Week 1 (CDV, Neosporosis, American Hepatozoonosis, Lepto, Lyme, Ehrlichia, Salmon Pois., RMSF)

What type of virus is canine distemper virus? What species does it affect?

- RNA paramyxovirus

- Affects dogs and many other carnivores (and large cats)

Which animals are most commonly affected by CDV?

- Young, non-vaccinated animals (though all ages can be affected)

How is CDV transmitted?

- All body secretions (shedding is transient after recovery)

- Note: The virus does not survive long in the environment

Describe how the host immune response to CDV determines the course of the disease.

- If there is a low response -> Systemic signs, acute encephalomyelitis (secondary to cytotoxic effect of virus)

- If there is a high response -> Subclinical infection and recovery (>75% of dogs) OR CNS signs (chronic encephalomyelitis secondary to deposition of antibody-antigen complexes)

What clinical signs are associated with the first 4-6 days post-infection with CDV?

- Transient fever

- Lymphopenia

What are the classic phases associated with CDV infection (often in young, non-vaccinated animals)?

- Epithelial phase (respiratory, GI, skin)

- Ocular phase

- Neurologic phase

Describe the epithelial phase of CDV.

- Occurs after the initial viremia (6-9 days post-infection)

- Results in vomiting/diarrhea, rhinitis/conjunctivitis, pneumonia (interstitial viral/secondary bacteria)

Describe the ocular phase of CDV.

- Results in keratoconjunctivitis, chorioretinitis, and optic neuritis

Describe the neurologic phase of CDV.

- Can occur simultaneously with systemic signs or be delayed

- Can involve subacute or chronic non-suppurative encephalomyelitis (inflammation and demyelination)

- In very young dogs, can involve acute encephalomyelitis (gray matter destruction, almost no inflammation)

- "Old dog encephalitis" can occur in well vaccinated adult dogs resulting in acute infection that persists in the brain and reactivates (lymphoplasmacytic encephalitis)

Describe the mortality of the nuerologic phase of CDV infections.

- Above 90%

What clinical signs are associated with the neurologic phase of CDV infection?

- Central vestibular signs (head tilt, nystagmus)

- Cerebellar signs (ataxia, intention tremors, hypermetria)

- Cerebral signs (behavioral changes, delirium, seizures - chewing-gun)

- Myoclonus (gets worse with rest - can be overcome consciously)

What laboratory abnormalities are associated with CDV infection?

- CBC: Lymphopenia initially with neutrophilic leukocytosis later

- CSF: Normal and/or mild to moderate increase in protein and cell count

How can CDV be definitively diagnosed?

- Viral inclusions

- RT-PCR of urine, serum or CSF (note that the modified live vaccine can have a positive PCR for a couple of days, in which case perform a qRT-PCR where high counts are indicative of disease)

How can serology be used for a presumptive diagnosis of CDV in conjunction with clinical signs?

- A 4-fold increase in IgG over a 2-3 week period or the presence of IgM are associated with the virus (either infection of vaccination), but that does not necessarily mean it is causing the clinical signs

- Titers in the CSF can indicate as well (in neurologic cases)

How are CDV infections treated?

- Treat secondary infections

- Dexamethasone may improve CNS signs, but does not improve survival, and is contraindicated in cases with acute encephalomyelitis

How is CDV prevented?

- Vaccination (core vaccine)

- Isolate sick dogs (preventing aerosol transmission)

What is the causative agent of neosporosis? What is the definitive host? In which species does neosporosis most commonly occur?

- Neospora caninum

- Dogs

- Dogs and cattle

There is a higher prevalence of neosporosis in which populations of dogs?

- Dogs in contact with calves

- Basset hounds, boxers, golden retrievers, labrador retrievers and greyhounds

How is neosporosis transmitted/

- Ingestion of oocysts from infected animal tissues (important in dogs)

- Ingestion of oocysts shed in dog feces

- Congenital (transplacental)

What is the typical presentation of neosporosis?

- Dogs under 6 months old

- Inflammation/granulomas/necrosis due to proliferation of tachyzoites within tissues which are more severe in congenitally infected puppies

What are the primary clinical signs associated with neosporosis?

