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Keywords:

  • Dyspnea;
  • Hemoptysis;
  • Thoracic radiographs

Abstract

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

Background: Leptospirosis in dogs is a multiorgan disease affecting mostly kidneys and liver.

Objectives: The objective was to characterize prevalence, clinical, and radiological features and outcome of dogs with leptospirosis and pulmonary abnormalities.

Animals: Fifty dogs with leptospirosis.

Methods: Medical records of dogs diagnosed with leptospirosis at the Small Animal Clinic, Berlin, were reviewed. Diagnosis was based on microscopic agglutination test, blood or urine polymerase chain reaction, and histopathology. Based on clinical and/or radiological signs, patients were grouped into dogs with lung abnormalities (group 1) or without (group 2). Severity of respiratory distress was scored as mild to moderate (grade 1) or severe (grade 2). Thoracic radiographs were scored based on pulmonary changes and location as grade 1 (caudal interstitial pattern), 2 (generalized mild to moderate reticulonodular interstitial pattern), or 3 (generalized severe reticulonodular interstitial pattern with patchy alveolar consolidations). Results of CBC and biochemistry were compared between groups.

Results: Thirty-five dogs had radiological pulmonary changes (grade 1: 5; grade 2: 14; grade 3: 16); 31 of them had pulmonary distress (grade 1: 13, grade 2: 18). Sixty-seven percent of the dogs with dyspnea grade 2 were mainly euthanized because of respiratory distress. Fifteen percent of the dogs with dyspnea grade 1 and 21% without clinical respiratory signs were euthanized because of acute renal failure or sepsis.

Conclusions and Clinical Importance: In 70% of dogs with leptospirosis pulmonary changes were detected. Lung involvement represented a severe complication causing increased case fatality depending on the severity of respiratory distress.

Abbreviations:
ALP

alkaline phosphatase

ALT

alanine aminotransferase

aPTT

activated partial thromboplastin time

DIC

disseminated intravascular coagulation

Hct

hematocrit

MAT

microscopic agglutination test

OIE

World Organization for Animal Health

PCR

polymerase chain reaction

PT

prothrombin time

Leptospirosis is a zoonotic disease of global importance. Recent concerns regarding leptospirosis have focused on the possibility of increasing prevalence of the disease in humans and dogs and the shift in serovars causing the disease.1–7 Acute renal and hepatic failure are the most frequently reported clinical manifestations in dogs with leptospirosis.4–9

Respiratory manifestations have been described in 27–85% of human patients with leptospirosis.10–12 Pulmonary signs ranging from chest pain, coughing, dyspnea, hemoptysis to acute respiratory distress syndrome have been reported for patients living in warm-climate rural and urban areas but also for patients living in urban temperate regions of Europe.10,13–17 Respiratory symptoms usually appear between the 4th and 6th day of disease and may lead to death in <72 hours.17 In a human study chest radiographs were abnormal in 65% of the patients with leptospirosis; 66% of the patients had interstitial patterns and 34% alveolar patterns.12 Other authors described 3 radiographic patterns in 64% of the cases: small nodular densities, confluent areas of consolidation, and diffuse, ground-glass density. Abnormalities were bilateral, nonlobar in all cases, and with a marked tendency toward peripheral distribution.18 Intra-alveolar hemorrhage was detected in the majority of patients, even in the absence of overt pulmonary symptoms.19 Case fatality rates of 13–60% have been described in patients with severe manifestation of the lung form and pulmonary involvement has become the main cause of death because of leptospirosis in some countries.12–14,17

Until now, there have been only a few reports of dogs suffering from leptospirosis that display lung abnormalities clinically and radiologically.4,5,8,9,20,21 In these studies pulmonary changes were described in 9–93% of the dogs.

The objectives of this study were to assess the prevalence and characteristics of pulmonary abnormalities in dogs with leptospirosis. Specific aims were (1) to document clinical and radiological signs with emphasis on respiratory symptoms and radiological pulmonary changes, (2) to compare the laboratory results of dogs with and without lung abnormalities, and (3) to correlate the severity of pulmonary distress and the outcome.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

The medical records of dogs diagnosed with leptospirosis at the Small Animal Clinic, University of Berlin, between May 2006 and November 2009 were retrospectively reviewed. Dogs with acute renal failure or hepatopathy were regarded as suspicious for leptospirosis if other causes were ruled out or seemed unlikely. Dogs were included in the study if the microscopic agglutination test (MAT, performed according to World Health Organization [WHO] guidelines22) or the urine or ethylenediamine tetra-acetate anticoagulated blood polymerase chain reaction (PCR, performed according to OIE23) were positive or if leptospira were detected in renal tissue (Levaditi-staining was used to visualize leptospira organisms).

