(or what) are AHVLA? - MERIAL Avian Forum 2013

Merial Avian Forum 2013
Istanbul, Turkey
17 – 19 April 2013
Richard Irvine BVetMed MSc(CIDA) MRCVS
Deputy Head, Avian Virology & Mammalian Influenza Group EU/OIE/FAO International Reference Laboratory for AI & ND
AHVLA‐Weybridge
Chair, AHVLA/SRUC Avian Expert Group
Vice‐chair NFU Poultry Health Group
Richard.Irvine@ahvla.gsi.gov.uk
Infectious Bronchitis Virus
An evolving pathogen
Introduction
• AHVLA: roles
• Infectious Bronchitis virus (IBV) overview
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Virus and disease
Epidemiology and evolution
Diagnosis
Prevention and Control
• Challenges • Concluding thoughts
Who (or what) are AHVLA?
• Animal Health and Veterinary Laboratories Agency
• Executive agency of Defra (Great Britain)
• Created from merger of the Veterinary Laboratories Agency
(VLA) with Animal Health in April 2011
• National and International Reference Laboratory for a wide range of animal diseases, including:
– OIE/EU/FAO International Reference Laboratory for Avian Influenza & Newcastle disease
AHVLA: What do we do?
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Disease surveillance & investigation
Laboratory diagnostics
Fundamental and applied R&D
Avian & mammalian Influenza
Newcastle disease
Emergency Disease Outbreak responses
The AHVLA laboratory network provides local catchment areas for submission, investigation and testing of diagnostic samples and carcase post‐mortems
Infectious Bronchitis Virus
An evolving pathogen
A veterinary perspective
Virus biology
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Group: IV (+)ssRNA
Order: Nidovirales
Family: Coronaviridae
Subfamily: Coronavirinae
Genus: Gammacoronavirus
– Large RNA genome: 27.6kb
– Surface Spike (S) protein
– S1 subunit mediates • Virus attachment
• Antigenicity
• Immunogenicity
Courtesy of Dave Everest, AHVLA Weybridge
Gammacoronaviruses infect many different avian species…
Sites of IBV replication
Respiratory tract
Kidneys
Proventriculus
Alimentary tract
Oviduct Testes
Clinical signs of IBV
Snicking (sneezing), tracheal râles, nasal discharge
Urates (wet litter)
Poor feed intake & uneven birds
Diarrhoea (wet litter)
Decrease in egg production & egg quality in hens
False layer syndrome
Enlarged kidneys due to infection with a nephropathogenic IBV strain
Images: AHVLA
Relevance of IBV: Poultry (1)
• 1930s: first demonstration of disease caused by coronavirus was IBV in domestic fowl in the USA
– Massachusetts (Mass) serotype
• 1950s: Connecticut (Conn) variant strains in USA
– Non‐Mass variants since identified from 1940s in USA
– Mass serotype strains in Latin America
• Development of live Mass‐type IBV vaccines
– International spread of Mass serotype IBV with poultry
• 1970s onwards: Reported emergence and evolution of other IBV variants around the world
Relevance of IBV: Poultry (2)
• Global distribution of many different IBV serotypes
– Variation within and between countries and regions
– Indigenous IBV variants in many regions
• IBV is of major economic, health and welfare importance to poultry & poultry industry worldwide
• Continued emergence and evolutionary divergence of IBV variants
– Changes in Spike (S) protein amino acids – Novel variants do not always persist & spread, but some do, causing major disease and control challenges
Global Distributions of IBV, 1950‐
IBV Serotypes identified
Europe
Asia
Americas
Australia
Mass
D207
D212
D3128
D3896
D1466
PL‐64084‐France
A224.74/Italy
B1648‐Belgium
UK/918/67
UK6/82
UK/142/86
UK793/B
624/Italy
QX (D388)
Mass
Conn
Gray
Ark 99
N1/52‐T
Kb8523‐Japan
793/B‐India
NRZ‐China
HV‐China
SAIB3‐China
KM91‐Korea
EJ95‐Korea
A1121‐Taiwan
QX
Mass
Conn
Florida
Clark 333
Ark 99
SE17
JMK
Iowa 97
Iowa 609
Holte
Gray
