emergency)managementof)the) leptospirosis)paentemergency)managementof)the) leptospirosis)paent...
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Emergency management of the leptospirosis pa3ent
Jus3ne A. Lee, DVM, DACVECC, DABT CEO, VetGirl [email protected] www.vetgirlontherun.com
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Financial disclosure
Jus3ne A. Lee, DVM, DACVECC, DABT CEO, VetGirl
Consultant, Merck
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Goals of this lecture • Leptospirosis • Pathophysiology: Why do we care? • Clinical signs • Treatment • Preven3on • Zoono3c risk
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Leptospirosis • Leptospira spp. Gram-‐nega3ve spirochete with hook ends
• Saprophy3c vs. pathogenic – Saprophy3c: don’t infect animals – Pathogenic: Over 250 serovars
• Geographic regional differences
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hTp://wwwnc.cdc.gov/eid/ar3cle/12/3/05-‐0809.htm
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Leptospirsosis: E3ology in dogs Species Serogroup Serovar
Leptospira interrogans
Icterohaemorrhagiae Canicola Pomona Australis Sejroe
Autumnalis
Icterohaemorrhagiae Canicola Pomona* Bra3slava
Autumnalis?
Leptospira kirschneri Grippotyphosa Grippotyphosa
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Hosts Serovar Reservoir Host L. grippotyphosa L. canicola L. Pomona L. icterohaemorrhagiae
Raccoons, voles, skunks Dogs Raccoons (?), skunks, pigs, caTle (?) Rats, raccoons (?)
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Leptospirsosis • Prior to vaccines, most common serovars infec3ng dogs: L. Icterohaemorrhagiae and L. Canicola
• Now: more L. Grippotyphosa, Pomona, Bra9slava, and Autumnalis(?)
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Geographic distribu3on • High rainfall; warm tropical loca3ons
• Humans: – Caribbean, La3n America, India, Asia – North America: Hawaii
• Dogs: (based on 3ters > 1,600) – Hawaii – West coast (CA, OR, WA) – Upper midwest – TX, CO, NE, mid-‐Atlan3c, SE
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Increasing incidence? • Chronic healthy carriers – 8-‐20%
• Urban areas (Ward JAVMA 2004)
• Smaller dogs < 15 kgs! (Lee JVIM 2013) – Past decade
• Male dogs
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How does it spread? • Shed from renal tubules of domes3c & wild animals
• Infec3on through intact mm or abraded skin from urine
– Rarely: via bite wound, inges3on of infected 3ssue, venereal, placental transfer
• Can remain viable in soil for weeks to months
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Leptospirosis
• Likes warm (>30°C) • Inac3vated by UV radia3on & freezing • Risk factors: – Slow-‐moving or stagnant water exposure – Outbreaks seen aper higher rainfall – Late fall – Roaming dogs (rural) – Urbanized wild animal exposure – Rodent exposure
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Why are we seeing more lepto?
• Global warming? – Warmer – WeTer – Flooding
• Urban growth: – Invasion of humans into wildlife’s environment
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Incuba3on • Several days
• Replicates rapidly within 1 day of infec3on
• Incuba3on period: – 7 days, but dependent on dose, strain, geographical loca3on, host immune response
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Clinical signs • Malaise, lethargy • Anorexia • Vomi3ng • Febrile • Dehydra3on • PU/PD • Weight loss?
RENAL + HEPATIC SIGNS = LEPTOSPIROSIS!
