Interaction of Gumboro and other Immunosuppressive Diseases on Respiratory Disease

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Interaction of Gumboro and other Immunosuppressive Diseases on Respiratory Disease FREDERIC J. HOERR II SEMINARIO INTERNACIONAL AVICOLA MERIAL PANAMA CITY, PANAMA JULY 10, 2014

Broiler Disease by Age Rickets Adenovirus - vertical Adenovirus - immunosuppression Ascites/Synovitis/Tendonosis/DPM Gangrenous Dermatitis/Cellulitis E. coli, Salmonella E. coli, Ornithobacterium, Enterobacter Bursal Dis / B-Cell CAV Blue Wing CAV Thymus Atrophy/T-Cell Necrotic enteritis Coccidia Vx or challenge E. maxima IBV/PMV Vx Reaction Harsh Immuno/cycling Bronchitis, PMV, LT Challenge Viral Enteritis Viral Proventriculitis Omphalitis, Aspergillus, Dehydration, Ammonia Feed manufacture and management, water, lights, ventilation, daily care 1 7 Feed 14 21 28 35 42 49 56 change

Immunosuppression & Respiratory Disease by Age E. coli, Salmonella E. coli, Ornithobacterium, Enterobacter Bursal Dis / B-Cell CAV Blue Wing CAV Thymus Atrophy/T-Cell IBV/PMV Vx Reaction Harsh Immuno/cycling Bronchitis, PMV, LT Challenge Viral Enteritis Omphalitis, Aspergillus, Dehydration, Ammonia Feed manufacture and management, water, lights, ventilation, daily care 1 7 Feed 14 21 28 35 42 49 56 change

No. Cases 25 20 15 10 5 Broilers: Intestinal Virus Detection by Age Astrovirus Rotavirus Reovirus N=258 Cases No. Cases 80 60 40 20 Broilers: Cases by Enteric Viruses Detected N=258 Cases 0 1 7 14 21 Age - Days 28 35 42 0 Astrovirus Rotavirus Reovirus AstroRota AstroReo Virus RotaReo AstroRotaReo

Viral Enteritis in Broilers Bursa and Thymus Atrophy Max Bursa Score (Mean) Virus Positive Broilers <20 days: Maximum Bursa Depletion Score 4 3 2 1 0 RSS Astrovirus Rotavirus Reovirus AstroRota Virus AstroReo N=134 Cases RotaReo AstroRotaReo Normal Max Thymus Score (Mean) Virus Positive Broilers <20 days: Maximum Thymus Depletion Score 4 3 2 1 0 RSS Astrovirus Rotavirus Reovirus AstroRota Virus AstroReo N=131 Cases RotaReo AstroRotaReo Normal

Marek s Disease Immunosuppression Occurs at a young age Difficult to confirm Assume - if problems exist in Marek s tumors or clinical disease Marek s Disease Control

Acute Marek s Disease and Immunosuppression Acute Marek s disease infection causes necrosis and depletion of the bursa of Fabricius, thymus, and cecal tonsils Cecal Tonsil: Heidari et al. Avian Diseases 58:262-270, 2014 Impact: Permissive environment for respiratory virus persistence and shed: Bronchitis and Newcastle

Infectious Bursal Disease Classical F.J. Hoerr

Variant Bursal Disease Virus No breeder vaccination Breeder vaccination Unchallenged control F.J. Hoerr

Bursa Acute Bursitis (Acute Gumboro) Normal Necrosis (acute)

Acute Bursal Disease: Necrosis The bird is susceptible to IBD at this age Maternal antibody diminished, or Variant challenge virus attacks through existing immunity, or Massive challenge virus overwhelms existing immunity Bursa contains abundant virus Good for virus isolation or detection by PCR Acute bursal disease marks the onset of transient or possible permanent immunosuppression.

Post-necrotizing Bursitis Follicular Repopulation/Restitution Grade 2 Grade 2.5 Large Follicle Grade 3 Grade 3.5 Grade 4

Bursa Grading: Broiler Case Study Early Bursal Disease Challenge Age Days Flock 14 21 25 28 A 1 1 1 1 1 1 1 1 3.5 3.5 B 1 1 1 1 1 1 3.5 3.5 3 3.5 3.5 C 1 1 1 1 N 3.5 3 3.5 D 1 1 1 3 3 3 3 3 3 3.5 3.5 3.5 E 1 1 1 N 3 3 3.5 3.5 3.5 3.5 3.5 3.5 F 1 1 1 N 1 1 N N 1 N 3.5 3.5 G N 1 3 4 3.5 3.5 3.5 3.5 3.5 3.5 H N 3 3 3.5 3.5 I N N 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5 J N 3.5 4 3.5 1= Normal 2=Mild Depletion 3=Moderate 3.5-4= Necrosis/Marked~ Severe

Chicken Infectious Anemia Crowther et al, J Virol. 2003 77: 13036 13041 AAAP Slide Set

Thymus Grade 4 Lymphocyte depletion (CAV) Normal Grade 4 Grade 4

Bursa and Thymus: First 14 Days Primary Lymphoid Organs Seed Secondary Organs B Lymphocytes T Lymphocytes Spleen Cecal Tonsil/Gut Gland of Harder

