Week 9 - Infectious Flashcards
What is Toxoplasma gondii?
- Obligate intracellular coccidian parasite
- Definitive host Felidae
- Intermediate hosts cats and other animals - any warm blooded
Bradyzoites exist as cysts in the ____
TISSUE
Bradyzoites are a bunch of tachyzoites together, essentially - latent infection
slow dividing
Toxoplasma oocysts are shed in the feces and transform into _______
tachyzoites, the actively forming dz that spread infection. they turn into bradyzoites
fast dividing
Sexual cycle (enteroepithelial life cycle) of Toxoplasma occurs in ___
ONLY CATS
There are 2 life cycles for Toxo - asexual can happen in any species warm blooded.
Sexual cycle does NOT cause clinical dz
What are the routes of infection for Toxoplasma?
- Transplacental/congenital - most severe in nature
- Bradyzoite cyst ingestion - hunting prey animals that are infected
- Oocyst-contaminated FOOD, water or soil ingestion (from feces)
- Blood product transfusion
- Organ transplantation
- Ingestion of infected goat milk
What is sporulation of the toxoplasma oocyst?
after defecating millions of eggs – the oocysts can sporulate, thus increase in resistance
takes 1-21 days
Cats do/don’t reshed infection after first exposure.
DON’T
- In immune/already exposed cats, the sexual cycle is ARRESTED and oocysts are not shed
- Immunity may last for several years to lifelong
What’s the difference between brady and tachy cyst/oocyst ingestion?
Bradyzoite cyst ingestion
* Oocysts produced by 97% of naïve cats
* Prepatent period (time between infection and shedding of dz) 3 to 10 days
* 100 million oocysts/day for 7-10 days
Tachyzoite/oocyst ingestion
* Oocysts produced by 20% of naïve cats
* Prepatent period is > 18 days
* Fewer oocysts shed for several weeks
How can reactivation of Toxo happen in cats/intermediate hosts?
- High doses steroids can cause animals to reshed oocysts
- Severe immune suppression that causes brady to become tachy
– High doses steroids
– HIV infection
– Chemotherapy
– Anti-rejection - PREGNANCY NOT associated with bradyzoite cyst reactivation!!
What are the general CS for Toxo?
- Most infections subclinical
- Young animals often most
susceptible - Age, sex, host
susceptibility/species, parasite
strain and number of organisms
may also be important
What are the CS for Toxo in cats?
- Enteroepithelial cycle usually subclinical
- Extraintestinal cycle
–Stillbirth, neonatal death
–Anorexia, lymphadenopathy, fever, dyspnea, coughing, CNS signs, vomiting, diarrhea, icterus, abdominal effusion, pancreatitis, splenomegaly, myositis
–Uveitis, chorioretinitis
Dogs
* Similar to cats
* Ocular disease less common
* Chronic neuromuscular disease
What are the CS for Toxo in humans?
- Immunocompetent
-Mild, flu-like illness - AIDS and transplant patients
-> 95% of cases due to bradyzoite cyst reactivation
-Encephalitis, chorioretinitis, occasional pneumonia - Transplacental infections
-Often asymptomatic at birth: later show chorioretinitis and mental
retardation
-Spread to fetus less common in early pregnancy but disease more
severe - < 20% of women show signs
How do you DIAGNOSE Toxo?
CLIN PATH
* +/- nonregenerative anemia, leukocytosis
* +/- hypoalbuminemia, hypoproteinemia
* Chronic infections may show hyperglobulinemia
* +/- increased CK, Tbili, ALP, ALT, lipase
CYTOLOGY
* CSF tap normal or increased protein and WCC
* Tachyzoites rarely seen in body fluids
RADIOLOGY
Thoracic
* Diffuse interstitial to alveolar pattern
* Pleural effusion
Abdominal
* Interstitial masses/mesenteric lymphadenopathy
* Hepatomegaly
* Peritoneal effusion
FECAL EXAMINATION
* Diseased cats RARELY shed oocysts and shedding period is short
* Examine FRESH feces to determine human health risk
* Sheather’s centrifugal sugar flotation
* Cannot differentiate from H. hammondii and B. darlingi
SEROLOGY
-high IgM within 2 weeks - consistent with dz
-IgM titers > 64
-or fourfold or greater, increasing or decreasing, IgG or other antibody titers
ORGANISM DETECTION
* Histopathologic detection of tachyzoites (NOT bradyzoite cysts), aided by immunohistochemistry
* PCR
What is the risk of owning a cat in terms of Toxo?
pets of low risk of infection
-30% of dogs and cats seropositive in the US
Pet cats of little risk
* Short shedding period
* Immunity to reshedding
* Uncommon reactivation
* Meticulous groomers
Seronegative cats greatest risk to seronegative women
What is Neospora?