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Clinical signs: Renal
• Renal: 90% of the 3me! – Inappetance – Vomi3ng – Diarrhea – Malaise – PU/PD – Dehydra3on – Abdominal pain – Oliguric/anuria – CKD
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Clinical signs: Hepa3c
• Hepa3c: 10-‐20% – Inappetance – Malaise – Vomi3ng – Melena – Icterus – Hepa3c failure – Chronic ac3ve hepa33s
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Less common clinical signs • Fever
– Shivering, mm tenderness, not moving
• Ocular – Uvei3s, conjunc3vi3s
• Pulmonary – Pulmonary hemorrhage Leptospiral pulmonary hemorrhage syndrome (LPHS) – Tachypnea – Dyspnea – ARDS – Vasculi3s
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Less common clinical signs • Coagulopathy à hepa3c failure, DIC, vascular damage by
spirochetes? – Hemoptysis – Melena – Epistaxis – Petechial hemorrhage – Hematochezia – Hematemesis
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Less common clinical signs
• Miscellaneous – Hematuria – Vasculi3s à Peripheral edema, pleural effusion, peritoneal effusion
– ECG altera3ons à myocardial damage (humans?) – Abor3on (caTle)
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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?
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Prognosis for Leptospirosis
• Acute – 80% survival – Fair to good with immediate treatment – $$$
• Chronic – Predisposed to chronic kidney disease – Chronic renal inflamma3on
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Darby, 5 yo, MC Papillion, 5 kgs
• PC: 2 day history of vomi3ng and anorexia, ADR X 3 days; pu/pd X 2 days
• PMHX: UTD; on seasonal preventa3ve
• Diet: On The Honest Kitchen diet
• Lives in St. Paul, MN
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Darby, 5 yo, MC Papillion, 5 kgs: Physical Examina3on
• 7% dehydrated • Equivocally icteric mm • Moderate pulse quality • CRT = 2 seconds • HR 160 • Splints on abdominal palpa3on • Moderate bladder
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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
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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?
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Darby: Clinicopathologic findings
• CBC – WBC 18,500 – Platelets: 150,000 – PCV: 55%
• Chemistry: – BUN: 88 – Crea3nine 4.2 – TBILI: 2.6 – AST: 800 – ALT: 1200 – ALP: 522 – TP: 8
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Leptospirosis: Clinicopathologic findings
• Neutrophilia • Lep ship • Lymphopenia • Hemoconcentra3on • Non-‐regenera3ve anemia • Hemolysis (caTle) • Thrombocytopenia (58%)
• Azotemia (> 80-‐90%) • é ALT, AST, ALP, TBILI (almost always seen with azotemia)
• Hypokalemia • é CK
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Leptospirosis: Clinicopathologic findings
• Isosthenuria • Bilirubinuria • Hematuria • Glucosuria • Proteinuria?
• é fibrinogen, D-‐dimers, FDP
• Prolonged PT/PTT (6-‐50%)
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Any other diagnos3cs? • Coagula3on panel: R/O DIC
• Chest radiographs – Nodular inters33al to alveolar paTerns
• Abdominal ultrasound – Renomegaly – Perirenal fluid accumula3on – Pylectasia – Medullary band of increased echogenicity – Increased cor3cal echogenicity – Mild abdominal lymphadenopathy
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DIAGNOSING LEPTOSPIROSIS
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Microscopic agglu3na3on test (MAT) • Standard test, most frequently used
• Looks for presence of an3bodies to leptospiral an3gens
• Tests for highest serum dilu3on causing agglu3na3on of 50% of the leptospires
• Tests for typically: canicola, icterohaemorrhagiae, pomona, grippotyphosa, hardjo, bra9slava – Highest an3body 3ter = infec3ng serovar
• Some cross-‐reac3vity?
• Poor laboratory quality control
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MAT • Interpret results based on:
– Dura3on of disease – Vaccine status of pa3ent
• 1:100-‐1:400, occasionally as high as 1:3200 • Persist for 6 months • May cross-‐react with other serovars (<1:100)
– Prior an3bio3c therapy? à blunt rise of an3body 3ter • Titer of > 1:800 with compa3ble clinical signs and lab tests = Leptospirosis
• Nega3ve 3ters early in course of disease – Typically in 1st week of illness
• Doing convalescent 3ters 2-‐4 weeks later? – 4 fold increase = recent infec3on
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Other diagnos3c tests for leptospirosis?
