Exam 4 Flashcards
Lecture 1 Bovine Respiratory Introduction and PE
Immunomodulation in Bovine Respiratory Disease
-Cortisol Increases due to stress
-BVD, IBR, PI-3
-Pasteurella hemolytic, P. multicocida, Haemophilus somnus.
-Neutrophils defective in function
-Cellular and molecular interference with neutrophils
Describe BRD associated risk factors and their mechanisms
BRD External Risk Factors
- Transportation
- Commingling
- Antibiotics and vaccination
- Disease and pathogen exposure
- Genetics and epigenetic
- Maternal microbiome
- Environment and housing
- Age
- Weaning
- Dietary changes
Immune system insults
-Stress
-Dehydration: Decreased aqueous layer = all cilia trapped in mucus layer = decreased clearance = increased airway irritation and organisms number
-Co-infections
-Inadequate nutrition
BRD Internal Risk Factors
- Anatomy: compared to horses, lung capacity is 1/2.
-Tortuous architecture
-Lobular structure: minimal collateral air circulation, limited ability to compensate for damaged areas - Innate Immunity
-Mucociliary apparatus
-Cellular component
-Cytokine component
-Immune modulation
Prevents/inhibits pathogens from colonizing in airway locations where they can cause disease
-Pathogenic bacteria can be normal inhabitants of upper airways. Primary or secondary
BRD Behavioral Risk Factors
- Prey animals: tend to disguise how they feel to avoid appearing vulnerable to predators
- Humans considered predators (not always) hinders identification of sick animals
Describe how to obtain a history and observe a farm for BRD risk factors
-Number of animals affected
-Age of animals affected: young more vulnerable
-New additions to the herd: naive herd, introduction of disease
-Vaccination history: what vaccines, how often, how efficacy
-Therapies given
-Client’s response accuracy: don’t know, won’t tell, forgot, etc.
On Farm Observations
-Drought, other environmental condition
-Hungry cattle
-Head and neck extension strongly suggests respiratory system
-Associated with feeding peanut vine hay
- Climate: cattle like cooler temperatures. Shield from hard snow, rain, wind
- BCS - Energy of herd
- Nutrition: pasture condition, concentrate, etc.
- Sanitation: ammonia, mud in dry lots
- Housing: pasture, dry lot, crowding, ventilation
- Storage and use of vaccines
- General management level
Describe how to perform a PE related to BRD and interpret findings
- BRD at a distance: “Natural behavior” vs. abnormal behavior
-Separation from others
-Minimal feed intake
-Drinking reduced, rumen fill
-Discharges, nasal ocular
Head and neck extended
Lethargic
-Reduced activity, shuffle feet, droopy ears, electronic monitoring (detect 2-4 days earlier)
-Chronic: wasting away - Body symmetry: bloat present?
-Death from suffocation due to pressure on thoracic cavity from rumen
-Always relieve bloat first - Breathing pattern: dyspnea present?
