your patient can make you sick – part 1 - leptospirosis

Your Patient Can Make You Sick

Part 1: Leptospirosis

Jonathan M. Chapman, DVM, MPH (c), CPH (c)Small Animal Veterinarian Intern

VCA Arboretum View Animal HospitalVeterinary Technician Educational Seminar

September 29, 2015

Presentation outline• What is leptospirosis?• Etiology• Host susceptibility, epidemiology, and transmission• Pathogenesis• Clinical findings• Diagnosis• Treatment• Prevention• Zoonotic risk• Summary and recommendations

What is leptospirosis?

• Zoonotic disease• Several pathogenic serovars• Affects virtually all mammals• Broad range of clinical effects– Mild, subclinical– Multiple organ failure and death

Etiology• Aerobic, gram-negative spirochete bacteria• Fastidious, slow growing, corkscrew-like motility• Previous classification

– Pathogenic Leptospira• Leptospirosis interrogans

– >250 different serovars (identified based on surface antigens)» Grouped into antigenically related serogroups

– Saprophytic Leptospira• Leptospirosis biflexa

• Current classification– 21 recognized genomospecies of leptospires including pathogenic, intermediate, and

non-pathogenic organisms– Some of the common leptospiral pathogens of domestic animals now have different

species names• Example: Leptospira interrogans serovar Grippotyphosa is now Leptospira kirschneri serovar

Grippotyphosa

Host susceptibility, epidemiology, and transmission

• Leptospirosis is found throughout the world– More prevalent in warm, moist climates– Endemic in the tropics– Seasonal in temperate climates– Highest incidence of disease after periods of rainfall

• Essentially all mammals are susceptible to infection with pathogenic Leptospira– Cattle, swine, dogs, and horses are most commonly recognized– Cats were previously thought to be resistant to infection

• Seroconvert upon exposure• Re-examine the role of leptospires in the pathogenesis of feline renal disease

• Wildlife, and sometimes domestic animals and livestock, serve as maintenance hosts for leptospirosis– Maintenance hosts are usually not detected until domestic animals or people become infected– High prevalence of infection– Mild acute clinical signs– Persistent infection in the kidneys and sometimes the genital tract– Diagnosis is difficult due to low antibody response and low presence of organisms in tissues


Leptospiral Serovar Maintenance Hosts

Canicola Dogs

Pamona Pigs, cattle, opossums, skunks

Grippotyphosa Racoons, muskrats, skunks, voles

Hardjo Cattle

Icterohaemorrhagiae Rats

Bratislava Pigs, mice, horses

Common maintenance hosts of pathogenic leptospires in the USA and Canada


• Characteristics of leptospirosis infection in incidental hosts are different– Low prevalence of infection– Severe clinical signs– Short renal phase of infection– Diagnosis is less difficult due to a marked antibody response and large number

of organisms in tissues• Characterization of a host as a maintenance or incidental host is not absolute

– Intermediate hosts exist• Example: Swine and cattle infected with leptospirosis serovar Pomona

– The organism persists in the kidneys even during a marked antibody response


• Transmission among maintenance hosts is often direct– Contact with infected fluids

• Urine• Placental fluids• Milk

– Venereal transmission– Transplacental transmission

• Transmission among incidental hosts is often indirect– Contact with areas contaminated with urine of reservoir maintenance hosts

• Environmental conditions are critical in the frequency of indirect transmission– Warm, moist climate– Temperatures between <10°C or >34°C (<50°F or >93.2°F)– Organisms are killed by freezing, dehydration, or direct sunlight

Pathogenesis• Leptospires penetrate exposed mucous membranes or damaged skin

– Incubation period is 4-20 days– Leptospires circulate in blood and replicate in many tissues for 7-10 days

• Acute clinical signs of leptospirosis occur• Agglutinating antibodies can be detected• Tissues colonized include:

– Liver– Kidneys– Lungs– Genital tract– CNS

• As leptospires are cleared from the body, clinical signs begin to resolve– Damaged organs may take time to return to normal function– Severely damaged organs may not recover

• Chronic disease• Death

Pathogenesis

• At this point, the disease in incidental and maintenance hosts diverges– Incidental hosts:

• Leptospires remain in renal tubules– Shed in urine for few days to several weeks

– Maintenance hosts:• Leptospires remain in renal tubules, genital tract, and eyes

– Organisms are shed in urine and genital secretions for months to years

– Leptospires often persist indefinitely despite high serum antibody levels» Become important reservoirs of infection

Clinical findings• Clinical signs depend on several factors

– Host species– Pathogenicity of the strain and serovar of Leptosira– Age– Physiologic state of host– Type of host

