Avian Influenza - surveillance, monitoring and vaccination Ian Brown Director of EU/OIE/FAO International Reference Laboratory for Avian Influenza, Newcastle Disease and Swine Influenza Animal and Plant Health Agency-Weybridge AVI AFRICA 2018, SAPA Conference & Exhibition 12 - 14 June 2018 Gauteng
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Avian Influenza - surveillance, monitoring and vaccination · Avian Influenza - surveillance, monitoring and vaccination Ian Brown Director of EU/OIE/FAO International Reference Laboratory
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Avian Influenza - surveillance, monitoring and vaccination
Ian BrownDirector of EU/OIE/FAO International Reference Laboratory for Avian Influenza, Newcastle Disease and Swine InfluenzaAnimal and Plant Health Agency-Weybridge
AVI AFRICA 2018, SAPA Conference & Exhibition12 - 14 June 2018 Gauteng
• Why are we looking for AI?
• Poultry surveillance options
• Characteristics of harmonised statistically relevant surveillance
• AI vaccination options and challenges
• Surveillance in vaccinated populations
Overview
• HPAIo HPAI causes very high mortality rates in most domestic poultry (reduced clinical signs
seen in waterfowl)
o Severe impacts on profitability of poultry farming
o Facilitate trade in poultry and poultry products
o Serious risk to public health
o Can be found in wild birds
Why are we looking for AIV?
• LPAIo Shows reduced clinical signs
o Subtypes H5 and H7 can mutate to HPAI in gallinaceous
poultry
Presenter
Presentation Notes
(Dutch outbreak in 2003 lead to the loss of 30% of their poultry sector) Some strains of HPAI transmit to humans leading to serious illness or death (H5N1 and more recently H7N9) – 449 reported deaths for H5
OIE DEFINITION OF SURVEILLANCE
• Guidance provided in Terrestrial Animal Health Code• http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_surveillan
ce_general.htm• provide guidance to the type of outputs that a surveillance system should
generate• provide recommendations to assess the quality of surveillance systems.
• Purpose• Structured population-based surveys• Structured non-random surveillance• Surveillance to demonstrate freedom from disease or infection• Surveillance for distribution and occurrence of infection
Section on AIhttp://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_avian_influenza_viruses.htm
o Presence, or suspected presence, of AI immediately notified to the competent authority
o Premise under restrictionso Laboratory testing carried outo Epidemiological enquiry initiated if positiveo Control measures applied if positive
• Private testing approved in some countries• Requirement for rapid reporting to competent authority and submission
to NRL if positive for confirmatory testing/investigation• Approved labs for testing using recommended test methods
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design• Scanning surveillance (passive or early warning)
Suspicion of disease reported
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority (WHO IS COMPETENT AUTHORITY IN PL?) - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design• Scanning surveillance (passive or early warning)
Suspicion of disease reported
Official vet visits premises to asses disease situation
Negated on clinical description
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority (WHO IS COMPETENT AUTHORITY IN PL?) - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design• Scanning surveillance (passive or early warning )
Suspicion of disease reported
Official vet visits premises to assess disease situation
Samples collected and sent to NRL
Negated on clinical description
Negated on clinical signs
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority (WHO IS COMPETENT AUTHORITY IN PL?) - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design• Scanning surveillance (passive or early warning )
Suspicion of disease reported
Official vet visits premises to asses disease situation
Samples collected and sent to NRL
Negated on clinical description
Negated on clinical signs
Negated on laboratory testing
Restrictions lifted
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority (WHO IS COMPETENT AUTHORITY IN PL?) - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design• Scanning surveillance (passive or early warning )
Suspicion of disease reported
Official vet visits premises to asses disease situation
Samples collected and sent to NRL
Laboratory testing confirms notifiable AI
Restriction and surveillance zonesEpidemiological enquiries
Stamping out
Negated on clinical description
Negated on clinical signs
Negated on laboratory testing
Restrictions lifted
Presenter
Presentation Notes
Presence, or suspected presence, of AI immediately notified to the competent authority (WHO IS COMPETENT AUTHORITY IN PL?) - clinical signs suggestive of AI or sudden mortality detected For early warning systems, production factors may also be monitored - 30% drop in feed/water intake, 5% egg drop,
Poultry surveillance design - ACTIVE
• Active surveillance (serological survey)Objectives Annual detection through active surveillance for:
“LPAI of subtypes H5 and H7 in gallinaceous birds (chickens, turkeys,
guinea fowl, pheasants, partridges and quails) and ratites thereby
complementing other existing early detection systems.”
“LPAI of subtypes H5 and H7 and highly pathogenic avian influenza
(HPAI) in domestic waterfowl (ducks, geese and mallards for re-stocking
supplies of game).”
