Infectious Diseases Flashcards
What is the a) causative agent, b) pathogenesis/life cycle, and c) clinicopathological changes encountered in schistosomiasis in dogs?
Graham JVIM 2021
a) Heterobilharzia americana (HA) - trematode parasite. Endemic to the Gulf Coast regions of the USA, also reported in Kansas, North Carolina & Indiana.
b) Exposure when immersed in freshwater lakes or streams harboring lymnaeid snails (intermediate host). Free swimming cercariae emerge from the infected snail, penetrate the dog’s skin, and then migrate hematogenously
to the lungs and liver, where sexual maturation takes place –> adult parasites travel via the portal system to the mesenteric veins to mate –> release fertilized eggs into the mesenteric veins and use proteolytic enzymes to migrate through the intestinal walls –> shed in faeces. Upon contact with fresh water, flagellated miracidia emerge from the eggs and infect the snails –> complete life cycle.
c) CSx - D+ +/- hematochezia, weight loss, hyporexia or anorexia, V+, , lethargy, PUPD. CBC - lymphopenia, eosinophilia, anemia, thrombocytopenia. Biochem - hyperglob (polyclonal gammopathy reported), azotemia, increased liver eyzymes, hyperCa (34-50%).
Ehrlichia canis - name:
- Vector
- Intracellular or extracellular
- Which cells affected
- Bloodwork changes with chronic infection
- Immune cells involved during infection
- Diagnostic methods
- Treatment
- Common co-infections
- Rhipicephalus sanguineus (brown dog tick)
- Intracellular
- Monocytes
- Pancytopenia
- T lymphocytes (impt for protective immunity during infection) - note immunosuppressive drugs that suppress T Lc
- Doxycycline 10mg/kg/d x4 wks - clears EC DNA from blood, BM, spleen, liver & lungs; but likely still persistent infection –> recrudescence possible.
Leptospirosis - which serogroups are covered by bivalent (L2) vs quadrivalent (L4) vaccines?
L2: Canicola, Icterohaemorrhagiae
L4: L2 + Australis, Grippotyphosa
Echinococcosis
1. Major species?
2. Intermediate & definitive hosts?
3. Main clinical manifestations in small animals & transmission routes?
4. Public health risk?
- E granulosis, E multilocularis (tapeworms)
- Dogs - definitive hosts, people - IH
- 2 main forms.
- Autochthonous cystic echinococcosis - common where dogs access infected livestock offal (sheep). Endemic in Alaska, north-central USA, some western states
- Alveolar echinococcosis - common where dogs eat rodents (IH). Northern hemisphere. (Also occurs in people, slowly progressive disease, 100% fatality if untreated). - Yes, zoonotic. People become infected by ingesting eggs after handling infected dog faeces, or petting infected dogs with ova on body, or contact with contaminated food/water/soil.
Organism?
Transmission route?
Treatment?
Which test is useful for diagnosis & monitoring tx response?
Pythiosis insidosum (dogs)
Ingestion of zoospores in water sources (ponds, wetlands etc.)
Surgical removal of infected tissues
Anti-fungal tx x 3-6mths – itraconazole, terbinafine, IV amp B
(medical manaement alone <10% cured)
ELISA-based anti-P insidiosum antibody assay (serum)
Organism?
Risk factors?
Major virulence factor & role?
Clinical presentations - dogs vs cats?
Blastomyces dermatitidis (NB: broad based budding)
Young adult, med to large-breed dogs, dogs involved in outdoor activities, access to water bodies/soil/excavation sites (NB: indoor cats can get it too)
BAD-1 (cell surface glycoprotein) - binds to host cell receptors on macrophages, also helps evasion of host immune response (influences cytokine secretion & impairs complement activation).
Dogs - pulmonary (65-85%) > diffuse lymphadneopathy, cutaneous lesions can be small & variable sized, lameness. GI, neuro uncommon.
Cats - GI & neuro more common. Cutaneous lesions usually large abscesses.
What are the two main pathogenic leptospirosis species?
What antigen is used for serotyping?
L interrogans & L kirschneri. (note species NOT serovar)
O antigen.
