New Castle Disease

NEWCASTLE DISEASE

Avian Distemper Ranikhet Disease Tetelo Disease Korean Fowl Plague Avian Pneumoencephalitis

Newcastle Disease

1. Definition 2. Etiology3. Epidemiology 4. Transmission5. Clinical Signs6. Post Mortem Lesions

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Definition

Newcastle disease is defined as an infection of birds caused by a virus of avian paramyxovirus serotype 1 (APMV-1) that meets one of the following criteria for virulence:

Definition

1. The virus has an intracerebral pathogenicity index (ICPI) in day-old chicks (Gallus gallus) of 0.7 or greater.

Or 2. The virus has multiple basic amino acids have been

demonstrated in the virus at the:– C-terminus of the F2 protein. – N-terminus of the F1 protein, which is phenylalanine at

residue 117.

Multiple Basic Amino Acids

Definition

The term ‘multiple basic amino acids’ refers to at least 3 arginine or lysine residues between residues 113 to 116.

Molecular Basis Of Pathogenicity Of ND

During replication, NDV particles are produced with a precursor glycoprotein, F0, which has to be cleaved to F1 and F2 for the virus particles to be infectious (Rott and Klenk 1988).

This post translation cleavage is mediated by host cell proteases (Nagai et al. 1976a).

Trypsin is capable of cleaving F0 for all NDV strains.


The cleavability of the F0 molecule was shown to be related directly to the virulence of viruses in vivo (Rott, 1979; Rott, 1985).

This allows these viruses to spread throughout the host, damaging vital organs.


Since the initial studies comparing the deduced amino acid sequences at the cleavage site of the F0 precursor of a number of virulent and avirulent ND strains (Collins et al, 1993), a large number of studies has confirmed the presence of multiple basic amino acids at that site in virulent viruses.


In highly virulent viruses, the sequence has been 113/RQK/RR ↓ F117.

In contrast, viruses of low virulence usually have the sequence 113K/RQG/ER ↓ L117.


The major influence on the pathogenicity of NDV is:The amino acid motif at the F0 cleavage site, the presence of basic amino acids at positions 113, 115 and 116 and phenylalanine at 117 in virulent strains means that cleavage can be effected by protease, proteases present in a wide range of host tissues and organs.


For viruses of low virulence, cleavage can occur only with proteases recognizing a single arginine, i.e. trypsin-like enzymes.

Such viruses are therefore restricted in the range of sites where they are able to replicate to areas with trypsin-like enzymes, such as the respiratory and intestinal tracts, whereas virulent viruses can replicate in a range of tissues and organs resulting in a fatal systemic infection (Rott, 1979).

Intra-Cerebral Pathogenicity Index

Intra-Cerebral Pathogenicity Index

ICPI Intra-Cerebral Pathogenicity Index

1. Fresh infective allantoic fluid with a HA titre >24 (>1/16) is diluted 1/10 in sterile isotonic saline with no additives, such as antibiotics.

2. 0.05 ml of the diluted virus is injected intracerebrally into each of ten chicks (24-40 hrs age) hatched from eggs from SPF flock.

3. The birds are examined every 24 hours for 8 days.

Criteria For NDV Pathogenicity

3. The birds are examined every 24 hours for 8 days. 4. At each observation, the bird is scored:

0 if normal. 1 if sick. 2 if dead.


The intracerebral pathogenicity index (ICPI) is the mean score per bird per observation over the 8-day period.

The most virulent viruses will give indices that approach the maximum score of 2.0, whereas lentogenic and asymptomatic enteric strains will give values close to 0.0.

Examples Of ICPI Of Several NDV Isolates

Virus Product ICPI

Ulster 2C Poulvac NDW 0.04 to 0.23

PHY.LMV.42 Cevac® VITAPEST L 0.16

Hitchner B1 Many 0.18

Clone 30 Nobilis® ND Clone 30 0.25

VG/GA AVINEW® 0.30

La Sota Many 0.4

Komarov 1.41

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Newcastle Disease Virus

Newcastle disease (ND) is caused by specified viruses of the avian paramyxovirus type 1 (APMV-I) serotype of the genus Avulavirus belonging to the subfamily Paramyxovirinae, family Paramyxoviridae.


APMV-1 isolates can also be separated into two clades;Class I Class II

Based on the genetic relationship between viruses.


Class I isolates have been found mainly in wild waterfowl, and are usually of low pathogenicity.

The vast majority of APMV-1 strains belong to class II, which is divided into at least 9 genotypes (I to IX).


Members of this family have a single stranded, linear, RNA, with an elliptical symmetry.

The total genome is roughly 16,000 nucleotides. Replication of the virus takes place in the cytoplasm of the

host cell.


The most important pathogen for poultry is the Newcastle disease virus, which is APMV-1.

APMV-2, APMV-3, APMV-6, and APMV-7 also cause disease in poultry.


IVPI Intra-Venous Pathogenicity Index

For 6 weeks susceptible chicks. Minimal score = 0.0 for Lentogenic strains. Maximal score = 3.0 for Velogenic strains.


