Parvovirus VETgirl

9/8/15

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What’s new with parvovirus: Pediatric cri:cal care

Jus:ne A. Lee, DVM, DACVECC, DABT CEO, VETgirl Jus:[email protected]

www.vetgirlontherun.com

Sponsorship

Thanks to Merck Animal Health for sponsoring today’s VETgirl webinar!

Introduc:on

Jus:ne A. Lee, DVM,

DACVECC, DABT

CEO, VetGirl

9/8/15

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Conflict of Interest Disclosure Jus:ne Lee has collabora:ons with:

Garret Pach:nger, VMD, DACVECC

COO, VetGirl

Introduc:on

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Goals of this lecture

•  E:ology •  Pathogenesis •  Signalment

•  Clinical signs •  Diagnosis •  Treatment

•  Preven:on

E:ology

•  Canine parvovirus (CPV-‐1) –  First discovered in 1967 – Mild diarrhea

•  CPV-‐2 –  Seen in 1978 – More severe disease –  Resembles panleukopenia in cats

– More subtypes seen (2a, 2b, 2c) due to gene:c evolu:on

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E:ology •  Naturally affects: –  Domes:c dogs –  Bush dogs –  Coyotes –  Foxes – Wolves

•  Experimental infec:ons in: –  Ferrets – Mink –  Cats

Pathogenesis

•  CPV: small, non-‐enveloped, single-‐stranded DNA virus – Very hardy due to lack of an envelope

•  Prefers rapidly dividing cells – Bone marrow – GIT – Myocardium (rare " cell division occurs first weeks of life)

E:ology

•  Incuba:on period: – As brief as 3-‐6 days – 7-‐14 days

•  Viremia seen in 1-‐5 days

•  Shed extensively in feces for 7-‐10 days (ELISA) to weeks (PCR)

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Pathogenesis

•  Intes:nal crypt epithelium infected by day 4 of infec:on

•  An:bodies develop ~ 5 days " maxes 7-‐10 days

•  Clinical signs develop 4-‐10 days aher infec:on

•  Dogs < 6 months of age – 6-‐20 weeks of age – Male intact dogs – Breeds: Doberman, Romweilers, pit bulls, GSD, Alaskan sled dogs, Labrador retrievers

– Dobies & Roues have increased monocyte TNF-‐alpha produc:on " increased suscep:bility?

Signalment

Increased suscep:bility due to: – Failure of passive transfer – Early weaning " maternal an:bodies

– Lack of vaccina:on – Passive maternal immunity preven:ng vaccine response

Signalment

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Why do they die?

•  CPV destroys mito:cally ac:ve cells: –  Bone marrow – GI tract – Myocardium (rare) –  Skin (rare) – Nervous :ssue (rare)

•  Secondary bacteremia and endotoxemia (gram-‐nega:ve, anaerobic) " DIC " thrombosis

Differen:als

•  Canine coronavirus •  Gastroenteri:s •  Parasi:c infec:on –  Intes:nal helminthes – Protozoa

•  Enteric bacteria •  Clostridium •  Campylobacter •  Salmonella

Clinical signs

•  Malaise

•  Lethargy •  Anorexia •  Vomi:ng

•  Diarrhea •  Dehydra:on •  Hemorrhagic diarrhea

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Clinical signs •  Fever •  Leukopenia

–  Lymphopenia –  Neutropenia

•  Systemic inflammatory response syndrome (SIRS)

•  Sepsis •  DIC " hypercoagulability

•  Death

Diagnosis

•  Based on clinical suspicion, history & clinical signs

•  Leukopenia

•  Paroviral fecal an:gen tests

•  PCR (if suspect parvo but nega:ve fecal an:gen)

Diagnosis

•  Some false posi:ves with amenuated live CPV vaccines " causes weak false + 4-‐8 days aher vaccina:on

•  Specific but poorly sensi:ve?