Sixteen antigens were used for the MAT: Canicola, Pomona, Grippotyphosa, Australis, Bratislava, Ballum, Copenhageni, Autumnalis, Tarassovi, Pyrogenes, Javanica, Sejroe, Icterohaemorrhagiae, Hardjo, Bataviae, and Saxkoebing. MAT titers beyond dilutions of ≥1 : 800 against all Leptospira serovars in nonvaccinated dogs or against nonvaccine serovars in vaccinated dogs with negative or low vaccination titers were recognized as positive. If titers against vaccine serovars were present in vaccinated dogs they had to be lower than the titers against nonvaccine serovars. Canicola, Icterohaemorrhagiae, and Copenhageni, which cross-react with the latter, were considered vaccine serovars. In vaccinated dogs, a titer of ≥1 : 3,200 against vaccine serovars was considered diagnostic. Moreover a greater than 2-fold rise of titers within 2–3 weeks regardless of the vaccination status was considered as diagnostic.

The medical records, including intensive care protocols, were reviewed for signalment, history, physical examination findings, results of CBCsa and biochemistries,b coagulation profiles including activated partial thromboplastin time (aPTT)c and prothrombin time (PT),d urinalyses, findings of thoracic and abdominal radiographs, measurement of urine production, central venous pressure, and outcome.

Based on respiratory signs, the dogs were grouped in severity grade 1 (mild to moderate dyspnea) or grade 2 (severe dyspnea with or without hemoptysis). Mild to moderate dyspnea corresponded to labored breathing and a respiratory rate of >35/min at rest. Severe dyspnea corresponded to severely labored breathing with a respiratory rate of >40/min and open mouth breathing, cyanotic mucous membranes, or hemoptysis.

Dogs were included in the study if at least 1 left-lateral thoracic radiograph obtained at the time of admission was available. If dogs developed dyspnea during course of disease a second thoracic radiograph had to be available. Abnormalities of the radiographs were graded based upon pulmonary patterns and location as grade 1 (caudal interstitial pattern), 2 (generalized mild to moderate reticulonodular interstitial pattern), or 3 (generalized severe reticulonodular interstitial pattern with patchy alveolar consolidations). The radiograph of each dog which displayed the most severe abnormalities was included in the evaluation.

The dogs were divided into 2 groups (group 1: with clinical and/or radiological lung abnormalities; group 2: without lung abnormalities).

Selected parameters of the CBC, biochemistry, and urinalysis were compared between groups; values with the largest deviations from the reference values were included in the evaluation and group comparison.

Statistics

Data were evaluated by the statistical software SPSS 17.0.e For comparison of the age between groups the Mann-Whitney U-test was used. The Pearson χ2-test was used to compare laboratory parameters of dogs with or without respiratory signs. Correlations of presence and severity of respiratory signs and course of disease were evaluated by the Pearson χ2-test. P-values of <.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

Leptospira Diagnostics

Fifty dogs with leptospirosis were included in the study. In 10 dogs renal tissue was examined histopathologically for leptospiral organisms, in 6 of these dogs (60%) leptospiral organisms were detected by Levaditi staining.

Fifteen of 37 (41%) dogs had a positive PCR result in either the urine or the blood.

In 48 dogs MAT titers were performed. In 31 dogs the diagnosis was based solely on the MAT titers. In 17 of these 31 (55%) dogs, diagnostic titers (≥1 : 800 against nonvaccine serovars) were detected at initial presentation. In 14/31 (45%) dogs, the MAT titers were low (<1 : 800) or absent at initial presentation; the 2nd MAT titers determined 14–21 days later were higher and were considered diagnostic. Six dogs displayed a combination of a diagnostic MAT titer and a positive urine/blood PCR. In 2 cases, leptospirosis was confirmed by both a positive urine PCR and histopathological examination. Seven dogs displayed only a positive urine or blood PCR. In 4 dogs, the diagnosis was solely based on a positive Levaditi staining.

