Canine leptospirosis (Proceedings)

Leptospirosis may be one of the most under-diagnosed diseases in veterinary medicine. We expect to see the classic triad of clinical disease: acute renal failure, hepatic failure, and intravascular hemolysis (usually low-grade). Although many dogs exhibit these forms of the disease, many exhibit clinical signs that are not routinely attributed to leptospirosis. Here are two atypical cases.

Case 1

A 9-year-old, spayed female German shepherd was presented for profound polyuria and polydipsia of several weeks duration. A complete blood count and serum chemistry profile were normal. The urinalysis showed hyposthenuria (urine specific gravity of 1.004), however the urine sediment was inactive and the culture was negative. Testing for hyperadrenocorticism was negative. A water deprivation test was performed and the dog failed to concentrate. Therapy with DDAVP also failed to resolve the clinical signs. A serologic test for leptospirosis was performed and the results showed a titer of 1:6400 for serovar Grippotyphosa and negative for all other serovars. Therapy with doxycycline for 4 weeks resolved the polyuria and polydipsia. Serology performed 3 months later showed conversion to negative on all serovars. The most important issue regarding this case was the constant exposure of the owner to leptospirosis-infected urine from the dog urinating in the house. We have seen a number of cases of non-azotemic PU/PD in dogs caused by leptospirosis.

Case 2

A 5-year-old, male Jack Russell terrier presented with a 2-day history of lethargy and depression associated with fever. On presentation, Buddy had a fever of 103.8, however the fever resolved within a few hours and Buddy was discharged without any medications. Buddy presented the following day with a temperature of 105 F. A CBC, chemistry profile, and urinalysis were completely normal. A PCR of the urine for leptospirosis organisms was strongly positive (the test was performed as part of a research project evaluating the utility of PCR in diagnosing leptospirosis: it was anticipated that this dog was ill for other reasons and would not have leptospirosis). A serology was subsequently performed and the dog had a titer of 1:12,800 against serovar Grippotyphosa. The dog was treated with doxycycline and responded rapidly to therapy. The other dog in the house, who was asymptomatic, also had a strong positive urine PCR for leptospirosis organisms and was also treated. The important aspect of this case is that the fever would have responded to amoxicillin, thereby eliminating further diagnostics, but the dog would have remained a public health risk by shedding leptospires in the urine. Treatment with doxycycline is necessary to eliminate the shedding phase.

Leptospirosis

Leptospirosis is a spirochetal bacterial zoonosis that is found world wide, most often in wetter climates. In man, leptospirosis infections can be subclinical, self-limiting febrile disease with or without meningitis, or a severe and potentially fatal illness known as Weil's syndrome that presents as hemorrhage, renal failure, and jaundice. As new communities encroach on areas inhabited by wildlife, the incidence of leptospirosis will continue to climb. In rural areas, pigs and cattle are the primary reservoirs of disease important for dogs, in suburban areas, rodents, deer, raccoons, possum, and other common wildlife are important reservoirs, and in the cities rats are the reservoir. The major concern with wildlife is the introduction of serovars that have been previously unrecognized, and for which there is no vaccination and they are not screened for on the available serologic tests. Infection with a different serovar that is not tested for and which does not cross-react can lead to a false negative diagnosis based on serology, however PCR typically should detect these infections.

     There are 3 classical presentations: hemorrhagic syndrome, icteric syndrome, and uremic syndrome. Dogs may have one, two, or all of these syndromes and any serovar can produce any clinical picture.

     Common clinical signs include arthralgia or myalgia (this may be the initial presenting complaint), vomiting and diarrhea, icterus, depression or lethargy, hematochezia or melena, intussusceptions, polyuria/polydipsia (may not be azotemic), dyspnea (from pulmonary hemorrhage or pneumonitis), oculonasal discharge, cough, and uveitis.

