Madeline Fujishiro, DVM
Kate E. Creevy, DVM, MS, DACVIM
Texas A&M University
Leptospirosis is a bacterial disease that is of importance in human and veterinary medicine due to its zoonotic potential. (1,2) With early and aggressive treatment that includes attentive monitoring, prognosis for recovery is excellent. Here is one case report.
A 1-year-old, castrated male miniature dachshund was presented for an acute onset of lethargy, anorexia, and vomiting.
The patient was evaluated upon referral for a 48-hour history of lethargy, anorexia, and vomiting. He was also noticeably polyuric and polydipsic during the 48 hours prior to presentation.
He was reported to be housed predominantly indoors and lived with one other dog, a Yorkshire terrier, who was unaffected. He had no history of prior illness and had received his complete series of puppy core vaccinations (distemper virus, parvovirus, adenovirus, and parainfluenza series; and rabies initial vaccine). He had not yet received his first adult boosters.
Physical Examination and Diagnostics
On original presentation to the referring veterinarian, the patient was depressed, weighed 3.0 kg, was assessed to be 5% to 7% dehydrated, and was febrile (102.8°F). A complete blood count (CBC) and serum biochemical profile were performed (TABLE 1). His urine specific gravity (USG) before fluid therapy was 1.012.
TABLE 1 Pertinent Referring Veterinarian Blood Work Results
|Complete Blood Count|
|White blood cells (103 cells/mcL)||27 (H)||4.0 - 15.5|
|Neutrophils (103 cells/mcL)||22.1 (H)||2.06 - 10.6|
|Monocytes (103 cells/mcL)||1.62 (H)||0 - 0.84|
|Hematocrit (%)||35 (L)||36 - 60|
|Platelet count (103 cells/mcL)||169 (L)||170 - 400|
|Serum Biochemical Profile|
|Alkaline phosphatase (U/L)||249 (H)||5 - 131|
|Blood urea nitrogen (mg/dL)||52 (H)||6 - 31|
|Cholesterol (mg/dL)||382 (H)||92 - 324|
|Creatinine (mg/dL)||1||0.5 - 1.6|
|Phosphorus (mg/dL)||10.5 (H)||2.5 - 6.0|
|Specific gravity||1.012 (L)||1.015 - 1.045|
|H, high; L low.|
The patient was administered 50% dextrose and Nutri- Cal (vetoquinolusa.com) orally. He was hospitalized for 8 hours and received IV fluid therapy, maropitant, famotidine, and ampicillin. He was sent home with sucralfate, famotidine, and instructions to feed a bland diet. When his lethargy and anorexia continued into the following day, referral was recommended.
TABLE 2 Pertinent Clinicopathologic Abnormalities
|Complete Blood Count|
|White blood cells (103 cells/mcL)||36.7 (H)||6.0 - 17.0|
|Neutrophils (103 cells/mcL)||28.26 (H)||3.0 - 11.5|
|Monocytes (103 cells/mcL)||5.87 (H)||0.15 - 1.25|
|Hematocrit (%)||35 (L)||36 - 60|
|Platelet count (103 cells/mcL)||clumped||200 - 500|
|Serum Biochemical Profile|
|Alkaline phosphatase (U/L)||473 (H)||24 - 147|
|Blood urea nitrogen (mg/dL)||69 (H)||5 - 29|
|Cholesterol (mg/dL)||394 (H)||120 - 247|
|Creatinine (mg/dL)||2.09 (H)||0.3 - 2.0|
|Phosphorus (mg/dL)||8.3 (H)||2.9 - 6.2|
|Specific gravity||1.012 (L)||1.015 - 1.045|
|Protein (mg/dL)||100 (H)||negative - trace|
|H, high; L low.|
PHYSICAL EXAMINATION AND INITIAL DIAGNOSTICS
On presentation, the patient was quiet and alert, adequately hydrated, weighed 3.18 kg, and was in adequate body condition (BCS 5/9). His rectal temperature was elevated (102.7°F). He appeared painful on palpation of his abdomen, and his kidneys were subjectively enlarged. The remainder of his physical examination revealed no abnormalities.
A CBC, serum biochemical profile, and urinalysis were performed (TABLE 2).