MAT Titers

In 37 dogs a diagnosis of leptospirosis was suggested based on MAT titers (titer ≥ 1 : 800 or convalescent titer). In these dogs, the highest titers were present against the following serovars or serovar combinations: Bratislava (n = 9 dogs; 1 : 800–1 : 25,600); Grippotyphosa (5 dogs; 1 : 1,600–1 : 6,400), Pomona (4 dogs; 1 : 800–1 : 3,200), Ballum (1 dog; 1 : 800), Pyrogenes (1 dog; 1 : 800), Saxkoebing (1 dog; 1 : 400), Copenhageni (1 dog; 1 : 800), Bratislava/Grippotyphosa (8 dogs; 1 : 800–1 : 6,400), Grippotyphosa/Pomona (3 dogs; 1 : 800–1 : 1,600), Pomona/Copenhageni (1 dog; 1 : 800), Bratislava/Grippotyphosa/Pomona (1 dog; 1 : 1,600), Bratislava/Pomona/Autumnalis (1 dog; 1 : 800), Grippotyphosa/Pomona/Autumnalis/Bataviae (1 dog; 1 : 800). There were no differences between groups 1 and 2 regarding Leptospira serovars detected by MAT. The age of the dogs ranged from 0.3 to 14 years (median, 5.9 years). Twenty-one dogs (42%) were male, 6 (12%) male-neutered, 17 (34%) female, and 6 (12%) female-neutered. Thirty-two dogs were purebred and belonged to 24 different breeds. Eighteen dogs were crossbreeds. The body weight ranged from 2.8–53 kg (median 21.0 kg). Thirty-four of 45 dogs with a known vaccination history were vaccinated against the serovars Canicola and Icterohaemorrhagiae within the last year.

The 50 dogs were presented because of lethargy (50, 100%), inappetence (42, 84%), vomitus (36, 72%), diarrhea (16, 32%), reluctance to move (10, 20%), labored breathing (7, 14%), polydipsia and polyuria (4, 8%), painful abdomen (2, 4%), or brownish urine (1, 2%).

Clinical signs on the day of admission included lethargy (45, 90%), anorexia (42, 84%), vomitus (36, 72%), diarrhea (25, 50%), painful abdomen (18, 36%), delayed capillary refill time (6, 12%), icteric mucous membranes (5, 10%), pale mucous membranes (5, 10%), stiff gait (4, 8%), fever (4, 8%), mild hypothermia (3, 6%), or severe dehydration (3, 6%).

Thirty-one dogs (62%) had signs related to the respiratory system: 19 had dyspnea at admission (day 1), 11 dogs developed dyspnea on day 2, and 1 dog on day 4.

Thirteen dogs suffered from mild to moderate dyspnea (grade 1); 18 dogs suffered from severe dyspnea (grade 2), and 7 of them developed hemoptysis.

In all dogs thoracic radiographs were taken initially and during the course of the disease if necessary. Of the 50 dogs suffering from leptospirosis, 35 (70%) displayed abnormal lung patterns. Thirty-one of these 35 dogs suffered from varying degrees of dyspnea.

Radiological pulmonary changes grades 1, 2, and 3 were detected in 5, 14, and 16 dogs, respectively (Fig 1). Of the 18 dogs with severe dyspnea, 11 dogs had radiological pulmonary changes grade 3, 4 dogs grade 2, and 3 dogs grade 1. Of the 13 dogs with mild to moderate dyspnea, 8 and 5 dogs displayed radiological pulmonary changes of grades 2 or 3, respectively. The pulmonary changes in the 4 dogs without dyspnea were of grade 1 (2 dogs) and grade 2 (2 dogs), respectively.

image

Figure 1.  Lateral thoracic radiograph of a 7-year-old female mixed-breed dog with leptospirosis and severe dyspnea: generalized severe reticulonodular interstitial lung pattern with patchy alveolar consolidations.

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Thoracic radiographs were available in 25 dogs on the day when dyspnea was most severe and in 6 dogs radiographs were taken the day before.

Based on clinical and thoracic radiological findings, 35 dogs were placed in group 1, ie, with lung abnormalities. Fifteen dogs had no clinical or radiological lung abnormalities (group 2).

Radiographs of the abdomen were performed for all dogs. A lack of detail was observed in 8 dogs (in 2 dogs localized in the cranial abdomen, in 6 dogs generalized lack of detail). Four dogs had hepatomegaly and 11 dogs a splenomegaly.