•  False nega:ves: –  Lubrica:on (KY) –  Intermiment shedding

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Clinicopathologic tes:ng:

•  Parvo fecal an:gen •  CBC •  Blood smear •  BIG 4 (PCV/TS/BG/AZO) •  Chemistry

•  Fecal float •  Direct fecal smear •  Abdominal radiographs •  Colloid osmo:c pressure

•  Blood pressure

Clinicopathologic tes:ng: SILVER

•  Parvoviral fecal an:gen •  CBC •  Blood smear

•  Chemistry

•  Fecal float •  Blood pressure

Clinicopathologic tes:ng: BRONZE

•  Parvoviral fecal an:gen •  PCV/TS/BG/AZO •  Blood smear

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Rex, 12 week-‐old, MI APBT, 6 kgs •  PC: 3 day history of vomi:ng, anorexia, and diarrhea

•  PMHX: Obtained from breeder in LAX and shipped to new home 3 days prior

•  Had two vaccines from the breeder prior to shipping

•  Diet: Inappetant since purchased

•  Lives in Minneapolis

Physical Exam

•  12% dehydrated •  T 96°F, HR 180, RR 40 •  Listless on table •  Sunken eyes •  Tacky pale pink mm •  Poor pulse quality •  Hypersaliva:ng

•  Diarrhea-‐stained rectum

•  Fluid filled loops of intes:ne

•  Malodorous

Plan

•  IV catheter •  BIG 4 – PCV/TS: 34%/7.2 g/dL – BG: 36 mg/dL – AZO: 30-‐40 mg/dL

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Plan?

•  Parvo SNAP (-‐) •  CBC •  Chemistry

•  Fecal: Toxocara

Rex: Plan

•  Start 200 mls warm LRS over 15 min

•  Start 1 ml/kg 50 % dextrose bolus

– Diluted

•  Fluid plan?

Results •  CBC – WBC 210 K/μL –  Platelets: 104,000 –  PCV: 34%/7.2 g/dL

•  Chemistry: –  BUN: 33 –  Crea:nine 1.1 –  Phosphorous: 12 –  ALP: 188 –  TP: 7.2 g/dL

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Parvovirus: Clinicopathologic findings

•  Hemoconcentra:on

•  Anemia •  Thrombocytopenia – Blood loss GIT – Bone marrow

•  Hypoglycemia

•  Leukopenia – Neutropenia – Lymphopenia – Leh shih

Parvovirus: Clinicopathologic findings

•  Electrolyte changes – # Na, Cl, K

•  Metabolic acidosis

•  Puppy findings •  SNAP + •  Coagulopathic •  Hypercoagulable

SNAP Fecal ELISA

•  False + –  Recent vaccine with modified live

•  False – –  Low viral concentra:on –  Dilu:onal effects from voluminous diarrhea

–  KY lubrica:on –  CPV-‐2c?

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Any other diagnos:cs?

•  Abdominal radiographs –  R/O intusscep:on, foreign body, etc.

•  Abdominal ultrasound?

•  Less common: –  Virus isola:on –  Hemagglu:na:on inhibi:on –  Electron microscopy

•  Coagula:on panel: R/O DIC

Goals of Cri:cal Care in the Pediatric Pa:ent

To correct:

•  Hypothermia •  Hypoglycemia •  Hypovolemia/Hydra:on

•  Hypoxemia

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HYPOTHERMIA

Temperature: hypothermia •  Exogenous source

•  Minnesota/Canada •  Hypothyroid •  Inappropriate shelter •  Inappropriate hair coat •  Body condi:on

•  Endogenous –  Cold, flat puppy$ hea:ng pad?

–  How’s that rectum?

Warming up hypothermic pa:ents

•  Acute warming without fluid resuscita:on vasodilates periphery " pulls blood from vital organs to warm non-‐vital organs.

•  Warm IV fluids + heat support

together!

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HYPOVOLEMIA/HYDRATION

Assessing Hydra:on or Hypovolemia in Pediatric Pa:ents

•  Difficult to assess because of:

–  Increased fat in skin and decreased water content " skin turgor

– Mucous membranes stay moist – Normal MAP = 49 mmHg un:l 2 months – Tachycardiac normally

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Why Do Pediatric Pa:ents Dehydrate So Quickly?

