Diagnostic kits only available for infectious bronchitis virus (IBV). For IBV antibody detection, commercial ELISA kits are available worldwide. Hemagglutination antigens are available for some of the serotypes. Virus neutralisation tests are always in-house methods, availability is poor. Commercial PCR kits (especially genotype specific tests) are available in many countries. Many in-house PCR’s are used.
See Section “Commercial diagnostic kits available worldwide”. List of commercially available tests (Diagnostics for Animals)
See Section “Commercial diagnostic kits available worldwide”.
No specific SOP’s or standards available. IBV is a moving target, new strains are detected every year, updating regularly is vital.
No specific SOP’s or standards available. Many in-house PCR’s are used.
Good. Many laboratories perform ELISAs for the detection of antibodies, the number of laboratories that perform PCRs is increasing.
No DIVA tests available. DIVA tests would be helpful to distinguish the live vaccines and the field strains of the same genotype. The same for the antibodies.
Tests that can reliably distinguish vaccines from field strains. Tests that indicate the level of cross-protection between the used vaccine(s) and the field strain.
Vaccines are only available for IBV. No vaccines are available for other AvCoVs. Concerning IBV many live-attenuated vaccines (administered by spray or in drinking water) and inactivated vaccines (administered by injection) are available. The most widely used of the live attenuated vaccines is of the Massachusetts (see list below). DNA vaccines, sub-unit and peptide vaccines, virus-like particles, vector-based vaccines and reverse genetic vaccines have also been developed as proof of concept however, none have yet been commercialized.
Many live attenuated and inactivated vaccines are available. Non-exhaustive list of vaccines available via this link.
Live attenuated vaccines: Most provide adequate protection against their homologous challenge virus; however, protection against heterologous challenge is variable. This can be improved by administering different live vaccines at the same time or in sequence with several weeks in between. This heavy use of live vaccines however could contribute to the continual genetic evolution of IBV.
Killed vaccines: Effective in boosting immune responses following vaccination with live attenuated vaccines but do not provide adequate protection alone. Method of delivery (intramuscular or subcutaneous injection) is complicated and time consuming.
Reverse genetic Vaccines : Are promising as proof of concept under experimental conditions, by nature have homogeneous viral genetic populations which should reduce viral genome evolution through selection. However are costly to produce and fall under GMO regulations.
Many vaccines already in circulation and more will come (see Section “Commercial vaccines authorised in Europe”).
No use of bivalent live attenuated IBV vaccines in France. Use of combinations of live vaccines is common in many areas of the world.
In general, many farm workers shower in and out and wear farm specific clothing that stays at the farm and is washed there.
This could be further improved: Gloves, face masks, temperature checks for workers are routinely done on many farms to prevent cross-species infection such as flu.
The list of references in this section is non-exhaustive.
Many different “molecular” vaccines have been developed and tested as proof of concept including
The ability to specifically design the molecular composition of these vaccines means that they have high potential as DIVA vaccines.
Many of the published alternatives also have major disadvantages compared to the present commercially available vaccines.
No curatives (antivirals) available.
Gammacoronavirus IBV and TCoV evolve quickly, would an antiviral treatment induce resistance to this drug easily?
Retailers and authorities should accept is before it could be used.
Only useful when very inexpensive (few cents), application by drinking water, feed or spray. Withdrawal period should be very short as well.
There are no antivirals available or allowed for food producing animals. New legislation would have to be developed.
See section “Regulatory & policy challenges to approval”.
Treatment should be very inexpensive (cents per chicken) to be attractive.
See section “Regulatory & policy challenges to approval”.
Tools for genotyping AvCoVs should be based on the parameters proposed by the European COST action on avian coronaviruses. This means amplification and sequencing of the full S1 ORF (Valastro et al., 2016b).Tools that could distinguish vaccines and field strains of the same genotype.
It would be of interest in ELISA development to have strain specific tests.
Unknown, this would depend on the type of test developed.
Unknown, this would depend on the cost of the technology required and its availability.
Good communication between diagnostic laboratories and field veterinarians, so that any new tests meet demands.
Attempts should be made to obtain the complete genome sequences or as much genetic data as possible for the identified viruses.
Development of on-site tests to identify AvCoV infection would be very useful. However, these should be capable of distinguishing wild type virus from vaccine (certainly in broilers). Alternatively, positive on farm samples could be further submitted to a lab for sequencing to differentiate field from vaccine virus.
Lack of complete genome sequence data for field and vaccine strains.
RT-PCR tests are available and sensitive. Showing freedom of virus would require sampling every bird in a flock.
Safe, highly effective, stable, inexpensive product that can be administered by mass-application unless a single vaccination in the hatchery would be highly effective and sufficient for protection), inducing high and long-lasting cross-protection against many different IBV strains, no or low interference with vaccines against other pathogens.