PROTOZOA - Neospora caninum
- Transplacental transmission following ingestion of tissue cysts by carnivores or oocysts by herbivores
- Dogs (especially farm dogs), cattle, sheep, horses, goats, deer
- Not cats or humans
*dogs definitive host
What are the CS of Neospora?
Herbivores
* Abortion
Dogs
* Neuromuscular abnormalities and sometimes dermatologic, pulmonary, hepatic, and myocardial disease
* Ascending paralysis and muscle atrophy
and stiffness in dogs < 6 months of age
What is the pathogenesis in dogs?
- Purebred dogs
- Chronically infected bitches REACTIVATE during gestation with transplacental infection
-Successive litters affected
-Most pups in the litter - Congenital subclinical infection may be followed by reactivation late in life following immunosuppression
- Postnatal infection probably uncommon
How do you DIAGNOSE Neospora?
- Serology (IFA)
-Serum and/or CSF
-Cross-reactions with T. gondii insignificant - PCR
How do you prevent Neospora?
- Limit access of dogs to raw meat and placental materials on farms
Which atypical bacteria are there?
Actinomyces, Nocardia, Mycobacteriosis
Actinomyces and Nocardia are similar. How?
-Filamentous, branching, Gram- positive bacteria
indistinguishable by Gram staining
-Opportunists
-Chronic pyogranulomatous inflammatory lesions
-Sulfur granules
-Sporadic disease
-Not transmitted between animals
What is the pathogenesis of Actinomyces?
-Actinomyces is commensal bacteria in oropharyngeal and GI inhabitant. ANAEROBE
-Not in the environment
-when mucous membranes break (foxtail, dog fight), actinomyces is then introduced
-Grass awns contaminated in the oropharynx, migrate from respiratory or GI tract ® thoracic and abdominal cavities
–Diagnosis may be delayed months to years
-Bite wound inoculation
–Cervicofacial actinomycosis
–Limb or subcutaneous tissue infections
-CNS actinomycosis: hematogenous spread, or extension from from head/neck (basilar meningitis)
Is nocardia anaerobe or an aerobe? Where is it found?
-aerobe
-found in soil - ubiquitous soil saprophyte
–House dust, beach sand, garden soil, swimming
pools
What is the signalment of Actinomycosis?
-Common - since found in mouth
-Young adult to middle-aged large breed dogs
-Usually immune competent
What is the signalment of Nocardiosis?
-Uncommon to rare
-Usually cats or young adult dogs
-1/4 to 1/3 of dogs (and humans) are immunosuppressed
–opportunistic infection when animals don’t have a good immune system
What is the pathogenesis for Norcardia?
-Inhalation ® pleural and/or systemic spread
-Bite, scratch, or foreign body wounds > subcutaneous nocardiosis
-Hematogenous dissemination to other organs
(CNS, eyes, joints, bones, kidney and heart)
What are skin CS for Actinomyces/Nocardia?
- Firm to fluctuant swellings, +/- draining tracts
-Contain serosanguinous to purulent fluid, sometimes
with ‘sulfur granules’
-Sulfur granules most common in actinomycosis
-Tomato soup-like exudate
What are other CS for Actinomyces/Nocardia?
- Fever, anorexia, weight loss
- Pleural effusion and pyogranulomatous pneumonia
- Bronchointerstitial patterns, hilar lymphadenopathy,
lobar consolidation, extrapulmonary masses, pleural
effusion
-Pericardial involvement - Abdominal involvement
-Abdominal distention, mass lesions, organomegaly - Retroperitoneal space involvement
-Spinal pain, sometimes pelvic limb paralysis/paresis - CNS involvement
-Neurologic signs such as hyperesthesia and tetraparesis
hilar lymphadenopathy can also be fungal too
How do you DIAGNOSE Actinomyces/Nocardia?
- Gram stain
-Thin, Gram positive, beaded branching filaments - Culture
-Alert laboratory
-Slow growing, susceptible to overgrowth
-Incubate 2-4 weeks
-Smooth and moist or wrinkly, velvety colonies (molar tooth)
-Multiple specimens, biopsy specimens if possible
Nocardia grows on simple media. May be acid fast – might retain stain.
Actinomyces is NOT ACID fast - does not retain stain
- Histopathology
How do you TREAT Actinomyces/Nocardia?
- Prolonged treatment with high doses of antimicrobials to prevent relapse
-Cutaneous infections 1-3 months
-Pulmonary infections 6 months
-Systemic infections 12 months - Drain abscesses or pyothorax first
Actinomycosis - PENICILLIN, good prognosis
Nocardia - TMS, guarded prognosis
Mycoplasmas are not mycobacteriums. What’s the major difference?
Mycobacteriums have THICK CELL WALLS.