CBCs and biochemistries were performed for all dogs every 1–2 days during hospitalization. Abnormal findings of the CBC at admission included thrombocytopenia (29/50; 58%), anemia (25/50; 50%), and leukocytosis (34/50; 68%). Differential cell count revealed neutrophilia (30/44, 68%), a left shift (11/44, 25%), monocytosis (30/44, 68%), lymphopenia (33/44, 75%), lymphocytosis (1/44, 2%), or eosinophilia (1/44, 2%). At admission in 50% (19/38) of the dogs aPTT was prolonged, and in 24% (9/39) PT was prolonged. Biochemistry showed both an increase of plasma creatinine and urea concentration in 88% (44/50) of the patients. Plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were increased in 78% (37/48) and 90% (42/47), respectively; hyperbilirubinemia was present in 73% (35/48) of the dogs. The urinalysis revealed an elevated urine-protein/creatinine-ratio in 94% (32/34), glucosuria in 82% (39/48), and microscopic hematuria in 68% (32/48). Sediment analysis was performed for 35 dogs; it revealed leukocytes in all dogs (100%), epithelial cells in 40% (14/35), crystals in 17% (6/35), cylinders in 34% (12/35), and erythrocytes in 66% (23/35).

The differences between groups 1 and 2 with respect to age (P= .42) or sex (P= .39) were not significant.

There was a correlation between the occurrence of thrombocytopenia and pulmonary signs (P= .03). The severity of thrombocytopenia differed not significantly between the groups (P= .08) (Table 1). Twenty-nine dogs (83%) of group 1 had platelet counts below the reference range (reference range: 180–500 × 103/μL; <50 × 103/μL [12/29; 41%], 51–100 × 103/μL [9/29; 31%], 101–179 × 103/μL [8/29; 28%]). In contrast, only 53% (8/15) of the dogs in group 2 had thrombocytopenia: <50 × 103/μL (4/8; 50%), 51–100 × 103/μL (1/8; 12%), 101–179 × 103/μL (3/8; 38%).

Table 1.   Comparison of laboratory parameters in dogs with leptospirosis with pulmonary abnormalities (group 1) and without pulmonary abnormalities (group 2) (at the time of detected maximal deviation from the reference range).
 Group 1 (n = 35)Dogs with Abnormal Values (Group 1)Group 2 (n = 15)Dogs with Abnormal Values (Group 2)
RangeMediann (%)RangeMediann (%)
Thrombocytes (× 103/μL) (n = 50)5.5–46191.129/35 (83)7.9–5251518/15 (53)
Hematocrit (%) (n = 50)16–513323/35 (66)25–443211/15 (73)
Leukocytes (× 103/μL) (n = 50)8–10425.626/35 (74)12.6–48.824.714/15 (93)
aPTT (s) (n = 38)11–432115/28 (54)12–4319.95/10 (50)
PT (s) (n = 39)10–32176/29 (21)10–32183/10 (30)
Creatinine (mg/dL) (n = 50)0.85–10.94.832 /35 (91)1.1–12614/15 (93)
Urea (mg/dL) (n = 50)28–59530032/35 (91)50–35124714/15 (93)
ALT (U/L) (n = 38)20–744018224/33 (72)69–52610713/15 (87)
ALP (U/L) (n = 37)33–369927829/32 (90)34–123524714/15 (93)
Bilirubin (mg/dL) (n = 48)0.2–441.029/33 (88)0.2–350.4211/15 (73)
Urine protein/creatinine ratio (n = 35)0.3–12.72.323/24 (96)0.2–17.82.510/11 (91)
Glucosuria (n = 48)  29/34 (85)  10/14 (71)

Comparison of the dogs of groups 1 and 2 revealed that a similar percentage suffered from anemia with 66% (23/35) and 73% (11/15), respectively. Eight, 10, and 5 of the 23 anemic dogs of group 1 displayed mild (hematocrit [Hct] 30–37%), moderate (Hct 20–29%), or severe (Hct < 19%) anemia, respectively. In contrast, the 11 anemic dogs of group 2 displayed mild (8) or moderate (3) anemia.

Five dogs of group 1 and 2 dogs of group 2 had increased aPTT and PT values in addition to thrombocytopenia. In these dogs a disseminated intravascular coagulation (DIC) was suspected.

There were only slight differences between groups 1 and 2 regarding the percentage of dogs with leukocytosis, azotemia, increased activities of ALT and ALP, hyperbilirubinemia, increase in urine-protein/creatinine-ratio, or glucosuria (Table 1).

