral with anti-inflammatory&growth promoting effects on recovery Pullets/Layers

39、.Guidelines&Application of Control Policies for Avian InfluenzaAfter Capua&Marangon(2003)Human InfectionSouth China Morning Post 20thJune 2005 Zoonotic DiseaseZoonotic DiseaseBird Flu Virus Infection in HumansBird Flu Virus Infection in Humans Zoonotic Potential of H9 SubtypesLi et al.2003US Bird Fl

40、u Virus Infection in Humans H5N1 detections in Wild BirdsSince February 2022 Outbreak 108.41 million birds have been affected Total 1,218 flocks in 48 States 533 flocks Commercial&685 flock BackyardNovember 15,2024Since February 2022 Outbreak 108.41 million birds have been affected Total 1,218 flock

41、s in 48 States 533 flocks Commercial&685 flock BackyardNovember 15,2024 Case detected 10,563 Counties affected 1,185November 12,2024 Case detected 10,563 Counties affected 1,185November 12,2024 Total Outbreak in Cattle 549confirmed in 15 StatesJuly 03,2024 Total Outbreak in Cattle 549confirmed in 15

42、 StatesJuly 03,2024NOVEMBER 18,2024https:/www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https:/www.cdc.gov/flu/avianflu/avian-flu-summary.htmConfirmed Total Reported Human Cases Human Exposure to H5 Avian Influenza near Migratory Shorebird Habitats Bird Flu H5N1 Treatment in Human1.There is

43、No Effective Treatment for HPAI in Poultry2.Drug Treatment possible in Human Cases Amantadine,Rimantadine used,resistance development quickly(Webster 1985)Newer analoques of Sialic acid(GG167,4-guanidineNeu5AC2en)effective in animal models(Hayden et al.,1992)Current available antiviral drugs:Oseltam

44、ivir,Zanamivir.EpilogueMultiage Flocks?All-in All-out Multi-site UnitsAvian Host&Avian Reservoir Dangerous ReservoirsBiosecurity-Biosecurity BiosecurityTake Home MessageNatural reservoirs of AIV infection are abundant&will not go awayDisease surveillance&Early Detection is the key to Control AIV Spr

45、eadEnhanced Biosecurity&Change of Farming Practice are the best long term Strategy to Prevent AIV infectionVaccination Strategy(in addition to Mass Culling method)will be more effective to stop the rapid spread Industry&Public Sector Corporation is vital for Successful Control&EradicationA need of Transparency&Openness in Disease Information Exchange&Reporting Need for a Global Approach in AI Control Strategy