-Normal adult: 15-35 bpm, Neonatal: 20-50 bpm
Dyspnea types
-Inspiratory effort = cranial to thoracic inlet
-Expiratory = intrathoracic disease
-Breathing through mouth or nose
- Rectal temp: “touching” contact
-Normal: 99-102.5F
-Viral 105-107F
-Heat stress also increases temp - Auscultation: lung fileds, upper airway (trachea)
-Behind elbow
-Mid-chest
-Dorsal lung field ~6-9th intercostal space
Bacterial pneumonia is cranial ventral, Lungworms and mycoplasma more dorsal
-Wheezes, whistles, crackles, increased sounds compared to normal
-Abnormal or absence of sound (consolidation) maybe significant
-Use rectal sleeve to induce deep breath
Heart Sounds
-Maybe muffled, normal, louder (referred through consolidated tissue)
-May obscure soft or subtle lung sounds
Percussion
-Simultaneous over rib and auscultation
-Identifies areas of consolidation
- Palpation of larynx and trachea
-Visualization: endoscope
-External palpation may elicit cough or pain: suggest tracheal irritation = respiratory problem - Head/neck symmetry, swellings
-Face, head, neck, eyes, airflow via nostrils, sinuses (swelling, percussion) - MMs, mouth, oral cavity
-Discharge, forth, foaming
-Mucosa color: pale (anemia), reddening (inflammation)
-Vesicles, ulcers, erosions
-Blunting of papilla
-Capillary refill time
-Odor of breath, maybe necrotic suggesting aspiration pneumonia - Nasal and ocular discharge
-Serous: early on
-Mucopurulent: later
-Unilateral, bilateral: localized vs. systemic/generalized disease
-Amount: increased, decreased, plugged nasolacrimal duct
Describe methods for sample collection and laboratory testing
Diagnostic Aids
-CBC not necessary if you hear typical pneumonic lungs sounds
-Parasitology: Baerman technique (lungworms)
-Thoracic radiographs (challenging in adults)
-Ultrasound
-Endoscopy
-Transtracheal washing
-Nasal or laryngeal swabs
-Blood analysis
Necropsy
-Appropriate samples for bacteriology, virology, histopathology
+/- Euthanasia of acute case for diagnosis
Dx
-Nasopharyngeal Swab: contamination, lower airway representation limited
-Transtracheal Wast or Aspirate: invasive
-Nonendoscopic Bronchoalveolar Lavage: contamination risk BAL
-Endoscopic Bronchoalveolar Lavage: Cost, equipment needs
Viruses vs. Bacteria, LOCATION!
-Work with diagnostic lab to develop protocol
-Recognize limitations and advantages of each Dx method/sampling
-Nasal swabs for viruses maybe helpful, PCR antemortem.
-Tracheal wash for viruses and bacteria identification
Summary
-Can’t culture from fixed tissues
-Hard to do histopath on frozen tissues
-Microbial culture for bacteria
-PCR mainly viruses
-Serology - antibodies
-Direct MALDI-TOF for bacteria
-Nonsequencing mainly viruses
Describe how to diagnose, treat, and manage diseases and conditions of the nasal cavity and sinuses
Nasal Cavity and Sinuses
- Nasal Granuloma
Mycotic Bovine Nasal Granuloma
-Sporadic, rare
-Fungi, bacteria involved
-Unilateral or bilateral
C/S
-Upper respiratory noise
-Mucopurulent discharge
-/+ epistaxis
Dx
-Endoscopy
-Biopsy of lesion and culture
Tx
-Difficult
-Surgical resection if possible
-Long-term iodine sodium therapy??
-Consider lavage
-Slaughter, auction region specific
- Allergic Rhinitis
-Usually adults, families
-Plant pollen or fungal spore causative agents
-May be seasonal
C/S
-Bilateral serous nasal discharge
-Stertorous breathing (reverse snoring like sound)
-Intense pruritic (rubbing of nose)
-May lead to multiple nasal granulomas
Tx
-Antihistamines
-Corticosteroids parenteral or topical
-Prolonged tx
-Live with or cull
- Sinusitis (post dehorning)
-Frontal sinus secondary to dehorning
-Maxillary sinus: extension from root infection
-Typically unilateral
C/S
-Anorexia
-Lethargy
-Nasal discharge (unilateral)
-Facial swelling/exopththalmos
Dx
-Percussion
-Radiographs
Best time to dehorn <4-5 mts of age
Tx
-Drain
-Flush with antiseptic solution
-Parenteral antibiotics
-NSAID for pain
-Sinusotomy via trephine
Describe how to diagnose, treat and manage diseases and conditions of the larynx, pharynx, and trachea
Larynx, Pharynx, and Trachea
- Pharyngeal trauma and abscess
-Secondary to iatrogenic injury Balling gun, stomach tube, esophageal feeder or rough, stemmy feeds.
-Prelube equipment, water or mineral can be used
C/S
-Respiratory dyspnea on inspiration
-Digestive trouble swallowing
-Palpate swellings, aspirate??