Traditional live attenuated vaccines usually take about 4-7 years to market. Inactivated IBV vaccines can be developed faster, however, these inactivated antigens are usually part of a multivalent vaccine (including other pathogens). Changing or adapting the IBV antigens in a vaccine means that all components have to be retested again: very costly and very time-consuming.
GMO vaccines (e.g. vector vaccines) for IBV are not yet on the market as the efficacy of these products has been moderate compared to the existing attenuated vaccines. Europe is also reluctant with accepting GMO vaccines compared to other parts of the world. Organic farming doesn’t accept GMO vaccines.
Very costly, over 1 million euro (easily).
Basic knowledge about the basis of cross-protection might make it possible to develop smartly designed vaccines that are more cross-protective than the existing vaccines.
Fundamental knowledge is lacking.
Demands for using medicines in chickens are very high and increasing. Safety, withdrawal times, cost and application route (oral) are important considerations. See discussion in relation to antibiotic free production.
Even if there would be effective and very safe pharmaceuticals that can be applied at very low costs and in via a convenient application route, the demands of the customers (retailers, society, human health) go the other way.
IBV is mutating at a high rate, development of resistance is a risk with any new treatment.
Unknown, many years before it could be on the market.
Unknown, very high.
Unknown, however strict assessment of the potential for new pharmaceuticals to generate escape mutants should be a priority.
There are currently three main coronaviruses (CoVs) affecting poultry industry IBV, TCoV and GfCoV, these are classified as follows according to the ICTV (2020):
The family Coronaviridae within the order Nidovirales consists of two subfamilies: (1) Orthocoronavirinae comprising the genera Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus and (2) Letovirinae comprising the genera Alphaletovirus. Avian coronaviruses (AvCoVs) are of the genera gamma and delta. Those in poultry are almost uniquely of the genus Gammacoronavirus and those of small wild birds of the genus Deltacoronavirus. To date the principal AvCoVs are (See also Table below):
These three viruses share a common genetic backbone but possess highly divergent genes encoding their surface glycoprotein (S) (Brown et al., 2016)
CoVs are enveloped and pleomorphic with an overall diameter of 60-120nm. Most CoVs contain four structural proteins: a large surface glycoprotein (spike or S protein visible as the corona), a small membrane protein (E), an integral membrane glycoprotein (M), and a nucleocapsid protein (N).
Table 1. Coronaviruses affecting poultry
IBV: IBV’s have now been isolated in all parts of the world where chickens are farmed and exist as many different antigenic and genotypes (Sjaak de Wit et al., 2011; Valastro et al., 2016a). All have been isolated from chickens and most cause respiratory problems in this species however renal and genital diseases can also occur which can vary in severity according to the IBV strain involved. Severity of respiratory disease is usually higher in chickens bread for consumption (broilers) than in those used for reproduction or egg production (layers). In layers a drop in egg production can occur and this is usually more notable in older birds.Some isolates of IBV have a particular tropism for the kidney and are often associated with higher rates of mortality, especially at young age. Several IBV strains have been shown to replicate in the enteric tract however, the clinical relevance of this seems to be limited.
TCoV: In comparison with IBV there are very few TCoV isolates available for characterization. One virus has been isolated in Europe (France) and the rest have been isolated in the United states of America. These viruses were isolated from the intestines of turkeys with multifactorial enteric disease.Isolates from the USA have an IBV backbone of US origin with an S gene of unknown origin while the European isolate has an IBV backbone of European origin and also an S gene of unknown origin.
GfCoV: In line with TCoV there are a limited number of GfCoV isolates compared to IBV. These have all been isolated from the intestines of guinea fowl with fulminating enteritis. Disease in this species, as the name suggests, is almost always associated with mortality.Isolates share the same IBV backbone as the European TCoV with an S gene of unknown origin closely related to that of North American TCoVs.
As with other viruses of the family Coronaviridae: AvCoVs have been shown to survive for up to 10 days at an ambient temperature of approximately 20°C (Guionie et al., 2013) and for up to 20 days at lower temperatures (+4°C)
Most common disinfectants used in the poultry house inactivate AvCoVs. A broad overview of the effect of biocidels on CoV’s is listed in a review by (Kampf et al., 2020a, 2020b). CoV is more stable at a low pH than at a high pH. Survival times are increased when in litter containing faeces (Jackwood & de Wit, 2020).
None reported to date.
Chickens are the natural reservoir for IBV.Turkeys for TCoV and Guinea fowl for GfCoV.IBV-like AvCoV’s (often just by PCR) have been detected in pheasants, peafowl, turkeys, teal, geese, pigeons, ducks and some other wild bird species (Cavanagh, 2005)Studies have shown that chickens can be susceptible for TCoV (Gomes et al., 2010).
