General infectious disease Flashcards
Name 4 core canine vaccines. What form do the vaccines come in?
- Canine parvovirus - attenuated live
- Canine distemper virus - attenuated live or recombinant
- Canine adenovirus 2 - attenuated live
- Rabies - inactivated whole organism
Name 4 core feline vaccines. What form do the vaccines come in?
- Feline panleukopenia virus - attenuated live or inactivated whole vaccine
- Feline herpes virus 1 - attenuated live or inactivated whole vaccine
- Feline calicivirus - attenuated live or inactivated whole vaccine
- Rabies - inactivated whole organism or recombinant canarypox
What complication can occur if the intranasal, avirulent live Bordetella vaccine is injected subcutaneously?
Fatal hepatic necrosis
What are depot adjuvants in vaccines? Give an example of one
- Protect antigens from degradation - prolong the immune response by causing sustained release of antigen over a period of time
- Oil in water emulsions
What are particle adjuvants in vaccine? Give an example of one
- Particles that effectively deliver antigens to DCs and enhance antigen presentation (soluble antigens alone are not trapped/processed very efficiently)
- Microparticles, liposomes, immune-stimulating complexes
How do aluminum based adjuvants work?
Cause the release of inflammatory molecules and cytokines, trigger innate immunity by causing tissue damage/inflammation
How do saponin based adjuvants work?
Detergent like molecules that cause local tissue damage and stimulate Th1 activity
Why are microbial products effective as adjuvants in vaccines?
Represent PAMPs that trigger innate immunity through TLRs => release of cytokines and Th1 or Th2 responses
- Ex. LPS, killed anaerobic Corynebacteria, killed Mycobacteria
What is the mechanism of action of acyclovir and peniciclovir?
Guanosine analogs - activated by viral thymidine kinase, interfere with viral replication by inhibiting viral DNA polymerase and DNA synthesis
What are the prodrugs of acyclovir and peniciclovir?
Valacyclovir and famciclovir, respectively
What are the side effects of acyclovir/valacyclovir in cats and why are they not recommended for treatment of herpes virus?
- Myelosuppression, renal tubular necrosis, hepatic necrosis
- These side effects can occur without effective suppression of viral replication
What is the mechanism of action for idoxuridine, trifluridine, and zidovudine?
All thymidine analogues that interfere with DNA synthesis
What is the mechanism of action of oseltamivir (Tamiflu)?
Inhibitor of influenza virus neuraminidase
What is the mechanism of action of pentoxifylline?
Phosphodiesterase inhibitor - inhibits cytokine production, activation of T and B cells, neutrophil chemotaxis
Beta lactam antibiotics are named because they contain a beta lactam ring in their chemical structure. Name 4 antibiotic classes that are beta lactams
- Penicillins
- Cephalosporines
- Carbapenems
- Clavulanate
Are beta lactam antibiotics bacteristatic or cidal?
Bactericidal
What is the mechanism of action of beta lactam antibiotics?
Covalently bind to and inhibit penicillin binding proteins - needed to catalyze the cross linking of the peptidoglycan layer of the bacterial cell wall (see photo on desktop)
What bacteria are susceptible to beta lactam antibiotics?
Gram positive»_space;»> gram negative
Gram positive bacteria are more reliant on peptidoglycan cell walls (50-100x thicker than in gram negatives)
What mediates resistance to beta lactam antibiotics?
- Primarily beta lactamases - gram negatives express just under the LPS layer, gram positives excrete into the environment
- Can also alter the structure of peptidoglycan
Are beta lactam antibiotics time or concentration dependent?
Time
What are clavulanic acid, sulbactam, and tazobactam?
- Beta lactamase inhibitors - can be administered in conjunction with penicillins to overcome resistance
- Have weak intrinsic antibacterial activity
In an animal with renal failure, how should you adjust the dose of penicillins?
Time dependent and renal excretion - increase the length of the dosing interval
What class of beta lactam antibiotics are highly resistant to all beta lactamases and lead to rapid lysis of bacteria?