Dx
-Endoscopy
-Radiographs
Tx
-Discrete abscesses can be drained preferably into pharynx (aspirate first)
-Cellulitis must be treated medically
-Antibiotics: broad spectrum or based on culture
-Consider slaughter
Prognosis
-Good for mild, discrete lesions
-Guarded or diffuse lesions
- Necrotic laryngitis (calf diphtheria)
-Fusobacterium necrophorum
-Young, 1-18 mts usually 1-4 mts of age
C/S
-URT infection
-Increased coughing leads to laryngeal trauma and erosion of mucosa over vocal processes and arytenoids (ulcers)
-Opportunistic infection of eroded mucosa by F. necrophorum
-Acute onset
-Anorexia
-Depression
-Fever
-Severe inspiratory dyspnea
-Foul odor breath
-Death possible
Recovered cases have roaring noise from misshapen larynx
Dx
-C/S, history, visual lesions, oral exam
Tx
-Antibiotics injection
Oxytet, Penicillin
-Anti-inflammatories: Dexamethosone
-/+ Tracheostomy: 1-2 weeks, when severe dyspnea, cyanosis.
Prognosis
-Fair for survival, some may need surgery
- Tracheal edema syndrome “Honker Cattle”
-Heavy feedlot cattle 2/3 of feeding period
-Unknown etiology
C/S
-Edematous thickening of the dorsal membranes of the trachea
-Inspiratory dyspnea
-Cyanosis
-Honking
-Death by asphyxiation <24 hours (tracheostomy needed)
Tx
-Antibiotics
-Corticosteroids
-Tracheostomy
Stertor vs. Stridor breathing
Stertor is a sound similar to snoring, while stridor, which is commonly associated with laryngeal disease, is a more high pitched sound. During upper airway obstruction, normal inspiration causes negative pressure inside the upper airways, resulting in collapse of weaker or less supported tissues
Lecture 2 Objectives
For each of the four major viruses, be able to describe in general each of the specific topics below
Virus characteristics
Name
Physical durability
Genetic features
Epidemiology: transmission, distribution, importance
Pathogenesis
C/S
Dx
Prevention and Control
Primary Viruses
- Infectious Bovine Rhinotraceitis (IBR) (BHV-1)
- Bovine Respiratory Syncytial Virus (BRSV)
- Parainfluenza-3 Virus (PI3)
- Bovine Viral Diarrhea Virus (BVD) BRD emphasis
Infectious Bovine Rhinotraceitis IBR “Red Nose”
Virus characteristics
-Single serotype, 3 subtypes based on disease caused
-Other diseases: Reproductive Infectious pustular vulvaginitis (IPV), balanoposthitis, abortion. Conjunctivitis, encephalomyelitis, mastitis
Name
-Bovine Herpes Virus -1
Physical durability
Genetic features
Epidemiology:
-Transmission via oronasal secretions, spreads quickly. Peak shedding 3-6 days post exposure. Shedding stops 12-14 days
Distribution
Importance
Pathogenesis
-Onset after loss of maternal immunity usually >6mts of age
-Incubation period: 2-6 days
-Latent infection trigeminal ganglia in recovered cattle. Reactivation possible, immune suppression via leukocyte dysfunction and reduced numbers.
