Laboratory Animal Medicine Blue Book, 3rd Ed. (2015) > Chapter 16. Biology and Diseases of Swine > Flashcards
Chapter 16. Biology and Diseases of Swine Flashcards
What group completed sequencing of the swine genome?
Swine Genome Sequencing Consortium
New diseases added to this edition of the swine chapter
Porcine circovirus-2 (PCV2), Nipah virus, porcine lymphotrophic herpes virus, Ebola virus
Swine taxonomy
Order:Artiodactyla (even-toed ungulates)
Family: Suidae
Species: Suc scrofa domestica
United States SPF status of swine
Proprietary connotation - a program based on management procedures that reduce or eliminate diseases that stunt growth
-Does NOT mean animals are completely free of diseases that may interfere with research
Age when swine reach sexual maturity & slaughter weight
- 5-6 months
- 115-130 kg at this age
Average birth weight of swine
- 4 kg
- Exponential growth phase during adolescence
Swine weight for research use
- Usually 15-30 kg at 8-12 weeks of age
- Commercial swine rarely used for long term projects
- Projects >3 weeks best performed using miniature swine
Breeds of miniature swine
- Common: Yucatan, Hanford, Sinclair, Hormel, Gottingen
- Limited availability: Panepinto, Vietnamese potbellied, Ohmini, Pitman-Moore, Chinese dwarf
- Generally health status of mini pigs is higher than SPF commercial swine
- Body weight range: 30-50 kg
Vendor suppliers for research swine
- Should be purchased from vendor herds validated brucellosis-free & qualified pseudorabies-negative by USDA
- Deworm at 4-6 week intervals & administer preventive treatments for ectoparasites
- Wealings vaccinated against erysipelas & leptospirosis
- Breeding animals also vaccinated for Bordetella bronchiseptica, Pasteurella mulocida, Escherichia coli
- Minimum 72 hr acclimation period after arrival - PE, screen for parasites
- Ideally pigs should be purchased from a single source with established health status to take advantage of natural herd immunity
- Herds that maintain SPF status have an odds ratio of 0.2 relative to conventional herds for development of diarrhea
Swine housing
- Pens rather than cages
- Pens constructed of chain-link fencing or stainless steel or aluminum bars (avoid wood b/c pig chew & difficulty to sanitize)
- Provide indestructible toys or balls for enrichment, satisfy rooting instinct
- Avoid smooth flooring; should have rough surfaces to provide traction & provide wear on hooves
- Cover floor in deep wood-chip bedding - keeps pigs clean & allows rooting; BUT they may eat bedding, esp when fasted
- Ideal = slatted fiberglass floors with grit to provide hoof wear
Watering for research swine housing
- Readily use automatic watering systems
- Check system daily b/c swine are susceptible to ‘salt poisoning’ neurologic syndrome if water deprived
Feeding for research swine housing
- Individual feeding bowls reduce food aggressive behavior
- Secure food bowls to cage or flooring
- Bowls should be made of indestructible material or pigs will chew
Social housing of swine
- Prefer to have contact with other pigs
- Dominance fighting will occur unless pigs are socialized; can provide cage walls that allow visual & snout contact but attempt to house in stable pairs or compatible groups
Swine restraint
- Sling - like the Panepinto sling (more humane than snout tying)
- Small swine can be restrained similar to dogs
- Train to walk on leash
- Restrained against side of cage with portable handheld panels (usually 60x80 cm)
IM injection technique for swine
Neck or hind limb
Venous access sites for swine
Auricular, cephalic, external & internal jugular, anterior vena cava, lateral saphenous, cranial abdominal (mammary), femoral, tail vein, accessory cephalic & common dorsal digital vein
- Cranial vena cava - to prevent damage to the recurrent laryngeal nerve, only collect from right side
- Femoral vein - palpate pulse to locate, not visualized on surface
- Most peripheral vessels are deep & not visible
- Most vessels can be accessed with standard sized needles; largest needed would be 20G, 1.5 inch needles
Intubation of swine
Perform in dorsal recumbency using a laryngoscope to lift the tongue & mandible to visualize the vocal cords
Swine cardiovascular models
Atherosclerosis, coronary arterial stenosis
and infarction, congenital heart disease, volume and
pressure-overload heart failure, electrophysiology,
and testing of grafts, stents, and interventional devices
-Ventricular septal defect (VSD)
-von Willebrand’s disease
Atherosclerosis models in swine
- Rapacz familial hypecholesterolemia
- Induced models: feed high cholesterol, fat-enhanced diets to standard breeds
- Some breed much more susceptible to diet-induced atherosclerosis
- Rapid form of inducing atherosclerosis = damaging endothelium with balloon catheter (balloon endarterectomy); benefit is that is produces lesion in a specific anatomic area
Gastrointestinal models in swine
- Omnivores & digestion physiology is similar to humans
- Nutrient absorption and growth, GI transport, hepatic metabolism, total parenteral nutrition, necrotizing enterocolitis
Renal models in swine
Renal hypertension, vesicoureteral reflex, intrarenal reflux, urinary obstruction
Surgical models using swine
-Laparoscopic & endoscopic procedures
-Catheter delivery of interventional devices
-Transplantation: heart, lung. liver, kidney, viscera (b/c ideal size of organs, surgical anatomy, response to immunosuppressiev therapy for translation)
-Xenotransplantation - transgenic strains developed
-Plastic surgery
-Fetal surgery
-Procedures in the musculoskeletal, central nervous, gastrointestinal,
urogenital, and cardiopulmonary systems
Other research models using swine
Systemic and dermal toxicology, septic and hemorrhagic shock, immunology, diabetes, malignant melanoma, malignant hyperthermia, and gastric ulceration
Cardiovascular system of swine
- Similar to humans, esp coronary artery - blood supply to coronary artery is R-side dominant & does NOT have preexisting collateral circulation - this makes flow similar to 90% of humans
- Electrophysiologic system more neurogenic than myogenic w/ prominent Purkinje fibers
- Left azygous (hemiazygous) vein drains the intercostal vessel into the coronary sinus (unlike other species) - vessel may be ligated or blocked with a balloon to provide total coronary venous drainage into the coronary sinus
- Aorta has true vaso vasorum like humans
GI tract anatomy of swine
- Stomach has muscular outpouching, the torus pyloricus, near the pylorus
- Bile duct & pancreatic duct enter duodenum separately in proximal portion
- Anatomic divisions between duodenum, ileum, & jejunum are indistinct
- Mesenteric vessel branches form vascular arcades in the subserosa of the intestine rather than in the mesentery like other species
- Majority of large intestine arranged in spiral colon in left upper quadrant of the abdomen = series of centrifugal & centripetal coils includes cecum, ascending, transverse, & majority of descending colon
- Tenia & haustra present on the cecum & large intestine
Lymph nodes of swine
INVERTED - germinal centers located in the internal portion of the node
Other unique anatomic features of swine
- Thymus located on ventral midline of trachea near thoracic inlet (rather than proximal to larynx) & fused lobes that appear as single organ
- Major portion of thymus is located in the neck & single pair of parathyroid glands located in medial aspect of this gland near larynx
- Penis fibromuscular with corkscrew-shaped tip located in preputial diverticulum near the umbilicus; has sigmoid flexure as it exits pelvic canal
- Pancreas bilobed & surrounds and encompasses superior mesenteric vein
- Liver organized into lobules by microscopic fibrous septae
- Cyctochrome P450 system similar to humans, but there are many subtle differences that impact toxicology studies
Male accessory sex glands in swine
Prostate, vesicular gland, bulbourethral glands
Female reproductive system in swine
Bicornuate uterus with lengthy, tortuous fallopian tubes
Swine nutrition
- Considerable variation in genetic capacity to accumulate lean body mass among breeds
- ‘Farm swine’ at 6 mth of age may have a lean body weight 5-6x greater than a micropig breed
- Small breeds often require fixed-quantity breeding to control obesity - necessitates higher margin of safety for many nutrient concentrations to prevent deficiencies
- Diets for microbreeds generally lower energy, higher fiber
Essential nutrients for swine
- Do NOT require elemental sulfur (ruminants do) in diet when adequate sulfur-containing amino acids (methionine & cysteine) available
- Sulfur essential for synthesis of various compounds incl taurocholic acid, chondriotin sulfate, glutathione, lipoic acid
- Methionine alone can meet the total sulfur-containing amino acid requirement in swine b/c can synthesize cysteine from methionine
- Amino acid requirements refer to the L-isomer = the most biologically active form in swine & most common form found in plants and animals
Sexual maturity in swine
- 3-7 mths of age
- Most mini breeds = 4-6 mths
Average litter size for swine
- Farm swine: 8-12 piglets per litter
- Mini breeds: 4-6 piglets per litter
- Litter size varies with parity - smallest at 1st parity, max size between 3rd & 7th parity, then stable or decreasing
Swine estrous cycle
- Average 21 days cycle, range 17-25 days
- Estrus lasts 48 hr (range 1-3 days)
- Prior to estrus onset, vulvar reddening & swelling, mucus discharge, nervousness, increased activity
- During estrus, sows will stand immobile when pressure applied to rump
- Silent estrus common in swine; presence of boar can facilitate estrus detection
Fertilization in swine
- Optimal fertilization when insemination takes place 12 hr prior to ovulation
- Variability in time between estrus & ovulation = difficult to determine when females will ovulate, so usually breed sow twice during estrus
- Litter size tends to increase with multiple matings per estrus
Mating schemes for swine
- Pen Mating = sow & boar left together during estrus
- Hand Mating = place sow & boar in same pen for 12-24 hr intervals during estrus until female no longer receptive
- AI = conception rates typically 10-15% lower compared to natural service; inseminate sows 10-30 h after beginning of estrus
Pregnancy detection in swine
1st sign of pregnancy = failure to return to estrus 18-24 days following mating
-Non-estrous sows most easily detected by exposure to a boar - pregnant sows decrease rooting, walking, standing, general activity & increase inactivity & sleeping
-Estrus detection reported as 98% accurate & can be used to determine pregnancy status soon after failure of conception or death of a litter
-Ultrasounf <90% accurate & cannot be performed prior to 4th week of gestation; amplitude depth US can reliably detect pregnancy btwn 30 and 90 days, as early as 18 days with some equipment - these handheld devices detect interfaces between fluid & tissues = reason why they lose sensitivity in early & late gestation
Doppler US can be used from 4 wks until farrowing & can be used to determine fetal viability in late gestation & litter size
-Progesterone assays (activity of corpora lutea) - <1 ng/ml on days 17-19 of estrous cycle typical of non-pregnant female; elevated progesterone on day 18 after breeding is indicative of pregnancy
-Estrone sulfate assays more accurate than progesterone - produced by fetus & reaches peak blood levels at 23-30 days gestation
Placentation in swine
Diffuse epitheliochorial placentation
-Necessitates colostrum for maternal antibody protection of the piglets
Gestation period in swine
114-115 days
Paturition in swine
- Vulvar swelling, reddening during last 3-4 days of gestation
- Development & distension of mammary glands durings last 2-3 days gestation - drops of clear to straw-colored fluid can be expressed
- Interval between initiation of abundant milk flow & parturition = 6-12 hrs
- Increased respiratory rate Most Reliable
- Restlessness, nesting, frequent urination, defecation, chewing or biting surrounding objects = 24 hr preceding farrowing
- Place sows in a quite room the week prior to anticipated farrowing w/ abundant bedding (wood chips) for nest building
- Environmental temp should be 85-95 F with a supplemental heat source to make 90 F at pig level; sow comfort level is 68-70 F but this higher temp necessary for piglets
- Duration of farrowing: <1 hr up to 8 hr, typically 3-4 hr
- ~15 min interval between births of piglets; assistance should be provided if more than 30-60 min has elapsed since last piglet
Neonatal care in swine
- Need to receive colostrum within first 12-24 HR of birth, before gut loses ability to absorb immunoglobulins
- Competition among littermates is normal & can result in inadequate colostrum intake in less dominant animals
- Neonates establish teat order on day of birth
- Day 1 Care: disinfect navel, clip canine ‘needle’ teeth, inject iron supplement, identify individual animals, weigh, clinical exam
Split suckling
Technique that involves removing half of the litter comprising the largest piglets 3-4x daily to allow smaller animals a chance to nurse adequately
Iron supplementation in piglets
- Nursing piglets require 21 mg of iron for each kg of growth & sow’s milk contains ~1 mg iron/L
- Microcytic, hypochromic anemia can develop
- Provide 100-200 mg iron dextran IM within 48 hr of farrowing to prevent iron deficienct anemia
Causes of preweaning mortality in swine
- Enzootic in most herds
- Poor viability at birth, chilling, starvation, trauma, diarrhea, other diseases
Savaging
- Behavior observed occasionally in some individuals, resulting in injury to and/or death of the piglets
- Only recourse is to remove piglets from the sow & cull sow from breeding herd
Environmental temps for preweaning pigs
- 85-90F = 3-4 weeks
- 75-80 F = 4-8 weeks
Weaning age in swine
3-5 weeks
-Weaned by allowing access to a solid ration
Behavior in swine
- Social & intelligent
- Highly developed smell
- Poor eyesight
- Frequently vocalize to each other when group-housed = if singly housed put cages close together with openings for contact
- Innate need to root = provide bedding material
- Enrichment can include toys like balls, chains, hoses; rotate toys for novelty; enrichment increases well-being & decreases fighting; prefer toys that are chewable & easily misshapen, soft, pliable
Training of swine
- Readily trained & respond well to positive reinforcement
- Acclimate & train swine to tolerate research equipment
- Gentle handling & use of a humane restraint sling at options
- Many pigs respond to gentle rubbing of ventral abdomen by rolling over onto their sides - allows for minor procedures
Swine immunology - CD4, CD8 cells
- Immune system influenced by animals health status (conventional status vs. SPF, gnotobiotic, or axenic conditions have significantly different immune parameters)
- Large population of T clls that express CD3, lack CD2, CD4 & CD8 = ‘null’ cells
- Lymphoid population largely comprised of γδ Τ cells - found in large numbers in various mucosal sites (like uterus); highly prominent in newborn; similar to γδ Τ cells described in ruminants
- Swine have unique lymphocyte subset that express BOTH CD4 & CD8 (mutually exclusive in humans, monkeys) = may represent a type of memory cell or lineage that differentiates from CD4+CD8- to CD8+
- CD8 marker (cytotoxic) expressed is part of α (and not β) chain
- CD4+CD8+ (αα) upregulation is commonly present in activated T cells
- In combination with CD45 and CD62L markers, central vs. peripheral & naive vs. activated T cells can now be identified in swine
- Increase in the identification of cluster of differentiation (CD) markers to phenotype lymphocyte subsets
Immunology tools available for swine
- Many hybridomas - Mass.. General Hospital Transplantation Biology Research Center
- Monclonal antiporcine CD3 antibody: capable of activating or depleting T cells in vitro & immunosuppressive in vivo; have the CD3 antibody linked with diptheria toxin
- Other swine specific T-cell-depleting antibodies - CD4, CD8
Bone marrow of swine
- More similar to humans than that of rodents, especially when dealing with toxicity in response to lethal irradiation
- Studies demonstrating benefit of T-cell depletion of donor tissues in preventing graft vs. host (GVH) disease
- Swine commonly used in transplantation models
Swine colostrum
- Neonates = COLOSTRUM dependent, no transfer of maternal immunity through placenta; need access to IgG right colostrum within first 6 hr - critical for 3 wk survival rate & weight gain
- Colostral leukocytes - mostly neutrophils & T cells - also absorbed in neonates by intracellular migration
- Intestinal closure for absorption of colostrum complete by 24-48 hr old
Immunoglobulins in swine
- Lack IgD - precursor to differentiation of IgM
- Large number of IgG subclasses: IgG1, IgG2a, IgG2b, IgG3, IgG4
- IgA circulates as dimer in blood & tissues, monomer in mucosal tissues
- IgE found in serum & mucosal tissues
- High endothelial venules of transplanted swine express adhesion molecules but info on relative homology of these ‘addressins’ limited d/t lack of reagents
Cytokines & lymphokines in pigs
- Studied in models of inflammation - sepsis, atrophic rhinitis, erysipela, arthritis, viral infx
- Similar biology to humans & mice; some limited homology
- Swine lymphocytes respond to recombinant human interleukin (IL)-2 in vitro & in vivo; when injected into pigs, upregulation of reg T cells for induction of tolerance has been attempted as a bridge to preclinical human transplantation; rejection at high concentration; may enhance antitumor responses
Swine leukocyte antigens (SLAs)
- Swine leukocyte antigens (SLAs) = equivalent to human MHC; expressed by all nucleated cells & function to restrict CD8+ T cell activation, particularly antiviral immune responses
- SLA class II (MHC-II) genes restricted to professional antigen presenting cells like B cells, macrophages, dendritic cells; upregulation occurs during inflammation
- Contrary to mice & similar to humans, SLAs class II genes also expressed in lymphocytes & endothelium
- SLA class III - involved in complement system; closely aligned with human systems of classical & alternate pathways of complement activation
- Difference btwn swine & humans = antigen-antibody immune complexes cleared through lung in pig vs. liver & spleen in humans
Red blood cell antigens in swine
-Very complex - 16 genetic systems having been developed that consist of 78 blood factors - either antigens of RBC itself or become cell-associated from other tissues when serum concentrations are high
-Knowledge of RBC surface expression important during transplantation: antibody-mediated hyperacute reaction - match blood types!
