Main immunosuppressive pathogens and the use of immunostimulants in poultry
Pathogens with immunosuppressive effect, especially those of viral etiology, such as Gumboro disease virus or Newcastle disease virus, are responsible for large economic losses in poultry worldwide.

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Immunosuppression is a temporary or permanent pathological status of immune system dysfunction, caused by a direct or indirect damage to the immune system.
Immunosuppression promotes the onset of secondary diseases, reduces vaccine response and affects the productive parameters of animals. A wide variety of pathogens capable of affecting the immune system of birds have been reported.
This article summarizes the main immunosuppressive diseases in Europe and how to prevent them.
Main immunosuppressive pathogens in poultry
The main immunosuppressive pathogens with interest in poultry have viral etiology, and the Gumboro disease virus (IBDV), the infectious bursitis virus, the Newcastle disease virus (NDV) and the infectious bronchitis virus (IBV) are the most important ones.
Immunosuppression states can be caused by the combination of these pathogens with different stressors, such as the presence of high temperatures, the presence of mycotoxins in feed or high breeding densities.
It is essential to ensure the correct prevention of immunosuppressive diseases to avoid secondary diseases and improve the farm profitability.
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Gumboro disease or avian infectious bursitis
Gumboro disease, also known as avian infectious bursitis (IBD), was first described in the United States in 1962. It is a disease caused by the avian infectious bursitis virus, a doble stranded and un enveloped RNA virus that belongs to the genus Avibirnavirus within the family Birnaviridae.
The IBDV has as target organs the lymphoid organs, especially the bursa of Fabricius (Figure 1). The virus replicates inside the lymphoid organ, initially causing inflammation and subsequently atrophy of this organ  In birds, the bursa of Fabricius is the organ responsible for the maturation of B lymphocytes to antibody-producing plasma cells, so its replication involves lymphoid depletion that limits the immune response of chicken. At the same time, the virus affects other lymphoid organs such as the thymus and spleen, damaging the cellular immune response.

There are two presentation forms of the disease, a clinical form that appears in birds between 3 and 6 weeks of age and a subclinical form in birds with less than 3 weeks of age.
In the clinical form of the disease the birds appear lethargic, with bristly feathers around the cloaca and with whitish faeces containing a large amount of urates. The course of the disease is from 5 to 7 days, with a high morbidity and mortality that can reach 20-30%. At necropsy, serous bursitis is initially observed that progresses into fibrinous bursitis and eventually the atrophy of the bursa of Fabricius.
In the subclinical form of the disease, clinical symptomatology is not observed, however, the virus produces the atrophy of the Fabricio bursa that leads to an immunosuppression status in the affected birds.
Vaccination is the main prevention tool against this disease. In the European union usually, animals are affected by subclinical strains such us, 887 and W2512, but in same countries like in Finland (2014) virulent strains of the IBDV have been described. The most common strains of Gumboro disease virus in the Middle East and Africa are the strains 228E and W2512. However, in some countries like Egypt, specific strains and more virulent strains have been detected in recent years. For these new strains there is not a commercial vaccine available, however the use autovaccines have shown promising results.
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Newcastle disease
Newcastle disease (ND) is one of the most important diseases in poultry in the world. It is a highly contagious disease produced by avian paramixovirus type I (APMV-1), which belongs to the family Paramyxoviridae of the genus Avulavirus. It is a single-stranded RNA virus, which is classified into three pathotypes based on their virulence: lentogenic strains (less virulent), mesogenic strains (moderately virulent), and velogenic strains (more virulent) (Figure 2). Velogenic strains can be divided into a neurotropic form, associated with neurological and respiratory signs and a viscerotropic form related to intestinal lesions.

The distribution of Newcastle disease varies depending on the strains. Velogenic strains are endemic in Africa, Asia, the Middle East and Latin America where they cause severe economic losses.
APMV-1 affects all types of birds, with poultry being the most susceptible to this disease. The virus is transmitted directly by inhalation or ingestion, from the respiratory secretions and faeces of infected animals. Fomites are also a source of infection, although the persistence of the virus depends on environmental conditions. The APMV-1 persists for long periods of time in the faeces, as well as in the eggshell.
APMV-1 affects various lymphoid tissues, especially Peyer´s patches and cecal tonsils, and immune organs such as thymus or spleen, decreasing the immune response of chicken.
In Europe, Newcastle disease is a notifiable disease. Large-scale vaccination is used as a prevention measure in most European countries except Sweden, Finland and Estonia, countries considered disease-free. The most common strains of the Newcastle virus in Europe are La Sota and B1 strains.
Although a large number of preventive measures are carried out, wild birds are a reservoir of the disease that allows the emergence of new outbreaks. In the last year, cases of Newcastle disease have been identified in Russia, Belgium, Romania and Turkey.
The most common genotypes in the Middle East of the Newcastle disease virus are VI and VII and have been described in various countries including, Israel, United Arab Emirates, Iraq, Jordan, Egypt, Lebanon and Saudi Arabia. In these countries there is a great tradition of breeding birds of prey, such as falcons, where the presence of the disease has also been described. These birds are a reservoir of the disease.
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Avian infectious bronchitis
Avian infectious bronchitis (IB) is a disease widely distributed worldwide and it is a notifiable disease in the European Union. IB is produced by a gamma coronavirus, a single-stranded RNA virus, belonging to the order Nidoviridae.
Infectious bronchitis is a highly contagious and acute disease, with a short incubation period, between 24-48 hours. The virus replicates in the upper respiratory tract, causing gasping, coughing and decay of affected birds.
There are strains of the virus with kidney cells tropism, which can cause nephritis, nephrosis and urolithiasis (Figure 3). In these cases, it is common to observe a marked decrease in water intake.