Carbapenams
What is the mechanism of action of glycopeptide antibiotics?
Inhibit synthesis of peptidoglycan by binding to amino acids in the cell wall, thus preventing addition of new units
What is an example of a glycopeptide antibiotic?
Vancomycin
What is the mechanism of action of fluoroquinolones?
Bind to DNA gyrase (aka topoisomerase II) and topoisomerase IV, which are the enzymes that cleave DNA during replication => disruption of DNA and protein synthesis
Why are fluoroquinolones more effective in gram negative bacteria?
- Gram negative primarily use DNA gyrase, while gram positives primarily use topoisomerase IV
- Fluoroquinolones usually have a lower affinity for topoisomerase IV => higher MICs for gram positives
- Newer generations inhibit BOTH more equally
What fluoroquinolones have greater efficacy against anaerobes?
Pradofloxacin»_space;> marbofloxacin > enrofloxacin
Are fluoroquinolones time or concentration dependent?
Concentration
Why does enrofloxacin result in blindness in cats? What are the physical exam findings?
- Causes acute retinal degeneration
- Bilateral mydriasis and tapetal hyperreflectivity
What effect can fluoroquinolones have on young animals?
- Can cause cartilage and joint toxicity by inhibiting proteoglycan synthesis
- Avoid prolonged (>7 day) use in rapidly growing dogs
What is the mechanism of action of metronidazole?
Accepts electrons from the electron transport chain, thus forming a nitroso free radical that damages DNA => bactericidal
What dose of metronidazole can cause neurotoxicity?
> 30mg/kg/day (lower if hepatic dysfunction exists)
What is the mechanism of action of rifampin?
Inhibits the beta subunit of DNA-dependent RNA polymerase => impaired RNA synthesis
Are fluoroquinolones bacteriostatic or bactericidal?
Bactericidal
What is an adverse effect of rifampin?
Can cause the tears or urine to be red-orange colored
What is the mechanism of action of TMS?
Inhibit folic acid metabolism by bacteria => interferes with purine and DNA synthesis
- Trimethoprim: inhibits dihydrofolate reductase
- Sulfonamides: analogs of PABA
Is TMS bacteriostatic or bactericidal?
Trimethoprim and sulfonamides separately are bacteriostatic. Together, they are bactericidal
What bacteria can be treated with TMS?
Gram positive and negative
- Enterococci are intrinsically resistant though
What is the mechanism of action of aminoglycosides?
- Bind electrostatically to the bacteria outer membrane and displace Mg and Ca, which link adjacent LPS molecules => increased cell permeability
- Once in the cell, bind to the 30S subunit of ribosomes => decreased protein synthesis
What bacteria are resistant to aminoglycosides?
Anaerobes - oxygen is required for movement into the cell
Aminoglycosides are water soluble and poorly lipid soluble. What tissues do they not penetrate well?
Prostate, brain, eye, CNS, bile
Are aminoglycosides bacteriostatic or bactericidal? Time or concentration dependent?
Bactericidal, concentration
What are the side effects of aminoglycosides?
Nephrotoxicity, ototoxicity, neuromuscular blockade
What is the mechanism of action of chloramphenicol?
Binds to the 50S unit of ribosomes and inhibits protein synthesis
Why do owners need to wear gloves when handling chloramphenicol?
In humans, even small amounts lead to irreversible aplastic anemia
What is the mechanism of action of macrolides (clindamycin)?
Binds to the 50S unit of ribosomes and inhibits protein synthesis
Are macrolides bacteriostatic or cidal? What bacteria do they treat?
Gram positives, bacteriostatic
What is the mechanism of action of tetracyclines?
Binds to the 30S unit of ribosomes and inhibits protein synthesis
Are tetracyclines bacteriostatic or cidal? Time or concentration dependent?