IBV is very infectious, transmission parameter (R0) is 20 (De Wit et al, 1998). Transmission can be by aerosol, faeces and fomites (mechanical spreading).
TCoV is also extremely infectious with one infected turkey infecting another every 2.5h under experimental conditions. The virus is also infectious beyond the limits of detection by real-time PCR (Brown et al., 2018) and is excreted as infectious virions for at least six weeks (Brown et al., 2018).Transmission is by oro-fecal route.
GfCoV like TCoV is shed in faeces and the development of clinical signs in infected guinea-fowl flocks suggest that this virus also spread easily. To date no experimental data on transmission rates and routes are available.
IBV: In young birds (e.g. broilers) clinical signs most commonly seen include respiratory problems (conjunctivitis, rales), depression, drop in feed consumption and growth. Morbidity is usually 100%. Depending on the circumstances, secondary bacterial infections will manifest and contribute to the increased mortality and condemnation rates. Some isolates of IBV have a particular tropism for the kidney and are often associated with higher rates of mortality due to nephritis and wet litter (drop in feed consumption increase of water consumption).In layers and breeders, a drop in feed consumption, egg production and egg quality (including hatchability for breeders) can occur and this is usually more notable in older birds. Clinical signs suggestive of respiratory or renal disease are usually rare.
TCoV: Acute, highly contagious enteric disease characterized by depression, anorexia, diarrhea and decreased weight gain. Morbidity is 100% and turkey breeders show a drop in egg production.
GfCoV: Fulminating enteritis, severe depression, anorexia diarrhea and decreased weight gain, often combined with high mortality. Morbidity is 100%.
IBV: Respiratory signs can appear within 1-2 days post infection
TCoV: 2-3 days
GfCoV: No data available.
IBV: Mortality due to IBV infections that have not been complicated due to secondary infections is usually low except when nephritis occurs in very young birds without sufficient protection.
TCoV: Uncomplicated infections usually are not associated with mortality. Under field conditions, mortality can be high depending on the age of the birds, co-infections and differences in management practices.
GfCoV: Unknown, no controlled experimental infections performed to date. Mortality due to the fulminating enteritis and complicating factors can reach 20% per day (Liais et al., 2014b).
Controlled studies are required to gain knowledge on the pathogenicity of strains of GfCoV in absence of complicating factors.
IBV: Shedding of IBV occurs via aerosol and faeces. Depending on the strain involved and the level of protection of the infected chicken, shedding by the respiratory tract varies from 1 to a few weeks. The length of faecal shedding depends on the strain and level of protection; it varies from 1-2 weeks to a few months.
TCoV: Shedding in faeces can occur for a number of weeks up to 2 months.
Shedding kinetics of IBV can vary significantly between different strains and serotypes. There is less information about the shedding kinetics of different TCoV strains and hardly any data on shedding of GfCoV.
IBV: In most cases animals recover from infection after 1-2 weeks but this can vary with strains and type of bird (broiler, layer, breeder, etc), involvement of co-infections and housing conditions. Thus, some IBV infections will have more impact on welfare than others. Prevention and control measures through non-invasive vaccination, reduced numbers of birds, and strict hygiene commonly only improve animal welfare.
TCoV and GFCoV: The multifactorial enteric diseases involving these viruses can result in high mortality. However, these cases are uncommon.In line with IBV, prevention and control measures through reduced numbers of birds and strict hygiene only improve animal welfare.
No reports of AvCoVs having an impact on endangered wild species.
Slaughter is not necessary according to EU rules.
IBV is widespread worldwide. In many areas, a number of genotypes are present. Some genotypes are present in a number of continents (like Mass, QX, 793B), others are locally restricted.
IBV: This virus is endemic, commercial poultry is vaccinated against IBV globally. In case of an introduction of a antigenetically new strain for which the used vaccination program does not raise sufficient protection, such a strain can spread rapidly through the region.
TCoV: This virus is found in most areas where turkeys are farmed.
GfCoV: The frequency of outbreaks is unknown as there are only few studies. The virus has only been described in 2010. Associated fulminating disease in Guinea fowl is uncommon.
IBV: Infections occur the entire year but clinical problems in the form of respiratory disease are seen more in seasons where climate control is more difficult (restricted ventilation of the house in case of cold, seasons with high variation in day-and-night temperature.
TCoV: Infections occur during the whole year.
GfCoV: As yet unknown, very few studies.
IBV: IBV is very infectious enveloped virus. It can spread by air but not very far due to the sensitivity to inactivation. Spreading by transport of infected birds or feces can cause spread over bigger distances. The extent of spatial spread is also depending on the success of vaccinations and vaccination programs on the farms around the outbreak.
