Emergency management of the leptospirosis patient

Emergency management of the leptospirosis patient THANK YOU! VETgirl Webinar Sponsor! Justine A. Lee, DVM, DACVECC, DABT - CEO, VETgirl Garret Pachtinger, VMD, DACVECC - COO, VETgirl Leah Cohn, DVM, PhD, DACVIM - University of Missouri Scott Weese, DVM, DVSc DACVIM - Ontario Veterinary College Introduction Garret Pachtinger, VMD, DACVECC COO, VETgirl Introduction Justine A. Lee, DVM, DACVECC, DABT CEO, VETgirl Introduction Leah Cohn, DVM, PhD, DACVIM Small Animal Internal Medicine University of Missouri Introduction Scott Weese, DVM, DVSc DACVIM Ontario Veterinary College 1

3/10/17 VETgirl On-The-Run VETgirl ELITE The tech-savvy way to get online veterinary CE! A subscription-based podcast and webinar service offering veterinary RACE-approved CE 50-60 podcasts/year plus 30+ hours of webinars! $199/year 40+ hours of RACE-CE Up to 5 members: $599/year Video Archives! Up to 10 members: $999/year > 10 members: Ping us New and improved video! Download our itunes podcasts free! 2

Social media and our blog! n n n n n Logistics: CE Certificates Type in questions Emailed to you 48 hours after the webinar Active participation = no quiz Watching video later, must complete quiz n ELITE members only Email / contact with ANY questions n garret@vetgirlontherun.com Justine A. Lee, DACVECC, DABT EMERGENCY MANAGEMENT OF n justine@vetgirlontherun.com LEPTOSPIROSIS: WHY DO WE CARE? Leptospirosis Goals of this lecture Pathophysiology: Why do we care? Clinical signs Diagnosis Treatment Prevention Zoonotic risk Leptospirosis Leptospira spp. Gram-negative spirochete with hook ends Saprophytic vs. pathogenic Saprophytic: don t infect animals Pathogenic: Over 250 serovars Geographic regional differences 3

Leptospirsosis: Etiology in dogs Species Serogroup Serovar Leptospira interrogans Icterohaemorrhagiae Canicola Pomona Australis Sejroe Autumnalis Icterohaemorrhagiae Canicola Pomona* Bratislava Autumnalis? Leptospira kirschneri Grippotyphosa Grippotyphosa Serovar L. grippotyphosa L. canicola L. Pomona L. icterohaemorrhagiae Hosts Reservoir Host Raccoons, voles, skunks Dogs Raccoons (?), skunks, pigs, cattle (?) Rats, raccoons (?) Leptospirsosis Prior to vaccines, most common serovars infecting dogs: L. Icterohaemorrhagiae and L. Canicola Now: more L. Grippotyphosa, Pomona, Bratislava, and Autumnalis(?) Geographic distribution High rainfall; warm tropical locations Humans: Caribbean, Latin America, India, Asia North America: Hawaii Dogs: (based on titers > 1,600) Hawaii West coast (CA, OR, WA) Upper midwest TX, CO, Northeast, mid-atlantic 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 domestic & wild animals Infection through intact mm or abraded skin from urine Rarely: via bite wound, ingestion of infected tissue, venereal, placental transfer Can remain viable in soil for weeks to months 4

Leptospirosis Likes warm (>30 C) Inactivated by UV radiation & freezing Risk factors: Slow-moving or stagnant water exposure Outbreaks seen after higher rainfall Late fall Roaming dogs (rural) Urbanized wild animal exposure Rodent exposure Why are we seeing more lepto? Global warming? Warmer Wetter Flooding Urban growth: Invasion of humans into wildlife s environment Incubation Several days Replicates rapidly within 1 day of infection Incubation period: 7 days, but dependent on dose, strain, geographical location, host immune response Garret Pachtinger, DACVECC CLINICAL SIGNS Malaise, lethargy Anorexia Vomiting Febrile Dehydration PU/PD Weight loss? Clinical signs RENAL + HEPATIC SIGNS = LEPTOSPIROSIS! Clinical signs: Renal Renal: 90% of the time! Inappetance Vomiting Diarrhea Malaise PU/PD Dehydration Abdominal pain Oliguric/anuria CKD 5

