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9/24/14
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Emergency management of the leptospirosis pa8ent
Jus8ne A. Lee, DVM, DACVECC, DABT CEO, VetGirl [email protected]
www.vetgirlontherun.com
Sponsorship
Thanks to Merck Animal Health!
Introduc8on
Jus8ne A. Lee, DVM,
DACVECC, DABT
CEO, VetGirl
Financial disclosure
Introduc8on
Garret Pach8nger, VMD, DACVECC
COO, VetGirl
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Goals of this lecture
• Leptospirosis • Pathophysiology: Why do we care?
• Clinical signs • Treatment
• Preven8on • Zoono8c risk
Leptospirosis
• Leptospira spp. Gram-‐nega8ve spirochete with hook ends
• Saprophy8c vs. pathogenic – Saprophy8c: don’t infect animals – Pathogenic: Over 250 serovars
• Geographic regional differences
h^p://wwwnc.cdc.gov/eid/ar8cle/12/3/05-‐0809.htm
Leptospirsosis: E8ology in dogs
Species Serogroup Serovar
Leptospira interrogans
Icterohaemorrhagiae Canicola Pomona Australis Sejroe
Autumnalis
Icterohaemorrhagiae Canicola Pomona* Bra8slava
Autumnalis?
Leptospira kirschneri Grippotyphosa Grippotyphosa
Hosts Serovar Reservoir Host
L. grippotyphosa
L. canicola
L. Pomona
L. icterohaemorrhagiae
Raccoons, voles, skunks
Dogs
Raccoons (?), skunks, pigs, ca^le (?)
Rats, raccoons (?)
Leptospirsosis
• Prior to vaccines, most common serovars infec8ng dogs: L. Icterohaemorrhagiae and L. Canicola
• Now: more L. Grippotyphosa, Pomona, Bra:slava, and Autumnalis(?)
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Geographic distribu8on • High rainfall; warm tropical loca8ons
• Humans: – Caribbean, La8n America, India, Asia – North America: Hawaii
• Dogs: (based on 8ters > 1,600) – Hawaii – West coast (CA, OR, WA) – Upper midwest – TX, CO, Northeast, mid-‐Atlan8c
Increasing incidence? • Chronic healthy carriers
– 8-‐20%
• Urban areas (Ward JAVMA 2004)
• Smaller dogs < 15 lbs! (Lee JVIM 2013) – Past decade
• Male dogs
How does it spread?
• Shed from renal tubules of domes8c & wild animals
• Infec8on through intact mm or abraded skin from urine
– Rarely: via bite wound, inges8on of infected 8ssue, venereal, placental transfer
• Can remain viable in soil for weeks to months
Leptospirosis
• Likes warm (>30°C) • Inac8vated by UV radia8on & freezing • Risk factors:
– Slow-‐moving or stagnant water exposure – Outbreaks seen aber higher rainfall – Late fall – Roaming dogs (rural) – Urbanized wild animal exposure – Rodent exposure
Why are we seeing more lepto?
• Global warming? – Warmer
– We^er – Flooding
• Urban growth: – Invasion of humans into wildlife’s environment
Incuba8on
• Several days
• Replicates rapidly within 1 day of infec8on
• Incuba8on period: – 7 days, but dependent on dose, strain, geographical loca8on, host immune response
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Clinical signs
• Malaise, lethargy • Anorexia • Vomi8ng • Febrile • Dehydra8on • PU/PD • Weight loss?
RENAL + HEPATIC SIGNS = LEPTOSPIROSIS!
Clinical signs: Renal
• Renal: 90% of the 8me! – Inappetance – Vomi8ng
– Diarrhea – Malaise
– PU/PD – Dehydra8on – Abdominal pain
– Oliguric/anuria – CKD
Clinical signs: Hepa8c
• Hepa8c: 10-‐20% – Inappetance – Malaise
– Vomi8ng – Melena
– Icterus – Hepa8c failure – Chronic ac8ve hepa88s
Less common clinical signs • Fever
– Shivering, mm tenderness, not moving
• Ocular – Uvei8s, conjunc8vi8s
• Pulmonary – Pulmonary hemorrhage Leptospiral pulmonary hemorrhage syndrome (LPHS)
– Tachypnea – Dyspnea – ARDS – Vasculi8s
Less common clinical signs • Coagulopathy " hepa8c failure, DIC, vascular damage by
spirochetes?