Diagnostic Laboratory Perspective Atrophy of the bursa and thymus are routinely observed in broiler chickens submitted to diagnostic laboratory Principle diagnoses Infectious bronchitis, vaccine strains isolated Coccidiosis, especially Eimeria maxima Gangrenous dermatitis Bursal atrophy is primarily associated with infectious bursal disease Thymus atrophy is primarily associated with chicken infectious anemia (PCR positive) Also possible Marek s

1993: CAV Infection& Thymus Atrophy after Depleted Maternal Immunity Agedays 1 Maternal antibody CAV Challenge No anemia observed 21 35 49 Immunosuppression Lymphocyte and macrophage suppression T-cell growth factor, interferon, and transformation Macrophage FC receptor expression, interleukin-1, phagocytosis and bactericidal activity McConnell, Adair & McNulty (Avian Dis 37:366-374, 1993)

Immunosuppression Markers in Field Cases: Bursa and Thymus Histopathology Scores Bursa Thymus 1 2 3 4

Summary of 6-year Study CAV infection was widespread Thymus atrophy associated with CAV infection CAV, thymus atrophy, and bursa atrophy were more prevalent in chickens with clinical disease Respiratory Gangrenous Dermatitis Coccidiosis Laboratory findings correlated with economic losses. Hagood et al. Avian Dis 44:803-808. 2000.

Alabama Broilers Lymphocytic Depletion by Age of Submission (N=631) Mean Depletion Score 4.0 3.5 3.0 2.5 2.0 1.5 1.0 10 15 20 25 30 35 40 45 50 55 60 Age at Submission to Laboratory (Days) Bursa Thymus

Thymus and Bursa Lymphocyte Depletion Bursa Lymphocyte Depletion by Maximum Thymus Depletion Mean Bursa Lymphocyte Depletion 4 3 2 a a,b b,c c Kruskal-Wallis P<0.0001 1 Thymus 1 Thymus 2 Thymus 3 Thymus 4 Maximum Thymus Lymphocyte Depletion

IBV Isolates Alabama Broilers Lymphocytic Depletion by Age of Submission (N=631) Mean Depletion Score 4.0 3.5 3.0 2.5 2.0 1.5 1.0 60 55 50 45 40 35 30 25 20 15 10 5 0 10 15 20 25 30 35 40 45 50 55 60 Age at Submission to Laboratory Days Bursa Thymus IBV Isolates

Alabama Broilers and Broiler Sentinels IBV Isolations 180 160 140 120 100 80 60 40 20 0 Ark Mass Conn GA 98 DE O72 Other 1996 1997 1998 1999 2000 2001 2002 2003 2004 1/1/2003

Clinical Signs: Tracheal Rales % Chickens with audible tracheal rales 100% 80% 60% 40% 20% 0% IBV CAV + IBDV +IBV 5 8 13 16 DPI Toro, et al. 2006 Avian Pathology 35:455-64

Anti-IBV IgA in Tears: ELISA 0.08 0.06 IBV CAV + IBDV +IBV Uninfected 0.04 0.02 0.00 2 5 8 11 14 17 20 23 26 29 DPI Toro, et al. 2006 Avian Pathology 35:455-64

Infectious Bronchitis Tears: RT-PCR Ark Field Strain Individual samples 11 dpi 14 dpi 16 dpi 20 dpi IBV CAV + IBDV + IBV 24 dpi Not done 28 dpi Not done Toro, et al. 2006 Avian Pathology 35:455-64

Interaction of Infectious Bronchitis Virus, Infectious Bursal Dis., and Chicken Infectious Anemia: Harderian Gland IBV-specific IgA response Van Ginkel et al. Avian Diseases: Vol. 52, No. 4, pp. 608 617. Gumboro and CAV, alone and in combination, reduce the number of IBV-specific IgA lymphocytes in the Harderian Gland

Gumboro and CAV infection influence the selection of IBV vaccine subpopulations Gallardo et al. Avian Pathology 41:5,451-458, 2012 Immunosuppression could change the anticipated performance of an infectious bronchitis vaccine through permissive replication of virus subpopulations.

Working model: Subpopulations at-risk Ammonia, Stress Marek s Ammonia, Stress Marek s Viral Enteritis Viral Enteritis CAV CAV Gumboro Gumboro

Immunosuppression Erosion of Health and Productivity A variable percentage of the flock is affected Goal Minimize the number of birds in the subpopulation 1% 100%

Recommendations Conduct mortality surveys paying attention to bursa and thymus Histopathology surveys to assess bursa and thymus health Evidence of viral enteritis at 10-14 days Monitor the bursal disease vaccination program Necropsy, histopathology, and define challenge strains Monitor thymus for atrophy CAV Marek s disease Virus isolation/molecular detection, and serology to understand respiratory challenge Typing of challenge viruses to define epidemiology

Thank You fred.hoerr@gmail.com www.vetdx.com II Seminario Internacional Avicola Merial