Therapy and Outcome

All dogs were treated with amoxicillin clavulanate or doxycycline and crystalloid infusion. Symptomatic therapy included antiemetic drugs (n = 37; metoclopramide or maropitant), H2-receptor antagonists (n = 50; ranitidine or famotidine), analgetics (n = 23; buprenorphine, dipyrone). Mannitol, furosemide, or both were administered as boli, as long-term infusion, or both in cases of oliguria (17/20). Two dogs were hemodialyzed.24 All 18 dogs with severe dyspnea received oxygen via nasal tubes; most of these dogs were treated with short-acting glucocorticoids (n = 13; prednisolone-21-hydrogen succinate), bronchial dilators (n = 12; theophylline), and furosemide (n = 14; bolus and/or long-term infusion).

Thirty-two of the 50 dogs (64%) survived whereas 18 (36%) had to be euthanized. Fifteen of the 35 dogs (43%) with lung abnormalities (group 1) had to be euthanized but only 3 of 15 dogs (20%) of group 2 were euthanized (P= .12).

The differences between dogs suffering from dyspnea grades 1 and 2 were significant with respect to the survival rate (P= .03). Twelve of the 18 dogs (67%) with severe dyspnea had to be euthanized; the main reason for euthanasia was respiratory compromise. In addition to dyspnea all 12 dogs had renal failure and 7 of 10 dogs increased liver enzymes or hyperbilirubinemia. The median survival time of these 12 dogs was 2 days (range: 1–3 days) after presentation. In contrast, only 15% (2/13) of the dogs with mild to moderate dyspnea were euthanized after 1 and 3 days due acute renal failure (1 dog had a catheter-related sepsis in addition). Of the 4 dogs with radiological lung abnormalities but without clinical dyspnea (group 1) 3 dogs survived, the other dog was euthanized on day 5 because of renal failure.

Three dogs in group 2 (20%) were euthanized because of acute renal failure 2–3 days after admission.

The survival rates of dogs with mild-to-moderate dyspnea and those without lung abnormalities revealed no significant difference (P= .67).

Pathological Findings

Ten of the dogs that had to be euthanized were submitted to a necropsy investigation of major organ systems. Tissue samples from the lung, kidney, and liver of these dogs were examined histopathologically. Nine of these dogs with radiological pulmonary changes had dyspnea grade 2. One dog had no clinical or radiological pulmonary signs. All 10 dogs had severe, diffuse, acute, pulmonary alveolar, and subpleural hemorrhage with multifocal to coalescing coagulative necrosis of alveolar walls, partly with hyalin membranes. The pulmonary changes were homogeneously distributed throughout the entire lungs. Alveoli were filled with varying amounts of edematous fluid and fibrin. Multifocal microvascular hyalin and fibrin thrombi were present, most prominent in areas of severe alveolar wall necrosis. Major airways were virtually unaffected. In addition, 1 dog had multifocal, acute suppurative pneumonia, and 2 dogs had mild, diffuse, interstitial, lymphocytic pneumonia. In the kidneys, acute, tubular necrosis was present in 8 dogs whereas 4 dogs had acute, multifocal, moderate hepatocellular necrosis in the liver. Levaditi stains failed to detect any leptospiral organisms in the lungs whereas typical spirochetoid organisms were identified in 6 of 10 kidneys. No quantitative or qualitative associations were observed between the pulmonary changes and other organ lesions.

Discussion

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

Results of this study demonstrate the frequent pulmonary abnormalities in 50 dogs diagnosed with leptospirosis in Northeast Germany. Pulmonary involvement including dyspnea and abnormal radiological lung patterns were present in 70% of the dogs. Thirty-eight percent of all dogs were dyspneic at admission. Another study reported a slightly higher percentage of dogs with leptospirosis displaying dyspnea at initial presentation, ie, 52% (14/27).21 It has to be considered, however, that labored breathing does not necessarily have to be related to the infection; other causes might be acidosis or pain.