- Multifocal CNS disease

- Polymyositis

What are some differential diagnoses (that we have discussed) for polymyositis?

- Toxoplasmosis

- Neosporosis

- Leptospirosis

What are the classic signs of neosporosis in young dogs under 6 months of age?

- Ascending paralysis

- Gradual muscle atrophy

- Stiffness of pelvic limbs

- Dysphagia

- Ataxia

What are the classic signs of neosporosis in older dogs?

- CNS signs (seizures/tremors)

- Polymyositis

- Myocarditis

What labwork abnormalities result from neosporosis?

- Chemistry: Increased CK and AST if there is muscle involvement

- CSF: Slight increase in protein and cell count (mostly small mononuclear cells)

How is neosporosis diagnosed?

- Demonstration of the organism in CSF or tissues (Rare)

- Serology (IgG titer over 1:200 - minimal cross-reactivity with T. gondii; Note that CSF titers may be high in cases with CNS signs)

What therapy is used for neosporosis?

- Supportive care

- Clindamycin for 4 weeks and Sulfonamide + trimethropin + Pyrimethamine for 4 weeks; If clinical improvement is slow, treat longer (until 2 weeks after clinical signs have plateued)

- Treat all littermates of affected puppies regardless or clinical signs

- Avoid glucocorticoids in seropositive dogs

How is neosporosis prevented?

- Bitches that whelped affected puppies should not be bred again

- Do not allow dogs to ingest bovine placental tissues, fetal membranes, or other raw meats

What is the causative agent of classic hepatozoonosis? What does it result in?

- Hepatozoon canis

- Leukocytosis and mild signs

What is the causative agent of American hepatozoonosis? What does it generally result in?

- Hepatozoon americanum

- Leukocytosis and myositis

How is American Hepatozoonosis transmitted? How does this relate to its geographical prevalence?

- Ingestion of the gulf coast tick (Amblyomma maculatum)

- Predominates near the Gulf of Mexico

What are some signs associated with American Hepatozoonosis?

- Fever

- Lethargy

- Stiff gait

- Reluctance to walk (will not walk for food, but still has appetite)

- Muscle wasting

- Ocular discharge

What labwork abnormalities are associated with American Hepatozoonosis?

- Leukocytosis (may be severe and may result in secondary artificial hypoglycemia)

- Increased ALP

- Periosteal proliferation on radiographs

How is American Hepatozoonosis diagnosed?

- Gamonts in blood smear

- Meronts in muscle biopsy (reliable method of obtaining definitive diagnosis)

- Serology (ELISA no longer available)

- Real time-PCR

What therapy should be utilized for American Hepatozoonosis?

- Supportive care (NSAIDs for pain, nutritional/hydration support)

- Avoid steroids

- Antiprotozoals (triple combination therapy of clindamycin, SMT and TMP, and Pyremethamine for 2 weeks OR with Ponazuril for 2 weeks)

- Prolonged (2 years) therapy with a quinolone anticoccidial agent (Decoquinate) is recommended to aid in the control of relapses

What is the prognosis of American Hepatozoonosis?

- May be able to achieve clinical cure, but not microbiological cure, and it can always come back

How should American Hepatozoonosis be treated in the event of a relapse?

- Ponazuril or triple therapy for 14 days

- Decoquinate for 2 years

What is your top differential diagnosis for a dog from Alabama presenting with neutrophilic leukocytosis and periosteal proliferation?

- American hepatozoonosis

True or false: Pathogenic serovars of leptospirosis multiple outside of the host.

- False

Describe the difference between genotype and serogroups with regards to leptospirosis.

- Genotypes confer pathogenicity and virulence factors while serogroups are simple a group of serovars not based on genotype (thus, pathogenic and non-pathogenic leptospira can belong to the same serovar)

What are the two key types of leptospira which result in leptospirosis in dogs?

- Leptospira interrogans

- Leptospira kirshneri

Briefly describe the epidemiology of leptospirosis.

- It is enzootic worldwide, occuring most in tropical and semi-tropical areas during rainy periods in alkaline soil with higher prevalence in the summer/early Fall (Late fall/early winter in OR)

Describe how a dog can acquire leptospirosis from the environment.