•  Increased total body water 60-‐180 ml/kg/day •  Pediatric pa:ents need more fluids: –  Extracellular fluid volume – ↑ Body surface area –  Greater surface area:body weight ra:o –  Lack of body fat – ↑ Metabolic rate – ↓ Ability to concentrate urine

•  Dehydra:on " hypovolemia

Fluid Therapy for Pediatric Pa:ents

•  Typically crystalloid with sodium ($) •  Maintenance: – 60-‐180 ml/kg/24hr

•  Dehydra:on: – % Dehydra:on X kg X 1000 mls – Replace over 4-‐6-‐12 hours

•  Ongoing losses: –  Vomi:ng –  Diarrhea

•  Shock dose: 90 ml/kg (dog) 60 ml/kg (cat) –  ½ dose then re-‐evaluate

Fluid Therapy for Pediatric Pa:ents

•  Colloidal support –  If TP < 3.5 mg/dL –  Albumin < 1.5 mg/dL

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Cau:ons with Fluid Therapy in the Parvovirus pa:ent

•  Hypokalemia due to ongoing losses

•  Dextrose supplementa:on at 2.5-‐5%

•  Bolus 50% dextrose (fast) with a mini-‐bolus so it’s less hyperosmolar

•  Difficult to “reassess” –  Serial physical examina:on –  Serial weight –  PCV, TP, “sp. gravity”

Catheteriza:on of Neonates/Pediatric pa:ents

•  Peripheral venous (22 to 24 ga.) •  Jugular catheters

Other Routes

•  Oral (PO) – Tube or syringe feed – Electrolyte solu:on, a/d slurry, etc.

•  Subcutaneous (SQ) –  Crystalloid –  No dextrose

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Rex’s fluid plan

•  6 kgs X 80 ml/kg/day = 480 mls/day = 20 mls/hr

•  12% dehydra:on X 6 kgs = 720 mls-‐200 ml bolus

•  Replace dehydra:on over 12 hours: 43 ml/hr

Treatment •  LRS at 63 mls/hr X 12 hours " reassess!

•  Goal of assessing hydra:on – Hemodilu:on (PCV/TS 30/4)

–  Isosthenuria (aim for 1.015-‐1.018) – Drinking water in the cage – Weight gain " weigh q. 6

•  Why is weight so important?

–  6 kgs + 720 mls of dehydra:on = 7.2 kgs

HYPOGLYCEMIA

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Why Hypoglycemia?

•  Increased demand

•  Increased loss –  Loss of glucose in the urine

•  Decreased ability to synthesize glucose –  Inefficient hepa:c gluconeogenesis

–  Decreased liver glycogen stores

Hypoglycemia

•  Bemer to prevent than treat –  Feeding/nutri:on

•  50% dextrose –  Diluted 1:4 IV, IP, or IO

•  Never subcutaneously! –  Can be followed by CRI

•  0.25 ml/25-‐30 g of 5-‐10% glucose by stomach tube q. 1

Nutri:on

•  Enteral nutri:on –  Improved mucosal integrity and repair

•  Starva:on " associated with small intes:nal mucosal atrophy

•  Early enteral nutri:on " associated with improved weight gain & clinical signs

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Feeding tubes?

•  NE/NG

•  Syringe feeding – 1 ml/kg of a/d

•  Control vomi:ng and nausea first

Treatment: GI support •  An:-‐eme:cs

– Maropitant 1 mg/kg IV q 24 –  Ondansetron 0.5 mg/kg IV q. 8

–  Study looked at both " more weight gain with maropitant dose – Metoclopramide CRI 1-‐2 mg/kg/day?

•  Antacids? –  Omeprazole or pantoprazole 1 mg/kg q 24 or

–  Famo:dine 1 mg/kg IV q 12

Treatment: An:bio:c therapy •  GI mucosal barrier disturbances " bacterial transloca:on +

leukopenia " sepsis

•  Broad-‐spectrum an:bio:cs: – Amoxicillin/Clavulanic acid (22-‐30 mg/kg IV q 8) –  Cefoxi:n (22 mg/kg IV q 8) –  If more severely affected: •  Cefazolin/Enrofloxacin •  Ampicillin/Enrofloxacin •  Cefazolin/Amikacin

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Rex: Treatment

•  LRS at 50 mls/hr + HES at 6 ml/hr

•  Unasyn 25 mg/kg IV q 8

•  NE tube Clinicare 6 mls/hour

•  Maropitant 1 mg/kg q 24

•  Metoclopramide 2 mg/kg/24 hours CRI IV

Treatment: Suppor:ve care

•  Monitoring TPR q. 6-‐8

•  Big 4: PCV/TS/BG/electrolytes q. 12-‐24 hours

•  Weight q. 6-‐8 hours

•  Blood pressure

Outcome

•  Tachypneic aher regurgita:ng large amount

•  Dyspneic and pulse ox’ing at 88%

•  Owner euthanized aher 48 hours

•  PCR posi:ve for parvovirus

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MISCELLANEOUS THERAPY

FFP

•  Fresh frozen plasma?