Bacteriostatic, time dependent
Name two slow growing mycobacterial species
Mycobacterium tuberculosis, bovis, microti, avium
What are the clinical signs of infection with slow growing mycobacterial species in cats?
- Cutaneous lesions most common: dermal nodules +/- ulceration +/- lymphadenopathy
- Can also affect the respiratory or GI tract
What are the clinical signs of infection with rapid growing mycobacterial species in cats?
Panniculitis - usually of the inguinal fat pad, but also described on the flanks and base of the tail. SubQ tissue becomes thickened, adherent to the dermis, nodules and draining tracts
What are the characteristics of Nocardia species?
Aerobic, branching, filamentous, gram positive, partially acid-fast bacteria
What are the characteristics of Actinomyces species?
Anaerobic or microaerophilic, filamentous, gram positive,
non-acid-fast bacteria
What are the typical clinical signs of infection with either Nocardia or Actinomyces?
- Typically form cutaneous, non-healing wounds, abscesses, or cellulitis (75% of cases); can become disseminated or cause intra-cavitary infections but it’s more rare
- Most common on the head, neck, and inguinal region
Sulfur granules (small, yellow, firm tissue grains) can be seen with what infection?
Actinomyces usually
Rarely Nocardia
How is Brucella canis transmitted? What is the most common route of infection?
- Penetrates the mucosal membranes of the conjunctiva, oral cavity, and vagina
- Oronasal contact with aborted fetal material or venereal are the most common routes of transmission
If a bitch is exposed to Brucella up to 20 days after conception, what occurs? If she’s exposed later in gestation?
Up to 20 days: Early embryonic death and resorption
Later: abortion around day 45-59
In problem kennels, how often should all dogs be tested by serology for Brucella? What is done if there is a positive test?
- Test every 3 months
- Positive dog is removed and the kennel is placed under quarantine until all dogs test negative by serology every 90 days for 3 tests
Before adding a new dog to the kennel, how should they be tested for Brucella?
- Tested using serology every 30 days for 3 tests before introduction
Brucella should be on your differential list in any dog presenting with what clinical signs, especially if intact?
- Uveitis
- Lameness, muscle weakness
- Spinal pain - vertebral osteomyelitis and disko
- Acute epididymitis and prostatitis
Why is spinal disease more common in male dogs with Brucella?
Prostate acts as a reservoir for the bacteria, leading to intermittent bacteremia
When will dogs test positive for Brucella on a rapid slide agglutination test?
As early as 2-4 weeks after infection BUT don’t trust a negative until 12 weeks after infection
Is the RSAT sensitive or specific for Brucella?
Highly sensitive but not overly specific - confirm all positives
What confirmatory tests are available for Brucella?
Agar gel immunodiffusion, tube agglutination, PCR
Is medical treatment of Brucella effective? Why or why not?
No - bacteria can live inside cells for extended periods of time, where they are protected from antimicrobials and the host immune response; bacteremia can be episodic and recrudescence is common
In IV catheters removed for clinical complications, what was the bacterial colonization rate? What was the most frequently isolated bacteria?
40%
Acinetobacter
How are dogs/cats infected with Francisella tularensis?
Contact with tissues of infected animals (rabbits, voles, ground squirrels, muskrats), tick or deerfly bites, rarely inhalation or ingestion
What are the clinical signs of F. tularensis infection in dogs and cats?
Pyrexia, lethargy, lymphadenopathy, mucopurulent oculonasal discharge, skin lesions/subQ abscesses, hepatomegaly, splenomegaly
Often self-limiting in dogs
Is hyperbilirubinemia +/- icterus more common with plague or tularemia in cats?
Tularemia
What is the treatment of choice for tularemia?
Aminoglycosides
Doxy, fluoroquinolones can be used but relapses may occur
How long should cats with Tularemia be housed in isolation?
First 72 hours of antibiotic treatment
What is “Alabama rot”?
