Newcastle disease; an old disease with new features EVPA Conference 2017 Newcastle disease; an old disease with new features Kang-Seuk Choi /OIE expert OIE Reference laboratory for Newcastle Disease Animal and Plant Quarantine Agency, Korea

Definition OIE definition of Newcastle disease (ND) : Infection of poultry by a virus of avian paramyxovirus type 1 (APMV-1) that meets one of the following criteria for virulence; An intracerebral pathogenicity index of > 0.7 Molecular Basis of F cleavage site Multiple basic amino acids at C-terminus of F2 Phenylalanine (F) at residue 117 of F protein (a) Biological pathotyping (b) Molecular biological pathotyping

Newcastle disease as food security (Miller et al., Infec Genet Evol, 2015)

What is the problem?

(1) Bio-security failures Transmission Mode

(2) No vaccination NDV epidemic event during 1980s in Korea (especially broilers)

(3) Suboptimal protective immunity (For young chicks) Immunity gap

(3) Suboptimal protective immunity (For egg-laying hens) Inappropriate vaccine program Short-term vaccine immunity Poor quality of vaccine used Flock HI titers in commercial layer flocks (n=60) Immunity and Egg drop Protection Challenged with virulent VII NDV (Kr-005 strain,106ELD50) Protection Egg drop Mortality (Unpublished data)

(4) Immune suppression The effect of IBDV infection on NDV protective efficacy In commercial broilers (32 days old) with B1 vaccination (2 weeks old) or B1 vaccination/subsequent IBD infection (Kim & Song, 1992)

Definition A highly contagious and fatal viral disease that primarily affects birds particularly domestic chickens (up to 100% mortality)

Newcastle Disease Virus Family Paramyxoviridae Genus Avulavirus Species Avian avulavirus type 1 Avian paramyxovirus type 1(APMV-1) Pleomorphic (100 to 500nm in diameter) Broad host range Single serotype

Genotype East Africa 2 class >19 genotypes Class II Class I Late genotype: after 1960s Genotypes V, VI, VII, VIII, XI Genome size: 15,192nt Class II (>18 genotypes) Early genotype: before 1960s Genotypes I, II, III, IV, IX, Genome size: 15,186nt Class I Class I Genome size: 15,198nt (1 genotype) Dimitrov et al., Infection, Genetics and Evolution (2016)

Recent distribution of Class II NDV genotypes (Late genotypes) Since 2000 XIV, XVII, XIII XVI V XI VII, XVII, XV VII, XIII VII VII, VIII, XII VI, VII VI XIII (VII) VII

Pandemic episodes versus emerging new genotype 1920 1930 1940 1950 1960 1970 1980 1990 2000 First Pandemic Second Third Fourth Epicenter estimated South East Central/South America Middle East Far East NEXT? Genotype II to IV V VI VII International spread Poultry(meat) Psittacine Pigeon Wild birds(?) What? When? Where? How?

Genotype VII new subtypes Pandemic potential? VIId VIIb 4th pandemic Poultry ( free-ranging birds) poultry Virus origin unknown VIIe VIIg PR China : (recombinants?) 2003- VIIf PR China : 1996-2008 VIIh Malaysia Indonesia/ Cambodia/Vietnam  China /Africa 2004- 2009-/2011- 2011- 2013- Indonesia : 1988-1990 Psittacine (lory, cockatto) VIIi Indonesia  Pakistan Israel  Bulgaria 2010 2011- 2011 2013 VIIIa India (1997), Europe(1997), South Africa (1995), Iran (2009-2011) India : Early 1980 Psittacine (cockatto) VIIIb Inidia (quail)  Pakistan  Iran, Russia, India, South America 2003 PJ Miller et al., Infect Genet Evol 29:216-229(2015)

Global spread of newly emerging NDVs VIIi VIIh XIIIb 2011 2009 Dec 2011 2012 2013 Global spread of newly emerging NDVs VIIh, VIIi, XIIIb: Pandemic potential? 2010 2003 2005

Newly emerging VIIh NDV Phylogenetic analysis Based on F gene From GenBank data Since 2010

Nucleotide sequence identity(%) of full genome NDV VIIh isolates from different countries South Africa/2013 1 2 3 4 5 6 7 8 ID 0.999 0.924 0.925 0.941 0.921 0.918 0.922 0.919 0.996 0.898 0.99 0.968 0.989 0.969 0.896 0.893 0.895 0.967 0.988 0.965 Malaysia/2004 Malaysia/2005 Malaysia/2011 Malaysia/2011 Malaysia/2013 China/2012 China/2011 1, MB128/04; 2, MB076/05; 3, IBS002/11; 4, IBS005/11; 5, IBS025/13; 6, chicken/Guizhou/1032/12; 7, egret/China/Guangxi/11; 8, turkey/SA/N2057/13.

Simplot analysis of NDV VIIh genotype isolates. Query virus: Malaysian isolate IBS002/11

Global spread of newly emerging NDVs VIIi VIIh XIIIb 2011 2009 Dec 2011 2012 2013 Global spread of newly emerging NDVs VIIh, VIIi, XIIIb; pandemic potential? 2010 2003 2005

Protection efficacy against VIIh NDV by vaccination Using 3 week-old SPF chickens Unpublished data

Protection efficacy against VIIh NDV by vaccination using commercial broilers with MDA ND vaccination ND Serology(HI, log2) NDV challenge (day 35) Day 1 Day 14 Day 1 Day 35 Mortality Virus shedding* (%) (viral copy no log10) G1 B1 spray La Sota 2.55±𝟎.𝟓𝟏 𝟓.𝟔𝟎±𝟐.𝟎𝟗 𝟎% 𝟎 𝟐𝟎 𝟏.𝟑𝟓±𝟑.𝟑𝟏 recVII (killed) (Drinking) G2 B1 spray La Sota 2.48±𝟎.𝟓𝟐 𝟓.𝟑𝟎±𝟏.𝟎𝟖 𝟏𝟓% 𝟑 𝟐𝟎 𝟕.𝟔𝟒±𝟑.𝟗𝟖 La Sota (killed) (Drinking) G3 No vaccination 2.55±𝟎.𝟓𝟐 <𝟐 𝟏𝟎𝟎% 𝟐𝟎 𝟐𝟎 𝟏𝟏.𝟏𝟎±𝟎.𝟔𝟏 (Roohani et al., J Vet Sci 16:447-457, 2015)

To minimize economic loss by genotype VII ND 1. Strengthen biosecurity measures to overcome incomplete protection conferred by vaccination Use more immunogenic vaccines to improve the protective immunity (eg, antigen matched vaccine) 3. Apply for appropriate vaccination program to enhance protective effect (eg, vaccination route, age) 4. Control immunosuppressive infectious diseases Especially infectious bursal disease (IBD)

Acknowledgement OIE ND Reference Laboratory Universiti Putra Malaysia Animal and Plant Quarantine Agency Dr. HJ Lee Dr. I Jang Universiti Putra Malaysia Institute of Bioscience Prof. AR Omar Dr. SW Tan Seoul National University College of Veterinary Medicine Prof. HJ Kwon Malaysian Veterinary Research Institute Dr. RM Rahman

Thank for your attention