August 15August 15thth 2011 2011
Newcastle Disease Outbreak Newcastle Disease Outbreak in vaccinated Broiler Breeders and Layersin vaccinated Broiler Breeders and Layers
The need for a new vaccineThe need for a new vaccine
Road Map
1.Newcastle Disease Virus
- Classification
2.The reason for ND vaccine breaks
3.Vaccination against ND
- Pathotypes vs genotypes- Vaccination trials with local ND vaccine- Challenge- Serology
Taxonomy:Family: ParamyxoviridaeGenus: AvulavirusSpecies: Avian Paramyxovirus 1 (Newcastle Disease virus)
1926 by Kraneveld in Buitenzorg, Indonesia1926 by Doyle in Newcastle, UK
Newcastle DiseaseNewcastle Disease
Newcastle Disease VirusNewcastle Disease VirusFusion protein
Hemaglutinin & Neuraminidase protein
Matrix protein
RNP complex• RNA• NP Nucleoprotein• P Phosphoprotein• L Polymerase
FHN
MP
L
N
RNA
Newcastle Disease Virus
2 antigenic 2 antigenic determinantsdeterminants
Classification of NDV
• Serotype• Pathotype• Genotype
NDV replication in the cytoplasma
• Air-borne or carried on contaminated shoes of workers, visitors, tyres, equipment, feed sacs, egg crates, wild birds.
• Mainly aerosol.
• Improperly cleaned houses and hospital pens are sources of NDV.
Transmission
Incubation period•4-6 days
Susceptibility:Susceptibility: (1)Hosts; natural outbreaks occur in chickens, other
domestic birds. Duck and geese no clinical signs.
(2)Breed; Layers are more susceptible than broilers. (3)Sex; male and females are equally susceptible.
in grower: breeder male higher density ND.(4)Age; resistance increases with age. (5) Season; ND is more common in the cold–dry as
well as cold-humid periods, season changes and windy periods of the year.
•Severe respiratory signs
•Oedema eyes and head
•Green diarrhoea
•Muscular tremors
•Torticollis
•Paralysis of legs and wings
•Opisthotonos
•Mortality up to 100 %
in susceptible birds
Clinical signsVVND pathotype
• Haemorrhagic lesions in intestine:
proventriculus, cecal tonsil and small intestines
• Haemorrhagic lesions and congestion in trachea
• Airsacculitis
• Egg yolk in abdominal cavity
• Haemorrhagic lesions of ovaries
• Vasodilations of blood vessels, e.g. brain
Gross lesions
•At least 236 species are susceptible
•Chickens are highly susceptible
•Ducks and geese --> few or no clinical sings
Pathogenesis
Current Field Observations
RevaccinationRevaccination: Yes, but wait - till acute phase has passed- till feed intake has been stabilized- with killed vaccine- antibiotic may help to prevent secondary infection
INSANITY :
DOING THE SAME THING OVER AND OVER AGAIN, EXPECTING DEFFERENT RESULT
( ALBERT EINSTEIN 1879 – 1955 )
Differential Diagnosis for egg fault/production Differential Diagnosis for egg fault/production dropdrop
ND IB Coryza EDS MG
Shell Problems + + - + +
Egg Drop + + + + +
Pale eggs + + - + -
Misshappen eggs - + - - -
Respiratory signs + + + - +
Affects interior quality
- + - - -
Shell-less eggs +/-* - - + -
Mortality +/- - - - +/-
*Feed intake problems
Infectious Bronchitis Newcastle Disease
Newcastle Disease in Broiler Breeder and Layer PulletsNewcastle Disease in Broiler Breeder and Layer Pullets
Newcastle Disease in Laying BirdsNewcastle Disease in Laying Birds
ND Virus disseminationND Virus dissemination
1. Initial infection
2. Viremia
2. Airsac
3. Proventiculus 3. Intestines
2. Lung
3. Brain
3. Liver
ND - Phases of infection
Replication
Viremia
Replication
Live vaccineLive vaccine Killed vaccineKilled vaccine
Perivascular cuffing of lymphocytes and plasma cells in brain (IHC)
…The vaccine homolgous with the challenge virus homolgous with the challenge virus reduced oral shedding significantly reduced oral shedding significantly more than the heterologous vaccines. NDV vaccines formulated to phylogenetically closer to the potential outbreak viruses may provide better may provide better ND control by reducing virus transmission ND control by reducing virus transmission from infected birds.
