Leptospirosis is a widely spread zoonosis of global concern. It is caused by spirochetes belonging to the genus Leptospira. All the pathogenic leptospires were formerly classified as members of the species Leptospira interrogans; the genus has recently been reorganised and pathogenic leptospires are now identified in several species of Leptospira. There are more than 200 distinct leptospiral serovars recognised and these are arranged in 23 serogroups. Canine outbreaks of leptospirosis in several countries are sparking discussion. Changing trend in the epidemiology of this disease is related to two primary factors that may strongly influence the epizootiology of Leptospira serovars. These factors are: 1) preventative vaccination has all but eradicated clinical disease in the domestic dog and 2) there has been an increased migration of wildlife, for which serovar infections with L. grippotyphosa and L. pomona are most prevalent.

The following article provides highlights recent findings on the disease in dogs, and it challenges veterinarians to learn more about this serious disease, which affects both animals and man.

Etiology

Leptospira is a flexible, spiral-shaped, Gram-negative spirochete. Pathogenic Leptospires belong to species Leptospira interrogans. Leptospira interrogans has many serovars based on cell surface antigens. More than 200 serovars have been identified. Leptospires become adapted to "primary reservoirs hosts" which are commonly wildlife species, the same Leptospira species also occur in almost any other mammalian hosts as "accidental or incidental hosts". L. icterohaemorrhagiae and L. canicola and L. grippotyphosa are the most common serovars identified causing canine leptospirosis. Although infection is rare in cats, L. bratislava, L. canicola, L. grippotyphosa and L. >pomona are the serovars isolated from cats.

Organisms are transmitted by direct contact with infected urine, bite wounds or ingestion of infected tissues, or indirectly, through contact with infected water, soil, food or bedding. The most common source of leptospirosis in dogs is contaminated water. Indirect transmission also occurs from vegetation, soil, or food contaminated by infectious urine.

Pathogenesis

The hallmark of infection with Leptospira species is its rapid hematogenous dissemination. After the organism gains entry into the host, rapidly invade the bloodstream and creates a leptospiremia. Leptospiremia peaks 4-12 days after. Organisms disseminates hematogenously to the kidney, where they colonize the apical surface of the proximal renal tubule, which allows shedding in the urine and transmission to new hosts. This leptospiral interstitial nephritis results in both acute and chronic kidney damage and loss of renal function.

The liver is the second major parenchymous organ damaged during leptospiremia. Profound hepatic dysfunction may occur without major histologic changes because of subcellular damage produced by leptospiral toxins. The degree of icterus in both canine and human leptospirosis usually corresponds to the severity of hepatic necrosis. Chronic active hepatitis has been a sequela to serovar grippotyphosa infection in dogs. Presumably, initial hepatocellular injury and persistence of the organism in the liver result in altered hepatic circulation, fibrosis, and immunologic disturbances that perpetuate the chronic inflammatory response. Extensive hepatic fibrosis and hepatic failure may result from this process.

Tissue edema and disseminated intravascular coagulation (DIC) may occur in rapid and severe leptospirosis that results in acute endothelial injury and hemorrhage Leptospira lipopolysaccharide stimulates neutrophil adherence and platelet activation, which may precipitate inflammatory and coagulation abnormalities. Other body systems, (e.g., CNS) also are damaged during the acute phase of leptospirosis.

Clinical and Laboratory Findings

Many Leptospira infections in dogs are subclinical. However, when clinically apparent, the dogs are classically presented for:

Laboratory findings

 Leukocytosis and thrombocytopenia

 Increased serum urea and creatinine concentrations

 Hyponatremia, hypochloremia, hypokalemia, and hyperphosphatemia

 Mild hypocalcemia is related to hypo-albuminemia

 Hypoglycemia

 Increased serum alanine aminotransferase (ALT), aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase (ALP) activities

 Bilirubin concentration also is increased

 The increase in serum ALP activity

 Urinalysis can include glucosuria, tubular proteinuria, and bilirubinuria. Microscopic examination of the urine sediment may reveal increased numbers of granular casts, leukocytes, and erythrocytes

Diagnosis

The differential diagnosis of peracute or acute disease in the dog includes heartworm disease, autoimmune hemolytic anemia, bacteremia, infectious canine hepatitis virus, hepatic neoplasia, trauma, lupus, Rocky Mountain spotted fever, Ehrlichiosis, toxoplasmosis, renal neoplasia, and renal calculi. The differential diagnosis of chronic disease, e.g., abortions, weak puppy syndrome, includes canine brucellosis, canine herpesvirus infection and distemper. Younger animals tend to be more severely affected. Diagnosis of leptospirosis is based on a combination of suggestive historical information, physical findings, nonspecific laboratory findings, and confirmatory testing. Dogs with chronic renal failure or increased liver enzyme concentrations should be screened for Leptospirosis.

