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Rafael Monleon, DVM, MSpVM, ACPV, PAS
Regional Veterinarian (Asia)
Poultry Health Conference
18th June 2013, Bangkok (Thailand)
Prevention and Control of
Infectious Bronchitis in Asia
Objectives
• Infectious Bronchitis Virus (IBV)
• Distribution and Prevalence
• Disease Manifestations
• Prevention & Control
– Diagnostics and Monitoring
– Current methods to control IBV
Infectious Bronchitis Virus (IBV)
• Single stranded RNA Coronavirus
– High mutation rate
• Highly contagious
• Airborne, mechanical vectors
• Short incubation period (18-36h)
• Replicates in respiratory, urinary,
genital and gastrointestinal tract
tissues
• Shed in respiratory tract and
faeces
– Persists After Clinical Signs Gone
• No trans-ovarian transmission
• Easily killed by disinfectants and
heat
– Except in presence of organic
material
Distribution & Prevalence
• From mid-2000s one of the biggest disease
problems in Asia
– Breeders and Broilers
• Massive egg production losses and mortality
• Sometimes hard to recognize as it is mixed with
other respiratory infections
– Often blame problems on ND/AI/APV/Mycoplasma
– Poor diagnosis facilities across the regions
• Vaccination with classic vaccines do not protect
– Variants not licensed
Distribution
Distribution
Countries where we have
seen signs or lesions
compatible with IBVv strains
Disease Manifestations
• Respiratory
• Nephritic-Nephropathogenic
• Reproductive
• Male Infertility
• Digestive-Enteric
Respiratory
• Any Age ; All Strains
• Main site of virus replication
• Respiratory signs
• Snicking, head shaking,
conjunctivitis, rales
– Chronic respiratory
disease
• E. coli / Mycoplasma
– Condemnations at
processing
• Often only sign prior to
reproductive form
© Dorko, 2009
© Dorko, 2009
Nephritic-Nephropatogenic
• Some Strains
• Mostly Young Chickens (week 2-5)
• High mortality
– Up to 20%
• Interstitial Nephritis and urolithiasis
– Structural alterations in the tubular epithelial cells of
the kidneys
– Impaired fluid and electrolyte transport
• Renal failure ; diarrhea
• Increased uric acid levels -> GOUT
• Secondary Bacterial Infections (é Mortality)
© Rafael Monleon / Aviagen
© Rafael Monleon / Aviagen
Nephritic-Nephropatogenic
Pathology
Reproductive
• Highly prevalent in Asia since 2000s
• Some strains
• 2 Critical Times
– Baby chick
– Sexual Maturation and onwards (>16-18wks)
• Variable pathology
– Egg yolk peritonitis
– Drops in egg production
– Oviduct Cysts
– Deterioration in eggshell
– Watery albumen
1.
2.
0w
0w
18wks
65wks
18wks
65wks
INFECTION IN BABY CHICKS
No homologous MDA, “false layers”
MATURE INFECTION FROM
DEVELOPMENT OF SEXUAL
MATURITY AND ONWARDS
Egg production loss
Poor egg quality
Reproductive
Period of infection
Source: Biochek
Reproductive
Effect on egg production
© R. Monleon
© R. Monleon
© R. Monleon
Reproductive
IBVv Egg Production
© R. Monleon
© R. Monleon
© R. Monleon
© R. Monleon
Reproductive
Pathology
© R. Monleon © R. Monleon
© R. Monleon
© R. Monleon
Reproductive
Pathology
Infertility & Enteric
• Infertility in Mature Cockerels
• USA and Brazil
• Bolz et al., 2004; Villareal et al., 2007
• Enteritis Broilers (Brazil)
• Villareal, 2007
• Proventricular Lesions (China)
• Wang, 2001
• Swollen / Hemorrhagic Ulcers
Diagnosis
• Histopathology
• Virus Isolation and Identification
• VN / HI
– Labour intensive and high cost
• ELISA
– Useful but cannot distinguish between serotypes
• Conventional PCR / Real-Time PCR
– Trachea, airsac, lung, kidney, proventriculus and caecal tonsils
– Sequencing
• Monoclonal Antibodies
Virus Neutralization
• Evaluation of field challenge
Source: Biochek
ELISA
ELISA: Evaluation Infection
Source: Biochek
• Vaccination Index (VI) a new parameter to
evaluate vaccination response
Mean Titer _
• VI = Coefficient Variation (%)
The higher the VI , the better the vaccination
The lower the VI, the poorer the vaccination
If VI > maximum limit, suspect of infection
Source: Biochek
ELISA: Vaccination Index
Source: Biochek
ELISA: Vaccination Index
Vac. Program IBV VI Normal VI Susp.