-Swine have been models of allotransplantation including pancreatic islet, kidney, intestine, liver,
composite tissue antigen, lung, heart, and bone marrow; combining donor bone marrow with skin or solid organ transplant may contribute to tolerance induction
Immunodeficient swine
- Human xenografts not rejected
- Acquired immunodeficiency = thymectomy, splenectomy & use of strong pan-immunosppressants
- Management-related or spontaneous cases of immunodeficiency - inadequate colostrum, stress, poor nutrition
- Autoimmune disease in swine largely undocumented except for hemolytic disease in neonates related to postnatal absorption of maternal Igs (erythroblastosis fetalis) & 2 forms of glomerulonephritis - 1)Norwegian Yorkshire swine, 2) spontaneous IgA nephropathy in Japanses slaughter pigs
Xenograft-defined flora
Term should be used rather than SPF to designate the appropriate health status of donor animals to avoid confusion with existing standards
Ethics of xenotransplantation from swine
-Organizations involved: 1) WHO = stressed importance of developing checks & balances for future clinical trials; 2) The Ethics Committee of the International Xenotransplantation Association = founded to promote xenotransplantation as a safe, ethical, effective therapeutic modality; 3) European Parliament and Council, FDA, & PHS have all published guidelines
Optimization of miniature swine for xenotransplantation
-Over 100 porcine protein sequences share the same amino acids as their human orthologs
-Development of disease-resistant swine organs as a strategy to circumvent transplantation failure from human centric infx like hepatitis B
-Cross-breeding mini swine from the Andes & Rockies to develop 3 lines of mini swine that are homozygous for different SLA alleles = SLAaa, SLAcc, and SLAdd; these 3 lines are fixed at the SLA loci & are heterozygous at minor histocompatibility loci = MHCs matched with minor mismatches or full mismatch transplants now possible
-Pairing donor and recipient within a line is used to
model for transplants between MHC identical human
siblings, between swine lines as a model for MHC full
mismatches, and between F1 hybrids for haplo-identical transplants, also known as parent-to-offspring
transplants
-Several recombinant strains bred with different SLA MHC-I or MHC-II; MHC-II thought to permit optimal function of regulatory T cells, which are dependent on MHC-II matching
-SLAdd line was further inbred and currently has >95% cosanguinity
-Swine to NHP transplantation models
Transplant hierarchy of tolerance
Liver > kidney > heart > lung > skin
Humoral xenotransplant rejection
1) Hyperacute rejection (HAR) = cause of immediate graft loss - driven by natural antibodies that recognized the sugar moiety Galα1-
3Galβ1-4GlcNAc (α1,3 Gal) which is present in porcine
endothelium - sugar is produced by the enzyme α-1,3-galactosyltransferase, which is present in most mammals but not humans or NHP; can avoid HAR by either absorbing natural anti-Gal antibodies or using grafts deficient of the Gal antigen
2) Acute humoral xenograft rejection (AHXR) = second potent antibody mediated response; generally caused by non-Gal xenoreactive antibodies; graft is lost over several days/weeks by complement activation; other noncomplement mechanisms may also be involved: decay accelarting factor DAF-/-(CD55-/-) donor mice into Gal-T KO mice
-Development of Gal-KO pigs permits study of non-humoral xenograft rejection mechanisms
-Control of CD4+ T helper cells will provide control of AHXR (humoral rejection)
Cell-mediated xenotransplant rejection
-T-cell-mediated rejection
-Rejection caused by NK cells, macrophages, neutrophils
-Delayed rejection through cell-mediated responses develops over 3-4 days, involving activation of endothelial cells of the graft - activation leads to loss of thombomodulin & adenosine trophosphate diphosphohydrolase - leads to prothrombosis, proinflamm gene activation increasing expression of adhesion molecules, prothrombotic factors, cytokines
-In immunodeficient rodent models, engrafted human CD4+ T cells mediate rejection of porcine xenografts as do MK cells & monocytes
-CD8+ T cell mediated cytolysis continues to be a potent method of rejection
-Activation of cells of the innate immune system via
pathogen-associated molecular patterns potentiates NK
cell and macrophage xenograft rejection: NK cells sense inhibitory signals through MHC ligations - b/c xenogenic MHC cannot provide the necessary ‘inhibitory’ signals to NK cells, rejection results = add human MHC expression to Gal-KO pigs
-Another NK cell mediated kill mechanism is via antibody-dependent cell cytotoxicity (ADCC) - both natural & IgG-specific antibody responses can induce ADCC rejection
-Macrophages phagocytose target tissues if they do not receive a negative signal through the interaction of CD172 (SIRPα) on the macrophage and CD47 on the cell surface molecule
Methods to remove anti-Gal xenoantibodies
- Immunoabsorption: efficient but incomplete & often xenoreactive natural antibodies rebound quickly
- In vitro: α-Gal immunoaffinity columns
- In vivo: extracorporeal perfusion of a donor organ (often the liver is chosen based on size & vascularity)
- No swine breed available with inherently low α-Gal or animals that have spontaneously lost the α-Gal gene
- Knocked out the gene in the most inbred of the MGH mini swine (the ‘D’ haplotype) = these pigs devoid of α-Gal from the SLAdd pigs = α-Gal KO
Xenograft rejection prevention
- Column immunoapheresis = nonspecific depletion of majority of recipient immunoglobulins of all isotypes - not clinically applicable as patient cannot survive long term without antibody-mediated protection
- Anti-CD20 monoclonal antibodies which kill B cells - but some B cells do not express CD20 & are not eliminated
- Cobra venom prevents activation of complement
- Use pigs expressing human complement inhibitory molecules like CD45, CD55, CD59; transgenic expression of CD59 in swine
- Development of immunological tolerance = most effective method
Developing immunological tolerance to prevent xenograft rejection
- Tolerance to fully MHC-mismatched allografts has been demonstrated in mice & primates by first creating a mixed allogeneic hematopoietic chimerism by engrafting donor bone marrow cells into recipient; but, this hematopoietic chimerism has been difficult to achieve in pig-primate models d/t species-specific regulatory cytokines & elements of the stromal microenvironment
- Primates undergo whole-body irradiation prior to infusion of pig bone marrow; primate anti-pig xenoantibodies were immuno-adsorbed by extracorporeal perfusion of recipient blood through a pig liver immediately before the IV infusion of porcine marrow - provided cyclosporine, 15-deoxyspergualin, recombinant pig stem-cell factor, IL-3; other calcineurin inhibitors like FK506 (Tacrolimus) are now being used instead
- Anti-thymocyte and/or anti-CD2 monoclonal antibodies to target T cells have also been used - allows decreased radiation dose
- Thymic specific irradiation to prevent host resident thymic T cells from rejecting new bone marrow donor derived thymic emigrants
- About 2% of the myeloid progenitors in the bone marrow of the recipient were of pig origin, and chimeras were unresponsive (or hyporesponsive) by mixed lymphocyte reaction when challenged with pig-specific stimulators
- Differences between swine & human bone marrow cultures in function of two ligands impt in hematopoiesis - CD44 & very late antigen-4 (VLA-4) - BUT diffs not significant enough to explain lack of effective porcine hematopoiesis in the primate marrow
- Gene therapy to express swine SLA class II antigens on baboon autologous bone marrow cells = limited success - xenografts rejected after 8-22 days
- Porcine thymic grafts in immunodeficient mice has been found to support normal development of polyclonal, functional human T cells & these T cells were specifically tolerate to SLA antigens of porcine thymus donor
- Bone marrow chimerism tolerance approach = longest survival & donor-specific tolerance
Porcine circovirus-2
-Relatively new agent
-Cofactor in porcine multisystemic wasting disease (PMWS), porcine dermatitis and nephropathy syndrome (PDNS), PCV-associated disease (PCVAD), acute pulmonary edema (APE), PCV-2 associated neuropathy (PAN), reproductive failure & mummification of fetuses at different gestational ages, granulomatous enteritis, necrotizing lymphadenitis, exudative epidermitis
-Non enveloped RNA virus - Family Circoviridae, Genus Circovirus = smallest virus to infect mammals
-Serotypes = PCV2a & PCV2b - often result in coinfection
-PCV2c, 2d, 2e have been identified in various countries - studies ongoing
-Diff btwn PCV2a & 2b is only TWO NUCLEOTIDES = differences in pathogenesis, disease severity; global shift occurring from PCV2a to 2b - current vaccines not protective
-PCV2b = pulmonary edema, granulomatous enteritis, lymphoid necrosis & depletion
-Transmission: highly prevalent in pig & feral swine population; shed in respiratory and oral secretions; highly resistant in environment; transmitted via feces, urine, direct transmission, transplacental, colostrum, seminal fluid
-Initially infects tonsils & LNs of the head - first type B lymphocytes then T cells & peripheral blood mononuclear cells
-Animals ~4 weeks old before clinical signs appear - suggest maternal antibodies are protective
-Pathogenesis: not fully known; lesions often seen only in animals coinfected with other agents like porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus (PRRSV), Mycoplasma hyopneumoniae which prime or activate the immune system; infects endothelial cells of macrophages directly - degeneration of endothelial cells, perivascular & intramural edema, fibrinoid necrosis, vascular thrombi; cytoskeleton maintenane, intracellular signaling, and RNA processing have all been implicated in pathogenesis; PCV2 targets fetal myocardiocytes and hepatocytes; virus requires cells in S-phase for DNA replication; lymphocytes most active postvaccination
-Mutation events within a specific epitope led to increased virulence of PCV2
-Macrophages in bone marrow, thymus, thymic lymphocytes label positive for PCV2 in infected animals - virus replicates in both thymus and bone marrow - lymphoblasts support active viral replication
-Heparin sulfate & chondroitin sulfate B are PCV2 attachment receptors
-All breeds susceptible; Landrace more susceptible to lesions/disease than Durocs & Large Whites
-Clin signs: differ with each syndrome
-Dx: complete tissue set needs to be examined = lymphoid organs, lung, digestive system, kidney, repro system, cardiovascular, CNS; IHC, in situ hybridization, PCR; dx not straightforward b/c involved in so many syndromes
-Ddx: PRV, African swine fever (ASFV), classic swine fever (CSF), ovine herpes virus, PRRSV,
Actinobacillus pleuropneumoniae (APP), Actinobacillus
suis, E. coli, Pasteurella multocida, Salmonella, and Streptococcus spp.
-Prevention/Control: inactivated subunit vaccines - continued evolution of virus may evade vaccines - like recent presence of PCV2b
-Research complications: can have subclinical dsiease with decreased average weight gain; if research study involves immunomodulation, may then see overt diseases; many organ systems potentially susceptible
Most common coinfections with Porcine circovirus 2?
-Mycoplasma hyopneumoniae, PPV, PRRSV, septicemia
Other coinfections with Porcine circovirus 2 (less common)?
Torque teno virus (TTV), porcine epidemic diarrhea virus (PEDV), SIV, porcine endogenous retrovirus, PCV1, pseudorabies virus (PRV), Lawsonia intracellularis, Salmonella, and bovine viral diarrhea virus
(BVDV)
What 3 criteria are required for diagnosis of porcine circovirus 2?
1) Compatible clinical signs
2) Characteristic microscopic lesions
3) PCV2 present within lesions
Postweaning Multisystemic Wasting Syndrome (PMWS)
- PCV2 involved
- Increased number of actively replicating cells within the LN correlates with upregulation of virus production
- Anemia, lymphopenia with decrease of CD8+ & IgM producing cells, monocytosis, neutrophilia; cytokine dysregulation with overexpression of IL-10 in the thymus assoc with thymic depletion & atrophy; overexpression of interferon (IFN)-γ in tonsils
- Cytokines decreased include: IL-2, IL-12p40 in spleen, IL-4 in tonsils, IFN-γ, IL10, Il-12p40, Il-4 in peripheral LNs = indicative of T cell immunosuppression
- Clin signs: age of onset 7-16 weeks in US, 5-12 weeks in EU - may be d/t differences in vaccination schedules?; progressive weight loss, lethargy, jaundice, respiratory disease, diarrhea, lymphadenitis, anemia
- In gnotobiotic piglets, PCV2 alone causes asymptomatic infx - when immune system activated with Freud’s & an immunogen, piglets develop severe PMWS
- Necropsy: generalized lymphadenopathy, hepatitis with icterus, edema, nephritis, pneumonia; lungs fail to collapse & are mottled white to tan; enlarged LNs have lymphoid depletion with histiocytic replacement; interstitial pneumonia, interstitial nephritis, granulomatous inflammation of liver, spleen, tonsil, thymus, Peyer’s patches; lesions angiocentric w/ lymphoplasmacytic and histiocytic to granulomatous inflamma & multinucleate giant cells; in the liver, PCV2 antigen found in Kupffer cells, hepatocytes, inflammatory cell infiltrates; renal lesions = tubulointerstitial, lymphoplasmacytic nephritis, interstitial granulomatous nephritis, or mixed patterns
- INTRACYTOPLASMIC BOTRYOID INCLUSION BODIES = common in epithelial cell of bronchi, renal tubules, bronchial glands & within macrophages
Porcine Dermatitis & Nephropathy Syndrome (PDNS)
- PCV2 involved
- Pathogenesis: immune complex deposition assoc w/ PCV2, but may also be caused by coinfx with PRRSV & TTV
- Clin signs: fever, lethargy, raised purple lesion on the skin esp rear legs - skin lesions are dark red papules/macules multifocally, primarily on hind limbs & perianal area
- Necropsy: kidneys enlarged, tan, waxy with petechial hemorrhages; pulmonary congestion, multiorgan fibrinoid necrotizing vasculitis with lesions in dermis, SC, stomach, kidneys, lung, spleen, liver; cutaneous lesions = severe necrotizing vasculitis in dermis & SC with leukocytoclastic inflamm of capillaries, small & medium venules, areterioles with epidermal necrosis, ulceration, dermal hemorrhage; renal lesions = exudative to fibrinonecrotic glomerulonephritis, interstitial nephritis, necrotizing arteritis; renal and inguinal LNs enlarged & reddened with necrosis of lymphocytes in cortex & paracortex, multinucleated giant cells; SYSTEMIC VASCULITIS IS HALLMARK LESION (similar to Type III hypersensitivity)
Porcine Respiratory Disease Complex (PRDC)
- PCV2 most commonly identified pathogen - PCV2b dominant subtype; usually d/t a coinfx w/ PCV2, PRRSV, SIV, Mycoplasma hyopneumoniae, APP, or Pasteurella multocida
- Pathogenesis: damage to lymphoid system after infx; activation of endothelial cells & diminshed coag time; suspected that blood vessels play a role
- Clin signs: decreased growth rate/feed efficiency, lethargy, anorexia, fever, cough, dyspnea
- Necropsy: GRANULOMATOUS BRONCHOINTERSTITIAL PNEUMONIA WITH PERIBRONCHIAL & PERIBRONCHIOLAR FIBROSIS = hallmark lesion; necrotizing ulcerative bronchiolitis; vascular lesions - lymphohistiocytic casculitis, necrotizing vasculitis, vasculitis with fibrinoid necrosis, intravascular thrombi; lung - acute edema & hemorrhage, hyaline membranes; PCV2 antigen present in endothelial cells, smooth muscle cells of tunica media, within infiltrating WBCs, intravascular & perivascular macrophages, intravascular monocytes
Reproductive Failure syndrome
- Transplacental infection of piglets from PCV2 infx sows; target cells depend on age - myocardiocytes in fetuses, lymphoid tissues in neonates; as fetus develops, replication of virus decreases
- Clin signs: time of gestation when sow infx determines course of dz; sow infx 57 days gestation = increased viral replication with edema, hepatomegaly, congestion of fetus; sow infx 90 days gestation = increased reproductive abnormalities; PCV2 infx of pregnant sows can lead to fetal death with mummification, late-term abortion, stillbirths, preweaning mortality
- Necropsy: Dams with repro failure have no lesions; in pigltes, heart most commonly affected & superficial LNs may be enlarged - myocardiocyte degeneration, necrosis, fibrosis, mineralization with surrounding lymphocytes, plasma cells, macrophages; INTRANUCLEAR BOTRYOID INCLUSION BODIES (+ for PCV2 antigen) may be within cardiomyocytes; lymphoid organs display depletion of lymphocytes with infiltration of multinucleated giant cells containing PCV2 antigen
Granulomatous Enteritis syndrome
- Pathogenesis: currently unknown; may involve L. intracellularis, PCV2 combined or only one or the other
- Clin signs: Affects 2-4 mth old pigs - resembles chronic ileitis with diarrhea, unthriftiness, decreased growth, increased mortality
- Ddx: L. intracellulare, Brachyspira hyodysenteriae, B. pilosicoli, Salmonella, and E. coli infection
- Necropsy: necrotizing ileitis & colitis indistinguishable grossly from proliferative ileitis caused by L. intracellularis; mesenteric LNs enlarged & intestinal mucosa diffusely thickened
- Histo: granulomatous enteritis w/ epithelioid cells, multinucleated giant cells, PCV2-type lesions in Peyer’s patches but not other lymphoid tissues; inflammation primarily in ileum but occasionally also colon & cecum; occasional gastric ulceration; CYTOPLASMIC INCLUSION BODIES, proliferation of immature enterocytes, edema in mesocolon
Acute Pulmonary Edema syndrome
- Involves PCV2, esp PCV2b
- Clin signs: rapid onset respiratory distress followed nearly immediately by death with no indications of previous disease; peracute death in PCV2-vaccinated herds assoc w/ PCV2 infx; nursery & younger finisher pigs most commonly affected
- Necropsy: clear fluid accumulates within thorax with wet, heavy lungs & expansion of interlobular septae with edema; cranioventral lobes consolidated
- Histo: diffuse interstitial macrophages & lymphocytes, fibrinoid necrosis of blood vessel walls, surrounding edema; most animals have diffuse lymphoid depletion
PCV2-associated Neuropathy
- Clin signs: wasting, neuro deficits that may be assoc w/ congenital tremors but this has not been confirmed
- Necropsy: acute hemorrhages & edema of cerebellar meninges & parenchyma d/t necrotizing vasculitis resulting in degneration and necrosis of gray & white matter
Other syndromes associated with porcine circovirus-2
- Exudative dermatitis - may have concurrent PPV or Staph hyicus infx
- Necrotizing lymphadenitis - differs from other PCV2-assoc diseases in that there is NO granulomatous inflamm
Salmonellosis in general
- Can be subclinical or present with multiorgan involvement - septicemia, pneumonia, meningitis, lymphadenitis, abortion, enterocolitis
- Etiology: over 2400 serotypesin Genus Salmonella but only 2 species: Salmonella enterica, Salmonella bangori
- Motile, nonsporeforming, facultative anaerobic G(-) bacilli w/ peritrichous flagella
- 3 serotypes that are the typical etiologic agents in swine: S. enteria ser. Choleraesuis var. kunzendorf, S. enterica ser. Typhimurium, S. enterica Typhisuis
- Carry over 200 virulence factors including those involved in adhesion, invasion, cytotoxicity, resistance to killin
- Synthesize over 30 proteins that are specific to evading intracellular killing by macrophages
- Invasive ability of organism along with neutrophil recruitment & transmigration are impt in pathogenesis
