ND ( New castle / Rani khait )

Etiology:-
Family Paramyxovirinae => subfamily - Paramyxoviridae => Genus - => 5 genera in which Avulaviruses
are related birds.

Sterotypes = 11 ( APMV Serotype -1 to APMV-11)

Serotype 1 is most important which related to our commercial & Domestic Poultry .

Note : All strain which cause ND related to Avian Paramyxoviridae Serotype -1 group ( APMV-1) . Only
VNDV ( virulent ND Virus cause ND in Poultry) . While LVNDv ( Low virulent ND doesn't cause clinical
disease untill bird don't attack by Environmental stress or secondary infection ).

( LNDv cause clinical respiratory signs only when their is environment stress/ secondary infection).

VNDV ( virulent ND Virus) => Velogenic Strains & Mesogenic

i) Velogenic Strains=> cause mortality upto 90% and drastically decrease in egg production in layers and
Breeders.

ii) Mesogenic Strains=> cause mortality Upto 10% . In many literature Velogenic ND Virus classified
under VNDv .

LNDv ( Low virulent ND Virus=> Lentogenic strains ( cause ND only in those birds which is already
infected or environmentally stress birds. )

Pathotypes ( Strains ) :-
i) Velogenic

ii) Mesogenic

iii) Lentogenic

iv) Asymptomatic enteric

i) Velogenic Strains=> Affect birds or any age and cause high Mortality upto 90% ( non vaccinated birds
).Example: Herts , GB Texas , Ca-1083 etc.

Velogenic Strains further divided into

a) viscerotropic Velogenic ND ( cause Hemorrhages in Gastrointestinal tract often sometimes with
neurological signs )

b) Neurotropic Velogenic ND ( cause neurological signs with or without respiratory signs )

ii) Mesogenic Strains=> ( these strains are less pathogenic and cause Neurological signs only in youngs
and mortality upto 10% .)

Example: Mukteswar , Komarov , Roakin

iii) Lentogenic strains=> cause disease only in immunocompromised birds . ( These strains are used as
vaccine strains )

Example: Lasota , F , Hitcher

( Clone 30 strain isn't a natural viral strain it's experimentally developed clone of lasota strain.

Similarly B¹ is also experimentally laboratory developed strain which have low ICPI mentioned below ICPI
of all important strains).

iv) Asymptomatic enteric strains => these strains have tropism for gastrointestinal tract and don't cause
disease ( used as vaccine strains. )

Example: Ulster 2c , VG/GA

These pathotypes are on Based on following test.

1) RMD ( Record mean death )

2) ICPI ( Intracerebral Pathogenicity index )

3) IVPI ( intravenous Pathogenicity index )

4) Plaque Test ( PT )
Vaccine strains are used on the basis of ICPI value .

Example:

Strain name | ICPI ( intracellular Pathogenicity index)

1- APathogenic strains:-

V⁴ strain | 0.0

PHY.LMV.42 | 0.0-0.16

Ulster 2c | 0.14-0.23

VH | 0.15

2- Lentogenic strains :-

B¹ | 0.18

F | 0.20

VG/GA | 0.35

Clone-30 | 0.25-0.30

Lasota | 0.40

• B¹ is laboratory strain( Clone-type ) of Hitchner strain , Similar Clone 30 is Clone of Lasota.

3- Mesogenic Strains :-

Mukteswar | 1.40

Komarov | 1.41

Roakin | 1.45

As ICPI value increases=> increase Pathogenicity of Virus. That's why it's recommended , first ND
vaccine ( priming) should be done with B¹/Ulster 2c /Clone 30 / VH/ V⁴ / F /PHY.LMV.42 . ( because
these strains have low ICPI means low risk of disease /post vaccine reaction.)

In some literature B¹ recommend first instead of "F" just because on basis of ICPI .
What is ICPI Test :-
inj. Diluted virus (0.05ml) intracerebral to day old chick. And observe for 24 hours upto 8 days.

Virulent ND ( VND ) strains cause clinical Disease ( viscerotropic & neurotrophic ) because they have
multiple basic Amino acid sequence at their C terminus of F² protein and Phenylalanine at their N
Terminus of F¹ protein. while Low virulent ND strains ( LvND ) have monobasic amino acids sequence
at their at their C terminus of F² protein and Leucein at their N Terminus of F¹ protein.

