Diagnosis, Treatment, and Management of Leptospirosis in Dogs
Leptospirosis is an emerging zoonotic disease found throughout most of the United States. Leptospirosis affects many organ systems and varies in severity; clinical signs range from none or mild and self-limiting to severe with acute kidney injury, hepatopathy, and/or vasculitis.
Dogs become infected when their mucus membranes or abraded skin comes into contact with Leptospira-infected urine or substrates contaminated with infected urine (e.g., water or soil) from a reservoir host. The most common reservoir hosts are wild animals such as rodents. Leptospira serovars have adapted to reservoir hosts, in which a carrier state is established and leptospires are intermittently shed in reservoir hosts’ urine.
Leptospirosis has conventionally been thought to most commonly affect young adult, male, large-breed or hunting dogs living in rural areas. Indeed, some studies have found intact male dogs and working dogs to be overrepresented among leptospirosis patients.1,2 However, other studies have found similar seroprevalence among dogs of large and small breeds, both sexes, and all age groups.3,4 In addition, living in an urban or suburban environment has been identified as a significant risk factor for the development of leptospirosis, resulting from increased interactions between dogs and wildlife in periurban settings.5 Thus, leptospirosis should be suspected in any dog with consistent clinical signs, regardless of signalment or perceived exposure.
The clinical signs and examination findings for dogs with leptospirosis can vary considerably, depending on severity of illness, infecting serovar, and the dog’s immune status.6,7 Leptospirosis is typically an acute disease; clinical signs become apparent in the first week after infection.6 Common clinical presentations can range from a mild febrile illness to acute kidney injury, hepatic injury, hemorrhagic disease, or some combination thereof (BOX 1). Other clinical findings include uveitis and reproductive failure.6,8-11
The most common clinicopathologic findings in dogs with leptospirosis are those associated with acute injury to the kidneys and liver. The most common abnormal biochemical abnormality is azotemia, found in 80% to 90% of dogs with leptospirosis.7,8,11 Elevated liver enzymes (e.g., alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) and bilirubin are noted in 30% to 50% of leptospirosis patients and may be present in the absence of azotemia.7,9,11,12 Other findings can include electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypochloremia, and/or hyperphosphatemia).9-11,13 In dogs with oligoanuria, serum potassium may be paradoxically normal or low because of alterations in the electrolyte transporters in the renal tubules.5 In dogs with myositis, creatine kinase levels can be elevated.7 Common hematologic abnormalities in dogs with leptospirosis include anemia, neutrophilia, and thrombocytopenia.8,9,11
Urinalysis findings in dogs with leptospirosis are typically compatible with acute kidney injury and include isothenuria, glucosuria, and proteinuria.7 Bilirubinuria may be noted in dogs with an associated hepatopathy. Leptospires cannot be visualized by routine light microscopy of urine sediment and do not readily grow on routine urine cultures.
In Europe, abnormalities have been found on up to 70% of thoracic radiographs of dogs with leptospirosis.14,15 Findings can range from a mild to moderate interstitial pattern to a nodular or alveolar pulmonary pattern in dogs with severe pulmonary hemorrhage (FIGURE 1).14,15 Common ultrasonographic changes include renomegaly, mild pyelectasia, medullary rim sign, or increased cortical echogenicity.16,17
Leptospira-Specific Diagnostic Testing
Several diagnostic assays, serologic and molecular, are available to aid in the diagnosis of leptospirosis. Often, a definitive diagnosis requires use of a combination of these assays.
The standard serologic reference for leptospirosis is the microscopic agglutination test (MAT), which provides a quantitative antibody titer. The results report titers to a panel of 6 to 8 Leptospira serovars, representing the common serogroups that infect dogs and that vary according to geographic location. Failure to include a member of the infecting serogroup in the panel could lead to false-negative results.
Testing of 2 serum samples, collected 7 to 14 days apart and representing acute- and convalescent-phase titers, is recommended.18 A 4-fold increase in titer indicates seroconversion and a diagnosis of leptospirosis.18 When paired samples are submitted, the sensitivity of the MAT is 100% and the specificity is 70% to 100%.19,20 A single acute serum sample is not as sensitive (50%) while antibodies are being produced and should not be relied on to rule out disease.19,20 Vaccination can result in positive MAT results; maximum titers can reach 1:6400. Titers of >1:1600 to vaccinal or nonvaccinal serovars can persist 1 year after vaccination.21-23 Therefore, although a single positive MAT result may be suggestive of leptospirosis, convalescent-phase testing is still recommended.18,24
Point-of-care assays have become commercially available and provide rapid diagnostic results. These assays are modified enzyme-linked immunosorbent assays and qualitatively detect Leptospira antibodies.25-28 As such, the limitations of these diagnostics are similar to those of the MAT. Results from these point-of-care diagnostic tests should be confirmed with paired MAT titers and/or polymerase chain reaction (PCR) results.18,24
Leptospira PCR detects bacterial DNA and is most often performed on blood or urine specimens. PCR sensitivity corresponds to the phase of disease; the bacteremic phase occurs in the first 10 days after infection, and the bacteriuric phase occurs after the first week of illness.6 Because the timeline of infection is often difficult to discern, to increase sensitivity of testing, both whole blood and urine samples should be collected before antimicrobial drugs are administered.18,24 A positive result in a dog with a compatible clinical presentation suggests leptospirosis; however, a negative result does not rule out leptospirosis because bacteremia is transient and bacteriuria is intermittent. The reported prevalence of positive urine PCR results (0% to 25%, depending on region) in the absence of clinical signs is low; therefore, positive PCR results should be interpreted in light of clinical signs.29-34 Recent vaccination does not interfere with PCR results.