- Outer membrane proteins, like lipid A & LPS, impt for celluar damage & microvascular thrombosis & endothelial necrosis which often lead to mucosal ischemia
- Dx: ELISA; definitive dx is via bacterial isolation + lesions
- Ddx for septicemic form = erysipelas, Streptococcus enterica ser. Suis
- Ddx for gastroenteritis in recently weaned swine = L. intracellularis, Serpulina hyodysenteriae, transmissible gastroenteritis (TGE), PCV2, rotavirus, Trichuris suis, coccidiosis
- Tx: clinical salmonellosis should NOT bet treated b/c recovered pigs remain as carriers - ZOONOTIC POTENTIAL
- Control: swine may shed Salmonella for 5 mths of more; euthanized affected & sanitize facility; remove stressors to minimize fecal shedding; medicated feed/water (carbadox, neomycin)
- Effective disinfectants = chlorine, iodine, phenols
- Research complications: do not maintain pigs that are clinically ill or shedding Salmonella - ZOONOTIC; Salmonella are present at a low subclinical level in majority of conventional swine herds - outbreaks of clinical dz assoc w/ stress
Salmonella enterica ser. Choleraesuis var. kunzendorf
- Contains large drug resistant plasmids
- Most frequent serotype in some parts of the world causing disease in swine = septicemia or pneumonia
- Source: other swine
- Transmission: both vertical & horizontal by fecal-oral or nasal secretions
- Incubation period of 2 days to several weeks; survivors become carriers that shed bacteria in feces for several months
- Some form of stress- shipping, food deprivation, concurrent dz, research protocols, mixing pigs - usually precedes clinical dz
- Stress also increases shedding by inapparent carriers
- Fairly host-specific for swine
- Lungs are the site of initial infx following oronasal exposure; if exposed orally can also invade mucosa of the ileum where it is taken up by macrophages - predominant entry site is Peyer’s patches, specifically through M cells - then disseminatio to spleen & liver via CD18(+) macrophages
- Prodces Shiga-like & cholera-like endotoxins = microthrombosis & ischemia of vessels in the lamina propria & then necrosis of enterocytes
- Rectal strictures, particularly of the cranial hemorrhoidal artery, are an outcome of porcine anatomy since pigs have poor to no collateral circulation to the rectum
- Malabsorptive diarrhea with extensive fluid loss
- Septicemia in pigs less than 5 months old = cough, dyspnea, pneumonia, cyanosis of ears & ventral abdomen, lethargy, anorexia, pyrexia of 40.5-41.6 C & sometimes jaundice; watery yellow diarrhea
- Control: MLV vaccination though to be protective & stimulate cell-mediated immunity
- Necropsy: severe pleuropneumonia, cyanosis of ears, feet, tail, abdomen; splenomegaly, hepatomegaly, edematous enlarged mesenteric LNs, erosion of the fundic mucosa of stomach; focal to diffuse necrotic typhlocolitis +/- necrotic ileitis
- Histo: paratyphoid nodules in the liver, necrotic lesions in intestinal mucosa, submucosa, lymphoid follicles; bronchopneumonia or hemorrhagic pleuropneumonia
- Up to 60% morbidity & 30% mortality
Salmonella enterica ser. Typhimurium
- Most frequently isolated serotype in North America
- Usually assoc w/ enterocolitis
- NOT host specific
- Transmission: oronasal route
- Organisms can be found in cecum, colon, ileal Peyer’s patches within 3 hr of infx
- Secreted proteins activate pathogen elicited epithelial chemotractant & protein kinase C which promotes secretion of IL-8 & other proteins
- Downregulates host local inflammatory response, specificall TH1 response genes, genes involved in cytoskeletal reorganiz
- Clin signs: initial diarrhea watery, yellow, sporadic hemorrhagic that lasts less than a week; anorexia, pyrexia, dehydration, distended abdomen d/t rectal strictures possible
- Some will be carriers and shed for several months
- Death in severely affected animals
- Control: killed bacterin vaccines may provide protection
- Necropsy: enterotyphlocolitis of ileum, cecum, spiral colon w/ thickened edematous walls, red roughened mucosa, multifocal to coalescing erosions & ulcers covered with PSEUDOMEMBRANOUS gray-yellow fibrinonecrotic debris +/- button ulcers; rectal strictures with mural fibrosis & resultant distension of colon; acute lesions include Peyer’s patch necrosis - later in disease may be hyperplastic
Salmonella enterica ser. Typhisuis
-Assoc w/ localized epizootics w/ chronic wasting, caseous lymphadentitis, diarrhea, pneumonia
Glasser’s Disease (Haemophilus, Porcine Polyserositis, Infectious Polyarthritis, Fibrinous Polyserositis, Arthritis)
- Haemophilus parasuis - Family Pasteurellaceae; small G(-) pleomorphic coccobacilli
- Currently 15 recognized serovars; both pathogenic & nonpathogenic strains exist
- Exposure to nonpathogenic strains can induce protective immunity
- Can be cutured from nasal cavities when animals are 1 week of age; part of normal upper resp tract flora
- 1st site of colonization in piglets = nasal mucosa
- Only known to infect swine; may be a primary etiologic agent in fibrinosuppurative bronchopneumonia
- Pathogenesis: opportunistic pathogen with PRRSV, PCV2, B. bronchiseptica; organisms adhere to epithelial cells of upper resp tract - induces apoptosis & cytokine release - resistance to phagocytosis likely assoc w/ capsule & enhances virulence
- Clin signs: in herds where enzootic, clin signs will be mild with low morbidity; in susceptible herds, clin signs occur within a week of exposure = fever of 40-41.7 C, anorexia, coughing, depression, swollen joints with lameness, neuro signs, dyspnea, sudden death; marked increase WBC & decrease PCV; long term sequelae include abortion & chronic arthritis
- Dx: oligonucleotide-specific capture plate hybridization assay - specific & more sensitive than culturing from lesions/nasal swabs
- Ddx: Mycoplasma hyorhinis, Erysipelothrix rhusiopathiae, Salmonella cholraesuis, Streptococcus suis
- Tx: parenteral antibiotics - start as soon as clin signs noted; oral abx less effective; high doses of penicillin to those with AND without clin signs; increasing resistance to tetracyline, erthromycin, penicillin
- Control: bacterins - only one commercial available & unlikely it will induce immunity to all pathogenic strains in the population; herd specific autogenous vaccines should be considered reduce stress; medicated early weaning can be successful if high doses of both parenteral & oral antibiotics used; antimicrobial feed, water to groups of swine at risk
- Necropsy: cyanosis of ears & tail, polyarthritis of one or more joints, fibrinous pleuritis, pericarditis, peritonitis, leptomeningitis
- Histo: peracute disease = fibrin thickening of alveolar walls & capillary thrombosis of glomerular tufts; acute disease = fibrinopurulent arthritis & synovitis, fibrinous to fibrinopurulent serositis, fibrinopurulent leptomeningitis
- Research complications: will confound cardiovascular studies b/c the chronic form can produce congestive heart failure & fibrinous pericarditis
Erysipelas (Swine Erysipelas [SE])
-Erysipelothrix rhusiopathiae: G(+) bacillus; 28 serotypes; majority of isolates from swine are serotypes 1 & 2
-Epizootiology/Transmission: domestic pig is primary reservoir & 30-50% of conventional swine are carriers; pigs harbor bacteria in lymphoid tissues (tonsils, Peyer’s patches) - shed in nasal secretions, saliva, feces; those w/ acute SE shed large quantities into environment & those with chronic form are long-term source of contamination; typically gains entry through contamined food and water (oral route) OR skin wounds
-Contact with infected sheep, turkeys, chickens, ducks, emus is a potential source of infection for swine
-Swine older than 3 mths & younger than 3 years = most likely to have clin sign
-Maternal antibodies protect young & acquired immunity from subclin infections protects mature animals
-Pathogenesis: organisms enter body via palatine tonsils or GALT & through skin wounds via direct contact or arthropod bites; virulence factors currently only partially characterized, but incl neuraminidase, capsular polysaccharies, surface proteins
-Clin signs: ACUTE = may be asymptomatic or have combination of RHOMBOID TO DIAMOND SHAPED URTICARIAL pink to purple skin lesions on snout, ears, abdomen, thighs; fever 40-42 C, anorexia, depression, stiff stilted gait, sitting posture, abortion, sudden death; skin lesions appaer 2-3 days post exposure = erythematous, raised, palpable, 1-8 cm across; fever & lesions resolve within 1 week; CHRONIC = stiff joints with slight to non-weight bearing lameness, usually hock & carpal joints most visibly affected; cardiac insufficiency w/ exercise intolerance, sudden death; chronic form may follow subclinical, subacute, & acute forms sometimes within 3 weeks
-Dx: PCR, formic acid, IHC
-Ddx: Acute = any bacterial septicemia, PDNS caused by PCV2; Chronic = other causes of lameness in swine - Haemophilus polyserositis, mycoplasmal polyserositis,
and trauma and other bacterial septicemias such as Actinobacillus suis
-Tx: penicillin for acute form; hyperimmune serum can be effective if given early in course of disease & provides about 2 weeks passive immunity; NSAIDs for arthritis of chronic form
-Control: vaccination worthwhile, though neither attenuate vaccines nor bacterins prevent chronic SE; immunization with purified protein antigen P64 is protective against experimental challenge; surface protein SpaA is potential antigen for new vaccines; attenuated vaccines can be injected, given in drinking water or delivered via aerosol; stop atnibiotic tx 10 days prior to giving attenuated live vaccines; ultimate prevention plan is obtain SPF animals via C-secion derivation or preweaning medication & maintain in barrier facility
-Eliminate chronically infected animals from facility
-Bacteria can survive long periods in environment; effective disinfectants = hypochlorite, quaternary ammonium, phenolic, alkali
-Necropsy: ACUTE phase = generalized coagulopathy; rhomboid to diamond slightly raised, firm skin lesions on abdomen, thighs, ears, snout, throat, jowls; congestion of spleen, lungs, liver; petechial & ecchymotic hemorrhages in cortex of kidenys, on atrial epi- & myocardium, within LNs; histo - damage to endothelial cells in capillaries and venulesl dermal papillae have fibrin deposition, microthrombi, lymphocytic & plasmacytic perivascular infiltrates, focal necrosis; CHRONIC phase = proliferative, NONsuppurative synovitis & arthritis w/ enlarged joints most commonly stifle, hock, carpus
-Research complications: losses due to sudden death with acute form; chronic form will affect orthopedic & cardiovascular studies since proliferative, nonsuppurative arthritis & vegetative proliferation on heart valves can results; ZOONOTIC (most human cases self-limiting)
Streptococcosis (Streptococcal Meningitis) in swine
- Streptococcus suis (Lancefield’s group D) - G(+) diplo or short chain cocci; capsular types 1-9 most often assoc w/ clinical disease in swine
- Capsular Type 2 MOST COMMON
- Another Strep spp - S. equisimilis - may be recovered from cases of septicemia assoc w/ subsequent development of swollen joints
- Transmission: between herds is via flies & carrier animals; newborns infected during parturition & suckling by direct contact, aerosols, fomites; most piglets are colonized before weaning age
- Subclinical carriers harbor in tonsilar crypts, nasal cavity, repro & GI tracts - when carrier introduced to susceptible herd, signs usually first seen in recently weaned young between 5-12 weeks old
- Cultured from wide variety of other animals incl birds & wild boar
- Coinfx with PRRSV or PRV can increase clinical severity
- Pathogenesis: beings with colonization of palatine & pharyngeal tonsils - then spread extracellularly or attached to monocytes via blood or lymph
- Hemolysin (suilysin) one of the best characterized virulence factors - toxic to epithelial, endothelial & phagocytic cells
- Bacteria & suilysin colocalize within neutrophils & macrophages localized in meningeal lesions
- Clin signs: swine aged 5-16 weeks most commonly affected; pyrexia to 42.5 C usually initial sign, then anorexia, depression, ataxia, paddling, opisthothonus, convulsions, death; pneumonia, rhinitis, polyarthritis; less commonly stillbirths, abscesses, vaginitis, myocarditis, otitis interna as a sequelae to meningitis with involvement of perilymphatic ducts
- Dx: PCR assay for detection of strains of serotypes 1 & 2 from tonsilar specimens; ELISA based on purified polysaccharide antigen; isolation of organism from an area other than nasal & oral cavity needed (b/c normal flora)
- Ddx: other streptococcal infections, H. parasuis, E. rhusiopathiae, S. enterica ser. Choleraesuis, and salt poisoning or water deprivation
- Tx: parenteral antibiotic to which the particular herd strain has been shown to be susceptible; resistance to several abx developing - tetracycline, tylosin, sulfonamides
- Control: rederivation by hysterectomy/hysterotomy & maintenance in barrier facility; depopulation & repopulation with clean animals
- Abx + early weaning does NOT eliminate
- Prevent: minimize stress, good sanitation, prophy abx, use of bacterin or autogenous vaccines - variable success, avoid mixing swine from differnt soures; susceptible to common disinfectants; oral penicillin, amoxicillin, florfenicol, gentamicin in feed or water can help control streptococcal meningitis; live avirulent strains & vaccines against cell-wall proteins or extracellular proteins (suilysin)
- Necropsy: encephalitis, cerebral edema, fibrinous pleuritis/pericarditis
- Histo: suppurative meningitis, choroiditis with hyperremic blood vessels, fibrinopurulent to suppurative epicarditis
- Research complications: direct losses from fatal meningitis; confounding for cardiovascular studies b/c endo- & myocarditis; S. suis Type 2 ZOONOTIC
Pseudorabies (PRV; Aujeszky’s disease) in swine
- Reportable; US eradication program implemented in 1989 & declared free of disease in 2005
- Suid herpesvirus 1 - Genus Varicellovirus, Subfamily Alphaherpesvirinae, Family Herpesviridae
- Suid herpesvirus 1 can affect pigs, catte, sheep, goats, dogs, cats, rodents, macaques, marmosets
- Transmission: movement of swine that are shedding viral particles; direct contact, fomites, insemination, inhalation or aerosolized particles, transplacental, consuming infected carcasses or feed; infective levels of virus can persist for up to 7 hr in air with relative humidity of 55%; can persist in caracasses of animals that died of disease; animals other than pigs (dead end hosts) typically die within 3 days
- Pathogenesis: virus enters mucosal epithelium in the nasopharynx & tonsils - replicates in epithelium - gains access to neurons of facial region (olfactory, trigeminal, glossopharyngeal nerves) - reaches neuronal cell bodies via axonal retrograde transport - spreads to medulla & pons where it replicates in neurons & spread to other parts of brain = latent infx in trigeminal ganglia - viremia disseminates virus to many other organs
- Clin signs: related to age of pig, strain of virus, infectious dose; predominantly impacts respiratory & CNS; trembling, hypersalivation, stumbling, nystagmus, opisthotonus, epileptiform-like seizures; dog-sitting d/t posterior paresis; circling, paddling, vomiting, diarrhea; death within 24-36 hr after CNS signs start; clin signs become less severe as pigs age & fewer develop CNS involvement, mortality declines; resp signs - sneezing, nasal discharge, cough = pigs infected at >9 weeks old, morbidity high but mortality low with uncomplicated, sporadic CNS signs like muscle tremors - clin signs last 6-10 days with rapid recovery unless secondary bacterial infx
- Coninfx with PRRSV, PCV2, SIV may result in severe proliferative & necrotizing pneumonia in weanling & postweanling pigs
- Sows & boars develop primarily resp signs; pregnant animals in first trimester resorb fetus & in second or third trimester abort
- Dx: serum neutralization is the standard test; ELISA, latex agglutination; virus isolation for definitive diagnosis - brain, tonsils, lung are organs of choice; IFA, IHC, in situ hybridization - trigeminal ganglia, olfactory ganglia, tonsils tissues of choice
- Ddx: SIV, rabies, CSF, ASFV, porcine teschovirus (PTV), Nipah virus
- Prevention/Control: MLV, killed, gene-deleted vaccines with foreign gene insertions available - protect against clinical signs & mortality but DON’T help eradicate; vaccinated animals shed less virus & have limited tissue invasion be organism; gene-deleted vaccines have advantage of producing vaccinated animals that lack antibody against the specific protein coded for by the delected gene to allow the vaccinated pigs to be differentiated serologically from infected pigs
- Necropsy: minimal to fibrinonecrotic rhintis, necrotic foci in tonsils, liver, spleen, lung, intestines, adrenals, occasional leptomeningeal hyperemia, endometritis, necrotizing placentits
- Histo: nonsuppurative meningoencephalitis & ganglioneuritis involving both gray & white matter, EOSINOPHILIC INTRANUCLEAR INCLUSIONS in neurons, astrocytes, oligodendroglia, endothelial cells; necrotizing bronchitis & alveolitis, necrotizing tonsillitis, lymphohistiocytic endometritis, necrotizing placentitis with inclusion bodies in necrotic & epithelial cells around the foci of necrosis
- Research complications: REPORTABLE
Encephalomyocarditis virus (EMCV)
- Genus Cardiovirus, Family Picornaviridae
- Outbreaks of acute myocarditis form in Europe
- Transmission: rodents thought to be reservoir & can infect food and water for pigs; infx pigs can excrete virus & dead pigs also potential source of infx
- Pathogenesis: oral exposure most likely - virus then found in myocardiocytes, tonsils, intestinal tract, macrophages
- Clin signs: 2 FORMS: 1) Acute Myocarditis - in young pigs may see sudden death, anorexia, listlessness, trembling, staggering, paralysis, dyspnea & 2) Reproductive Failure in sows - abortion, mummified or stillborn fetuses
- Dx: virus isolation, virus neutralization, ELISA
- Prevention: vaccination, minimize stress
- Necropsy: acute infx = epicardial hemorrhage may be only lesion +/- hydropericardium, hydrothorax, pulmonary edema; myocardial lesions most prominent in R ventricle, gray-white in color; Histo = nonsuppurative myocarditis, encephalitis
- Research complications: infects NHP; maybe risk of human infx with porcine-to-human xenografts
Porcine Teschovirus (Teschen disease; PTV; Talfan disease)
- Family Picornaviridae, Genus Teschovirus; several serotypes
- Transmission: pig is only known host; virus ubiquitous worldwide with no herd shown to be free of virus; sporadic disease; fecal-oral & fomite transmission; virus particles highly resistant in environment
- Pathogenesis: replicates in tonsils & intestinal tract; in some animals there is viremia with spread to CNS
- Clin signs: polioencephalomyelitis, reproductive disease, enteric disease, pericarditiis, myocarditis, pneumonia - signs seen depend on serotype; abortion, enteric disease
- Highly virulent PTV-1 strain causes Teschen disease = polioencephalomyelitis, fever, anorexia, ataxia, opisthothonus, coma, paralysis; death common 3-4 days after initial clin signs
- Talfan disease = less virulent PTV-1 strain; signs milder than Teschen disease - benign enzootic paresis
- Dx: PCR; virus can be found in spinal cord, brainstem, cerebellum with Teschen disease
- Tx: animals with mild disease may recover; no effective tx
- Prevention/Control: prevent import of animals from enzootic areas; elimination is difficult & virus has been isolated from SPF herds - maybe due to transplacental infx?