Fusion protein => precursor F⁰ is cleaved by host cells proteases ( like trypsin , elastase, chymotrypsin
etc. ) Into => F¹ and F² .

A wide range of cells have these proteases.

This cleavage helps Virus to fuse it's membrane with host cells membrane after which viral genome is
transferred into host cell's cytoplasm and replication starts.

Multiple basic Amino acid sequence means their is atleast 3 Amino acids arginine/ Lysin in-between
113-116 at C terminus ( carboxyl end of peptide). Also virulent ND strains have phenylalanine at 117
residue of C terminus.

While Low virulent ND strains don't have such sequence that's why they don't cause clinical disease
untill secondary infection/ environmental stress is not present.

Note : [ Fusion protein ( F ) is a protein which is made upto of peptide which are Linked to each other by
disulfide bonds ]

Proteases ( elastase, chymotrypsin. don't cleave F protein for attachment of Low virulent ND( LvND)
strains because LvND strains have monobasic amino acid sequence at their C terminus of F² protein
while leucine at their N Terminus of F¹ protein. ( F⁰ protein of LvND strains are only cleaved by Trypsin
like enzymes into F¹ and F² which helps virus attached to host cell's membrane . Trypsin like protease (
enzyme ) are present in respiratory and Gastrointestinal tract of chicken. )

Different microbes are also secrete Trypsin like enzymes due to which bird is more susceptible LvND .
Also LvND don't express V genes ( which produce V protein => inhibit interferon Alpha & beta and also
cause induction of Apoptosis. )

• Interfone are natural antivirals Produce by host cells against viruses.

Viral morphology:-
• M protein ( Matrix protein )

• HN protein ( Haemglutinin and Neuraminidase Glycoprotein )

• F protein ( Fusion protein )

• N protein ( Nucleocapsid )

• P protein (it's a phosphoprotein attached with Nucleocapsid)

• L protein ( Large polymerase )

• V protein (inhibit interferons Alpha / beta which are natural antivirals produced by host cell's against
viruses. V protein also cause apoptosis of host cells after viral genome replication because it's gene( v
gene ) express at the end of genome replication.)

Genome of NDv:
Single strand negative sense RNA( capped 5 end and polyA tail 3 end ) having Nps( non structural
protein which is basically enzyme called RNA dependent RNA polymerase/ RdRpol also known as L/large
protein) & Structural proteins ( M , N ,P ,HN and F )

*Because viral genome is RNA , so replication would be in cytoplasm.*

Exception [ i) Orthomyxovirus which cause Avian influenza in birds => RNA virus but replicates in
nucleus because it's 5 end of RNA is non caped . For cannibalization ( capping ) it's 5 end it's replication
occurs in nucleus .

ii) Retrovirus which cause tumors’ diseases( e.g. leucosis in chickens ) in poultry=> also has RNA viral
genome.

It's replication also occur in nucleus because this virus has reverse transcriptase enzyme ( which reverse
transcribed DNA to form viral associated proteins)

Note:

Except Orthomyxoviruses & Retroviruses all RNA viruses ( regardless they are positive sense or negative
sense ) replicate in cytoplasm of Host's cell.
Transmission:
• Aerosol ( almost 5 km => virus can travel)

• Direct contact ( Bird 🐦 to bird 🐦)

• Indirect contact ( Contaminated litter , utensils , visitors etc. )

• Wild birds

• Mixing infected birds in flock etc.

Vertical transmission:
Although virus damage to reproductive tract and also their is viral shedding through feces and therefore
contamination of egg ( because of contaminated feces) but due to poor egg shell quality & misshapen
eggs which never hatched. That's why vertical transmission doesn't occur. [ Although their is complete
cessation of egg production during vND(virulent ND) outbreak ].

Factors :
i) Environment ( Temp. & Humidity )

ii) Ventilation ( Poor ventilation=> increase Ammonia & other harmful gases=> Damage to respiratory
tract =>damage to mucosal membrane which is first line of defence of immunity )

iii) Poor hygiene conditions

iv) Immunocompromised birds

v) Affecting birds of all age but youngs are more susceptible ( bcz of their developing immunity )

vi) In winter season spread is more than in summer

Vii) Virulence of strain

viii) Dose of virus

ix) other Respiratory diseases ( IB , CRD , MG etc.)