Poultry surveillance design - ACTIVE
Target populations
Gallinaceous• Laying hens• Free range laying hens• Chicken breeders• Turkey breeders• Fattening turkeys• Farmed game birds (gallinaceous)• Ratites
May also include large FR broiler holdings and backyard flocks, where significant.
RISK-BASED• Preferred method - targeted and resource efficient 1. Exposure to wild bird ‘target species’
o Proximity to waterbodies (ponds, swamps, lakes, rivers, sea)o Areas where high densities of migratory birds (TS) gathero Proximity to resting and breeding places for migratory wild water birds
(esp. where migration linked to HP H5N1 areas)o Free range poultry holdingso Low biosecurity on holdings (feed storage/surface water)
Presenter
Presentation Notes
Thinking about how AI can get into a poultry holding, and targeting surveillance at more ‘risky’ holdings.
Poultry surveillance design - ACTIVE
RISK-BASED2. Spread between poultry holdings
o Mixed species on a holding (including waterfowl)o Holdings with species that have increased detection rate (ducks and re-
stocking game (mallards))o Location of holdings in high density poultry areaso High levels of trade/imports/movements of vehicles/people on/off siteo Long lived poultry categories
Presenter
Presentation Notes
Thinking about how AI can get into a poultry holding, and targeting surveillance at more ‘risky’ holdings.
Poultry surveillance design – ACTIVE
REPRESENTATIVE SAMPLINGo Where evidence based assessment of risk factors is not possible
o Sampling is stratified throughout the whole territory of the Member State.
o Number of holdings to be sampled is based on the number of holdings for each poultry type/production category
o Number of holdings to sample are provided in legislation
Poultry surveillance design - ACTIVENumber of holdings to sample
o Same for risk based and representative survey
o Poultry holdings (excluding duck, goose and mallard)o Detection of 1 holding where prevalence >5%, 95% confidence
Number of holdings per poultryproduction category per MS
Number poultry holdings to be sampled
Up to 34 All
35-50 35
51-80 45
81-250 53
>250 60
Presenter
Presentation Notes
Thinking about how AI can get into a poultry holding, and targeting surveillance at more ‘risky’ holdings.
Poultry surveillance design - ACTIVENumber of holdings to sample
o Same for risk based and representative survey
o Duck, goose and mallard holdingso Detection of 1 holding where prevalence >5%, 99% confidence
Number of holdings per poultryproduction category per MS
Number poultry holdings to be sampled
Up to 46 All
47-60 47
61-100 59
101-350 80
>350 90
Presenter
Presentation Notes
Higher level of confidence required as evidence that duck, goose holdings are less likely to be detected by passive surveillance/early detection.
Poultry surveillance design - ACTIVE
Number of birds to sample per holdingo Same for risk based and representative survey
o 95% probability of detection if seroprevalence >=30%o Gallinaceous – at least 5-10 blood samples taken
o Waterfowl – 20 blood samples per holding
Presenter
Presentation Notes
Difference between gallinaceous and waterfowl is due to reduced test sensitivity in waterfowl species
Poultry surveillance design - ACTIVE
Laboratory testingo EU AI Diagnostic manual 2006/437/EC or OIE Manual of Diagnostic Tests and
Vaccines for Terrestrial Animals
o Purpose; harmonisation, transparency and creditability of programme
o Haemagglutination-inhibition test using strains approved by EURL
o Positives must be followed up with PCR/virus isolation testing
Other surveillance approaches
High risk circumstances (ie outbreaks elsewhere in region or country; DPPA area with species not showing clinical signs)
• Pre-movement testing (including to slaughter) by PCR• Routine checking of ‘baseline’ mortality• High frequency of serological testing in some risk sectors (ie 4-6
times per year/premise)• LP focus unless species not showing disease signs with HP
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Wild bird surveillance design
• Passive surveillance – sick and dead birds
Objective“Timely detection of HPAI of the subtype H5Nx in wild birds in order to protect poultry in poultry holdings and safeguard veterinary public health”
28 MS participated in the poultry survey in 2014 19,813 poultry holdings were sampled (in 2013 25,220) - the most sampled category was laying hens (conventional & free-range) 29% n = 5,832 Number of holdings sampled varied by MS from 17 – 5,733
Cross year analysis
Presenter
Presentation Notes
Higher proportion of ducks & geese and game bird detections were H5, rather than H7. This is seen across the production sectors for ducks & geese. Higher relative proportion of H7 detections were seen in backyard flocks, fattening turkeys and FR/non-FR layers.
Vaccination
Desired results of vaccination against AI
• freedom from disease• no effect on production or other serious expense• no trade embargoes• Eradication if enzootic infection
APHA 2017 27
Avian influenza vaccination
Current vaccines can result in:• Protection against clinical signs• Decrease bird susceptibility to infection• Reduction in virus excretion• Reduction in transmission (birds and humans)BUT………….