- Necropsy: diffuse chromatolysis throughout CNS, esp ventral columns of spinal cord, cerebellar cortex, brain stem
- Research complications: REPORTABLE
Atrophic Rhinitis (AR)
- Toxigenic strains of Pasteurella multocida, Bordetella bronchiseptica, Hemophilus parasuis
- P. multocida strains A & D = P. multocida toxin (PMT) which causes progressive nasal turbinate atrophy = alone & in combo with B. bronchiseptica is called ‘progressive atrophic rhinitis’ (PAR)
- B. bronchiseptica = heat-labile dermonecrotic (DNT) - alone will produce moderate self-limiting form of disease = alone is called ‘nonprogressive atrophic rhinitis’ (NPAR)
- H. parasuis = mild turbinate atrophy
- P. multocida + B. bronchiseptica = most severe form of AR
- 2 or more infx organisms required to produce clinical dz with permanent nasal distortion & turbinate atrophy
- Porcine cytomegalovirus (CMV) - does NOT cause nasal turbinate atrophy (causes inclusion body rhinitis) BUT may damage the nasal mucosa predisposing to bacterial colonization
- Environmental air pollutants, high ammonia (50-100 ppm), dust, genetics may also play role
- Transmission: majority of swine herds infected with B. bronchiseptica, smaller proportion have strains A & D of P. multocida
- B. bronchiseptica spread by aerosol droplets, snout-snout contact; most severe lesions if infected when <4 weeks old, almost no lesions if 9 weeks or older;
- P. multocida usually enters herd through introduction of carrier pigs; spreads by aerosols & direct contact; pharynx (esp tonsils) & vagina of sows are infx sources for piglets; older pigs (3-4 mths) WILL have lesions (unlike B. bronchiseptica)
- Pathogenesis: B. bronchiseptica colonizes ciliated nasal epithelium, sequential virulence factors only expressed at temps >77 F = DNT (impairs bone formation), adenylate cyclase toxin (ACT; disruption of innate immune function), tracheal cytotoxin (TCT; interacts with LPS, impairs ciliary function); also toxin believed to penetrate lamina propria & initiate inflammation & atrophy of osseous cores; cytotoxic for alveolar macrophages; IgG & IgA BOTH required for complete clearance of B. bronchiseptica
- P. multocida - toxin that causes necrosis of osteoblasts & stimulation of osteoclastic bone resorption in the nasal turbinates = turbinate atrophy; in order for P. multocida to colonize, decreased ciliary function & increased mucus usually needed - caused by increased ammonia, B. bronchiseptica; PMT toxin disrupts G-protein & rho-dependent pathways & stimulates mitogenesis resulting in degenerative & hyperplastic changes esp in bony tubinates, alters cytokines & soluble factors affecting osteoclast number and/or inhibition of osteoblastic bone formation; replacement of turbinate bones by fibrous connective tissue
- Exposure of piglets to 20 ppm ammonia for 2 weeks will markedly exacerbate P. multocida colonization of upper resp tract
- Clin signs: NPAR = pigs <4 weeks old with sneezing, snuffling, mucopurulent nasal discharge, in very young pigs (3-4 days old) can have severe bronchopneumonia with mild fever (39.5-40 C), marked ‘whooping’ cough, dyspnea, high morbid/mortality possible
- PAR = signs typically start at 1-3 mths old; sneezing, snuffling - progress to more violent sneezing, mucopurulent nasal discharge, epistaxis, inflammation & occlusion of nasolacrimal duct w/ tear staining, lateral deviation of snout, brachygnathia d/t slower bone growth in upper jaw, stunted growth (may be d/t effect of PMT on skeletal system)
- Coninfx with B. bronchiseptica & P. multocida = severe upper resp signs with epistaxis, brachygnathia, lateral deformity of snout
- Dx: PCR for PMT toxin - nasal & tonsilar swabs, colostrum; ELISA
- Ddx: other causes of facial deformities - paranasal abscesses and breed variations; CMV
- Tx: no cure; best to prevent
- Prevention/Control: medicate feed of sows during last month of pregnancy; oral antibiotics - tilmicosin, sulfonamides, tetracyclines; can give piglets weekly/biweekly injections of oxytetracycline, potentiated sulfonamides, ceftiofur, pencillin/strerptomycin; medicated feed/water for 4-5 weeks in older weaned pigs at risk; vaccination (against PMT particularly) - vaccinate sow prefarrowing to increase colostral immunity; facility disinfection, adequate air changes; agents sensitive to most common disinfectants; develop SPF swine facility using C-section
- Necropsy: B. bronchiseptica = lesions in young pigs include catarrhal rhinitis, atrophy of turbinates (most severe to ventral scroll), bilateral suppurative bronchopneumonia of apical & cardiac lobs; lungs - severe vasculitis, endothelial cell hyperplasia, hemorrhage, alveolar & perivascular fibrosis
- P. multocida = deformity of snout & nasal septum; distortion & atrophy of turbinates (most severe ventral scroll but also dorsal & ethmoid); atrophy of osseous core of turbinates & replacement with fibrous connective tissues, metaplasia of respiratory epithelium to stratified squamous, inflammatory cell infiltrates in lamina propria
- Research complications: toxigenic P. multocida strains can induce liver & kidney lesions; B. bronchiseptica can induce pneumonic lesions in very young pigs
Pasteurellosis in swine
- Pasteurella multocida - G(-) coccobacillus, facultative anaerobe; Capsular serotypes A, B (most severe), D reported in swine
- Serotype A = pneumonic lungs; Serotype B = septicemia
- Common inhabitant of upper respiratory tract in swine; can be cultured from nose and tonsils of healthy pigs
- Transmission: direct contact, aerosols
- Pathogenesis: usually not a primary pathogen - adherence facilitated by presence of other agents (M. hyopneumoniae, PRV, hog cholera, PRRSV, parasites, or B. bronchiseptica); poorly phagocytized by swine alveolar macrophages & capsule of organism interferes with uptake by neutrophils
- Clin signs: Acute = dyspnea. cough, anorexia, fever to 41.7 C, decreased growth possible; Chronic = intermittent cough, low fever of 39.5-40 C
- Acute form clinically similar to pleuropneumonia (APP) withouth the frequency of sudden death; Chronc form similar to mycoplasmal pneumonia of swine (MPS), S. enterica ser. Choleraesuis, Metastrongylus elongatus, Ascarisus uim
- Tx: parenteral antibiotic; oxytetracycline, ceftiofur, penicillin, florfenicol, enrofloxacin, doxycycline in feed some resistance developing
- Prevention/Control: treat concurrent pathogens b/c P. multocida usually secondary; control environmental air temp, humidity, ammonia levels; veccination & medicated feed and water
- Necropsy: consolidated, red to gray cranioventral lung lobes, frothy exudate in trachea, suppurative pleuritis & pericarditis, pleural adhesions, pulmonary abscesses; Histo = severe suppurative bronchopneumonia with interstitial thickening, fibrinosuppurative pleuritis, well-defined abscesses
- Research complications: accumulation of fluid in airways will complicate anesthesia; confound cardiovascular and respiratory system studies
Pleuropneumonia (APP)
- Actinobacillus pleuropneumoniae (APP) - G(-) encapsulated coccobacillary rod; requires nicotinamide adenine dinucleotide (NAD or factor V) for growth
- 15 serotypes (1-15)
- Extracellular hemolytic toxins ApxI, ApxII, ApxIII; all serotypes secrete more than one Apx toxin
- Transmission: prevalent worldwide, diff countries tend to have diff serovars; transmission = snout to snout or aerosol; recovered swine become chronic carriers; spread is likely through movement of animals; piglets usually infected in farrowing pen - carrier sow is source; all age groups affected
- Pathogenesis: depends on virulence of specific Apx toxins; death can occur in as little as 3 hrs; APP binds squamous cells in the tonsil then Type I pneumoncytes in the lower respiratory tract- interactions with host immune system & released cytokines determine pathologic outcome; primary damage to capillary endothelium in alveoli d/t endotoxin = severe edema & fibrin deposition, thrombosis of capillaries & ischemic necrosis of pulmonary parenchyma; tissue damage primarily caused by host immune response & from factors released by these cells when killed by Apx toxins; death primarily d/t endotoxic shock from APP LPS
- Clin signs: PERACUTE = rapid fever to 41.7 C, anorexia, depression, increased HR, cyanotic skin, open-mouth breathing, foamy blood-tinged nasal/oral discharge near death, death without other signs; ACUTE = fever of 40.5-41.1, depression, anorexia, reddening or congestion of skin, severe dyspnea with marked abdominal component, sometimes deaths within 36 hr; CHRONIC = variable cough, decreased weight gain, pleuritis, abortion endocarditis, arthritis, abscesses
- Serotype 2 = connected with lameness d/t necrotizing osteomyelitis & fibrinopurulent arthritis in 8-12 wk old pigs
- Ddx: A. suis, MPS, pasteurellosis, PRRS, S. enterica
ser. Choleraesuis - Treatment: parenteral antibiotics can reduce mortality in acute stage; marked resistance to amoxicillin, oxytet, metronidazole; medicated feed or water; combo of oral & parenteral meds often gives best results; antibiotics will NOT eliminate chronic form or carrier animals
- Prevention/Control: maintain closed, APP-free herd through strict isolation; AI or embryo transfer to introduce new genetics; ELISA for ApxII available to screen animals or PCR on mixed bacterial cultures from tonsils; segregated early weaning to try to eliminated APP = difficult b/c colonizes animals early; depop & restock with hysterectomy-derived SPF animals; vaccination with killed whole-cell, cell-free antigens, subunit type (Apx I/ApxII/ApxIII); maintain optimal temps, humidity, ventilation
- Necropsy: fibrinous pleuritis, pulmonary edema, bloody growth or clotted fibrin plugs in trachea & bronchi; bilateral lesions in lungs that are dark red & firm, mostly in caudodorsal areas; bloody nasal discharge; lung abscesses & necrotic areas
- Histo: necrotizing fibrinous & hemorrhagic pneumonia, vasculitis with thrombosis of vessels & lymphatics; bone necrosis with lysis of growth plates & suppurative osteomyelitis assoc w/ Serotype 2
- Research complications: affects research of cardiovascular, respiratory systems d/t pleurisy, pneumonia, pericarditis; if animals survive lungs often contain bacterial sequestrae
Actinobacillus suis
- G(-) bacterium, Family Pasteurellaceae
- Colonizes upper resp tract in many herds; do not always see clin signs
- Pathogenesis: produces toxins similar to APP, but less virulent
- Clin signs: septicemia, sudden death, dyspnea, cough, lameness, fever, weakness, wasting, abscesses, neuro signs, abortion, cyanosis, diffuse hyperemia
- 3 FORMS of DISEASE
- SEPTICEMIA: affected suckling & recently weaned
- RESPIRATORY: growers & finishers with cough, fever, sometimes found dead
- ACUTE SEPTICEMIA: adults with lethargy, anorexia, fever, RHOMBOID SKIN LESIONS, abortion
- Dx: clin signs, gross lesions, bacterial culture
- Ddx: APP, causes of septicemia, erysipelas
- Tx: antibiotics; no reports of resistance
- Prevention/Control: vaccination
- Necropsy: petechiae to ecchymoses in lung, kidney, heart, liver, spleen, skin, GI tract; petechiae on ears, abdomen, skin; ACUTE = hemorrhages in multiple organs & serofibrinous exudates in thoracic and abdominal cavities; Histo: necrotic foci in numerous organs with bacterial thromboemboli; RESPIRATORY = necrohemorrhagic pneumonia with petechiae in serosal surfaces of abdominal & thoracic organs; ACUTE ADULT SEPTICEMIA = petechiae & serofibrinous exudates in thorax and abdomen
Mycoplasmal Pneumoniae (Enzootic Pneumonia, Mycoplasmal Pneumonia of Swine)
-Mycoplasma hyopneumoniae = Common pathogen that colonizes the ciliated epithelium of porcine respiratory tract
-Mycoplasma are small (02-0.3 um), lack cell wall; nonmotile, fastidious, G(-) facbultative anaerobes; Class Mollicutes; smallest free-living cells
-Enzootic disease most commonly seen
-Transmission: direct contact with respiratory secretions & aerosols from carriers; transmitted from infected sows to suckling piglets prior to weaning; all ages susceptible; most common chronic pneumonia in swine
-Pathogenesis: not a significant sole cause of disease; adheres to ciliar & apical plasma membrane of respiratory epithelium in the trachea, bronchi, bronchioles - loss of cilia, ciliostasis, filling of alveoli with cellular debris & exudate - organisms further suppress innate & acquired pulmonary immunity allowing other bacteria to proliferate & can potentiate some viruses
-Humoral immunity impt role in infx & macrophage activity is altered by M. hyopneumoniae; IL-10, IL-12, IL-18 increased, IFN-γ decreased; tissue damage d/t inflammatory cell factors not direct damage by organism
-Clin signs: 2 Forms - EPIZOOTIC = coughing, respiratory distress, pyrexia, death; ENZOOTIC = dry cough typically when animals are aroused, decreased appetite, fever; generally clin signs are not obvious until pigs are 3-6 months of age; uncomplicated MPS involves reduced growth rate & chronic cough during exrecise; high morbidity, low mortality unless complicated by concurrent viral or bacterial infx or stress; plays role in PDC when concurrent infx with PRRSV, PCV2
-Complicated infections with other agents: malaise, anorexia, fever, labored respirations, possibly death
-Ddx: these also frequently complicate MPS - P. multocida, B. bronchiseptica, A. pleuropneumoniae,
S. enterica ser. Choleraesuis, and S. suis
-Dx: IFA, IHC, PCR, ELISA
-Treatment: antimicrobials - lincomycin, tetracyclines, doxycycline - in feed, tiamulin, quinolones - can reduce severity of pneumonia & weight loss; doxycycline may have greater in vitro activity than oxytet against M. hyopneumoniae, A. pleuropneumoniae, and P. multocida
-Prevention/Control: only allow SPF animals; create free herd with hysterectomy/hysterotomy, medicated early weaning, segregated early weaning - monitor success of these techniques using ELISA of serum or milk, PCR of BAL fluids or lung tissue, necropsy exam of lungs; provide optimal environment; vaccination may alleviate disease but nor colonization
-Necropsy: lungs fail to collapse, edema of lungs; lungs = pale gray or dark red foci of consolidation in apical & cranioventral aspects of middle, accessory, caudal lobes; catarrhal exudate in bronchi; if secondary bacteria present may have mottled lungs with exudate distended alveoli - mucopurulent
-Histo: perviascular, peribronchial, peribronchiolar infiltrations of large numbers of lymphoretricular cells - in chronic lesions may induce lymphoid nodules; differentiation of cuboidal epithelium to pseudostratified epithelium in bronchioles
-Research complications: interferes with study of respiratory system, complicated infx may interfere with study of cardiovascular system
Mycoplasmal Polyserositis & Arthritis
- Mycoplasma hyorhinis - common contaminant of cell culture lines; ubiquitous in swine population
- Harbored in resp tract of carrier swine - most likely first exposure for piglets is aerosolization or direct contact with nasal secretions from sow prior to weaning
- Spreads rapidly through facility; usually no clin signs unless animals stressed
- Pathogenesis: adheres to cilia similar to M. hyopneumoniae; considered NORMAL FLORA of resp tract; once gains entry to other sites, causes polyserositis & polyarthritis in pigs <8 weeks old; in older pigs 3-6 months old, ONLY arthritis
- Clin signs: most commonly affects 3-10 week olds; lethargy, anorexia, labored respirations, arched back with tucked abdomen, lameness, slight fever, swollen joints; signs abate in about 2 weeks except lameness with swollen joints may persist for several months; intranasal inoculation may cause eustachitis & otitis media
- Ddx: H. parasuis, S. suis, and M. hyosynoviae
- Tx: prophy tx of entire herd with medicated feed or water - lincomycin, tylosin; antibiotic tx of clinically affected individuals unrewarding
- Prevention/Control: eliminate stressors; concurrent infx with M. hyorhinis & PRRSV can cause severe pulmonary lesions
- Necropsy: serofibrinous or fibrinopurulent leuritis, pericareditis, peritonitis; serofibrinous arthritis with increased synovial fluid, swollen reddish yellow synovial membranes; joints most frequently involved = STIFLE (also tibiotarsal, cubital, coxofemoral, shoulders); chronic cases = pannus, erosions of articular cartilage, fibrous adhesions