What type of pathogen is Brucella canis?
What testing is available?
Treatment?
G- bacteria.
- Serology (rapid slide agglutination (RSAT) - good sensitivity >95% but if positive, need to repeat test with 2-mercaptoethanol (2ME) to increase Sp & also confirm with AGID/TAT
- Agar gel immunodiffusion (AGID)) but can take up to 12 weeks to seroconvert.
- PCR good Sn & Sp but $$$$.
- Blood and/or fluid culture options (but zoonotic risk)
Tx
- No abx is 100% effective. Usually enro, rifampicin + doxy combo.
- Castration (NB can still persist in prostate with urine shedding)
- Ideally euth :(
What is the agent that causes Lyme disease?
How is it transmitted?
Name a diagnostic test.
What types of vaccines exist against it?
Borrelia bugdorferi sensu lato.
Tick-borne (Ixodes sp.)
Serology - C6 antibody assay (also detects Abt o OspF)
Vaccines include bacterin (lysed spirochetes) or subunit (often OspA & OspC proteins)
Lyme disease (Bb) - describe the roles of its outer surface proteins.
How are these Osps useful for diagnostic, treatment & prevention purposes?
OspA - allows spirochete to adhere to tick mid-gut (A for adhere)
OspC - upregulated when tick ingests mammalian blood (OspA is downregulated). OspC binds tick salivary gland protein to evade immune response + binds to mammalian plasminogen & disseminate within host. Acute infection (3 weeks) C for chomp, circumvent & conquer
VlsE lipoprotein - undergoes recombinational shuffling of genetic code to evade host immunity. V for vary
**OspF **- chronic infection. F for forever
Utility:
- SNAP 4dx + quantitative ELISA (C6) - detects Ab against VlsE
- Multiplex fluorescent assay - Ab against OspA, OspC, OspF
- Bb vaccines induce anti-OspA Ab +/- other Osp. So tests to detect C6, VIsE OspC & OspF can differentiate between natural vs. vaccine-induced Ab as these Ab are not in the vaccine.
Name the agent most commonly implicated in:
- SNA Aspergillosis in dogs
- SNA Aspergillosis in cats
- SOA Aspergillosis in cats
- Disseminated Aspergillosis in dogs
- Disseminated Aspergillosis in cats
- SNA: A fumigatus (dogs & cats)
- SOA: A felis (cats)
- Disseminated: A terreus (dogs), A fumigatus (cats)
Pneumonyssoides caninum - what is this organism? What clinical signs can this cause?
Nasal mite.
URT signs - reverse sneezing.
What agent?
Vector?
Most common hematologic abnormality?
Treatment?
Borrelia turicatae & Borrelia hermsii (spirochetes) aka Tick Borne Relapsing Fever.
Vector = Ornithodoros spp. (soft ticks)
Thrombocytopenia
Tetracyclines
Agent?
Mode of transmission?
Other diagnostic methods?
Treatment?
Cytauxzoon felis. Schizont in macrophage (rare in blood film but usually find at feathered edge).
Tick borne disease (vector = Amblyomma americanum (Lone Star) tick). Bobcats are reservoir host.
Dx: positive PCR or seeing piroplasm merozoites in RBCs (NB: can be present in clinically silent carrier infections)
Atovaquone & azithromycin (superior to imidocarb)
Causal agent (including stage)?
Vector?
Treatment options (include those from recent literature)?
Trypanosoma Cruzi, trypomastigotes (looks like seahorse)
Reduviid (kissing bugs) - Triatoma spp.
No labelled drugs. Current recc - benznidazole, nifurtimox
New drugs - amiodarone & itraconazole (synergistic in disrupting parasite ergosterol synthesis & calcium homeostasis)
- What is the life stage of Leishmania in the sandfly vs host?
- What is the vector?
- Treatments for Leishmaniasis & MOA?
- Clinical response
- Promastigote in the sandfly. Amastigote in the host.
- Sandflies
- Meglumine antimoniate & allopurinol (meglumine monotherapy rarely effective to clear infection, drug combo is synergistic + reduced risk of drug resistance)
* Meglumine selectively inhibit the leishmanial enzymes required for glycolytic and fatty acid oxidation.