Forty-two percent of the dogs in this study with respiratory signs displayed mild to moderate dyspnea and 58% severe dyspnea at the time of most severe respiratory compromise. Another study described mild and moderate to severe dyspnea in 27% (4/15) and 73% (11/15) of the dogs, respectively.25 In our study 23% (7/31) of the dyspneic dogs developed fatal hemoptysis, whereas other authors reported a percentage of 48% (10/21).21

Similar to earlier studies the most frequent diagnostic titers against Leptospira serovars in dogs included Grippotyphosa, Bratislava, and Pomona.4,5,7,9 Interestingly, leptospirosis is of increasing importance and prevalence in the rural areas of Berlin where the population of urban wild boars is growing dramatically, and these wild boars have recently been shown to represent a significant reservoir for Leptospira serovars Pomona and Bratislava.26

There was no correlation between the serovars with the highest MAT titers and the presence or absence of pulmonary lesions in our study. However, serovars with the highest MAT do not always correspond to the infecting serovar but at this time there is no other appropriate method for serovar recognition.27 Moreover, laboratory variation makes standardization difficult and strict criteria for active leptospiral infection have not been established yet. In a study on human patients performed in Barbados, the correlation was approximately 50% between the infecting serogroup according to MAT and the actual infecting serovar identified from culture after isolation.27 In a recent North American study it was suggested that only minor clinically relevant differences exist among serogroups. However, Leptospira serogroup Pomona caused more severe renal disease and was associated with a worse outcome compared with disease caused by other serogroups.5

Hematologic manifestations are common in leptospirosis, and the most common finding in severe cases is thrombocytopenia.28 Thrombocytopenia was found in 83% of the dogs with and in 53% of the dogs without lung findings. There was controversy in the literature whether thrombocytopenia is associated with DIC in patients with leptospirosis.28 Because of prolonged PT and aPTT, in addition to thrombocytopenia DIC was suspected in only 18% of our patients. However, the plasma coagulation parameters were not established for all patients; and PT and aPTT were measured only once in most dogs. Further parameters, such as D-Dimers or fibrinogen, were determined only in a few dogs. In a guinea pig leptospirosis model all infected animals developed pulmonary hemorrhage and thrombocytopenia but the thrombocytopenia did not correlate with the occurrence of DIC. According to the authors of this study the platelet aggregation and Kupffer cells phagocytosis might be potential causes of thrombocytopenia in severe leptospirosis.28 In humans with leptospirosis thrombocytopenia did not seem to be related to DIC, but rather to activation, adhesion, and aggregation of platelets to the stimulated vascular endothelium.29 A role of immune-mediated platelet destruction as a cause of thrombocytopenia in severe leptospirosis has been suggested.30 Recently, a positive platelet-bound antibody test has been described in dogs with leptospirosis and thrombocytopenia.31 A flow cytometry platelet-bound antibody test was negative in 5 dogs of our study (data not shown). A further cause of low platelet counts in these patients might be sequestration in an enlarged spleen. Thrombocytopenia, uremia, and coagulation disorders, individually or as a group might be contributing factors that worsen pulmonary bleeding episodes.32

In the present study no significant difference was observed between dogs with lung abnormalities and those without with regard to the severity of anemia. With 45 and 54%, anemia was also a common finding in earlier studies on canine leptospirosis.5,6 Anemia can be caused by hemolysis, which is related to the effect of leptospiral toxins on plasma membranes of erythrocytes.33 Furthermore, blood loss can occur via the gastrointestinal or respiratory tract. Severe inflammatory reactions may impede hematopoiesis.34

All dogs with dyspnea in this study had altered radiological lung patterns. In contrast, a previous study found significantly less radiological pulmonary changes; only 9% of the dogs (2/22) suffering from leptospirosis had mild pulmonary opacities.5 In a study from Switzerland, patchy to confluent interstitial to alveolar changes were detected in 85% (23/27) of the dogs.21 Mild to severe reticulonodular pulmonary opacities accentuated in the caudodorsal lung field were described for 5 dogs suffering from leptospirosis.20–23 A possible explanation for this type of distribution was the increased exposure of the capillaries to toxic products leading to more severe hemorrhage in the caudodorsal parts of the lung.20–23

The severity of dyspnea correlated with the percentage of dogs that survived. Sixty-seven percent suffering from severe dyspnea had to be euthanized because of respiratory distress. Other authors reported that 48% (10/21) of the dogs suffering from pulmonary leptospirosis died or had to be euthanized because of refractory dyspnea.21

On necropsy, macroscopic and histological evidence of severe, acute alveolar, and subpleural hemorrhage was found in all dogs, even in 1 dog without clinical or radiological lung abnormalities. Similarly, in humans intra-alveolar hemorrhage has been detected even in patients without overt pulmonary symptoms.19 Therefore, lung abnormalities in dogs with leptospirosis might be more common than detected by clinical signs or thoracic radiography. The pathological findings are similar to lesions found in human patients with pulmonary leptospirosis.13,29 Varying amounts of edematous fluids were found in the alveoli of most dogs. Fluid overload might have contributed to the lung abnormalities but due to the severe hemorrhage was not suspected to be the main underlying pathology. Moreover, dogs were monitored closely to prevent fluid overload, which is a common complication in dogs with acute renal failure.