C/S
-Mild to severe disease, secondary bacterial pneumonia
-Fever >105F often
-Off-feed
-Cough
-Excessive salivation
-Inflammed nose “RED NOSE”
-Dyspnea if larynx is occluded with purulent material
Lesions
-Inflamed tissues with serous or serofibrinous exudate, blood tinged
-Larynx, trachea, sinuses
-Nasal cavity lesion externally seen
-Grayish, necrotic foci on membranes (pustules)
-Pseudodiphtheritic yellow plaques later on
-Erosions, ulcers, generalized infections in young animals
Dx
-C/S and lesions
-PCR from nasal secretions
-Serology antibodies
-Tissues from necropsy
-Secondary bacteria and viral co-infections
Tx
-Treat secondary bacterial pneumonia
Prevention and Control
-Vaccination: modified live vax
-Avoid in pregnant cattle
-Intranasal vax safe in pregnant animals
-Killed vax - whole virus
-Biosecurity
-Eradicated in Europe with DIVA vax
Bovine Respiratory Synsytial Virus
Virus characteristics
-Cytopathic effect
-Only causes respiratory disease
-Possible antigenic subtypes
-Associated with BRD in young beef and dairy
Name
-Pneumovirus in Paramyxovirus RNA
Physical durability
Genetic features
Epidemiology
-Transmission: initial exposure by respiratory tract = severe disease, mild during subsequent exposures
-Distribution: worldwide indigenous in cattle populations: sheep goats can be affected
-Importance: high morbidity, 0-20% mortality
Pathogenesis
-LRT infection
-epithelial cells = destroys mucocilliary apparatus
-Alveolar macrophages
-Promotes secondary bacterial infections
C/S
-Fever 104-108F
-Lethargy
-Deceased feed intake
-Increased RR
-Cough
-Nasal and lacrimal discharge
-Dyspnea
-Open mouth breathing in later stages
-Subcutaneous
-Occasional biphasic disease pattern - mild then severe
Lesions
-Diffuse interstitial pneumonia
-Subpleural and interstitial edema
-Pulmonary emphysema “pulmonary bullae”
-Bronchopneumonia due to secondary bacteria is often present
Dx
-Histopath: multinucleate giant cells (syncytial) inclusion bodies, secondary bacteria = Fibrinous pneumonia
-Virus isolation
-PCR nasal swab
-Tissues IHC, FA
-Serology antibody
Tx
-Treat secondary bacterial infection
-Supportive therapy
-NSAIDs, fluids for dehydration
-Antihistamines
-Corticosteroids
Prevention and Control
-Vaccines killed and MLV
-Often combination IBR, BVD and PI3
-Also Mh and Pm IM and intranasal administration
PI3
Virus characteristics
-RNA virus
-Grows in cell culture
-Hemagglutinates erythrocytes - serology
-Primary invader
Name
-Paramyxovirus
Physical durability
Genetic features
Epidemiology
-Transmission: by aerosol and direct contact
-Healthy calves often seroconvert
-Distribution: widespread in cattle
-Importance
Pathogenesis
-Only infects respiratory tract epithelial cells
-Nefcrosis of ciliated epithelial cells = impaired mucocilliary clearance
-Incubation 24-36 hours
C/S
-Fever
-Lethargy
-Off-fed
-Cough airway disease
-Increased respiratory rate
-Dyspnea
-Nasal and ocular discharge
-Altered lung sound
-Suggests pneumonia
-Cranioventral lung consolidation
Dx
-Histopath: bronchiolitis and alveolitis
-Intracytoplasmic inclusions: nasal epithelium
-Syncytia formation
-PCR nucleic acid
-Antigen detection
-Virus isolation
-IHC, FA
-Hemagglutination inhibition (HI)
Tx
-Address secondary bacterial infection
-Vaccination MLV, parenteral with IBR, BVD, BRSV, intranasal with IBR
-Killed vax
Prevention and Control
BVD
Virus characteristics
-Genus Pestivirus
-Type 1: sub genotypes a and b. Type Ib most common
-Type 2
-Similar to border disease virus and classical swine fever virus
Name
-Flaviviridae, Pestivirus
Physical durability
Genetic features
-ssRNA
-Enveloped
-Spherical capsid
Epidemiology
-Biotype Cytopathic and non-cytopathic
-Cytopathic rare
-Transmission: biting insects, fomites, semen, biologic products, wild animals??
-Distribution endemic worldwide, most important in some countries
-Importance
Pathogenesis
-3-24 months of age
-Causes immunosuppression = secondary bacterial pneumonia
-NCP: Persistently infected calf gestation day 30-110.