Cutaneous and renal glomerular vasculopathy - thrombotic microangiopathy that begins as ulcerated skin lesions (often on the distal limb) and progresses to oligoanuric renal failure ~4 days later
What cardiac biomarker was higher in dogs with infectious endocarditis than in dogs with MMVD or immune mediated disease? What level predicted endocarditis?
Cardiac troponin I - serum >0.625 ng/dL had a 100% specificity and 52% sensitivity for diagnosis
Name 4 complications that can occur with infectious endocarditis
- Congestive heart failure from damage to cardiac valves
- Arrhythmias
- Thromboembolic disease
- Immune complex disease
What are the 2 major Duke criteria for the diagnosis of endocarditis?
- Echocardiogram findings: vegetative lesions, new valvular insufficiency, erosive lesions
- Positive blood cultures with a typical organism: 2 cultures taken >12 hours apart
What are the minor Duke criteria for the diagnosis of endocarditis?
- Fever
- Predisposing cardiac disease (sub aortic stenosis)
- Evidence of thromboembolic disease
- Evidence of secondary immune complex disease
- Microbiologic findings not meeting major criteria
What criteria must be met for a diagnosis of endocarditis?
2 major criteria OR 1 major and 3 minor
What was the survival rate of dogs with endocarditis in the 2021 JVIM paper?
Survival to discharge: 70%
1 month survival: 54%
What risk factors were associated with mortality in endocarditis cases?
CHF (OR 12), thromboembolic events (6), AKI (6.2)
What factor was associated with survival in dogs with endocarditis?
Administration of antithrombotics- MST not reached vs 92 days
Infection of what heart valve has historically been associated with a poorer outcome in endocarditis?
Aortic - not shown in the 2021 JVIM study though
What rare disease was found to be the cause of mesenteric lymphadenopathy in 3 young to middle aged cats?
Listeria - 2 were fed a raw meat diet
What antibiotic is used to treat Actinomyces? Nocardia?
Actinomyces - penicillins (amoxicillin)
Nocardia - TMS
In 106 cats presenting with pyrexia, what was the most common disease category and specific disease?
Infectious disease most common - 40%
Of those FIP was the most common - 20%
Describe the changes in vitamin D status in dogs with blastomycosis?
- Lower 25(OH)D, lower PTH
- Higher ionized calcium
Was vitamin D concentration associated with survival in dogs with blastomycosis? What other factors were associated with survival?
- Vit D was not
The following were: - Lactate concentration
- Bone, skin, and LN involvement/number of affected sites
- Presence of respiratory signs
What are the most common clinical signs of coccidioidomycosis in dogs and cats?
- Dogs: lameness from osteomyelitis, 80% with disseminated disease have respiratory signs
- Cats: dermatologic disease
How is coccidioidomycosis diagnosed?
Serology by AGID or ELISA - BUT there is overlap in low positive titers between clinical and subclinical infections and clinical disease can occur without seroconversion
In dogs with intracranial coccidioidomycosis, what are the most common clinical signs?
Generalized tonic-clonic seizures
What two forms of intracranial coccidioidomycosis are seen on MRI in dogs?
- Granulomatous form - 1 or more distinct, contrast enhancing foci
- Diffuse, bilateral, symmetric lesions of the caudate nuclei and frontal lobes
What is intracranial coccidioidomycosis treated with and what is the 1 year survival rate?
- Treatment of cerebral edema (mannitol, hypertonic saline, dexamethasone)
- Fluconazole for 6-18 months, anti-inflammatory prednisone (tapered after 7-10 days)
- 82% alive at one year (what?? wild)
What effect can coccidioidomycosis have on the kidneys?
Can induce ICGN - 54% of dogs had histopathologic evidence of ICGN
What is the most common systemic fungal disease in the cat?
Cryptococcus
Inflammatory arthritis with lameness as the presenting complaint has been described in cats with what fungal disease?
Histoplasmosis - organisms often found in joint fluid
Renal function may influence what fungal diagnostic test in cats?