Based on the patient’s signalment, history, physical examination, and initial blood work results, the primary differentials for renal azotemia with concurrent inflammatory leukogram included:
- Toxin exposure, including ethylene glycol
- Bacterial pyelonephritis
ADDITIONAL DIAGNOSTICS AND DIAGNOSIS
Abdominal radiographs revealed bilateral renomegaly and mild hepatomegaly.
Abdominal ultrasound confirmed the presence of renomegaly with bilateral pyelectasia (FIGURE 1). Scant peritoneal and retroperitoneal effusion was also present.
Aerobic culture of urine was reported as “no growth” after 3 days of incubation.
Blood and urine samples were submitted for leptospirosis polymerase chain reaction (PCR) testing and microscopic agglutination test (MAT) titers. PCR results were negative in blood and positive in urine for leptospirosis. MAT titers were strongly supportive of natural leptospirosis infection (TABLE 3).
TABLE 3 Microscopic Agglutination Test Titers
THERAPY FOR LEPTOSPIROSIS
The patient was treated supportively with IV fluid therapy, maropitant, famotidine, and buprenorphine.
IV ampicillin and sulbactam was initiated due to the high suspicion for leptospirosis. The patient improved clinically with these therapies within a few days. Once leptospirosis MAT titers and PCR results were received, he was transitioned to oral doxycline.
The patient was hospitalized for 8 days. Serial biochemical profiles supported a positive response to therapy (TABLE 4).
TABLE 4 Serial Biochemical Profile Abnormalities
|Day of Hospitalization|
|Alkaline phosphatase (U/L)||24 - 147||473||323||392||308||374||468||463||504|
|Blood urea nitrogen (mg/dL)||5 - 29||69||40||68||67||34||31||23||43|
|Cholesterol (mg/dL)||120 - 247||394||353||358||316||292||*||*||*|
|Creatinine (mg/dL)||0.3 - 2.0||2.09||1.3||2.87||2.94||1.56||1.26||1.14||1.4|
|Phosphorus (mg/dL)||2.9 - 6.2||8.3||5.9||7.6||6.7||5.7||*||*||*|
|*Value not measured|
A week after discharge from the hospital, blood work performed by the referring veterinarian revealed no abnormalities, and creatinine had remained within the normal reference range (1.4 mg/dL). Convalescent MAT titers performed by the same laboratory revealed a 4-fold decrease in the serovar Grippotyphosa (1:400), further supporting the diagnosis of leptospirosis.
DISCUSSION: OVERVIEW OF LEPTOSPIROSIS
Leptospirosis is a bacterial disease with a worldwide distribution and is of importance in human and veterinary medicine due to its zoonotic potential.1,2
Naming conventions for leptospiral pathogens are unusual, as the organisms are commonly described by serovar names, rather than species names. There are hundreds of known serovars of the genus Leptospira, and disease in dogs is caused by the pathogenic serovars of the species Leptospira interrogans and Leptospira kirschneri.2,3
Different serovars are adapted to various reservoir hosts, including the raccoon (FIGURE 2), opossum, vole, and rat; the dog is likely the reservoir host for serovar Canicola.1–3 These hosts excrete the organisms in their urine. Incidental hosts, such as humans and dogs, are infected when their intact mucous membranes or abraded skin comes into direct or indirect contact with infected urine.1,2
Leptospires prefer a warm and wet environment, therefore, disease is found more predominantly in warmer climates with higher annual rainfall.1,2 The incubation period ranges from a few days to a week and varies based on infecting dose, strain, and immune response of the host.1
Disease may manifest as peracute disease or subclinical infection, with the severity of clinical illness depending on infecting strain, geographical location, and immune response of the host.1,2
Common clinical presentations include lethargy, anorexia, vomiting, abdominal pain, or changes in urination (polyuria, oliguria, or anuria).2,4 Leptospirosis should be suspected in dogs with evidence of febrile renal or hepatic disease, vasculitis, uveitis, or pulmonary hemorrhage (TABLE 5).1,2
TABLE 5 Common Clinical Syndromes and Manifestations Associated With Leptospirosis
|CLINICAL SYNDROME||CLINICAL MANIFESTATION|
|Renal failure||Polyuria, oliguria, or anuria Polydipsia Abdominal pain Dehydration Azotemia Hyperphosphatemia|
|Hepatic injury||Icterus Cranial organomegaly Coagulopathy Hyperbilirubinemia Elevated liver enzyme activity|
|Vasculitis||Peripheral edema Pleural effusion Peritoneal effusion Petechiation Epistaxis Uveitis Pulmonary hemorrhage syndrome (appears to be more prevalent in European cases)|
Most consistent hematologic findings include leukocytosis, anemia, and thrombocytopenia. Biochemical abnormalities reflect renal damage and reduced glomerular filtration rate (azotemia, hyperphosphatemia) and/or hepatic injury (hyperbilirubinemia, elevated liver enzyme activity).2,4 Bleeding tendencies are likely multifactorial in origin, reflecting both vascular and hepatic injury.