• Darkfield microscopy (dark ages) – Low specificity – Technically difficult
• Silver staining renal biopsy 3ssue – Low sensi3vity & specificity – False nega3ves
• Fluorescent an3body tes3ng & PCR: urine or 3ssue – PCR: affected by an3bio3c therapy!
• Idexx leptospirosis PCR & an3body ELISA in-‐clinic test
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Darby’s fluid plan
• 5 kgs X 60 ml/kg/day = 300 mls/day = 13 mls/hr
• 7% dehydra3on X 5 kgs = 350 mls
• Replace dehydra3on over 12 hours: 30 ml/hr
• Ongoing pu/pd?
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Treatment • Plyte-‐148 at 50 mls/hr • Goal of assessing hydra3on – Hemodilu3on (PCV/TS 35/5) – Isosthenuria (aim for 1.015-‐1.018) – Drinking water in the cage – Weight gain à weigh q. 6
• Why is weight so important? – 5 kgs + 350 mls of dehydra3on = 5.4 kgs
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URINE OUTPUT • Normal: 1-‐2 ml/kg/hour
• Oliguric: 0.5 ml/kg/hour • Decreased renal func3on or your fault? • sp. gr. > 1.018 • Solve with IVF not furosemide (yet!)
• Anuric: < 0.5 ml/kg/hour • Blood-‐3nged urine
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Calcula3ng ins and outs • Simple!
• If FUO urinates 160 mls over 4 hours…UOP è 160/4 = 40 ml/hour
• If you gave 80 mls of IV fluids over 4 hours… 80/4 = 20 ml/hour
• In vs. out?
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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
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Treatment: GI support • Suspect uremic ulcers – Omeprazole or pantoprazole 1 mg/kg q 24 or – Famo3dine 1 mg/kg IV q 12
• Phosphate binder PO q. 6-‐8
• Sucralfate 250 mg PO q. 8
• An3-‐eme3cs (e.g., maropitant 1 mg/kg IV q 24)
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Treatment: An3bio3c therapy • Goals: – Eliminate leptospiremia – Eliminate organisms from the renal tubular cells and renal carrier state
• An3bio3cs: – 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)
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Symptoma3c suppor3ve care
• Monitoring – UOP – Blood pressure – Baseline renal panel/PCV/TS/elytes
• Nutri3onal support
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Prognosis • Fair to good, but risk for CRF
• Treat aggressively • Why preven3on is impera3ve – Small dogs: 90% rats trapped in inner ci3es were carrying leptospirosis (PCR, Vinetz et al, 1996)
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Zoono3c risk • Start appropriate an3bio3cs immediately – Pre-‐treatment blood work!
• Gloves/proper hygiene when handling bodily fluids (e.g., blood, urine, 3ssue)
• Wash hands aper handling pets
• Disinfect with iodine-‐based solu3ons
• Vaccinate other pets in the house
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Preven3on! • Discuss zoono3c risk with owners
• Rodent control/fencing from wild animals
• Decrease access to swampy, marshy areas
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Preven3on: Vaccines • To vaccinate or not to vaccinate?
• Leptospirosis endemic – yes!
• 2-‐way (old) vs. 4-‐way (new!) – Leptospira Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona
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Vaccines
• Annual vaccina3on with 4-‐serovar vaccines – Regardless of breed – At-‐risk (e.g., urban, backyard, roaming, swimmer, hunters, etc.)
• Wide margin of safety; adequate protec3on and coverage
• Ideally, use a vaccine that: – Protects against disease and mortality – Prevents shedding of leptospires in urine to prevent zoono3c risk and exposure
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Special thank you!
• To Merck!
• Free Merck webinars on VetGirl!
• Download Leptospirosis proceedings at: – hTp://vetgirlontherun.com/proceedings-‐publica3ons-‐veterinary-‐con3nuing-‐educa3on-‐podcasts-‐webinars/page/2/
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@VetGirlOnTheRun VetGirlOnTheRun @drjus3nelee Dr Jus3ne Lee
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