1. Pathological Diagnosis of Mycoplasmosis in Swine
Swine Mycoplasma Pneumonia Workshop
FDA / CVM
March 6,7 of 2002
Kansas City, MO
Kent Schwartz

2. Swine Pneumonia: Early Years
“Normal” for pigs to cough / scratch
Enzootic (Mycoplasma + Pasteurella)
Ascarid Migration
1918: H1N1 Swine Influenza
Atrophic rhinitis (Bordetella and Pasteurella)
Small farms / “home remedies”

4. Mechanization: Trend to Confinement and Larger Herds
M hyo, SIV, ascarids, AR
More science, agents, diagnostics
PRV, Actinobacillus pleuropneumonia
Pasteurella multocida with M hyo
Age of therapeutics (antimicrobials)
“Vaccination” products

6. Era of Altered Ecology/New Agents
Segregated rearing / larger populations / Altered herd immunity / altered ecology
M hyo, SIV, App remain
Bacterial “Opportunists” Emerge
Hemophilus parasuis, Streptococcus suis
Actinobacillus suis, Salmonella sp. others
“New” agents; respiratory and systemic
PRRSV, PCV, SIV H3N2, PRCV
Porcine Respiratory Disease Complex (PRDC) is a multifactorial culmination

7. “Immune Confusion” Respiratory Tract: mixing vessel for:
Systemic diseases (PRRSV, PCV, bacteria)
Respiratory agents (SIV, bacteria)
M hyo
“Herd immunity” is variable for agents
Sow herd “stability” influences maternal immunity
Piglet infection status variable and sequential
Immune status is variable
Many permutations of agents involved
Many permutations in sequence of infections and sequence may matter

8. M hyo remains Central and Primary
Infection is common; not easily eliminated
Infection persists for months
Alters mechanical clearance of debris
Inflammation / immune-mediated damage
Altered, nonproductive immune response
“Immunologically privileged” site of infection so clearance is compromised
Provides sites for opportunists
Synergy with other lung pathogens

9. Clinical Disease: M hyo alone
Mild malaise
No fever
Cough: nonproductive / chronic
Moderate morbidity / no mortality
Altered growth performance
ADG
Feed efficiency

10. Enzootic pneumonia=M hyo + bacteria
M hyo facilitates bacterial infections
Cough, malaise and anorexia
Moderate fevers
Expiratory dyspnea / “thump”
Variable morbidity and mortality
Stunting, chronic pneumonia, death
Strategic interventions (medication or vaccination) can influence outcome and/or subsequent disease severity

11. PRDC = Enzootic pneumonia + virus (M hyo + bacteria + virus)
Severe depression, high fever, anorexia
Expiratory dyspnea (thump)
Rapid loss of condition
Medication less efficacious
High morbidity and frequently high mortality (5-20%)

12. Gross Pathology: Bronchopneumonia Interstitial pneumonia
Cranioventral, firm, exudate in airways
Interstitial pneumonia
Diffuse, mottled, lobular distribution
Edema fluid in airways
Both can occur simultaneously: common in field cases of PRDC

13. Normal Lung: Gross

14. Actinobacillus pleuropneumniae

15. Bronchogenic pneumonia Bacterial (B. bronchiseptica)

16. Interstitial pneumonia (Viral, bacterial septicemia)

17. M hyo: mild and “early”

18. Early / mild M hyo.

19. SIV can be cranioventral

20. Lesion is not pathognomonic

21. Enzootic: Mhyo + P. multocida

22. PRDC: Enzootic + viral (M hyo + P. multocida + PRRSV)

23. PRDC: Mhyo + P. multocida + PRRSV

24. Enzootic: Can resolve over time

25. Enzootic: Resolution takes time

26. M hyo: Gross Diagnosis Early: 10 days-4 weeks Active: 2-6 weeks
Cranioventral, lobular, red, firmness
Active: 2-6 weeks
Clearly demarcated, grayish, atelectasis
Airways prominent with mucopus
Resolution: 5-20 weeks
Gray fissures of atelectasis
Distorted lobe structure of normal lung tissue
A population will have animals at all stages of disease with variable severity

27. Histopathology: Basics
Bronchopneumonia
Extends from small airways
Bronchiolitis with exudate and debris
Adjacent alveoli, interstitium
Interstitial pneumonia
extends from alveolar septae
can involve small airways
Both often present in chronic disease or in mixed infections.