Patients with suspected or confirmed leptospirosis should receive a combination of antimicrobial therapy (as outlined by consensus guidelines18) and supportive care tailored to each patient according to severity of clinical signs and affected organ systems. If the index of suspicion for the disease is high, these treatments should not be delayed while awaiting confirmatory diagnosis.
The recommended antibiotics for dogs with leptospirosis are IV penicillin derivatives or oral doxycycline.18 Because clinical signs in dogs often include vomiting or decreased appetite, initial therapy should be given parenterally rather than orally (BOX 2). After gastrointestinal signs have resolved, oral doxycycline should be administered (BOX 2) for 2 weeks to clear leptospires from the renal tubules and eliminate the carrier status.18,24
Other antibiotics have been investigated for use in people with leptospirosis. These drugs include ceftriaxone or azithromycin;35,36 however, their use in dogs has not been fully investigated and they are not recommended as first-line therapies. Because in experimental models, fluoroquinolones do not seem to completely clear leptospires, these drugs are not recommended for treatment of leptospirosis.22
Dogs with leptospirosis may require different levels of supportive care, depending on the severity of illness and affected organ systems. Recommendations commonly include maintaining adequate hydration with IV fluid therapy; correcting electrolyte and acid-base derangements; and administering anti-emetics, anti-hypertensives, pain control medications, and nutritional support.
Dogs that have leptospirosis-associated kidney injury and are polyuric may require high rates of fluid administration; however, those that are oliguric or anuric may become iatrogenically overhydrated after initial fluid resuscitation if not monitored diligently (FIGURE 2). Because fluid requirements can change rapidly throughout the course of disease, hydration status should be monitored regularly by observing changes in body weight, respiratory rate, blood pressure, central venous pressure (if possible), and urine output. Indwelling urinary catheter placement may be needed to closely monitor urine output; if oliguria or anuria is a concern, referral to a 24-hour facility should be considered. Renal replacement therapy (hemodialysis) is recommended for patients with oliguria (urine output less than 2 mL/kg/hour) or anuria despite overhydration, progressive hyperkalemia, or progressive azotemia in the face of appropriate therapy.
Leptospirosis-associated hepatic injury can lead to clinical manifestations of hepatic insufficiency (e.g., hepatic encephalopathy and hypoglycemia). Treatment for these conditions is supportive and typically leads to improved hepatic function.
A severe consequence of leptospirosis is leptospirosis-associated pulmonary hemorrhage syndrome, for which oxygen therapy and mechanical ventilation are recommended, according to the severity of clinical signs. In people, improvements have been noted with cyclophosphamide therapy37 and plasma exchange38 but not with dexamethasone and desmopressin;39 however, these therapies have not been investigated in dogs.
BOX 3 lists precautions that should be taken when leptospirosis patients are hospitalized.
For these dogs, renal function, electrolytes, acid-base status, packed cell volume, and serum protein levels should be monitored daily (or more frequently if markedly abnormal). During the course of hospitalization, complete blood counts every 48 hours are recommended to assess for thrombocytopenia. Biochemical changes often normalize within 1 to 2 weeks of therapy. As the polyuria resolves and the patient can maintain adequate hydration without additional fluid support, IV fluids can be tapered off and the dog can be discharged from the hospital. However, these patients should be re-examined within 1 week of discharge and then every 1 to 3 weeks thereafter until clinically stable.
Other Household Dogs
In addition to the leptospirosis patient, any other dogs living in the same household should receive oral doxycycline therapy for 2 weeks (BOX 2). Treatment is recommended because the dogs’ exposure histories are probably similar.18,24
If aggressive and appropriate medical therapy is administered, including hemodialysis when indicated, the prognosis for dogs with leptospirosis is good. The rate for survival to hospital discharge is approximately 80%.40 For dogs with mild to moderate disease that is treated conservatively and for dogs with severe azotemia treated with hemodialysis,40 the short-term prognosis is also good. However, the prognosis for dogs that need hemodialysis but do not receive it is grave. If severe pulmonary hemorrhage syndrome develops, the prognosis becomes worse and survival rates drop to 40% to 50%.15 Some leptospirosis patients will have lasting chronic renal changes and will need long-term monitoring and care for chronic kidney disease.41
Any dog with suspected or confirmed leptospirosis should be handled appropriately because leptospires in the urine and/or blood present a zoonotic threat (BOX 3). The zoonotic risk is thought to decrease significantly after the patient has received appropriate antimicrobial therapy for 72 hours.18
In addition to the leptospirosis patient, any other dogs living in the same household should receive oral doxycycline therapy for 2 weeks.
Several tests are available for diagnosing leptospirosis, and the greatest accuracy is achieved with use of a combination of these tests. Although many patients require aggressive therapy, if appropriate care is provided, the prognosis is ultimately good.
Dr. Sykes receives honoraria and research funding from Boehringer Ingelheim, Zoetis, and IDEXX Laboratories.
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