Infection
H120, MA5,
IB primer, IBMM-ARK
10 - 90 > 110
H120 + 4/91, H120 +
CR88
50 - 200 > 200
PCR + Sequencing
Figure 4. Phylogenetic tree based on the amino acid sequences of selected strains of IBV. The neighbour-joining and Nei!Gojobori methods were used to compute the relatedness. The amino acid se
Downloaded by [Dr Rafael Monleon] at 00:26 15 June 2013
Diagnosis Challenges
• Difficult in Asia
– No Many Available Labs
• Samples
– Difficulties Due to AI Restrictions
• FTA
• Serum / Tissues
• Laboratories
– UGA-PDRC
– Deventer - Holland
– IZE – Italy
– CESAC – Spain
Prevention & Control
• Management
• Biosecurity
• Vaccination
Control of IBV
• Management
• Biosecurity
• Vaccination
• Feed
– Highly nutritious / balanced formulation
– Good physical quality
– Clean contaminants
• Water
– Good P-C quality / Sanitized
• Temperature
– Brooding
• Ventilation
– Formaldehyde
• Lighting
Control of IBV
Management
• Immunosuppressive Agents
– IBD / CAV / MD / Reovirus
– Others
• Clinical vs. Subclinical
• Vaccination
– IBD / CAV / Reovirus
• Offspring vs. Parents
• Can Affect Greatly The Response
From the Birds to Vaccination and
Disease Challenge!
© R. Monleon
© R. Monleon
© R. Monleon
Control of IBV
Management - Immunosuppression
• Mycotoxins play a very important role on IBV
control
• Aflatoxins are potent immunosuppressant agents
Liver Damage > Low Immunoglobulin > Low Immunity
> Vaccination Failures
• Detection / Monitoring Difficult
– Even slightly increased levels should raise flags
Control of IBV
Management - Mycotoxins
Control of IBV
• Management
• Biosecurity
• Vaccination
• First and cheapest barrier of prevention
• Many times neglected especially in PS-Broiler
– Poor structural facilities
– Poor cleaning + disinfection
– Decreased downtime
• Poor biosecurity = High challenge for baby chick
Control of IBV
Biosecurity
• Seal the Farm …Keep disease out
– Do not let disease come into your farm
• Avoid unnecessary visits
• Disinfection of equipment
• Shower In-Out
• Clothing
• Manure
• Mortality / Cull disposal
Control of IBV
Biosecurity - Basics
• Cleaning technique
• Removal Equipment
• Cleaning (Detergent + Hot Water)
• Disinfectants – Correct Dilution
• Waste Water
• Hand Sanitizers
• Pest Control
• Monitoring
Salmonella Rodents, Darkling Bettle, Flies
Mycoplasma Rodents
E. coli Rodents, Darkling Bettle, Flies
Aspergillus Darkling Bettle
NDV Darkling Bettle, Flies
IBDV Darkling Bettle, Flies
Ascaris & Taenias Darkling Bettle, Flies
© R. Monleon
Control of IBV
Biosecurity – Cleaning and Disinfection
• Very important to allow resting the farm
• Dry – UV -> bad for pathogens
• Minimum 14d Broilers / 1 months PS / 2 months GP
• Do Not Rush to Place Birds!