-Herd bull may become acutely infected if exposed to infected cows during breeding
-PI animals often die by 2 years of age
-PI cows always give birth to PI calves
C/S
-Reproductive dysfunction
-Respiratory complications
-Diarrhea
-Gastrointestinal ulcers/erosions
-Respiratory BRD
-Immune
-Integumentary
-Cardiovascular: hemorrhagic syndrome
-Reproductive: abortion anytime during gestation
-Biphasic fever
-Lethargy
-Inappetence
-Increased RR
-Excessive nasal secretions
-Diarrhea
Lesions
-Oral ulcers/erosion
-Coronary band eruptions
-Diarrhea
-Petechial hemorrhages in mucosal membranes
-Penumonia
Dx
-History and C/S
-Gross and microscopic lesions
-Necropsy: spleen, LNs, ulcerated GI tract segments
-PI calves: ear notch, fixed in formalin - IHC (single time point; high antigen amount compared to transient infection)
-VI buffy coat, PCR, antigen ELISA
-Repeat test >3 weeks to determine persistence
-Serology paired samples >4 fold increase in titer
Tx
-Secondary bacterial pneumonias and other infections
-Supportive
Prevention and Control
-Vaccination type I and type II combo
-Test for PI
-Biosecurity
-Quarantine for 2-4 weeks
-Herd control programs, screen milk/blood for PI cattle
Bovine Adenovirus
Virus characteristics
-Multiple serotypes 10
-Non-enveloped
-Resistant in environment
Name
Physical durability
Genetic features
Epidemiology
-Transmission
-Distribution
-Importance
Pathogenesis
-Widespread respiratory and GI infections
-Clinically inapparent
C/S
-No signs
-No known disease causation
Dx
-Culture
-PCR
-NGS
Prevention and Control
-No vax available
Bovine Coronavirus (BCV)
-RNA virus
-Enveloped unstable in environment
-Tropism for respiratory tract
-Single serotype
-Associated with neonatal calf diarrhea “winter dysentery”
-Co-infections common
-BRD clinical signs
-Difficult to isolate in culture
-Dx: PCR, standard methods
-Vax for enteric but not respiratory disease
Bovine Rhinitis A and B
-Associated with BRD cases
-USA Rhinitis A virus 1
-Seropostive rates via IFA
Bovine Influenza D and C virus (IDV)
-Orthomyxovirus
-RNA enveloped
-First detected in pigs
-Believed to play a role in BRD
Zoonotic complications
-Replicates in ferrets
-91% of cattle co-workers seropositive
Bovine Respiratory Disease Complex
AKA: shipping fever, pneumonia, etc
-Most costly disease to the U.S cattle industry
-1 billion per year loses
Occurs around times of stress
-Weaning
-Commingling
-Shipping
-Weather
-Diet change
-Castration
-Dehorning
-Induction of abortion
-Branding
Disease progression
- Stress
- Viral component
- Bacterial component
- Lung tissue Damage: lung lesions
C/S
-Lethargic
-Depression
-Away from herd
-Fever
-Cough
-Nasal discharge
-Dyspneic
-Tachypneic
-Found dead!
Common life stages affected
Risk Factors
Occurs around times of stress
-Weaning
-Commingling
-Shipping
-Weather
-Diet change
-Castration
-Dehorning
-Induction of abortion
-Branding
Major Bacterial Pathogens Associated with BRDC
Name and describe the major 4
Associated Conditions/diseases
- Manheimia hemolytica
-AKA: Pateurella haemolytica
-Most common bacterial pathogen
Causes the most lung damage
-Leukotoxin: causes death of neutrophils and release of enzymes, other inflammatory products
Fibrinopurulent bronchopneumonia
-Often cranioventral
-Can be sudden death
-Commensal bacteria in URT
-May carry antimicrobial resistant genes (MDR)
-Vaccines questionable efficacy
- Pasteurella multicocida
-Five serogroups
-Serogroup A in cattle
-Commonly in young calves
-Enzootic pneumonia in dairy calves
-Milder disease than Mh
-Less fibrin
-Part of normal flora in URT
- Hemophilus somni
-Other forms of disease: myocarditis, arthritis, TEME (thromboembolic meningeoncephalopathy)
-More common in certain geographic areas
- Mycoplasma bovis
-No cell wall, frustrating pathogen
-Beta lactase not effective
-Difficult to treat, especially after clinical signs have started
-Can be primary pathogen BRDC or secondary
-Found at necropsy after other pathogens are gone
Other manifestations: arthritis -lameness, otitis media - head tilt, mastitis
- Others:
-Bibersteinia treholsi
-Mycoplasma bovirhinis
-Chlamydia psittaci
-Salmonella
-Trueperella pyogenes