Main 209
DE/072/92
Chile 14
50/96‐Brazil
22/97‐Honduras
A‐Vac1
B‐Vic S
C‐N1/62
D‐N9/74
E‐01/73
F‐V2/71
G‐V1/71
H‐N1/75
I‐N2/75
J‐N3/63
K‐T1/82
L‐N1/88
M‐03/88
0‐NT2/89
P‐N1/81
Q‐V18/91
Adapted from: Ignjatovic, J. & Sapats, S. (2000) Avian Infectious Bronchitis virus. Rev. Sci. Tech. Off. int. Epiz.,19 2, pp. 493‐508. Data also from: de Wit et al (2010) Infectious bronchitis virus in Asia, Africa, Australia and Latin America ‐ history, current situation and control measures. Rev. Bras. Cienc. Avic. 12(2),pp.97‐106; de Wit et al (2011) Infectious bronchitis virus variants: a review of the history, current situation and control measures. Avian Pathology, 40(3),pp.223‐235; Jackwood, M. (2012) Review of Infectious Bronchitis Around the World. Avian Diseases, 56,pp.634‐641.
Global Distribution & Diversity of IBV
de Wit, J.J. et al (2011) Infectious bronchitis virus variants: a review of the history, current situation and control measures Avian Pathology, 40(3),pp.223‐235
Contemporary IBV genotypes in Western Europe (2002‐2006)
Worthington et al (2008) A reverse transcriptase‐polymerase chain reaction survey of infectious bronchitis virus genotypes in Western Europe from 2002 to 2006, Avian Pathology,37:3,pp.247‐257
The emergence and evolution of IBV variants can occur by:
‐ Mutation
‐ Recombination Shu‐Ming, K. et al (2013) Evolution of infectious bronchitis virus in Taiwan: Positively selected sites in the nucleocapsid protein and their effects on RNA‐binding activity. Vet Micro, 162(2), pp.408‐418. IBV variants have different properties
Mutation Recombination IBV variants
Variations in phenotype & genotype
Virus Antigenicity
Vaccinal & host responses
interactions
Virulence
Clinical signs
Tissue tropism
Pathology
After: Montassier, H.J. (2010) Molecular Epidemiology and Evolution of Avian Infectious Bronchitis Virus. Rev. Bras. Cienc. Avic. [online] 12(2)pp.87‐96
Diagnosis of IBV: Field
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Observed clinical signs and history
Flock production type, targets and records
Vaccination and flock husbandry conditions
Veterinary investigation ‐ site visit
Clinical signs and gross pathology can be similar to those caused by other diseases, including AI & ND
– Consideration of differential diagnoses is essential!
• Flock sampling – Swab & blood samples
• Post‐mortem examination – Batch of affected birds/culls
Laboratory methods (1)
• Virus isolation
• Serology
– ELISA
– HIT
– AGP, VNT
• Electron microscopy
• Molecular methods ‐ PCR
• S1 gene sequencing
AHVLA Weybridge
Laboratory methods (2)
• Virus isolation: live virus Costly, takes time
• Serology: antibody detection
Need serial samples – ELISA
– HIT
– AGP, VNT
Diagnosis & monitoring Interpretation of results complicated by use of IBV vaccines
• Electron microscopy
Insensitive, costly • Molecular methods: viral RNA • S1 sequencing: IBV genotypes
Rapid, sensitive, specific and cost‐effective
Day 0: Samples received
≤ 7 days: IBV PCR positive
≤ 14 days: IBV genotype result
7 days: Egg passage (EP) 1
21 days: Negative – EP3
Suspect IBV for typing
28 days: Negative – VI complete
Suspect IBV for typing
Diagnosis of IBV: Lab
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AHVLA has developed and validated a real‐time RT‐PCR and partial S1 sequencing method
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Supports timely disease prevention and control decision‐
making, including IBV vaccination
Nucleic acid extraction
Real‐time RT‐PCR
RRT‐PCR results
Jones, R.M., et al (2011). Development and Validation of RT‐PCR Tests for the Detection and S1 Genotyping of Infectious Bronchitis Virus and other Closely Related Gammacoronaviruses within Clinical Samples. Transboundary and Emerging Diseases, 8(5), pp.411–420.