Control of IBV
Biosecurity – Downtime
Control of IBV
• Management
• Biosecurity
• Vaccination
• Most Controversial Area
• Mass type vaccines alone DO NOT PROTECT
• Research Work Shows good protection by combination of
Mass + Variant
– No need for new vaccine for every new variant
– Research Done of Protection Respiratory Tract
• NEED MORE RESEARCH ON THIS AREA
• Interaction of Maternal Antibodies
– Lack Maternal Antibodies for IBVv in certain areas
• Some Past Programs: Mass d0 + Variant d14
– Did not take consideration of “day 0 challenge”
• Poor Biosecurity + Management
Control of IBV
Vaccination
Source: WP
Control of IBV
Need of Variant IBV Vaccines
• Early challenge difficult to control with vaccination
– Maternal antibodies are a great asset
• Limited research on IBVv and maternal antibodies
– Wit JJ (Sjaak) de, 2011
• Generally homologous serotypes protect well from IBV
– not that good heterologous challenges
• Baby chicks lack Maternal Antibodies specific for the
variant present
– ALMOST SPF BIRDS
• Biosecurity + Adjustment of Vaccination
Control of IBV
Vaccination – Maternal Antibodies
Control of IBV
Vaccination – Factors
• Determination of challenge
– Laboratory Confirmation
• Vaccine selection
• Vaccine scheduling
• Vaccination hatchery vs. farm
• Vaccine handling / application
• Control vaccine reactions
• Revaccination during production
– MAb
• Titer Monitoring
First vaccine Challenge Outcome
Mass type Mass type Protection
793/B No protection
Mass type
None or Little protection Against Non–Mass Strains
Control of IBV
IB Live Vaccination
Based on MSD
First vaccine Challenge Outcome
IB88 -
4/91
Mass type
Protection
793/B
No protection
IB88 -
4/91
Even Revaccination With Same Vaccine Strain Will
Not Give Cross Protection
Control of IBV
IB Live Vaccination
Based on MSD
First vaccine Challenge Outcome
Mass type
Protection
793/B
IB88 -
4/91*
IB88 -
4/91*
Second vaccine
Mass
Mass
Protection
Expected to give general
protection against other IBV
*Second Vaccine can be combined with First Vaccine to cover opportunity
window at day of age
Control of IBV
IB Live Vaccination
First vaccine Challenge Outcome
D388 (QX)
IB88 -
4/91
Second vaccine
Mass Protection
Control of IBV
IB Live Vaccination
There is no need to develop a vaccine for each new serotype, as
different “old” serotypes generally confer protection over “new”
serotypes – PROTECTOTYPE CONCEPT
Based on MSD
Vaccine Protection
Source: MSD
Control of IBV
Vaccination – Breeders High Challenge
• Day 0 – Mass + Variant
• Day 14 Mass
• Week 4 - Mass
• Week 6 – Variant
• Week 8 – Mass
• Week 12 – IB (K) Multi Variant
• Week 16 – Variant + IB (K) Multi Variant
Disclaimer: This is an example of IBVv vaccination program. Always consult your
veterinarian before implementing a new vaccination program in your flocks
Control of IBV
Vaccination – Broilers High Challenge
• Day 0 – Mass + Variant
• Day 12-14 Mass
Disclaimer: This is an example of IBVv vaccination program. Always consult your
veterinarian before implementing a new vaccination program in your flocks
• Classic
– H120; Ma5; M41; H52; 28/86
• Variants
– 793/B
• Nobilis 4/91 (793/B) (MSD)
• Gallivac IB88 (793/B) (Merial)
• Vir 117 (793/B) (BioVac)
– D274
• IB Primer (Holland + D274) (Zoetis)
• Nobilis IBmulti / IB3 (MSD)
• Vaksindo (M41, QX, IB 771)
– Others
• Conn (SP)
• Poulvac IB QX (Pfizer)
• Nobilis D1466 (MSD)
• Ark-99 (Zoetis)
• QX-like strain Korea (K2)
• Australian VIC S / A3
Control of IBV
Vaccination – Vaccines Available
The Road Ahead
IBV Challenges
• Overlapping with Other Diseases
– ND / AI / APV / Mycoplasma / Others
• Diagnosis
– Laboratories
• Poor Biosecurity
– Formaldehyde withdrawal
• Vaccine Availability