-Gram positive, aerobic, nonmotile bacteria
-Cell wall rich in mycolic acid (lipid):
–Acid-fast: retains carbol fuschin after heating and acid exposure
-Resistant to phagocytosis
-Resistant in the environment
-Resist many disinfectants
-inactivated by direct sunlight and dilute household bleach
What are etiologic agents of mycobacterium?
M. tuberculosis (humans) and M. bovis (cattle) > (MTBC - tuberculosis)
M. avium complex
M. lepraemurium
What are MTBC Mycobacteria?
-Highly pathogenic
-Facultatively or obligately intracellular
-Differentiation difficult
-Maintained by infection of reservoir mammalian hosts
-Survives only 1-2 weeks in the environment
-Reverse zoonosis
Who is most susceptible to M.t uberculosis?
DOGS
-Pulmonary predilection
-Most dogs subclinically infected
-Potentially zoonotic, this is the bad guy
How is M. Bovis transmitted?
-Ingestion of unpasteurized milk or uncooked meat or offal
-target in cats: GI
-traget in dogs: respiratory
Non-tuberculosis mycobacterium
-saprophytic, survive > 2 years in the environment
-Slow-growing (M. avium complex)
–Produce tuberculous lesions, disseminate
-Rapidly-growing (RGM)
–M. thermoresistible, M. fortuitum, M. smegmatis
What is the pathogenesis of M. avium?
-Acid soils high in organic matter
-Avian carcasses or feces
-No spread from animals to people
-Lesions resemble TB lesions
-Cats and dogs are quite resistant to infection
–Miniature schnauzers, Bassett hounds
Which are the rapidly growing mycobacterium?
-M. smegmatis and M. fortuitum most common
-Inoculated into skin via trauma
-Enhanced pathogenicity in adipose
-Cats most susceptible
What are CS for rapidly growing mycobacterium? (M. smegatis and M fortuitum)
Cutaneous and subcutaneous granulomas (mycobacterial
panniculitis)
-Especially inguinal area
-Resemble cat fight abscesses, later ulcerate, drain
-No systemic signs
What is Lepromatous mycobacteria?
-M. leprae, M. lepraemurium
-Localized cutaneous nodules which may ulcerate
-difficult/impossible to culture
What dz can Lepromatous mycobacteria cause?
Canine leproid granuloma syndrome
-CA, Australia
-short-coated breeds
-Usually head, pinnae
-Never cultured
How do you DIAGNOSE mycobacteria?
1.Presentation + acid fast stained cytology
2.Tuberculous granulomas
–Focal necrosis surrounded by plasma cells, macrophages and a fibrous tissue capsule
–Giant cells uncommon in dogs and cats
–Calcification may be present
3.RGM and lepromatous mycobacteria
–Pyogranulomatous inflammation
- Isolation
-Multiple deep tissue biopsies
- Tuberculous mycobacteria may take 4-6 weeks to grow on solid media, faster in liquid media
- RGM: 3-5 days
- Requires egg-enriched media (eg. L-J media) - PCR
How do you TREAT M. tuberculosis?
-Combinations of drugs for > 6 months
-Isoniazid-ethambutol/pyrazinamide- rifampin/streptomycin in humans
-Treatment of affected dogs and cats not recommended, but has been successful
-Streptomycin, isoniazid, rifampin
How do you TREAT M. Avium complex?
-Treatment difficult
-Fluoroquinolones, doxycycline and/or
clarithromycin/azithromycin
How do you TREAT Rapidly growing mycobacterium?
Skin lesions
-High doses fluoroquinolone or doxycycline, then surgical excision
-3-6 months of doxycycline or a FQ
-Rarely, lifelong treatment
What are the ground rules when choosing to use IMMUNOSUPPRESSIVE DRUGS
- Do everything possible to ensure immune-
mediated disease is really immune-mediated disease
-may need a lot of testing - Warn the owner that infection or neoplasia may go undetected despite your best efforts to uncover it
- Think before you clip - bc glucocorticoids slow hair growth
- Minimize excessive immunosuppression
* Degree of immunosuppression relates to
* drug and number of drugs used,
frequency, dose, chronicity
* Pre-existing immune defects/concurrent
disease
* Including age and breed
* Never use more than 2 drugs at a time
* Target is “pulse” immunosuppression - Maintain contact with your patient
Examples of glucocorticoids
Prednisone, prednisolone, dexamethasone
dex more potent than pred
MOAs of glucocorticoids
- Suppression of cytokine production
- Decreased antibody response
- Reduced T cell activation
- Decreased phagocytosis
- Decreased inflammatory cell influx
- Decreased Fc receptor expression by macrophages
- Lymphopenia, eosinopenia - stress leukogram
Glucocorticoids stop which pathway?
the Arachidonic Acid Pathway
no production of Prostaglandins, Thromboxanes, or Leukotrienes
What is the starting dose for Glucocorticoids?