The pathogenesis of lung abnormalities in leptospirosis is currently under investigation. Because lung tissue usually shows much lower numbers of leptospires than liver and blood tissue, pulmonary abnormalities may be attributable to autoimmune mechanisms or to exposure of circulating toxins produced by the pathogen at distant sites, such as the liver.13,35,36 The pathogenesis of lung and organ injury might also involve inducible nitric oxide synthase and nitric oxide production causing severe hypotension and bradycardia accompanied by autonomic dysfunction.37 Unfortunately, blood pressure and ECG monitoring was not routinely performed in the dogs of our study. The suggested immune-pathogenic mechanism may justify the use of short-acting glucocorticoids in cases of severe dyspnea and pulmonary hemorrhage which has been described in human medicine.38 Glucocorticoids were administered to 13 dogs of this study with severe pulmonary abnormalities. However, glucocorticoid treatment was not randomized and the case number was low. In dogs with leptospirosis and pulmonary hemorrhage successful treatment options have yet to be defined.

Footnotes

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

a Kone Lab 30i, Thermo Electron GmbH, Dreieich, Germany

b Cell-Dyn, Abbott Diagnostika, Wiesbaden, Germany

c Pathromtin SL, Dade Behring Marburg GmbH, Marburg, Germany

d Hepato Quick, Diagnostica Stago, Asnieres, France

e SPSS 14.0 for Windows, Microsoft, Redmont, WA

Acknowledgments

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References

We thank K. Radeke and Prof Dr P.F. Suter for her help with this study; the Hanns Seidel Foundation and Intervet/Schering Plough Animal Health for their financial support.