– Hemoptysis – Melena
– Epistaxis – Petechial hemorrhage
– Hematochezia – Hematemesis
Less common clinical signs
• Miscellaneous – Hematuria
– Vasculi8s " Peripheral edema, pleural effusion, peritoneal effusion
– ECG altera8ons " myocardial damage (humans?) – Abor8on (ca^le)
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What about cats? • Yes but rare
• Serologic evidence of exposure – Canicola – Grippotyphosa – Pomona
• Can cause histopathologic changes
• Exposure through rodent contact?
Prognosis for Leptospirosis
• Acute – 80% survival – Fair to good with immediate treatment – $$$
• Chronic – Predisposed to chronic kidney disease – Chronic renal inflamma8on
Darby, 5 yo, MC Papillion, 5 kgs
• PC: 2 day history of vomi8ng and anorexia, ADR X 3 days; pu/pd X 2 days
• PMHX: UTD; on seasonal preventa8ve
• Diet: The Honest Kitchen diet
• Lives in St. Paul, MN
Darby, 5 yo, MC Papillion, 5 kgs: Physical Examina8on
• 7% dehydrated • Equivocally icteric mm • Moderate pulse quality • CRT = 2 seconds • HR 170 • Splints on abdominal palpa8on • Moderate bladder
Darby, 5 yo, MC, 5 kg Papillion: Plan
• IV catheter • BIG 4
– PCV/TS: 55%/8 – BG: 133 mg/dL – AZO: 50-‐80 mg/dL – Slightly icteric serum
Darby, 5 yo, MC Papillion, 5 kg: Plan
• CBC • Chemistry
• UA • Urine culture -‐ hold
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Darby: Plan
• Start 150 mls Plyte148 over 30 minutes – 20-‐30 ml/kg bolus
– Why not LRS?
• Fluid plan?
Darby: Clinicopathologic findings
• CBC – WBC 18,500 – Platelets: 150,000 – PCV: 55%
• Chemistry: – BUN: 88 – Crea8nine 4.2 – TBILI: 2.6 – AST: 800 – ALT: 1200 – ALP: 522 – TP: 8
Leptospirosis: Clinicopathologic findings
• Neutrophilia • Leb shib • Lymphopenia • Hemoconcentra8on
• Non-‐regenera8ve anemia • Hemolysis (ca^le) • Thrombocytopenia (58%)
• Azotemia (> 80-‐90%)
• # ALT, AST, ALP, TBILI (almost always seen with azotemia)
• Hypokalemia • Hyperphosphatemia
• # CK
Leptospirosis: Clinicopathologic findings
• Isosthenuria • Bilirubinuria • Hematuria • Glucosuria • Proteinuria?
• # fibrinogen, D-‐dimers, FDP
• Prolonged PT/PTT (6-‐50%)
Any other diagnos8cs?
• Coagula8on panel: R/O DIC
• Chest radiographs – Nodular inters88al to alveolar pa^erns
• Abdominal ultrasound – Renomegaly – Perirenal fluid accumula8on – Pylectasia – Medullary band of increased echogenicity – Increased cor8cal echogenicity – Mild abdominal lymphadenopathy
DIAGNOSING LEPTOSPIROSIS
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Microscopic agglu8na8on test (MAT) • Standard test, most frequently used
• Looks for presence of an8bodies to leptospiral an8gens
• Tests for highest serum dilu8on causing agglu8na8on of 50% of the leptospires
• Tests for typically: canicola, icterohaemorrhagiae, pomona, grippotyphosa, hardjo, bra:slava – Highest an8body 8ter = infec8ng serovar
• Some cross-‐reac8vity?
• Poor laboratory quality control
MAT • Interpret results based on:
– Dura8on of disease – Vaccine status of pa8ent
• 1:100-‐1:400, occasionally as high as 1:3200 • Persist for 6 months • May cross-‐react with other serovars (<1:100)
– Prior an8bio8c therapy? " blunt rise of an8body 8ter
• Titer of > 1:800 with compa8ble clinical signs and lab tests = Leptospirosis
• Nega8ve 8ters early in course of disease – Typically in 1st week of illness
• Doing convalescent 8ters 2-‐4 weeks later? – 4 fold increase = recent infec8on
Other diagnos8c tests for leptospirosis?
• Darkfield microscopy (dark ages) – Low specificity – Technically difficult
• Silver staining renal biopsy 8ssue – Low sensi8vity & specificity – False nega8ves
• Fluorescent an8body tes8ng & PCR: urine or 8ssue – PCR: affected by an8bio8c therapy!
• Idexx leptospirosis PCR & an8body ELISA in-‐clinic test
Darby’s fluid plan
• 5 kgs X 60 ml/kg/day = 300 mls/day = 13 mls/hr
• 7% dehydra8on X 5 kgs = 350 mls
• Replace dehydra8on over 12 hours: 30 ml/hr
• Ongoing pu/pd?
