Exam 3 Flashcards
General Features of Mycobacterium
o aerobic, “Gram-positive rods” o Facultative intracellular specific to macrophages o non-spore forming, non-motile o mycolic acids & lipids in cells wall o must be acid-fast stained o grow very slowly o Complex egg-based media is required for growth o Chronic/progressive dz
Major Pathogenic Mycobacteria
M. bovis:
• Primarily infects cattle
• Can affect others
M. tuberculosis
• Primarily Human, but dogs, rodents, swine can get infected
M. avium (paratuberculosis )
• Cattle, sheep and goats
Non-tuberculous Mycobacterium (NTMs)
• Several species
Bovine Tuberculosis (M bovis) source of infection & survival in environment
- Infected animals are source of infection.
- Bacteria are in exhaled respiratory droplets, sputum, milk, feces, urine, vaginal discharge.
- Survives in environment for 4 - 28 days
- May survive longer in presence of organic material.
Bovine Tuberculosis (M bovis) Entry, Multiplication, Spread, Damage
- Bacteria inhaled or ingested ->
- taken up by macrophages.
- multiply intracellularly and travel inside of macrophages to regional lymph nodes ->
- May enter lymphatics and blood and disseminate widely ->
- Two possible outcomes:
- Latency
- tuberculosis & systemic granulomas (Pathognomonic Lesion)
Bovine Tuberculosis (M bovis) Clinical Signs, Diagnosis, Treatment
Clinical Signs
• Respiratory signs:
moist cough, dyspnea, weight loss
• Rarely mastitis
• Enlarged bronchial, mediastinal and mesenteric nodes
Diagnosis
• Caudal fold test (cross-reactivity common)
• tubercles on necropsy
• culture (time consuming)
• PCR (definitive & fast but difficult if no clinical signs)
Treatment & Control
• No treatment = slaughter
• Test new animals
• No Vx
Bovine Paratuburculosis or Johne’s (M. avium) Encounter, Entry, Multiplication, Spread
Encounter
• Environment contaminated w/ fecal material from infected animals
Entry, Multiplication, Spread
• Feces Ingested shortly after birth ->
• Invades macrophages in Peyer’s patches ->
• Multiply & kill macrophages ->
• Spread to adjacent cells ->
• Inflammatory response ->
• Thickened intestine & loss of absorption
Bovine Paratuburculosis or Johne’s (M. avium) Clinical Signs, Diagnosis, Treatment
Clinical Signs
• Perinatal period
• reduced milk production, diarrhea, weight loss, normal appetite.
• shedders are often not clinically ill
Diagnosis • Direct microscopy • DNA based PCR test • Johnin test • Culture of organisms from manure or ileal node (good, takes long time, need multiple samples)
Treatment/Control
• No treatment = slaughter
• Do not accept new animals
Non-Tuberculous Mycobacterium (NTM) Clinical Signs & Diagnosis
Clinical Signs
• Granulomatous inflammation in dogs & cats
• Localized or systemic
• Skin infections, pneumonia, or GI infection
Diagnosis of NTMs
Histology
• Acid fast stain
• Pyogranulomatous inflammation
PCR
• On tissue sections or culture
Culture & Sensitivity
• Use for treatment w/ antibiotics
Basics of Mycoplasma
o Facultative anaerobes o Smallest self-replicating bacteria o obligate parasites o no cell walls o need giemsa stain o resistant to penicillin, cephalosporin o Extremely fragile o “fried egg” colonies o “fastidious bacteria” (must use special media w/ penicillin to ward off gram (+) & thallium acetate to ward off gram (+) )
Encounter/Entry Mycoplasma
Encounter
o introduced by clinically healthy carrier animals
o Prefer upper respiratory, intestinal, genital tract, joints, conjunctiva and mammary glands
Entry
• direct droplet of oral, ocular, or genital secretions
• contaminated equipment or blood transfusion)