Co‐circulation of IBV genotypes & H9 in Iraq
• UNFAO and AHVLA
• Clinical disease and high mortality in broiler flocks from seven regions of Iraq
• European QX‐ and Variant 2 (US)‐like IBV genotypes
Reid et al (2013) WPSA, Oral presentation
Co‐circulation of IBV genotypes in UK
• ~3,500 samples tested (PCR)
• Non‐pooled & Pooled samples
• Health problems in poultry flocks from across UK
• Multiple genotypes circulating
• Widespread live vaccine use
Prevention of IBV
• Biosecurity
– Prevent introduction of all diseases, including IBV • Different serotypes of IBV do not cross‐protect
• However, some IBV strains can induce cross‐protection against other serotypes • Live attenuated primer from day‐old (growers)
• Inactivated (killed) booster (point‐of‐lay hens)
Cross‐protection between IBV strains varies with S1 gene homology
de Wit, J.J. et al (2011) Infectious bronchitis virus variants: a review of the history, current situation and control measures Avian Pathology, 40(3),pp.223‐235
Vaccines are an important tool
• Mass‐type live attenuated vaccines – Good protection if Mass IBV serotype in‐region
– Variable/poor protection if infection with heterologous variant IBV challenge (or other causes of disease!)
• Use of two different serotypes of live IBV vaccine (eg. Mass + variant) can provide broader protection and efficacy against different IBV types
– IBV ‘protectotypes’ so not always need new vaccine
– Many and various ‘double live vaccine’ schedules
• However, may not protect against all IBV variants
Prevention & Control of IBV as a cause of flock health problems
• Prompt veterinary investigation of flocks
• Consider differential diagnoses and correct sampling • Robustly validated, appropriate & timely lab testing
• Diagnostic information to inform disease prevention & control decision‐making
– Appropriate vaccine selection
– Correct vaccine handling, storage and administration
• Biosecurity is good for your business
• Surveillance – systematic (scanning vs. active)
Global challenges faced
• Livestock production & disease problems
• Globalisation
• Climate change
• Population growth
• Public health threats
• Antimicrobial resistance
“When all people at all times have access to sufficient, safe, nutritious food to maintain a healthy and active life” World Food Summit, 1996 Poultry value chains make safe, quality and nutritious food available for people worldwide
Inputs and production efficiency gains from Vet & Ag Services
Outline commercial broiler system value chain
Some requirements to meet global poultry health
challenges
• Veterinary and public health disease surveillance
• Disease awareness & knowledge transfer
• Early reporting and investigation of disease problems
• Rapid response and tools to detect & control disease
• Supply chain infrastructure, integration & collaboration – Farmers, Industry, Pharma, Vets, Scientists, Labs
• Strategic & multi‐disciplinary research Declare the past, diagnose the present, foretell the future
Hippocrates, 400 BC
Epidemics, Second Constitution, Book 1, Section XI
Translated by WHS Jones Cambridge: Harvard University Press, 1995. BMJ (2002), 324:1448
Acknowledgements
• Avian Virology & Mammalian Influenza Group, Weybridge – Ian Brown, Dennis Alexander, Ruth Manvell
– Jill Banks, Sharon Brookes, Chad Fuller, Scott Reid & teams
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Poultry Industry Poultry owners & keepers
Private Veterinary Surgeons
AHVLA Regional Laboratories & Field staff
Defra
EU
OIE
FAO
Merial
Thank you for your attention
Richard.Irvine@ahvla.gsi.gov.uk