– Licensing / Vaccine Stock
• Vaccine Misuse
– Technique (i.e. eye drop) / Scheduling
Summary - IBV
• IBV continue to be reported with high prevalence in many
Asian countries and causes a significant damage;
however lately has improved
• Diagnostics and monitoring are sometimes scarce,
however utmost necessary to control the disease
• Biosecurity + Vaccination are currently the most effective
ways of protection
• Current Vaccination programs across the area are not
homogenous and are based in combination of scientific
and empiric beliefs, therefore further research is needed
Thank You
rmonleon@aviagen.com

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Prevention and Control of Infectious Bronchitis in Asia

  • 1. Rafael Monleon, DVM, MSpVM, ACPV, PAS Regional Veterinarian (Asia) Poultry Health Conference 18th June 2013, Bangkok (Thailand) Prevention and Control of Infectious Bronchitis in Asia
  • 2. Objectives • Infectious Bronchitis Virus (IBV) • Distribution and Prevalence • Disease Manifestations • Prevention & Control – Diagnostics and Monitoring – Current methods to control IBV
  • 3. Infectious Bronchitis Virus (IBV) • Single stranded RNA Coronavirus – High mutation rate • Highly contagious • Airborne, mechanical vectors • Short incubation period (18-36h) • Replicates in respiratory, urinary, genital and gastrointestinal tract tissues • Shed in respiratory tract and faeces – Persists After Clinical Signs Gone • No trans-ovarian transmission • Easily killed by disinfectants and heat – Except in presence of organic material
  • 4. Distribution & Prevalence • From mid-2000s one of the biggest disease problems in Asia – Breeders and Broilers • Massive egg production losses and mortality • Sometimes hard to recognize as it is mixed with other respiratory infections – Often blame problems on ND/AI/APV/Mycoplasma – Poor diagnosis facilities across the regions • Vaccination with classic vaccines do not protect – Variants not licensed
  • 6. Distribution Countries where we have seen signs or lesions compatible with IBVv strains
  • 7. Disease Manifestations • Respiratory • Nephritic-Nephropathogenic • Reproductive • Male Infertility • Digestive-Enteric
  • 8. Respiratory • Any Age ; All Strains • Main site of virus replication • Respiratory signs • Snicking, head shaking, conjunctivitis, rales – Chronic respiratory disease • E. coli / Mycoplasma – Condemnations at processing • Often only sign prior to reproductive form © Dorko, 2009 © Dorko, 2009
  • 9. Nephritic-Nephropatogenic • Some Strains • Mostly Young Chickens (week 2-5) • High mortality – Up to 20% • Interstitial Nephritis and urolithiasis – Structural alterations in the tubular epithelial cells of the kidneys – Impaired fluid and electrolyte transport • Renal failure ; diarrhea • Increased uric acid levels -> GOUT • Secondary Bacterial Infections (é Mortality)
  • 10. © Rafael Monleon / Aviagen © Rafael Monleon / Aviagen Nephritic-Nephropatogenic Pathology
  • 11. Reproductive • Highly prevalent in Asia since 2000s • Some strains • 2 Critical Times – Baby chick – Sexual Maturation and onwards (>16-18wks) • Variable pathology – Egg yolk peritonitis – Drops in egg production – Oviduct Cysts – Deterioration in eggshell – Watery albumen
  • 12. 1. 2. 0w 0w 18wks 65wks 18wks 65wks INFECTION IN BABY CHICKS No homologous MDA, “false layers” MATURE INFECTION FROM DEVELOPMENT OF SEXUAL MATURITY AND ONWARDS Egg production loss Poor egg quality Reproductive Period of infection
  • 14. © R. Monleon © R. Monleon © R. Monleon Reproductive IBVv Egg Production
  • 15. © R. Monleon © R. Monleon © R. Monleon © R. Monleon Reproductive Pathology
  • 16. © R. Monleon © R. Monleon © R. Monleon © R. Monleon Reproductive Pathology
