LEPTOSPIROSIS

Infectious Diseases -  Nephrology & Urology

Leptospirosis is a bacterial disease for which humans and domestic animals act as incidental hosts. Clinical leptospirosis is rarely reported in cats. Leptospira primarily target the kidneys and liver but can also cause disease in other organs. Some infections may lead to disseminated intravascular coagulation (DIC).

Leptospirosis is still an important infectious disease of dogs despite the fact that vaccines against certain serovars (canicola, icterohemorrhagiae) have been in use for more than 30 years. It has a worldwide distribution. Wild animals (skunks, raccoons, opossums) are a major source of infection, although pigs, rats and other animals may harbor the organism and serve as reservoirs.

Once Leptospira penetrate the body through contact with infected urine, bite wounds or ingested infected tissue, they enter the bloodstream and multiply rapidly. Leptospira cause the blood vessels to become inflamed. The organism then penetrates the inflamed endothelium and invades organs such as the kidneys, liver, spleen, eyes and reproductive tract. The immune system is capable of eliminating the organism from most organs, but it tends to persist in the kidneys, and can be released into the urine for several weeks or months.

Depending on the virulence of the infecting serovar and the strength of the immune response, the damage to an affected organ can be mild or severe. Some serovars can cause sudden hemorrhage or liver damage, but most commonly, kidney damage is resultant.

Leptospirosis can be transmitted to humans. The Centers for Disease Control has reported an average of 50 to 100 cases per year for the past 20 years. A few cases are attributed to contact with rats or dogs. The majority of human infections, however, are among those who engage in watersport activities or experience occupational exposure to wildlife or domestic animal hosts. Leptospirosis has a very low fatality rate in humans.

DIAGNOSIS OF LEPTOSPIROSIS

ETIOLOGY AND RISK FACTORS

• Causes - Leptospirosis is caused by a spirochete. There are multiple serovars of Leptospira interrogans. The serovars that are associated with disease in dogs include L. icterohaemorrhagiae, L. canicola, L. grippotyphosa, L. pomona and L. brastislava.
  
  Dogs may contract leptospirosis directly through contact with infected urine, bite wounds, eating infected tissue or transplacentally. Indirect transmission can occur if susceptible animals are exposed to contaminated food, soil, water or bedding. Stagnant or slow-moving warm water provides an excellent habitat for the organism, which explains the increase in cases during periods of flooding.
• Risk factors
• Age - No known risk but young animals are more severely affected than adults
• Breed/genetics - No known risk but large breed dogs are more commonly affected
• Sex - No known risk
• Geographic/environmental - Direct spread of leptospirosis is enhanced by crowding of animals, such as in kennel situations. Outdoor dogs are more prone to infection
• Other medical disorders - No known risk
• Prevention - Vaccination is currently the most recognized way to reduce the incidence and severity of leptospirosis. Unfortunately, vaccination does not prevent subclinical infection or urinary shedding of the organism. Previously, vaccines have afforded protection against the canicola and icterohaemorrhagiae serovars. Such a vaccine does not provide cross protection against other serovars. For this reason, the incidence of disease caused by the grippotyphosa, pomona and brastislava serovars has risen. A new vaccine (Duramune DA₂P+Pv/LCI-GP), immunizes dogs against four serovars of the leptospirosis organism. The duration of immunity is approximately six to eight months. Dogs in endemic areas or at high risk may require vaccination bi-annually.
  
  In addition to vaccination, rodent control and minimizing contact with wild animals may also help reduce the risk of developing leptospirosis, since such animals serve as reservoirs.

HISTORY AND CLINICAL SIGNS

• Species affected - Dog
• Presenting signs and historical problems - Leptospirosis can cause irreversible kidney damage, liver damage, uveitis and damage to other organs. Signs of illness vary and include oliguria, anuria, polyuria, fever, generalized muscle tenderness, vomiting, hematemesis, melena, epistaxis, petechiae, icterus, ascites, dyspnea and coughing.

PHYSICAL EXAMINATION FINDINGS

• General
• Attitude - Mental status may vary from mild depression to coma
• Body condition - In the early stages, body condition is often normal. As the disease progresses, emaciation may develop.
• Vital signs - Some affected dogs may be febrile. A percentage of dogs may develop dyspnea.
• Mucous membranes - The mucous membranes may be congested or icteric. Petechiae may be present, especially if the dog has developed DIC.
• Hydration status - Many dogs are dehydrated on presentation.
• Head and neck - Epistaxis may be present.
• Eyes - Aqueous flare and decreased intraocular pressure, characteristic of uveitis, may be present.
• Oral cavity - Uremic oral ulcers are possible but are uncommon.
• Thorax (cardio-pulmonary) - Unremarkable
• Abdomen (gastrointestinal/urinary) - Abdominal pain, ascites, renal pain and hepatomegaly are possible.
• Reproductive system - Abortion and stillbirth may occur.
• Lymph nodes - Unremarkable
• Integumentary system - Petechiae and ecchymoses may develop in association with vasculitis, thrombocytopenia and/or DIC.
• Neurologic examination - Although uncommon, meningitis or hepatic encephalopathy may occur. Mental status may vary from mild depression to stupor or coma.
• Musculoskeletal examination - Some dogs may have generalized muscle pain and reluctance to move.