 Darkfield microscopy and fluorescent antibody (FA) testing of urine. Absence of the organism does not rule-out infection.

 Culture of the Leptospira organism in blood (early in the course of disease) or urine (later in the course of disease). Samples should be collected prior to initiating antibiotic therapy!

 FA examination. FA should be done on all tissues submitted for postmortem examination, especially important are kidney and liver specimens.

 Polymerase chain reaction (PCR). With the advent of PCR tests, rapid and genus and serovar specific detection of leptospiras from clinical specimens should be possible.

 The microscopic agglutination test (MAT) has been the "gold standard" confirmatory test for the past 70 years and is most likely based on seroreactivity with the LPS antigens. MAT and is very useful in diagnosis acute infections. It is best performed on paired sera taken more than 14 days apart, especially if the animal has been vaccinated.

 ELISA is for detection of anti-leptospiral antibodies. In general, ELISAs are quite sensitive. An ELISA that measures canine IgG and IgM against various Leptospiral serovars has been developed and evaluated in Europe. Anti-leptospiral IgM is detectable in this assay as early as 1 week after infection. Before agglutinating antibodies are present. IgG antibodies are detectable in infected dogs beginning 2 weeks after infection and persists for long periods of time. Therefore, dogs with acute leptospirosis have high IgM titers and relatively low IgG titers; dogs that are vaccinated or have had previous Leptospiral infections have high IgG titers but low IgM titers.

Treatment and Control

The aims of treatment for acute cases of canine leptospirosis are to control the infection and to suppress the leptospiruria. Severely ill, acute cases require supportive care. Initial antimicrobial therapy, where there is evidence of renal dysfunction and/or leptospiremia, should include the use of penicillin G (25,000 to 40,000 units/kg IM, IV every 12 hours) or until kidney function returns. Ampicillin 22 mg/kg every 8 hours, IV. For elimination of leptospires from the renal interstitial tissues to control the carrier state Doxycycline is administered orally, 5.0 mg per kg SID Aminoglycosides cannot be used in patients until kidney function has been restored.

Until recently, bacterins contained only two serovars (L. canicola and L. icterohaemorrhagiae) and cross protection between leptospiral serovars does not occur, these products did not provide protection from infection by other serovars. In recent years, in the newer vaccines, L. grippotyphosa and L. pomonahave been added. The prominence of these latter serovars stems from the use of vaccination and the greater exposure of unnatural hosts such as dogs to wildlife reservoir hosts Leptospirosis vaccines, protect against clinical disease but do not prevent subclinical infection to a "carrier" state. That is, a dog that is annually vaccinated may harbor infectious organisms of L. icterohaemorrhagiae or L. canicola which will pose a risk of contagion to dogs that are not vaccinated or in which vaccination for these serovars has been discontinued. As with most bacterins, immunity is not as long lasting as is immunity to viral antigens. Yearly boosters are recommended for at risk dogs, and immunity may not even last a complete year. Leptospira bacterins do not prevent infection or shedding of the organisms in the urine, even when they reduce or eliminate the clinical signs of disease. Thus, the public health threat from organisms being shed in the environment persists.

Urine is the most important source of leptospiral contamination after acute infection. Veterinary clinicians and staff should wear protective latex gloves when handling any dog with possible leptospirosis, as well as blood and bodily fluids from the animal. Areas soiled by the dog's urine should be cleaned with an iodine-based disinfectant (protective gloves should be worn during cleaning). Leptospires may continue to be shed in the urine for months despite clinical recovery and an effective immune response.

Control methods should, therefore, include vaccination; special attention to kennel sanitation to eliminate contact with potential sources of infected urine; knowledge that high risk dogs are hunter breeds, show dogs, and other dogs with access to water such as ponds; institute rodent control of households and kennels.

References

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