Urine histoplasmosis EIA - decreased in cats with renal compromise, kidney disease may impact sensitivity
What dogs more commonly had disseminated histoplasmosis? What dogs more commonly had histoplasmosis confined to the GI tract?
- Disseminated: working and herding breeds
- GI: toy breeds
What are the clinical signs of Sporothrix infection in cats?
- Usually infects the subcutaneous space => multiple skin lesions, subcutaneous ulcers and nodules
- Respiratory or systemic involvement is more rare
What may be an effective treatment for Sporothrix infection in cats?
Combination cryosurgery and itraconazole cured 11/13 cats
What compounded anti-fungal drug should not be used in cats due to poor absorption?
Compounded oral itraconazole
The blastomyces urine antigen concentration correlated with what other diagnostic?
Radiographic lung score
What diagnostics provided prognostic information in dogs with pulmonary blastomycosis?
Urine antigen concentration <5ng/dL and mild (0-1) radiographic lung score = greater survival
What protocols have been described for managing GI pythiosis?
- Itraconazole, terbinafine, prednisone (0.5mg/kg/day)
- Itraconazole, terbinafine, mefenoxam
During the initial phase of infection, how does Leptospirosis avoid the immune response?
Binds inhibitors of complement on the surface of the organisms
What renal lesions are seen in the acute phase of leptospirosis?
Acute interstitial nephritis with tubular cell necrosis
In dogs with leptospirosis, what endothelial makers were correlated with survival?
VEGF and sICAM-1 - both higher in non survivors
In dogs with leptospirosis, what endothelial marker predicted the development of pulmonary hemorrhage?
s-ICAM1
Dogs with leptospirosis may display a hypercoagulable or hypocoagulable profile. Hypocoagulation was associated with what?
- Hemorrhagic diathesis
- Higher mortality rate
What percent of dogs had a positive urine PCR after doxycycline treatment?
38% - lasted as long as 18 days
What recommendation did the JVIM paper make regarding repeated urine PCR testing?
- Repeat urine PCR testing after 7 days of appropriate antibiotic therapy
What leptospirosis serovar has been shown to cause hepatic involvement (ELE) without clinically relevant renal involvement? What are the histopathologic findings on liver biopsy?
- L. interrogans/kirschneri
- Chronic granulomatous hepatitis
Dogs with leptospirosis and AKI may develop what electrolyte abnormality?
Hypokalemia - due to proximal tubular damage, may be severe
Vaccine against Leptospirosis typically target what serovars?
- Bivalent vaccine: Canicola, Icterohemorrhagiae
- Quadrivalent: Canicola, Icterohemorrhagiae, Pomona, Grippotyphosa
In dogs in the US, what was the most common leptospirosis serovar?
Grippotyphosa
After exposure to Leptospirosis, how long does seroconversion take?
Occurs by day 10 with the WITNESS test and day 14 with the MAR - same for all 4 serovars tested
SNAP Lepto was terrible
Cuterebra infection in small breed dogs can lead to SIRS and DIC. What breed is most susceptible?
Yorkies
What is the treatment of choice for Trypanosoma cruzi in dogs?
Benznidazole
If not available, can try amiodarone, hydrochloride, and itraconzole
How is Heterobilharzia treated?
Fenbendazole, praziquantel
Kittens infected with congenital toxoplasmosis typically display what clinical signs?
Chorioretinitis or uveitis
What is the mechanism of action of the anti-FIP drug GS-441524?
Adenosine nucleoside analogue
What are the MRI findings in cats with FIP?
Meningeal and ependymal contrast enhancement, ventriculomegaly, syringomyelia, foramen magnum herniation
How do you perform the Rivalta’s test?
8mL of distilled water, 1 drop of 98% acetic acid, one drop of effusion
- If the drop of effusion stays attached to the surface of the liquid, retains its shape with a connection to the liquid, or floats to the bottom = positive for an exudate
- If the drop disappears and the solution is clear = negative