• Some transmitted via tick bite (mechanical)
4 Virulence Factors of Mycoplasma
Adhesins
• used for binding of bacteria to
the host cells
Capsules
• For biofilm = impede host defense & persist in environment
Hydrogen peroxide
• Affects ciliary movement in trachea and induces hemolysis
Biofilm
• resistance for dessication, heat and complement mediated lysis
Chronic Respiratory Disease caused by M gallisepticum Basics, Encounter, & Entry
o Affects chickens, turkeys, game birds
o Localized mycoplasma infection
o exogenous
Encounter/Entry
• Infection via respiratory route or thru infected eggs
• Stress = asymptomatic carriers become sick & shed in respiratory aerosols
Chronic Respiratory Disease caused by M gallisepticum Multiplication/spread, damage, symptoms
Multiplication / Spread
• attaches ciliated epithelium of trachea & multiplies
Damage
• Damages cilia
• Sinusitis, tracheitis, airsacculitis
Symptoms
• coughing, sneezing, nasal discharge, dyspnea, reduced growth, decreased egg production
• high morbidity, low mortality
Chronic Respiratory Disease caused by M gallisepticum Diagnosis, Treatment, Control
Diagnosis • Culture • FA • PCR from exudate & tissue • ELISA on serum
Treatment
• Tylosin, tiamulin, chlortetracycline, lincomycin
Control
• Depopulation & disinfection
Basics of Invasive Mycoplasma Infections; two outcomes
o penetrate epithelial barriers and enter the blood stream
infection / acute septicemia
o fever and sudden death
Brief period of inapparant mycoplasmemia
o localization in serosal cavities and joints ->
o chronic inflammation
Feline hemotrophic mycoplasmosis Basics & mycoplasmas involved
- cause of hemolytic anemia in cats
- can be endogenous or exogenous
Mycoplasmas involved
• M hemofilis (clinical symptoms)
• M hemominutum
• M turicensis
Feline hemotrophic mycoplasmosis Predisposing Factors & Encounter for Exogenous infection
Predisposing factors:
o Surgical stress, FIV/FelV, abscess, corticosteroids
Encounter for Exogenous • Arthropod vectors? • Biting and fighting • queens to new borne • blood transfusion
Feline hemotrophic mycoplasmosis 4 Phases
Pre-parasitemic phase
o Lasts 1-3wk post infection
o Bacteria not detectable
o Mild reduction HCT
Acute Phase
o ~30 days
o cyclic high number of bacteria in blood
o Parasitized RBCs sequestered in spleen w/ release of non-parasitized RBCs
o rapid decrease in HCT followed by rapid increase
o W/o treatment, 1/3 die of anemia
Recovery Phase
o time from last bacteremia until HCT has stabilized
o sufficient immune response or treated w/ antibiotics & recover
o regenerative bone marrow response
Chronic/Carrier Phase
o recovery from acute infections = clinically normal & chronically infected
o Low numbers of organisms may/may not be detectable
Feline hemotrophic mycoplasmosis Damage & Clinical Signs
Damage • Regenerative anemia w/ polychromasia & reticulosytosis • Precipitous drop in HCT Clinical Signs Acute o Fever, o marked mental depression, o tachypnea, o weakness, o anorexia, o pale mucous membranes, o dehydration
Chronic
o Mild anemia
Feline hemotrophic mycoplasmosis Diagnosis, Treatment
Diagnosis • No culture • Reduced HCT, reticulocytosis, icteric plasma • Blood smear may show mycoplasma on RBC • PCR highly sensitive
Treatment
• Tetracycline / doxycycline (gold standard)
• Enrofloxacin (alternative)
• Antibiotic does not clear parasite
Defense Mechanisms of Mammary Glands
Physical Barrier • Sphincter muscle tightens teat canal • Keratin plug • Keratinized squamous epithelium (prevents adherence) • Flushing milk
Innate & Adaptive Immune Response
