Study Notes on the ACVIM Consensus Statement on Leptospirosis in Dogs

Which Subclades of of leptospira typically cause severe disease in dogs?

P1 subclades; considered pathogenic and highly virulent; Lepto interrogans, borgepetersenii, kirschneri

(Only occasionally do P2 species cause severe disease)

Infections with Lepto spp occur when….

• Mucous membranes or abraded skin are exposed to pathogenic strains shed from renal tubules of reservoir hosts

• Can also be from direct contact with reservoir hosts (predation, bite wounds, veneral, palcental)

• Rattus norvegicus*** common spread worldwide

• organisms contaminate soil and water, can remain viable in environment for weeks

• Biofilms contribue to persistence

• Spirochete can replicate in water-saturated soil

Do cats get lepto?

• Pathogenic leptospires are detected in urine of up to 20% of healthy cats

• can act as reservoir hosts

• Rare reports of clinical disease

Ways that lepto evades the immune system

• Corkscrew motion - efficiently invades hot tissues at gel-liquid borders (vascular walls), and emigrating from vascular space by binding to vascular endothelial cadherin and weakening endothelial cell barriers

• Breakdown of endothelial cell barrier —→ pulmonary hemorrhage sydnrome

How does lepto affect liver cells?

Disruption of hepatocyte intercelllular junctions by spirochetes, with leakage of bile into the cirulcation = cholestatic hepatopathy

How does lepto affect platelets?

Direct cytotoxic effects, causing platelet destruction and and de-adherence

Where can lepto persist once it’s been cleared by the blood?

Biofilm in the eye

Renal tubules; progression to tubulo-interstitial nephritis

List all of the Clinical manifestations of lepto

• AKI

• Cholestatic hepatopathy

• Leptospiral pulmonary hemorrhage syndrome

• Coagulopathy

• Vasculitis

• Pancreatitis

• Ocular involvement - uveitis, conjunctivitis, retinal hemorrhages

• Myocarditis

• Enteritis

• Myositis

• Repro tract - abortion, infertility

• Skin - calcinosis cutis

Most common CBC findings for lepto

• Neutrophilia

• Increased band neutrophils

• Lymphopenia

• Monocytosis

• Thrombocytopneia

• Mild-moderate nonregenerative anemia

Serum biochemistry abnormalities for lepto

• AKI (increased BUN, creat)***

• Elevated phosphate

• Increased ALP***

• Increased ALT

• Increased AST

• Elevated bilirubin***

• Mild-mod hypoalbuminemia*

• Elevated CRP

• Electrolyte abnormalities; may relate to GI loss, kidney dysfunction, or direct inhibition of tubular Na+K+ATPase by leptospiral edotoxin

• Hyperkalemia, hypokalemia

• Hyponatremia, hypochloremia

• Elevated CK (44%)

• Increased serum topnonin 1

• Increased amylase, lipase

Urinalysis findings for lepto

• Isosthenuria or hyposthenuria

• Renal glucosuria (tubular damage)

• Cylinduria (tubular damage)

• Proteinuria *** - defective tubular reabsorption

• ± pyuria

• Hematuria

• Bilirubinuria

Hemostasis evaluation in lepto

• Hemostatic abnormalities in up to 83%

• Can progress to DIC

• Thrombocytopenia

• Hypofirbinogenemia

• Prolonged PT, PTT

• Low antithrombin

• Hyper AND hypocoagulable profiles on TEG

Radiographic changes indicative of LPHS

• Usually bilateral

• Caudodorsal

• Mild interstitial to reticulonodular, or a focal or generalized alveolar infiltrates

True or False: CXR are recommended in all dogs suspected of lepto, even in the absence of respiratory signs?

YES - radiographic findings with LPHS can aid in diagnosis of lepto, and should prompt judicious fluid therapy and close monitoring of respiratory function

AUS findings with lepto

• Kidney: renomegaly, cortical and sometimes medullary hyperechogenicity, perirenal fluid accumulation

• Hepatobiliary: hepatomegaly, hypoechogenicity, thickening of GB wall

• Peritoneal effusion

• Thickening of gastic, less-commonly SI wall

• Intusussception

• Splenomegaly ± mottled texture

• Lymphadenomegaly

Leptospirosis should be considered a differential in any dog evaluated for:

AKI

± hepatic dysfunction

± pulmonary hemorrhage

Leptospirosis should be considered in cats with

• AKI

• equal to or greater than 1 additional clinicopathologic finding suggestive of systemic infection, and no other explanation for their clinical signs

Optimization of diagnosis of lepto is made by

A combination of serologic assays and organism detection tests

The reference standard test for diagnosis of lepto is?

Acute and convalescent serologic MAT

The incubation period for leptospirosis is

2-14 days

Sensitivity of a single acute MAT titer >1:800 in dogs is?

about 50%

Conversely, unless very high (>1:3200) a single positive MAT titer lacks specificity and high titers in the first few days of illness should raise suspicion for recent previous vaccination, recent subclinical exposure, or longer duration of illness

True or False: Diagnosis of lepto can be based off a single MAT?

False; not recommended.

Especially not when it includes a limited number of serovars

What is the recommended interval of acute an convalescent titers for lepto?

7-14 days to demonstrate seroconversion

OTHER: Practitioners should submit samples to labs that participate in the International Leptospirosis Society’s Leptospira proficiency testing platform

SNAP Lepto (IDEXX) detects? Agreement with MAT?

• antibodies (membrane protein LipL32)

• 83.2% agreement with MAT when MAT was >1:800

• Specificity 96%

• CAN DETECT ANTIBODIES UP TO 1 YEAR AFTER VACCINATION

Witness Lepto Rapid test detects?