  • 17. Infertility & Enteric • Infertility in Mature Cockerels • USA and Brazil • Bolz et al., 2004; Villareal et al., 2007 • Enteritis Broilers (Brazil) • Villareal, 2007 • Proventricular Lesions (China) • Wang, 2001 • Swollen / Hemorrhagic Ulcers
  • 18. Diagnosis • Histopathology • Virus Isolation and Identification • VN / HI – Labour intensive and high cost • ELISA – Useful but cannot distinguish between serotypes • Conventional PCR / Real-Time PCR – Trachea, airsac, lung, kidney, proventriculus and caecal tonsils – Sequencing • Monoclonal Antibodies
  • 20. • Evaluation of field challenge Source: Biochek ELISA
  • 22. • Vaccination Index (VI) a new parameter to evaluate vaccination response Mean Titer _ • VI = Coefficient Variation (%) The higher the VI , the better the vaccination The lower the VI, the poorer the vaccination If VI > maximum limit, suspect of infection Source: Biochek ELISA: Vaccination Index
  • 23. Source: Biochek ELISA: Vaccination Index Vac. Program IBV VI Normal VI Susp. Infection H120, MA5, IB primer, IBMM-ARK 10 - 90 > 110 H120 + 4/91, H120 + CR88 50 - 200 > 200
  • 24. PCR + Sequencing Figure 4. Phylogenetic tree based on the amino acid sequences of selected strains of IBV. The neighbour-joining and Nei!Gojobori methods were used to compute the relatedness. The amino acid se Downloaded by [Dr Rafael Monleon] at 00:26 15 June 2013
  • 25. Diagnosis Challenges • Difficult in Asia – No Many Available Labs • Samples – Difficulties Due to AI Restrictions • FTA • Serum / Tissues • Laboratories – UGA-PDRC – Deventer - Holland – IZE – Italy – CESAC – Spain
  • 26. Prevention & Control • Management • Biosecurity • Vaccination
  • 27. Control of IBV • Management • Biosecurity • Vaccination
  • 28. • Feed – Highly nutritious / balanced formulation – Good physical quality – Clean contaminants • Water – Good P-C quality / Sanitized • Temperature – Brooding • Ventilation – Formaldehyde • Lighting Control of IBV Management
  • 29. • Immunosuppressive Agents – IBD / CAV / MD / Reovirus – Others • Clinical vs. Subclinical • Vaccination – IBD / CAV / Reovirus • Offspring vs. Parents • Can Affect Greatly The Response From the Birds to Vaccination and Disease Challenge! © R. Monleon © R. Monleon © R. Monleon Control of IBV Management - Immunosuppression
  • 30. • Mycotoxins play a very important role on IBV control • Aflatoxins are potent immunosuppressant agents Liver Damage > Low Immunoglobulin > Low Immunity > Vaccination Failures • Detection / Monitoring Difficult – Even slightly increased levels should raise flags Control of IBV Management - Mycotoxins
  • 31. Control of IBV • Management • Biosecurity • Vaccination
  • 32. • First and cheapest barrier of prevention • Many times neglected especially in PS-Broiler – Poor structural facilities – Poor cleaning + disinfection – Decreased downtime • Poor biosecurity = High challenge for baby chick Control of IBV Biosecurity
  • 33. • Seal the Farm …Keep disease out – Do not let disease come into your farm • Avoid unnecessary visits • Disinfection of equipment • Shower In-Out • Clothing • Manure • Mortality / Cull disposal Control of IBV Biosecurity - Basics
  • 34. • Cleaning technique • Removal Equipment • Cleaning (Detergent + Hot Water) • Disinfectants – Correct Dilution • Waste Water • Hand Sanitizers • Pest Control • Monitoring Salmonella Rodents, Darkling Bettle, Flies Mycoplasma Rodents E. coli Rodents, Darkling Bettle, Flies Aspergillus Darkling Bettle NDV Darkling Bettle, Flies IBDV Darkling Bettle, Flies Ascaris & Taenias Darkling Bettle, Flies © R. Monleon Control of IBV Biosecurity – Cleaning and Disinfection
  • 35.
  • 36.