• Macrophages (normal 66-88%)
• Neutrophils (normal should not have many)
• Abs neutralize bacteria/toxins
• B & T cells enhance immune response & kill infected cells
Soluble mediators
• Lactoferrin: iron binding protein prevents bacterial iron usage
• Lysozyme: cleaves peptidoglycans in gram (+) cell wall
Risk Factors for Mastitis
Host
• Age, stage of lactation, teat lesions, genetics
Environment
• Poor milking hygiene, milking technique, contaminated env
Microbial
• Contagious Vs environmental agent, virulence factors, habitat
Entry of Pathogens in Mastitis
o Systemic infection with localization in mammary gland
o Lymphatic spread
o Direct penetration
Breakdown of teat sphincter barrier (most COMMON)
• Teat sphincter open 2hrs post milking
• Bacteria ascend during this period
Pathogenesis of Mastitis
o If not eliminated by immune response -> multiply in mammary ->
Produce virulence factors • Adhesins: help adhere to mammary epithelial cells • Capsule: Anti-phagocytic • Exotoxins: produced by Gram (+) & (–) • Endotoxin: Released by Gram (-)
Induce leukocytes and epithelial cells to release chemo-attractants, including cytokines ->
Infiltration of polymorphonuclear neutrophils (PMNs) to the site of infection
• engulf/destroy bacteria
• destroy few epithelial cells = reduced milk production & release of enzymes
PMNs destroyed by macrophages ->
Dead epithelial cells & leukocytes secreted into milk = high milk somatic cell counts (SCCs) ->
Bacteria may spread into deeper mammary ductal system (eg., Staphylococcus aureus) or may float in milk secretion (eg., E. coli).
• Systemic signs from system infection OR endotoxin
Damage in Mastitis
o No persistent damage w/ proper treatment
Persistent infection • Damage to mammary gland alveoli • Breach of blood-milk barrier • Extensive damage can result in leakage of blood in milk • swelling w/in mammary epithelium
Chronic Dz due to uncleared infection
• Abscessation and gangrenous reaction
• Atrophy of mammary alveoli
• Fibrosis of mammary tissue leading to further damage
Clinical Signs & Diagnosis of Mastitis
Clinical Signs
o Clinical
• Inflammation (SHARP)
• Abnormal milk (flecks, clots, off color)
o Subclinical
• No visible signs
• (+) SSC, CMT, & sterile milk culture
Diagnosis
o Direct Tests
• Multiple samples of Sterilely collected milk & gram’s stain or bacterial culture
• Biopsy (uncommon)
o Indirect Tests
• Somatic cell count (milk tank)
• California mastitis test (MST) – increased DNA = gel
• Electrical conductivity of milk to look for Na & Cl
Contagious Pathogens in Mastitis
o Obligate parasites o Obligate pathogens o Subclinical mastitis more common o Mycoplasma bovis o Staph aureus o Strep agalactiae
Clinical significance of mycotic infections & fungal structure
Clinical Significance
o mimic other types of diseases
o frequently associated with local debilitation or immune deficiency
Fungal Structure
o Eukaryotes (antibiotics don’t work)
o cells have ergosterol and zymosterol
(target for antifungal)
o cell walls high in polysaccharide (used for diagnosis w/ histochemical stain)
o anti-phagocytic capsule
Growth/Repro of Fungus
Molds
• Multicellular
• Hyphal elongation & division
• Mycelium: tangled hyphae (cottony) seen on agar for diagnosis
Yeasts
• Unicellular
• Reproduce by budding & form moist colonies
Dimorphic • Yeast in tissue • Mold in environment • Transition mediated by temp change • Exception: Candida albicans forms pseudo hyphae in tissue but yeast in culture
Important Fungi not Dimorphic
• Aspergillus fumigatus = mold in environment and tissue
• Cryptococcus neoformans is always yeast.