MDT in 9 days embryonated chicken eggs.

Embryo mortality:40 : 60 hours in Velogenic strains60 : 90 hours in Mesogenic strains> 90 hours Lentogenic starins

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Morbidity/Mortality

Morbidity: up to 100% Mortality: 90%

Varies greatly depending on:1. Virulence and strain.2. Avian species and susceptibility of host.3. Environmental conditions.4. Vaccination history.

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Virus Transmission

APMV-1 can be transmitted by inhalation or ingestion (fecal/ oral route).

Birds shed virus in both feces and respiratory secretions. Some birds excrete APMV-1 for 1-2 weeks.

Virus Transmission

The virus survives for long periods in the environment especially in feces, and may be transmitted through:

1. Direct contact with:1. Feces or respiratory secretions.2. Carcass of infected bird.

2. Indirect contact with contaminated:1. Feed and water.2. Equipment.3. Human clothing.

Virus Transmission

Incubation period2 to 15 days with average of 5 to 6 days, depending on

severity of the strain and susceptibility of birds.

Human Transmission

People can become infected with vNDV and show signs mild conjunctivitis.a) Resolves quickly.b) Virus shed in ocular secretions for 4-7 days.c) Infected individuals should avoid contact with avian

species during this period. Lab workers and vaccination crews most at risk. No cases from handling or consuming poultry products. No human-to-human spread.

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CLINICAL SIGNS

1. Drop in egg production.2. Numerous deaths within 24 to 48 hours.3. Deaths continue for 7 to 10 days.4. Surviving birds may have neurological or reproductive

damage.

CLINICAL SIGNS

1. Edema of head, especially around eyes.2. Greenish, dark watery diarrhea.3. Respiratory and neurological signs.4. Neurologic signs may include:

a) Muscle tremors.b) Drooping wings.c) Dragging legs.d) Twisting of the head and neck, circling, depression,

inappetence, or complete paralysis.

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POST MORTEM LESIONS

There are no specific diagnostic post mortem lesions seen with vND.

Gross lesions can be very similar to highly pathogenic avian influenza, so laboratory isolation and identification is important for a definitive diagnoses.

POST MORTEM LESIONS

Lesions may include: 1. Edema of the interstitial tissue of the neck, especially near the

thoracic inlet2. Congestion and sometimes hemorrhage on the trachael

mucosa3. Petechiae and small ecchymoses on the mucosa of the

proventriculus

POST MORTEM LESIONS

4. Edema, hemorrhage, necrosis or ulceration of lymphoid tissue in the intestinal mucosa including Peyer’s patches

5. edema, hemorrhages, or degeneration of the ovaries. 6. Edema or necrosis of the cecal tonsil and lymphoid tissue of

the intestinal wall is especially suggestive of ND.

NEWCASTLE VACCINATION

Newcastle Vaccination 1. Introduction

2. Types of ND vaccines1. Live

1. Apathogenic strains.2. Lentogenic strains,

conventional.3. Lentogenic strains, cloned.4. Mesogenic strains.

2. Inactivated vaccines.3. Recombinant vaccines.

Types of ND Vaccines

Newcastle Vaccination

Before 1933• Vaccination with the inactivated

virus was considered a possibility for the control of ND at the time of the apparent emergence of the virus.

After 1933• in England, an attenuated live

vaccine was produced which was called strain H.

• Later, the naturally occurring USA isolates of low virulence, Hitchner B1 (HB1) and La Sota, became the most used veterinary vaccines throughout the world.


The principle of vaccination against a viral disease is well-known: To elicit an immunological response against the virus in a way

that does not cause the disease.


• Take the virus, kill it, and then inject it into the bird.Inactivated vaccine

• Select a naturally occurring virus that is not virulent enough to cause serious disease, and infect the birds with this virus.

Live vaccine

• Take a non virulent natural virus and select a clone from the virus population with desirable properties, such as lack of vaccine reactions.

Cloned live vaccine

• Genetically engineer a vaccine by, for example, taking part of the genetic material of the virus that codes for a surface antigen, and inserting this into another.

Recombinant vaccine

Immunity Against ND

• Protects young bird through circulating Ig.• Half life span 4.5 days.

Passive immunity (MDA)

• Secretory (IgA, IgG) (resp. + Intes. + HG.)• Cell mediated.• Appear as early as 2-3 days post vaccination.

Active Immunity

• Starts 6-8 days post vaccination.• Maximized 3-4 weeks post vaccination.• Declined much slower than development .• Directed against HN and F glycoprotein surface antigen

Humoral immunity

Live Vaccine Vs Inactivated

Live vaccines differ from inactivated vaccines in that they can replicate in the host.


Advantage:1. It is not necessary to vaccinate every bird individually

Vaccine virus can spread on its own from one bird to another. 2. Easy application

They can be applied to the drinking water or with an eye-dropper.