28. Histopathology is Fallible
Agents and agent combinations outnumber possible responses
Chronic lesions are less specific
“Classic” lesions only with single agents at some stages of disease
Few lesions are pathognomonic or “etiologically specific”
“Lesions are compatible with….”

29. M hyo: Histopathological Diagnosis
Early: 10 days-4 weeks
peribronchiolar lymphohistiocytic inflammation; scattered neutrophils
Active: 2-12 weeks
mucopus, atelectasis
Resolution: 5-20 weeks
BALT hyperplasia
A population will have animals at all stages of disease with variation in lesion severity

30. What else can “look” like M hyo ?
Chronic persistence of antigen/agent
Lymphoid hyperplasia / airway cuffs
Subacute SIV = Early M hyo
Ascarid migration; resolving
Chronic bacterial pneumonia
Chronic viral pneumonia
It is often difficult to demonstrate organisms in chronic lesions

31. Mh IHC

32. M. hyopneumoniae: IFA

33. M. hyopneumoniae: Histopathology

34. M hyo: BALT hyperplasia

35. Key Points: Pathological Diagnosis
Gross lesions are “compatible with but not specific for” M hyo
Microscopic lesions are “compatible with but are not specific for” M hyo
Sensitivity and Specificity of pathology??
Most field cases are mixed infections
M hyo, bacteria, viruses
Time for resolution varies with:
Severity and extent of initial lesion
Presence of concurrent pathogens

36. Etiologic diagnosis requires:
Demonstration of specific agent
M hyo isolation is not routine
Demonstration of specific antigen
IHC, FAT, ELISA
Demonstration of specific agent nucleic acid
PCR and PCR based assays
Serology confirms antibody but is NOT a definitive etiologic diagnosis

37. Diagnosis of Swine Pneumonia
Research / Infection models
controlled infection, controlled specimen collection, and standardized evaluations
Predictable outcomes / valid measures
Field Cases: variability is uncontrolled
Descriptive pathology has limitations
Demonstrate agents: specimen dependant
age, stage, specimens, interventions
Interpret results in the context of clinical signs, history and population dynamics

38. An accurate and useful field diagnosis uses all available information
Clinical signs, history, diagnostic records
Production records
Compatible gross lesions
Compatible microscopic lesions
Identify agents with appropriate tests
Primary agents, secondary agents
Define epidemiology in the population
Serologic: cross-sectional or longitudinal
In population, infection and immunity status varies so need statistical sampling techniques

39. Mixed agents, duration, population variability makes definitive diagnosis a challenge

40. Diagnostic profiles change over time

41. Summary: M hyo in swine M hyo is common in swine populations
M hyo alone is mild disease with cough, suppression of growth and feed efficiency
M hyo duration of effect (3-20 weeks) creates opportunities for co-infections
Not all are affected equally/simultaneously
Enzootic pneumonia is M hyo + bacteria
PRDC is M hyo + bacteria + viruses

42. Summary: M hyo in swine Takes time for lesions to develop / resolve
Pathology is useful to describe severity
Variability of lesion severity in populations
Most field cases are mixed infections
Field measures of current interventions
Reduced prevalence of clinical pneumonia
Reduced lesion prevalence and severity
Reduced medication cost, treatments
Less variation in growth rate
Control of M hyo disease severity often does mitigate severity of other endemic diseases
Infection models are useful to evaluate M hyo intervention strategies and disease interactions