Pathogenesis:
Inhalation/ conjuctiva => Virus affect upper respiratory tract of birds=> replicate within cells of upper
respiratory tract which is lined by pseudostratified columnar ciliated epithelium => After replication
viremia ( virus enter in blood) => Again replicate at their strains/ serotypes specific sites . During second
viremia virus ( neurotrophic virulent strains get into CNS ) .

• Viral Replication:

ND virus => inhale => Viral protein( HN ) bind on sialic acid receptors & integrins . After binding F⁰
cleaved by host enzyme ( proteases like elastase, chymotrypsin , trypsin etc. ) And F⁰ converted into by
changing it's configuration=> F¹ and F².

These F( fusion) protein leads to fusion of viral envelope with host cell membrane and internalization of
viral genome. Now Viral Genome in cytoplasm of Host's cell. RdRNApol( RNA dependant RNA
polymerase) start it's working and make positive strand from viral parental negative RNA . From this
Positive strand RNA => proteins are made. On the other hand from parental negative RNA strand more
positive sense strands RNA are made from which further more negative sense RNA strands are
synthesized. After completion of protein synthesis and negative sense RNA strands. Viral assemble
itself. And get it's envelope from host's organelle ( endoplasmic reticulum ) . Now virus comes out from
host cells. As we know their is another important surface protein named "N protein" . N protein (
neuraminidase) helps viral progeny ( newly synthesized virus) to avoid sticking with host cell during
existing cell. Because in starting of Pathogenesis as mentioned HN protein bind to sialic acid receptors ,
so this avoidance is mediated by Neuraminidase during progeny existing.

Clinic signs:-
Enteric signs
• Anorexia

• increase thirst ( because of diarrhoea)

• Greenish Mucoid diarrhoea ( which is not characteristic because same coloured diarrhoea may
present in spirochetosis or compylobacteriosis ) .

• severe depression

• In Breeders and layers=> Small , soft and pale eggs .

• Lacrimation may be present which leads to cloudiness of eye.

 Respiratory signs
Clinical signs:- ( youngs )

• Lacrimation

• Nasal discharge/ sneezing

• Coughing ( bird's don't have diaphragm also phrenic nerve and also bird's lungs don't expendable. In
birds frequent sneezing consider as coughing. Birds cough up virus, so use anti-histsminic drugs rather
than antitussives for limiting viral spread. )

• Gasping & Dyspnea [ Because of excessive Mucus production in upper respiratory tract/ trachea .
Because Virus irritate sensory receptors in mucus membrane of upper respiratory tract which leads to
stimulate Vagus nerve ( Cranial Nerve 10 originate from medio-lateral medulla oblongata ) => efferent
signals to Mucus ( goblet cells ) => excessive Mucus production ( for removing irritant ) . Also when virus
enters cell => different mediators( e.g. cytokines ) release which directly stimulate excessive Mucus
production => narrow airways passage => open mouth breathing/Gasping) .

• Abnormal Respiratory Sounds (Mucus=> narrow airways passage ).

• Cyanosis of comb/wattles ( bcz of Decease PO² )

[ pO² = partial pressure of Oxygen which is due to Respiratory distress ]

Nervous signs
• Drooling/ salivation ( because loose of swallowing reflux which is mediated by Cranial Nerve 9,10,12 )

• Torticolis/Stargazing ( because damage to brain stem )

• Colonic Spasm / Convulsion / muscular tremors ( because of excitatory neurotransmitter firing of

nerves ) .

