infectious bronchitis holistic appraoch
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Transcript of infectious bronchitis holistic appraoch
Nuevos desafíos para combatir la bronquitis aviar
Jane K A Cook Consultant Microbiologist
Huntingdon, UK
Plan of talk
• The virus and disease it causes
• Variants – what they are; how they arise
• Variants - worldwide situation
• Variants – how to improve control
What is infectious bronchitis (IB)?
• A highly infectious disease of chickens of all ages and type
• Primary infection site – upper respiratory tract
• Spreads systemically in the chicken, causing: – nephritis - poor egg production and egg quality • Worldwide importance – in areas free of ND & AI
IB in broilers Respiratory infection
Section of a normal tracheal section
5 days post infection
Renal damage
Birds appear depressed
Scouring, wet litter
Kidneys pale & swollen
Urate deposits in ureters
Increased condemnation
Mortality may reach 30% in severe cases
IB in laying hens
0
20
40
60
80
30 32 34 36 38 40 42 44 46 48
Inoculated ControlAge (weeks)
% egg production
0
20
40
60
80
22 24 26 28 30 32 34 36 38 40 42
% egg production
Age (weeks)
Pale shelled eggs
Left: normal egg Right: “watery white”
Egg production Egg quality
Transmission of IBV
• Highly infectious
• Spread by aerosol and faeces
• May persists in the chicken for many weeks
• May survive in litter for many days
• All very important for IB epidemiology
Control of IBV infections
• Good hygiene
• Strict biosecurity
• Both essential, but not enough:
• Vaccination is necessary - live attenuated and inactivated vaccines used
Infectious bronchitis virus
• A coronavirus; single-stranded RNA virus
• Therefore able to change continually by:
- random mutation - genetic recombination • This results in changes in
the genome structure
• Significant when changes occur in the surface spike (S) protein
The spike (S) protein
A few amino acid changes in S resulting from mutation or recombination may result in a new IB variant
IB variants • Result from mutation or genetic mutation • A new variant is recognised in the laboratory by:
• serotyping (traditional method; now used less)
• genotyping (increasingly used)
• The number of new variants is increasing all the time
• This has serious implications for the implementation of effective control measures
Typing IB variants
Virus/ serum
USA Br. Hond Isr. Japan Taiwan S A UK
USA 560 _ _ _ _ _ _ _
Brazil _ 110 _ _ ND _ ND _
Hond _ _ 240 _ _ ND _ _
Israel _ _ _ 870 _ _ _ _
Japan _ _ _ _ 560 _ ND _
Taiwan _ _ _ _ _ 1000 _ _
S Africa _ _ _ _ _ _ 490 _
UK _ _ _ _ _ _ _ 800
Genetically by PCR – phylogenetic tree
Serologically- by neutralisation test
May not get identical results with the two methods
Value of molecular techniques to study IB variants Using reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis of S glycoprotein gene
• Use of RT-PCR enables variants to be detected much more quickly than before
• Realisation that IBV treated with phenol can be analysed was very important
• Availability of FTA cards makes it easy to send samples worldwide
PCR – a word of caution!! How do we interpret the results?
Virus
PCR Virus isolation
Disease?
A
Yes Yes Yes
B
Yes++ No Rarely
C
Yes Yes Yes
Detection of an IB variant by PCR does not always mean it is an important cause of disease
History of IB variants
• 1st report – Connecticut, USA 1950s; did not protect against the original isolate from Massachusetts
• Variants may have existed since before then
• Much work in Europe & UK in 1970s (improved techniques to study them)
• 1990- availability of molecular techniques revolutionised study of IB variants
• Now detected in increasing numbers
Variants can behave very differently!