Clinical signs: Hepatic Hepatic: 10-20% Inappetance Malaise Vomiting Melena Icterus Hepatic failure Chronic active hepatitis Less common clinical signs Fever Shivering, mm tenderness, not moving Ocular Uveitis, conjunctivitis Pulmonary Pulmonary hemorrhage Leptospiral pulmonary hemorrhage syndrome (LPHS) Tachypnea Dyspnea ARDS Vasculitis Less common clinical signs Coagulopathy à hepatic failure, DIC, vascular damage by spirochetes? Hemoptysis Melena Epistaxis Petechial hemorrhage Hematochezia Hematemesis Less common clinical signs Miscellaneous Hematuria Vasculitis à Peripheral edema, pleural effusion, peritoneal effusion ECG alterations à myocardial damage (humans?) Abortion (cattle) Prognosis for Leptospirosis Acute 80% survival Fair to good with immediate treatment $$$ Chronic Predisposed to chronic kidney disease Chronic renal inflammation Garret Pachtinger, DACVECC DARBY, 5 YO, MC, PAPILLION 6

Darby, 5 yo, MC Papillion, 5 kgs PC: 2 day history of vomiting and anorexia, ADR X 3 days; pu/pd X 2 days PMHX: UTD; on seasonal preventative Diet: The Honest Kitchen diet Lives in St. Paul, MN Darby, 5 yo, MC Papillion, 5 kgs: Physical Examination 7% dehydrated Equivocally icteric mm Moderate pulse quality CRT = 2 seconds HR 170 Splints on abdominal palpation Moderate bladder Darby, 5 yo, MC, 5 kg Papillion: Plan IV catheter BIG 4 PCV/TS: 55%/8 (55/80 g/l) BG: 133 mg/dl (7.4 mmol/l) AZO: 50-80 mg/dl (35-57 mmol/l) Slightly icteric serum Darby, 5 yo, MC Papillion, 5 kg: Plan CBC Chemistry UA (pre-fluids!) Urine culture - hold Darby: Clinicopathologic findings Leptospirosis: Clinicopathologic findings CBC WBC 18,500 Platelets: 150,000 PCV: 55% Chemistry: BUN: 88 (62 mmol/l) Creatinine 4.2 (371 mmol/l) TBILI: 2.6 (44 mmol/l) AST: 800 IU/L ALT: 1200 IU/L ALP: 522 IU/L TP: 8 (80 g/l) Neutrophilia Left shift Lymphopenia Hemoconcentration Non-regenerative anemia Hemolysis (cattle) Thrombocytopenia (58%) Azotemia (> 80-90%) é ALT, AST, ALP, TBILI (almost always seen with azotemia) Hypokalemia Hyperphosphatemia é CK 7

Leptospirosis: Clinicopathologic findings Isosthenuria Bilirubinuria Hematuria Glucosuria Proteinuria? é fibrinogen, D-dimers, FDP Prolonged PT/PTT (6-50%) Any other diagnostics? Coagulation panel: R/O DIC Chest radiographs Nodular interstitial to alveolar patterns Abdominal ultrasound Renomegaly Perirenal fluid accumulation Pylectasia Medullary band of increased echogenicity Increased cortical echogenicity Mild abdominal lymphadenopathy Confirmatory Diagnosis Leah A. Cohn, DVM, PhD, DACVIM (SAIM) DIAGNOSIS OF LEPTOSPIROSIS Culture isolation of leptospires Dark field or FA testing of urine Serologic testing MAT - microscopic agglutination testing Point-of-Care antibody testing ELISA test Immunochromatographic test Identification of genetic material PCR polymerase chain reaction Renal biopsy and identification of organisms Dark Field Microscopy Isolation of Organisms Intermittent shedding Poor sensitivity Poor specificity Technically difficult Fresh urine from untreated animal Biohazard risk Limited availability Urine Blood Tissue Slow-growing, fastidious organism Culture requires up to many MONTHS http://www.pixnio.com/science/microscopy-images/leptospirosis-leptospira 8

Identification of Genetic Material Polymerase chain reaction (PCR) Optimum when urine AND blood are tested ASAP Very susceptible to antibiotics (even one dose) Not affected by vaccination Positive test confirms infection, BUT. A negative PCR can NEVER rule out disease! Serologic Testing Tried and True Microscopic agglutination test (MAT) standard Serial dilutions of sera with culture organisms to look for 50% agglutination Vaccination induced titers Knowing vaccination history very helpful Acute titers often negative (takes a week or two to make Ab) Four-fold increase diagnostic Single high titer in unvaccinated dog confirms but vaccinated? Serovar specific Ag (cross-reactivity inherent) Highest titer may not reflect infecting serovar Serologic Testing Brand New Point-of-Care Antibody Testing Zoetis Witness Lepto immunochromatographic IgM NOT available in USA as of today IDEXX SNAP Lepto ELISA LipL32 (outer membrane protein) No cross reaction with B. burgdorfi (another spirochete) Test either positive or negative (not quantitative) Vaccination may result in positive test Duration of vaccine Ab response varies, unpredictable Renal Biopsy Invasive rarely used antemortem Routine histopathology Lymphoplasmacytic tubulo-interstitial change Silver stain Immunohistochemistry So. Err on the side of caution in handling and treatment, but try to confirm the diagnosis PCR Point-of-Care MAT No antibiotics yet Very early illness Vaccination status moot Results now Quantitative info Serovar info (?) Best days into illness Convalescent sample helpful Antibiotics don t matter Vaccination status impacts results Justine A. Lee, DACVECC, DABT TREATMENT 9