References

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Footnotes
  7. Acknowledgments
  8. References
  • 1
    Nardone A, Capek I, Baranton G, et al. Risk factors for leptospirosis in metropolitan France: Results of a national case-control study, 1999–2000. Clin Infect Dis 2004;39:751753.
  • 2
    Jansen A, Schoneberg I, Frank C, et al. Leptospirosis in Germany, 1962–2003. Emerg Infect Dis 2005;11:10481054.
  • 3
    Steger-Lieb A, Gerber B, Nicolet J, et al. An old disease with a new face: Canine leptospirosis does not lose its relevance. Schweiz Arch Tierheilkd 1999;141:499507.
  • 4
    Adin CA, Cowgill LD. Treatment and outcome of dogs with leptospirosis: 36 cases (1990–1998). J Am Vet Med Assoc 2000;216:371375.
  • 5
    Goldstein RE, Lin RC, Langston CE, et al. Influence of infecting serogroup on clinical features of leptospirosis in dogs. J Vet Intern Med 2006;20:489494.
  • 6
    Geisen V, Stengel C, Brem S, et al. Canine leptospirosis infections—clinical signs and outcome with different suspected Leptospira serogroups (42 cases). J Small Anim Pract 2007;48:324328.
  • 7
    Gerlach T, Stephan I. Epidemiologische Situation der caninen Leptospirose in Norddeutschland in den Jahren 2003-2006. Tierärztl Prax 2007;38:421429.
  • 8
    Harkin KR, Gartrell CL. Canine leptospirosis in New Jersey and Michigan: 17 cases (1990–1995). J Am Anim Hosp Assoc 1996;32:495501.
  • 9
    Birnbaum N, Barr SC, Center SA, et al. Naturally acquired leptospirosis in 36 dogs: Serological and clinicopathological features. J Small Anim Pract 1998;39:231236.
  • 10
    Tattevin P, Leveiller G, Flicoteaux R, et al. Respiratory manifestations of leptospirosis: A retrospective study. Lung 2005;183:283289.
  • 11
    Courtin JP, Di Francia M, Du Couedic I, et al. Respiratory manifestations of leptospirosis. A retrospective study of 91 cases (1978-1984). Rev Pneumol Clin 1998;54:382392.
  • 12
    Paganin F, Bourdin A, Dalban C, et al. Leptospirosis in Reunion Island (Indian Ocean): Analysis of factors associated with severity in 147 confirmed cases. Intensive Care Med 2007;33:19591966.
  • 13
    Dolhnikoff M, Mauad T, Bethlem EP, et al. Pathology and pathophysiology of pulmonary manifestations in leptospirosis. Braz J Infect Dis 2007;11:142148.
  • 14
    Carvalho CR, Bethlem EP. Pulmonary complications of leptospirosis. Clin Chest Med 2002;23:469478.
  • 15
    Segura ER, Ganoza CA, Campos K, et al. Clinical spectrum of pulmonary involvement in leptospirosis in a region of endemicity, with quantification of leptospiral burden. Clin Infect Dis 2005;40:343351.
  • 16
    Jansen A, Nockler K, Schonberg A, et al. Wild boars as possible source of hemorrhagic leptospirosis in Berlin, Germany. Eur J Clin Microbiol Infect Dis 2006;25:544546.
  • 17
    Silva JJ, Dalston MO, Carvalho JE, et al. Clinicopathological and immunohistochemical features of the severe pulmonary form of leptospirosis. Rev Soc Bras Med Trop 2002;35:395399.
  • 18
    Im JG, Yeon KM, Han MC, et al. Leptospirosis of the lung: Radiographic findings in 58 patients. Am J Roentgenol 1989;152:955959.
  • 19
    Levett PN. Leptospirosis. Clin Microbiol Rev 2001;14:296326.
  • 20
    Baumann D, Fluckiger M. Radiographic findings in the thorax of dogs with leptospiral infection. Vet Radiol Ultrasound 2001;42:305307.
  • 21
    Francey T, Schweighauser A. Pulmonary hemorrhage as an emerging complication of acute kidney injury due to canine leptospirosis. Proceedings 18th ECVIM-CA Congress, Ghent, 2008.
  • 22
    World Health Organization. Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. Malta: World Health Organization; 2003.
  • 23
    OIE. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Paris, France: OIE; 2004.
  • 24
    Cowgill LD, Francey T. Acute uremia. In: EttingerSJ, FeldmanEC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Philadelphia, PA: WB Saunders; 2005:17311751.
  • 25
    Schweighauser A, Francey T. Treatment of pulmonary hemorrhage in canine leptospirosis with Desmopressin and Dexamethasone. Proceedings 18th ECVIM-CA Congress, Ghent, 2008.
  • 26
    Jansen A, Luge E, Guerra B, et al. Leptospirosis in urban wild boars, Berlin, Germany. Emerg Infect Dis 2007;13:739742.
  • 27
    Levett PN. Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis. Clin Infect Dis 2003;36:447452.
  • 28
    Yang HL, Jiang XC, Zhang XY, et al. Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation. BMC Infect Dis 2006;6:19.
  • 29
    Nicodemo AC, Duarte MI, Alves VA, et al. Lung lesions in human leptospirosis: Microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia. Am J Trop Med Hyg 1997;56:181187.
  • 30
    Davenport A, Rugman FP, Desmond MJ, et al. Is thrombocytopenia seen in patients with leptospirosis immunologically mediated? J Clin Pathol 1989;42:439440.
  • 31
    Kohn B, Engelbrecht R, Leibold W, et al. Clinical findings, diagnostics and treatment results in primary and secondary immune-mediated thrombocytopenia in the dog. Kleintierpraxis 2000;45:893907.
  • 32
    Nicodemo AC, Del Negro G, Amato Neto V. Thrombocytopenia and leptospirosis. Rev Inst Med Trop Sao Paulo 1990;32:252259.
  • 33
    Lee SH, Kim KA, Park YG, et al. Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar lai. Gene 2000;254:1928.
  • 34
    Ottenjann M, Weingart C, Arndt G, et al. Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis. J Vet Intern Med 2006;20:11431150.
  • 35
    Nally JE, Chantranuwat C, Wu XY, et al. Alveolar septal deposition of immunoglobulin and complement parallels pulmonary hemorrhage in a guinea pig model of severe pulmonary leptospirosis. Am J Pathol 2004;164:11151127.
  • 36
    Bharti AR, Nally JE, Ricaldi JN, et al. Leptospirosis: A zoonotic disease of global importance. Lancet Infect Dis 2003;3:757771.
  • 37
    Chen HI, Kao SJ, Hsu YH. Pathophysiological mechanism of lung injury in patients with leptospirosis. Pathology 2007;39:339344.
  • 38
    Trivedi SV, Chavda RK, Wadia PZ, et al. The role of glucocorticoid pulse therapy in pulmonary involvement in leptospirosis. J Assoc Physicians India 2001;49:901903.