• wings paralysis/droopy wings ( Nerve damage which innervate serratus anterior muscle )

• Leg paralysis
Postmortem Lesions:-
1- Lentogenic
• Tracheitis ( Reddening of trachea / Mucus present in Tracheal lumen )

• Cloudy air sac & lungs involvement ( in case of lower respiratory tract infection )

• Mild conjunctivitis ( swelling of conjuctiva )

• mild Enteric signs may be present or absent

2- Velogenic
• Vent staining with greening diarrhoea

• severe Tracheitis ( Reddening of trachea & Hemorrhagic but blood will not present )

[ Tracheal exudate ( Viremia cause cytokines release which leads to increase permeability=> leakage of
plasma + proteins in Tracheal lumen => exudate( odema) ]

• Air sac => cloudy ( because of transudate )

• odema of facial and neck region [ because of increase in Vascular permeability=> leakage of plasma=>
transudate ( odema ) ].

• Hemorrhages in proventiculus ( mucosal and/or Sub mucosal)

• Cecal tonsil Hemorrhages ( characteristic for ND )

• Button ulcers in Intestine ( characteristic)

• Hemorrhages on pericardial fat

• Congested enlarged spleen ( initially, because spleen also act as immune organ. )
 Mortality %
• Velogenic Strains cause mortality upto 80-100%

• Mesogenic Strains cause mortality upto 30%

• Lentogenic strains cause negligible mortality ( when uncomplicated )

Note:-

There is no plug formation because virus after replication escape cell without destroying any specific
structure of Host's cell. Therefore no damage => no Fibrin deposition=> no plug formation.

Diagnosis :-
• Sudden onset of disease

• Morbidity

• PM lesions

• Serological tests ( ELISA , VN , DI , AGP etc..)

Differential Diagnosis :-

1) Mycoplasma:

Low morbidity

2 ) ILT :

Low morbidity

Usually effects growers/ adults

More severe signs in iLT than ND [ observe usually in night because parasympathetic system dominant=>
bronchonstriction by binding of acetylcholine on M3( mucranic receptor which are Gq in nature) usually
in night & blood present in Tracheal lumen in severe attack.]
Blood in Trachea because of hemorrhage.

4) Infectious coryza:

Mostly occurs in winter with facial swelling ( mortality & morbidity & Postmortem are different from ND
)

5) ViT-E deficiency

( mortality & morbidity & Postmortem are different from ND )

6) AI

Vaccination/ immunization:
Apathogenic strains & Lentogenic strains are used .

Live IB and ND vaccination can be done at same time.

Killed & Live vaccine also available

Immunity
Live vaccine done in early age by oral / conjuctival / inhalant route

Preferred route : eye drops/ spray ( inhalant route)

During spray => droplet 💧 should be coarse in Young birds ( fine drop goes down deep in lower
respiratory tract => severe post vaccine reaction ) .

Inactive / killed vaccine :

Vaccinate birds before production.

Killed vaccine cause higher level of circulating antibodies. Thus don't stimulate mucosal (Local immunity
which is first line of defence) .
Treatment:
• Electrolytes + Multivitamins in D/W

• Antibiotics ( avoid secondary bacterial infection)

• Nsaid / Na-salicylate in D/W

• Mucokinetics + Mucolytics in D/W ( Helps in Gasping & Dyspnea)

[ Mucokinetics ( Essential oils / Ammonium chloride / Guaifenesin ) + Mucolytics ( Bromhexin /

Ambroxol/ Acetylcysteine / carbocysteine ) ] .

• Fat soluble vitamins ( ADEK )

• Antivirals are available ( Zanamivir & Amantadine ) .

[ zanamivir => Bind with neuraminidase inhibit escape of viral progeny from infected cell .

Zanamivir more superior than Amantadine because amantadine inhibit the growth of virus by blocking
the ion channel formation of M ( matrix) protein during the early stage of infection. Substitution
mutation) of amino acids within M protein results in loss of antiviral capability of amantadine.. while
Zanamivir inhibits neuraminidase ( N protein ) ] .
Regards:-
Dr Hamza Mohsin ( DVM , BZU Multan )

Dr Awais Mohsin ( DVM , BZU Multan )

Dr Sonia Mohsin ( DVM , BZU Multan )

Dr Mudassar Ahmed ( DVM , Riphah international University Lahore )

Dr Beenish Abbas ( DVM , BZU Multan)

Dr Shakeel Ahmed ( DVM , SBBUVAS Sakrand )

Dr Saira Muzammil ( DVM , UVAS Lahore )

Dr Umair Dildar ( DVM , BZU Multan)

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