     Common laboratory findings include:

          1.      mild anemia: this often confuses the diagnosis, making the clinician think that chronic renal failure is present

          2.      thrombocytopenia

          3.      leukocytosis (most do not have a left shift)

          4.      azotemia (elevated BUN, creatinine, phosphorous)

          5.      elevated serum alkaline phosphatase (this is often dramatic with minimal increase in serum alanine transaminase)

          6.      hyperbilirubinemia

      A high index of suspicion is important in the diagnosis of leptospirosis

The diagnosis can be confirmed by serology, especially when a 4-fold rise in titers over a 2-4 week period or a single high titer with appropriate clinical signs and response to therapy are documented. Initial titers may be negative (can get early peak leptospiremia in 2-4 days, i.e. clinically ill, but antibodies are not evident until 10 days post-infection), titers may stay low if treated early and with appropriate antibiotics, and titers can revert to negative in 30-45 days if treated appropriately. Culture of blood or urine is difficult to do and requires special media and handling. Darkfield microscopy of urine has a very low yield.

Polymerase Chain Reaction (PCR) on blood or urine allows for very early diagnosis but is not commercially available. We are currently evaluating this diagnostic modality at Kansas State University. The test that we are evaluating is not specific for serovars and has been shown to detect the 6 major serovars, including 25 additional serovars. It is likely that our test will detect most known serovars of Leptospirosis. We have found this test to be very sensitive and have detected asymptomatic carriers of leptospirosis. The PCR can be performed on urine or tissue and is available from the diagnostic laboratory at Kansas State University. Contact them at 785-532-5650 for submission information or contact Dr. Ken Harkin at harkin@vet.k-state.edu. Submission information can also be found online at www.vet.ksu.edu, then follow the link to "Diagnostic Lab" and then to "Submission Forms". Write in "Leptospirosis PCR" or "Leptospirosis Serology". The Diagnostic Lab will establish an account for you after you submit the sample.

      The therapy of leptospirosis is straightforward

          1.      Manage the acute renal failure with aggressive fluid therapy: LRS or 0.9% saline are appropriate; replace fluid deficits over 6 hours, maintain fluid rate at 2-3 times maintenance; monitor CVP if necessary, monitor weight q6-8h, monitor urine output (subjectively or quantitatively). Everyone handling the dog and cleaning the cages should wear gloves and wash hands after handling or contact. Most commercial cleaners used in veterinary hospitals should destroy the leptospires.

          2.      Intravenous ampicillin @ 22 mg/kg IV q8h for the acute disease until oral doxycycline is tolerated.

          3.      Doxycycline @ 5 mg/kg PO q12h or 10 mg/kg PO q24h. I currently recommend a minimum of 3 weeks and a maximum of 4 weeks. This step is required to clear the leptospires from the renal tubules.

          4.      Enrofloxacin is probably effective since Ciprofloxacin does appear to be effective. The 1st generation cephalosporins (cephalothin, cefazolin, cephalexin) are not effective.

          5.      Past recommendations for 2 weeks of IM injections of procaine penicillin G followed by 2 weeks of injections of streptomycin should not be followed. This is an inhumane method of medicating the patient.

          6.      Clients should notify their doctor if they develop flu-like symptoms or worse. Pregnant women, regardless of symptomatology, may want to consider acute and convalescent titers.

          7.      If the azotemia persists for more than 7-14 days, it is a good idea to perform the PCR to evaluate whether the dog is still shedding leptospires. If the dog is still PCR positive, a change in antibiotics to a fluoroquinolone, such as enrofloxacin, is indicated.

My current recommendation is that dogs that are considered at risk should be vaccinated yearly with a multivalent vaccine (4 serovars). At risk dogs include farm dogs, dogs allowed to roam, hunting dogs, dogs living in suburban areas that have high wildlife traffic in their yards, dogs living in urban areas where rodents are a significant problem, and dogs living in any community where a significant number of cases of leptospirosis have been identified. Additionally, administration of the leptospirosis vaccine at a time separate from other vaccinations is recommended, both to reduce adverse events associated with a large antigen load and to document the vaccine responsible for adverse events.

      Other points

          •      Even if post-vaccinal titers do not persist for 12 months, there is evidence that the dogs are still protected.

          •      In a study evaluating shedding of leptospires from healthy dogs, none of the dogs that were known to be vaccinated were found to be shedding leptospires in the urine.