* Allopurinol inhibits Leishmania spp activity by limiting available purines in the host that are required for protozoal survival. Allopurinol is taken up by the protozoa and metabolized into a toxic compound (4-amino-pyrazole-pyrimidine), which incorporates into the parasite’s RNA, causing death. - Remission in 65-100%, can take months
What is the case definition of a rabies-positive animal?
IFA positive (preferably on CNS tissue) or isolation of rabies in cell culture or a lab animal.
In which of the systemic mycoses is antigen testing NOT recommended?
Coccidiodomycosis - poor Sn 20%. Antibody testing (EIA) is sensitive and specific, so preferred.
Features differentiating atypical bacteria (nocardia, mycobact, actinomyces)?
Nocardia: acid-fast, filamentous, monomicrobial
Actinomyces: non-AF, filamentous, polymicrobial
Mycobact: AF, intracellular (in Mp/Np), bacilli
What % of dogs infected with Brucella suis remain asymptomatic?
40% subclinical
What is a highly sensitive first-line test for diagnosis of Brucella canis in dogs? What additional step in the test assay can be performed to increase specificity? What should you do if you have a positive result for this first-line test?
RSAT (rapid slide agglutination test), Sn >95%. Low false neg (ddx abx up to 4-6wks prior, not yet seroconverted ~4-12wks).
False pos due to X-rxn with other G- bact.
If RSAT positive, either:
- Add 2-ME (2-mercaptoethanol) to inhibit IgM X-rxn & increase test specificity.
- Repeat test with AGID or tube agglutination test (TAT)
- Repeat test at 12wks
What drug is used for monotherapy to treat Leishmaniasis & MOA? What stages of disease may monotherapy be considered?
Allopurinol. MOA - inhibits protozoal activity by interfering with the purine pathway & protozoal RNA synthesis. Drug uptake by Leish is metabolised into a toxic compound (4-amino-pyrazole-pyrimidine) which incorporates into its RNA & causes death. Given long-term (min 6 months, usually 1 year+)
Stage 1 (mild CSx, normal bloodwork, non-azotemic, non-proteinuric) OR
Stage 4 (stage 3-4 CKD with nephrotic syndrome, UPC >5, PTE) - as antimony drugs are nephrotoxic
Pneumocystis canis:
- Where does its life cycle occur?
- Predisposed breeds
- Treatments?
Alveolar epithelial cells (trophozoites > cysts)
Young CKCS, Mini Dach
TMPS, folic acid, supportive care. NOT anti-fungals (resistant).
What are the main species & vector(s) causing Bartonellosis in dogs vs cats?
What are the virulence factors of Bartonella?
D/C: B. henselae - C felis (fleas)
D: B. vinsonii & rochalimae - Rhipicephalus sanguineus
C: also B. clarridgeae - fleas
Virulence factors - type IV secretory systems (T4SS) (transports protozoal effector proteins to target cells) + adhesions (allows binding to endothelial cells). Inhibit host cell apoptosis which allows continuous replication > reach critical #s in circulation without causing hemolysis but enough to be picked up by arthropod during bite.
What are the clinical manifestations of Bartonellosis? Which ones are most common in dogs vs cats?
Dogs: 5 mechanisms. Intravascular infection most common - endocarditis 30% (aortic valve, CHF likely, increased morbidity vs other bact causes), pyrexia, lameness. Also - immune-mediated dz, lymphatic dz > effusions, pyogranulomatous inflammation (visceral organs/disseminated), peliosis hepatis.
Cats: subclinical most common. Gingivitis & lymphadenopathy common if FIV+. Can get uveitis, SQ abscesses, neuro signs, endocarditis rare.
What diagnostic tests have the highest sensitivity for diagnosis of Bartonellosis in dogs?
What tests are poorly specific for Bartonellosis in cats and why?
Dogs:
Bartonella enriched culture + PCR (using BAPGM = bartonella alpha proteobacteria growth medium). Thriple blood draw (3 samples over 3 days).