• Maintenance host– Subclinical infections

• Incidental host– Acute, systemic disease– Febrile– Icterus– Renal damage– Hepatic damage– Other less common clinical signs

» Uveitis, pancreatitis, hemorrhage, hemolytic anemia, muscle pain, respiratory disease• Pregnant incidental and maintenance hosts

– Localization and persistence of infection in uterus– Fetal infection– Abortion– Stillbirth– Birth of weak neonates– Persistently infected offspring

Diagnosis

• The basis for diagnosis depends on several factors– Clinical history– Vaccination history– Laboratory testing

• Detect serum antibodies• Detect organisms in tissues and body fluids

• The most commonly used technique to diagnose leptospirosis is serological assays– Microscopic agglutination test (MAT)

• Used most frequently– Enzyme-linked immunosorbent assay (ELISA)

Diagnosis

• Microscopic agglutination test (MAT)– Complex test– Requires maintenance of leptospiral cultures– Mix dilutions of serum with live leptospries of

serovars present in a region– Agglutination of leptospires indicates presence of

antibodies– The titer is equal to the highest dilution of serum

that results in 50% agglutination

Diagnosis

• Enzyme-linked immunosorbent assay (ELISA)– Commercially available test to detect canine

leptospirosis– Detect antibodies to LipL32• Membrane protein found on pathogenic leptospires

– Provides qualitative negative or positive result– Detects antibodies induced by vaccination

Diagnosis• Comparison of MAT to ELISA has not been definitively reported

– Diagnostic hypothesis: Numerical titers of MAT > qualitative results of ELISA• Although, interpretation of serological results from MAT is complicated by several

factors– Cross-reactivity of antibodies– Antibody titers induced by vaccination

• Animals develop relatively low agglutinating antibody titers– Persist for 1-4 months after vaccination– Some animals develop high titers that persist for ≥6 months

– Lack of consensus about the level of antibody titer that indicates infection• 4-fold rise in antibody titer of paired serum samples collected 7–10 days apart

– Recommended method– Titer is often low in maintenance hosts and acute infections

• Single serum sample diagnosis – Compatible clinical history– Vaccination >3 months ago– Extremely elevated titer values

• The value of MAT is to provide a numerical titer to allow comparison of acute and convalescent values.

Diagnosis• Other methods of diagnosis

– Immunofluorescence• Identifies leptospires in formalin-fixed tissue

– Tissues– Blood– Urine sediment

• Rapid• Reasonable sensitivity• Interpretation requires skilled laboratory technician

– PCR• Allow detection of pathogenic leptospires in blood, urine, or tissue samples

– Do not determine the infecting serovar• Procedure may be variable in different laboratories• The performance of commercially available PCRs has not be validated

– Culture• Requires specialized media• Blood

– May show positive results early in the clinical course of infection• Urine

– More likely to be positive 7-10 days after clinical signs appear• Rarely positive after starting antibiotic therapy• Provides little value overall and thus rarely done

Treatment

• IV fluids for dehydration and shock• Blood transfusion if hemorrhage or DIC present• Diuretics after rehydration if oliguria or anuria

present• Medication options

– Doxycylcine 5 mg/kg PO or IV q12hrs x 2-4wks– Dihydrostreptomycin 10-15 mg/kg IM q12hrs x 2-4wks– Procaine penicillin G: 40,000-80,000 U/kg IM q24hrs x 2-4wks– Ampicillin: 22 mg/kg PO q6-8hrs x 2-4wks– Amoxicillin: 22 mg/kg PO q8-12hrs x 2-4wks

Prevention

• Avoid exposure to free-range wildlife and domestic animals– Rodents– Raccoons– Opossums– Skunks

• Vaccination– Immunity is serovar specific

• Used to prevent clinical signs of disease• Some vaccines reduce renal colonization and urine shedding• Vaccines are formulated for various species to relevant serovars

Zoonotic risk• People are incidental hosts and susceptible to infection• Different types of exposures can lead to infection

– Occupational exposure• Veterinarians• Veterinary Technicians• Veterinary staff• Livestock producers• Dairy workers

– Recreational exposure• Water

– Animal ownership• Companion animals• Livestock

Zoonotic risk• The main route of infection in people is contact with infectious body fluids

– Blood• Direct contact or transplacental transmission

– Urine– Breast milk

• Leptospirosis infection in people ranges from subclinical to severe or even fatal infection– Clinical signs of leptospirosis in people include:

• Fever• Headaches• Rash• Ocular pain• Myalgia• Malaise• Icterus• Renal failure• Hepatic failure• Abortion