Treatment • Plyte-‐148 at 50 mls/hr
• Goal of assessing hydra8on – Hemodilu8on (PCV/TS 35/5)
– Isosthenuria (aim for 1.015-‐1.018) – Drinking water in the cage – Weight gain " weigh q. 6
• Why is weight so important?
– 5 kgs + 350 mls of dehydra8on = 5.4 kgs
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URINE OUTPUT
• Normal: 1-‐2 ml/kg/hour
• Oliguric: 0.5 ml/kg/hour • Decreased renal func8on or your fault? • sp. gr. > 1.018 • Solve with IVF not furosemide (yet!)
• Anuric: < 0.5 ml/kg/hour • Blood-‐8nged urine
Calcula8ng ins and outs • Simple!
• If FUO urinates 160 mls over 4 hours…UOP $ 160/4 = 40 ml/hour
• If you gave 80 mls of IV fluids over 4 hours… 80/4 = 20 ml/hour
• In vs. out?
Darby • Treatment:
– Blood pressure monitoring – UOP monitoring (UCS) – Polyuric at 6 ml/kg/hour
Day 1 88 4.2
Day 1
Day 2 60 3.1
Day 3 32 1.7
50 ml/hr
50 ml/hr
50 ml/hr
30 ml/hr
BUN mg/dL Creat mg/dL UOP Fluid rate PCV TS kg
55 8
40 7
35 5
34 4.8
Polyuric
Polyuric
Polyuric
Polyuric
5
5.2
5.4
5.4
Treatment: GI support
• Suspect uremic ulcers – Omeprazole or pantoprazole 1 mg/kg q 24 or – Famo8dine 1 mg/kg IV q 12
• Phosphate binder PO q. 6-‐8
• Sucralfate 250 mg PO q. 8
• An8-‐eme8cs (e.g., maropitant 1 mg/kg IV q 24)
Treatment: An8bio8c therapy • Goals:
– Eliminate leptospiremia – Eliminate organisms from the renal tubular cells and renal carrier state
• An8bio8cs: – Penicillin-‐type
• Penicillin 25,000-‐40,000 U/kg q 12 IV or IM for 14 days) • Ampicillin, amoxicillin, amoxicillin/clavulanic acid X 14 days
– Doxycycline (5-‐10 mg/kg BID PO X 14 days)
Symptoma8c suppor8ve care
• Monitoring – UOP – Blood pressure – Baseline renal panel/PCV/TS/elytes
• Nutri8onal support
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Prognosis
• Fair to good, but risk for CRF
• Treat aggressively
• Why preven8on is impera8ve – Small dogs: 90% rats trapped in inner ci8es were carrying leptospirosis (PCR, Vinetz et al, 1996)
Zoono8c risk • Start appropriate an8bio8cs immediately
– Pre-‐treatment blood work!
• Gloves/proper hygiene when handling bodily fluids (e.g., blood, urine, 8ssue)
• Wash hands aber handling pets
• Disinfect with iodine-‐based solu8ons
• Vaccinate other pets in the house
Preven8on! • Discuss zoono8c risk with owners
• Rodent control/fencing from wild animals
• Decrease access to swampy, marshy areas
Preven8on: Vaccines • To vaccinate or not to vaccinate?
• Leptospirosis endemic – yes!
• 2-‐way (old) vs. 4-‐way (new!) – Leptospira Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona
Vaccines
• Annual vaccina8on with 4-‐serovar vaccines – Regardless of breed – At-‐risk (e.g., urban, backyard, roaming, swimmer, hunters, etc.)
• Wide margin of safety; adequate protec8on and coverage
• Ideally, use a vaccine that: – Protects against disease and mortality
– Prevents shedding of leptospires in urine to prevent zoono8c risk and exposure
Special thank you!
• To Merck!
• Free Merck webinars on VetGirl!
• Download Leptospirosis proceedings at: – h^p://vetgirlontherun.com/proceedings-‐publica8ons-‐veterinary-‐con8nuing-‐educa8on-‐podcasts-‐webinars/page/2/
9/24/14
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Dr. Jus=ne Lee • Oct 1-‐3, 2014 -‐ Asian Pacific Veterinary
Conference, Bangkok, Thailand. • October 13-‐16, 2014 – Atlan8c Coast
Veterinary Conference. Atlan8c City, NJ • NAVC 2015 • WVC 2015
Dr. Garret Pach=nger • October 13-‐16, 2014 – Atlan8c Coast
Veterinary Conference. Atlan8c City, NJ • NAVC 2015
Check out our 2014-2015 upcoming VetGirl appearances!
@VetGirlOnTheRun
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