-Foreign animal disease: Mycoplasma mycoides contagious bovine pleuropneumonia
BCDC Diagnosis
-Postmortem/necropsy
-Visual, temp, lung sounds, Ultrasound, TTW, NPS
-Bacterial culture/sensitivity
-PCR
-Confounding issues: calves may have been treated before you see them, only resistant bacteria left, secondary infection present
Methods of measuring the severity of lung damage
Lung lesions
-Percentage of lobe damaged
-Consolidation, nonfunctional lung tissue
-Way to measure severity of disease
-Found at necropsy
-Determined at slaughter
Important factors in mitigating BRDC, Prevention
- Vaccination
-Vaccination - viral pathogens
-Vaccination - bacterial pathogens
-Commercial and autogenous: M. haemolytica, P. multicocida, H. somni, M. bovis
-Autogenous: others
- Pre-condition
-Wean on farm
-Learn feed bunk
-Vaccinate properly: two doses prior to weaning
- Reduce Stress
-Bedding
-High fiber/roughage
-Water access
-Group with like cattle
-Shade
-Space
-Wind break
Tx
-Antimicrobials
-Metaphylaxis
-Mass treat
-Pull/treat
-NSAIDs: fever reduction
-Immune modulator
-Extra label treatments
Lecture
Bovine Respiratory Disease Complex Treatment
BRD definition
-Temp 104F or >
-Shows C/S, lethargy, depression, nasal discharge, dyspnea, others.
-Usually scale 1-4
-Treatment, treatment failure, relapse
Morbidity
-How many of a group get sick, percentage
Mortality
-How many of a sick group died, percentage
Case fatality rate
-Of those treated, how many died
-Goal <10%
-Measure of treatment efficacy
Metaphylaxis
-Treatment administered on arrival at farm/stockyard, etc
-Control, not prevention
Treatment
-Usually up to three times
-Pull/chronic “railer” not recovered despite treatment
Mass treatment
-Entire group
-Percentage treated daily
High risk
-/+ 50% pull rate
-High mortality
-Young, light weight, unknown vax status, shipping, commingled.
Medium risk
-Preconditioned
-/+ vaccinated
-Morbidity 10-30%
-Mortality 1-5%
Low risk
-Morbidity <10%
-Mortality <1%
Development of a treatment plan
Prior to arrival
-Determine risk classification: +/-metaphylaxis and antibiotic selection accordingly
-Identify sick animals: case definition, C/S, temp, etc.
-Accurate diagnosis
Chose Drug
+/- metaphylaxis and treatment (up to 3)
-Label indication
-Efficacy
-Cost
-Single, multiple dose
-Volume of dose
-Syringeability
-Route of admins
-Storage
Record Keeping
-Animal ID
-Withdrawal times
-Date of admins
-End of withdrawal
-Dose
-ROA
-Injection site
Treatment timing
-Metaphylaxis: not prevention
-After arrival: accurate diagnosis
-Antibiotics: usually up to 3 times, different antibiotics
-Chronic after 3 treatments
Common Antibiotics Available
Class
Common route of administration
Duration of treatment
Withdrawal times and limitations for use based on age, production status and extra-label use regulations
Antimicrobial Drug Classes
- Macrolides
Not for use in lactating dairy cattle
Tulathromycin (Draxxin)
Tilmicosin (Micotil)
Tildiporosin (Zuprevo)
Gamithomycin (Zactran)
Tylosin (Dylan) OTC
-MOA: inhibit protein synthesis at ribosome
-Typically bacteriostatic, can be bactericidal
-Newer molecules known for duration time above MIC
Spectrum: G (+), BRD (G-), anaerobes
-Distribution: weakly based, highly lipid soluble, poor CSF distribution
- Fenicols/Phenicols
Not for use in lactating dairy cattle
Florfenicol (Nuflor, Nuflor Gold)
Resflor Gold (Florfenicol + Flunixin meglumine)
-MOA: Inhibit protein synthesis at 50s Subunit of ribosome
-Typically bacteriostatic, some bacterial isolates bactericidal
-Broadspectrum
-Rickettsial
-Distribution: lips soluble, including CSF
- Fluoroquinolones
No extra label use
-Enrofloxacin (Baytril)
-Danofloxacin (Advocin)
-MOA: Inhibits DNA gyros and topoisomerase IV
-G (-), Rickettsia, Mycoplasma, Top 4 bacterial BRD pathogens, some G (+)
-Bactericidal
-Concentration dependent
-Good intracellular distribution
-Low plasma protein binding, CSF
- Beta Lactams
Anaphylaxis
PPG 30, 120 days withdrawal time
Penicillin (PPG, ampicillin)
Cephalosporins - Ceftiofur (Naxcel, Excel, Excede)
Ampicillin (Polyflex)
(more broad spectrum than penicillin)
-MOA: inhibit cell wall synthesis
-Narrow spectrum: G (+), anaerobes, fastidious G (-).