Serology: Ab >1:512 useful for endocarditis but poor Sn for local dz/other body systems.
NB: cats also recc enriched culture + PCR.
Cats:
Serology (Ab) & PCR poor Sp as high prevalence, IgG titres persist for long time, & positive result doesn’t indicate cause of dz.
Treatment options for Bartonellosis in dogs/cats?
Dual abx to reduce resistance dvpt. Start 2nd abx 5-7d after 1st abx as endotoxins from rapid bact death can cause SIRS/severe rxn
CNS infx: doxy/azithro + rifampin
Home tx: doxy + enro
Endocarditis: doxy + amikacin (in-hosp)
Generally 4-6 wks, recheck enriched culture + PCR 2-6 weeks after abx stopped. +/- reduction in Ab titres.
Cats: prado + doxy; only tx clinical cats
What diagnostic tests are recommended for diagnosis of Anaplasma phagocytophilum in cats? Discuss limitations.
In-house SNAP 4dx Plus or Multi-Analyte (Ab): canine assay. Discordant results between assays.
Blood smear - detect morulae in neutrophils/granulocytes. Disadv: can’t differentiate with E. ewingii, cats have lower #s cf dogs so false negs.
PCR (spleen, blood, buffy coat, BM) - high Sn/Sp in acute infx, but false negs possible in chronic infx.
IFAT or ELISA (Ab titres): increase/decrease Ab titre by 4x within 4wks confirms acute infx.
What infectious agent is the LipL32 protein associated with? What is its diagnostic utility?
Leptospirosis. LipL32 protein = membrane protein expressed only by pathogenic leptospires and is conserved across serogroups.
PCR identifies lipL32/hap1 gene. Newer ELISA assays detect LipL32 protein (not commercially available yet)
Which serogroups do the bivalent vs quadrivalent lepto vaccines protect against?
Bivalent - Icterohaemorrhagiae, Canicola
Quadrivalent - bivalent + grippotyphosa + australis.
What is the incidence of amicrofilariaemic (a-MF) infections in dogs with HWD? What diagnostic tests are used to evaluate microfilaria status in antigen-positive dogs?
What treatment may be considered only for dogs with a-MF infections & what is the main AE?
10-20%
Modified Knott’s test, filter test - concentrates MF.
Diethylcarbamazine (anthelmintic): possibly paralyses worm.
- AE: immune mediated rxn in 30% cases if MF present but missed (occurs within 1hr = depression, ptyalism, vomiting, diarrhea, weak pulse, pale MM, poor CRT, bradycardia; can become recumbent, dyspnoeic and tachycardic. Fatal in 18% dogs with ADR.)
- Note drug is not recommended
Summarise key findings with different classes of HWD in dogs?
Class I - positive Ag, asymptomatic, mild TXR changes.
Class II - positive Ag, moderate dz. Split S2 heart sound. +/- mild-moderate proteinuria. Moderate TXR changes.
Class III - positive Ag, severe dz. R-CHF (ascites). TXR - +/- pleural effusion. Pulmonary hypertension. +/- severe proteinuria.
Class IV - class III + caval syndrome. Intravascular hemolysis & hemoglobinuria (RBC lysis from shearing forces of blood across tricuspid valve),. hepatic & renal failure.
Recommended treatments for HW & MOA of drugs?
MLs: L3 & L4 larvae. E.g. selamectin, milbemycin, ivermectin. (some have adulticidal activity at high doses).
MOA - increase Cl- channel ions in parasite cell memb to Cl- > inhibit electrical activity of muscle & nerve cells; also increase GABA-receptor activity (inhibitory NTR)
Melarsomine dihydrochloride: L5 & adults.
MOA unknown (arsenical compound).
Is anti-thrombotic therapy recommended for dogs with HWD, and if so when?
CURATIVE 2022
HWD dogs are considered HIGH risk for thrombosis. Dilofilaria antigen itself is thrombogenic; but presence of worm/worm fragments are associated with persistent thrombosis. Recommended for severe dz & those receiving adulticide tx.
