VDPAM 445 Swine Topics Respiratory Disease Control Dr. Alex Ramirez Veterinary Diagnostic and Production Animal Medicine Iowa State University

General introduction

Endemic Pneumonia App- continual outbreaks, chronic pleuropneumonia Sometimes other bacteria as well Enzootic Pneumonia Mycoplasma hyopneumoniae Pasteurella multocida Porcine Respiratory Disease Complex All of the above (especially M. hyo) PRRSV SIV Others: PCV2, PRV, H. parasuis, S. suis,

Diagnostics Gross pathology: APP versus all others APP & A. suis vs. others Organism identification Culture FA PCR IHC: immunohistochemistry (with histopath) Fixed tissue, easy sample preservation Histopath Prove disease, organism presence is insufficient

Question: Is this mycoplasma?

Diagnostics Serology: serological profiling Sampling issues Timing of infection but not necessarily timing of disease Sampling issues Tissue preservation in formalin Buffered Multiple sites <1cm tissue thickness Number of animals Example on next slide Sick (necropsy) versus healthy (slaughter checks)

Diagnostic Sampling Strategies Small numbers of pigs will result in missed diagnosis PRDC case: 21 pigs submitted for necropsy Pathology/microbiology: No lesions =5 Gastric ulcer = 2 PMWS = 5 PRRSV = 2 SIV? = 1 APP? = 3 (non-typeable) P. mult. = 2 Bordetella = 2 Strep suis = 1 M. hyo = 8 Serology: M. hyo+, SIV+, PRRSV (late +) Slaughter check: Low average percent pneumonia, a few pigs severe

Diagnostic Considerations: Value of Tests Laboratory tests should fit with clinical observations Pigs cough: Pursue rule-outs (M. hyo, influenza) Pigs grow slowly without overt disease - diets/environment? Specific versus non-specific tests Necropsy and slaughter exams (disease severity) Laboratory tests (agent identification) Record analysis (rarely identifies a specific cause) Documenting management activities “Gum shoe” approach One revealing observation is often worth more than 100 serological tests SOP vs. Actual

Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae Primary cause of enzootic pneumonia Most herds are infected except SPF herds Transmission is via aerosol Air is PCR positive Difficult to prevent between herd spread Disease often manifested in finishing Organism very slow to grow (weeks) A few get infected from sows  spreads slowly through nursery pigs Lateral transmission from older pigs

Mycoplasma hyopneumoniae Diagnosis Clinical signs: only cough 10 days after challenge Severe sickness with infection of SPF herds? Mild - minimal consequence in otherwise disease free pigs Macroscopic lesions Anterior-ventral consolidation Not specific to M. hyo

Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae Diagnosis Histopathology: peribronchiolar lymphocytic cuffing Organism ID FA- need fresh tissue, approx. 50% sensitivity Culture - slow grow, overgrowth by M. hyorhinis PCR - “It’s everywhere” IHC Serology: several ELISA’s available Vaccination will also induce titers that persist for a short time

Mycoplasma Vaccination Second most common vaccine used in growing pigs Common in population Potentiator of other respiratory disease Issues Mandatory (?) in herds with continuous flow, multiple rooms within the same building, virulent PRRSV One vs. two dose products Use one dose in “controlled” situations or if labor is a big concern Two doses will almost always be better Start early (3weeks) Product cost is usually equal Many combine with PCV2 vaccination

Mycoplasma Vaccination Maternal antibody interference Probably will not interfere with vaccine induced protection No real reason to vaccinate sows pre-farrow Only vaccinate gilts before entering herd PRRS eradication  Mycoplasma eradication Consider where pigs will be grown and finished May still need to vaccinate pigs

M. hyo Treatment plan Antibiotics? Control other diseases Vaccination Now Earlier Routes Water Feed Injectable Control other diseases Vaccination Other groups Timing – watch for PRRS seroconversion

Actinobacillus pleuropneumoniae (APP)

Actinobacillus pleuropneumoniae (APP) Cause of contagious pleuropneumonia Transmission by close contact and short distance aerosols Many pigs harbor organism in upper airways Clinical disease occurs with environmental stress in many cases Malfunctioning curtain controller  temperature fluctuation  organism gains entrance to lung  severe (bad), rapidly developing necrotizing and hemorrhagic pneumonia with pleuritis

Actinobacillus pleuropneumoniae (APP) Clinical signs Sudden death Sudden onset of rapid, deep breathing Minimal cough (not an airway irritant) Fever initially or if mild-to-moderate; subnormal in severely affected pigs Hemoptosis and blood from nostrils in agonal phase (euthanize if possible) Mortality can reach 10% of barn in one day Pigs quit eating AND DRINKING

Actinobacillus pleuropneumoniae (APP) Post-mortem lesions Necrotizing, hemorrhagic, usually multi-focal pneumonia Pleuritis will be present if pig survives for at least 18 hours after challenge Similar lesions can be seen with Actinobacillus suis If APP  mass treatment via injection often indicated; other types of pneumonia treated less aggressively; can’t wait for test results to start therapy