If you want to truly understand something, try to change it.
Kurt Lewin (1890 -1947)
Newcastle Disease….• Prevention:
(1) Control and reduce movement Control and reduce movement of visitors, workers, equipment and vehicles. (2) Change clothes and boots between flocks & houses. (3) Properly dispose sick and dead birds. Sick birds should be culled and slaughtered immediately. (4) Clean, disinfect and fumigate house and equipment between flocks. Leave the house empty and sealed for 21 days. (5) Vaccination with live vaccines, monitored by serology- detection of the presence and titre level of antibodies in serum.
ND vaccines (history)
Live – 1946Live – 1946- Mesogens- MesogensRoakin (1948), Komarow, Herts, Mukteswar
- Lentogens- LentogensB1 – introduced in 1950Lasota – introduced in 1952
Killed – 1970 -1980Killed – 1970 -1980- longer immunity, adjuvants
Immunogenicity
Available ND vaccines in the market Available ND vaccines in the market
Immunogenicityefficacious
Safetymild
Safety
Genotype I
Genotype II
ND vaccine technology is more than 50 years old.
Seed virus can only protect against Seed virus can only protect against mortalitymortality, but cannot prevent replication, dissemination and shedding.
ND vaccine efficacy
Serotype
Pathotypes
Genotypes
Serotypes
•HN (HA activity)
•1 Serotype (Cross reaction in serology and protection against mortality)
• Relationship between antigenicity and efficacy is still unclear.
Doubling Dilutions
Log Titres
1 02 14 28 316 4
32 564 6
128 7256 8512 9
1024 10
2048 11
Field Challenge and Seroconversion Post Infection
Killed Booster Vaccine
Interpretation
No immunity Maternal Immunity
Poor Immunity
Live Prime Vaccine
Live Booster VaccineProtection Against Mortality, No Protection Against Egg
Production Drop
Common Interpretation of ND titresCommon Interpretation of ND titres
Pathotype ICPI IVPI MDT
Viscerotropic velogenic
> 1.5 – 2.0 2.0 – 3.0 < 60 hours
Neurotropic velogenic
> 1.5 – 2.0 2.0 – 3.0 < 60 hours
Mesogenic > 0.7 – 1.5 0.0 – 0.5 > 60 h – 90 hours
Lentogenic 0.2 – 0.7 0.0 > 90 hours
Asymptomatic 0.0 – 0.2 0.0 > 90 hours
PathotypesBefore RNA Isolation & DNA Sequencing of the fusion cleavage site – based on virulence based on virulence in poultryin poultry
FFHN
MP
L
N
RNA
GenotypingGenotyping based on F-gene Sequence
2 antigenic 2 antigenic determinantsdeterminants
Total: 15,192 nucleotides with 82.7 % identity to ND Lasota
University of Maryland
Genotypes of NDV
Strain Host Year of isolation
Sequence Length (nt)
Genotype F cleavage site
Virulence* ICPI GenBank No.
cockatoo/Indonesia/14698/90
cockatoo 1990 complete genome
15192 VII RRQKRF V 1.84 AY562985
ID-1/88 cockatoo 1988 partial F 325 VII RRQKRF V NA EU604253
moluccan/Indonesia/904/87
NA 1987 partial M & F
1195 VII RRQKRF V NA AY444497
chick/Indonesia/W3/89
chicken 1989 partial F 395 VII RRQKRF NA NA AF503645
Bali-1/07 chicken 2007 partial F 315 VII RRQKRF V 1.77 AB426628
Only few published genome sequences of NDV isolated from Indonesia
Since the late 80’s Indonesian NDV belong to genotype VII
* V, virulent .
