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

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”

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

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

“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

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

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

Enzootic pneumonia=M hyo + bacteria M hyo facilitates bacterial infections Cough, malaise and anorexia Moderate fevers 1030-1050 Expiratory dyspnea / “thump” Variable morbidity and mortality Stunting, chronic pneumonia, death Strategic interventions (medication or vaccination) can influence outcome and/or subsequent disease severity

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%)

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

Normal Lung: Gross

Actinobacillus pleuropneumniae

Bronchogenic pneumonia Bacterial (B. bronchiseptica)

Interstitial pneumonia (Viral, bacterial septicemia)

M hyo: mild and “early”

Early / mild M hyo.

SIV can be cranioventral

Lesion is not pathognomonic

Enzootic: Mhyo + P. multocida

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

PRDC: Mhyo + P. multocida + PRRSV

Enzootic: Can resolve over time

Enzootic: Resolution takes time

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

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.

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….”

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

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

Mh IHC

M. hyopneumoniae: IFA

M. hyopneumoniae: Histopathology

M hyo: BALT hyperplasia

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

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

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

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

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

Diagnostic profiles change over time

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

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