• Majority fail to replicate
• Some persist for only a short time
• Some are found only in very small areas (maybe only one country)
• Some are found (almost) worldwide e.g. Massachusetts
• A few continue to be found for many years and are of major welfare & economic importance
IB variants in the field
More than one type may be present in a flock at the same time
Type 1
2
Year 3
4
5
6
A + + - - - -
B - + - - - -
C - - + + + +
D - - - + - -
E - - - - + +
Prevalent type may change with time
Type M
N
Flock P
S
T
A + + + - -
B - + - + +
F - + + - -
G - - - + +
Survey in USA: (Jackwood et al., Avian Diseases (2005) 49; 614)
• 1511 IB isolates obtained over an 11 year period
• 82 different variants identified
• Only 2 persisted & caused widespread disease
Evolution of IB variants
IB variants in USA - historically
Many different ones reported: • Massachusetts (first IBV to be described) • Connecticut • Holte (first to be associated with nephritis) • Grey • Iowa 97 • Iowa 609 • Florida • JMK ………………………………….. many more
IB variants in USA – current situation
1. Arkansas • First reported in 1997; still causing problems • Subtypes are now recognised • Existing vaccines still effective if used carefully
2. Delaware 072 (DE072) • Major disease in vaccinated flocks • Genetic shift & recombination is occurring • New variant has evolved (Georgia 98) • New vaccines needed!
• Other variants emerging in different states
IB variants – the European situation well studied
• Variants known since the 1980s -D274; D1466 etc
• Many different ones identified in Europe (some widespread; some in only small areas)
• 1990s – 793B (4/91; CR88) first reported and became a major problem; interesting pathology
• More recently, RT-PCR surveys have led to the detection of many more ……….
IB variants in Western Europe 2002-2006 (RT-PCR)
IB genotype % distribution Mass 24.1 793B 33.8 It02 12.6 QX 10.0 D274 8.5 D1466 2.3 Arkansas 6.0 B1648 0.3 Others 2.5
From: Worthington et al, (2008).Avian Pathology, 37, 247
* D1466, only from 2005
IB variants from the Middle East
Israel
• Variant I. >90% similar to 4/91/793B (Jackwood et al.)
• Variant II. 80% similar to D274 (Jackwood et al.)
Jordan & Iran • 4/91–like viruses detected by RT-PCR
Egypt • Egypt/Beni-Seuf/01. Also found elsewhere in the region. (In Israel called IS/885)
IB variants in Asia Work being done in many countries, including: • Malaysia, Singapore and Taiwan Local variants detected as well as ones found elsewhere • Japan • Thailand Variants “unique” to Japan/Taiwan as well as ones similar to those found in USA & China, (Mase et al., Shieh et al., 2004; Hwang et al., 2004)
• Korea
• China
IB in Asia - Korea
• IB problems since at least 1980s
• Mass vaccination initially successful
• Now – increased incidence of kidney problems in vaccinated flocks
• At least 4 local IB variants recognised
IB in Asia - China
• IB probably under control before 1980s
• Many groups now working on IB
• Large amounts of data are being produced
• Local variants as well as ones found elsewhere
• Globally important variants have come from this area, including QX and Q1
QX – an IB variant of global concern
• First described in China; then spread to Russia
• Now present in many European countries
• A cause of nephritis in broilers
• “False layers” after infection at a very young age
• Birds appear healthy during rear but infection causes permanent damage to the oviduct • Egg laying performance is severely affected
• Birds showed peculiar stance (penguin-like) and
pendulous abdomen
• Poor production (30%- 55%) in “healthy” flocks • Post mortem: frequently cystic oviducts with watery
content (one litre), or (partially) atrophic oviducts with large cystic dilatations
• Thin, transparent oviduct wall in cystic areas
• Functional, normal ovaries
Infectious Bronchitis QX in layers
Infection with IB QX
QX – an IB variant of global concern
• Nephritis may now be more important than the effect on egg laying performance
• This is now reported in many countries worldwide (not USA)
• Question: Is better vaccination preventing very early infection?
• Point to remember: QX is different from Q1 (both 1st described in China!)
IB variants in Australia
• Because Australia has maintained ‘closed’ boarders, IB has evolved uniquely
• Many different variants, found only there (and possibly New Zealand)
• Different from those in all other countries
IB variants from different areas showing wide diversity
De Wit et al., Avian Pathology, 2011
Taiwan
Thailand
4/91/793B
Australia
China (Q1)
China (QX)
History of IB variants in Latin America
• 1950s: IB reported in Brazil (Hipolito)
• 1960s: 1st variant (Arkansas) reported in Brazil (Branden & Da Silva) • 1976: IB first reported in Chile (Hidalgo et al)
• 1980s: 1st report of variants in Chile (Hidalgo et al)
• 1990: More variants; Mass vaccines gave poor protection (Cubillos et al.)