Darby: Plan Start 150 mls Plyte148 over 30 minutes 20-30 ml/kg bolus Why not LRS? Fluid plan? Darby s fluid plan 5 kgs X 60 ml/kg/day = 300 mls/day = 13 mls/hr 7% dehydration X 5 kgs = 350 mls Replace dehydration over 12 hours: 30 ml/hr Ongoing pu/pd? Plyte-148 at 50 mls/hr Treatment Free water for AKI! Goal of assessing hydration Hemodilution (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 dehydration = 5.4 kgs Normal: 1-2 ml/kg/hour URINE OUTPUT Oliguric: 0.5 ml/kg/hour Decreased renal function or your fault? sp. gr. > 1.018 Solve with IVF not furosemide (yet!) Anuric: < 0.5 ml/kg/hour Blood-tinged urine Simple! Calculating ins and outs 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? 10

Darby Treatment: Blood pressure monitoring UOP monitoring (UCS) Polyuric at 6 ml/kg/hour BUN mg/dl Creat mg/dl UOP Fluid rate PCV TS kg Day 1 88/63 4.2/371 Day 1 Day 2 60.43 3.1/274 Day 3 32/23 1.7/150 Polyuric Polyuric Polyuric Polyuric 50 ml/hr 50 ml/hr 50 ml/hr 30 ml/hr 55 8 40 7 35 5 34 4.8 5/50 5.2/52 5.4/54 5.4/54 Garret Pachtinger, DACVECC OTHER TREATMENT Treatment: GI support Suspect uremic ulcers Omeprazole or pantoprazole 1 mg/kg q 24 or Famotidine 1 mg/kg IV q 12 Phosphate binder PO q. 6-8 Sucralfate 250 mg PO q. 8 Anti-emetics (e.g., maropitant 1 mg/kg IV q 24) Treatment: Antibiotic therapy Goals: Eliminate leptospiremia Eliminate organisms from the renal tubular cells and renal carrier state Antibiotics: 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) Symptomatic supportive care Monitoring UOP Blood pressure Baseline renal panel/pcv/ts/elytes Nutritional support Prognosis Fair to good, but risk for CRF Treat aggressively Why prevention is imperative Small dogs: 90% rats trapped in inner cities were carrying leptospirosis (PCR, Vinetz et al, 1996) 11

What is the zoonotic risk? Largely unknown Scott Weese, DVSc DACVIM ZOONOTIC RISKS Anecdotal reports Mainly in veterinary technicians handling infected dogs and urine soaked items Some with contact with items but not dogs Risk to owners Seems low High concern groups Pregnant Immunocompromised Young children Things to remember Zoonotic issues Source of infection: urine and urine soaked items +/- blood, saliva Route of infection mucous membranes and broken skin Dog-human transmission seems to be rare Risk is highest at first arrival Avoiding lepto exposure Keep it in mind Use good routine barriers and hand hygiene Lepto suspects Isolate (as much as possible) Reduce direct and indirect contact/contamination Enhanced personal protective equipment Don t forget about splashes/aerosols Handle dog and urine contaminated objects as infectious Brown and Prescott, CMAJ 2008 12

Poorly defined When does risk end? Likely shortly after antimicrobials are started My approach 48h after start of appropriate antimicrobials Bath and hot air dry (ideal) Disinfect environment or move animal at the same time Cleaning and Disinfection Avoid high pressure washing on runs Avoid aerosols when cleaning cages Highly susceptible to drying and disinfectants Prevention: Vaccines To vaccinate or not to vaccinate? Leptospirosis endemic yes! Justine Lee, DACVECC, DABT HOW DO WE PREVENT IT? 2-way (old) vs. 4-way (new!) Leptospira Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona Vaccines Annual vaccination with 4-serovar vaccines Regardless of breed At-risk (e.g., urban, backyard, roaming, swimmer, hunters, etc.) THANK YOU! VETgirl Webinar Sponsor! Wide margin of safety; adequate protection and coverage Ideally, use a vaccine that: Protects against disease and mortality Prevents shedding of leptospires in urine to prevent zoonotic risk and exposure 13

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