Types of Fungal Dz’s
cutaneous mycoses (ringworm)
subcutaneous mycoses (sporotrichosis, Rhinosporidium)
systemic mycoses
• opportunists (Candida albicans)
• primary pathogens (Blastomyces dermatitidis, Histoplasma capsulatum)
Encounter for Fungal Dz
o Most free living in environment o Some specific in animals • H. capsulatum : bat or chicken feces • Cryptococcus neoformans: pigeon feces • Microsporum canis: obligate paraiste • Candida albicans: skin & mucous membranes o inhalation or traumatic implantation from an exogenous source o usually not contagious o some have carriers
What Allows Entry of Fungal Dz
o Innate resistance from skin barrier (low pH, fatty acids, normal flora)
o Infection usually self-limiting
o Weakly virulent
Requires diminished host resistance • Loss of cutaneous barrier • Loss of normal flora • Local Immunosuppression • Decreased systemic resistance (malnuitrition or immunosuppression)
Multiplication/Spread & Damage for Fungal Dz
Multiplication/Spread o Most are aerobes o Don’t multiply well in body temp o Growth limited due to need for Fe++ o First line of defense is phagocytosis o 2nd line defense = T lymphocytes
Damage
o No toxins
o destruction of tissue by fungal multiplication & host inflammatory response
o granuloma formation is hallmark
Diagnosis of Fungal Dz; why pursue? presumptive & difinitive
Why pursue etiologic diagnosis?
• differentiate from other diseases characterized by loss of functional tissue by cellular infiltration
• differentiate between opportunistic and pathogenic fungi
• selection of appropriate drugs
presumptive diagnosis
• identification of hyphae or yeast on smear & cytology or histo & biopsy
• serology or skin tests
definitive diagnosis
• Saboraud’s Dextrose Agar (with antibiotics)
• Blood Agar
• up to 3-4 weeks for diagnosis
Antifungal Therapy basics; therapeutic index, dosing strategy
o Some may not need treatment
o opportunistic infections resolve when underlying problem corrected
o anti-fungal drugs toxic to host
o limited anti-fungal drugs
o fungi can develop resistance but sensitivity testing not done
therapeutic index:
• ratio between antimicrobial efficacy and toxic effects to host animal
dosing strategy • target organ • lowest effective dose • schedule • combination therapy
Polyene Anti-fungal Drug; compounds, mechanism, uses, notes
Compounds
• amphotericin B, nystatin
Mechanism
• Disturbs cell membrane (higher affinity for ergosterol than cholesterol)
Uses
• systemically (IV) for systemic infections
• topically for superficial infections (candidiasis)
Notes • Not water soluble • must be given IV for systemic infections • poorly penetrate CSF • nephrotoxic
Allylamines Anti-fungal Drug; compounds, mechanism, uses,
Compounds
• Terbinafine
Mechanism
• inhibits ergosterol biosynthesis
Uses
• Broad spectrum
• oral or topical for superficial & sub-cutaneous infections
• less toxic than amphotericin B
Azoles Anti-fungal Drug; compounds, mechanism, uses,
Compounds
• clotrimazole, miconazole, itraconazole, fluconazole, ketoconazole
Mechanism
• inhibits ergosterol biosynthesis
Uses • Broad spectrum • PO, IV for systemic infections • topically for superficial infections (ringworm), • less toxic than amphotericin B
Pyrimidine Anti-fungal Drug; compounds, mechanism, uses, notes
Compounds
• 5-fluorocytosine (5FC)
Mechanisms
• inhibits DNA and RNA synthesis
Uses
• PO for systemic infections
Notes
• Narrow spectrum
• resistance develops rapidly (use combo w/ other)
• enters CSF in high concentration
Grisines Anti-fungal Drug; compounds, mechanism, uses, notes
Compounds
• griseofulvin
Mechanisms
• inhibits microtubule assembly
Uses
• PO for superficial infection
Notes
• Not effective topically
• Teratogenic especially in cats
Cutaneous Mycoses; common name. 3 main sources
o Ringworm
Geophilic:
• dermatophytes that live (grow & replicate) in soil.
• prefer warm and humid climate
• poorly transmitted in animals
Zoophilic:
• dermatophytes that are obligate parasites
• spread rapidly among animals
• zoonotic
Anthropophilic:
• dermatophytes that are obligate animal parasites but predominately found on humans
• Ex: Athlete’s foot
Ringworm Host-parasite relationships in domestic animals
Microsporum canis
o natural host is the cat (is zoophilic)
o 15% human ringworm = zoonotic
o children very susceptible
Microsporum gypseum o reservoir is soil (is geophilic) o 1-10% cat infections o 25% dog infections o most common ringworm in horses in southern U.S. o poorly zoonotic