- Research complications: confound cardiovascular studies & surgical models b/c pericarditis, pleuritis, peritonitis; confound orthopedic studies
Inclusion Body Rhinitis (IBR)
- Porcine cytomegalovirus (PCMV) - Subfamily Betaherpesvirinae, Genus Proboscivirus
- CYTOMEGALY & BASOPHILIC INTRANUCLEAR INCLUSIONS in cytomegalic cells of nasal mucosa
- Agent is species specific, able to induce latent infx; shedding of virus can occur even with circulating antibodies
- Transmission: can recover virus in nasal and ocular secretions, urine, fluids associated with pregnancy, male reproductive organs; transmit via nasal secretion, urine, transplacental; viral excretion highest at 3-8 weeks of age; reactivation of excretion when animals stressed; reservoir of infx = lung macrophages
- Pathogenesis: virus enters through mucosa - replicates inside epithelial cells of mucosal, Harderian, and lacrimal glands - viremia seeds mucosal glands, renal tubular epithelium, neonates or fetuses, reticuloendothelial cells, capillary endothelium - virus inhibits T cell function & thus modifies the host defense mechanisms
- Clin signs: usually subclinical in pigs >3 weeks; unexpected fetal & piglet death, runting, rhinitis, conjunctival discharge, pneumonia, neuro signs, poor weight gain; some pigs born anemia with edema of jaw & tarsal joints; adults exposed for first time may have mild anorexia, lethargy
- Coinfx with PCMV & PCV2 exacerbates PRDC
- Dx: serum ELISA, virus isolation, PCR - whole blood, nasal secretions/scraping
- DDx: PPV, PCV2, PRRSV, CSF, PRV, and enterovirus
- Prevention/Control: supportive therapy; caution when introducing new animals; stressors
- Necropsy: piglets = nasal passages may have serous rhinitis in early stages of disease & purulent exudate in older lesions; sinusitis, if disease becomes systemic - petechial hemorrhages & edema in lungs, LNs, SC tissues, pericardial & pleural effusions; kidneys - petechiae, dark purple color
- Histo: BASOPHILIC INTRANUCLEAR INCLUSIONS in epithelial cells of mucosa & mucosal glands; pneumonia & foci of necrosis in liver, kidney, CNS, adrenals with inclusions in capillary endothelium, sinusoidal cells throughout body
- Research Complications: may be passed to humans during porcine to human xenotransplantation - consequences unknown
Swine Influenza
-Type A influenza virus - distributed worldwide; Family of RNA viruses Orthmyxoviridae
-Type A viruses further classified based on glycoprotein spikes that extend from viral particle: hemagglutinin [H] and neuraminidase [N]
-In contrast to human strains, swine H1N1 has shown little antigenic variation over time
-Strains H3N2 & H1N2 prevalent in swine; may also be infected with H3N3, H4N6, H5N1, H5N2, and H9N2
-Typically appears as result of new animals entering herd; outbreaks spread rapidly; likely to recur unless group depopulation
-Transmission: direct contact with viral particles in nasal secretions; NO evidence of carrier state - persists via passage to young susceptible animals or animals that have lost protective antibody titers
-Very WIDE HOST RANGE: incl humans and birds; acute respiratory disease in humans; also infects wild boar, domestic turkeys, free-ranging waterfowl
-Pathogenesis: virus enters via respiratory epithelium - viral hemagglutinin attaches to host cells via sialic acid containing receptors - virus positive cells are ONLY in resp tract - bronchial & bronchiolar epithelial cells - then neutrophils infitrate lungs; subclin infx vs disease determined by viral load & cytokines released
-Disease & inflammation precipitated by increased IFN-α, IFN-γ, tumor necrosis factor (TNF)-α, and IL-1, IL-6, and IL-12
-May be secondary infection with H. parasuis, P. multocida, A. pleuropneumoniae, M. hyopneumoniae, or S. suis-2
-Clin signs: very ill with anorexia, labored open-mouth breathing, strong reluctance to move, fever, rhinitis, nasal discharge, coughing during recovery; recover rapidly in 5-7 days; high morbidity, low mortality; clin signs similar between common swine serotypes
-Dx: virus isolation from nasal mucosa swabs, BAL, nasal, tonsil, oropharynx swabs; serology in weanling pigs difficult d/t maternal immunity persisting up to 4 mths
-Ddx: bacterial pneumonias, porcine respiratory coronavirus, M. hyopneumoniae, and PRRSV
Tx: amantidine may reduce fever & shedding of virus - used in humans; supportive care; antibiotics to prevent secondary bacterial infx
-Prevention/Control: vaccination; prevent influx of animals from unknown sources; prevent contact with birds & infected humans - PPE
-Necropsy: fibrinous to mucopurulent exudate in nasal passages, trachea, bronchi, bronchioles; sharply demarcated dark-red to purple firm foci of consolidation in apical & cardiac lobs of lung & interlobular edema
-Histo: necrotizing bronchitis, bronchiolitis, bronchointerstitial pneumonia, airways filled with celluar debris & neutrophils
-Research complications: may affect lung studies; ZOONOTIC/reverse zoonosis
Verminous Pneumonia (Verminous Bronchitis)
-Metastrongylus spp = M. salmi, M. pudendotectus, M. elongates api - this one most common; adults are white, males 25 mm length & female 50 mm; oval eggs 40-50 um diameter and larvated
-Ascaris suum = pinkish-yellow nematodes; males 15-25 cm & females 20-40 cm; oval eggs 40-60 x 50-80 um with rough/mammilated appearance
-Both Metastrongylus spp & A. suum cause verminous bronchitis in pigs
-M. elongatus apri = indirect life cycle with earthworm intermediate host - eggs coughed up from lungs, swallowed, excreted in feces - swine eat an earthworm that contains infective larvae - migrates to mesenteric LN & right heart and lungs - mature in bronchi & bronchioles in diaphragmatic lung lobes; prepatent period is 28 days
-Ascarids = direct life cycle - ingested larvated eggs hatch in small intestine & invade wall of cecum & colon - larvae then migrate through liver & lungs - in the lungs, larvae enter the alveoli and migrate up the airways - coughed up and swallowed & then return to small intestine where molt into adults; prepatent period is 40-53 days
-Pathogenesis: M. elongatus apri larvae migrate through lung parenchyma = alveolar hemorrhage, inflamm & consolidation of lungs - maturing larvae migrate to bronchioles & bronchi where mature into adults, lay eggs that produce more irritation/inflamm; A. suum = liver lesions (white spots) that peak at about 1 week post infx & heal in 3-8 weeks - similar lung lesions pathogenesis to M. elongatus
-Clin signs: dyspnea, decreased weight gain, icterus if ascarids migrate into the common bile duct
-Dx: ELISA for anti-A. suum IgG MORE SENSITIVE than fecal exam
-DDx: all bacterial, mycoplasmal, viral causes of pneumonia in swine
-Tx: M. elongatus susceptible to: doramectin,
ivermectin, benzimidazoles, and levamisole; A. suum susceptible to: avermectins, ivermectin, benzimidazoles, pyrantel, piperazine, levamisole, dichlorvos, and hygromycin B; doramectin SQ has persistent activity of at least 7 days
-Prevention/Control: sanitation (steam will kill eggs); neopredisan (p-chloro-m-cresol) efficacious ovicide & larvicide for A. suum; if using outdoor pens, house on concrete or bring animals indoors to prevent access to earthworms; feral Sus scrofa in US and EU have these parasites
-Necropsy: adult M. elongatus apri can be found in trachea, bronchi, bronchioles; larvae may be in lung parenchyma; mucoid plugs containing adults & eggs obstruct bronchioles in diaphragmatic lobes producing atelectasis
-adult A. suum found in small intestine - white focal spots on liver (ascarid migration) ‘milk spots’; larval migration through lungs produces hemorrhage, inflamm, emphysema, secondary bacterial pneumonia
-Research complications: will damage lung, liver, other tissues d/t migration; A. suum ZOONOTIC = visceral laraval migrans
Swine dysentery
- Brachyspira hyodysenteriae - G(-) anaerobic spirochete; one of 6 Brachyspira spp known to infect pigs
- Disease less severe in gnotobiotic swine so other microorganisms normally found in the lower bowel believed to contribute to lesion development; nutritional factors also important - diet rich in rapidly fermentable carbs may exacerbate clin signs, while highly digestible diets or those high in inulin are protective
- Transmission: fecal-oral - direct contact or fomites; organism can survive up to 60 days in moist ground or feces but readily eliminated in absence of organic material; recovered animals continue shedding
- Pathogenesis: very efficient in penetrating mucus & attaching to colonic epithelium - do not invade gut wall below lamina propria; produce hemoylsin = cytotoxic & an endotoxin
- Diarrhea d/t malabsorption from failure of colonic epithelial cells to transport sodium & chloride from lumen to blood; dehydration & fluid loss d/t failure to reabsorb endogenous secretions
- Clin signs: rarely peracute death; severe diarrhea with fever, dehydration, weight loss, weakness over several days; diarrhea is watery with large amounts mucus, flecks or blood & white mucofribinous exudate; pigs with chronic diarrhea may pass red to black soft stools; nursing pigs not typically affected but may develop catarrhal enteritis iwthout hemorrhage
- Mixed infections with Yersinia pseudotuberculosis, S. enterica ser. Typhimurium, or B. pilosicoli commonly result in more extensive lesions, affecting the cecum as well as the colon
- Dx: culture, PCR
- Ddx: hemorrhagic diarrhea in piglets that are newborn to several weeks of age = swine dysentery or Clostridium perfringens; also hemorrhagic enteritis of Salmonella, L. intracellularis, and Trichuris suis
- Tx: supportive care; carbadox, tiamulin, lincomycin
- Prevention/Control: usually introduced by purchase of asymptomatic carrier pig; wild rodents are reservoirs; purchase from SPF herds; quarantine & treat or euthanize affected pigs & review vendor health reports and rodent control; nursing pigs protected by colostrum & can be source of Brachyspira-free pigs if weaned early & housed in clean facility
- Necropsy: dehydration, rough or fecal stained coats; large bowel reddening, edema of gut wall, mucosa, mesenteric LNs, fibrinous blood-flecked membrane covering the mucosa; older lesions less edematous but with thick MUCOSAL PSEUDOMEMBRANE of fibrin, mucus, blood
- Histo: elongated colonic crypts, goblet cell hyperplasia, necrosis of sheets of epithelial cells resulting in damage to exposed capillaries & exudation of fluid, fibrin, blood, inflamm cells; large numbers of spirochetes in crypts & lumen
- Research complications: morbidity & mortality
Brachyspira pilosicoli (Porcine intestinal/colonic spirochetosis)
-Relatively newly recognized; nonfatal diarrhea in grower & finisher pigs
-Found in contaminated water, colonizes chickens, wild ducks, immunocompromised humans
-Transmission: fecal-oral
-Pathogenesis: organisms attach only to mature apical enterocytes (NOT immature cells in crypts); disease may be influenced by dietary factors - non-pelleted diets assoc w/ reduced prevalence of diseases vs. pelleted diets increase risk of colonization
-Clin signs: watery green to brown mucoid diarrhea with flecks of blood; occurs soon after weaning or when placed on new diet
-Concurrent disease may exacerbate signs - swine dysentery, salmonellosis, proliferative enteropathy, or PCV2 infection
-Dx: PCR
-Ddx: B. hyodysenteriae, salmonellosis, L. intracellularis, E. coli, Yersinia spp., T. suis, PCV2, or nonspecific colitis
Tx: antimicrobials, decrease stress, change diet; vaccination may ameliorate symptoms but will not prevent infx
-Necropsy: gross lesions in cecum & colon = flaccid and fluid-filled, enlarged LNs; serosal edema, congestion of mucosa with erosions and necrotic areas
-Histo: dilated elongated crypts distended with mucus, cellular debris, degenerate inflammatory cells, occasional Brachyspiral organisms, organisms may also be in goblet cells; lamina propria commonly distended with neutrophils & lymphocytes
-Research complications: ZOONOTIC - may colonize immunocompromised humans = PPE
Proliferative Enteropathy (PE)
-Excessively proliferative lesions found in terminal ileum; affects multiple species - pig, hamster, fox, dog, ferret, horse, rat, rabbit
-Lawsonia intracellularis - microaerophilic bacterium - obligate intracellular in enterocytes; can only grow in tissue culture
-Transmission: other spp like rodent could be source of infection; shed in feces; transmission is fecal-oral; can remain viable in feces for at least 2 weeks; also reported in wild pigs that may serve as a reservoir
-Pathogenesis: organism endocytosed by cells via a vacuole which rapidly breaks down - multiplies in cytoplasm - organisms enter the immature proliferating crypt epithelial cells & multiply within the apical cytoplasm without an inflammatory reaction - infected crypt cells fail to mature & are not shed so crypts become elongated & tortuous w/ decreased nutrient absorption; acute hemorrhagic proliferative enteropathy version not fully understood
-Clin signs: postweaning pigs 6-20 weeks old; dullness, anorexia, diarrhea or no clin signs; diarrhea moderate with loose to watery stools of normal color; reduced growth rate; young adults may have more severe hemorrhagic enteritis, acute death, anemia secondary to hemorrhagic diarrhea; chronic form has black tarry feces; abortion
-Dx: fecal PCR or use of specific antibody incorporated into a fecal immunoassay, serology by ELISA; intracellular organisms in histo sections
-Ddx: rotavirus, coronavirus, S. enterica ser. Typhimurium, B. hyodysenteriae, PCVAD, nutritional
causes, and esophogastric ulceration
-Tx: can be self-limiting; antibiotics - challenging d/t lack of data on antibiotic sensitivity; in tissue culture, penicillin, erythromycin, difloxacin, virginiamycin, chlortetracycline most effective; tylosin phosphate can be used for prevention & tx
-Prevention/Control: purchase from PE free vendor; house newly arrived pigs separately; oral live attenuated vaccine - provides protective immunity & controls disease; quarantine & tx or euth affected pigs; sanitize equipment; review rodent control
-Necropsy: ileum, cecum, proximal 1/3 of spiral colon = marked thickening of gut wall & mucosa with multiple transverse or longitudinal folds
-Histo: marked elongated branching crypts lined by immature epithelial cells & lack goblet cells; SILVER STAINING, ACID-FAST (MODIFIED ZIEHL-NEELSEN) organisms free in apical cytoplasm; inflammatory response in lamina propria may be minimal; more severe cases may have coagulative necrotic enteritis with caseous mats adherent to jejunal/ileal mucosa
-Hemorrhagic form = confined to ileum, no erosions, fibrinous membrane, lumen may contain blood clots; colonic contents may be black & tarry; histo = extensive degeneration and necrosis of ileal epithelium, crypt abscesses, extensive accumulation of proteinaceous fluids in lamina propria of villi = distension of villi
-Granulomatous inflamm has also been associated
-Research complications: clinically affected pigs unsuitable for research
Colibacillosis in swine
-MOST IMPORTANT diarrheal disease of young swine; common in neonates born to nonimmune sows or piglets in heavily contaminated environments
-Susceptible animals are those recently weaned & animals stressed by new housing or diet change
-Etiology: pathogenic E. coli - G(-) facultative anaerobic rod - in pigs cause postweaning diarrhea (PWD) & edema disease (ED)
-Antigenic serotype: somatic (O), capsular (K), flagellar (H), and fimbrial adhesins (F)
-Pathogenic E. coli also posses one or more virulence factors encoded on either bacterial genome or plasmids = enterotoxigenic strains of E. coli (ETEC), which produce heatstable (ST) or heat-labile (LT) enterotoxins. Necrotoxic E. coli (NTEC) produce cytotoxic necrotic factors (CTF) which lead to diarrhea. Enteropathogenic E. coli (EPEC), also referred to
as attaching and effacing strains (AEEC), attach to the
enteric epithelium using fimbrial adhesins, and efface the microvilli and invade the epithelial cells. Strains of E. coli that cause hemorrhagic gastroenteritis are referred to as enterohemorrhagic E. coli (EHEC).