Starting dose 1 mg/kg PO q12h
No higher than 30 mg to 40 mg total q12h
NEVER WITH NSAIDs - leads to GI perforation
What are side effects of glucocorticoids? (Pred)
-hair loss
-muscle atrophy - temporal muscle
-calcionosis cutis
-fat redistribution to belly
- PUPD, polyphagia (D)
- Panting (D)
- Muscle wasting, weakness (D)
- Hepatomegaly (D)
- Calcinosis cutis (D)
- Hypercoagulability (D)
- GI ulceration with anemia (D)
- Alopecia, thin skin, impaired hair regrowth (D, C)
- Lethargy, behavioral changes (D, C)
- Opportunistic infections (especially bacterial) (D, C)
- Sodium retention (D, C) (C>D)
- Early growth plate closure (D, C)
- Diabetes mellitus (C)
What is Cyclosporine A?
- Cyclic peptide
- Interacts with cyclophilins in lymphocytes, blocking formation of transcription factors needed for T cell
activation and cytokine synthesis (mainly Il-2)
-inflammation-mediator
-leads to DECREASED IL-2
- Sandimmune®
- Neoral®
- Atopica®
- Gengraf®
- Topical formulations for KCS
(Optimmune)
What’s the dose of Cyclosporine A for immune suppression?
- 3-5 mg/kg q12h initial
For atopic dermatitis
* 5 mg/kg q24h until clinical improvement (1-2 months)
* Taper to q48h then q72h
What are adverse effects of cyclosporine A?
- GASTROINTESTINAL SIGNS – MOST COMMON
-give with food - Gingival hyperplasia
- Verrucous dermatopathy
- Hirsuitism
- Hepatotoxicity
- Nephrotoxicity
- Lameness
- Neoplasia (lymphoma, up to 10% chance)
- gammaherpesvirus?
- Opportunistic infections
what type of metabolism is cyclosporine A?
- p450 enzyme metabolism
What kind of immunosuppressive drug is Azothioprine?
Nucleocide Analog - stops cellular replication
chemo drug – targets rapidly dividing cells
- Almost always used in combination with glucocorticoids
- Delayed onset of action
- 1-2 mg/kg q24h PO until remission (10-14 days), then q48h
- Glucocorticoid-sparing
-hepatotoxic!
Azathioprine (Imuran): Adverse Effects - Dogs
- Gastrointestinal upset - Most common
- Impaired hair growth
- Bone marrow suppression
-Monitor CBC q2 weeks for first 3 months then
every 2-3 months
-Uncommon - Hepatotoxicity
-Monitor liver enzymes q2-4 weeks - Pancreatitis
- Profound muscle weakness and tetraparesis
Can Azothioprine be used in cats?
NO NO NO
Severe adverse effects in
cats, especially marrow
suppression
How does Azathioprine affect the enzyme Thiopurine S-methyltransferase (TPMT)?
- Converts active metabolites of azathioprine to inactive metabolites
- Human patients with GENETICALLY LOW TPMT ACTIVITY ARE AT RISK FOR MYELOTOXICITY
- Dogs TPMT activity > cats (another reason not to give to cats)
- Dog levels vary but poorly correlated with myelotoxicity
What is Chlorambucil?
-chemo drug
-Used most often in cats
–2 mg every other to every 3rd day
- IBD, lymphoma, immune disease
- Low potency
- Adverse effects uncommon
–GI adverse effects
–Bone marrow suppression
-not rapidly acting, nor super potent
What 4 things should we keep in mind when tapering meds?
-Use objective measure to assess remission
-Aim for <6 months of therapy
-Taper by ~25% at each check-in
-Balance adverse effects
IMHA is a Type 2 hypersensitivity. What are some prognostic factors for IMHA?
- Intravascular hemolysis
- Absence of regeneration
- Auto-agglutination
- Thrombocytopenia
- Hyperbilirubinemia
IMPA is a type 3 hypersensitivity. What does IMPA stand for?
immune mediated poly arthritis
COMMON in dogs, UNCOMMON in cats
Usually NONEROSIVE polyarthritis
Genetic predisposition may exist
-DLA-DRB1 alleles
How do you TREAT IMPA?
Consider adding azathioprine, cyclosporine
* Most commonly azathioprine
* Cyclosporine alone an option (ie. no
prednisone)
* No concurrent NSAIDs with prednisone!!
- Monitor joint fluid cytology?
- May relapse
- Avoid vaccinations?
- Erosive polyarthritis may be refractory
Which drugs trigger IMPA?
- Chloramphenicol
- Itraconazole
- Propofol
- Trimethoprim-sulfamethoxazole
- Metronidazole