• Mexico - Several unique variants (Escorcia et al., 2000)
• Honduras – Variant identified; Mass vaccines do not protect (Cook et al.,,1999)
• Colombia – Several variants identified (Alvarado et al. 2005)
• Chile - Variants a cause of major concern
• Brazil – many different variants; Mass vaccines give poor protection (di Fabio, et al., 2000; Abreu et al, 2006; Villarreal et al., 2007a; b; Montassier et al, 2008; Villarreal et al., 2010)
Variants from Latin America
Example of genotyping Brazilian IB isolates
Villarreal et al., Avian Diseases. (2010)
Some group with 4/91
Some group with Mass
Some are unique to Brazil
IB in Chile since late 2000s
The problem: • Broilers: respiratory disease, high condemnation
rates, nephritis
• Breeders: respiratory problems, poor egg production, enteric problems
• Current vaccination programmes not effective
• IB variant Q1 commonly identified by RT-PCR
What about the current situation in South America?
• Argentina – 3 variant groups identified in 2000s (Rimondi et al., 2009)
• IB now causing major problems in Argentina, as in
Chile
• Situation may be similar elsewhere, but research has not been undertaken in all countries
• Many variants identified, but frequently Q1
What can be done to improve control of IB variants?
First things: • Attention to improving management and biosecurity • Careful use of available vaccines
This may not be enough: • Apply the “protectotype” concept • Consider using an IB vaccine to a variant strain in the
programme • Used successfully in many areas (Arkansas in USA;
4/91-type elsewhere)
The protectotype concept
• IB variants arise because of very small changes in the genetic makeup of the virus
• Most of the virus has not changed
• Good protection using vaccines already available
• Use two very different live-attenuated IB vaccines (Must be strong immunogens and genetically different)
• Mass & 4/91-type meet these criteria (probably others too, such as Arkansas in USA)
How does it work?
Day old 2 weeks Mass None None 4/91-type Mass + 4/91-type None None None
Vaccination
Challenge at 5 weeks
Assess protection 5-7 days later based on damage to ciliated epithelium of the trachea (ciliostasis test)
Normal IB infected
Ciliostasis test
Give a score to the damage and quantify protection
Benefit of using two different IB vaccines in protecting against variants from Asia
0
20
40
60
80
100
No vaccine Ma5 IB 4/91 Both vaccines
% Protection
IB vaccines used
0
20
40
60
80
100
No vaccine Ma5 IB 4/91 Both vaccines
Protection against challenge with an IB variant from Honduras
0
20
40
60
80
100
No vaccine Ma5 IB 4/91 Both vaccines
% Protection
IB vaccines used
Protection against challenge with a Mexican IB variant
0
20
40
60
80
100
No vaccine Ma5 IB 4/91 Both vaccines
% Protection
IB vaccines used
Protection against challenge with a Brazilian IB isolate
0
20
40
60
80
100
No vaccine Ma5 IB 4/91 Both vaccines
% Protection
IB vaccines used
Timing of IB vaccinations
0
10
20
30
40
No vaccine Both(do) M(do);B(2w)0
10
20
30
40
No vaccine Both(do) M(do);B(2w)
Homologous challenge Heterologous challenge
Heterologous challenge; benefit from delaying 2nd vaccination
How we can improve control of IB variants
• Optimise the use of the IB vaccines already licensed
• Consider using a second IB vaccine in the programme
• Ideally, do not introduce vaccines to strains not already present
• Sometimes this may be necessary
• Ideally, leave 2 weeks between the 2 vaccines, but in some situations, it is necessary to give both together at day-old and this is beneficial
None
Ma5(day-old)
Ma5+4/91
0
20
40
60
80
100
Isolate 1 Isolate 2 Isolate 3 Isolate 4
% Protection
Protection against challenge with recent IB variants isolated in Chile
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
Conclusions • IB variants are a global problem
• Because of the type of virus that IBV is, new variants will continue to occur
• Some will have limited geographical distribution/ limited importance
• Others will be found in many countries
• Some will disappear quickly
• Some will persist for many years, causing economic and welfare problems
• How can we deal with the problem……….?
What can we do about IB variants?
• Improve management practices
• Good biosecurity
• Careful use of the vaccines available
• Learn from experiences in other countries because a new vaccine may be needed
• Continue to watch the situation carefully
• We have to learn to live with the problem!
Thank you for your attention