Interactions Between M. hyopneumoniae and Other Pathogens

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Interactions Between M. hyopneumoniae and Other
Pathogens

• Eileen L. Thacker
• DVM, PhD, DACVM
• Iowa State University

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Porcine Respiratory Disease Complex (PRDC)

• Economically significant to the swine industry in
  the U.S.

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Pathogens Associated with PRDC

• PRRSV
• Mycoplasma hyopneumoniae
• Swine influenza virus (SIV)
• Actinobacillus pleuropneumoniae
• Streptococcus suis
• Pasteurella multocida
• Aujeszkys disease (Pseudorabies virus )

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Enzootic pneumonia

• Mycoplasma hyopneumoniae
• Mycoplasmal pneumonia
• M. hyopneumoniae plus
• Pasteurella multocida
• Bordetella bronchiseptica
• Haemophilus parasuis
• Actinobacillus pleuropneumoniae
• Etc.

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M. hyopneumoniae P. multocida(Enzootic
Pneumonia)
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PRDC

• Enzootic pneumonia
• PRRSV
• SIV
• PCV 2?

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Which Diseases are Considered the Biggest Problem
in PRDC?

• Varies from farm-to-farm
• Porcine respiratory disease complex common
  problem in finishing pigs
• NOT in the scope of this talk to discuss all
  pathogens
• results of current research

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Mycoplasma hyopneumoniae

• Cause of enzootic pneumonia
• Other secondary pathogens
• APP
• Pasteurella multocida
• PRRSV
• Clinical signs-M. hyopneumoniae alone
• mild, dry, nonproductive cough

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Pathogenesis

• Very slow to colonize and multiply
• 2 weeks to induce observable lesions
• 4-6 weeks before serum antibodies produced
• 4-8 weeks to resolution
• Organisms never eliminated from pig?

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• Adheres only to cilia of airways
• Does not invade lung tissues

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Disease

• Decrease the function of the mucociliary
  apparatus
• decrease clearance of other pathogens and debris
• Modulation of the immune system
• immunosuppression-macrophages - APP
• immunostimulation-lymphocytes
• cytokine production

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Pathology

• Chronic pneumonia
• 2-3 weeks for pneumonic lesions to appear
• mild
• focal, well-demarcated area of cranioventral
  consolidation

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Histopathology

• Bronchopneumonia
• Perivascular and peribronchiolar cuffing
• Influx of lymphocytes and macrophages
• primarily B cells
• non-specific

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Evasion of the Immune System

• Mucosal pathogen
• location
• Structure and make up of surface
• slime layers
• capsule
• no cell wall

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Proinflammatory Cytokines

• TNF-?
• IL-1
• IL-6
• Important in further inducing inflammation in the
  lungs

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Dual infection of Pigs with PRRSV and
Mycoplasma hyopneumoniae

• E.L. Thacker, P.G. Halbur, B.J. Thacker and R. F.
  Ross
• Iowa State University

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Porcine Reproductive and Respiratory Syndrome
Virus
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PRRSV

• An Arterivirus
• Enveloped RNA virus
• all infect macrophages
• all cause prolonged infections
• High mutation rate due to method of replication
  constant minor changes
• Accounts for differences between isolates
• No such thing as strains

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Clinical Signs

• Severe to no clinical disease in the field
• In our experimental model
• maximum pneumonia is 10 days
• fever, respiratory distress, lethargy, anorexia
• no cough
• pneumonia resolved by 21-28 days

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Pathology

• Diffuse, tan-mottled consolidation of the lungs

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Evades the Immune System

• Persists
• gt 100 days
• Very slow to ineffective systemic immune
  response
• viremia in presence of antibodies
• can be reinfected by different strains
• alteration of immune response by directing
  cytokines

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Experimental Design

• Three different inoculation protocols
• PRRSV first (-10 days)
• M. hyopneumoniae first (-21 days)
• concurrent (0 days)
• Three necropsy dates
• 3 DPI
• 10 DPI maximum PRRSV pneumonia
• 28 DPI maximum mycoplasma pneumonia

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Conclusions

• Pigs infected with both M. hyopneumoniae and
  PRRSV
• S
• significantly increased clinical respiratory
  disease
• macroscopic lesions consistent with PRRSV-induced
  pneumonia lasted significantly longer
• increased M. hyopneumoniae-induced pneumonia at
  10 days post infection with both

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PRRSV - 28 DPI
PRRSV- 10 DPI
M. hyopneumoniae - 28 DPI
Dual Infection - 28 DPI
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Conclusions (cont.)

• No long term increase in M. hyopneumoniae-induced
  pneumonia macroscopically
• Pigs with minimal to no macroscopic mycoplasmal
  pneumonia lesions exhibited potentiation of
  PRRSV-induced pneumonia

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WHY?

• Pathogenesis complement each other
• M. hyopneumoniae attracts macrophages for PRRSV
  to infect
• both induce inflammation
• both direct the immune response from a Th1
  towards a Th2 response
• production of IFN-? is correlated to virus
  clearance
• delayed in pigs infected with both pathogens

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Why?

• Immune system
• both evade the immune system
• both modulate the immune system
• both chronic
• PRRSV-persistance
• M. hyopneumoniae chronic

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Interaction between M. hyopneumoniae and SIV

• E. Thacker, B. Thacker
• and B. Janke
• Iowa State University

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What do we know

• M. hyo
• infect epithelial cells (cilia)
• causes a chronic pneumonia

• SIV
• infects epithelial cells
• causes acute pneumonia but will last 3 weeks
  histologically

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Experimental Design

• M. hyopneumoniae strain 232 intratracheally (-21
  Trial Day)
• ISU SIV inoculum (H1N1) nebulized intranasally (0
  Trial Day)
• Pigs necropsied at 3, 7, 14 and 21 days post SIV
  infection

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Confusing Appearance
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Results

• Dual infected pigs had highest coughing scores
• Pneumonia lasted longer-additive in nature

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Conclusions

• Unlike with PRRSV, SIV and M. hyopneumoniae
  appear to be additive
• Both infect epithelial cells important for
  secondary pathogens
• Different pathogenesis than with PRRSV

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Circovirus (PMWS)
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• PCV 2 alone induces minimal disease
• Combined with PRRSV, Porcine Parvovirus results
  in significant increase in pneumonia
• Interaction and role of M. hyopneumoniae?
• Role of vaccination?
• Mechanism is unknown
• Can bet immune system is involved

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Conclusions

• M. hyopneumoniae and PRRSV are both important
  factors in PRDC
• The pigs in our studies had no other pathogens
• these contribute to and interact with each other
• These studies are aimed at beginning to
  understand the interaction between the various
  pathogens

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Conclusions (cont.)

• PCV 2 increasing in importance of disease
  interactions
• Other pathogens such as P. multocida and B.
  bronchiseptica present add to the disease
• Diagnostics become very important on individual
  farm settings to implement the appropriate
  controls

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Conclusions (cont.)

• As our understanding of the pathogenesis
  increases, appropriate intervention strategies
  can be developed
• vaccines very important
• new and current
• antibiotics
• strategic timing of above

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