Kelly N. Monaghan, DVM, DACVIM
Internal Medicine Specialist
Leptospirosis is an infection caused by the pathogenic spirochete bacteria of the genus Leptospira. There are nine pathogenic Leptospira species and the two of greatest significance in dogs are L. interrogans and L. kirschneri. Leptospira are further grouped into serovars according to the antigenic relatedness of the lipopolysaccharide found in their outer membrane; there are more than 250 pathogenic serovars. The most common serovars incriminated in canine leptospirosis include Canicola, Icterohaemorrhagiae, Grippotyphosa, Pomona, Bratislava, and possibly, Autumnalis although this is currently unclear. There is no clear correlation between the suspected infecting serovar based on antibody testing and clinical manifestations of disease in the dog.
Leptospires are aerobic organisms that prefer high humidity and warm temperatures. Cold winters will inactivate the organism. It is commonly found in stagnant or slow moving fresh warm water (shallow lakes, ponds, puddles) and moist soil. The organisms can survive for months in fresh water or moist soil that has been saturated with infected urine. As expected, outbreaks are most common following periods of high rainfall and flooding. The organism is maintained in nature through the chronic subclinical colonization of renal tubules in wild and domestic animal reservoir hosts who in turn, shed their leptospires into the environment intermittently via urine. Such hosts include rodents, dogs, horses, skunks, raccoons, opposums, cattle, and pigs. Pet dogs can become infected through exposure to water contaminated with infected urine or via contact with reservoir hosts (wildlife, livestock).
Infection
Leptospires penetrate intact mucous membranes of the mouth, nose, or eyes or damaged or water-softened skin after contact with infected urine or urine-contaminated soil, water, or food. Infection may also occur through bite wounds, ingestion of infected tissues, and placental transfer. The incubation period after exposure is about 5-14 days after which the acute (leptospiremic) stage develops and lasts about 3-7 days. It is during this phase that the organism replicates rapidly in the blood causing a vasculitis. The leptospires then invade and replicate in various tissues including the kidney, liver, spleen, CNS, eye, and genital tract. Beginning at day 4-30, is the convalescent (leptospiruric) stage. During this stage, you will see complications associated with infiltration of tissues and more severe symptoms; although, the extent of this damage is quite variable. This stage is characterized by antibody production and excretion of the organism in the urine. Clinical signs of infection can range from mild or no signs to severe illness or death.
The main clinical presentations in dogs involve renal or hepatic disease. Acute kidney injury (AKI) is the most common presentation and is seen in 80-90% of infected dogs. The organism replicates and persists in renal proximal tubular epithelial cells resulting in proximal tubular dysfunction. Signs can range from polyuria/polydipsia without azotemia to anuric renal failure. Acute liver disease can occur with or without AKI, although the former is more likely. Liver enzymes are typically a cholestatic pattern (ALP>ALT) with hyperbilirubinemia. In addition to renal and hepatic dysfunction, dogs may also experience coagulopathies and thrombocytopenia secondary to vasculitis and endothelial cell dysfunction. Pulmonary complications have also been reported and are thought to be due to vasculitis or leptospiral pulmonary hemorrhage syndrome (LPHS).
Diagnostic Considerations
The most commonly utilized and practical diagnostic tests for canine leptospirosis are PCR of blood and/or urine and serology via the microscopic agglutination test (MAT). PCR assays do not differentiate between serovars/serogroups but they can be quite useful early in the course of an infection before an antibody test would be positive and before antibiotic administration. In the first week of infection, blood PCR is most likely to be positive; whereas, urine PCR is more likely to be positive beyond the first week. False negatives may occur with low numbers of organisms or shortly after starting antibiotic therapy. Additionally, the tubular shedding of organisms can be intermittent so there is a risk of false negative results with urine PCR. Data regarding sensitivity, specificity, and positive and negative predictive value is not available at this time.
Antibody testing [via MAT] may become positive about 5-7 days after the onset of signs so false negatives are likely early in the disease. MAT is intended to be a serogroup-specific assay, however, there is extensive cross-reaction of antibodies between serogroups making this quite unreliable. There is considerable variation in the results between labs performing the MAT with respect to serogroup result and degree of titer elevation. Therefore, MAT cannot be used to predict the infecting serogroup and there is no consensus for what titer level should be used as a cut-off for a positive or negative result. Importantly, a positive result does not necessarily correlate with clinical disease and may represent only exposure or recent vaccination to leptospirosis. Vaccines are capable of producing high post-vaccinal titers, so it is not possible to use the degree of titer elevation to differentiate between vaccination and natural exposure. Additionally, high titers to Bratislava and Autumnalis can be seen post-vaccination due to serogroup cross-reactivity. High titers in a non-vaccinated animal or a 4-fold increase in convalescent titer can be used to support a true infection in a patient with compatible signs.
Treatment
Depending upon the severity of clinical disease, patients may require extensive supportive care and hospitalization, with the worst cases requiring renal replacement therapy (dialysis). Doxycycline is the antibiotic of choice to terminate both the leptospiremic and carrier states. The recommended dose is 5mg/kg every 12 hours for 2 weeks. Alternatively, in patients that cannot tolerate doxycycline in the early phases of treatment due to nausea or vomiting or for whom the cost of injectable doxycycline is prohibitive, ampicillin may be given intravenously to terminate the leptospiremic state. Penicillins do not, however, eliminate the carrier state, so they must be followed by a 2 week course of doxycycline for this purpose.
Prognosis
The overall prognosis for leptospirosis is good with early and aggressive therapy with reported survival around 80% including patients treated with dialysis. Patients that develop LPHS (leptospiral pulmonary hemorrhage syndrome) have a significantly worse prognosis with around 50-60% survival. It is important to discuss the zoonotic potential of leptospirosis with the guardians of any dog with a suspected infection. Though it is not a common disease in people, they should still discuss it with their physician.
Practice Points
1. Leptospirosis most commonly results in kidney and/or liver injury and acute kidney injury (AKI) is the most common presentation, seen in 80-90% of infected dogs. Signs can range from polyuria/polydipsia without azotemia to anuric renal failure. Acute liver disease can occur with or without AKI, although the former is more likely.
2. With respect to PCR testing, blood PCR is most likely to be positive in the first week of infection, whereas, urine PCR is more likely to be positive beyond the first week.
3. MAT testing must be interpreted with caution. It may be negative in the first week of infection. Additionally, vaccines are capable of producing high titers, false positives may occur in vaccinated animals. MAT also cannot be used to predict the infecting serogroup and there is no consensus for what titer level should be used as a cut-off for a positive or negative result.
4. Doxycycline is the antibiotic of choice to terminate both the leptospiremic and carrier states. Ampicillin may be given intravenously to terminate the leptospiremic state but must be followed with doxycycline to resolve the carrier state.
5. The overall prognosis for leptospirosis is good with early and aggressive therapy with reported survival around 80%.