• IgM antibodies

• Detection of post-vaccinal antibodies up to 12 weeks post-vaccination

• Specificity >97%

If a dog tests positive on a SNAP or Witness test, should MAT be performed?

Yes - recommended as part of acute and convalescent titer evaluation to document recent exposure

Also, a negative POC test does not rule out lepto, and should be followed by a second antibody test 7-14 days later to document seroconversion

NAAT (nucleic acid amplification tests) to detect lepto DNA - what samples?

• Blood and urine

• Collect before antibiotics

• Sensitivities vary widely

• Affected by timing of urine shedding, heparin, stability of DNA

True or False: a positive NAAT for lepto on blood is considered diagnostic?

YES - in conjunction with consistent clinical signs

(DNA of pathogenic leptospires can be found in urine of up to 20% healthy dogs)

Should you use darkfield microscopy to diagnose lepto?

No - low sensitivity, and needs technical expertise

Case Definition for Leptospirosis in Dogs

A confirmed case meets the clincal criteria and has 1 or more confirmatory laboratory criteria

Clinical criteria:

• Onset of systemic illness (fever, lethargy, polyuria, polydipsia, anorexia, or some combo) with or without other clinical signs, in the past 2 weeks:

  • GI

  • Pulmonary

  • Ocular

  • Clinical suspicio for AKI

  • Icterus

  • Hemorrhage

• AND

• 2+ of the following clinicopathologic abnormalities:

  • Neutrophilic leukocytosis, ± left shift

  • Thrombocytopenia

  • AKI (isosthenria, increased creat, or inc SDMA)

  • Cholestatic hepatopathy

  • Pancreatitis (amylase, lipase)

  • Increased CK

  • Glucosuria (with normal BG)

  • Active urine sediment (pyuria, casts)

  • Radiographic findings consistent with LPHS

  • AUS findings consistent

  • EKD-documented arrhythmias or increased tropnin

Supportive testing laboratory criteria

• Leptospira MAT 1:800+ in 1 or more serum specimens

• Detection of IgM antibodies in an acute phase serum specimen

• Detection of pathogenic leptospires in NAAT

• Visualization of spirochetes in blood or urine using darkfield microscopy

Confirmatory diagnosis lepto testing

• 4+ increase in Leptospira agglutination titer at a single lab between acute and convalescent speciments

• Detection of pathogenic leptospires in blood using an NAAT

• Isolation of Leptospira from a clinical speciment using a Lepto reference lab

Antibiotic therapy for Lepto

• Initially treated with ampicillin (20-30 mg/kg IV q6-8), amoxicillin (20-30 mg/kg IV q6-8), Pen G (25k-40k IV q6-8) —- double the administration interval in dogs with AKI Grade 4 and higher —→ if unable to take PO meds

• Then treat with Doxycycline at 5 mg/kg PO q12 for two weeks

• Treatment should not be delayed pending results of diagnostic testing

• Ideal length of treatment is not exactly known

Dogs with suspected or confirmed lepto should be fed what kind of food?

Highly digestible

Normal to high protein

Liver protection in lepto

SAMe, Silymarin, Vitamin E, or ursodiol can be used

cannot officially recommend yet, no investigations done yet

When is dialysis recommended for lepto?

Early! prevent the morbidity of AKI rather than as a delayed salvage for failed conventional management

Early referrals to centers with dialysis should be considered for dogs in IRIS AKI Grade 4, when creat >5.

Dialysis restores fluids, acid-base balances, opportunity for nutritional support, establish QOL

Recent study of 36 lepto dogs reported 80%+ recovery with severe AKI treated with dialysis after failing med mgmt

IHD and CHD have been successful

How often to check a chemistry in lepto dogs?

every 24 hours - renal function, bilirubin, LE, protein, CRP, electrolytes, acid-base

Also consider PCV q24

CBC q48

Consider a u-cath to monitor UOP, manage potentially infectious urine

Negative prognostic factors for dogs with lepto?

Hyperbilirubinemia (0.6 strongly assoc with death or euth)

Hypocoagulability

LPHS mortality up to 70%

Normalization of CPR parallels favorable clinical course of disease

North American bacterin leptospirosis vaccines contain which serovars?

Icterohemorrhagiae

Canicola

Grippotyphosa

Pomona

How to start vaccinating for lepto?

• 2 initial injections spaced 4 weeks apart, puppies 12+ weeks or older

• Vaccines should be administered annually to all dogs starting at 12 weeks of age, regardless of breed —- zoonotic!

• Shelter dogs - 2 vaccines, 3 weeks apart

• No evidence that seasonal timing matters

• Even after recovery from Lepto infection - dogs are at ongoing risk of exposure, unknown whether or not life-long immunity results from natural infection

How high is the risk of zoonotic transmission of lepto from sick dogs to humans?

Low, especially when basic precautions are taken

When should we suspect lepto?

• All dogs with AKI until an alternate diagnosis has been made

• Standard hygiene is always recommended

Is isolation required for dogs with lepto?

No - not easily trasmitted.

Has potential to negatively impact the level of care required for critically ill dogs

Place in floor-level cages, away from high-traffic areas, avoid needle-stick injruies

Wear gloves, disposable gown, and full face protection if aerosolization of urine is possible

Walk frequently vs u-cath

Urinate in a restricted area

Normal hand hygiene before and after handling patient

Normal laundering

10% bleach

When does leptospiruria occur?

• 7-10 days after infection

Timeline for owners to avoid urine?

48 hours treatment with doxycyclie - wear gloves and eye protection when cleaning up urine

Should other dogs in a home be treated?

Because of the zoonotic potential of leptospirosis, after risk assessment, practitioners should consider prophylactic treatment of other dogs in the household that may have been exposued, ideally with monitoring acute+convalescent titers. —- more evidence is needed

We do NOT need to prophylactically treat humans

Uncertain about cats