CVC Highlight: Canine leptospirosis: When to suspect it, how to manage it

The dog is the primary companion animal in the United States affected by Leptospira species infection and can experience illness that ranges from mild to severe. The risk of infection has been shown to be greater for intact male, outdoor, working dogs, but dogs of any age, breed, or sex can become infected. Even dogs that live predominantly in the house can become infected-wild animals act as reservoirs for some serovars, and increasing encroachment on wildlife habitats by people increases the likelihood of interaction between pets and wildlife. 

Although transmission can occur through bite wounds from infected animals, most dogs acquire infection when their mucous membranes or abraded skin comes into contact with soil, food, water, or other materials contaminated by urine from Leptospira species-infected domestic or wild animals.

Clinical signs

Clinical signs seen with leptospirosis can be mild or severe. Although general manifestations of illness such as fever and malaise may be present, signs related to the acute development of renal failure or hepatopathy should raise your index of suspicion for leptospirosis. Manifestations of acute renal failure frequently include polyuria/polydipsia (PU/PD) or oliguria/anuria, gastrointestinal (GI) signs, and abdominal pain. PU/PD can also be seen without renal failure and may be a consequence of acquired nephrogenic diabetes insipidus. Manifestations of hepatopathy often include GI signs, icterus, and bilirubinuria. 

Be sure to perform an ophthalmologic evaluation since conjunctivitis and uveitis can be identified in some patients. Reluctance to move related to muscle pain may be present. Also be aware that vasculitis can occur, producing peripheral edema or cavitary effusion and hemorrhage manifested as petechiae, GI or urinary tract bleeding, hemoptysis, or epistaxis. In some cases, tachypnea or dyspnea may develop because of pulmonary hemorrhage or acute respiratory distress syndrome.

History

Ask about the patient's environment, including travel history and the status of additional household pets. Determine the pet's vaccination status-if leptospirosis is a potential diagnosis, information about vaccination for leptospirosis, including the date of administration and the serovars included in the vaccine, could be particularly important. Although most patients with leptospirosis have a history and clinical findings compatible with acute disease, leptospirosis should also be considered as an underlying cause in patients with chronic renal and hepatic disease. 

Laboratory findings

The most common clinicopathologic abnormalities identified in patients with leptospirosis are related to acute kidney and liver injury. Azotemia has been reported in ≥ 80% of affected dogs in multiple regions of the United States and Canada.1 Elevated liver enzyme activities and bilirubinemia frequently accompany azotemia-a combination of abnormalities that should prompt you to move leptospirosis higher on your list of differential diagnoses that should also include toxicoses, neoplasia, hypoadrenocorticism, and other infectious diseases such as systemic mycoses. 

Evidence of renal failure is further supported by the frequent findings of hyperphosphatemia and isosthenuria along with the possible findings of hyposthenuria, glucosuria, proteinuria, and cylindruria. Multiple electrolyte abnormalities may be present, particularly hypokalemia. However, hyperkalemia can be found if the patient develops oliguria or anuria. 

One of the most common complete blood count (CBC) findings is thrombocytopenia. Neutrophilia with or without a left shift and anemia may also be identified. The anemia is generally mildly to moderately nonregenerative but occasionally can be severe and regenerative in instances in which GI or pulmonary hemorrhage has occurred. In addition to thrombocytopenia, other coagulation profile abnormalities may be found such as increases in fibrin degradation products, D-dimer, prothrombin time, and partial thromboplasin time values, especially if disseminated intravascular coagulopathy becomes a complication. 

Imaging and histologic examination

Imaging and histopathology can be considered as additional diagnostic procedures in cases of suspected leptospirosis. Renal ultrasonographic findings compatible with Leptospira species infection include bilateral renal enlargement, increased renal echogenicity that sometimes includes a more distinct band in the medullary area, and perirenal fluid. Thoracic radiography frequently reveals diffuse lung changes that can include an interstitial or alveolar pattern. 

Renal and hepatic histologic findings in leptospirosis typically include varying degrees of renal interstitial nephritis, renal tubular necrosis, neutrophilic periportal hepatitis, and hepatic necrosis. Leptospira species organisms can sometimes be identified in tissue by using special stains (e.g. silver, peroxidase).