Although attempts have been made, no consistent correlation between infecting serovar and clinical presentation has been identified.1 This is likely at least partly attributable to the inability of antibody tests to predict the infecting serovar.1
There is no single “gold standard” test for an antemortem diagnosis of canine leptospirosis. The diagnosis is based on the combination of clinical signs, clinicopathologic abnormalities, and methods of organism detection, including MAT titers, acute and convalescent titers, PCR, culture, histopathology, and IDEXX SNAP Lepto Test (idexx.com).
MAT titers. MAT is an antibody test that assesses the ability of serial dilutions of patient serum to cause agglutination of live leptospires via dark field microscopy.2 The reported titer is the highest patient serum dilution causing 50% agglutination of leptospires in the reaction.1 There is no consensus on the cutoff value for a negative titer.
Natural infection should be strongly suspected with a single MAT titer of 1:800 or greater with consistent clinical signs and clinicopathologic abnormalities without leptospiral vaccination within the past 4 months.2,3 MAT titers cannot be used to predict the infecting serovar due to cross-reactivity among different serogroups from shared leptospiral antigens.1,5
Acute and convalescent titers. Dogs frequently have negative MAT results in the acute phase of infection.1 If there is a high index of suspicion for disease, and the initial titer does not support infection, convalescent titers in 2 to 4 weeks should be performed. A 4-fold change (increase or decrease) in a titer supports recent infection with leptospirosis.1–3
PCR testing. PCR can be used to detect pathogenic leptospiral nucleic acids. During the first 10 days of infection, organism numbers are highest in blood. Afterwards, they are found in the highest concentration in urine.1 Because timing of infection is not often known, pairing blood and urine PCR testing may increase diagnostic sensitivity.
False-negative results may occur with recent antimicrobial treatment or when the number of sampled organisms is low.1 Recent vaccination does not interfere with PCR assays.2 PCR testing should be paired with other diagnostic methods like MAT titers.1
Culture. Leptospires can be cultured on special media; however, the diagnostic utility is limited because the organism is both fragile under transport conditions and slow growing (up to a 3- to 6-month incubation period).1,2
Histopathology. Organisms may be visualized with silver stains, immunohistochemistry, or fluorescence in situ hybridization on biopsied kidney tissue.6
SNAP Lepto Test. This point-of-care test detects antibodies to Leptospira species by enzyme-linked immunosorbent assay (ELISA) and reports a qualitative positive or negative result. Independent studies of its utility in field conditions have not yet been reported.
Appropriate supportive therapy should be provided to each patient based on the clinical manifestation of disease.
IV fluid therapy must be initiated for the treatment of acute kidney injury associated with leptospirosis and to correct for dehydration. Urine output should be monitored and fluids adjusted accordingly once hydration is restored. Ideally, these patients should be hospitalized at 24-hour care facilities, and referral for dialysis should be offered for patients in oliguric or anuric renal failure.7 Acute kidney injury in dogs has been comprehensively and practically reviewed elsewhere.8
The current recommendation for treatment of leptospirosis is doxycycline 5 mg/kg PO q12h for 2 weeks. In clinically ill patients that cannot tolerate doxycycline, IV ampicillin can be administered to eliminate the leptospiremic phase. Once tolerated, a 2-week course of doxycycline is required to eliminate the organism from the renal tubules.1,2
With early and aggressive treatment that includes attentive monitoring, prognosis for recovery is excellent. Urine output should be monitored; development of oliguric renal failure significantly worsens the prognosis and prompts escalation of therapy.8
Resolution of azotemia occurs within 10 to 14 days, however, damaged renal tissue may continue to regenerate for more than than 4 weeks after treatment. Some dogs may suffer from permanent renal damage.1,6
Hyperbilirubinemia, if present, may be slower to resolve.