Aspirin/dipyridamole or ticlopidine (P2Y12-R inhibitor)
Note not recommended in AHS guidelines
List key differences between cats vs dogs with HWD (in terms of life cycle, pathogenesis, clinical manifestations & treatment).
Cats
- More resistant to infx
- Lower worm burden (usually 1-4, <10)
- Commonly no to low MF counts - so MF testing poorly Sn
- Shortened worm lifespan (up to 4yrs)
- Lower % patent infections (<20%), longer pre-patent period (7-8mths post infx)
- 50% cats that reject infx at immature L5 develop respiratory dz (HARDS/pulmonary larval dirofilariasis)
- More severe inflammatory response to less # worms as pulmonary arterial tree is smaller with less collateral circulation.
- Dx: antibody good screening test (high Sn for early infx). Antigen tests high Sp but low Sn (single male infx in 30% cats)
- Tx: adulticide not recommended (no clear benefit & risk of PTE). Use short course pred + monthly preventative to manage respiratory signs
Which structure/component of FeLV is detected in routine diagnostic tests?
p27 antigen. Viral capsid protein, MW 27kDa.
- POC (SNAP) test, ELISA - detects free circulating p27 Ag. Initial viremia (~1st 3 wks). Good screening test.
- Direct FAT - detects intracellular p27 Ag (after virus infects BM > Ag within platelets & granulocytes). Not as a screening test but used to confirm positive results.
What are the 4 classes of FeLV infection and what are expected diagnostic test findings?
- Abortive - complete virus elimination. Ag -, PCR -, Ab + (variable titres)
- Regressive - infection not in BM cells. Still infectious via blood transfusions. Ag -, PCR -, Ab + (high titres)
- Latent - infection alr in BM cells. Ag -, PCR +/-
- Progressive - poor immunity, high mortality. Ag +, PCR +, Ab -/low lvls
(Also atypical/localised infx. Test Ag negative but still infectious e.g. mammary glands in lactating queens)
Describe the different FeLV subtypes & associated disease manifestations?
- FeLV-A: only subtype that is naturally transmitted (horizontally). Can mutate into other subgroups (B & C have higher pathogenicity).
- FeLV-B: commonly associated with malignancies esp T-cell mediastinal LSA (also multicentric LSA).
- FeLV-C: pure red cell aplasia, see macrocytic anemia w/o retics. Receptor interaction blocks the differentiation of erythroid progenitors by interfering with signal transduction pathways essential for erythropoiesis.
- FeLV-D: unsure if pathogenic or not
- FeLV feline acquired immunodeficiency syndrome: highly immunopathogenic, infects CD41 & CD81 T Lc & B Lc in blood, LNs, myeloid cells.
What are the clinical manifestations of canine parvovirus?
In-utero or <8wks exposure:
- Generalised infx > death <2wks old
- Myocarditis (arrhythmias & sudden death or survive but develop chronic myocardial fibrosis, pulm oedema, CHF)
> 8wks exposure: enteritis (SI crypt necrosis, reduced absorption, incr permeability). CNS signs (secondarye.g. neuroglycopenia, sepsis, electrolyte derangements > primary), BM/lymphoid tissue > neutropenia, lymphopenia, GI bact translocation > 2’ infx –> sepsis, SIRS
CPV-2 is susceptible to which disinfectant(s)?
Sodium hypochlorite (1 part common household bleach to 30 parts water), minimum 10 mins exposure.
NOT inactivated by most disinfectants/detergents.
What is the causal agent for feline panleukopenia, and its characteristics?
Carnivore protoparvovirus 1 or FPV. SS DNA, non-enveloped virus.
What % paroviral infection in cats are due to FPV vs CPV variants?
Can FPV affect dogs, and why/why not?
90-95% FPV, 5-10% CPV variants
No. FPV can replicate in lymphoid tissues of dogs (thymus & BM) but cannot bind to the canine transferrin receptor (TfR), which is critical for efficient infection, so onward transmission of infection does not occur.
Diagnostic tests for cryptosporidium parvum?
Treatment?