-Low volume distribution, no CSF, confined to plasma
-Ceftiofur: 3rd generation, fairly broad spectrum, less G (+). Time dependent, bactericidal.
- Tetracyclines
Oxytetracycline (LA 200, Bio-Mycin 200, Noromycin 300 LA)
Oxytetracycline + flunixin meglumine (Hexasol)
-MOA: Inhibits protein synthesis at 50s subunit of ribosome
-Bacteriostatic, bactericidal at high dose, concentration dependent
-Broadspectrum: G (+)? Rickettsial, Mycoplasma
-Distribution good except CSF
-Oral absorbed - calcium inhibits
-Slow IV, Nephrotoxic, irritating SQ IM
Oral Tetracyclines
-Water: No VFD, most common water med in pigs
-Feed: VFD required, variable dose in swine
-Labeled uses: scours, BRD, anaplasmosis
Sulfonamides
Except Albon, Prohibited in lactating dairy cattle
Sulfadimethoxime (Albon and others)
-OTC
-Water, injectable
-No potentiated sulfonamides labeled, human drugs used in pigs
Sulfamethazine (Sustain III bolus & others)
-Scour, calf diphtheria
-OTC
AS700 oral pre-mix
-Sulfamethazine
-Chlortetracycline
How to formulate antibiotic treatment protocols for BRD based on the animal, products available, administration and dosing constraints and economics
Withdrawal Times
0 days for milk: Cephalosporins Ceftiofur (Excede)
18 days for meat: Macrolides (Draxxin)
28 days BAL fluid: Tildipisorin (Zuprevo)
28 days for meat: Fenicols (Nuflor)
38 days for meat: Fenicols (Restflor Gold)
28 days for meat: Fluoroquinolones (Baytril)
13 days for meat: Beta lactams, Cephalosporins - Ceftiofur
28 days for meat: Tetracyclines
Duration of Therapy
-Macrolides (Draxxin) 10 days+
-Fenicols: short 48-72 hrs
-Fluoroquinolones: single dose
-Beta lactase, Cephalosporins Ceftiofur (Excede): 7 days
-Tetracyclines: 24-48 hours, 4 days max
Describe how and why supportive therapeutic products such as NSAIDs are used of treating BRD
-Reduce stress
-NSAIDs: Benamine labeled for controlled of fever
-Corticosteroids
-Vitamins
-Antihistamines
-Immune stimulant/modulator: Zelnate, Plasmid DNA in liposome, stimulates innate immune system
Describe the potential pitfalls encountered when formulating, implementing, and executing antibiotic treatment protocols
Read Product labels
-Indications
-Dosage
-ROA
-Withdrawal times
-Warnings
-More
**No extra label use for fluoroquinolone **
-Restricted use for cephalosporins
Treatment Failure
-Wrong diagnosis
-Viral BRDS
-Improper treatment dose
-Improper drug
-Antimicrobial resistance
-Relapse
-Treatment administered too late
-Lung damage/lesion too severe
Lecture
BRD Vax, product approvals, adverse effects
Available Respiratory Vaccines
Viral
-IBR: IN, MLV
-BVD Type 1&2: SQ, MLV
-BRSV: IN, MLV
-PI3: IN, MLV
-Corona? IN, MLV
Bacterial
-Pasteurella multicocida: IN, MLV
-Mannheimia Haemolytica: IN, MLV
-Histophilus somni: SQ, Killed
Describe the window of susceptibility with regard to passive and active immunity
-Between birth and weaning
-When Maternal antibodies protection end and Active immunity is not fully stimulated
-Passive immunity decreases
-Active immunity begins to increase
The rate of maternal antibody decay rate is not constant across pathogens
Guiding principles
-FPT is not uncommon, navel ill, septic arthritis
-Maternal antibody titers (protection) wane over time
-Decay rate is pathogen specific
Maternal antibodies can interfere with active immunization
Vax goal is to stimulate active immunity before passive is gone