-ETEC E. COLI = MOST IMPORTANT IN PIGS; EPEC may also cause PWD; Shiga-toxin producing E. coli or ED assoc E. coli (STEC/EDEC) cause ED
-Transmission: newborn pigs encountering large numbers of E. coli carrying appropriate virulence factors will develop colibacillosis if colostrum not available or sow not immune
-Pathogenesis: some pigs inherently resistant b/c lack receptors on their epithelial cell brush borders to which the fimbriae bind; K1 polysaccharide enhances bacterial resistance to complement-mediated killing by inhibiting the alternative pathway to complement activation; O-chain polysaccharide chains in cell wall bind membrane attack complex resulting from complement activation distant from the cell membrane so that it cannot lyse the cell; specialized fimbriae - K88(F4), K99(F5), F6, F41 - permit adherence and colonization of the enterocytes
-ETEC: produce toxins (STa, STb, LTI, LTII, and EAST-1) after attachment to the apical surface of enterocytes - enterotoxins change water-electrolye flux in small intestine which leads to diarrhea if fluid not resorbed in large intstestine; STa & EAST-1 bind receptors leading to fluid/electrolyte secretion; STb binds to a receptor & increases cellular uptake of calcium inducing secretion of water and electrolyes; LT is endocytosed & permanently activates adenylyl cyclase, which increases water & electrolyte secretion
-ETEC have F4(K88) or F18 fimbrial adhesions - fimbria produced determines where in the GI tract the organism colonizes
-When EPEC is involved in PWD, it causes attaching & effacing lesions via a complex secretion system
-STEC/EDEC that secrete STx2e = MOST PATHOGENIC OF STEC/EDEC b/c STx2w damages blood vessel walls resulting in increased permeability and edema; also have F18 fimbrial adhesions
-Clin signs: diarrhea that varies in severity based on virulence factors present; severe dehydration, metabolic acidosis, weight loss, peracute death without diarrhea; neonatal colibacillosis can develop within hours of birth - clear watery diarrhea or loose stools that are white to brown; older pigs have less severe disease
-Litters born to gilts more frequently affected than litters born to sows
-Hemorrhagic gastroenteritis can occur peracutely (sudden death) or acutely in previously healthy, unweaned or recently weaned
-Ddx: for yellow to white, watery diarrhea in piglets newborn to several weeks = salmonellosis, coronavirus, rotavirus, nematodiasis, and coccidiosis
-ED = SWELLING OF EYELIDS & FOREHEAD, usually no diarrhea
-Tx: broad-spectrum abx; most isolates are sensitive to aminoglycosides, potentiated sulfa drugs, and cephalosporins; phages have a potential for prophy use against diarrhea and shedding of ETEC; oral fluid therapy
-Prevention/Control: farrowing should be ‘all in all out’; can immunize problem herds with commercial vaccine or autologous bacterin during gestation; minimize environmental stress
-Necropsy: PWD = dehydration, distended stomach with fundic hyperemia, edema in small intestine; ED = marked edema of mesenteric LNs, mesocolon, mesentery, wall of stomach, large intestine, SC LNs, eyelids, SC tissue, lungs, liver, gallbladder; degenerative angiopathy present in above tissue & brain
-Research complications: morbidity & mortality; can shed ZOONOTIC EHEC
Clostridial enteritis
- Clostridium perfringens - encapsulated, G(+) bacillus that produces a variety of endotoxins
- C. perfringens Type A = normal inhabitant of swine intestine but some strains cause enteric disease
- C. perfringens Type C = fatal necrotic enteritis
- Transmission: from sow to pigs by fecal-oral; exists in environment as vegetative form that persist for at least a year; Type C usually introduced by a carrier sow
- Disease most common in pigs aged 12 hr to 7 days & peaks at 3 days of age; also observed in older pigs 2-4 weeks old; diarrhea explosive; 100% mortality in pigs born to nonimmune sows
- Pathogenesis: Type A = when large numbers build up in jejunum & ileum produce CPA toxin & maybe also CPB2 toxin - do not invade enterocytes; Type C = attaches to enteric epithelium at apex of villi - desquamation and proliferation of organisms along the basement membrane - produce a trypsin sensitive β-toxin that causes much of the necrotizing lesions, CPB2 toxin may also be involved - attach to enterocytes with initial loss of microvilli on enterocytes t tips & damage to terminal capillaries w/ increased capillary permeability - then rapid, progressive necrosis of remaining villus enterocytes, crypt cells, mesenchymal structures in lamina propria & muscularis mucosa - some organisms may penetrate to the muscle layers & produce emphysema of the gut wall and thrombosis of vessels
- C. difficile produces C. dif toxin A (cytotoxin) & C. dif toxin B (endotoxin)
- Clin signs: depend on immune status of the herd & age of naive exposed animals; Type A disease develops within 48 hr of birth with rough pelage, perineal staining, creamy or pasty diarrhea which may become pink & mucoid & last up to 5 days, majority of pigs recover; Type C disease includes hemorrhagic diarrhea, weakness, lethargy, peracute death in piglets 12-36 hr old - acute = 2 days reddish-brown diarrhea with gray necrotic debris & death by 3 days old, subacute = persistent nonhemorrhagic diarrhea that is yellow inititially then changes to clear liquid with flecks of necrotic debris, chronic = intermittent or persistent diarrhea for several weeks, with mucoid yellow-gray feces
- Dx: difficult for Type A b/c normal flora; Type C = ELISA, culture, fecal smear, histology
- Ddx: hemorrhagic diarrhea in newborn piglets to those several weeks old = C. perfringens, B. hyodysenteriae, Salmonella, L. intracellularis, and T. suis
- Tx: once clinical signs develop, often unresponsive to treatment; oral antibiotics (ampicillin) given soon after birth & for first 3 days of life may prevent clinical disease; prophy with ceftiofur + bacitracin methylene disalicylate may be given to sows before & after farrowing; fluid therapy
- Prevention/Control: routine vacination of sows to prevent disease; can vaccinate sows with toxoid at time of breeding or midgestation and again 2 weeks prior to farrowing; colostrum from immune sows will protect piglets; isolate & treat affected piglets; piglets at risk from recent exposure should be vaccinated with recombinant toxoids α and β; medicated feeds can control clinical signs
- Necropsy: Type A = flaccid, thin walled intestine that is gas-filled with watery contents, necrosis of superficial villus tip & fibrin; white pasty fecal matter in distended large intestines
- Type C = segmental transmural necrosis with emphysema in SMALL intestine & sometimes cecum & proximal colon; affected gut wall dark red to black, may be gas bubbles; severe hemorrhage in SMALL intestines & blood-tinged peritoneal fluid, necrotic membrane overlying submucosa, severe necrosis of villi & crypts
- Research complications: overgrowth of C. perfringens from perioperative use of antibiotics may cause acute losses, interrupt surgical studies
Transmissible Gastroenteritis (TGE)
- High contagious viral enteritis assoc w/ vomiting, severe diarrhea, high mortality in piglets < 2 weeks old
- Alphacoronavirus 1 - pleomorphic enveloped viruses with (+) sense ssRNA; Genus Alphacoronavirus, Subfamily Coronavirinae, Family Coronaviridae
- 1 of 4 members that naturally infect pigs: TGEV, hemagglutinating encephalomyelitis virus, porcine respiratory coronavirus (PRCV), and the emerging disease, porcine epidemic diarrhea virus (PEDV)
- Develops within days when majority of animals susceptible; pattern of enzootic TGE will follow if viral challenge exceeds protection provided by maternal immunity or as passive immunity wanes; when enzootic older animals asymptomatic & diarrhea in 1-2 week old pigs - in these enzootic cases morbidity & mortality are lower
- Only recently reported in US
- Pathogenesis: uses aminopeptidase-N receptor on porcine enterocytes to gain access to cell - receptors are only found on enterocytes with microvilli & only cells midvillus to tip - enterocytes replaced during neonatal period when cell type changes from fetal to adult = why neonates primarily susceptible - virus multiples in midvillus enterocytes - slough leading to villar blunting & fusion of nonepithelialized basement membranes decreasing digestive surface area
- Clin signs: anorexia, vomiting, and/or diarrhea develop in 18-72 hr in susceptible animals of all ages, particularly in winter; nursery pigs have TRANSIENT VOMITING & profuse watery yellowish diarrhea, dehydration, rapid weight loss; malodorous diarrhea contains milk curds; piglets <2 weeks old have high mortality secondary to dehydration; piglets over 3 weeks typically survive but growth may be stunted
- Ddx: for yellow to white watery diarrhea in piglets newborn to several weeks of age = colibacillosis, rotavirus, coccidiosis, and nematodiasis
- Tx: no specific treatment; supportive care; antibotics effective for concurrent bacteria in piglets 2-5 weeks old
- Prevention/Control: purchase from serologically negative herd; vaccination of boars, gilts, sows moderately reduces clinical signs; moratorium on purchase of new animals & vaccination of repro stock will eventually contain an outbreak; stress exacerbates disease
- Necropsy: stomach distended with milk, gastric petechiation, distended thin walled small intestine filled with watery material & curdled milk; severely dehydrated = no chyle in lymphatics of mesentery
- Histo: SEVERE VILLOUS ATROPHY IN JEJUNUM & ILEUM (villous:crypt ratio 1:1 vs. normally 7:1); enterocytes vacuolated, low cuboidal or flattened, lymphoid depletion of Peyer’s patches, minimal inflamm response in lamina propria; virus particles in cytoplasm of villous enterocytes, M cells, lymphocytes, macrophages within Peyer’s patches
- Research complications: signs severe enough to make animals unsuitable for experimental use unless sufficient time is available for clinical recovery
Porcine Epidemic Diarrhea Virus (PEDV)
- Alphacoronavirus related to TGEV; lab test required to differentiate
- Many variants of virus; newly circulating variant in US has 90-95% mortality in suckling pigs & vomiting and diarrhea from all agea
- Mice and cats can act as vectors
- Vaccines available in Asia, not US or EU
- Prevention: biosecurity
- REPORTABLE
Porcine Rotavirus
-Major cause of morbidity & mortality from acute diarrhea in very young pigs, particularly if piglets colostrum deprived or raised gnotobiotic
-Family Reoviridae - nonenveloped, dsRNA viruses
-Four (A, B, C, E) of seven (A-G) serogroups have been described in swine; GROUP A most common in swine; within these serogroups, rotavirsues fall into 2 major serotypes based on exprssion of 2 surface antigesn - VP4 & VP7
-Enzootic in most herds; clinical disease only apparent if viral challenge exceeds passive maternal immunity; piglets born to gilts at greater risk; virus is stable in environment & relatively resistant to effects of temp, pH, disinfectants; subclinical infx may persist in adults with periodic shedding
-Pathogenesis: rotaviruses replicate in cytoplasm of enterocytes & M cells overlying Peyer’s patches; Group A & C cause diarrhea d/t destruction of enterocytes on tips of villi & SEVERE VILLOUS ATROPHY compared to Groups B & E; osmotic diarrhea d/t decreased resorption of sodium, water, disaccharides in jejunum & ileum = intestinal contents are hyperosmolar
-Clin signs: most severe in naive pigs first exposed at 1-5 days of age; 18-96 hr incubation period then anorexia, lethargy, vomiting, fever, profuse watery diarrhea that is white to yellow & contains flocculent material - slowly resolves over 3-5 days; clin signs less severe if exposure occurs after 7 days of age; usually subclinical in animals 21-28 days of age or older; usually mild & self-limiting if no concurrent infx
-Severe disease & 50-100% mortality in 1-5 day old gnotobiotic or colostrum-deprived piglets
-Ddx: for yellow to white watery diarrhea in piglets newborn to several weeks old: rotavirus, colibacillosis,
TGE, coccidiosis, and nematodiasis
-Tx: supportive care
-Prevention/Control: exclusion difficult because enzootic in most herds; minimize viral challenge through good sanitation & boosting passive immunity by exposing replacement gilts to feces from herd prior to first parturition; MLV & inactivated virus vaccines for sows & nursing pigs - BUT immunity is serotype-specific
-Necropsy: LESIONS CONFINED TO SMALL INTESTINE; wall of distal half of small intestine thin, dilated, contains watery material; mesenteric LNs small & tan; cecum & colon dilated with watery contents; gross lesions variable or absent in pigs >21 days old
-Histo: degentration or loss of enterocytes on tips of villiy as early as 16 hr postinoculation, increased thickness of lamina propria d/t neutrophils & mononuclear cells, reduction in villous height from duodenum to ileocecal juncture; fusion of villi d/t exposed lamina propria in villus cores
-Research complications: morbidity & mortality in young piglets; subclinical in postweaning animals
Balantidiasis
- Balantidium coli = ciliated protozoan; trophozoites colonize cecum & anterior colon of swine, usually as commensal; trophozoites are large (25x150 um), ciliated ovoid structures containing a macronucleus & food vacuoles; trophozoites can differ in nucleic acid content, suggesting clinical dz may be assoc w/ different strains
- Transmission: ingestion of trophozoites or cysts thatare shed in feces; most infx subclinical; if clinical, may be cofactors of other infex or management problems
- Pathogenesis: secondary invasion occurs when there is compromise of the colonic mucosa
- Clin signs: acute typhlitis or colitis; but more commonly no effect; can cause fatal severe ulcerative enterocolitis; weight loss, anorexia, weakness, lethargy, watery diarrhea, tenesmus, rectal prolapse
- Tx: antibiotics - oxytetracycline
- Prevention/Control: herd-health management to reduce risk of clinical signs; isolate & treat infected pigs
- Necropsy: shown to invade lesions caused by Oesophagostomum & Trichuris suis; NOT considered a primary pathogen
- Research Complications: usually nonpathogenic, but ZOONOTIC - may want to euthanized piglets shedding in high numbers
Coccidiosis
-Usually subclinical
-Eimeria spp., Cryptosporidium parvum, Isospora suis = 3 genera that infect swine & other mammals
-8 species of Eimeria that infect up to 95% of swine housed on dirt lots in US; Eimeria spp considered nonpathogenic in swine
-C. parvum typically causes subclinical infx in swine that are 6-12 weeks of age
-Clinical neonatal coccidiosis = I. suis = MOST IMPT PROTOZOAL DZ OF 1-2 WEEK OLD PIGLETS
-Transmission: fecal-oral; warm temps & high humidity assoc w/ indoor farrowing favor rapid sporulation of oocysts; contaminated environments pose greatest risk to naive piglets
-Pathogenesis: ingest sporulated oocysts - development of sporozoites in intestinal lumen - invage enterocytes & form trophozoites, which then form merozoites - results in rupture of cell membranes releasing into intestinal lumen
-Clin signs: clinical dx in piglets 1-2 weeks old = yellow to gray diarrhea that varies in consistency from watery to pasty; weight loss; dehydration; PIGLETS CONTINUE NURSING
-Ddx: colibacillosis, C. perfringens, TGE, rotavirus,
and Strongyloides ransomi
-Tx: individually dose piglets with amprolium or furazolidone, sulfonamides, trimethoprim-sulfa; drug therapy may only delay onset of clin signs; fluid therapy
-Prevention/Control: purchase from vendors with established health profile; quarantine newly arrived piglets & test by fecal flotation; control with ‘all in all out’ husbandry & thorough cleaning
-Necropsy: gross lesions confined to jejunum & ileum = SMALL INTESTINE = necrotic enteritis involving entire thickness of mucosa; yellow fibrinonecrotic pseudomembrane may be present o foci of mucosal ulceration
-Histo: mod to severe segmental villous atrophy & necrotic enteritis; villous enterocytes flattened, irregularly shaped, crypt epithelial hyperplasia, lamina propria condensed & infiltrated with large numbers of mononuclear cells
-Least involved sections of mucosa contain varying stages of coccidia in vacuoles in the enterocytes of the distal 2/3 of the villi
-Research complications: high morbidity; low to mod mortality; stunted growth
Giardiasis
- Trophozoites commonly found in domestic swine are typically Giardia duodenalis (G. lamblia & G. intestinalis also seen)
- Trophozoites colonize surface of intestinal crypts of SMALL INTESTINE from duodenum to ileum, maximal numbers in cranial part of upper jejunum
- Commensal in vast majority of domestic swine; cysts intermittently shed in feces; fecal-oral transmission
- Clin signs: anorexia, depression, formless feces; Giardia may be primary cause of enteritis or coincidental finding
- Dx: Zinc Sulfate fecal flotation
- Tx: 5 days of metronidazole
- Prevention/Control: remove feces daily or house pigs on slatted floors to reduce contact with feces; quarantine & treat clinical cases
- Necropsy: no pathologic lesions; GIEMSA STAINED fecal smears & histologic sections
- Research complications: debilitation from diarrhea & dehydration; ZOONOTIC
Nematodiasis in swine
- Hyostrongylus rubidus, Globocephalus urosubulatus Macracanthorhynchus hirudinaceus, Oesophagostomum
spp. , Ascaris suum, T. suis, and Strongyloides ransomi can infect young swine - Macracanthorhynchus hirudinaceus - requires intermediate host
- Hyostrongylus rubidus, Globocephalus urosubulatus, Oesophagostomum
spp. - infection is associated with pasture maintenance, which is an unlikely issue in lab animal research facilities
Trichuris suis
-Swine whipworm; colonizes SMALL INTESTINE & CECUM; lesions also in COLON morbidity, possible mortality in postweaning swine
-Bipolar, thick shelled eggs intermittently shed in feces; after 3-4 weeks in environment eggs are infective & remain so for up to 6 years - ingested eggs hatch in small intestine & cecum - larvae penetrate cells lining crypts - larvae migrate from lamina propria into submucosa over several weeks - after series of molts, adult worms can be found with anterior end buried in the mucosa & posterior end free in intestinal lumen
-Prepatent period: 6-7 weeks
-Life span of adult worm: 4-5 months
-Damage to mucosa permits colonization by pathogenic bacteria
-Clin signs: anorexia, mucoid to hemorrhagic diarrhea, growth retardation, dehydration, death in severe cases
-Ddx: for hemorrhagic diarrhea in piglets that are newborn to several weeks old = colibacillosis, C. perfringens, and B. hyodysenteriae; older pigs = Salmonella & L. intracellularis
-Tx: fenbendazole, dichlorvos, levamisole hydrochloride; ivermectin less effective for Trichuris vs. Ascaris, Oesophagostomum,
and Metastrongylus
-Prevention/Control: good sanitation to remove eggs before infective; test new animals by fecal flotation & treat during quarantine; steam clean housing areas & equipment to destroy eggs & infective larvae
-Necropsy: gross lesions primarily in cecum & colon - intestinal wall thickening, appear as bands between coils of gut, foci of hemorrhages on serosal surface; mesenteric LNs enlarged & congested; gut lumen filled with bloody fluid, hemorrhagic catarrhal colitis & typhlitis - portionso f mucosa replaced by yellow, crumb-like fibrinonecrotic membrane
-Histo: parasites embedded in mucosa between villi & in crypts which may be cystic or parasites may penetrate into muscularis mucosa & lamina propria is infiltrated by mononuclear cells; foci of hemorrhage found in mucosa & ulcers which are covered by fibrinonecrotic membrane
-Research complications: severe infx causes bloody scours in young pigs; POTENTIAL HUMAN HEALTH HAZARD
Strongyloides ransomi
-SMALL INTESTINAL threadworm of swine; most prevalent in warm climates & causes morbidity in suckling pigs
-Transmission: larvae can infect pigs in utero, oral, percutaneous, transcolostral; eggs shed in feces hatch within hours & release larvae that are directly infective within 24 hrs or males & females that reproduce resulting in more larvae within 72 hr
-Pathogenesis: larvae enter bloodstream - transported to lungs - coughed up and swallowed
-Clin signs: poor body condition, decreased weight gain, dehydration, death within first 2 weeks of life
-Ddx: for nonhemorrhagic diarrhea in piglets aged upward of 14 days: colibacillosis, salmonellosis,
rotavirus, TGE, giardiasis, coccidiosis, and nematodiasis
-Tx: past formulations of thiabendazole; ivermectin, levamisole
-Prevention/Control: breeding animals should receive anthelmintics several weeks before farrowing to control shedding & transcolostral spread; remove feces daily or house on slatted floors
-Necropsy: dehydration, stunted growth; adult forms of parasite found in small intestine, ova in feces
-Research Complications: important cause of parasitic debilitation in nursing pigs in southeastern US
Mycoplasma suis
- Recently reclassified from Eperythrozoon suies based on 16S RNA; host specific disease in swine
- Epicellular & membrane bound intracellular, round to oval organisms found within or attached to the outer surfaces of RBCs & free within plasma - change size and shape as they mature so look like 2 separate organisms
- GIEMSA stain, NOT Gram stain