In the case of laying birds, the virus causes a marked drop in laying and a higher proportion of eggs with eggshell alterations. In addition, the IBV can also affect the oviduct of young chicks. The lesion caused by the IBV can be observed in the right oviduct of the bird (at the left side while performing the necropsy). Even in healthy birds, this oviduct is atrophied, but in infected birds it is filled with water, a lesion known as hydrosalpingitis (Figure 4). In the case of layers and breeders, affected birds may develop normally but will not be able to produce eggs.
Avian infectious bronchitis causes immunosuppression in animals by making them susceptible to secondary infections, especially bacterial infections with E. coli.
Infectious bronchitis was first diagnosed in the United Kingdom in 1948. Today, it remains one of the most interesting infectious pathologies throughout the European continent, in fact, it is endemic in all those countries where intensive bird breeding takes place. The most common strain described in Europe is the Massachusetts strain (Ma5). In recent decades two new strains of the virus known as Italian-02 and QX have been described, in different European countries. The strain Italian-02 is not related with clinical symptoms, while the QX strains is related with respiratory sings in broiler older than 4 weeks of age causing a mortality between 30% to 55%.
The more common strains in Middle East and Africa are the strains 491 and H120. The wild birds play an important role in the transmission of the disease from Europe to Middle East and Africa.
Use of immunostimulants in poultry
The immunosuppression status generated by various types of microorganisms, especially the mentioned viruses, but also those generated by various types of bacteria, fungi and mycotoxins, increase the susceptibility of birds to suffer of secondary diseases, which decrease productivity and reduce the vaccine response.
A first-day vaccination is usually performed against these three viral diseases. The timing of revaccination depends on the antibody titers generated by the birds after the first vaccination.
It is important to note that the vaccine response that an animal can generate after vaccination depends on the animal’s immune status prior to the administration of the vaccine. Thus, if an animal is immunocompromised before receiving the vaccine, it will not generate an adequate vaccine response and will not be protected against the disease.
Currently, natural immunostimulant products, based on pronutrients, are available on the market, Immunostimulant pronutrients are active molecules of botanical origin that act at the metagenetic level by increasing the expression of genes related to humoral and cellular immune response.
Immunostimulant pronutrients have been shown to improve cellular immune response, stimulating macrophage and neutrophil activity and the synthesis of pro-inflammatory cytokines. At the same time, they boost the humoral immune response, stimulating the synthesis of antibodies by plasma cells (Figure 5).

Numerous studies have been conducted demonstrating how the use of immunostimulant pronutrients improves antibody titers against major immunosuppressive pathogens with interest in poultry (Graphic 1). The use of these active molecules ensures the vaccine response of animals, allowing the use of less virulent vaccine strains.

In addition, these are molecules of botanical origin that do not require withdrawal period, so they can be used to ensure the immune status of animals in the last stage of the production cycle where the use of antibiotics is not allowed.
Alquernat Immuplus is the patented product based on immunostimulant pronutrients marketed by Biovet S.A. It is a patented technology result from the research made by the R&D department of Biovet. The specific composition of Alquernat Immuplus, boost both the specific and the unspecific immune respond ensuring the vaccine response.
Conclusion
Pathogens with immunosuppressive effect, especially those of viral etiology, such as Gumboro disease virus or Newcastle disease virus, are responsible for large economic losses in poultry worldwide.
Vaccination is used as the main prevention measure against these diseases. However, it is necessary to ensure the immune status of the animals prior to the administration of the vaccine in order to obtain an adequate vaccine response.
The use of immunostimulant pronutrients, active molecules of botanical origin, stimulate the cellular and humoral immune system. Administration of these molecules promotes the synthesis of antibodies, ensuring the vaccine response. The use of immunostimulant pronutrients improves natural resistance to infections.
Immunostimulant pronutrients are marketed under the name Alquernat Immuplus of Biovet S.A.