Fluorescein-labeled monoclonal antibody staining of faecal smear
ZN/acid-fast staining of faecal smear - oocysts stain pink
Faecal PCR
Faecal float/smear not useful as oocysts are too small & hard to see even at 100x
ELISA Ab not useful (positive in most animals)
Tx tylosin or azithromycin - but no tx stops oocyst shedding
Sample of faecal smear. Organism? Treatment?
Cystoisospora spp (Coccidiosis)
Tx TMPS, toltrazuril/ponazuril (coccidiocidal)
Treatment options for Bartonellosis in dogs/cats?
Dual abx to reduce resistance dvpt. Start 2nd abx 5-7d after 1st abx as endotoxins from rapid bact death can cause SIRS/severe rxn
CNS infx: doxy/azithro + rifampin
Home tx: doxy + enro
Endocarditis: doxy + amikacin (in-hosp)
Generally 4-6 wks, recheck enriched culture + PCR 2-6 weeks after abx stopped. +/- reduction in Ab titres.
Cats: prado + doxy; only tx clinical cats
What larval stage is the infective stage of heartworm disease?
L3
How long does it take to see microfilaria on testing in heartworm infection?
6-8 months because this is how long it takes for adults to mature and reproduce
Dogs/cats are more efficient at clearing heartworm larvae in immature stages
Cats
What is the only FDA approved adulticide for treatment of heartworm disease?
Melarsomine
Piroplasms/piriform inclusions are seen in RBCs with what disease
Babesia
Remember piro means pear
Babesia, Cytauxzoon, and Bartonella are ERYTHROCYTIC/LEKOCYTIC/THROMBOCYTIC/EXTRACELLULAR/ENDOTHELIAL
Erythrocytic
Ehrlichia, Anaplasma, and Hepatazoon are ERYTHROCYTIC/LEKOCYTIC/THROMBOCYTIC/EXTRACELLULAR/ENDOTHELIAL
Leukocytic
A. platys is ERYTHROCYTIC/LEKOCYTIC/THROMBOCYTIC/EXTRACELLULAR/ENDOTHELIAL
Thrombocytic
Borrelia is ERYTHROCYTIC/LEKOCYTIC/THROMBOCYTIC/EXTRACELLULAR/ENDOTHELIAL
Extracellular
Rickettsia is ERYTHROCYTIC/LEKOCYTIC/THROMBOCYTIC/EXTRACELLULAR/ENDOTHELIAL
Endothelial
Rhipicephalus sanguineus/”Brown dog tick” carries what dieases?
Babesia sp.
Ehrlichia canis
Bartonella vinsonii ss berkhoffi
Amblyoma ammericanum/”Lone star tick” carries what diseases?
Ehrlichia chaffensis
Ehrlichia ewingii
Cytauxzoonosis
Ixodes scapularis/”eastern black leg tick” carries what diseases?
Babesia sp.
Anaplasma phagocytophilum
Borrelia
Dermacentor variabilis/”American dog tick” carries what diseases?
Babesia sp.
Rock mountain spotted fever
Cytauxzoonosis
Is Babesia zoonotic?
NO - species that infect cats and dogs have not been found to infect people
What subspecies of Babesia canis are most prevalent in North America?
Babesia canis vogeli
Babesia gibsoni
What breed of dogs are inherently susceptible to Babesia canis vogeli?
Greyhounds
What breed of dogs are associated with increased rates of Babesia gibsoni infection?
Pitbulls
This is thought to be b/c transmission is more from fighting (and less from ticks)
T/F: Babesia felis is common in cats in the US
False - rare, most common in cats in South Africa
What is the infective form of Babesia canis that is transmitted in tick saliva?
Sporozoites - this is the form that penetrates RBCs
What is the circulating form of Babesia canis in dogs?
Merozoites
Sporozoites will undergo merogony (binary fission) in RBCs then lyse the RBC and be released as merozoites
Where does the sexual phase of Babesia canis happen in the tick?
Midgut
What are clinical signs of Babesia?
Lethargy
Anorexia
Weakness
Pyrexia
Weight loss
Less common signs are seizures, paresis, ataxia, masticatory myositis, ascites, edema, hemorrhage, respiratory distress