Genotype
II
I
IV
V
VI
VII
III
Class I
Class II
Nucleotide identity (%) of complete genome
Sukorejo/019
Cockatoo/90
LaSota Ulster Phy-LMV 42
Banjarmasin/010
92.0 92.3 82.6 85.1 84.7
Sukorejo/019 92.0 82.7 84.6 84.2
Cockatoo/90 85.5 86.7 85.9
S. Samal & T. Prajitno
GRRQKR↓FI......↓........↓........↓........↓..GRRRKR↓FI...R..↓.....R..↓.....R..↓.....R..↓.....R..↓...G.QG.↓L..G.QG.↓L..GKQG.↓L..GKQG.↓L.
Banjarmasin/010 Banjarmasin/010 Gianyar/013 Gianyar/013 Sragen/014 Sragen/014 Kudus/017 Kudus/017 Kudus/018 Kudus/018 Sukorejo/019Sukorejo/019Makassar/003 Makassar/003 Bali/020 Bali/020 Linggasari/050Linggasari/050Parungkuda/058Parungkuda/058Kisaran/069Kisaran/069LaSotaLaSotaPhy.LMV42Phy.LMV42
Alignments of F cleavage sites ICPI1.711.921.911.92
Genetic variability - NDV
Early (I, II, III; IV)
and recent (V, VII, VIII) lineages
(Virus Res, 120:36-48, 2006)
VII
V,VI, VIII
III-IV
II
I R&D Vaksindo
Vaccine strains
Genotypes of NDV
ND-affected countries in the world and its genotypesND-affected countries in the world and its genotypes
VII
VII, VIII, IXV
VII
VII
VII
R&D Vaksindo
Inactivated ND vaccine (Genotype VII)
Vaksinasi Challenge
ND HI Titer dengan Antigen yang berbeda
Vaksinasi
ND HI Titer dengan Antigen yang berbeda#trial 2
Vaksinasi Challenge
Control bird (SPF):DiarrheaConjunctivitisTracheitisSwollen spleenHemorrhagic proventiculusHyperemiaetc.
ETIKET Label
Week Day Vaksin Dosis Aplikasi Jenis0 2-4 ND-IB Live 1 dsTetes Mata kanan ND apatho-IB H-120 ND L 0,2ccInjeksi sc 1 10 ND-IB Live 1 dsTetes Mata Kiri ND Clone -IB H120 2 14 Gumboro Intermediate plus 1 dsCekok IBD M 3 22-23 Gumboro Intermediate plus 1 dsCekok IBD M ND Live 1 dsTetes Mata Kanan ND Lasota 5 35 Pox 1 dsTusuk Sayap ND-AI (H5NI) 0,5 ccInjeksi sc ND-AI 6 42 Coryza I (Alum) 0,5 ccInjeksi Dada Kanan Trivalen/Tetra
10 70 ND/IB Kill Variant 0,5 ccInjeksi Dada Kiri ND-IBmulti ND-IB Live 1 dsTetes Mata Kiri ND Lasota-IB M41
11 80 AI (H5NI) 0,5 ccInjeksi Dada Kiri Bivalent13 ND L 0.5 ccIM ND Genotype 7
15 105 ND/EDS/IBmulti 0,5 ccInjeksi Dada Kanan ND/EDS/IBmulti
16 112 ND-IB Live 1 dsTetes Mata Kiri ND Lasota-IB M41 Coryza II (Alum) 0,5 ccInjeksi Dada Kanan Trivalen/Tetra
18 AI (H5NI) 0,5 ccInjeksi Dada Kiri Bivalent19 ND L 0,5 ccIM
Contoh program vaksin untuk kontrol ND
1. Egg production drop – main issue in breeders and layers2. HI antigens suggests protection, but is not.3. Diagnosis and sound vaccination program is important4. Current ND vaccines protects against clinical signs, but cant prevent shedding and spread5. Emergency live ND vaccination in face of challenge protects against clinical signs, but severely affects egg production6. ND outbreaks in vaccinated poultry flocks are due to the emergence of antigenic variants (Genotype VII). Genotype VII vaccine is needed.7. ND vaccine seed is out of date8. Trial with inactivated ND vaccine (Genotype VII) proved against mortallity and egg production drop
In a NutshellIn a Nutshell
If nothing ever changed, there'd be no butterflies. Author Unknown
Thank You