LONG ISLAND CANINE RENAL/HEPATIC SYNDROME IS LIKELY DUE TO LEPTOSPIROSIS

Diane M. Levitan, VMD, Dip ACVIM

Over the past several months we have found a large number of dogs (over 50 cases; no age or breed predilection) with a disease syndrome characterized by several days of anorexia, vomiting, lethargy, depression, and occasionally diarrhea. To our knowledge, this syndrome has not been recognized in cats or any other species. Physical examination reveals varying degrees of depression, fever, dehydration, icterus and abdominal pain. The most common abnormalities on bloodwork are hyperbilirubinemia (bilirubin ranging from 3-50 mg/dl),azotemia (creatinine ranging from 3-20mg/dl), hyperphosphatemia, hemoconcentration, elevated white blood count and thrombocytopenia. The urinalysis is consistent with acute renal failure (isosthenuria, proteinuria, glucosuria, and cellular casts). A related syndrome has been seen in which acute renal failure is present with no evidence of hepatic disease. In advanced stages of the disease seizures, anuria, disseminated intravascular coagulation (DIC), and death may occur.

Preliminary testing of multiple tissue and serum samples from affected dogs has implicated Leptospira kirschneri serovar grippotyphosa as the most likely underlying etiologic agent. The microscopic agglutination test (MAT) is the standard serologic test for leptospirosis. In routine testing, serum agglutination titers are obtained for the five most prevalent serovars in the United States (icterohaemorrhagiae, canicola, grippotyphosa, hardjo, and pomona) however, there are many serogroups and within those groups there are over 200 serological varieties (serovars) each of which has a different clinical, epidemiologic, diagnostic and prognostic significance. A limitation of the MAT is cross-reactivity between serovars which can prevent definitive identification of the infecting serovar and may result in titers to multiple serovars in an infected animal. Typically, serovar grippotyphosa has been associated with acute renal failure, and only rarely has there been a hepatic component. The reason for such dramatic hepatic involvement is unclear at this time, however it may be the result of infection with a related serovar. Further work on tissue and blood samples is being performed by Cornell University's Veterinary Diagnostic Laboratory to isolate the organism in order to definitively identify the causative serovar.

Titers to serovar grippotyphosa have consistently been found in affected dogs, however the titers have not been as high as would be expected for such severe clinical disease. This may be because during the acute phase of disease there is little to no detectable antibody, or it may be due to detection of a related serovar (i.e., not specifically serovar grippotyphosa). A four-fold rise in antibody titers in paired acute and convalescent serum samples is diagnostic for infection and single titers of >1:400 are considered indicative of infection. Some infected dogs will not develop titers >1:100, especially if they have received early treatment with appropriate antibiotics. Early diagnosis of acute leptospirosis is difficult but may be accomplished by detection of the organism in urine or hepatic and renal biopsy specimens by fluorescent antibody or immunohistochemical tests.

HOW TO APPROACH TO THESE CASES:

THE KEY TO SUCCESSFUL TREATMENT IS EARLY RECOGNITION AND RAPID APPROPRIATE AGGRESSIVE SUPPORTIVE CARE.

If you suspect this syndrome in a dog, it would be advisable to collect blood and urine samples as soon as possible. Immediate in house assessment of packed cell volume, total protein, blood urea nitrogen (azo stickŪ), blood glucose, and urine for specific gravity, proteinuria, glucosuria, and bilirubinuria will help identify cases early and allow for immediate hospitalization and treatment while awaiting further blood results. Blood work-up should include complete blood count and platelet count, full chemistry profile, urinalysis and culture, and leptospirosis titer. If you are not sure if the dog fits the syndrome, submit extra serum so that additional tests (such as leptospirosis titers and tick serology for Rocky Mountain Spotted Fever [RMSF] and Ehrlichia) can be added on as soon as you assess your blood test results (IF USING ANTECH DIAGNOSTICS, ADD-ON BLOOD TESTS SHOULD BE REQUESTED WITHIN 3 DAYS OF SUBMISSION). Follow up and convalescent serum titers should also be done in each case (at least 7-10 days into disease and 14-21 days after recovery).

Please be advised that the initial presentation can mimic many diseases and all rule outs should be considered. Rule outs should include viral or toxic gastroenteritis, pancreatitis, hepatitis, obstructive hepatic disorders or neoplasia. Acute renal failure can be seen with severe pyelonephritis, ethylene glycol toxicity, RMSF or obstructive urinary tract disease.

IF YOU SUSPECT THAT AN ANIMAL HAS THIS SYNDROME OWNERS SHOULD BE ADVISED AND THE DOG SHOULD BE HOSPITALIZED IN AN ISOLATED AREA AND TREATED IMMEDIATELY. NECESSARY PRECAUTIONS SHOULD BE TAKEN BY STAFF HANDLING THIS ANIMAL. (Details to follow)

TREATMENT PLAN:

Treatment should include intravenous fluid therapy with 0.9% NaCl or Lactated Ringer's solution with appropriate amounts of potassium chloride added depending on blood electrolyte evaluation. Fluids should be administered at least two times maintenance rate (approximately 60 ml/pound/day). It is essential to monitor urine output to insure that the animal is able to adequately eliminate urine (the volume of fluids going in should be similar to the amount of urine being produced). If you find that the animal is not producing adequate volumes of urine (oliguria), steps must be taken to improve renal function. Oliguria is a poor prognostic sign and may be followed by anuria despite appropriate measures. Electrolytes and renal chemistries should be closely monitored while on fluid therapy.