Disadvantage: 1. Post-vaccine reaction– Since an infection with a live virus is involved, this may

result in clinical signs because of the virulence of the vaccine virus or by exacerbating other organisms that may be present, especially in the respiratory tract.

– The severity of this reaction depends on the vaccine strain (Westbury et al., 1984) and the presence of concurrent infection with other pathogens.

Live Vaccines

Although NDV has essentially only one serotype, there is a wide difference in the pathogenicity of different strains, ranging from those that cause virtually no signs to those that kill within a few days.

Value Of Using Live Vaccine


1. It is based primary on stimulation of the local immunity in the Harderian gland and in the upper respiratory tract and/or the gastrointestinal tract.

2. The development of humoral immunity occurs secondly.3. Vaccination via the eye-drop method with Hitchner B1 vaccine

at day one increases the protection to 90% as a result of enhancing the local immunity which adds the passive humoral immunity.


4. The maternal antibody present on day one provide 75% protection.

5. Moreover, the same vaccination to chicks which have no maternal antibodies increase the protection on day one from 0% to 60% (Bennejean et al., 1978).

Apathogenic Enteric Vaccines

Apathogenic enteric strains :VG/GA (Avinew from Merial) PHY.LMV.42 (Vitapest from Ceva) Ulster 2C (Poulvac NDW from FORTE DODGE)– Low virulence – Enteric tropism nullifies the risks of any post-vaccinal

reaction associated with their use.

ICPI

0.05ml of a diluted virus Injected intracerebrally Into 10 one-day-old chicks.

The birds are examined every 24 hours for 8 days.

At each observation the birds are scored: 0 if normal. 1 if sick. 2 if dead.

Virus Product ICPI

Ulster 2C Poulvac NDW 0.04 to 0.23

PHY.LMV.42 Cevac® VITAPEST L 0.16

Hitchner B1 Many 0.18

VG/GA AVINEW® 0.30

Clone 30 Nobilis® ND Clone 30 0.25

La Sota Many 0.4

Komarov 1.41

Assessing Apathogenic Pneumotropic Vaccine Strains

Conventional Lentogenic Vaccines

The level of vaccine reaction is an important consideration for intensive commercial poultry.


HB1 Because HB1 has very mild vaccine reactions, it has been

widely used for initial vaccination of intensive poultry.


La Sota La Sota produces moderate vaccine reactions, especially in

immunologically naive birds and is not usually recommended for primary vaccination.

In theory, La Sota would also be unsuitable for vaccinating a multi-age population. This is because the virus spreads and it is not practical to isolate the adults from the chicks.


In practice, the degree of reaction from La Sota as a primary vaccine depends on:1. The residual level of antibodies, which could protect the

birds from post vaccine reactions2. The extent of other concurrent infections, such as

Mycoplasma spp, pathogenic E. coli, or infectious bursal disease virus and other respiratory viruses.

3. In intensive systems, vaccination using spray delivery systems which produce small particle sizes, may also exacerbate the vaccine reaction.

Conventional lentogenic vaccines

Some lentogenic vaccines have been cloned by taking a single infectious virus and growing a homogenous population from it, with the aim of selecting a virus which gives less vaccinal reactions than a La Sota-like virus, while retaining its superior immunogenicity compared to a HB1-like virus.

An example of this kind of vaccine is “clone 30”.

Mesogenic Vaccines

These produce severe vaccine reactions in an immunologically naive population.

The use of this kind of vaccine is not advisable in situations where chickens are without any immune protection against the virus.

Mesogenic Vaccines

Normally mesogenic vaccines, such as Komarov (Saifuddin et al., 1990) and Mukteswar (Alexander, 1997) are used as secondary vaccines after a primary vaccination with a lentogenic vaccine.

Inactivated Vaccines

Inactivated vaccines are produced by:1. Growing a ND virus in eggs.2. Then treating the infective allantoic fluid with an inactivating

agent, such as formalin or betapropiolactone. 3. An adjuvant, such as mineral oil, is usually then added to

make the inactivated virus more immunogenic.


Since the vaccine is no longer capable of replication or spread, it has to be injected individually into every bird needing vaccination.

It is normally injected into the back of the thigh muscle or the breast muscle, using 0.3 or 0.5 ml per bird.


Inactivated vaccines produce very high levels of antibodies against NDV, and provide good protection against the virulent virus.

Inactivated vaccines are usually applied after an initial priming vaccination with a live vaccine.

Recombinant Vaccines

NDV has two surface glycoproteins:1. Fusion [F] 2. Haemagglutinin/neuraminidase [HN].

The genes coding for either of these can be inserted into a different kind of virus to make a recombinant vaccine.

For example, the fusion gene inserted in herpes virus of turkeys produced a vaccine which gave good protection against virulent NDV (Morgan et al., 1993).


Advantage:1. The host virus may have better stability than NDV. 2. Antigens for multiple different pathogens can be inserted into

the same host virus to produce a single vaccine against several different diseases.


Disadvantage of recombinant vaccines is:High cost.

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