- Maintenance hosts (Asymptomatic rodents, cats, wild and domestic animals (dogs)), infect an incidental host (i.e., dog) or contaminate soil/surface water which a dog then drinks via urine contacting broken skin or intact mucous membranes.

What are some risk factors for dogs regarding leptospirosis infection?

- Adult (4-7 YO), male dogs

- Classically, hounds, working and herding breeds (though this predisposition is merely behavioral and less true today)

Once a dog is infected with leptospirosis, in conentrates in the __________ and ___________. Clinical signs start ___________ post-exposure and they may clear the infection in ______________________ or develop which conditions?

- Liver and kidneys

- 7 days

- 2-3 weeks

- Chronic renal failure or chronic hepatitis

Describe how a dog's immune response determines the course of clinical disease in regards to leptospirosis.

- Adequate immune response -> Organism eliminated and no disease

- Moderate immune response -> Leptospiremia -> Asymptomatic or mild signs -> The organism will either be eliminated from the kidneys or there will be renal colonization (leptospiruria)

- Minimal to no immune response -> Leptospiremia -> Vascular damage (thrombocytopenia, coagulopathy, liver/kidney failure -> Death or chronic disease (hepatitis/kidney failure) -> Renal colonization -> Leptospiruria

- In cases where there is leptospiruria, the organisms can persist in the renal tubules w/o causing disease and evade the immune system and can be excreted for years, even in treated patients

What are some clinical signs associated with leptospirosis?

- Fever

- Uveitis

- Vomiting/diarrhea (renal/liver failure)

- Muscle pain

What labwork abnormalities are associated with leptospirosis?

- CBC: Leukopenia (rare), leukocytosis (subacute), thrombocytopenia

- UA: Glucosuria, isosthenuria, proteinuria

- Chemistry: Increased ALT/ALP if liver failure, increased bilirubin

- Radiographs: Lepto lung (Patchy, diffusive interstitial pattern)

- U/S: Normal to large kidneys with subcapsular fluid

How is leptospirosis diagnosed?

- Clinical Signs and Serology (serology alone indicates very little - you will find many positive animals and detection of antibodies could indicate an active infection, but also previous vaccination/exposure)

- PCR (urine and blood)

What serological findings may be most indicative of an active leptospirosis infection?

- MAT titer over 3200 (or 4-fold increase in titers over 2 weeks)

- Positive dot ELISA

- Positive lateral flow assay for IgM (more sensitive)

Why is it important to PCR both urine and blood for leptospirosis? What is the limitation of PCR as a diagnostic for leptospirosis?

- Blood will be positive in the first ten days, but urine will be positive after that

- May be positive for years after recovery

What therapy should be used for leptospirosis?

- IVF (maintain hydration/preserve renal function

- Treat renal failure (CRRT or hemodialysis)

- Treat hepatic disease

- Antibiotics (best choice hasn't been test, but ampicillin or Penicillin G work well initially for IV treatment. However, they don't clear the kidneys of the carrier state, so use doxycyline for 2 weeks as well to clear the kidneys)

Describe the prognosis of leptospirosis.

- With respiratory complications: 30-50% mortality

- Otherwise: 20% mortality

- Expect BUN/Creatinine to decline over 10-14 days, and bilirubin will decline more slowly than liver enzymes

How is leptospirosis best prevented?

- Wear gloves (all serovars can potentially infect humans)

- Vaccines (Core; can reduce severity of disease and eliminate carrier state)

Describe leptospirosis in humans.

- In 90% of cases leads to flu-like symptoms

- In 10% of cases leads to Weil's Disease (hepatitis, renal failure, months for recovery or death)

What is the causative agent of lyme disease? What is the vector?

- Borrelia burgdorferi

- Ixodes tick (does not infect host until attached for 24 hours)

Describe the prevalence of Lyme disease.

- Worldwide distribution

- Predominantly in NE US

Describe the lifecycle of Lyme Disease and the disease progression upon transmission to a dog.