AI vaccination - caution
• AI virus may infect and replicate in vaccinated birds without clinical signs
• As a corollary HPAI as defined by OIE may still be confirmed in such birds
• Coverage rates in key at risk populations need to be >60% (ideally 80%)
• Infection with HPAI virus without clinical signs may lead to spread and an endemic situation
Vaccination will only work when applied in combination with other
measures
Vaccination is not a substitute for weak farm biosecurity
Challenges associated with use of vaccination
• Clearly defined objectives/Exit strategy• Supplementary tool for control of outbreaks
– Biosecurity– Stamping out of infected flocks– Buffer zones
• Proactive surveillance necessary in vaccinated populations– DIVA– Serological monitoring– Use of sentinels
• Antigenic variability in field strains• Target populations?• Ease of delivery• System for control of statutory disease needs to be subject to supervision by
competent veterinary authority• Trade impacts• Management of public health implications/assurance• Effective tool for control of HPAI?
Veterinary inactivated vaccines for AI (advantages and disadvantages)
• Inactivated whole AI virus – with adjuvant; produced versus field strain (ie rg viruses in China versus evolving H5)
• Relatively cheap, multiple hosts, easy to standardise, can be adapted to field virus, licensure
• Generally 2 doses for protection; NO mass application, lack DIVA, poor in overcoming maternal antibody, or hatchery application
Text in footer 32
Veterinary vectored vaccines for AI (advantages and disadvantages)
• Live vector – avian virus carrying an AI gene insert ie H5 HA
• Number of delivery vectors (Avian Avulavirus [APMV1] 1, DVE, Fowlpox, Herpesvirus Turkey
• Relatively cheap, easy to standardise, can be adapted to field virus, mass application including at hatchery, DIVA applicable
• Host specificity (define target population), licensure for field, natural immunity in population to vector
Text in footer 33
Veterinary other vaccines for AI (advantages and disadvantages)
• In vitro produced HA• Adaptable to changing virus, DIVA, multiple hosts• Poor knowledge for field application, expensive to
produce, delivery? • Nucleic acid
• Adaptable to changing virus, DIVA, multiple hosts• Poor knowledge for field application, expensive to
produce, delivery?, 2 doses minimum
Text in footer 34
APHA 2017 35
Potential application in a South Africa setting?
• Continual risk with epizootic waves
• Risk populations?
• Define aim
• Preventative- match to threat viruses; duration of programme?
• Emergency application to live (?) in buffer zones (?) as component of control strategy towards eradication
• delivery on scale challenges; time to induce flock immunity
Text in footer 36
Potential application in a South Africa setting?
• Challenges• Vaccine bank provision?• Ensure appropriate high quality vaccines• Efficacy versus changing virus• DIVA can be applied• Licensure issues• Cost benefit?
• Consider wider impacts• Trade, • Surveillance intensity/cost to prove freedom, • Vaccine escape• Public health perception/threat
Text in footer 37
Implications of vaccination upon surveillance• Passive surveillance; by definition severely compromised since
even poorly efficacious vaccines will reduce disease signs• Active surveillance will need to be enhanced if surety of absence
of infection is required (ie underpinning trade)Approaches• Depends on vaccine used but immunity to HA is protective• Differentiating Infected from Vaccinated Animals (DIVA) then
serological test possible ie vectored vaccines may only use HA of the virus
• Detect responses to another part of the virus (M or NP proteins) induced following natural infection
• No DIVA: PCR (inefficient unless moving/trading birds)• No DIVA: Sentinel birds (non vaccinated) placed in flocks: dead
birds tested for AI• Limitations Text in footer 38
Summary • Surveillance design needs to be adapted to country, region or population
specific factors
• Passive surveillance will detect AI if causing disease
• Active Surveillance will detect potentially detect evidence of silent infection if serology based
• Programmes of active surveillance can be applied on a risk basis and can form part of flock assurance ie in relation to trade
• Vaccination: multi-faceted considerations for implementation
• Vaccine choice will directly influence options for downstream surveillance; DIVA poorly available or validated for ‘Asian’ origin H5 HPAI
Text in footer 39
APHA 2017 40
Acknowledgements
IRL, Animal and Plant Health AgencyNicola LewisSteve EssenNatalie McGinnJames SeekingsSusan CollinsHolly EverestSharon BrookesRichard Ellis, Bioinformatics, APHAHelen Roberts & team, IDM, APHA
Funding EURL- EU commission & Defra/UK DAs
OFFLU (OIE/FAO)EFSA/ECDCWHO CCs London & Atlanta
EU MS national reference labs for Avian InfluenzaThird countries sharing biologicals and data with APHA
Celia Abolnik, University of Pretoria
University of CambridgeNicola LewisDivya VenkateshSara Lopes
USDA-ARSAmy VincentErasmus MCRon Fouchier Marjolein PoenWHO/OFFLU H5 evolution working group
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