Differences between killed and MLV, cost, reactivity, routes of administration
MLV
-Broader spectrum
-Less expensive to manufacture than killed
-More costly to develop
-Less reactive than killed if fully attenuated
-Can provide protection when given IN
Killed
-Less risk of contamination
Immune stimulation Mechanism of mucosal immunization and overcoming maternal antibody interference
-Inherent responses compared to parenteral (SQ)
-Limited to MLV
-Depends on somewhat the level of “infection” induced by MLV
-Avoiding maternal antibody interference: because it is local, very low levels on mucosal surfaces, maternal AB are systemic
Overcoming Maternal Interference
-IN vaccines have shown to overcome maternal interference in: PI3, BHV-1, BRSV, BVDV, P. multicocida, IBR, BVD 1&2
-IN vaccines replicate in mucosa
-Prime mucosal immune system with little interference from maternal antibodies
Mucosal Immune Response, M cell
-Mucosal-Associated Lymphoid Tissue
-Specialized epithelial (M-cells) sample the environment
-Oral cavity, small intestines, caecum, large intestine, rectum, respiratory tract.
-Take up antigen, transported and released at the basal surface, dendritic cells (activated T cells)
-Activated B cells provide humoral response. IgG, IgM, IgA produced
SQ administration does not induce local IgA, IgM
BVD SQ works <4 mts old
IBR, BRSV SQ <4 mts does not work
Outcomes of excessive endotoxin levels in vaccines
-Derived from Gram (-) bacteria
-Capsular substance in the cell outer membrane
-Stimulate mediators of shock
-Inflammatory mediators released
-Decrease WBC count
-Increase temp
-Pulmonary edema
-Abortion and death
Avoid endotoxin “stacking”
-Simultaneous immunization of 2 or more vaccines
Mucosal surfaces and Endotoxins
-Adapted to manage and metabolize endotoxin
-Constantly exposed to gram (-)
-Very young animals better
-Reduce risk of disease
Regulatory process for the approval of animal health products, agencies, pharmas and insecticides
Regulated by FDA so Phases are similar to Human Studies
-Preliminary studies
-Approval studies can be complicated: require field-based efficacy studies
-Pre-development
-Development: Minimum protective dose. Duration of immunity. Primary variables (disease), secondary variables (tissue levels and shedding). Field safety study required. Potency test validation for serial release.
- Target Animal Safety
- Effectiveness
- Human Food Safety
- Chemistry, Manufacturing, and Controls
- Environmental Impact
- All other information
- Labeling
- The Freedom of Information Summary
Types of post-licensing studies
- Post market studies: usually directed by tech service; address customer questions
-Example PCV2 vax - Life cycle management: performed by R and D; label extensions (mostly indications)
Role of practitioner in reporting adverse effects
Types of Adverse Effects
-SLEE: suspected lack of expected efficacy
-SAR: Suspected adverse reaction
-Also product defects
Who initiates - Everyone
-Attending vet
-Producer, customer, client, staff, others
-Found in public domain
Complaints to
-Regulatory agency
-Manufacturer
-Requirements to report: within firm, Pharma: report to FDA in X number of business days
-Bios: keep on file, may be reviewed during routine CVB inspection
Regulatory agencies
FDA: Drugs
USDA: Vaccines
External chemicals: EPA