- Nymph and adult ticks feeding on humans/dogs

- Results in local skin infestation followed by a generalized infection (CT, Joint capsules, muscle, LNs) with an incubation time of 2-5 months

What is the most common clinical manifestation of Lyme Disease in dogs?

- Often subclinical, chronic, non-erosive polyarthritis (though it can be septic- or immune-mediated)

What are some systemic signs of Lyme Disease?

- Anorexia

- Weight loss

- Lethargy

- Lymphadenomegaly

- Renal Disease with PLN and acute progressive renal failure (Lyme nephritidis)

- Lyme myocarditis

- CNS inflammation

What are some laboratory findings associated with Lyme disease?

- Leukocytosis with left shift, monocytosis and mild anemia (not thrombocytopenia - if they have it, could be anaplasma which is transmitted by same tick)

- Proteinuria

- Azotemia

- Neutrophilic inflammation

How is Lyme Disease diagnosed?

- Clinical signs combined with positive serologic testing (Seropositivity much higher than disease - subclinical disease common; documents exposure)

- Serologic testing can include Snap4Dx, VetScan Rapid, quantitative tests, and AccuPlex4

- If doing quantitative, treat the disease if positive, and then re-evaluate at 3 and 6 months to look for decreased antigen load

How should the following dogs with a positive Lyme Disease serology test be managed?

A. Asymptomatic, non-proteinuric

B. Symptomatic, proteinuric

C. Asymptomatic, proteinuric

D. Symptomatic, non-proteinuric

A. Nothing

B. Treat underlying Lyme disease

C. Periodic recheck, treat proteinuria (renal diet, ACE inhibitors, Angiotensin-receptor blockers), treat Lyme disease

D. Immunosuppressive agents and Antimicrobials

How should Lyme disease be treated?

- Doxycycline - Also treats anaplasmosis (10 mg/kg q12-24h for 28 days)

- Amoxicillin

- Cefovecin

- Supportive therapy

What is the prognosis of Lyme Disease?

- If treated, polyarthritis improves in 48 - 72h (may have recurrent episodes which are responsive to ABX)

- Lyme nephritidis has a grave prognosis (try immunosuppressive agents)

- There is no microbiologic cure, only clinical treatments

How is Lyme disease prevented?

- Strict tick control

- Vaccination (Consider vaccination of high risk dogs before the tick season)

What are the various types of Lyme Disease vaccines available?

- OspA vaccine single protein (Go inside tick and kill organism before it gets to the dog)

- OspA and OspC dual protein (OspC is what the borrelia expresses in the temperature of the dog; OspA is what the borrelia expresses in the temperature of the tick; Should kill organism in both locations -> More effective)

- Chimeric recombinant -> OspA and 7 types of OspC (does not include samples from Pacific)

Ehrlichiosis and Anaplasmosis are caused by gram ________________, ___________-cellular bacteria which infect _________________ and __________________.

- Negative

- Intra

- Platelets and Leukocytes

What are the two forms of Ehrlichiosis? What about Anaplasmosis?

- Ehrlichiosis: Canine monocytic and Canine granulocytic

- Anaplasmosis: Canine granulocytic and canine thrombocytic

Why are ticks not considered a "true reservoir" of ehrlichiosis and anaplasmosis?

- They don't transmit from one generation to the next generation and thus have to find an infected host to acquire the organism

What agents result in canine monocytic ehrlichiosis? What about canine granulocytic ehrlichiosis?

- Canine Monocytic: Ehrlichia canis, Ehrlichia chaffeensis, and Ehrlichia muris eauclairensis

- Canine Granulocytic: Ehrlichia ewingii

What is the vector for canine monocytic ehrlichiosis?

- E. canis: Brown dog tick (Rhipicephalus linnaei; Tropical and temperate)

- E. chaffeensis and E. muris eauclairensis: Amblyomma americanum

What is the vector for canine granulocytic ehrlichiosis?

- Ixodes scapularis

As a general rule, Ehrlichiosis is a ____________________ weather disease while anaplasmosis is a __________________ weather disease.

- Warm

- Cold

Adult ticks which transmit canine monocytic ehrlichiosis survive how long? For how long do they transmit the pathogen once infected?

- 2 years

- At least 150 days