Actinobacillus pleuropneumoniae (APP)

Actinobacillus pleuropneumoniae (APP) Diagnosis Initially: clinical signs and gross pathology Culture: isolation followed by capsular serotyping Some relationship between capsular serotype and virulence: Type 1’s are worst; followed by 5’s USA: 1, 5, 7 and 3 are most common (odd numbers) Europe: 2 and 6 are most common Serology Complement fixation: recent infection ELISA’s: capsule, endotoxin, cross-reactivity problems Hemolysin neutralization: cross-reactions with A. suis

APP Vaccination Most commercial vaccines are bacterins Administer 2X at 2-4 week interval prior to finishing Capsular serotypes must be matched Use autogenous vaccines if: Commercial vaccines don’t contain the correct serotype May have within serotype heterogeneity Marginally effective: lack ApX toxins which are the main virulence factors for causing disease Side effect potential: Injection site reactions Fever, off-feed, reduced daily gain

APP Vaccination Riboflavin deficient mutant Newer vaccines Capsular deficient mutant (MLV): BINOBL Given IM Frozen product: order, shipped on dry ice, use immediately Limited replication at injection site Sufficient production of ApX toxins to induce a protective immune response Riboflavin deficient mutant Not commercially available Knock out riboflavin synthetase Add riboflavin to organism and inject IM

APP Treatment Plan Antibiotics Ventilation Vaccination ? YES!! ASAP INJECTABLE Water Feed Duration of treatment Ventilation Vaccination ? Different source of pigs

Actinobacillus suis

Actinobacillus suis Will behave like APP but less severe and short term Problem with “healthier” herds Generalized septicemia like H. parasuis, erysipelas Produces Type I hemolysin No commercial vaccines available Autogenous vaccines used in refractory cases

A. suis Treatment Plan Antibiotics Correct diagnosis is critical APP vs A. suis need immediate action Sources Injectable Water Feed ??? Correct diagnosis is critical Vaccination with autogenous??

Pasteurella multocida

Pasteurella multocida Pneumonia Not a primary cause of pneumonia Experimental infection only with active M. hyo infection present “Fuzzy thinking”: not important because secondary pathogen but primary causes are nearly always present!! Medication of pigs with non-App pneumonia is mostly directed at P. multocida Acute swine influenza outbreaks Enzootic pneumonia or PRDC Environmental mishaps

Pasteurella multocida Pneumonia Little known about pathogenesis Studies just beginning Generally Type A, non-AR toxin producing Normal inhabitant of upper airways Can cause pleuritis Diagnosis Culture and sensitivity Sort out primary causes

P. multocida Treatment Plan Antibiotics Injectable Water Feed Environment – Ventilation Address other diseases PRRS Mycoplasma Etc.

Atrophic Rhinitis (AR)

Atrophic Rhinitis Bordetella bronchiseptica Pasteurella multocida Causes atrophic rhinitis Enables P. multocida to colonize nasal epithelium Pasteurella multocida Causes progressive atrophic rhinitis Produces AR toxin (dermatonecrotoxin) Highly potent: inject small quantity  turbinate atrophy Mainly capsular Type D but also Type A

Atrophic Rhinitis Clinical signs Lesions Deviated snout: side ways or pushed up Tear staining at medial canthus Sneezing Bleeding from nostrils Lesions Turbinate atrophy: primarily ventral scroll of ventral turbinate Septal deviation

Atrophic Rhinitis

Atrophic Rhinitis Severity influenced by: Air quality and environment; especially in nurseries Genetics Yorkshires more susceptible to developing severe lesions Age of sow herd: immunity of dams Colostral antibody levels Level of shedding  vertical transmission Age at infection Weaning age: <14 days eliminates vertical transmission

Atrophic Rhinitis Stepwise approach Sow vaccination pre-farrowing Gilts pre-breeding is always recommended LA200 (200 mg/ml oxytetracycline) to piglets 15 mg/# dose 1, 7, 14, 21 days or 1, 7-10, weaning Naxcel (2 mg/# dose) instead of LA200 No benefit against Bordetella bronchiseptica Vaccinate pigs Two doses: 7 days and weaning One dose: weaning

AR Treatment Plan Antibiotics Prevention Environment Water Feed Injectable Prevention Vaccination Environment

Psuedorabies (Aujesky’s or PRV)

Pseudorabies Virus Eradicated from the USA commercial herds in late 2003 to early 2004 Respiratory disease in any age pigs in addition to CNS signs in neonates and reproductive disease in sows Occasional necrotic rhinitis  crusty nose and nasal discharge Important rule-out (along with SIV and PRRS) for sow herd off-feed Will have fever