Leptospirosis in cats

Although leptospirosis appears to be primarily a disease in dogs in the household pet population, cats can be infected but have been thought to experience mild manifestations of disease. Leptospira canicola, pomona, and grippotyphosa have been isolated from cats. Leptospires have been identified in the blood and urine of experimentally infected cats along with evidence of renal and hepatic inflammation. 

Results from a recent Canadian study looking at Leptospira species in healthy cats and cats with kidney disease suggested that Leptospira organisms may play a role in the development of acute and chronic kidney disease in cats and that cats may play a role in transmission of these organisms through urine shedding.1 In endemic areas, leptospirosis should be a consideration in cats with evidence of renal or hepatic disease or nonspecific illness. Doxycycline therapy may be an effective means of treating cats with leptospirosis.

Reference

1. Rodriguez J, Blais MC, Lapointe C, et al. Serologic and urinary PCR survey of leptospirosis in healthy cats and cats with kidney disease. J Vet Intern Med 2014;28(2):284-293.

Specialized tests

MAT. The most common diagnostic test performed in patients suspected of having leptospirosis is the microscopic agglutination test (MAT), which uses patient sera and multiple serovars to detect antibody formation in acute and convalescent phases of illness. The highest serum dilution causing 50% agglutination of the organisms for each serovar tested is reported. False negative results can occur if the infecting serovar has not been included in the serovars tested. This possibility will be decreased if the laboratory selected for testing uses serovars more commonly found in the region from which the patient sample originated. 

For a variety of reasons, it has been difficult to establish a precise titer level indicating definitive infection with a particular serovar. However, a single titer > 800 is highly suggestive of infection with the leptospire being tested, especially if compatible clinical signs are present and no recent vaccination for leptospirosis has occurred. Cross-reactivity can occur among serovars and lower titers, depending on the time of vaccination, are often present for serovars included in the vaccine. MAT results can be negative in the acute phase of illness, so obtaining convalescent titers about two to four weeks after acute phase testing is advisable. Remember when evaluating acute and convalesent titers that a fourfold increase or decrease in Leptospira species serovar titer is considered indicative of recent infection.

PCR and culture. Leptospirosis can also be diagnosed by polymerase chain reaction (PCR) and culture methods. These methods can be especially useful in acute phase patients with negative or questionable MAT results that have not yet received antimicrobial therapy and patients with chronic renal or hepatic disease. Although blood is usually the sample of choice for PCR and culture techniques, a urine sample is often a better choice later in the course of disease when organisms reach a higher concentration in the urine. 

Although culture can be a more accurate way of serotyping Leptospira species organisms, this diagnostic procedure requires aseptic sample collection, special culture media and handling, and three to six months for growth and identification of leptospires. PCR testing will identify Leptospira nucleic acid but not necessarily the specific serovar. Both false positive and negative results can occur with PCR testing, making concurrent acute and convalescent titer evaluation desirable.

Treatment

If leptospirosis is a reasonable differential diagnosis, initiate appropriate therapy immediately without waiting for confirmation of the diagnosis. Hospitalization is generally needed for adequate treatment. Therapy most commonly encompasses specific therapy for the Leptospira species organism as well as supportive care for acute renal failure and, in some cases, hepatic damage.

Keep in mind that leptospirosis is a zoonotic disease and that appropriate measures should be taken to prevent disease transmission through disinfection and protected handling of both the patient and waste materials. In addition, treatment of other dogs in the patient's household with a two-week course of doxycycline is recommended. 

Prognosis

The prognosis for most patients is favorable for recovery with appropriate medical care. Discharge from the hospital setting can occur after tapering fluid therapy and when the patient is stable, is not showing serious outward clinical signs of illness, has normal or consistently improved laboratory values, and is able to adequately eat and drink. Azotemia may not completely resolve for weeks. Occasionally, patients will sustain permanent impairment of kidney function.

Recognition of which serovar is most likely responsible for infection of the patient will help identify environmental risk factors for reinfection and infection of additional dogs in the household. Annual vaccination of the recovered patient with a four-serovar vaccine starting one year after recovery is currently recommended.2

References

1. Greene CE. Leptospirosis. In: Infectious diseases of the dog and cat. 3rd ed. Philadelphia: Elsevier, 2006.

2. Sykes JE, Hartmann K, Lunn KF, et al. 2010 ACVIM Small Animal Consensus Statement on Leptospirosis: Diagnosis, Epidemiology, Treatment, and Prevention. J Vet Intern Med 2011;25(1):1-13.