In the United States, vaccines for prevention of leptospirosis contain the serovars Icterohaemorrhagiae and Canicola and may include Grippotyphosa and Pomona. Vaccines effectively prevent disease after challenge with serovars included in the vaccine, and disease is rare in dogs vaccinated with the four-serovar vaccine; however, cross-protection of vaccines against other pathogenic serovars requires further investigation.1,3,6
Vaccines have been shown to provide immunity from serovar-specific challenge for 1 year, but longer duration of immunity has not been demonstrated. While previously associated with a type I hypersensitivity reaction, the vaccine is no longer considered more reactive than other vaccines.6
Vaccination is recommended annually in “at-risk” dogs.9 At-risk dogs include those with exposure to wildlife reservoirs and/or contaminated water sources.1
Additional disease prevention includes avoidance of environmental water sources and contact with wildlife. Wildlife reservoirs of leptospirosis, such as rats and raccoons, are present in urban and suburban environments. As evidenced by this case, even small-breed dogs traditionally thought to have a low risk of exposure can contract the disease.
Similar to dogs, humans can become infected with leptospires from contaminated water sources or contact with reservoir hosts. Reports of transmission of disease from incidental hosts to other animals (eg, dogs to humans) are rare; however, in-hospital precautions should be taken to minimize the risk of zoonotic transmission (BOX 1).6
BOX 1 Precautions For Leptospirosis Patients
- Place a warning sign on cage designating animal as leptospirosis patient (suspected or diagnosed)
- Avoid patient contact with pregnant or immunocompromised humans
- House patient away from high-traffic areas
- Minimize patient movement around hospital
- Disinfect urine spills promptly
- Wash hands before and after handling patient
- Wear personal protective equipment, including gloves, disposable gown, protective eyewear, and facemask when handling patient
- Place an indwelling urinary catheter, if necessary, to monitor urine output or control incontinence
- Walk uncatheterized dogs outside frequently to urinate in a restricted area that is easily decontaminated
All dogs presenting with acute renal failure should be handled as having leptospirosis until proven otherwise. At home, owners should avoid contact with their dog’s urine, wearing gloves to clean up spilled urine until antimicrobial therapy is complete.1
- 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.
- Lunn KF. Leptospirosis. In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy XV. St. Louis, MO: Elsevier; 2014:1286-1289.
- Green CE, Sykes JE, Moore GE, et al. Leptospirosis. In: Green CE, ed. Infectious Diseases of the Dog and Cat. 4th St. Louis, MO: Elsevier; 2012:431-447.
- Goldstein RE, Lin RC, Langston CE, et al. Influence of infecting serogroup on clinical features of leptospirosis in dogs. J Vet Intern Med 2006;20:489-494.
- Harkin KR, Hays MP. Variable-number tandem-repeat analysis of leptospiral DNA isolated from canine urine samples molecularly confirmed to contain pathogenic leptospires. JAVMA 2016;249(4):399-405.
- Sykes JE. Leptospirosis. In: Sykes JE, ed. Canine and Feline Infectious Diseases. St. Louis, MO: Elsevier; 2014:474-485.
- van de Maele I, Claus A, Haesebrouck F, et al. Leptospirosis in dogs: a review with emphasis on clinical aspects. Vet Rec 2008;163(14):409-413.
- Ross L. Acute kidney injury in dogs and cats. Vet Clin North Am Small Anim Pract 2011;41(1):1-14.
- Klaasen HL, Molkenboer MJ, Vrijenhoek MP, et al. Duration of immunity in dogs vaccinated against leptospirosis with a bivalent inactivated vaccine. Vet Microbiol 2003;95(1-2):121-132.