PRV Vaccination Vaccines were highly effective Regulatory based vaccination in Stage II areas Vaccinated sow herd 4 times per year- IM Vaccinated pigs once IM by 12 weeks of age In herds with active infections Vaccinated pigs at birth intra-nasally Used vaccines that were approved for IN use, must replicate in the nasal epithelium to be effective Vaccinated pigs twice IM Vaccine reduced shedding in individual pigs Can stop shedding on a population basis

PRV Eradication Blanket vaccination to reduce/eliminate shedding and transmission Improve internal biosecurity AIAO production People, equipment movement Improve external biosecurity Hog truck sanitation Monitor closely via serology to determine where failure (active infection) is occurring

Other Viruses

Other Viruses PRCV Inclusion body rhinitis Mild respiratory disease in young pigs Natural deletion mutant of TGE virus Can’t attach to intestinal epithelium Significance ????? Test cross reacts with TGE Inclusion body rhinitis Porcine cytomegalovirus Common disease in early nursery pigs High pitched sneezing Minimal clinical impact if no other problems Severely affected will develop necrotic rhinitis

Other bacteria

Other bacteria Will be discussed in other sections Salmonella cholerasuis Interstitial pneumonia – Wet lung Septicemia – purple pigs +/- diarrhea Steptococcus suis Cranioventral consolidation Haemophilus parasuis

Agents Discussed in future

Swine Influenza (SIV)

Swine Influenza Virus (SIV) Type A influenza virus H1N1: traditional strain in US H3N2: new strain in US 1998 Present in Europe for many years Some evidence for presence in US before Spread throughout country in 2-3 years H1N2: Detected in Indiana 1999 Combination of H1N1 and H3N2 Others: Exposure to water fowl  outbreak limited to a one or a few herds

Swine Influenza Virus (SIV) Clinical signs Short term disease: <4-7 days Fever: variable Respiratory signs: 1-2 days after challenge Increased rate “Thumps”: abdominal breathing “Wet Cough”: minimal with pure infection Gross lesions Look like M. hyo

Answer: SIV

SIV Vaccination Strains: H1N1 (traditional), H3N2 (new) Sow herd vaccination: common, concerns? Pig vaccination Two doses recommended, often one dose given Relatively high cost Multivalent vaccines and/or autogenous Role of maternal antibody interference Vaccinate sows pre-farrowing  protective titers until 12 weeks of age MDA’s may interfere until 8-10 weeks of age  small time frame to vaccinate Original antigenic sin

Porcine Reproductive and Respiratory Syndrome Virus (PRRS) Discussed in another lecture

Circovirus (PCV2 & PCVAD) See Dr. Baker’s Lecture

Porcine Circovirus Type II Type I: cause of infectious congenital tremors?; porcine cell line contaminant Type II: Cause of PCVAD (Porcine Circovirus Associated Disease); old name = PMWS (post-weaning multi-systemic wasting syndrome) Depletion of germinal centers in lymph nodes and Peyer’s patches are characteristic lesions Much virus located in these tissues Virus also present in normal pigs and tissues Lesions like PRRS Disease in US: PRRS associated, mild, older pigs Disease in Europe: devastating, younger animals

PCV2 Small DNA virus none-enveloped Present in most pigs Hard to disinfect Present in most pigs Exposure is VERY common Negative herds ??? Concern with present case definition (PMWS/PCVAD) Wasting Lymphoid depletion PCV2 Excellent web site  www.pcv2.org

Vaccines Just on the market in 2006 In Europe have had a vaccine from Merial but for sows only! ISU involved in development of one vaccine (chimeric with Fort Dodge) Results? So far looking VERY PROMISSING!

PCV Vaccines

PCVAD is usually seen in 4-10 week old pigs in Canada and Europe PCVAD is typically seen in the 10-20 week old pigs in the US -Morbidity 2-25% -Mortality 1-10% Courtesy Dr. J. Harding

Markedly enlarged inguinal lymph nodes are commonly observed in pigs with PCVAD

Porcine Dermatitis and Nephropathy Syndrome (PDNS) Etiology unknown PRRS PCV2 PRRSV + PCV2 P. multocida Streptococcus sp.

PCV2 coinfections in 484 U.S. field cases: ISU-VDL 9 164 10 77 13 3 92 68 37 11 20 40 60 80 100 120 140 160 180 PCV2 Alone PCV2+PRRSV PCV2+PRRSV+SIV PCV2+PRRSV +M.hyo. PCV2+SIV PCV2+SIV +M.hyo. PCV2+M. hyo. PCV2+Bacterial septicemia PCV2+Bacterial pneumonia PCV2+ Others Number of Cases Rarely see PCV2 singular infection

PCV2 Treatment Plan Vaccination Work on co-infections! Earlier the better Work on co-infections!

Acknowledgements I would like to recognize others for their significant contributions to this presentation: Dr. Brad Thacker Dr. Locke Karriker Dr. Pat Halbur

Questions ?