- Reservoir is domestic swine; serology will not detect every latent carrier & some infected pigs never show disease
- Transmission: mechanical by blood-sucking arthropods - lice, reuse of blood contaminated equipment, orally if swine lick fresh wounds, in utero
- Pathogenesis: ACUTE disease = anemia that can be fatal, infected RBCs are fragile & rapidly removed by spleen; endothelial cells are invaded & activated by the organism as well
- Clin signs: ACUTE disease is usually seen in suckling or newly weaned pigs or other pigs that have been stressed = fever 40-42 C, anemia, jaundice, pale MMs, cyanosis of ears, weakness, poor weight gain; all ages can be clinically affected; acutely affected sows anorexic, febrile, decreased milk production, vulvar & mammary gland edema
- CHRONIC = affects older pigs & usually subclinical but may see unthriftiness, pallor, urticaria, adverse effect on reproduction in sows - anestrus, low conception rates, abortions, weak piglets, small litters
- Dx: PCR, ELISA; GIEMSA stained fresh blood dmear
- Ddx: iron deficiency anemia and other causes of anemia in piglets and toxicity producing icterus or anemia
- Tx: parenteral or in food or water oxytetracycline will control clinical signs but doesn’t elminate organism; iron dextran; blood transfusion; eliminate stress
- Prevention/Control: eliminate ectoparasites, sanitize equipment; allow only negative animals into facility
- Necropsy: icterus, distended gallbladder filled with gelatinous bile, splenomegaly, pale MMs, ascites, hydrothorax, swollen & yellow-brown liver
- Histo: hemosiderosis in hepatocytes & Kupffer cells, fatty degeneration & centrilobular necrosis of hepatocytes & hyperplastic bone marrow
- Organisms can be found in RBCs on blood smear = 0.8-1 um diameter rings with a pale center
- Research complications: autoimmune hemolytic anemia - can be exacerbated by stress of research protocols; predisposes animals to respiratory and GI disease
Exudative epidermitis: Greasy pig disease
- Staphylococcus hyicus - G(+) coccus that is normal flora on pig skin
- Present worldwide & in many herds does not cause disease; outbreaks seen when naive animals introduced
- Transmission: newbors likely infected during parturition & cross-contamination can occur when weanlings from different litters group housed; bacterium very persistent in environment; damage to skin from abrasions, fighting, mange mites, vesicular disease facilitates entry of S. hyicus; morbidity can reach 20% and mortality 80% in piglets
- Assoc w/ PCV2
- Pathogenesis: At least six antigenically distinct exfoliative toxins (ExhA, ExhB, ExhC ExhD, ShetA, ShetB) - toxins target the stratum granulosum in the epidermis, similar to S. aureus toxins
- Clin signs: lethargy, depresion, anorexia, erythematous skin; pigs aged 5 days-2 mths are suceptible, older pigs more resistant; lesions progress to exudative dermatitis characterized by exfoliation & crusting - begins on groin, axillae, behind ears, areas of damaged skin - within 24-48 hr, lesions on head expand, coalesce & extend posteriorly; haired areas typically affect but can also see lesions on tongue & oral mucosa; generally self-limiting lasting 2-3 months; can see erosions at coronar band & vesicles or ulcers in mouth, tongue, on snout; d dermatitis may cover majority of body in 3-5 days; NONPRURITIC; adults may be mildly affective in small areas on back and sides; also arthritis in piglets less than 12 weeks old
- Ddx: swine pox, mange, ringworm, and pityriasis rosea
- Tx: abx tx challenging d/t resistance to beta lactams, erythromycin, streptomycin, tetracycline, and sulfonamide = base on C&S; topical antibiotics, antiseptic shampoos/dips; treatment most effective when started early
- Prevention/Control: autogenous bacterins given to nonimmune sows useful to protect litters; exfoliative toxin & bacterial cells should be included as antigens in vaccine - use indirect ELISA or phage typing to select toxigenic strain for vaccine; wash sows with antibacterial prior to farrowing & check for ectoparasites; remove sharp or abrasive surfaces in pens
- Necropsy: erosive lesions with reddening, edema, thickening & covered in exudate of sebum, cerum & sweat; lesions most commonly on ears, around eyes, ventral thorax, abdomen
- Histo: superficial & deep pyoderma that may extend to subcutis; coalescing foci of necrosis of stratum corneum, brownish exudate, formation of rete pegs by the hyperplastic stratum germinativum
- Research complications: complicate studies involving young piglets
Swine Pox
-Only member of genus Suipoxvirus, Family Poxviridae
-Pig is only known host; exists primarily in herds with poor sanitation
-Reservoir is infected swine; virus may persist in active form in dry skin scabs for up to 1 year
-Transmission: horizonta via nasal, oral secretions contacting abraded skin possible, but primary method is mechanical via the PIG LOUSE; transplacental; once virus established in herd, usually persists; can have high morbidity in young animals, mortality very low
-Pathogenesis: virus replicates in cells of stratum spinosum - suspected to spread from initial site to secondary sites via as yet undetected viremia - viremia also thought to be responsible for transplacental infx & disease in neonates
-Clin signs: initially macules form (reddening) - then papules (reddening with edema); transient vesicles (fluid within lesions), then pustules & finally crusts (brown to black color); progression of lesions take 3-4 weeks; younger animals <4 months old affected more severely & may have lesions over entire body; older animals tend to only have focal lesions; location of lesions follow vector preferences - pig louse lower parts of body, flies top of body; adults primarily have lesions on belly, udder, ears, snout, vulva
-Dx: typical lesions in typical locations
-Ddx: any of the vesicular diseases, pityriasis rosea,
allergic skin reactions, sunburn, or staphylococcal or streptococcal epidermitis
-INTRACYTOPLASMIC INCLUSION BODIES + CENTRAL NUCLEAR CLEARING in affected epithelial cells = hallmark sign
-Tx: supportive care
-Prevention/Control: isolate affected animals; sanitation & pest control
-Necropsy: gross lesions most commonly on abdomen, chest, legs; severe cases involve oral cavity, main airways
-Histo: viral replication in stratum spinosum = hydropic degeneration, necrosis of epithelial cells, formation of pustules involving full thickness of epidermis w/ 1-3 EOSINOPHILIC INTRACYTOPLASMIC POXVIRUS INCLUSION BODIES IN EPITHELIAL CELLS
Mange (Scabies)
-Sarcoptes scabiei var. suis - Family Sarcoptidae; most significant extoparasite of swine
-Mite is 0.5mm in length; 4 pairs of legs, completes entire life cycle in epidermis; time from egg hatch to develop a mature egg laying female = 10-25 days
-Demodectic mange (Demodex phyloides) is RARE in swine
-Trnamission: common in small conventional herds in US; nursing piglets obtain mites from infected sow through direct contact; breeding sows with hyperkeratotic encrustation in ears are primary reservoirs; group housing of pigs from various sources facilitates spread; mites can survive off host for several days; other species not known to harbor this mite
-Pathogenesis: PRURITIC d/t hypersentivity response - generally occurs several weeks post infection; first 3 weeks of infx = females burrow into skin, covering of keratinized encrustations develop which falls off after 7 weeks when mites leave burrows
-Clin signs: 2 FORMS. 1) ACUTE PRURITIC: allergic hypersensitive form affects younger, grower pigs - intensely pruritic, erythematous papular dermatitis on ventral abdomen, flank, rump that develops 2-11 weeks after infection - pigs rub affected areas = hair loss, abrasions, thickened keratinized skin; reduced growth rate; harder to find mites on scrapings in this form 2) CHRONIC FORM: hyperkeratotic form in mature sows & boars; thick crusty scabs begin on pinnae & spread to neck, head - contain numerous mites easy to find on scraping
-Dx: ELISA for serum antibody to S. scabiei
-Ddx: causes of dermatitis
in swine, such as exudative epidermitis, dermatomycosis,
swine pox, parakeratosis, niacin and biotin deficiencies, sunburn, photosensitization, and insect bites
-Tx: ivermectin orally or SC for 14 days; doramectin IM - greater persistent efficacy than ivermectin; amitrax, phosmet, diazinon; 2 or more tx at 1-2 week intervals usually necessary to eliminate; cull swine that develop unusually severe chronic hyperkeratosis; cleaning of environment
-Prevention/Control: only allow mange-free SPF animals into facility; treat sows with single dose ivermection 8 days prior to farrowing prevents transmission to piglets; feasible to maintain a free herd with good biosecurity & surveillance program
-Necropsy: papular dermatitis in growing swine - papules are manifestations of hypersensitivity rxn, contain eosinophils, mast cells, lymphocytes with assc eosinophilic perivasculitis
-Histo: mites in deep stratum corneum & straum malpighii, producing hyperkeratosis & acenthosis
-Research complications: should not result in direct loss of animals for study b/c mortality rare but intense rubbing is potential threat to surgical incisions, implants
Lice (Pediculosis)
- Haematopinus suis: females 4-6 mm long, males 3.5-4.75 mm; eggs are 1-2 mm long & attach to hair shafts; sucking lice; ONLY SPECIES OF LOUSE THAT AFFECTS SWINE
- Transmission: direct contact; louse does not survive more than 2-3 days off host; life cycle is 23-32 days & entirely in skin of pigs; vector for swine pox & M. suis
- Pathogenesis: 3 instars of the nymph stage & egg-laying females suck blood, causing irritation, pruritis, anemia
- Clin signs: young pigs may have pruritis, poor growth, anemia; lice prefer skin on flank, neck, axilla, groin, inner ears
- Tx: same tx that are effective for mites incl sprays, dips, dusts, oral & injectable ectoparasiticides - given 2 treatments 2 weeks apart; avermectins (doramectin) & ivermectin also effective for ascarids & lungworms
- Prevention/Control: allow only free lice free swine into facility; feral populations are reservoirs
- Necropsy: allergic dermatitis & mechanically induced lesions with hemorrhage
- Research complications: anemia in severely infested young pigs; louse treatments might interfere with some studies; rubbing may damage surgical incision
Brucellosis
- Brucella suis biovars 1, 2, & 3 - only spp of Brucella that causes systemic infx, clinical dz in swine
- Biovar 3 currently most common
- Nonmotile, non spore forming, small G(-) aerobic bacillus or coccobacillus
- Domestic swine populations are primary source for B. suis; European hare (Lepus capinensis) carrier for biovar 2; feral pigs are reservoirs; in US, B. suis biovars 1 & 3 have been eradicated
- Transmission: via contaminated discharges (aborted fetuses, fetal membranes) or tissues from infected swine being ingested by susceptible animals, contaminated feed/water; nursing piglets infected suckling infected sows; B. suis present in semen of infected boars - can spread via breeding or AI
- Pathogenesis: mucosal exposure - organisms enter through follical-assoc epithelial cells (M cells) or by phagocytosis - travel to local LNs - gain entrance to macrophages & neutrophils & multiply - then bacteremia with seeding of organisms in other LNs, genital tract, placenta, joint fluids, bone marrw
- Clin signs: abortion, infertility, metritis, orchitis, lameness, spondylitis, posterior paralysis; piglets of weaning age = spondylitis, posterior paralysis
- Ddx: other causes of infertility and abortion in swine, such as PPV and leptospirosis
- Tx: infected swine should be euthanized; antimicobials unlikely to eliminate
- Prevention/Control: allow only brucellosis-free swine from validated herds into facility; live bacterin vaccines NOT effective in eradicating & can create antibodies that interfere with serologic testing; combine vaccination with test & removal procedures & sanitation measures
- Necropsy: abscesses, erosions of MMs, seminal vesiculitis; aborted fetuses may appear normal or there may be edema, evidence of suppurative placentitis
- Histo: granulomatous inflamm of endometrium, uterine glands, placenta; fetus: suppurative seminal vescilitis, pyogranulomatous foci in liver, caseous necrotic foci adjacent to growth plate cartilage in vertebrae; abscesses in kidneys, spleen, ovaries, lungs, brain, other tissues
- Research complications: ZOONOTIC & REPORTABLE - one of the most common species implicated in human brucellosis; BSL-3 containment needed for working with brucellosis, performing necropsy, etc.; US is considered Brucella free = health certificates from USDA accredited vet needed for travel
Leptospirosis
-G(-) motile aerobic spirochetes; in swine, several serovars of Leptospira interrogans & Leptospira borgpetersenii
-Serovar POMONA = most common cause of clinical leptospirosis in swine; serovars Bratislava & Muenchen common on serology & sometimes cause clinical disease; other serovars that occasionally infect swine = Icterohaemorrhagiae, Sejroe, Hardjo, Canicola,
Grippotyphosa, and Tarassovi
-Transmission: direct or indirect contact with a carrier animal which harbors leptospires in renal tubules or genital tract - leptospires are shed in urine & genital fluids into the environment; feral swine are potential sources of serovars Pomona & Bratislava
-Venereal transmission thought to be the mode of spread for serovar Bratislava b/c sows & boars harbor in repro tract & urinary excretion relatively low
-Survival of bacteria outside of host favored by warm, moist conditions
-Route of infection = via MMs of mouth, nasal passages, eye, vagina
-Swine are typically maintenance hosts for serogroups of Pomona, Australis (servars Bratislava & Muenchen), Tarassovi; infection with other serovars considered incidental; typically only a limited number of serovars will be endemic in a given area & host species
-Pathogenesis: bacteremia develops - seeds organisms in most organs incl liver, pregnant uterus, proximal renal tubules - organisms multiply
-Clin signs: ACUTE form = mild transient anorexia, listlessness, diarrhea, pyrexia resolves in a week; rarely piglets <12 weeks infected with serogroup Icterohaemorrhagiae & have hemoglobinuria & jaundice; CHRONIC form = abortions, stillbirths, weak newborns - esp Pomona serovars infxs; Pomona does NOT affect repro performance after abortion; infertility in sow d/t Bratislava
-Dx: microscopic agglutination test for serologic monitoring; serology for antibodies or demonstration of leptospires in tissues
-Ddx: parvovirus, brucellosis,
and PRV
-Tx: medicated feed for 4 weeks with oxytet or chlortetracycline will help control clinical signs until a vaccination program established; individual dosing of pigs with dihydrostreptomycin-
penicillin G, oxytetracycline, erythromycin, or tylosin may help eliminate serovar Pomona from the renal tubules
-Prevention/Control: biosecurity program to prevent potential vectors (rodents, feral swine); AI to reduce spread of Bratislava; vaccination with bacterins will reduce incidence of infx but not eliminate disease from herd - immunity short-lived = revaccinate every 6 mths
-Necropsy: acute = petechial/ecchymotic hemorrhages in lungs, kidneys; chronic disease = lesions confined to kidneys & consist of small, gray lesions on renal cortex, swollen or atrophic glomeruli, cellular casts in lumen of tubules lined by atophic endothelial cells - primary lesion is damage to endothelial cell membranes
-Research complications: interferes with studies of reproduction or fetal surgery; increased rate of late-term abortions
Porcine parvovirus (PPV)
-Characterized by embryonic & fetal infx - stillbirths, mummification, embryonic death, infertility (SMEDI) when susceptible sows & gilts exposed btwn 6 & 70 days gestation; usually no clinical signs in the adult female
-Major infectious cause of embryonic & fetal death
-Porcine parvovirus-1 - ssDNA virus, Genus Parvovirus, Family Parvoviridae; novel porcine paroviruses recently identified include PPV2, hokovirus, PPV4,
and PPV5 - role of these in swine remains unclear
-Ubiquitous in swine worldwide & infx enzootic in most herds so most sows are immune; gilts usually contract before conception & develop active immunity that persists through life; disease occurs when gilts don’t have circulating antibodies to virus
-Transmission: oronasally, transplacentally; pigs transmit in feces for about 2 weeks post exposure but pens remain infective for up to 4 months - fomites/environment
-Nursing pigs absorb protective PPV antibody from colostrum - titers diminish below protection at 3-6 months of age
-Major reservoir for PPV is environmental - virus is thermostable & resistant to many disinfectants
-Immunotolerant carriers of PPV, resulting from early in utero infx but not death, may also be carriers; boars may play role in dissemination - during acute infx, can shed virus in semen & virus can be isolated in scrotal LNs up to 35 days post exposure
-Pathogenesis: virus replicates initially in tonsils - reaches lymphatic system leading to cell free viremia; placental cells do not support infection not can virus cross the epitheliochorial plaenta; virus may infect fetal lymphocytes within the circulatory system of pregnant sows; virus requires host DNA polymerase to replicate & thus can only produce viral particles in S-phase = propensity to invade rapidly dividing cells
-Clin signs: subclinical in postnatal & pregnant dams; pigs will have transient mild leukopenia within 10 days of initial exposure; maternal reproductive failure it major clin sign; NO evidence that PPV impacts fertility or libido of boars; dams may cycle back into estrus, farrow fewer pigs per litter, or farrow large proportion mummified - usually infected fetuses have crown-rump length of 17 cm b/c those infected after day 70 are able to respond to virus & survive; infertility, abortion, stillbirth, neonatal death, prolonged gestation, reduced neonatal viability
-Lack of maternal illness, abortions or fetal developmental abnormalities differentiates from other causes of repro failure in swine; also mummified fetus crown-rump length <17 c strongly indicates PPV
-Dx: viral antigen by IF microscopy of fetal tissues; serology ELISA (only when fetal tissues not available) - sine ubiquitous, presence of antibody in a single sample is meaningless; detection of antibody in fetus/stillborn before nursing is evidence of in utero infection
-Ddx: PRRSV, brucellosis,
leptospirosis, PRV, toxoplasmosis, and nonspecific uterine infection
-Prevention/Treatment: no tx for repro failure; prevention - either naturally infecting gilts (can promote through herd management) or vaccinating with MLV vaccine prior to pregnancy (administer several weeks before conception); vaccination of boars also recommended
-Necropsy: gross lesions confined to placenta - may be edematous, have white mineralized deposits and stunted fetuses with prominent blood vessels on their surfaces, petechial hemorrhages, edema, enlarged dark liver & kidneys, serosanguinous fluid in body cavities, mummification
-Histo: in fetuses - vasculitis with hypertrophy of endothelial cells, perivascular accumulations of mononuclear cells around vessels in the gray & white matter of the cerebrum, brainstem, meninges; interstitial area around glomeruli, portal areas of liver, placenta
Porcine Reproductive & Respiratory Syndrome (PRRS)
- HALLMARK SIGNS: reproductive disorders, high piglet mortality, respiratory disease seen in a wide age range
- Also called SIRS - swine infertility and respiratory syndrome
- Now endemic in many countries & is a major cause of repro losses & resp dz in swine
- ssRNA virus, Order Nidovirales, Family Arteriviridae, Genus Arterivirus; agent shares structural & functional organization with others in genus, incl lactate dehydrogenase-elevating virus, equine arteritis virus, simian hemorrhagic fever virus; these viruses known to have high mutation rates
- 2 Genotypes = Type 1 (Lelystad) - found primarily in EU & Type 2 (VR-2332) - found primarily in US; US isolates differ genomically but cross react serologically; immunization does not protect across all isolates; if there is enough antigenic variation btwn strains, a new strain may also cause disease in an enzootically infected herd
- Transmission: direct contact, aerosol possible though routinely only over short distances; route of fetal infection has not been identified; once infected, pigs are persistently infected in a transmissible viable state without stimulating antibody production = serology screening is UNreliable; virus infects macrophages located in mucosal surfaces; virus found in serum, orpharyngeal fluids, semen, feces, urine; animals susceptible to infx via skin breaks (tail docking, tattooing); virus inactivated by heat & drying but remains infective in cool temps & high humidity
- Pathogenesis: virus enters nasal epithelium, bronchial epithelium, & tonsilar and pulmonary macrophages - replication in alveolar macrophages with a subsequent viremia & spread to lymphoid organs & lungs - PRRSV replicates in CD163(+)/sialoadhesin(+) macrophages, incl pulmonary alveolar macrophages, pulmonary intravascular macrophages, lymphoid tissue macrophages - migration of infected macrophages across placenta may be a mechanism of fetal infx?