– Provides limited onco:c support – An:-‐CPV an:body concentra:ons are minimal in recently recovered pa:ents

– Associated with increased pro-‐inflammatory cytokines

– Trigger for future transfusion reac:on? –  Indicated if coagulopathic

Miscellaneous therapy

•  Immunotherapy – Passive immunotherapy using convalescent plasma from recently recovered dogs " did not improve clinical outcome, survival, cost, dura:on of hospitaliza:on, severity of clinical signs or viral load

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•  Equine endotoxin an:serum " reduce the effects of gram-‐nega:ve bacterial toxins – Mixed results

–  Lack of proven efficacy

An:-‐virals •  Tamiflu/Oseltamivir

•  Neuraminidase (NA) inhibitor for treatment of human influenza virus

•  Not shown to be effec:ve in improving survival or outcome

•  Increased resistance in human medicine


•  G-‐CSF (Neupogen) " controversial

•  Recombinant human granulocyte colony-‐s:mula:ng factor (rhG-‐CSF) " no benefit

•  Human recombinant bactericidal/permeability-‐increasing protein (rBP121) to reduce SIRS " no benefit

•  Feline interferon-‐omega (Intercat) –  Weakly associated with improved survival –  Not readily available –  $$$

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NEWEST STUDY?

Outpa:ent therapy

•  Sullivan LA, Twedt DC, Boscan PL. Evalua:on of an outpa:ent protocol in the treatment of canine parvoviral enteri:s J Vet Emerg Crit Care, In press.

•  Prospec:ve, randomized study

•  N = 20 inpa:ent; 20 outpa:ent

Both received IVF resuscitaEon & hypoglycemia treatment

•  Inpa:ent: –  IVF –  Cefoxi:n (22 mg/kg IV q 8) –  Maropitant (1 mg/kg IV q 24)

–  IV dextrose + K supplementa:on

–  Syringed 1 ml/kg PO a/d q 6

Both received IVF resuscitaEon & hypoglycemia treatment

•  Outpa:ent: –  SQF (30 ml/kg q6)

–  Convenia (8 mg/kg SQ once) –  Maropitant (1 mg/kg SQ q 24)

–  Oral dextrose + K supplementa:on

–  Syringed 1 ml/kg a/d q 6

Sullivan et al.

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Sullivan et al.

•  Inpa:ent: –  Survival: 90% –  Dura:on hospitaliza:on: 4.6 days + 2 days

•  Outpa:ent: –  Survival: 80% –  Dura:on hospitaliza:on: 3.8 + 1.8 days

–  Frequent electrolyte disturbances •  50% needed dextrose •  60% needed potassium

–  Non-‐survivors (OP): •  Low body weight < 4 kg •  Young age < 4 mo

Symptoma:c suppor:ve care

•  Monitoring – Blood glucose – Blood pressure – Baseline renal panel/PCV/TS/elytes

•  Nutri:onal support

PREVENTATIVE CARE

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Vaccine Status

•  Was mom vaccinated? – And colostrum nursed?

•  Owner educa:on – “One vaccine” – Breeds at risk: 16-‐22 weeks

•  Why shelters vaccinate q. 2 weeks

Preven:on! •  Educa:on

•  Work with shelters appropriately on vaccines

•  Isolate from doggy daycares, dog parks, etc. un:l fully vaccinated

•  Discuss high contagious nature with owner

•  Isolate from other dogs " shedding

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Puppy Vaccina:on Protocol in Parvovirus Problem Areas

•  4 weeks of age -‐ Nobivac® Puppy DPv •  7 weeks of age -‐ Nobivac® Puppy DPv •  10 weeks of age -‐ Nobivac® Canine 1-‐DAPPv •  12 weeks of age -‐ Nobivac® Canine 1-‐ DAPPv and Rabies

•  14 weeks of age -‐ Nobivac® Canine 1-‐DaPPv+L4 •  16 weeks of age -‐ Nobivac® Canine 1-‐DAPPv+L4

Special thank you!

Thanks to Merck Animal Health for sponsoring today’s VETgirl webinar!

@VetGirlOnTheRun

VetGirlOnTheRun

@drjus:nelee

Dr Jus:ne Lee

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