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– 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 pneumoniaBacterial (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 – 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