Zoonotic risk• Definitive diagnosis is confirmed through laboratory testing• Some extra precaution may be needed when working in the veterinary

field– General

• Handle animal body fluids using gloves• Routine hand washing

– Patients suspected to be infected with leptospirosis• Gowns• Gloves• Closed-toed shoes• Shoe covers• Face shields• Be cautious of aerosolization

– Handling wet bedding– Cleaning cages, stalls, or runs

VCA Arboretum View Animal Hospital leptospirosis protocol

• Any pet that presents with acute liver failure or acute renal failure without known toxin exposure or known infection should be suspect for leptospirosis• Especially if anorexia, vomiting, thrombocytopenia, or leukocytosis is present

• Procedure– Place patient on floor level cage, away from other patients, and away from heavy

foot traffic with cage card saying “lepto suspect”– Pregnant and immunocompromised humans should avoid contact– Place tape border on floor in front of cage to delineate buffer zone– Use disposable bedding, otherwise bedding will need to be washed twice in

bleach solution without coming into contact with other laundry or it needs to be destroyed

– Dedicate a sharps container to the patient within a taped-off area and label it as “lepto suspect” with the patient’s full name


– Label a red biohazard bag as “lepto suspect” with the patient’s full name and place in the taped-off zone

– Always treat the lepto suspect patient last during hourly treatments

– Wash and disinfect your hands after contact with the patient or items associated with the patient before and after taking off gloves.

– Cages should be thoroughly cleaned and disinfected daily.– Clean all non-porous surfaces that the patient came in

contact with using 1:1 aqueous dilution of 10% bleach solution, iodine-based disinfectants, and quaternary ammonium solutions. Let the disinfectant sit for at least 10 minutes before wiping clean.


– All contact with the patient requires gloves, goggles, face mask, and water resistant gowns for the first 48 hours after initiation of antibiotic therapy. After 48 hours, only gloves are required to be worn.

– A foley catheter of a size appropriate to prevent leakage is placed and attached to a closed collection set and should be emptied as infrequently as possible. If urine production needs to be quantified, the collection system should be weighed on a gram scale or as directed by a veterinarian

– Urine collected from lepto suspect patient should be inactivated using previously described disinfectant solutions and properly disposed in a biohazard bag. With collection systems, the disinfectant should be injected directly into the collection bag before disposing of the urine in a biohazard bag.


– Movement of patients suspected to have leptospirosis should be minimalized and areas of contact should be disinfected

– Patients should be moved through the hospital on a gurney– Dogs with suspected leptospirosis should be brought to the far

northeast corner of the parking lot to eliminate. The area should be hosed off to dilute the urine. Treat with disinfectant such as a 10% bleach solution if on gravel or cement.

– All blood, urine, and tissues from lepto suspect patients should be treated as medical waste, sealed in biohazard bags, and placed in biohazard collection bins for incineration.

– If a patient dies or is euthanized, all remains should have an alert that there is zoonotic potential


– If leptospirosis testing (PCR, acute and convalescent titers) comes back positive, the staff will be notified and sent for testing as necessary

– Veterinarians should educate owners of the zoonotic potential of leptospirosis and recommend the owners seek medical attention

– All human, especially the immunocompromised, should be referred to their medical practitioner for advice

– Routine vaccination of dogs at risk of developing leptospirosis may decrease the risk of zoonotic transmission

– Stress that the full duration of antibiotics be given to prevent the patient from becoming a chronic carrier or a zoonotic risk

Summary and recommendations• Zoonotic disease• Mild to severe clinical signs occur including death• Clinical signs, antibodies, and vaccine status can cause confusion• Difficult to definitively diagnose• Disease prevention is important• Always vaccinate your animals and recommend vaccination to other

pet owners• Consider leptospirosis in animals exhibiting clinical signs of infection,

especially icterus• When in doubt, use caution, wear personal protective equipment,

ask about vaccine status, and recommend testing for leptospirosis• Don’t forget to consult the VCA Arboretum View protocol binder

Acknowledgements

• Joao Felipe de Brito Galvao, MV, MS, DACVIM• Kathleen Van Lanen, DVM, DACVECC• Elizabeth Norberg, CVT, BS• The entire staff at VCA Arboretum View

Animal Hospital

Any questions?

References

• Lunn, Katharine F., BVMS, MS, PhD, MRCVS, DACVIM. "Overview of Leptospirosis." Merck Veterinary Manual. Merck Sharp & Dohme Corp., Apr. 2015. Web. 13 Sept. 2015.

• Tilley, Lawrence P. "Leptospirosis." Blackwell's Five-minute Veterinary Consult: Canine and Feline. Oxford: Wiley-Blackwell, 2011. 745-46. Print.

your patient can make you sick – part 1 - leptospirosis

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