Antibiotic administration can shorten the duration of the illness and urine shedding of the organism and will reduce renal and hepatic damage. Initial therapy with Procaine penicillin G (40,000 units/kg IM or SC every 24 hours or a divided dose given every 12 hours) is the antibiotic of choice for leptospiremia. The dosage should be adjusted down if the animal is in renal failure (approximate adjustment is by dividing the dose by the serum creatinine concentration). Intravenous ampicillin or amoxicillin (22mg/kg every 6-8 hours) have also been used successfully during initial therapy. A form of penicillin should be used for 14 days or until resolution of the azotemia. The animal can be switched to an oral medication once the azotemia resolves (amoxicillin [22 mg/kg every 8 hours]). Two weeks of initial penicillin therapy should be followed by treatment with doxycycline (5 mg/kg twice daily) for 6-8 weeks for elimination of the carrier state.

IMPORTANT CONCERNS:

WHAT IS THE ZOONOTIC POTENTIAL? Leptospirosis is a zoonotic disease. Animal urine is the most important vehicle of infection for man. Direct contact with infected animals can also be a mode of transmission. The organism will cross mucous membranes or enter the blood stream through abraded skin. To date, there have been no reports of human leptospirosis infection associated with any of the infected dogs we have seen while investigating this syndrome, be it in an owner, owner's children, veterinarian handling the case, veterinary technician or hospital staff member. In addition there have been no recent reports of human cases of leptospirosis on Long Island. For humans, leptospirosis is a reportable disease and all human cases are reported to the state health department. Owners should be made aware of the zoonotic potential and human health risks and the fact that urinary shedding of organisms may occur for up to three months after infection. Owners should be advised to keep dogs out of children's play areas (playgrounds, sandboxes, ponds, wading areas, etc.).

While a patient is in your hospital: Suspected or infected animals should be isolated to avoid exposure to other animals. Anyone handling these animals should be wearing gloves and be extremely careful when handling blood, urine and tissues of infected animals. Dogs should be walked in a confined area and areas contaminated with infected urine should be washed and disinfected with an iodine-based solution.

What are the symptoms of leptospirosis in humans? Symptoms include fever, headache, chills, vomiting, jaundice and anemia. Symptoms in people can be mild, but in general people with leptospirosis are usually very ill and are often hospitalized. Anyone who has been in contact with an infected dog who develops a flu-like illness should consult their physician and inform them that they may have been infected with leptospirosis. Leptospirosis in humans is a reportable disease and all cases should be reported to the local health department.

Why the sudden high incidence on Long Island? How is this being transmitted? We do not know why there is such a high incidence of this disease in dogs on Long Island. Cases have been seen in Nassau and Suffolk counties, but the majority of cases are in Suffolk county. The Animal Medical Center in New York City has not seen any documented cases and there has been no increased incidence noted in Westchester county that we are aware of. There has however been a recent concern about an increased incidence in the dog populations in the suburban Philadelphia area. The disease is transmitted primarily from animal host reservoirs by urine. The pathogenic organism can survive free in the environment in moist, alkaline soil and in surface waters, drains and mud. The most likely species responsible for transmission of serovar grippotyphosa are raccoons, opossums, skunk, and to a lesser extent small rodents (rats, mice, voles).

Disease prevention: Is the vaccine protective against this disease syndrome? Vaccines currently available for leptospirosis are bacterins derived from serovars canicola and icterohaemorrhagiae. These may protect against clinical disease for these serovars only. This vaccine does not protect an animal from any other serovars. THEREFORE, VACCINATION WITH THE AVAILABLE VACCINE WILL NOT PREVENT THIS SYNDROME.

This syndrome has affected over 150 dogs throughout Long Island, and we will likely see more over the next several months. Please make yourselves and you staff aware of the disease and its zoonotic potential. When caught early in the course of the disease and treated appropriately, many dogs will survive. If normal precautions are taken when handling these animals, risk of transmitting disease to humans is very low. If you have any further questions or concerns, please contact me (Dr. Diane Levitan) at Mobile Veterinary Ultrasound & Endoscopy (516-462-6004) or at Antech Diagnostics (800-872-1001). If I am unavailable, you may speak with Dr. Rhett Nichols at Antech Diagnostics. Two excellent reference articles are:

Rentko VT, Ross LA. Canine leptospirosis. In: Kirk RW, Bonagura JD, eds. Current veterinary therapy XI small animal practice. Philadelphia: WB Saunders, 1992:260-3.

Harkin KR, Gartrell CL. Canine Leptospirosis in New Jersey and Michigan: 17 cases (1990-1995). J Am Anim Hosp Assoc 1996;32:495-501.

If you have a case, we would greatly appreciate hearing from you as there is still a great deal of information to be obtained to completely elucidate this problem. We are hoping to collect serum, urine, fresh frozen and formalinized tissues from as many patients as possible, preferably before antibiotic therapy has commenced. Convalescent serum titers are also very important. I am collecting information about the cases, and particularly names of owners for each case in order to further investigate the human health risks. Thank you in advance for your assistance and cooperation in this matter.

Finally, the etiology of this syndrome would not have been identified without the dedicated efforts of many of the Long Island veterinarians who followed cases and submitted information for this study. In addition, Antech Diagnostics and Cornell University's Veterinary Diagnostic Laboratory have been extremely committed to getting to the bottom of this matter and have provided a tremendous amount of financial and technical support.

PLEASE NOTE:

THE NEW YORK STATE HEALTH DEPARTMENT AND CENTER FOR DISEASE CONTROL ARE AWARE OF THE HIGH INCIDENCE OF THIS SYNDROME. THE HEALTH DEPARTMENT OF THE STATE OF NEW YORK HAS ISSUED GUIDELINES WHICH ARE INCORPORATED IN THIS ARTICLE.

 


VIN General Veterinary Library, 1997
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