  • 37. • Very important to allow resting the farm • Dry – UV -> bad for pathogens • Minimum 14d Broilers / 1 months PS / 2 months GP • Do Not Rush to Place Birds! Control of IBV Biosecurity – Downtime
  • 38. Control of IBV • Management • Biosecurity • Vaccination
  • 39. • Most Controversial Area • Mass type vaccines alone DO NOT PROTECT • Research Work Shows good protection by combination of Mass + Variant – No need for new vaccine for every new variant – Research Done of Protection Respiratory Tract • NEED MORE RESEARCH ON THIS AREA • Interaction of Maternal Antibodies – Lack Maternal Antibodies for IBVv in certain areas • Some Past Programs: Mass d0 + Variant d14 – Did not take consideration of “day 0 challenge” • Poor Biosecurity + Management Control of IBV Vaccination
  • 40. Source: WP Control of IBV Need of Variant IBV Vaccines
  • 41. • Early challenge difficult to control with vaccination – Maternal antibodies are a great asset • Limited research on IBVv and maternal antibodies – Wit JJ (Sjaak) de, 2011 • Generally homologous serotypes protect well from IBV – not that good heterologous challenges • Baby chicks lack Maternal Antibodies specific for the variant present – ALMOST SPF BIRDS • Biosecurity + Adjustment of Vaccination Control of IBV Vaccination – Maternal Antibodies
  • 42. Control of IBV Vaccination – Factors • Determination of challenge – Laboratory Confirmation • Vaccine selection • Vaccine scheduling • Vaccination hatchery vs. farm • Vaccine handling / application • Control vaccine reactions • Revaccination during production – MAb • Titer Monitoring
  • 43. First vaccine Challenge Outcome Mass type Mass type Protection 793/B No protection Mass type None or Little protection Against Non–Mass Strains Control of IBV IB Live Vaccination Based on MSD
  • 44. First vaccine Challenge Outcome IB88 - 4/91 Mass type Protection 793/B No protection IB88 - 4/91 Even Revaccination With Same Vaccine Strain Will Not Give Cross Protection Control of IBV IB Live Vaccination Based on MSD
  • 45. First vaccine Challenge Outcome Mass type Protection 793/B IB88 - 4/91* IB88 - 4/91* Second vaccine Mass Mass Protection Expected to give general protection against other IBV *Second Vaccine can be combined with First Vaccine to cover opportunity window at day of age Control of IBV IB Live Vaccination
  • 46. First vaccine Challenge Outcome D388 (QX) IB88 - 4/91 Second vaccine Mass Protection Control of IBV IB Live Vaccination There is no need to develop a vaccine for each new serotype, as different “old” serotypes generally confer protection over “new” serotypes – PROTECTOTYPE CONCEPT Based on MSD
  • 48. Control of IBV Vaccination – Breeders High Challenge • Day 0 – Mass + Variant • Day 14 Mass • Week 4 - Mass • Week 6 – Variant • Week 8 – Mass • Week 12 – IB (K) Multi Variant • Week 16 – Variant + IB (K) Multi Variant Disclaimer: This is an example of IBVv vaccination program. Always consult your veterinarian before implementing a new vaccination program in your flocks
  • 49. Control of IBV Vaccination – Broilers High Challenge • Day 0 – Mass + Variant • Day 12-14 Mass Disclaimer: This is an example of IBVv vaccination program. Always consult your veterinarian before implementing a new vaccination program in your flocks
  • 50. • Classic – H120; Ma5; M41; H52; 28/86 • Variants – 793/B • Nobilis 4/91 (793/B) (MSD) • Gallivac IB88 (793/B) (Merial) • Vir 117 (793/B) (BioVac) – D274 • IB Primer (Holland + D274) (Zoetis) • Nobilis IBmulti / IB3 (MSD) • Vaksindo (M41, QX, IB 771) – Others • Conn (SP) • Poulvac IB QX (Pfizer) • Nobilis D1466 (MSD) • Ark-99 (Zoetis) • QX-like strain Korea (K2) • Australian VIC S / A3 Control of IBV Vaccination – Vaccines Available
  • 51. The Road Ahead IBV Challenges • Overlapping with Other Diseases – ND / AI / APV / Mycoplasma / Others • Diagnosis – Laboratories • Poor Biosecurity – Formaldehyde withdrawal • Vaccine Availability – Licensing / Vaccine Stock • Vaccine Misuse – Technique (i.e. eye drop) / Scheduling
  • 52. Summary - IBV • IBV continue to be reported with high prevalence in many Asian countries and causes a significant damage; however lately has improved • Diagnostics and monitoring are sometimes scarce, however utmost necessary to control the disease • Biosecurity + Vaccination are currently the most effective ways of protection • Current Vaccination programs across the area are not homogenous and are based in combination of scientific and empiric beliefs, therefore further research is needed