- PRRSV induces increased IL-10 - results in downregulation of cytokines involved in virus clearing (IFN-α, IFN-γ, TNF-α and IL-12p40); cytokines released in PRRS thought to originate from septal macrophages not the infected macrophages
- Clin signs: depends on age of pig & gestation status; infected during third trimester = late gestational abortion; delayed parturition & premature farrowing resulting in mummified or stillborn fetuses; infected females may have anorexia, fever, pneumonia, agalactia, red/blue discoloration of ears & vulva, SC edema, delated return to estrus; newborns - dyspnea, tachypnea most common, also periocular & eyelid edema, conjunctivitis, blue discoloration of ears, diarrhea, CNS signs, mortality up to 100%; pigs at postweaning age - fever, pneumonia, failure to thrive, significant mortality from otherwise non lifethreatening bacteria; PRRSV should be suspected in litters delivered prematurely but after 100 days gestation; lymphopenia, neutropenia, monopenia at 4 days post infx with concurrent increase in band neutrophils; 4 week old pigs have decreased RBCs, hemogolbin, Hct
- Dx: virus isolation, fluorescent antibody examination, IHC, PCR; if pigs vaccinated with MLV vaccine cannot differentiate vaccine virus from field with serology - these pigs can also transmit vaccine virus to naive pigs resulting in infection & seroconversion of naive animal; virus best located in lung, lymphoid tissue, heart, brain, nasal turbinates - MLV vaccine virus can also be found in these tissues
- Ddx: PPV, PRV, CSF, CMV, PCV2, SIV, and leptospirosis
- Tx: supportive care (vitamins, food supplements until appetite regained), antibiotics for concurrent bacterial infx
- Prevention/Control: vaccination with MLV - not universally protective against all isolates; obtain pigs from PRRSV free sources
- Necropsy: litters contain normal pigs, small weak piglets, fresh stillborn, autolyzed stillborn, mummified fetuses - gross lesions in young pigs = mottled lungs with tan foci of consolidation, lymphadenopathy of mesenteri & middle iliac nodes (tan, may contain cysts), mod enlarged & rounded hearts, clear fluid in pericardial space & abdominal cavity
- Histo: multicodal lymphohistiocytic myocarditis, interstitial pneumonia with mononuclear cell infiltrates = septal thickening, peribronchial & peribronchiolar lymphohistiocytic cuffing, hypertrophy & hyperplasia of type II pneumocytes; filling of alveolar spaces with necrotic & normal macrophages; follicular hypertrophy, hyperplasia, & necrosis in lymphoid tissues, lymphohistiocytic choroiditis with cuffing of vessels in meninges, choroid plexus, brain; lesions in fetuses include myocarditis with fibrosis, arthritis, encephalitis
Foot and Mouth Disease (FMD)
- Family Picornaviridae, Genus Aphthovirus
- Enzootic in large parts of Africa, Asia, Middle East, South America; affects members of Order Arteriodactyla
- Transmission: via contact of MMs, abrasions, cut in skin or ingestion of contaminated feed, AEROSOL; secretions from infected animals contain infectious virus & can remain infectious within environment for extended periods
- Pathogenesis: pharynx is primary site of infection, unless virus enters through skin wound - needs access to live cells on surface & doesn’t enter through cornified tissue; after initial replication, virus enters circulation & disseminates to areas of amplification like skin, tongue, mouth
- Clin signs: fever, vesicles around mouth and feet; foot lesions often interdigital w/ coronary band predisposed d/t vascularity; lameness & ‘dog-sitting’; depression, anorexia, abortion
- Dx: RT-PCR - has replaced combined ELISA/virus isolation system
- Tx: no tx; euthanized all animals at the infected site
- Prevalence/control: increased biosecurity; vaccines will NOT prevent infx but decrease clinical signs
- Necropsy: vesicles at mouth & on feet, also at snout, teats, mammary gland, prepuce, vulva; oral lesions most commonly affect tongue; foot lesions most often interdigital, at heel bulb, & coronary bands; may have sloughing of claws
- Histo: ballooning degeneration in stratum spinosum of cornified squamous epithelium - then intracellular edema, necrosis, infiltration of mononuclear cells & granulocytes
- Research complications: REPORTABLE; need to euthanize animals
Swine Vesicular Disease (SVDV)
- Enterovirus, Family Picornaviridae
- Transmission: movement of animals, fomites, contaminated waste food; virus can remain infectious for months; NOT aerosol; enters via abrasions in skin or via MMs
- Clin signs: mild fever, rare lameness
- Dx: virus isolation, RT-PCR
- Tx: no tx; euthanasia
- Prevalence/Control: has only been isolated in Asia & Europe; one OIE list because lesions indistinguishable from FMD; Italy actively screes for SVD antibodies so suspected present in more countries than reported
- Necropsy: vesicles at coronary bands, snout, tongue, lips
- Research complications: euthanasia; REPORTABLE
Vesicular Exanthema of Swine (VES)
- Genus Vesisvirus; Family Caliciviridae
- Indistinguishable from VES in wild sea lions in California & occasionally in wildlife
- Clin signs: after a fever, vesicles appear on snout, lips, tongue, oral mucosa, sole, interdigital space, coronary band
- REPORTABLE
Vesicular Stomatitis (VS)
- Indistinguishable from FMD = REPORTABLE & ZOONOTIC
- Genus Vesiculovirus, Family Rhabdoviridae
- Transmission: AEROSOL, contact with experimental transmission via flies
- Infection localized to site of inoculation; if area unhaired (oral mucosa, snout, coronary bands) = vesicles in 1-3 days; area haired = seroconversion & subclinical disease
- Clin signs: excessive salivation, foot lesions with possible separation of claw, lameness
- Dx: virus detection in tissue tags, vesicular fluid, biopsy
- Tx: supportive care; disinfection crucial
Classical Swine Fever (CSF)
- Genus Pestivirus, Family Flavivirus; also called hog cholera
- Pigs only natural reservoirs & it should already be eradicated from all commercial breeds in US; continues to circulate in China, Africa, Central America, South America
- Transmission: oronasal, ingestion of infected material, seminal, airborne in experimental conditions; virus can survive in certain conditions for prolonged periods
- Pathogenesis: primary viral replication is in the tonsils - then spreads to LNs, peripheral blood, bone marrow’ not fully understood effects on immune system, endothelium, epithelial cells & thrombocytopenia, consumption coagulopathy followed by DIC; platelet activation followed by macrophage activation & phagocytosis of platelets, which may explain the thombocytopenia; bone marrow megakaryocytic dysmegakaryocytopoiesis; primary cytokines involved = TNF-alpha, IL-6, IL-1alpha
- Clin signs: pyrexia, anorexia, lethargy, conjunctivitis, resp signs, constipation followed by diarrhea; signs are same in acute & chronic disease
- Dx: virus isolation, RT-PCR, virus neutralization, ELISA
- Ddx: African swine fever, BVDV, PRRSV, PCV2, salmonellosis, erysipelas, streptococcosis, leptospirosis, and coumarin poisoning
- Prevention/Control: some free areas try to maintain ‘no vaccination’ policy & eradicate infected herds; those in endemic areas vaccinate to prevent disease
- Confounding Factors: BVDV is usually only pathogenic for fetal pigs, but can also infect pigs naturally & lesions can be indistinct from CSF = infection with BVDV confounds accurate detection of CSF; infx typically cross-species & BVDV lesions may be mistaken for CSF
- Necropsy: presence of lesions variable - most commonly hemorrhage of peripheral LNs & renal petechiae & ecchymoses, SPLENIC INFARCTION = NEARLY PATHOGNOMONIC; lesions of DIC
Nipah Virus
- ssRNA (-) sense, Family Paramyxovirus, Genus Henipavirus; strain differences between geographic regions
- Pigs are amplifying host; bats are reservoir host & secrete virus in urine - pigs may ingest contaminated items; transmission requires close contact
- Pathogenesis: vascular, nervous, lymphoreticular systems are targets for virus; virus able to circumvent the host interferon response
- Clin signs: pigs are asymptomatic or have acute febrile disease with resp/CNS signs
- Tx: euthanasia
- Prevention/Control: recombinant vaccines used in pigs
- Necropsy: enlarged LNs, congestion & edema in meninges, pulmonary consolidation, distended interlobular septa; syncytial cells located in areas of interstitial pneumonia contain INTRACYTOPLASMIC INCLUSION BODIES
- Research Complications: BSL-4 agent; ZOONOTIC
Porcine Lymphotropic Herpesvirus (PLHV)
- Assoc w/ porcine lymphotropic disease with high mortality, similar to human post-transplantation lymphoproliferative disease, in pigs immunosuppressed for transplantation studies; also concern that pig-human xenotransplantation may result in human disease
- Family Herpesviridae, Subfamily Gammaherpesvirinae, Genus Macavirus, Species suid herpes-3, -4, -5
- Suid herpesvirus-3, -4, -5
- Appear to be present in pigs worldwide with no outward disease in healthy animals
- Predominantly infects B cells
- Clin signs: no disease unless animal immunosuppressed; if immune suppressed = profound B cell prolieration & majority of animals die; lethargy, fever, anorexia, enlarged LNs
- Dx: PCR specific for each lymphotropic virus (PLHV-1, -2, -3)
- Prevention/Control: C-section derivation may reduce prevalence
- Necropsy: enlarged lymphoreticular organs, airway obstruction, respiratory failure
- Research Complications: concern in xenotransplantation studies that lymphoproliferative disease d/t PLHV will occur after immunosuppression of host
Ovine Herpesvirus-2
- Naturally occurring disease similar to malignant catarrhal fever (MCF); rare in pigs
- Ovine Herpesvirus-2 = Family Herpesviridae, Subfamily Gammaherpesvirinae, Genus Macavirus
- Transmission: mode uncertain, suspected to be via nasal secretions; pigs may be ill after having contact with sheep
- Clin signs: high persistent fever, anorexia, depression, recumbency, foul-smelling nasal discharge, ocular discharge, bilateral corneal edema, keratoconjunctivitis, ataxia, tremors, convulsions
- Dx: clin signs, histology, presence of virus-specific antibodies
- Ddx: PRV, CSF, ASFV, porcine enterovirus, PCV2, rabies
- Prevention/Control: currently no vaccine in pigs; decrease interactions with sheep
- Necropsy: multifocal cyanotic areas or petechiae on skin, crust on skin, enlarged hyperemic LNs, mucopurulent exudate in airways; spleen & liver engorged
- Histo: ACUTE VASCULITIS in CNS & other organs with adventitial & transmural mononuclear cells with fibrinoid necrosis of vessel walls in many tissues; myocardium, spleen, CNS, skin, kidneys commonly affected (panarteritis)
Hepatitis E
- Genus Hepevirus; 4 known genotypes - 3 genotypes infect pigs
- Usually no clinical signs, but Genotype 3 = multifocal lymphoplasmacytic hepatitis & focal necrosis,but NO elevation in liver enzymes
- Transmission: fecal-oral
- Exposure of humans to infected swine can transmit to humans; swine veterinarians have shown detectable antibody titers to the virus
Ebola virus
- Family Filoviridae, Genus Ebolavirus, Species Reston evolavirus (REBOV)
- Pigs showed signs consistent with severe PRRSV & in some cases infected with PRRSV, REBOV & PCV2
- Ddx: PRRSV
- When experimentally infected with Zaire ebolavirus able to transmit to NHP
- Subclinical in pigs & only causes lesions if infection occurs via a systemic route; current knowledge indicates only involved in outward disease if another agent present
Japanese Encephalitis (JEV)
- Family Flaviviridae, Genus Flavivirus
- Mosquitos transmit, pigs are natural reservoir
- Clin signs: testicular degeneration, infertility, mummified fetuses, piglets with birth defects, repro failure, stillbriths
- Repro failure only seen if sows infected before 6-70 days gestation
- Experimental infx of 3 week old piglets = nonsuppurative encephalitis of frontal & temporal lobes & spinal cord also affected
- Dx: virus isolation
- Ddx: PPV, PRV, PRRSV, toxoplasmosis, and leptospirosis
- Humans can also be infected but only by mosquito
Porcine Stress Syndrome (PSS) (Malignant Hyperthermia)
-Occurs in pigs that have mutation of calcium-release channel protein = ryanodine receptor (RYR) - mutation results in hypersensitive triggering mechanism of the calcium-release channel in skeletal muscle sarcoplasmic reticulum in response to stressors - lack of calcium control within the membranous portions of the sarcoplasmic reticulum & mitochondria thought to initiate cascade of events
-Stress susceptible pigs can also overespond to stress via: excessive β-adrenergic
receptor stimulation, lower rates of lactate, alanine, and
aspartate conversion to carbon dioxide by the liver,
abnormal phosphorus metabolism, and a much higher
cortisol and thyroxine turnover rate
-Animals with genetic defect found throughout world
-Mutation arose from single founder animal; found in 5 major breeds = Landrace, Yorkshire, Duroc, Pietrain, Poland China & mini potbellied pigs
-Autosomal recessive with varied penetrance
-Largely bred out with genetic testing
-NEWLY identified mutation = R1958W in the dystrophin gene - responsible for loss of animals d/t transport stress
-Syndrome also reported in humans, dogs, cats, horses
-Clin signs: in lab, most commonly assoc with exposure to HALOTHANE, SUCCINYLCHOLINE (also methoxyflurane, enflurane, isoflurane); course of disease variable; tachycardia, tachypnea, muscle rigidity, hyperthermia, metabolic acidosis, myoglobinemia, hyperkalemia, hyperglycemia, cardiovascular collapse, death
-Signs less pronounced in young pigs & those heterozygous for the trait
-Early signs in non-anesthetized pigs are muscle & tail tremors - then dyspnea, blanched & reddened areas on skin, increased body temp, cyanosis, muscular rigidity, cardiovascular collapse
-Tx: discontinue anesthesia & give 100% oxygen; active cooling with ice packing, IV cooled fluids, gastric or rectal lavage with iced saline; Dantrolene - decreases release of calcium from the sarcoplasmic reticulum while allowing calcium uptake to occur - highly effective; monitor closely for 48 hr as syndrome can redevelop from minor stressors; Dantrolene 3.5-5 mg/kg can also be given as preventive therapy
-Prevention/Control: eliminate animals with mutation from breeding stock; DNA based test available to screen for mutation
-Necropsy: very rapid development of rigor mortis; muscles very pale & soft, almost watery d/t high lactic acid content in muscles that occurs postmortem; lesions in animals with dystrophin mutations incl cardiomyofiber degeneration
Salt Poisoning (Sodium Ion Toxicosis)
- Caused directly by animals consuming excessive amounts of sodium, feeding milk byproducts like whey (high sodium content)
- Most common initiator = WATER DEPRIVATION
- Signs are initiated after a minimum of 24 hr of water deprivation, but the condition can also occur after just a few hours
- Pathogenesis: causes hyperosmolarity of CNS, then when animal rehydrates the osmotic pressure causes water to be drawn into the CNS = edema, swelling
- Clin signs: initially very thristy, constipated; CNS involvement may be delayed for days, then apprehensive, ears pricked & starting ahead with head slightly elevated, nose twitching, closed eyes, rhythmic chomping of jaws; animals may appear blind or deaf, pigs near death may paddle; if d/t excessive salt consumption rather than water deprivation = vomiting, diarrhea
- Dx: clin sign + known water deprivation + gastritis, constipation, enteritis; laminar subcortical necrosis is subacutely affected; hypernatremia
- Ddx: PRV, hog cholera, and edema disease; other causes of toxicosis, such as food poisoning
- Tx: treatment generally ineffective & condition exacerbated by rehydration
- Pathology: eosinophilic cuffing of meningeal & cerebral vessels
Gastric Ulcers
- PARS OESOPHAGEA
- Pathogenesis remains speculative, may be related to Helicobacter pylori-like organisms, high carbohydrate diet
- Fasted pigs exposed to stress have higher incidence, higher incidence if feed finely ground feeds
- Clin signs: peracute = found dead; acute = pale, weak, increased resp rate, vomiting blood, passage of bloody, tarry feces; subacute or chronic = anemia, anorexia, passage of dark feces; BODY TEMP = NORMAL OR SUBNORMAL
- Ddx: swine dysentery, S. enterica ser. Choleraesuis, TGE, and intestinal hemorrhagic syndrome - all these, except for intestinal hemorrhagic syndrome, result in high temp
- Tx: nonabsorbable antacids, and vitamin E and selenium, as well as H-2 blockers (cimetidine, Zantac, etc.)
- Prevention: feed appropriate diet - more coarsely ground, not excessive unsaturated fatty acids, right balance of Vit E & selenium; avoid stressful conditions
- Necropsy: pars oesophagea contains no glands & is covered in stratified squamous epithelium continuous with esophagus - in healthy animals appears white and smooth; lesions = rough, irregular surface, ulceration; blood or blood clots at ulceration or in GI tract; chronic ulcer = fibrous tissue & contraction of area of ulceration
- Histo: early stages of ulcer = parakeratosis of epithelium, some polymorphonuclear cell infiltrate but usually inflamm cells absent; epithelium weakened & erosion of tissue eventually occurs d/t parakeratosis - then diffuse necrosis & bleeding; chronic ulcers have fibrous connective tissues in the underlying lamina propria, muscularis mucosae may hypertrophy or degenerate & be replaced by fibrous tissues; occasionally ulcer penetrates serosa
Melamine-Cyanuric Acid Toxicity
- Melamine + cyanuric acids = when fed together cause toxicity
- Weight loss, pallor, rough hair coat, increased mortality; kidneys swollen with yellow discoloration
- Histo: lesions in the proximal & distal tubules and collecting ducts with epithelial degeneration, necrosis, crystals - round, yellow to brown with radiating striations
Catheter infections in swine
- Bacteremia with seeding of multiple organs - septic emboli in lungs, kidney, spleen; thrombi dislodged from catheters during flushing can cause infarcts in kidney, etc.
- Clin signs: febrile, decreased appetite, discharge around catheter
- Ddx: foreign body reactions to foreign materials
- Tx: blood culture or culture from implant site - antibiotics
- Prevention/Control: adequate flushing of lines, adherence to aseptic technique, use flushes that have anticoagulants adequate to prevent thrombus formation
- Necropsy: suppurative exudate are implant; suppurative pneumonia with consolidation, suppurative emboli in multiple organs, renal infarcts
- Histo: cellulitis, myositis, suppurative pneumonia, suppurative emboli, infarcts in kidneys
Neoplasia of young pigs
Lymphosarcoma, embyronal nephroma, and melanoma
Neoplasia reported in older Vietnamese potbellied pigs
-Smooth muscle tumors of uterus or broad ligament, adenoma, adenomyosarcoma, uterine leiomyomas (similar to human fibroids), uterine adenocarcinoma
Lymphosarcoma in pigs
-Primarily younger pigs of either sex
-Most cases multicentric; next most common is thymic lymphosarcoma
-Histo: infiltration of liver, spleen, kidney; usually lymphocytic lymphosarcoma in pigs (lymphoblastic,
histiocytic, and mixed types do occur)
Embryonal nephroma in pigs
- Affect pigs <1 year of age, predominantly females
- Tumor arises in kidney parenchyma, typically unilateral, may spread to lungs & liver
- Histo: classifications most commonly nephroblastic and epithelial
Melanoma in pigs
- Occur as congenital lesions in SINCLAIR mini pigs (85% incidence at 1 year old) & in Duroc, Iberian, Hormel
- Tumors can be single or multiple
- May affect only skin or have mets to internal organs
- Initially, skin tumor is flat black spot - becomes raised nodule; tumor initiates as a focus of melanocytic hyperplasia within the basal layer
- Spontaneous regression occurs in majority of cases - thought to be d/t cytotoxic effects of infiltrated tumor specific T lymphocytes
- Target specific genes in pigs to generate ‘oncopigs’ that are prone to specific tumors
Thrombocytopenia purpura
- GOTTINGEN; either sex
- Extensive multifocal SC hemorrhage, thrombocytopenia & anemia - leads to subcapsular hemorrhage of LNs & hemorrhages of urinary bladder urothelium; ulceration of torus pyloricae, hemorrhages in other tissues; vascular lesions in renal pelvis & coronary arteries, primarily within small to medium muscular arteries that display neointimal proliferation, thrombosis, medial deposits of myxoid matrix
- Renal glomeruli have membranoproliferative lesions that label for immunoglobulins and C1q
- increased numbers of immature and apopototic megakaryocytes within bone marrow
- TYPE III HYPERSENSITIVITY RXN