TCoV and GfCoV: No vaccines are available for TCoV and GfCoV, the viruses can spread in an area depending on the level of biosecurity.
Occurrence of IBV, TCoV and GfCoV strains is often transboundary.
IBV: Principally, direct contact of infected birds with susceptible birds. Aerosol and or oro-faecal transmission.
TCoV: Principally, direct contact of infected birds with susceptible birds. oro-faecal transmission.
GfCoV: Most likely direct contact of infected birds with susceptible birds and oro-faecal transmission due to the enteric nature of the virus and its isolation from intestinal tissues and content. However, as of yet there is no experimental data.
Vertical transmission of IBV seems to be very uncommon but not impossible (Cook & Garside, 1967). Also see Section “Reservoir (animal, environmental)“.
Poor hygiene, high density flocks, poor vaccination (in the case of IBV) may complicate pathogen spread.
For young birds, the local immunity is the major means of protection. Neutralizing antibodies can be detected in the blood from 2-3 weeks after infection (De Wit, 2000). In young birds, the correlation between humeral antibodies and protection is not strong, seronegative birds can be well protected post vaccination. For layers, there is a much higher correlation between detection of hemagglutinating or neutralizing antibodies against the challenge strain and level of protection against a drop in egg production post challenge (Box et al., 1988).
For IBV, many antibody tests are available. No commercial tests are available for detection of antibodies to TCoV and GfCoV. TCoV ELISA’s have been described. Some use IBV as antigen, others recombinant TCoV nucleoprotein or spike protein (Guy, 2020).
CoV’s are enveloped viruses and therefore sensitive to treatment with soaps and disinfectants.
Cleaning, disinfection and biosecurity.
Many diagnostic tests are available for IBV. For TCoV, PCR tests are available, the availability of antibody test is limited due to the lack of commercially available ELISAs.For GfCoV, little diagnostics are available due to the small market.
For IBV, live attenuated and inactivated vaccines are widely used (see section 2). For TCoV and GfCoV, no vaccines are available.
There are no treatments available.
IBV, TCoV and GfCoV can be spread by infected manure and fomites. Short distance airborne infections are possible for IBV.
IBV is endemic worldwide.
Vaccination is needed to control IBV.
Eradication of IBV and TCoV has never been successful, prevalence is also far too high.
Eradication would be extremely costly due to the high prevalence.
IBV, TCoV and GfCoV are not zoonotic.
IBV, TCoV and GfCoV are not zoonotic.
In general, both IBV, TCoV and GfCoV are capable of having a major impact on production of chicken, turkey and guinea fowl, respectively.
According to the World Bank, IBV is the second most damaging virus for the global poultry production after Avian Influenza (WorldBank & TAFS-Forum, 2011).
No direct impact of public control measures.Biosecurity measures need to be in place for a number of diseases and not just CoVs including all-in, all-out principles, change of clothes and boots, strict disinfection regimens, limit to visitors, disinfection of incoming vehicles.Costs of vaccination for IBV. A very high percentage of poultry flocks worldwide are vaccinated for IBV.
Indirect impact mainly by disruption of production.
While it is likely that improvements in CoV vaccines and diagnostic tools could be achieved, new approaches should be focussed on delivering broad protection and identifying the optimal diagnostic window.
AvCoVs, continue to cause severe losses to the poultry industry despite (in the case of IBV) the use of different vaccines and vaccine programmes over the last 70 years. AvCoVs seem to have a strong capacity for rapid evolution and perhaps this is why they continue to cause problems. However, fundamental studies (epidemiological and experimental) unravelling how and why AvCoVs, especially IBV, can create such diversity are lacking. Thus more AvCoV studies are required that focus on genomic evolution, its dynamics and the driving factors involved (environmental, physical etc) so that better control measures can be conceived.
To help answer these questions the developments in molecular and serological laboratory tests suggested above would be very helpful.
Paul Brown, French Agency for Food, Environmental and Occupational Heath Safety (ANSES), France – [Leader]
Sjaak De Wit, Royal GD and Veterinary Faculty of Utrecht University, The Netherlands
Tanja Opriessnig, The Roslin Institute, University of Edinburgh, UK and Iowa State University, USA
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AvCoV Infections can occur during the whole year but clinical problems in the form of respiratory disease are seen more in seasons in when climate control is more difficult (restricted ventilation of the house in case of cold, seasons with high variation in day-and-night temperature.
IBV, TCoV and GfCoV are seen in all climates.
Not relevant for the viruses themselves. However, the severity of infection also depends on the occurrence of co-infections. Several co-infections such as Coryza are sensitive to climate change.