DIAGNOSTIC STUDIES

• Clinical laboratory tests
• CBC - Early in the disease, leukopenia may be present. As the disease progresses, neutrophilia with a left shift usually develops. In later stages, thrombocytopenia may be observed.
• Serum biochemical tests - Various biochemical changes may be present, reflective of organs involved:
  ↑ BUN, creatinine and phosphorus
  ↑ ALT, AST and ALKP
  ↑ Bilirubin
  ↑ Bile acids
  Various electrolyte abnormalities
• Urinalysis - Urinalysis is often abnormal, especially if the kidneys are affected. Urinalysis may reveal proteinuria, bilirubinuria, glucosuria, isosthenuria and/or pyuria.
• Coagulation profile - Prolonged bleeding times may be present if DIC has developed.
• Serology/immunologic tests - There are two commonly used serology tests. The microscopic agglutination test (MAT) is a blood test that detects antibodies against the leptospirosis organism. A single high titer is not diagnostic but may be suggestive. A more definite diagnosis can be made if the antibody level increases fourfold two to four weeks later.
  
  The other serologic test is the IgM-IgG enzyme-linked immunosorbent assay (ELISA) titer. Within the first week of infection, IgM typically becomes positive and remains positive for approximately two weeks. Two to three weeks after initial infection, IgG becomes positive and usually remains positive for months.
• Microbiology - The leptospira bacteria are slow growing and very difficult to culture. Therefore, culture is rarely attempted for diagnosis.
• Diagnostic imaging
• Radiographs (thoracic/abdominal) - Thoracic and/or abdominal radiographs may be recommended to help determine the extent of disease.
• Ultrasound (abdominal) - Abdominal ultrasound may likewise be recommended to assess the liver and kidneys.
• Pathology
• Biopsy/histopathology - Renal biopsy is uncommonly performed. A silver stain to detect leptospires can be performed. Unfortunately, this test often gives falsely negative results.

DIAGNOSIS AND PROGNOSIS

• Differential diagnosis - Diseases causing similar symptoms in dogs include other causes of renal failure or liver failure. These include:
• Acute renal failure
• Chronic renal failure
• Antifreeze poisoning
• Infectious hepatitis
• Chronic active hepatitis
• Hepatic neoplasia
• Recommended tests - Serology (MA or ELISA), CBC, biochemical profile and urinalysis
• Summary of diagnostic criteria - Serology with appropriate clinical signs is the most common way to diagnose leptospirosis.
• Prognosis - Dogs with mild disease often recover without chronic manifestations. Dogs that present with or develop anuria and/or DIC have a poor prognosis.

TREATMENT OF LEPTOSPIROSIS

TREATMENT PRINCIPLES

Antibiotic therapy is the mainstay of treatment. Animals with renal failure or hepatic failure will need additional supportive care.

INITIAL/HOSPITAL THERAPY

• Antibiotic therapy - Antibiotic therapy is performed in two phases:
  
  Phase I is to treat leptospiremia. The preferred antibiotic is penicillin, given at a dose of 25,000 to 40,000 units/kg intravenously twice daily. Another alternative is ampicillin, dosed at 22 mg/kg IV two to three times daily.
  
  Phase II is for elimination of leptospires in the tissues and body fluids as phase I antibiotics do not prevent the carrier state. Doxycycline at a dose of 5mg/kg PO or IV for two weeks is most commonly used.
• Supportive therapy - Supportive care is directed at the other affected organ systems. Most patients are dehydrated as a result of vomiting and diarrhea, and require intravenous fluid therapy. Animals in acute renal failure who become anuric/oliguric in the presence of adequate hydration (or over-hydration) may benefit from cautious use of a diuretic such as furosemide or mannitol to help restore urine flow. If urine flow cannot be restored, dialysis should be considered. Blood transfusions may be needed if bleeding disorders result in active bleeding and a decrease in hematocrit.

LONG-TERM/HOME THERAPY

When the dog is able to receive oral medications, a change can be made from injectable penicillin or ampicillin to amoxicillin (22 mg/kg orally two to three times daily). Treatment should be continued for two weeks. To eliminate the carrier state after treatment, doxycycline (5 mg/kg orally twice daily) should be administered for two weeks.

FOLLOW-UP CARE

Repeated CBC, biochemical profile and urinalysis may be needed to monitor the effectiveness of the treatment and assess the final extent of renal or hepatic damage. Dogs may shed leptospira organisms for months or years, especially if not treated with doxycycline to eliminate the carrier state. Dogs should be isolated from other dogs during treatment to prevent spread of the infection. Treatment may take up to four weeks.